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<div>*** START OF THE PROJECT GUTENBERG EBOOK 45962 ***</div>
<h1 class="pg">The Project Gutenberg eBook, The Organism as a Whole, by Jacques Loeb</h1>
<p> </p>
<p> </p>
<table border="0" style="background-color: #ccccff;margin: 0 auto;" cellpadding="10">
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<td valign="top">
Note:
</td>
<td>
Images of the original pages are available through
Internet Archive/American Libraries. See
<a href="https://archive.org/details/organismaswholef00loeb">
https://archive.org/details/organismaswholef00loeb</a>
</td>
</tr>
</table>
<p> </p>
<div class="transnote"><p><b>Transcriber’s note</b>:</p>
<p>In this transcription a black dotted underline indicates a hyperlink
to a specific page or illustration; hyperlinks also show aqua highlighting
when the cursor hovers over them. Page numbers appear in the right margin.</p>
</div>
<hr class="full" />
<p> </p>
<div class="figcenter" style="width: 448px">
<img src="images/title.jpg" width="448" height="700" alt="title page" />
</div>
<div class="tac prewrap page-before">
<h1>The
Organism as a Whole</h1>
<div class="t1">From a Physicochemical Viewpoint</div>
<div><b>By</b></div>
<div class="t2"><span class="fs130"><b>Jacques Loeb,</b></span> M.D., Ph.D., Sc.D.</div>
<div class="t3">Member of the Rockefeller Institute for Medical Research</div>
<hr class="r8" />
<div class="t4"><i>With 51 Illustrations</i></div>
<hr class="r8" />
<div class="mt6em"><span class="fs120">G. P. Putnam’s Sons</span>
<span class="fs105">New York and London</span>
<img src="images/logo1.png" width="155" height="13" style="padding-top: 0.3em;" alt="logo" /></div>
<hr class="r30" />
<div><span class="smcap fs70">Copyright, 1916
by</span>
<span class="fs80">JACQUES LOEB</span></div>
<div class="figcenter mt6em" style="width: 235px">
<img src="images/logo2.png" width="235" height="14" alt="logo" /></div>
<hr class="r30" />
<div class="t5">To
<span style="font-size: 80%">THE MEMORY OF</span>
DENIS DIDEROT
<span style="font-size: 110%">Of the <i lang="fr" xml:lang="fr">Encyclopédie</i> and the <i lang="fr" xml:lang="fr">Système de la nature</i></span></div>
</div>
<p class="smblk fs85">“He was one of those simple, disinterested, and intellectually
sterling workers to whom their own personality is as nothing in the
presence of the vast subjects that engage the thoughts of their
lives.”<br />
<span class="ml65"><span class="smcap">John Morley.</span></span><br />
(Article Diderot, <cite>Encyclopædia Britannica</cite>.)</p>
<hr class="chap" />
<p><span class="pagenum" title="v"><a name="Page_v" id="Page_v"></a></span></p>
<h2>PREFACE</h2>
<p>It is generally admitted that the individual physiological processes,
such as digestion, metabolism, the production of heat or of
electricity, are of a purely physicochemical character; and it is also
conceded that the functions of individual organs, such as the eye
or the ear, are to be analysed from the viewpoint of the physicist.
When, however, the biologist is confronted with the fact that in the
organism the parts are so adapted to each other as to give rise to a
harmonious whole; and that the organisms are endowed with structures
and instincts calculated to prolong their life and perpetuate their
race, doubts as to the adequacy of a purely physicochemical viewpoint
in biology may arise. The difficulties besetting the biologist in this
problem have been rather increased than diminished by the discovery of
Mendelian heredity, according to which each character is transmitted
independently of any other character. Since the number of Mendelian
characters in each organism is large, the possibility must be faced
that the organism is merely a mosaic of independent hereditary
characters. If this be the case<span class="pagenum" title="vi"><a name="Page_vi" id="Page_vi"></a></span> the question arises: What moulds these
independent characters into a harmonious whole?</p>
<p>The vitalist settles this question by assuming the existence of a
pre-established design for each organism and of a guiding “force”
or “principle” which directs the working out of this design. Such
assumptions remove the problem of accounting for the harmonious
character of the organism from the field of physics or chemistry. The
theory of natural selection invokes neither design nor purpose, but it
is incomplete since it disregards the physicochemical constitution of
living matter about which little was known until recently.</p>
<p>In this book an attempt is made to show that the unity of the organism
is due to the fact that the egg (or rather its cytoplasm) is the future
embryo upon which the Mendelian factors in the chromosomes can impress
only individual characteristics, probably by giving rise to special
hormones and enzymes. We can cause an egg to develop into an organism
without a spermatozoön, but apparently we cannot make a spermatozoön
develop into an organism without the cytoplasm of an egg, although
sperm and egg nucleus transmit equally the Mendelian characters. The
conception that the cytoplasm of the egg is already the embryo in the
rough may be of importance also for the problem of evolution since
it suggests the possibility that the genus- and species-heredity are
determined by the cytoplasm of the egg, while the Mendelian heredi<span class="pagenum" title="vii"><a name="Page_vii" id="Page_vii"></a></span>tary
characters cannot contribute at all or only to a limited extent to
the formation of new species. Such an idea is supported by the work
on immunity, which shows that genus- and probably species-specificity
are due to specific proteins, while the Mendelian characters may be
determined by hormones which need neither be proteins nor specific or
by enzymes which also need not be specific for the species or genus.
Such a conception would remove the difficulties which the work on
Mendelian heredity has seemingly created not only for the problem of
evolution but also for the problem of the harmonious character of the
organism as a whole.</p>
<p>Since the book is intended as a companion volume to the writer’s former
treatise on <cite>The Comparative Physiology of the Brain</cite> a discussion of
the functions of the central nervous system is omitted.</p>
<p>Completeness in regard to quotation of literature was out of the
question, but the writer notices with regret, that he has failed to
refer in the text to so important a contribution to the subject as
Sir E. A. Schäfer’s masterly presidential address on “Life” or the
addresses of Correns and Goldschmidt on the determination of sex.
Credit should also have been given to Professor Raymond Pearl for the
discrimination between species and individual inheritance.</p>
<p>The writer wishes to acknowledge his indebtedness to his friends
Professor E. G. Conklin of Princeton, Professor Richard Goldschmidt
of the Kaiser Wilhelm<span class="pagenum" title="viii"><a name="Page_viii" id="Page_viii"></a></span> Institut of Berlin, Dr. P. A. Levene of the
Rockefeller Institute, Professor T. H. Morgan of Columbia University,
and Professor Hardolph Wasteneys of the University of California who
kindly read one or more chapters of the book and offered valuable
suggestions; and he wishes especially to thank his wife for suggesting
many corrections in the manuscript and the proof.</p>
<p>The book is dedicated to that group of freethinkers, including
d’Alembert, Diderot, Holbach, and Voltaire, who first dared to follow
the consequences of a mechanistic science—incomplete as it then
was—to the rules of human conduct and who thereby laid the foundation
of that spirit of tolerance, justice, and gentleness which was the hope
of our civilization until it was buried under the wave of homicidal
emotion which has swept through the world. Diderot was singled out,
since to him the words of Lord Morley are devoted, which, however, are
more or less characteristic of the whole group.</p>
<p class="inrt">J. L.</p>
<p class="address fs85"><span class="smcap">The Rockefeller Institute</span><br />
<span class="smcap">for Medical Research</span>,<br />
<i>August, 1916</i></p>
<p><span class="pagenum" title="ix"><a name="Page_ix" id="Page_ix"></a></span></p>
<h2>CONTENTS</h2>
<table width="75%" cellpadding="1" summary="table of contents">
<col width="90%" /><col width="10%" />
<tr><td></td><td class="tar vab">PAGE</td></tr>
<tr><td class="tac ptbch">CHAPTER I</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Introductory Remarks</span></td><td class="tar vab">1</td></tr>
<tr><td class="tac ptbch">CHAPTER II</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">The Specific Difference between Living and Dead Matter and the Question of the Origin of Life</span></td><td class="tar vab">14</td></tr>
<tr><td class="tac ptbch">CHAPTER III</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">The Chemical Basis of Genus and Species:</span></td><td class="tar vab">40</td></tr>
<tr><td class="tal pl5hi"><span class="hide">I</span>I.—<span class="smcap">The Incompatibility of Species not Closely Related</span></td><td class="tar vab">44</td></tr>
<tr><td class="tal pl5hi">II.—<span class="smcap">The Chemical Basis of Genus and Species and of Species Specificity</span></td><td class="tar vab">53</td></tr>
<tr><td class="tac ptbch">CHAPTER IV</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Specificity in Fertilization</span></td><td class="tar vab">71</td></tr>
<tr><td class="tac ptbch">CHAPTER V</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Artificial Parthenogenesis</span></td><td class="tar vab">95</td></tr>
<tr><td class="tac ptbch">CHAPTER VI</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Determinism in the Formation of an Organism from an Egg</span></td><td class="tar vab">128</td></tr>
<tr><td><span class="pagenum" title="x"><a name="Page_x" id="Page_x"></a></span></td></tr>
<tr><td class="tac ptbch">CHAPTER VII</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Regeneration</span></td><td class="tar vab">153</td></tr>
<tr><td class="tac ptbch">CHAPTER VIII</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Determination of Sex, Secondary Sexual Characters, and Sexual Instincts:</span></td></tr>
<tr><td class="tal pl5hi"><span class="hide">I</span>I.—<span class="smcap">The Cytological Basis of Sex Determination</span></td><td class="tar vab">198</td></tr>
<tr><td class="tal pl5hi">II.—<span class="smcap">The Physiological Basis of Sex Determination</span></td><td class="tar vab">214</td></tr>
<tr><td class="tac ptbch">CHAPTER IX</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Mendelian Heredity and its Mechanism</span></td><td class="tar vab">229</td></tr>
<tr><td class="tac ptbch">CHAPTER X</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Animal Instincts and Tropisms</span></td><td class="tar vab">253</td></tr>
<tr><td class="tac ptbch">CHAPTER XI</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">The Influence of Environment</span></td><td class="tar vab">286</td></tr>
<tr><td class="tac ptbch">CHAPTER XII</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Adaptation to Environment</span></td><td class="tar vab">318</td></tr>
<tr><td class="tac ptbch">CHAPTER XIII</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Evolution</span></td><td class="tar vab">346</td></tr>
<tr><td class="tac ptbch">CHAPTER XIV</td><td class="tar vab"></td></tr>
<tr><td class="tal pl3hi"><span class="smcap">Death and Dissolution of the Organism</span></td><td class="tar vab">349</td></tr>
<tr><td class="tal ptbch pl3hi"><span class="smcap">Index</span></td><td class="tar vab">371</td></tr>
</table>
<hr class="chap" />
<h2>The Organism as a Whole</h2><p><span class="pagenum" title="1"><a name="Page_1" id="Page_1"></a></span></p>
<h2>CHAPTER I</h2>
<h3>INTRODUCTORY REMARKS</h3>
<p>1. The physical researches of the last ten years have put the atomistic
theory of matter and electricity on a definite and in all probability
permanent basis. We know the exact number of molecules in a given
mass of any substance whose molecular weight is known to us, and we
know the exact charge of a single electron. This permits us to state
as the ultimate aim of the physical sciences the visualization of
all phenomena in terms of groupings and displacements of ultimate
particles, and since there is no discontinuity between the matter
constituting the living and non-living world the goal of biology can be
expressed in the same way.</p>
<p>This idea has more or less consciously prevailed for some time in the
explanation of the single processes occurring in the animal body or
in the explanation of the functions of the individual organs. Nobody,
not<span class="pagenum" title="2"><a name="Page_2" id="Page_2"></a></span> even a scientific vitalist, would think of treating the process
of digestion, metabolism, production of heat, and electricity or even
secretion or muscular contraction in any other than a purely chemical
or physicochemical way; nor would anybody think of explaining the
functions of the eye or the ear from any other standpoint than that of
physics.</p>
<p>When the actions of the organism as a whole are concerned, we find
a totally different situation. The same physiologists who in the
explanation of the individual processes would follow the strictly
physicochemical viewpoint and method would consider the reactions of
the organism as a whole as the expression of non-physical agencies.
Thus Claude <span class="nowrap">Bernard,<a name="FNanchor_1_1" id="FNanchor_1_1"></a><a href="#Footnote_1_1" class="fnanchor">1</a></span> who in the
investigation of the individual life processes was a strict mechanist,
declares that the making of a harmonious organism from the egg cannot
be explained on a mechanistic basis but only on the assumption of a
“directive force.” Bernard assumes, as Bichat and others had done
before him, that there are two opposite processes going on in the
living organism: (1) the phenomena of vital creation or organizing
synthesis; (2) the phenomena of death or organic destruction. It
is only the destructive processes which give rise to the physical
manifestations by which we judge life, such as respiration and
circulation or the activity of glands, and so on.<span class="pagenum" title="3"><a name="Page_3" id="Page_3"></a></span> The work of creation
takes place unseen by us in the egg when the embryo or organism is
formed. This vital creation occurs always according to a definite plan,
and in the opinion of Bernard it is impossible to account for this plan
on a purely physicochemical basis.</p>
<div class="blockquot">
<p>There is so to speak a pre-established design of each being
and of each organ of such a kind that each phenomenon by
itself depends upon the general forces of nature, but when
taken in connection with the others it seems directed by some
invisible guide on the road it follows and led to the place it
occupies. . . .</p>
<p>We admit that the life phenomena are attached to physicochemical
manifestations, but it is true that the essential is not explained
thereby; for no fortuitous coming together of physicochemical
phenomena constructs each organism after a plan and a fixed
design (which are foreseen in advance) and arouses the
admirable subordination and harmonious agreement of the acts of
life. . . .</p>
<p>We can only know the material conditions and not the intimate
nature of life phenomena. We have therefore only to deal with
matter and not with the first causes or the vital force derived
therefrom. These causes are inaccessible to us, and if we believe
anything else we commit an error and become the dupes of metaphors
and take figurative language as real. . . .
Determinism can never be but physicochemical determinism. The vital
force and life belong to the metaphysical world.</p>
</div>
<p>In other words, Bernard thinks it his task to account for individual
life phenomena on a purely physicochemical basis—but the harmonious
character of the<span class="pagenum" title="4"><a name="Page_4" id="Page_4"></a></span> organism as a whole is in his opinion not produced
by the same forces and he considers it impossible and hopeless
to investigate the “design.” This attitude of Bernard would be
incomprehensible were it not for the fact that, when he made these
statements, the phenomena of specificity, the physiology of development
and regeneration, the Mendelian laws of heredity, the animal tropisms
and their bearing on the theory of adaptation were unknown.</p>
<p>This explanation of Bernard’s attitude is apparently contradicted by
the fact that <span class="nowrap">Driesch<a name="FNanchor_2_2" id="FNanchor_2_2"></a><a href="#Footnote_2_2" class="fnanchor">2</a></span> and v. <span
class="nowrap">Uexküll,<a name="FNanchor_3_3" id="FNanchor_3_3"></a><a href="#Footnote_3_3" class="fnanchor">3</a></span> both brilliant biologists, occupy
today a standpoint not very different from that of Claude Bernard.
Driesch assumes that there is an Aristotelian “entelechy” acting as
directing guide in each organism; and v. Uexküll suggests a kind of
Platonic “idea” as a peculiar characteristic of life which accounts for
the purposeful character of the organism.</p>
<p>v. Uexküll supposes as did Claude Bernard and as does Driesch
that in an organism or an egg the ultimate processes are purely
physicochemical. In an egg these processes are guided into definite
parts of the future embryo by the Mendelian factors of heredity—the
so-called genes. These genes he compares to the foremen for the
different types of work to be<span class="pagenum" title="5"><a name="Page_5" id="Page_5"></a></span> done in a building. But there must be
something that makes of the work of the single genes a harmonious
whole, and for this purpose he assumes the existence of <span
class="nowrap">“supergenes.”<a name="FNanchor_4_4" id="FNanchor_4_4"></a><a href="#Footnote_4_4" class="fnanchor">4</a></span> v. Uexküll’s ideas concerning
the nature of a Mendelian factor and of the “supergenes” are expressed
in metaphorical terms and the assumption of the “supergenes” begs the
question. The writer is under the impression that this author was led
to his views by the belief that the egg is entirely undifferentiated.
But the unfertilized egg is not homogeneous, on the contrary, it has
a simple but definite physicochemical structure which suffices to
determine the first steps in the differentiation of the organism.
Of course, if we suppose as do v. Uexküll and Driesch that the egg
has no structure, the development of structure becomes a difficult
problem—but this is not the real situation.</p>
<p>2. Claude Bernard does not mention the possibility of explaining the
harmony or apparent design in the organism on the basis of the theory
of evolution, he simply considers the problem as outside of biology. It
was probably clear to him as it must be to everyone with an adequate
training in physics that natural selection does not explain the origin
of variation. Driesch and v. Uexküll consider the Darwinian theory a
failure. We may admit that the theory of a forma<span class="pagenum" title="6"><a name="Page_6" id="Page_6"></a></span>tion of new species
by the cumulative effect of aimless fluctuating variations is not
tenable because fluctuating variation is not hereditary; but this
would only demand a slight change in the theory; namely a replacement
of the influence of fluctuating variation by that of equally aimless
mutations. With this slight modification which is proposed by de
<span class="nowrap">Vries,<a name="FNanchor_5_5" id="FNanchor_5_5"></a><a href="#Footnote_5_5" class="fnanchor">5</a></span> Darwin’s theory still serves
the purpose of explaining how without any pre-established plan only
purposeful and harmonious organisms should have survived. It must be
said, however, that any theory of life phenomena must be based on our
knowledge of the physicochemical constitution of living matter, and
neither Darwin nor Lamarck was concerned with this. Moreover, we cannot
consider any theory of evolution as proved unless it permits us to
transform at desire one species into another, and this has not yet been
accomplished.</p>
<p>It may be of some interest to point out that we do not need to make any
definite assumption concerning the mechanism of evolution and that we
may yet be able to account for the fact that the surviving organisms
are to all appearances harmonious. The writer pointed out that of all
the 100,000,000 conceivable crosses of teleost fish (many of which are
possible) not many more than 10,000, <i>i. e.</i>, about one-hundredth
of one per cent., are able to live and propagate. Those that live and
develop are free from the grosser type<span class="pagenum" title="7"><a name="Page_7" id="Page_7"></a></span> of disharmonies, the rest are
doomed on account of a gross lack of harmony of the parts. These latter
we never see and this gives us the erroneous conception that harmony
or “design” is a general character of living matter. If anybody wishes
to call the non-viability of <span class="nowrap">99<span class="fraction"><span class="fnum">99</span><span class="bar">/</span><span class="fden">100</span></span></span> per cent. of possible teleosts
a process of weeding out by “natural selection” we shall raise no
objection, but only wish to point out that our way of explaining the
lack of design in living nature would be valid even if there were no
theory of evolution or if there had never been any evolution.</p>
<p>3. v. Uexküll is perfectly right in connecting the problem of design
in an organism with Mendelian heredity. The work on Mendelian heredity
has shown that an extremely large number of independently transmissible
Mendelian factors help to shape the individual. It is not yet proven
that the organism is nothing but a mosaic of Mendelian factors, but no
writer can be blamed for considering such a possibility. If we assume
that the organism is nothing but a mosaic of Mendelian characters it
is difficult indeed to understand how they can force each other into a
harmonious <span class="nowrap">whole<a name="FNanchor_6_6" id="FNanchor_6_6"></a><a href="#Footnote_6_6" class="fnanchor">6</a></span>; even if we make ample
allowance for the law<span class="pagenum" title="8"><a name="Page_8" id="Page_8"></a></span> of chance and the corresponding wastefulness
in the world of the living. But it is doubtful whether this idea of
the rôle of Mendelian factors is correct. The facts of experimental
embryology strongly indicate the possibility that the cytoplasm of
the egg is the future embryo (in the rough) and that the Mendelian
factors only impress the individual (and variety) characters upon
this rough block. This idea is supported by the fact that the first
development—in the sea urchin to the gastrula stage inclusive—is
independent of the nucleus, which is the bearer of the Mendelian
factors. Not before the skeleton or mesenchyme is formed in the sea
urchin egg is the influence of the nucleus noticeable. This has been
shown in the experiments of Boveri in which an enucleated fragment of
an egg was fertilized with a spermatozoön of a foreign species. If this
is generally true, it is conceivable that the generic and possibly also
the species characters of organisms are determined by the cytoplasm of
the egg and not by the Mendelian factors. </p>
<p><span class="pagenum" title="9"><a name="Page_9" id="Page_9"></a></span></p>
<p>In any case, we can state today that the cytoplasm contains the rough
preformation of the future embryo. This would show then that the idea
of the organism being a mosaic of Mendelian characters which have to be
put into place by “supergenes” is unnecessary. If the egg is already
the embryo in the rough we can imagine the Mendelian factors as giving
rise to specific substances which go into the circulation and start
or accelerate different chemical reactions in different parts of the
embryo, and thereby call forth the finer details characteristic of the
variety and the individual. The idea that the egg is the future embryo
is supported by the fact that we can call forth a normal organism
from an unfertilized egg by artificial means; while it is apparently
impossible to cause the spermatozoön to develop into an organism
outside the egg.</p>
<p>4. The influence of the whole on the parts is nowhere shown more
strikingly than in the field of regeneration. It is known that pieces
cut from the plant or animal may give rise to new growth which in many
cases will restore somewhat the original organism. Instead of asking
what is the cause of this so-called regeneration we may ask, why the
same pieces do not regenerate as long as they are parts of the whole.
In this form the mysterious influence of the whole over its parts
is put into the foreground. We shall see that growth takes place in
certain cells when certain substances in the circulation can collect
there. The<span class="pagenum" title="10"><a name="Page_10" id="Page_10"></a></span> mysterious influence of the whole on these parts consists
often merely of the fact that the circulating specific or non-specific
substances—we cannot yet decide which—will in the whole be attracted
by certain spots and that this will prevent them from acting on other
parts of the organism. If such parts are isolated the substances can
no longer flow away from these parts and the parts will begin to grow.
It thus becomes utterly unnecessary to endow such organisms with a
“directing force” which has to elaborate the isolated parts into a
whole.</p>
<p>5. The same difficulty which we have discussed in regard to
morphogenesis exists also in connection with those instincts which
preserve the life of the organism and of the race. The reader need
only be reminded of all the complicated instincts of mating by which
sperm and eggs are brought together; or those by which the young
are prevented from starvation to realize the apparently desperate
problems in store for a mechanist, to whom the assumption of design
is meaningless. And yet we are better off in regard to our knowledge
of the instincts than we are in regard to morphogenesis, as in the
former we can show that the apparent instincts in some cases obey
simple physicochemical laws with almost mathematical accuracy. Since
the validity of the law of gravitation has been proved for the solar
system the idea of design in the motion of the planets has lost its
usefulness, and this fact must serve us as<span class="pagenum" title="11"><a name="Page_11" id="Page_11"></a></span> a guide wherever we attempt
to put science beyond the possibility of mysticism. As soon as we
can show that a life phenomenon obeys a simple physical law there is
no longer any need for assuming the action of non-physical agencies.
We shall see that this has been accomplished for one group of animal
instincts; namely those which determine the relation of animals to
light, since these are being gradually reduced to the law of Bunsen and
Roscoe. This law states that the chemical effect of light equals the
product of intensity into duration of illumination. Some authors object
to the tendency toward reducing everything in biology to mathematical
laws or figures; but where would the theory of heredity be without
figures? Figures have been responsible for showing that the laws of
chance and not of design rule in heredity. Biology will be scientific
only to the extent that it succeeds in reducing life phenomena to
quantitative laws.</p>
<p>Those familiar with the theories of evolution know the extensive
rôle ascribed to the adaptations of organisms. The writer in 1889
called attention to the fact that reactions to light—<i>e. g.</i>,
positive heliotropism—are found in organisms that never by
any chance make use of them; and later that a great many
organisms show definite instinctive reactions towards a galvanic
current—galvanotropism—although no organism has ever had or
ever will have a chance to be exposed to such a current except in
laboratory experiments. This<span class="pagenum" title="12"><a name="Page_12" id="Page_12"></a></span> throws a different light upon the
seemingly purposeful character of animal reactions. Heliotropism
depends primarily upon the presence of photosensitive substances
in the eye or the epidermis of the organism, and these substances
are inherited regardless of whether they are useful or not. It is
only a metaphor to call reactions resulting from the presence of
photosensitive substances “adaptation.” In this book other examples
are given which show that authors have too often spoken of adaptation
to environment where the environment was not responsible for the
phenomena. The blindness of cave animals and the resistance of certain
marine animals to higher concentrations of sea water are such cases.
Cuénot speaks of “preadaptation” to express this relation. The fact
is that the “adaptations” often existed before the animal was exposed
to surroundings where they were of use. This relieves us also of the
necessity of postulating the existence of the inheritance of acquired
characters, although it is quite possible that the future may furnish
proof that such a mode of inheritance exists.</p>
<p>6. We have mentioned that according to Claude Bernard two groups of
phenomena occur in the living organism: (1) the phenomena of vital
creation or organizing synthesis (especially in the egg and during
development); (2) the phenomena of death or organic destruction. These
two processes are briefly discussed in the first and last chapters.</p>
<p><span class="pagenum" title="13"><a name="Page_13" id="Page_13"></a></span></p>
<p>These introductory remarks may perhaps make it easier for the reader to
retain the thread of the main ideas in the details of experiments and
tables given in this book.</p>
<hr class="chap" />
<p><span class="pagenum" title="14"><a name="Page_14" id="Page_14"></a></span></p>
<h2>CHAPTER II</h2>
<h3>THE SPECIFIC DIFFERENCE BETWEEN LIVING AND DEAD MATTER AND THE QUESTION
OF THE ORIGIN OF LIFE</h3>
<p>1. Each organism is characterized by a definite form and we shall see
in the next chapter that this form is determined by definite chemical
substances. The same is true for crystals, where substance and form
are definitely connected and there are further analogies between
organisms and crystals. Crystals can grow in a proper solution, and can
regenerate their form in such a solution when broken or injured; it
is even possible to prevent or retard the formation of crystals in a
supersaturated solution by preventing “germs” in the air from getting
into the solution, an observation which was later utilized by Schroeder
and Pasteur in their experiments on spontaneous generation. However,
the analogies between a living organism and a crystal are merely
superficial and it is by pointing out the fundamental differences
between the behaviour of crystals and that of living organisms that
we can best<span class="pagenum" title="15"><a name="Page_15" id="Page_15"></a></span> understand the specific difference between non-living
and living matter. It is true that a crystal can grow, but it will
do so only in a supersaturated solution of its own substance. Just
the reverse is true for living organisms. In order to make bacteria
or the cells of our body grow, solutions of the split products of
the substances composing them and not the substances themselves
must be available to the cells; second, these solutions must not be
supersaturated, on the contrary, they must be dilute; and third,
growth leads in living organisms to cell division as soon as the mass
of the cell reaches a certain limit. This process of cell division
cannot be claimed even metaphorically to exist in a crystal. A correct
appreciation of these facts will give us an insight into the specific
difference between non-living and living matter. The formation of
living matter consists in the synthesis of the proteins, nucleins,
fats, and carbohydrates of the cells, from the split products. To give
an historical example, Pasteur showed that yeast cells and other fungi
could be raised on the following sterilized solution: water, 100 gm.,
crystallized sugar, 10 gm., ammonium tartrate, 0.2 gm. to 0.5 gm., and
fused ash from yeast, <span class="nowrap">0.1 gm.<a name="FNanchor_7_7" id="FNanchor_7_7"></a><a href="#Footnote_7_7" class="fnanchor">7</a></span> He
undertook this experiment to disprove the idea that protein or organic
matter in a state of decomposition was needed for the origin of new
organisms as the defenders of the idea of spontaneous generation had
maintained. </p>
<p><span class="pagenum" title="16"><a name="Page_16" id="Page_16"></a></span></p>
<p>2. That such a solution can serve for the synthesis of all the
compounds of living yeast cells is due to the fact that it contains
the sugars. From the sugars organic acids can be formed and these
with ammonia (which was offered in the form of ammonium tartrate) may
give rise to the formation of amino acids, the “building stones” of
the proteins. It is thus obvious that the synthesis of living matter
centres around the sugar molecule. The phosphates are required for the
formation of the nucleins, and the work of Harden and Young suggests
that they play also a rôle in the alcoholic fermentation of sugar.</p>
<p>Chlorophyll, under the influence of the red rays of light, manufactures
the sugars from the CO<sub>2</sub> of the air. This makes it appear as though
life on our planet should have been preceded by the existence of
chlorophyll, a fact difficult to understand since it seems more natural
to conceive of chlorophyll as a part or a product of living organisms
rather than the reverse. Where then should the sugar come from, which
is a constituent of the majority of culture media and which seems a
prerequisite for the synthesis of proteins in living organisms?</p>
<p>The investigations of Winogradsky on <span class="nowrap">nitrifying,<a name="FNanchor_8_8" id="FNanchor_8_8"></a><a href="#Footnote_8_8" class="fnanchor">8</a></span> sulphur and perhaps
also on iron bacteria have to all appearances pointed a way out
of this difficulty. It<span class="pagenum" title="17"><a name="Page_17" id="Page_17"></a></span> seemed probable that there were specific
micro-organisms which oxidized the ammonia formed in sewage or in
the putrefaction of living matter, but the attempts to prove this
assumption by raising such a nitrifying
micro-organism on one of the usual culture media, all of which
contained organic compounds, failed. Led by the results of his
observations on sulphur bacteria it occurred to Winogradsky that
the presence of organic compounds stood in the way of raising these
bacteria, and this idea proved correct. The bacteria oxidizing ammonia
to nitrites were grown on the following medium; 1 gm. ammonium
sulphate, 1 gm. potassium phosphate, 1 gm. magnesium carbonate, to
1 litre of water. From this medium, which is free from sugar and
contains only constituents which could exist on the planet before
the appearance of life, the nitrifying bacteria were able to form
sugars, fatty acids, proteins, and the other specific constituents of
living matter. Winogradsky proved, by quantitative determination, that
with the nitrification an increase in the amount of carbon compounds
takes place. “Since this bound carbon in the cultures can have no
other source than the CO<sub>2</sub> and since the process itself can have no
other cause than the activity of the nitrifying organism, no other
alternative was left but to ascribe to it the power of assimilating
<span class="pagenum" title="18"><a name="Page_18" id="Page_18"></a></span><span class="nowrap">CO<sub>2</sub>.”<a name="FNanchor_9_9" id="FNanchor_9_9"></a><a href="#Footnote_9_9" class="fnanchor">9</a></span> “Since the oxidation of NH<sub>3</sub>
is the only source of chemical energy which the nitrifying organism
can use it was clear <i lang="la" xml:lang="la">a priori</i> that the yield in assimilation must
correspond to the quantity of oxidized nitrogen. It turned out that an
approximately constant ratio exists between the values of assimilated
carbon and those of oxidized nitrogen.” This is illustrated by the
results of various experiments as shown in Table I.</p>
<p class="tac">TABLE I</p>
<table width="60%" summary="Results of experiments into the assimilation by organisms of carbon and nitrogen">
<tr><td class="btr"></td><td class="tac ball ptb03"><i>No. 5</i></td><td class="tac ball ptb03"><i>No. 6</i></td><td class="tac ball ptb03"><i>No. 7</i></td><td class="tac btl ptb03"><i>No. 8</i></td></tr>
<tr><td class="br"></td><td class="tac brl"><i>mg.</i></td><td class="tac brl ptb03"><i>mg.</i></td><td class="tac brl ptb03"><i>mg.</i></td><td class="tac btl ptb03"><i>mg.</i></td></tr>
<tr><td class="br">Oxidized N</td><td class="tac brl">722.0</td><td class="tac brl">506.1</td><td class="tac brl">928.3</td><td class="tac bl">815.4</td></tr>
<tr><td class="bbr">Assimilated C</td><td class="tac brl"><span class="hide">0</span>19.7</td><td class="tac brl"><span class="hide">0</span>15.2</td><td class="tac brl"><span class="hide">0</span>26.4</td><td class="tac bbl"><span class="hide">0</span>22.4</td></tr>
<tr><td class="bbr ptb03">Ratio N : C</td><td class="tac ball ptb03"><span class="hide">0</span>36.6</td><td class="tac ball ptb03"><span class="hide">0</span>33.3</td><td class="tac ball ptb03"><span class="hide">0</span>35.2</td><td class="tac bbl ptb03"><span class="hide">0</span>36.4</td></tr>
</table>
<p>It is obvious that 1 part of assimilated carbon corresponds to about
35.4 parts oxidized nitrogen or 96 parts of nitrous acid.</p>
<p>These results of Winogradsky were confirmed in very careful experiments
by E. Godlewski, <span class="nowrap">Sr.<a name="FNanchor_10_10" id="FNanchor_10_10"></a><a href="#Footnote_10_10" class="fnanchor">10</a></span></p>
<p>The nitrites are further oxidized by another kind of micro-organisms
into nitrates and they also can be raised without organic material.</p>
<p>Winogradsky had already previously discovered that<span class="pagenum" title="19"><a name="Page_19" id="Page_19"></a></span> the hydrogen
sulphide which is formed as a reduction product from CaSO<sub>4</sub> or in
putrefaction by the activity of certain bacteria can be oxidized by
certain groups of bacteria, the sulphur bacteria. Such bacteria,
<i>e. g.</i>, <i class="taxonomic">Beggiatoa</i>, are also commonly found at the outlet of
sulphur springs. They utilize the hydrogen sulphide which they oxidize
to sulphur and afterwards to sulphates, according to the scheme:</p>
<div class="blockquot">
<p>(1) 2H<sub>2</sub>S + O<sub>2</sub> = 2H<sub>2</sub>O + S<sub>2</sub></p>
<p>(2) S<sub>2</sub> + 3O<sub>2</sub> + 2H<sub>2</sub>O = 2H<sub>2</sub>SO<sub>4</sub></p>
</div>
<p>The sulphuric acid is at once neutralized by carbonates.</p>
<p>Winogradsky assumes that the oxidation of H<sub>2</sub>S by the sulphur
bacteria is the source of energy which plays the same rôle as the
oxidation of NH<sub>3</sub> plays in the nitrifying bacteria, or the oxidation
of carbon compounds—sugar and others—in the case of the other lower
and higher organisms. Winogradsky has made it very probable that
sulphur bacteria do not need any organic compounds and that their
nutrition may be accomplished with a purely mineral culture medium,
like that of the nitrite bacteria. On the basis of this assumption they
should also be able to form sugars from the CO<sub>2</sub> of the air.</p>
<p><span class="nowrap">Nathanson<a name="FNanchor_11_11" id="FNanchor_11_11"></a><a href="#Footnote_11_11" class="fnanchor">11</a></span> discovered in the sea water
the existence<span class="pagenum" title="20"><a name="Page_20" id="Page_20"></a></span> of bacteria which oxidize thiosulphate to sulphuric
acid. They will develop if some Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub>, is added to sea
water. These bacteria can only develop if CO<sub>2</sub> from the air is
admitted or when carbonates are present. For these organisms the CO<sub>2</sub>
cannot be replaced by glucose, urea, or other organic substances.
Such bacteria must therefore possess the power of producing sugar
and starch from CO<sub>2</sub> without the aid of chlorophyll. Similar
observations were made by Beijerinck on a species of fresh-water <span
class="nowrap">bacteria.<a name="FNanchor_12_12" id="FNanchor_12_12"></a><a href="#Footnote_12_12" class="fnanchor">12</a></span></p>
<p>Finally the case of iron bacteria may briefly be mentioned though
Winogradsky’s views are not accepted by Molisch.</p>
<p>We may, therefore, consider it an established fact that there are a
number of organisms which could have lived on this planet at a time
when only mineral constituents, such as phosphates, K, Mg, SO<sub>4</sub>,
CO<sub>2</sub>, and O<sub>2</sub> besides NH<sub>3</sub>, or SH<sub>2</sub>, existed. This would lead
us to consider it possible that the first organisms on this planet may
have belonged to that world of micro-organisms which was discovered by
Winogradsky.</p>
<p>If we can conceive of this group of organisms as producing sugar, which
in fact they do, they could have served as a basis for the development
of other forms which require organic material for their development.</p>
<p><span class="pagenum" title="21"><a name="Page_21" id="Page_21"></a></span></p>
<p>In 1883 the small island of Krakatau was destroyed by the most violent
volcanic eruption on record. A visit to the islands two months after
the eruption showed that “the three islands were covered with pumice
and layers of ash reaching on an average a thickness of thirty metres
and frequently sixty <span class="nowrap">metres.”<a name="FNanchor_13_13" id="FNanchor_13_13"></a><a href="#Footnote_13_13" class="fnanchor">13</a></span> Of course
all life on the islands was extinct. When Treub in 1886 first visited
the island, he found that blue-green algæ were the first colonists on
the pumice and on the exposed blocks of rock in the ravines on the
mountain slopes. Investigations made during subsequent expeditions
demonstrated the association of diatoms and bacteria. All of these were
probably carried by the wind. The algæ referred to were according to
Euler of the nostoc type. Nostoc does not require sugar, since it can
produce that compound from the CO<sub>2</sub> of the air by the activity of its
chlorophyll. This organism possesses also the power of assimilating
the free nitrogen of the air. From these observations and because
the <i class="taxonomic">Nostocaceæ</i> generally appear as the first settlers on sand the
conclusion has been drawn that they or the group of <i class="taxonomic">Schizophyceæ</i>
to which they belong formed the first settlers of our <span
class="nowrap">planet.<a name="FNanchor_14_14" id="FNanchor_14_14"></a><a href="#Footnote_14_14" class="fnanchor">14</a></span> This conclusion is not quite safe
since in the settlement of Krakatau as well as in the first colonizing
of sand<span class="pagenum" title="22"><a name="Page_22" id="Page_22"></a></span> areas the nature of the first settler is determined chiefly by
the carrying power of wind (or waves and birds).</p>
<p>We may now return from this digression to the real object of our
discussion, namely that the nutritive solutions of organisms must
be very dilute and consist of the split products of the complicated
compounds of which the organisms consist. The examples given
sufficiently illustrate this statement.</p>
<p>The nutritive medium of our body cells is the blood, and while we
take up as food the complicated compounds of plants or animals, these
substances undergo a digestion, <i>i. e.</i>, a splitting up into
small constituents before they can diffuse from the intestine into the
blood. Thus the proteins are digested down to the amino acids and these
diffuse into the blood as demonstrated by Folin and by Van Slyke. From
here the cells take them up. The different proteins differ in regard
to the different types of amino acids which they contain. While the
bacteria and fungi and apparently the higher plants can build up all
their different amino acids from ammonia, this power is no longer found
in the mammals which can form only certain amino acids in their body
and must receive the others through their food. As a consequence it
is usually necessary to feed young animals on more than one protein
in order to make them grow, since one protein, as a rule, does not
contain all the amino acids needed for the manufacture of all<span class="pagenum" title="23"><a name="Page_23" id="Page_23"></a></span> the
proteins required for the formation of the material of a growing <span
class="nowrap">animal.<a name="FNanchor_15_15" id="FNanchor_15_15"></a><a href="#Footnote_15_15" class="fnanchor">15</a></span></p>
<p>3. The essential difference between living and non-living matter
consists then in this: the living cell synthetizes its own complicated
specific material from indifferent or non-specific simple compounds of
the surrounding medium, while the crystal simply adds the molecules
found in its supersaturated solution. This synthetic power of
transforming small “building stones” into the complicated compounds
specific for each organism is the “secret of life” or rather one of the
secrets of life.</p>
<p>What clew have we in regard to the nature of this synthetic power?
We know that the comparatively great velocity of chemical reactions
in a living organism is due to the presence of enzymes (ferments) or
to catalytic agencies in general. Some of these catalytic agencies
are specific in the sense that a given catalyzer can accelerate
the reaction of only one step in a complicated chemical reaction.
While these enzymes are formed by the action of the body they can be
separated from the body without losing their catalytic efficiency. It
was a long time before scientists succeeded in isolating the enzyme of
the yeast cell which causes the alcoholic fermentation of sugar; and
this gave rise to the<span class="pagenum" title="24"><a name="Page_24" id="Page_24"></a></span> premature statement that it was not possible to
isolate this enzyme since it was bound up with the life of the yeast
cell. Such a statement was even made by a man like Pasteur, who was
usually a model of restraint in his utterances, and yet the work of
Buchner proved him to be wrong.</p>
<p>The general mechanism of the action of the hydrolyzing enzymes is
known. The old idea of de la Rive, that a molecule of enzyme combines
transitorily with a molecule of substrate; the further idea, which may
possibly go back to Engler, that the molecule of substrate is disrupted
in the “strain” of the new combination and that the broken fragments
fall off or are easily knocked off by collision from the ferment
molecule which is now ready to repeat the process, seems to be correct.
On the assumption that the velocity of enzyme reaction is proportional
to the mass of the enzyme and that de la Rive’s idea was correct,
Van Slyke and Cullen were able to calculate the coefficients of the
velocity of enzyme reactions for the fermentation of urea and other
substances, and the agreement between calculated and observed values
was <span class="nowrap">remarkable.<a name="FNanchor_16_16" id="FNanchor_16_16"></a><a href="#Footnote_16_16" class="fnanchor">16</a></span></p>
<p>While the hydrolytic action of enzymes is thus clear the synthesis
in the cell is still a riddle. An interesting suggestion was made by
van’t Hoff, who in 1898 expressed the idea that the hydrolytic enzymes
should<span class="pagenum" title="25"><a name="Page_25" id="Page_25"></a></span> also act in the opposite direction, namely synthetically.
Thus it should not only be possible to digest proteins with pepsin
but also to synthetize them from the products of digestion with the
aid of the same enzyme. This expectation was based on the idea that
the enzyme did not alter the equilibrium between the hydrolyzed and
non-hydrolyzed part of the substrate but only accelerated the rate
with which the equilibrium was reached. Van’t Hoff’s idea omitted,
however, the possibility that in the transitory combination between
enzyme molecule and substrate a change in the molecular configuration
of the substrate or in the distribution of intramolecular strain may
take place. The first apparently complete confirmation of van’t Hoff’s
suggestion appeared in the form of the synthesis of maltose from grape
sugar by the enzyme maltase, which decomposes maltose into grape sugar.
By adding the enzyme maltase from yeast to a forty per cent. solution
of glucose Croft <span class="nowrap">Hill<a name="FNanchor_17_17" id="FNanchor_17_17"></a><a href="#Footnote_17_17" class="fnanchor">17</a></span> obtained a good
yield of maltose. It turned out, however, that what he took for maltose
was not this compound but an isomer, namely isomaltose, which has a
different molecular configuration and cannot be hydrolyzed by the
enzyme maltase.</p>
<p>Lactose is hydrolyzed from kephyr by an enzyme lactase into galactose
and glucose; by adding this enzyme to galactose and glucose a synthesis
was<span class="pagenum" title="26"><a name="Page_26" id="Page_26"></a></span> obtained not of lactose but of isolactose; the latter, however, is
not decomposed by the enzyme lactase.</p>
<p>E. F. Armstrong has worked out a theory which tries to account for
this striking phenomenon by assuming “that the enzyme has a specific
influence in promoting the formation of the biose which it cannot <span
class="nowrap">hydrolyze.”<a name="FNanchor_18_18" id="FNanchor_18_18"></a><a href="#Footnote_18_18" class="fnanchor">18</a></span> The theory is very ingenious
and seems supported by fact. This then would lead to the result that
certain hydrolytic enzymes may have a synthetic action but not in the
manner suggested by van’t Hoff.</p>
<p>The principle enunciated by Armstrong, that in the synthetic action of
hydrolytic enzymes not the original compound but an isomer is formed
which can not be hydrolyzed by the enzyme, may possibly be of great
importance in the understanding of life phenomena. It shows us how
the cell can grow in the presence of hydrolytic enzymes and why in
hunger the disintegration of the cell material is so slow. It was at
first thought that the formation of isomers contradicted the idea of
the reversible action of enzymes, but this is not the case; on the
contrary, it supports it but makes an addition which may solve the
riddle of what Claude Bernard called the creative action of living
matter. We shall come back to this problem in the last chapter.</p>
<p>Kastle and Loevenhart demonstrated the synthesis of a trace of
ethylbutyrate by lipase if the latter enzyme<span class="pagenum" title="27"><a name="Page_27" id="Page_27"></a></span> was added to the
products of the hydrolysis of ethylbutyrate, ethyl alcohol, and
butyric acid by the same <span class="nowrap">enzyme.<a name="FNanchor_19_19" id="FNanchor_19_19"></a><a href="#Footnote_19_19" class="fnanchor">19</a></span> <span
class="nowrap">Taylor<a name="FNanchor_20_20" id="FNanchor_20_20"></a><a href="#Footnote_20_20" class="fnanchor">20</a></span> obtained the synthesis of a slight
amount of triolein</p>
<div class="blockquot">
<p>by the addition of the dried fat-free residue of the castor bean
to a mixture of oleinic acid and glycerine. . . .
No synthesis occurred with acetic, butyric, palmitic, and stearic
acids with glycerine, mannite, and dulcite, and the experiments
with the last two alcohols and oleinic acid likewise yielded no
synthesis.</p>
</div>
<p>This suggests possibly a specific action of the enzyme. If this
slight reversible action had any biological significance (which might
be possible, since in the organism secondary favourable conditions
might be at work which are lacking <i lang="la" xml:lang="la">in vitro</i>) there should be a
parallelism between masses of lipase in different kinds of tissues and
fat synthesis. Loevenhart indicated that this might be a fact, but a
more extensive investigation by H. C. Bradley has made this very <span
class="nowrap">dubious.<a name="FNanchor_21_21" id="FNanchor_21_21"></a><a href="#Footnote_21_21" class="fnanchor">21</a></span></p>
<p>Very little is known concerning the reversible action of the hydrolytic
protein enzymes. A. E. Taylor digested protamine sulphate with trypsin
and found that after adding trypsin to the products of digestion a
precipitate was formed after long standing; and we<span class="pagenum" title="28"><a name="Page_28" id="Page_28"></a></span> may also refer to
experiments of Robertson with pepsin on the products of caseinogen
to which we shall return in the next chapter. It therefore looks at
present as if van’t Hoff’s idea of reversible enzyme action might hold
in the modification offered by Armstrong. It remains doubtful, however,
whether this reversibility can explain all the synthetic processes in
the cell. No objection can be offered at present if any one makes the
assumption that each cell has specific synthetic enzymes or some other
synthetic mechanisms which are still unknown.</p>
<p>The mechanisms for the synthesis of proteins must have one other
peculiarity: they must be specific in their action. We shall see in the
next chapter that each species seems to possess one or more proteins
not found in any other but closely related species. Each organism
develops from a tiny microscopic germ and grows by synthetizing the
non-specific building stones (amino acids) into the specific proteins
of the species. This must be the work of the yet unknown synthetic
enzymes or mechanisms. The elucidation of their character would seem
one of the main problems of biology. Needless to say crystallography is
not confronted with problems of such a nature.</p>
<p>The fact that the living cell grows after taking up food has given
rise to curious misunderstandings. Traube has shown that drops of a
liquid surrounded with a semipermeable membrane may increase in<span class="pagenum" title="29"><a name="Page_29" id="Page_29"></a></span> volume
when put into a solution of lower osmotic pressure. This has led and
is possibly still leading to the statement that the process of growth
by a living cell has been imitated artificially. Only one feature has
been imitated, the increase in volume; but the essential feature of the
process in the living cell, <i>i. e.</i>, the formation of the specific
constituents of the living cell from non-specific products, has of
course not been imitated.</p>
<p>4. The constant synthesis then of specific material from simple
compounds of a non-specific character is the chief feature by which
living matter differs from non-living matter. With this character
is correlated another one; namely, when the mass of a cell reaches
a certain limit the cell divides. This is perhaps most obvious in
bacteria which on the proper nutritive medium take up food, grow, and
divide into two bacteria, each of which takes up food, divides, and
grows <i lang="la" xml:lang="la">ad infinitum</i>, as long as the food lasts, provided the harmful
products of metabolism are removed. If it be true that specific
synthetic ferments exist in each cell it follows that the cell must
synthetize these <span class="pagenum" title="30"><a name="Page_30" id="Page_30"></a></span><span class="nowrap">also,<a name="FNanchor_22_22" id="FNanchor_22_22"></a><a href="#Footnote_22_22" class="fnanchor">22</a></span> as otherwise
the synthesis of specific proteins would have to come to a standstill.</p>
<p>This problem of synthesis leads to the assumption of immortality of the
living cell, since there is no <i lang="la" xml:lang="la">a priori</i> reason why this synthesis
should ever come to a standstill of its own accord as long as enough
food is available and the proper outside physical conditions are
guaranteed. It is well known that Weismann has claimed immortality for
all unicellular organisms and for the sex cells of metazoa, while he
claimed the necessity of death for the body cells of the latter. Leo
Loeb was led by his investigations on the transplantation of cancer to
assume immortality not only for the cancer cell but also for the body
cell of the organism. He had found in transplanting a malignant tumor
from one individual to another that the tumor grew; that it was not
the cells of the host but the transplanted tumor cells of the graft
which grew and multiplied, and that this process could be repeated
apparently indefinitely so that it was obvious that the transplanted
tumor cells outlived the original animal. Such experiments have since
been carried on so long that we may now say that an individual cancer
cell taken from an animal and transplanted from time to time on a new
host lives apparently indefinitely. Leo Loeb had found that these
tumor cells are simply modified somatic cells. He therefore suggested
that the somatic cells might be considered immortal with the same
right<span class="pagenum" title="31"><a name="Page_31" id="Page_31"></a></span> as we speak of the immortality of the germ cells of such <span
class="nowrap">animals.<a name="FNanchor_23_23" id="FNanchor_23_23"></a><a href="#Footnote_23_23" class="fnanchor">23</a></span></p>
<p>This view receives its support first from the fact that certain trees
like the <i class="taxonomic">Sequoia</i> live several thousand years and may therefore be
considered immortal and second, from the method of tissue culture.
The method of cultivating tissue cells in a test tube, in the same
way as is done for bacteria, was first proposed and carried out by
Leo Loeb, in <span class="nowrap">1897,<a name="FNanchor_24_24" id="FNanchor_24_24"></a><a href="#Footnote_24_24" class="fnanchor">24</a></span> but his test-tube
method did not permit the observation of the transplanted cell under
the microscope. This was made possible by a modification of the method
by Harrison, who established the fact that the axis cylinder grows
out from the ganglionic cell. Harrison and Burrows then perfected the
method for the cultivation of the cells of warm-blooded, animals,
and with the aid of these methods Carrel succeeded in keeping
connective-tissue cells of the heart of an early chick embryo alive
more than four years, and these cells are still growing and <span
class="nowrap">dividing.<a name="FNanchor_25_25" id="FNanchor_25_25"></a><a href="#Footnote_25_25" class="fnanchor">25</a></span> Only very tiny masses of cells can
be kept alive in this way since all the cells in the centre of a piece
die on account of lack of oxygen;<span class="pagenum" title="32"><a name="Page_32" id="Page_32"></a></span> and every two days a few cells from
the margin of the piece have to be transferred to a new culture medium.</p>
<p>This effect of lack of oxygen explains also why the immortality of
the somatic cells is not obvious. Death in a human being consists in
the stopping of heart beat and respiration, which also terminates the
action of the brain or at least of consciousness. Immediately after the
cessation of heart beat and respiration the cells of muscle and of the
skin and probably many or most other organs are still alive and might
continue to live if transferred to another body with circulation and
respiration. As a consequence of the lack of oxygen supply in the dead
body they will, however, die comparatively rapidly. It may be stated
that hearts taken out of the body after a number of hours can still
beat again when put into the proper solutions and upon receiving an
adequate oxygen supply.</p>
<p>The idea that the body cells are naturally immortal and die only if
exposed to extreme injuries such as prolonged lack of oxygen or too
high a temperature helps to make one problem more intelligible. The
medical student, who for the first time realizes that life depends upon
that one organ, the heart, doing its duty incessantly for the seventy
years or so allotted to man, is amazed at the precariousness of our
existence. It seems indeed uncanny that so delicate a mechanism should
function so regularly for so many years. The<span class="pagenum" title="33"><a name="Page_33" id="Page_33"></a></span> mysticism connected with
this and other phenomena of adaptation would disappear if we could be
certain that all cells are really immortal and that the fact which
demands an explanation is not the continued activity but the cessation
of activity in death. Thus we see that the idea of the immortality of
the body cell if it can be generalized may be destined to become one
of the main supports for a complete physicochemical analysis of life
phenomena since it makes the durability of organisms intelligible.</p>
<p>5. This generalized idea of the immortality of some or possibly most
or all somatic cells has a bearing upon the problem of the origin of
life on our planet. The experiments of Spallanzani, Schwann, Schroeder,
Pasteur, Tyndall, and all those who have worked with pure cultures of
micro-organisms, have proved that no spontaneous generation of living
from non-living matter can be demonstrated; and the statements to the
contrary were due to experimental errors inasmuch as the new organisms
formed were the offspring of others which had entered into the culture
medium by mistake.</p>
<p>In the last chapter of that most fascinating book <cite>Worlds in the</cite>
<span class="nowrap"><cite>Making</cite>,<a name="FNanchor_26_26" id="FNanchor_26_26"></a><a href="#Footnote_26_26" class="fnanchor">26</a></span> Arrhenius discusses the
possibility of life being eternal and of living germs of very small
dimensions—<i>e. g.</i>, the spores of micro-organisms—being carried
through space from one planet to another<span class="pagenum" title="34"><a name="Page_34" id="Page_34"></a></span> or even from one solar system
to another. If it be true that there is no spontaneous generation;
if it be true that all cells are potentially immortal, we may indeed
seriously raise the question: May not life after all be eternal? Such
ideas were advocated by Richter in a rather phantastic way and more
definitely by Helmholtz as well as Kelvin. The latter authors assumed
that in the collision of planets or worlds on which there is life,
fragments containing living organisms will be torn off and these
fragments will move as seed-bearing stones through space. “If at the
present instant no life existed upon this earth, one such stone falling
upon it might . . . lead to its becoming covered with
vegetation.” Arrhenius points out the difficulties which oppose such
a view, as, <i>e. g.</i>, the fact “that the meteorite in its fall
towards the earth becomes incandescent all over its surface and any
seeds on it would therefore be deprived of their germinating power.”</p>
<p>Arrhenius suggests another and much more ingenious idea based on the
fact that for particles below a certain size the mechanical pressure
produced by light waves—the radiation pressure—can overcome the
attractive force of gravitation.</p>
<div class="blockquot">
<p>Bodies which according to Schwarzschild would undergo the strongest
influence of solar radiation must have a diameter of 0.00016 mm.
supposing them to be spherical. The first question is therefore:
Are there any living seeds of such extraordinary minuteness? The
reply of the botanist<span class="pagenum" title="35"><a name="Page_35" id="Page_35"></a></span> is that spores of many bacteria have a size
of 0.0003 or 0.0002 mm., and there are no doubt much smaller germs
which our microscopes fail to disclose.</p>
</div>
<p>This assumption is undoubtedly correct.</p>
<div class="blockquot">
<p>We will, in the first instance, make a rough calculation of
what would happen if such an organism were detached from the
earth and pushed out into space by the radiation pressure of
our sun. The organism would first of all have to cross the
orbit of Mars; then the orbits of the smaller and of the outer
planets. . . . The organisms would cross the orbit
of Mars after twenty days, the Jupiter orbit after eighty days,
and the orbit of Neptune after fourteen months. Our nearest solar
system would be reached in nine thousand years.</p>
</div>
<p>For the assumption of eternity of life only the transference of germs
from one solar system to another would have to be considered and the
question arises whether or not germs can keep their vitality so many
thousands of years. Arrhenius thinks that this is possible on account
of the low temperature (which must be below -220° C.) at which no
chemical reaction and hence no decomposition and deterioration are
possible in the spores; and on account of the absence of water vapour.</p>
<p>The question then arises: Have we any facts to warrant the assumption
that spores may remain alive for thousands of years under such
conditions and retain their power of germination? We know that seeds
have a very limited vitality, and the statement that<span class="pagenum" title="36"><a name="Page_36" id="Page_36"></a></span> grain found
in the Egyptian tombs was still able to germinate has long been
recognized as a myth. Miss <span class="nowrap">White<a name="FNanchor_27_27" id="FNanchor_27_27"></a><a href="#Footnote_27_27" class="fnanchor">27</a></span>
found that in wheat grains, there appeared a well-marked drop in
their germinating power after about the fourth year, reaching zero
in eleven to seventeen years. In a drier climate they last longer
than in a moist climate. It is of importance that the hydrolyzing
enzymes in the seeds, such as diastase, erepsin, remained unimpaired
even after the germinating power of the seeds had disappeared. The
seeds were able to resist for two days the temperature of liquid air,
though the subsequent germination was delayed by this treatment. <span
class="nowrap">Macfadyen<a name="FNanchor_28_28" id="FNanchor_28_28"></a><a href="#Footnote_28_28" class="fnanchor">28</a></span> exposed non-sporing bacteria, viz.,
<i class="taxonomic">B. typhosus</i>, <i class="taxonomic">B. coli communis</i>, <i class="taxonomic">Staphylococcus pyogenes aureus</i>,
and a <i class="taxonomic">Saccharomyces</i> to liquid air.</p>
<div class="blockquot">
<p>The experiments showed that a prolonged exposure of six months
to a temperature of about -190° has no appreciable effect on the
vitality of micro-organisms. To judge by the results there appeared
no reason to doubt that the experiment might have been successfully
prolonged for a still longer period.</p>
</div>
<p>Paul <span class="nowrap">Becquerel<a name="FNanchor_29_29" id="FNanchor_29_29"></a><a href="#Footnote_29_29" class="fnanchor">29</a></span> found that seeds which
possess a very thick integument may live longer than the grain in Miss
White’s experiments. The thickness of the integument prevents the
exchange of gases between air<span class="pagenum" title="37"><a name="Page_37" id="Page_37"></a></span> and seed. Thus seeds of leguminoses
(<i class="taxonomic">Cassia bicapsularis</i>, <i class="taxonomic">Cytisus biflorus</i>, <i class="taxonomic">Leucæna leucocephala</i>,
and <i class="taxonomic">Trifolium arvense</i>) had retained their power of germination
for eighty-seven years. Becquerel has shown that the dryness of the
membrane is very essential for such a duration of life, since when dry
it is impermeable for gases and the slow chemical reactions inside the
grain become impossible.</p>
<p>In the cosmic space there is no water vapour, no atmosphere, and a
low temperature, and there is hence no reason why spores should lose
appreciably more of their germinating power in ten thousand years than
in six months. We must therefore admit the possibility that spores may
move for an almost infinite length of time through cosmic space and yet
be ready for germination when they fall upon a planet in which all the
conditions for germination and development exist, <i>e. g.</i>, water,
proper temperature, and the right nutritive substances dissolved in the
water (inclusive of free oxygen).</p>
<p>While thus everything is favourable to Arrhenius’s hypothesis,
Becquerel raises the objection that the spores going through space
would yet be destroyed by ultraviolet light. This danger would
probably exist only as long as the germ is not too far from a sun. The
difficulty is a real one since the ultraviolet rays have a destructive
effect even in the absence of oxygen. It is possible, however, that
there are spores which can<span class="pagenum" title="38"><a name="Page_38" id="Page_38"></a></span> resist this effect of ultraviolet light.
Arrhenius’s theory can not of course be disproved and we must agree
with him that it is consistent not only with the theories of cosmogony
but also with the seeming potential immortality of certain or of all
cells.</p>
<p>The alternative to Arrhenius’s theory is that living matter did
originate and still originates from non-living matter. If this idea is
correct it should one day be possible to discover synthetic enzymes
which are capable of forming molecules of their own kind from a simple
nutritive solution. With such synthetic enzymes as a starting point
the task might be undertaken of creating cells capable of growth and
cell division, at least in the apparently simple form in which these
phenomena occur in bacteria; viz., that after the mass has reached a
certain (still microscopic) size it divides into two cells and so on.
If Arrhenius is right that living matter has had no more beginning
than matter in general, this hope of making living matter artificially
appears at present as futile as the hope of making molecules out of
electrons.</p>
<p>The problem of making living matter artificially has been compared to
that of constructing a <i lang="la" xml:lang="la">perpetuum mobile</i>; this comparison is, however,
not correct. The idea of a <i lang="la" xml:lang="la">perpetuum mobile</i> contradicts the first law
of thermodynamics, while the making of living matter may be impossible
though contradicting no natural law.</p>
<p>Pasteur’s proof that spontaneous generation does<span class="pagenum" title="39"><a name="Page_39" id="Page_39"></a></span> not occur in the
solutions used by him does not prove that a synthesis of living
from dead matter is impossible under any conditions. It is at least
not inconceivable that in an earlier period of the earth’s history
radio-activity, electrical discharges, and possibly also the action
of volcanoes might have furnished the combination of circumstances
under which living matter might have been formed. The staggering
difficulties in imagining such a possibility are not merely on the
chemical side—<i>e. g.</i>, the production of proteins from CO<sub>2</sub>,
and N—but also on the physical side if the necessity of a definite
cell structure is considered. We shall see in the sixth chapter that
without a structure in the egg to begin with, no formation of a
complicated organism is imaginable; and while a bacterium may have a
simple structure, such a structure as it possesses is as necessary for
its existence as are its enzymes.</p>
<p>Attempts have repeatedly been made to imitate the structures in the
cell and of living organisms by colloidal precipitates. It is needless
to point out that such precipitates are of importance only for the
study of the origin of structures in the living, but that they are
not otherwise an imitation of the living since they are lacking the
characteristic synthetic chemical processes.</p>
<hr class="chap" />
<p><span class="pagenum" title="40"><a name="Page_40" id="Page_40"></a></span></p>
<h2>CHAPTER III</h2>
<h3>THE CHEMICAL BASIS OF GENUS AND SPECIES</h3>
<p>1. It is a truism that from an egg of a species an organism of this
species only and of no other will arise. It is also a truism that
the so-called protoplasm of an egg does not differ much from that
of eggs of other species when looked at through a microscope. The
question arises: What determines the species of the future organism?
Is it a structure or a specific chemical or groups of chemicals? In a
later chapter we shall show that the egg has a simple though definite
structure, but in this chapter we shall see that the egg must contain
specific substances and that these substances which determine the
“species” and specificity in general are in all probability proteins.
Since solutions of different proteins look alike under a microscope we
need not wonder that it is impossible to discriminate microscopically
between the protoplasm of different eggs.</p>
<p>The idea of definiteness and constancy of species, a matter of daily
observation in the case of man and<span class="pagenum" title="41"><a name="Page_41" id="Page_41"></a></span> higher animals in general, was
not so readily accepted in the case of the micro-organisms, which on
account of their minuteness and simplicity of structure are not so
easy to differentiate. There existed for a long time serious doubt
whether or not the simplest organisms, the bacteria, possessed a
definite “specificity” like the higher organisms, or whether they
were not endowed, as Warming put it, with an “unlimited plasticity,”
which forbade classifying them according to their form into definite
species as Cohn had done. An interesting episode in this discussion,
which was settled about twenty-five years ago arose concerning the
sulphur bacteria, which often develop in large masses on parts of
decaying plants or animals along the shore. Sir E. Ray Lankester
found collections of red bacteria covering putrefying animal matter
in a vessel and forming a continuous membrane along its wall. These
red bacteria were of very different shape, size, and grouping, but
they seemed to be connected by transition forms. They had a common
character, however, namely, their peach-coloured appearance. This
common character, together with their association in the same habitat,
led Lankester to the then justifiable belief that they all belonged to
one species which was protean in character and that the different forms
were only to be considered as phases of growth of this one species. The
presence of the same red pigment “<i>Bacterio-purpurin</i>” seemed justly
to indicate the existence of<span class="pagenum" title="42"><a name="Page_42" id="Page_42"></a></span> common chemical processes. Cohn, on the
contrary, considered the different forms among these red bacteria (they
are today called sulphur bacteria since they oxidize the hydrogen
sulphide produced by bacteria of putrefaction to sulphur and sulphates)
as definite and distinct species, in spite of their common colour and
their association. Later observations showed that Cohn was right.
<span class="nowrap">Winogradsky<a name="FNanchor_30_30" id="FNanchor_30_30"></a><a href="#Footnote_30_30" class="fnanchor">30</a></span> succeeded in proving by
pure culture experiments that each of these different forms of sulphur
bacteria was specific and did not give rise to any of the other forms
of the same colour found in the same conditions.</p>
<p>The method of pure line breeding inaugurated by <span
class="nowrap">Johannsen<a name="FNanchor_31_31" id="FNanchor_31_31"></a><a href="#Footnote_31_31" class="fnanchor">31</a></span> has shown that the degree of
definiteness goes so far that apparently identical forms with only
slight differences in size may breed true to this size; but for reasons
which will become clear later on we may doubt whether they are to be
considered as definite species.</p>
<p>The fact of specificity is supported by the fact of constancy of forms.
de Vries has pointed out that regardless of the possible origin of new
species by mutation the old species may persevere. Walcott has found
fossils of annelids, snails, crustaceans, and algæ in a precambrian
formation in British Columbia whose age<span class="pagenum" title="43"><a name="Page_43" id="Page_43"></a></span> (estimated on the rate of
formation of radium from uranium) may be about two hundred million
years and estimated on the basis of sedimentation sixty million years.
And yet these invertebrates are so closely related to the forms
existing today that the systematists have no difficulty in finding
the genus among the modern forms into which each of these organisms
belongs. W. M. Wheeler, in his investigations of the ants enclosed
in amber, was able to identify some of them with forms living today,
though the ants observed in the amber must have been two million
years old. The constancy of species, <i>i. e.</i>, the permanence of
specificity may therefore be considered as established as far back
as two or possibly two hundred millions of years. The definiteness
and constancy of each species must be determined by something equally
definite and constant in the egg, since in the latter the species is
already fixed irrevocably.</p>
<p>We shall show first that species if sufficiently separated are
generally incompatible with each other and that any attempt at fusing
or mixing them by grafting or cross-fertilizing is futile. In the
second part of the chapter we shall take up the facts which seem
destined to give a direct answer to the question as to the cause of
specificity. It is needless to say that this latter question is of
paramount importance for the problem of evolution, as well as for that
of the constitution of living matter.</p>
<p><span class="pagenum" title="44"><a name="Page_44" id="Page_44"></a></span></p>
<h4><i>I. The Incompatibility of Species not closely Related</i></h4>
<p>2. It is practically impossible to transplant organs or tissues from
one species of higher animals to another, unless the two species
are very closely related; and even then the transplantation is
uncertain and the graft may either fall off again or be destroyed.
This specificity of tissues goes so far that surgeons prefer, when a
transplantation of skin in the human is intended, to use skin of the
patient or of close blood relations. The reason why the tissues of a
foreign species in warm-blooded animals cannot grow well on a given
host has been explained by the remarkable experiments of James B.
Murphy of the Rockefeller <span class="nowrap">Institute.<a name="FNanchor_32_32" id="FNanchor_32_32"></a><a href="#Footnote_32_32" class="fnanchor">32</a></span>
Murphy discovered that it is possible to transplant successfully any
kind of foreign tissue upon the early embryo of the chick. Even human
tissue transplanted upon the chick embryo will grow rapidly. This
shows that at this early stage the chick embryo does not yet react
against foreign tissue. This lack of reaction lasts until about the
twenty-first day in the life of the embryo; then the growth of the
graft not only ceases but the graft itself falls off or is destroyed.
Murphy noticed that this critical period coincides with the development
of the spleen and of lymphatic tissue in the chick and that a certain
type of migrating cells,<span class="pagenum" title="45"><a name="Page_45" id="Page_45"></a></span> the so-called lymphocytes, which develop
in the lymphatic tissue, gather at the edge of the graft in great
numbers, and he suggested that these lymphocytes (by a secretion of
some substance?) rid the host of the graft. He applied two tests
both of which confirmed this idea. First he showed that when small
fragments of the spleen of an adult chicken are transplanted into the
embryo the latter loses its tolerance for foreign grafts. The second
proof is still more interesting. It was known that by treatment with
Roentgen rays the lymphocytes in an animal could be destroyed. It was
to be expected that an animal so treated would have lost its specific
resistance to foreign tissues. Murphy found that this was actually the
case. On fully grown rats in which the lymphocytes had been destroyed
by X-rays (as ascertained by blood counts) tissues of foreign species
grew perfectly well. These experiments have assumed a great practical
importance since they can also be applied to the immunization of an
animal against transplanted cancer of its own species. Murphy found
that by increasing the number of lymphocytes in an animal (which can
be accomplished by a mild treatment with X-rays) the immunity against
foreign grafts as well as against cancer from the same species can
be increased. It is quite possible that the apparent immunity to a
transplantation of cancer produced by Jensen, Leo Loeb, and Ehrlich
and Apolant through the previous transplantation of tissue in such an
animal<span class="pagenum" title="46"><a name="Page_46" id="Page_46"></a></span> was due to the fact that this previous tissue transplantation
led to an increase in the number of lymphocytes in the animal. The
medical side, however, lies outside of our discussion, and we must
satisfy ourselves with only a passing notice. The facts show that
each warm-blooded animal seems to possess a specificity whereby its
lymphocytes destroy transplanted tissue taken from a foreign species.</p>
<p>A lesser though still marked degree of incompatibility exists
also in lower animals for grafts from a different <span
class="nowrap">species.<a name="FNanchor_33_33" id="FNanchor_33_33"></a><a href="#Footnote_33_33" class="fnanchor">33</a></span> The graft may apparently take hold,
but only for a few days, if the species are not closely related. Joest
apparently succeeded in making a permanent union between the anterior
and posterior ends of two species of earthworms, <i class="taxonomic">Lumbricus rubellus</i>
and <i class="taxonomic">Allolobophora terrestris</i>. Born and later Harrison healed pieces
of tadpoles of different species together. An individual made up of two
species <i class="taxonomic">Rana virescens</i> and <i class="taxonomic">Rana palustris</i> lived a considerable time
and went through metamorphosis. Each half regained the characteristic
features of the species to which it belonged. It seems, however, that
if species of tadpoles of two more distant species are grafted upon
each other no lasting graft can be obtained, <i>e. g.</i>, <i class="taxonomic">Rana
esculenta</i> and <i class="taxonomic">Bombinator igneus</i>. These experiments were made at
a time when the nature and bearing of the problem of<span class="pagenum" title="47"><a name="Page_47" id="Page_47"></a></span> specificity
was not yet fully recognized. The rôle of lymphocytes in these cases
has never been investigated. The grafted piece always retained the
characteristics of the species from which it was taken.</p>
<p>Plants possess no leucocytes and we therefore see that they tolerate
a graft of foreign tissues better than is the case in animals. As
a matter of fact heteroc grafting is a common practice in
horticulture, although even here it is known that indiscriminate
heteroplastic grafting is not feasible and that therefore the
specificity is not without influence. The host is supposed to furnish
only nutritive sap to the graft and in this respect does not behave
very differently from an artificial nutritive solution for the raising
of a plant. The law of specificity, however, remains true also for the
grafted tissues: neither in animals nor in plants does the graft lose
its specificity, and it never assumes the specific characters of the
host, or <i lang="la" xml:lang="la">vice versa</i>. The apparent exceptions which Winkler believed
he had found in the case of grafts of nightshade on tomatoes turned
out to be a further proof of the law of specificity. Winkler, after
the graft had taken, cut through the place of grafting, after which
operation a callus formation occurred on the wound. In most cases
either a pure nightshade or a pure tomato grew out from this callus. In
some cases he obtained shoots from the place where graft and host had
united, which on one side were tomato, on the other side nightshade.
What<span class="pagenum" title="48"><a name="Page_48" id="Page_48"></a></span> really happened was that the shoots had a growing point whose
cells on the one side consisted of cells of nightshade, on the other
side of <span class="nowrap">tomato.<a name="FNanchor_34_34" id="FNanchor_34_34"></a><a href="#Footnote_34_34" class="fnanchor">34</a></span> We know of no case in
which the cell of a graft has lost its specificity and undergone a
transformation into the cell of the host.</p>
<p>3. Another manifestation of the incompatibility of distant species
is found in the domain of fertilization. The eggs of the majority of
animals cannot develop unless a spermatozoön enters. The entrance
of a spermatozoön into an egg seems also to fall under the law of
specificity, inasmuch as in general only the sperm of the same
or a closely related species is able to enter the egg. The <span
class="nowrap">writer<a name="FNanchor_35_35" id="FNanchor_35_35"></a><a href="#Footnote_35_35" class="fnanchor">35</a></span> has found, however, that it is
possible to overcome the limitation of specificity in certain cases
by physicochemical means, and by the knowledge of these means we
may perhaps one day be able to more closely define the mechanism
of specificity in this case. He found that the eggs of a certain
Californian sea urchin, which cannot be fertilized by the sperm of
starfish in normal sea water, will lose their specificity towards
this type of foreign sperm if the sea water is rendered a little more
alkaline, or if a little more Ca is added to the sea water, or if both
these variations are effected. Godlewski has confirmed the efficiency
of this method for the fertilization of sea-urchin eggs with the sperm
of crinoids. </p>
<table class="figrt" summary="figures 1-2">
<tr><td><div class="figcenter" style="width: 340px;">
<img src="images/fig_001.png" width="340" height="146" alt="" />
<p><span class="smcap">Fig. 1.</span> Five-days-old larvæ
from a sea urchin (Strongylocentrotus purpuratus) ♀ and a starfish
(Asterias) ♂. (Front view.)</p></div></td></tr>
<tr><td><div class="figcenter" style="width: 340px;">
<img src="images/fig_002.png" width="340" height="141" alt="" />
<p><span class="smcap">Fig. 2.</span> Five-days-old
larvæ of Strongylocentrotus purpuratus produced by artificial
parthenogenesis. (Side view.) The larvæ in Figs. 1 and 2 are identical
in appearance, proving that heterogeneous hybridization leads to a
larva with purely maternal characters.</p></div></td></tr>
</table>
<div class="figleft" style="width: 375px;">
<img src="images/fig_003.png" width="375" height="143" alt="" />
<p><span class="smcap">Fig. 3.</span> Five-days-old larvæ
of two closely related forms of sea urchins (S. purpuratus ♀ and S.
franciscanus ♂). In this case the larva has also paternal characters as
shown by the skeleton.</p></div>
<p><span class="pagenum" title="49"><a name="Page_49" id="Page_49"></a></span></p>
<p>If such heterogeneous hybridizations are carried out, two striking
results are obtained. The one is that the resulting larva has only
maternal characteristics (Figs. 1 and 2), as if the sperm had
contributed no hereditary material to the developing embryo. This
result could not have been predicted, for if we fertilize the egg of
the same Californian sea urchin, <i class="taxonomic">Strongylocentrotus purpuratus</i>, with
the sperm of a very closely<span class="pagenum" title="50"><a name="Page_50" id="Page_50"></a></span> related sea urchin, <i class="taxonomic">S. franciscanus</i>, the
hereditary effect of the spermatozoön is seen very distinctly in the
primitive skeleton formed by the <span class="nowrap">larva.<a name="FNanchor_36_36" id="FNanchor_36_36"></a><a href="#Footnote_36_36" class="fnanchor">36</a></span>
(Fig. 3.) In the case of the heterogeneous hybridization the
spermatozoön acts practically only as an activating agency upon the egg
and not as a transmitter of paternal qualities.</p>
<p>The second striking fact is that while the sea-urchin eggs fertilized
with starfish sperm develop at first perfectly normally they begin to
die in large numbers on the second and third day of their development,
and only a very small number live long enough to form a skeleton; and
these are usually sickly and form the skeleton considerably later than
the pure breed. It is not quite certain whether the sickliness of these
heterogeneous hybrids begins or assumes a severe character<span class="pagenum" title="51"><a name="Page_51" id="Page_51"></a></span> with the
development of a certain type of wandering cells, the mesenchyme cells;
it would perhaps be worth while to investigate this possibility. The
writer was under the impression that this sickliness might have been
brought about by a poison gradually formed in the heterogeneous larvæ.</p>
<p>He investigated the effects of heterogeneous hybridization also in
fishes, which are a much more favourable object. The egg of the marine
fish <i class="taxonomic">Fundulus heteroclitus</i> can be fertilized with the sperm of almost
any other teleost fish, as <span class="nowrap">Moenkhaus<a name="FNanchor_37_37" id="FNanchor_37_37"></a><a href="#Footnote_37_37" class="fnanchor">37</a></span>
first observed. This author did not succeed in keeping the hybrids
alive more than a day, but the writer has kept many heterogeneous
hybrids alive for a month or <span class="nowrap">longer,<a name="FNanchor_38_38" id="FNanchor_38_38"></a><a href="#Footnote_38_38" class="fnanchor">38</a></span>
and found the same two striking facts which he had already observed
in the heterogeneous cross between sea urchin and starfish: first,
practically no transmission of paternal characters, and second, a
sickly condition of the embryo which begins early and which increases
with further development. The heterogeneous fish hybrids between,
<i>e. g.</i>, <i class="taxonomic">Fundulus heteroclitus</i> ♀ and <i class="taxonomic">Menidia</i> ♂ have usually
no circulation of blood, although the heart is formed and beats and
blood-vessels and blood cells are formed; the eyes are often incomplete
or abnormal though they may be normal at first; the growth of the
embryo is mostly retarded.<span class="pagenum" title="52"><a name="Page_52" id="Page_52"></a></span> In exceptional cases circulation may be
established and in these a normal embryo may result, but such an embryo
is chiefly maternal.</p>
<p>This incompatibility of two gametes from different species does not
show itself in the case of heterogeneous hybridization only, but also
though less often in the case of crossing between two more closely
related forms. The cross between the two related forms <i class="taxonomic">S. purpuratus</i>
♀ and <i class="taxonomic">S. franciscanus</i> ♂ is very sturdy and shows no abnormal
mortality as far as the writer’s observations go. If, however, the
reciprocal crossing is carried out, namely that of <i class="taxonomic">S. franciscanus</i>
♀ and <i class="taxonomic">S. purpuratus</i> ♂, the development is at first normal, but
beginning with the time of mesenchyme formation the majority of larvæ
become sickly and die; and again the question may be raised whether
or not the beginning of sickliness coincides with the development of
mesenchyme cells. If we assume that the sickliness and death are due to
the formation of a poison, we must assume that the poison is formed by
the protoplasm of the egg, since otherwise we could not understand why
the reciprocal cross should be healthy.</p>
<p>All of these data agree in this one point, that the fusion by grafting
or fertilization of two distant species is impossible, although the
mechanism of the incompatibility is not yet understood. It is quite
possible that this mechanism is not the same in all the cases mentioned
here, and that it may be different when two<span class="pagenum" title="53"><a name="Page_53" id="Page_53"></a></span> different species are
mixed and when incompatibility exists between varieties, as is the case
in the graft on mammals.</p>
<h4>II. <i>The Chemical Basis of Genus and Species and of Species Specificity</i></h4>
<p>4. Fifty or sixty years ago surgeons did not hesitate to transfuse
the blood of animals into human beings. The practice was a failure,
and <span class="nowrap">Landois<a name="FNanchor_39_39" id="FNanchor_39_39"></a><a href="#Footnote_39_39" class="fnanchor">39</a></span> showed by experiment
that if blood of a foreign species was introduced into an animal the
blood corpuscles of the transfused blood were rapidly dissolved and
the animal into which the transfusion was made was rendered ill and
often died. The result was different when the animals whose blood
was used for the purpose of transfusion belonged to the same species
or a species closely related to the animal into which the blood was
transfused. Thus when blood was exchanged between horse and donkey or
between wolf and dog or between hare and rabbit no hemoglobin appeared
in the urine and the animal into which the blood was transfused
remained <span class="nowrap">well.<a name="FNanchor_40_40" id="FNanchor_40_40"></a><a href="#Footnote_40_40" class="fnanchor">40</a></span> This was the beginning
of the investigations in the field of serum specificity which were
destined to play such a prominent rôle in the development of medicine.
Friedenthal was able to show later that if to<span class="pagenum" title="54"><a name="Page_54" id="Page_54"></a></span> 10 c.c. of serum of a
mammal three drops of defibrinated blood of a foreign species are added
and the whole is exposed in a test tube to a temperature of 38°C. for
fifteen minutes the blood cells contained in the added blood are all
cytolyzed; that this, however, does not occur so rapidly when the blood
of a related species is used. He could thus show that human blood serum
dissolves the erythrocytes of the eel, the frog, pigeon, hen, horse,
cat, and even that of the lower monkeys but not that of the anthropoid
apes. The blood of the chimpanzee and of the human are no longer
incompatible, and this discovery was justly considered by Friedenthal
as a confirmation of the idea of the evolutionists that the anthropoid
apes and the human are blood <span class="nowrap">relations.<a name="FNanchor_41_41" id="FNanchor_41_41"></a><a href="#Footnote_41_41" class="fnanchor">41</a></span></p>
<p>This line of investigation had in the meanwhile entered upon a new
stage when Kraus, Tchistowitch, and Bordet discovered and developed the
precipitin reaction, which consists in the fact that if a foreign serum
(or a foreign protein) is introduced into an animal the blood serum of
the latter acquired after some time the power of causing a precipitate
when mixed with the antigen, <i>i. e.</i>, with the foreign substance
originally introduced into the animal for the purpose of causing the
production of antibodies in the latter; while, of course, no such
precipitation occurs if the serum of a<span class="pagenum" title="55"><a name="Page_55" id="Page_55"></a></span> non-treated rabbit is mixed
with the serum of the blood of the foreign species.</p>
<p>In 1897 Kraus discovered that if the filtrates from cultures of
bacteria (<i>e. g.</i>, typhoid bacillus) are mixed with the serum of
an animal immunized with the same serum (<i>e. g.</i>, typhoid serum)
it causes a precipitate; and that this precipitin reaction is specific.
This fact was confirmed and has been extended by the work of many
authors.</p>
<p>Tchistowitch in 1899 observed that the serum of rabbits which had
received injections of horse or eel serum caused a precipitate when
mixed with the serum of these latter animals.</p>
<p>Bordet found in 1899 that if milk is injected into a rabbit the serum
of such a rabbit acquires the power of precipitating casein, and Fish
found that this reaction is specific inasmuch as the lactoserum from
cow’s milk can precipitate only the casein of cow’s milk but not that
of human or goat milk. Wassermann and Schütze reached the same result
independently of each other.</p>
<p>Myers and later Uhlenhuth showed that if white of egg from a hen’s egg
is injected into a rabbit, precipitins for white of egg are found in
the serum of the latter, and <span class="nowrap">Uhlenhuth<a name="FNanchor_42_42" id="FNanchor_42_42"></a><a href="#Footnote_42_42" class="fnanchor">42</a></span>
found, by trying the white of egg of different species of birds, that
the precipitin reaction<span class="pagenum" title="56"><a name="Page_56" id="Page_56"></a></span> called forth by the blood of the immunized
animal is specific, inasmuch as the proteins from a hen’s egg will call
forth the formation of precipitins in the blood of the rabbit which
will precipitate only the white of egg of the hen or of closely related
birds.</p>
<p>To <span class="nowrap">Nuttall<a name="FNanchor_43_43" id="FNanchor_43_43"></a><a href="#Footnote_43_43" class="fnanchor">43</a></span> belongs the credit of
having worked out a quantitative method for measuring the amount
of precipitate formed, and in this way he made it possible to draw
more valid conclusions concerning the degree of specificity of the
precipitin reaction. He found by this method that when the immune
serum is mixed with the serum or the protein solution used for the
immunization a maximum precipitate is formed, but if it is mixed
with the serum of related forms a quantitatively smaller precipitate
is produced. In this way the degree of blood relationship could be
ascertained. He thus was able to show that when the blood of one
species, <i>e. g.</i>, the human, was injected into the blood of a
rabbit, after some time the serum of the rabbit was able to cause a
precipitate not only with the serum of man, or chimpanzee, but also of
some lower monkeys; with this difference, however, that the precipitate
was much heavier when the immune serum was added to the serum of
man. The method thus shows the existence of not an absolute but of a
strong quantitative specificity of blood serum. This statement may<span class="pagenum" title="57"><a name="Page_57" id="Page_57"></a></span> be
illustrated by the following table from Nuttall. The antiserum used
for the precipitin reaction was obtained by treating a rabbit with
human blood serum. The forty-five bloods tested had been preserved for
various lengths of time in the refrigerator with the addition of a
small amount of chloroform.</p>
<p class="tac">TABLE II</p>
<p class="tac"><span class="smcap">Quantitative Tests with Anti-Primate Sera</span></p>
<p class="tac"><i>Tests with Antihuman Serum</i></p>
<table width="80%" summary="Precipitin reactions by various species against anti-human serum">
<col width="38%" /><col width="2%" /><col width="20%" /><col width="35%" />
<tr><th class="btr" colspan="2"><span class="smcap">Blood of</span></th><th class="ball"><i>Precipitum<br />Amount</i></th><th class="btl"><i>Percentage</i></th></tr>
<tr><td class="bt pt03"><i>Primates</i></td><td class="btr"></td><td></td><td class="btl"></td></tr>
<tr><td class="pl10">Man</td><td class="br"></td><td class="tac">.031<span class="hide">0</span></td><td class="bl pl03">100</td></tr>
<tr><td class="pl10">Chimpanzee</td><td class="br"></td><td class="tac">.04<span class="hide">00</span></td><td class="bl pl03">130 (loose precipitum)</td></tr>
<tr><td class="pl10">Gorilla</td><td class="br"></td><td class="tac">.021<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>64</td></tr>
<tr><td class="pl10">Ourang</td><td class="br"></td><td class="tac">.013<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>42</td></tr>
<tr><td class="pl10">Cynocephalus mormon</td><td class="br"></td><td class="tac">.013<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>42</td></tr>
<tr><td class="pl10">Cynocephalus sphinx</td><td class="br"></td><td class="tac">.009<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>29</td></tr>
<tr><td class="pl10">Ateles geoffroyi</td><td class="br"></td><td class="tac">.009<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>29</td></tr>
<tr><td><i>Insectivora</i></td><td class="br"></td><td class="tac"></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Centetes ecaudatus</td><td class="br"></td><td class="tac">.0<span class="hide">000</span></td><td class="bl pl03"><span class="hide">00</span>0</td></tr>
<tr><td><i>Carnivora</i></td><td class="br"></td><td class="tac"></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Canis aureus</td><td class="br"></td><td class="tac">.003<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>10 (loose precipitum)</td></tr>
<tr><td class="pl10">Canis familiaris</td><td class="br"></td><td class="tac">.001<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>3</td></tr>
<tr><td class="pl10">Lutra vulgaris</td><td class="br"></td><td class="tac">.003<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>10 (concentrated serum)</td></tr>
<tr><td class="pl10">Ursus tibetanus</td><td class="br"></td><td class="tac">.0025</td><td class="bl pl03"><span class="hide">00</span>8</td></tr>
<tr><td class="pl10">Genetta tigrina</td><td class="br"></td><td class="tac">.001<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>3</td></tr>
<tr><td class="pl10">Felis domesticus</td><td class="br"></td><td class="tac">.001<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>3</td></tr>
<tr><td class="pl10">Felis caracal</td><td class="br"></td><td class="tac">.0008</td><td class="bl pl03"><span class="hide">00</span>3</td></tr>
<tr><td class="pl10">Felis tigris</td><td class="br"></td><td class="tac">.0005</td><td class="bl pl03"><span class="hide">00</span>2</td></tr>
<tr><td><i>Ungulata</i></td><td class="br"></td><td class="tac"></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Ox</td><td class="br"></td><td class="tac">.003<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>10</td></tr>
<tr><td class="pl10">Sheep</td><td class="br"></td><td class="tac">.003<span class="hide">0</span></td><td class="bl pl03"><span class="hide">0</span>10</td></tr>
<tr><td class="pl10">Cobus unctuosus</td><td class="br"></td><td class="tac">.002<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>7</td></tr>
<tr><td class="pl10">Cervus porcinus</td><td class="br"></td><td class="tac">.002<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>7</td></tr>
<tr><td class="pl10">Rangifer tarandus</td><td class="br"></td><td class="tac">.002<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>7</td></tr>
<tr><td class="pl10">Capra megaceros</td><td class="br"></td><td class="tac">.0005</td><td class="bl pl03"><span class="hide">00</span>2</td></tr>
<tr><td class="pl10">Equus caballus</td><td class="br"></td><td class="tac">.0005</td><td class="bl pl03"><span class="hide">00</span>2</td></tr>
<tr><td class="pl10">Sus scrofa</td><td class="br"></td><td class="tac">.0<span class="hide">000</span></td><td class="bl pl03"><span class="hide">00</span>0</td></tr>
<tr><td></td><td class="tac"><span class="pagenum" title="58"><a name="Page_58" id="Page_58"></a></span></td></tr>
<tr><td><i>Rodentia</i></td><td class="br"></td><td class="tac"></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Dasyprocta cristata</td><td class="br"></td><td class="tac">.002<span class="hide">0</span></td><td class="bl pl03"><span class="hide">00</span>7 (concentrated serum clots)</td></tr>
<tr><td class="pl10">Guinea-pig</td><td class="br"></td><td class="tac">.0<span class="hide">000</span></td><td class="bl pl03"><span class="hide">00</span>0</td></tr>
<tr><td class="pl10">Rabbit</td><td class="br"></td><td class="tac">.0<span class="hide">000</span></td><td class="bl pl03"><span class="hide">00</span>0</td></tr>
<tr><td><i>Marsupialia</i></td><td class="br"></td><td class="tac"></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Petrogale xanthopus</td><td class="bbr" rowspan="7"><img src="images/115x10brk.png" width="10" height="115" alt="" /></td><td></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Petrogale penicillata</td><td></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Onychogale frenata</td><td></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Onychogale unguifera</td><td class="tac">.0<span class="hide">000</span></td><td class="bl pl03"><span class="hide">00</span>0</td></tr>
<tr><td class="pl10">Onychogale unguifera</td><td></td><td class="bl pl03"></td></tr>
<tr><td class="pl10">Macropus bennetti</td><td></td><td class="bl pl03"></td></tr>
<tr><td class="pl10 pb03 bb">Thylacinus cynocephalus</td><td class="bb"></td><td class="bbl"></td></tr>
</table>
<div class="blockquot">
<p>Among the Primate bloods that of the Chimpanzee gave too high a
figure, owing to the precipitum being flocculent and not settling
well, for some reason which could not be determined. The figure
given by the Ourang is somewhat too low, and the difference between
Cynocephalus sphinx and Ateles is not as marked as might have been
expected in view of the qualitative tests and the series following.
The possibilities of error must be taken into account in judging of
these figures; repeated tests should be made to obtain something
like a constant. Other bloods than those of Primates give small
reactions or no reactions at all. The high figures (10%) obtained
with two Carnivore bloods can be explained by the fact that one
gave a loose precipitum, and the other was a somewhat concentrated
<span class="nowrap">serum.<a name="FNanchor_44_44" id="FNanchor_44_44"></a><a href="#Footnote_44_44" class="fnanchor">44</a></span></p>
</div>
<p>We have mentioned that even the proteins of the egg are specific
according to Uhlenhuth. Graham Smith, one of Nuttall’s collaborators,
applied the lat<span class="pagenum" title="59"><a name="Page_59" id="Page_59"></a></span>ter’s quantitative method to this problem and confirmed
the results of Nuttall. A few examples may serve as an illustration.</p>
<p class="tac">TABLE III</p>
<p class="tac"><span class="smcap">Tests with Anti-Duck’s-Egg Serum</span></p>
<table width="60%" summary="Precipitin reactions by various species against anti-duck's-egg serum">
<tr><th colspan="2" class="btr"><i>Material tested</i></th><th class="ball"><i>Amount of<br />precipitum</i></th><th class="btl"><i>Percentage</i></th></tr>
<tr><td class="bt pt03">Duck’s</td><td class="tal btr pt03">egg-albumin</td><td class="tac pt03">.0384</td><td class="tac btl pt03">100</td></tr>
<tr><td>Pheasant’s</td><td class="tal br">   "</td><td class="tac">.0328</td><td class="tac bl"><span class="hide">1</span>85</td></tr>
<tr><td>Fowl’s</td><td class="tal br">   "</td><td class="tac">.0234</td><td class="tac bl"><span class="hide">1</span>61</td></tr>
<tr><td>Silver Pheasant’s</td><td class="tal br">   "</td><td class="tac">.0140</td><td class="tac bl"><span class="hide">1</span>36</td></tr>
<tr><td>Blackbird’s</td><td class="tal br">   "</td><td class="tac">.0065</td><td class="tac bl"><span class="hide">1</span>15</td></tr>
<tr><td>Crane’s</td><td class="tal br">   "</td><td class="tac">.0051</td><td class="tac bl"><span class="hide">1</span>14</td></tr>
<tr><td>Moorhen’s</td><td class="tal br">   "</td><td class="tac">.0046</td><td class="tac bl"><span class="hide">1</span>12</td></tr>
<tr><td>Thrush’s</td><td class="tal br">   "</td><td class="tac">.0046</td><td class="tac bl"><span class="hide">1</span>12</td></tr>
<tr><td>Emu’s</td><td class="tal br">   "</td><td class="tac">.0018</td><td class="tac bl"><span class="hide">10</span>5</td></tr>
<tr><td>Hedge-Sparrow’s</td><td class="tal br">   "</td><td class="tac">trace</td><td class="tac bl"><span class="hide">10</span>?</td></tr>
<tr><td>Chaffinch’s</td><td class="tal br">   "</td><td class="tac">·</td><td class="tac bl"><span class="hide">10</span>0</td></tr>
<tr><td>Tortoise serum</td><td class="tal br"></td><td class="tac">trace</td><td class="tac bl"><span class="hide">10</span>?</td></tr>
<tr><td>Turtle serum</td><td class="tal br"></td><td class="tac">"</td><td class="tac bl"><span class="hide">10</span>?</td></tr>
<tr><td class="bb pb03">Alligator serum</td><td class="tal bbr pb03"></td><td class="tac bb pb03">·</td><td class="tac bbl pb03"><span class="hide">10</span>0</td></tr>
</table>
<div class="blockquot">
<p>Frog, Amphiuma, and Dogfish sera, as well as Tortoise and Dogfish
egg-albumins, were also tested, with negative results.</p>
</div>
<p class="tac">TABLE IV</p>
<p class="tac"><span class="smcap">Tests with Anti-Fowl’s-Egg Serum</span></p>
<table width="60%" summary="Precipitin reactions by various bird species against anti-fowl's-egg serum">
<tr><th colspan="2" class="btr"><i>Material tested</i></th><th class="ball"><i>Amount of<br />precipitum</i></th><th class="btl"><i>Percentage</i></th></tr>
<tr><td class="bt pt03">Fowl’s</td><td class="tal btr pt03">egg-albumin (old)</td><td class="tac pt03">.0159</td><td class="tac btl pt03">100</td></tr>
<tr><td>Fowl’s</td><td class="tal br">   "   (fresh)</td><td class="tac">.0140</td><td class="tac bl"><span class="hide">1</span>88</td></tr>
<tr><td>Silver Pheasant’s</td><td class="tal br">   "</td><td class="tac">.0075</td><td class="tac bl"><span class="hide">1</span>47</td></tr>
<tr><td>Pheasant’s</td><td class="tal br">   "</td><td class="tac">.0075</td><td class="tac bl"><span class="hide">1</span>47</td></tr>
<tr><td>Crane’s</td><td class="tal br">   "</td><td class="tac">.0046</td><td class="tac bl"><span class="hide">1</span>29</td></tr>
<tr><td>Blackbird’s</td><td class="tal br">   "</td><td class="tac">.0046</td><td class="tac bl"><span class="hide">1</span>29</td></tr>
<tr><td>Duck’s</td><td class="tal br">   "</td><td class="tac">.0037</td><td class="tac bl"><span class="hide">1</span>23</td></tr>
<tr><td class="bb pb03">Moorhen’s</td><td class="tal bbr pb03">   "</td><td class="tac bb pb03">.0028</td><td class="tac bbl pb03"><span class="hide">1</span>18</td></tr>
</table>
<p><span class="pagenum" title="60"><a name="Page_60" id="Page_60"></a></span></p>
<div class="blockquot">
<p>Thrush, Emu, Greenfinch, and Hedge-sparrow egg-albumins were tested
and gave traces of precipita, as also did Tortoise and Turtle sera.
The egg-albumins of the Tortoise, Frog, Skate, and two species of
Dogfish did not react. Alligator, Frog, Amphiuma, and Dogfish sera
also yielded no <span class="nowrap">results.<a name="FNanchor_45_45" id="FNanchor_45_45"></a><a href="#Footnote_45_45" class="fnanchor">45</a></span></p>
</div>
<p>By improving the quantitative method in various ways, Welsh and
<span class="nowrap">Chapman<a name="FNanchor_46_46" id="FNanchor_46_46"></a><a href="#Footnote_46_46" class="fnanchor">46</a></span> were able to explain why the
precipitin reaction with egg-white was not strictly specific but gave
also, though quantitatively weaker, results with the egg-white of
related birds. They found that by a new method devised by them “it is
possible to indicate in an avian egg-white antiserum the presence of
a general avian antisubstance (precipitin) together with the specific
antisubstance.”</p>
<p>The Bordet reaction was not only useful in indicating the specificity
and blood relationship for animals but also among plants. Thus
Magnus and <span class="nowrap">Friedenthal<a name="FNanchor_47_47" id="FNanchor_47_47"></a><a href="#Footnote_47_47" class="fnanchor">47</a></span> were able
to demonstrate with Bordet’s method the relationship between yeast
(<i class="taxonomic">Saccharomyces cerevisiæ</i>) and truffle (<i class="taxonomic">Tuber brumale</i>).</p>
<p>5. We must not forget, while under the spell of the problem of
immunity, that we are interested at the moment in the question of the
nature of the specificity of living organisms. It is only logical to
conclude<span class="pagenum" title="61"><a name="Page_61" id="Page_61"></a></span> that the fossil forms of invertebrate animals and of algæ
and bacteria, which Walcott found in the Cambrian and which may be two
hundred million years old, must have had the same specificity at that
time as they or their close relatives have today; and this raises the
question: What is the nature of the substances which are responsible
for and transmit this specificity? It is obvious that a definite answer
to this question brings us also to the very problem of evolution as
well as that of the constitution of living matter.</p>
<p>There can be no doubt that on the basis of our present knowledge
proteins are in most or practically all cases the bearers of this
specificity. This has been found out not only with the aid of the
precipitin reaction but also with the anaphylaxis reaction, by
which, as the reader may know, is meant that when a small dose of a
foreign substance is introduced into an animal a hypersensitiveness
develops after a number of days or weeks, so that a new injection
of the same substance produces serious and in some cases fatal
effects. This hypersensitiveness, which was first analysed by <span
class="nowrap">Richet,<a name="FNanchor_48_48" id="FNanchor_48_48"></a><a href="#Footnote_48_48" class="fnanchor">48</a></span> is specific for the substance which
has been injected. Now all these specific reactions, the precipitin
reaction as well as the anaphylactic reaction, can be called forth by
proteins. Thus Richet, in his earliest experiments, showed that only
the protein-containing part of the extract of actinians, by which he
called forth anaphy<span class="pagenum" title="62"><a name="Page_62" id="Page_62"></a></span>laxis, was able to produce this phenomenon, and
later he showed that it was generally impossible to produce anything
resembling anaphylaxis by non-protein substances, <i>e. g.</i>, cocain
or <span class="nowrap">apomorphin.<a name="FNanchor_49_49" id="FNanchor_49_49"></a><a href="#Footnote_49_49" class="fnanchor">49</a></span> Wells isolated from
egg-white four different proteins (three coagulable proteins and one
non-coagulable) which can be distinguished from each other by the
anaphylaxis reaction, although all come from the same biological <span
class="nowrap">object.<a name="FNanchor_50_50" id="FNanchor_50_50"></a><a href="#Footnote_50_50" class="fnanchor">50</a></span> Michaelis as well as Wells found that
the split products of the protein molecule are no longer able to call
forth the anaphylaxis reaction. Since peptic digestion has the effect
of annihilating the power of proteins to call forth anaphylaxis, we are
forced to the conclusion that the first cleavage products of proteins
have already lost the power of calling forth immunity reactions.</p>
<p>A pretty experiment by Gay and <span
class="nowrap">Robertson<a name="FNanchor_51_51" id="FNanchor_51_51"></a><a href="#Footnote_51_51" class="fnanchor">51</a></span> should be mentioned in this
connection. Robertson had shown</p>
<div class="blockquot">
<p>that a substance closely resembling paranucleins both in its
properties and its C, H, and N content can be formed from the
filtered products of the complete peptic hydrolysis of an
approximately four per cent. neutral solution of potassium
caseinate by the action of pure pepsin at 36°C.</p>
</div>
<p>He considered this a case of a real synthesis of proteins from
the products of its hydrolytic cleavage. This<span class="pagenum" title="63"><a name="Page_63" id="Page_63"></a></span> interpretation was
not generally accepted and received a different interpretation by
Bayliss and other workers. Gay and Robertson were able to show that
paranuclein when injected into an animal will sensitize guinea-pigs
for anaphylactic intoxication for either paranuclein or casein
and apparently indiscriminately. The products of complete peptic
digestion of casein had no such effect, but the synthetic product of
this digestion obtained by Robertson’s method has the same specific
antigenic properties as paranuclein, thus making it appear that
Robertson had indeed succeeded in causing a synthesis of paranuclein
with the aid of pepsin from the products of digestion of casein by
pepsin.</p>
<p>There are a few statements in the literature to the effect that
the specificity of organisms might be due to other substances than
proteins. Thus Bang and Forssmann claimed that the substances
(antigens) responsible for the production of hemolysis were of a lipoid
nature, but their statements have not been confirmed, and Fitzgerald
and <span class="nowrap">Leathes<a name="FNanchor_52_52" id="FNanchor_52_52"></a><a href="#Footnote_52_52" class="fnanchor">52</a></span> reached the conclusion that
lipoids are non-antigenic. Ford claims to have obtained proof that a
glucoside contained in the poisonous mushroom <i class="taxonomic">Amanita phalloides</i> can
act as an antigen. But aside from this one fact we know that proteins
and only proteins can act as antigens and<span class="pagenum" title="64"><a name="Page_64" id="Page_64"></a></span> are therefore the bearers of
the specificity of living organisms.</p>
<p>Bradley and <span class="nowrap">Sansum<a name="FNanchor_53_53" id="FNanchor_53_53"></a><a href="#Footnote_53_53" class="fnanchor">53</a></span> found that
guinea-pigs sensitized to beef or dog hemoglobin fail to react or react
but slightly to hemoglobin of other origin. The hemoglobins tried were
dog, beef, cat, rabbit, rat, turtle, pig, horse, calf, goat, sheep,
pigeon, chicken, and man.</p>
<p>6. It would be of the greatest importance to show directly that
the homologous proteins of different species are different. This
has been done for hemoglobins of the blood by Reichert and <span
class="nowrap">Brown,<a name="FNanchor_54_54" id="FNanchor_54_54"></a><a href="#Footnote_54_54" class="fnanchor">54</a></span> who have shown by crystallographic
measurements that the hemoglobins of any species are definite
substances for that species.</p>
<div class="blockquot">
<p>The crystals obtained from different species of a genus are
characteristic of that species, but differ from those of other
species of the genus in angles or axial ratio, in optical
characters, and especially in those characters comprised under the
general term of crystal habit, so that one species can usually be
distinguished from another by its hemoglobin crystals. But these
differences are not such as to preclude the crystals from all
species of a genus being placed in an isomorphous series (p. 327).</p>
</div>
<p><span class="pagenum" title="65"><a name="Page_65" id="Page_65"></a></span></p>
<p>As far as the genus is concerned it was found that the hemoglobin
crystals of any genus are isomorphous.</p>
<div class="blockquot">
<p>In some cases this isomorphism may be extended to include several
genera, but this is not usually the case, unless as in the case of
dogs and foxes, for example, the genera are very closely related.</p>
</div>
<p>The most important question for us is the following: Are the
differences between the corresponding hemoglobin crystals of different
species of the same genus such as to warrant the statement that they
indicate chemical differences? If this were the case we might say
that blood reactions as well as hemoglobin crystals indicate that
differences in the constitution of proteins determine the species
specificity and, perhaps, also species heredity. The following
sentences by Reichert and Brown seem to indicate that this may be true
for the crystals of hemoglobin.</p>
<div class="blockquot">
<p>The hemoglobins of any species are definite substances for
that species. But upon comparing the corresponding substances
(hemoglobins) in different species of a genus it is generally
found that they differ the one from the other to a greater or
less degree; the differences being such that when complete
crystallographic data are available the different species can be
distinguished by these differences in their hemoglobins. As the
hemoglobins crystallize in isomorphous series the differences
between the angles of the crystals of the species of a genus are
not, as a rule, great; but they are as great as is usually found
to be the case with<span class="pagenum" title="66"><a name="Page_66" id="Page_66"></a></span> minerals or chemical salts that belong to an
isomorphous group (p. 326).</p>
</div>
<p>As Professor Brown writes me, the difficulty in answering the question
definitely, whether or not the hemoglobins of different species
are chemically different, lies in the fact that there is as yet no
criterion which allows us to discriminate between a species and a
Mendelian mutation except the morphological differences. It is not
impossible that while species differ by the constitution of some or
most of their proteins, Mendelian heredity has a different chemical
basis.</p>
<p>It is regrettable that work like that of Reichert and Brown cannot be
extended to other proteins, but it seems from anaphylaxis reactions
that we might expect results similar to those in the case of the
hemoglobins. The proteins of the lens are an exception inasmuch as,
according to Uhlenhuth, the proteins of the lens of mammals, birds, and
amphibians cannot be discriminated from each other by the precipitin
<span class="nowrap">reaction.<a name="FNanchor_55_55" id="FNanchor_55_55"></a><a href="#Footnote_55_55" class="fnanchor">55</a></span></p>
<p>7. The serum of certain humans may cause the destruction or
agglutination of blood corpuscles of certain other humans. This fact
of the existence of “isoagglutinins” seems to have been established
for man, but Hektoen states that he has not been able to find any
isoagglutinins in the serum of rabbits, guinea-pigs, dogs, horses,
and cattle. Landsteiner found the<span class="pagenum" title="67"><a name="Page_67" id="Page_67"></a></span> remarkable fact that the sera of
certain individuals of humans could hemolyze the corpuscles of certain
other individuals, but not those of all individuals. A systematic
investigation of this variability led him to the discovery of three
distinct groups of individuals, the sera of each group acting in
a definite way towards the corpuscles of the representatives of
each other group. Later observers, for example Jansky and Moss,
established four groups. These groups are, according to <span
class="nowrap">Moss,<a name="FNanchor_56_56" id="FNanchor_56_56"></a><a href="#Footnote_56_56" class="fnanchor">56</a></span> as follows:</p>
<div class="blockquot">
<p>Group 1. Sera agglutinate no corpuscles.<br />
<span class="ml4em">Corpuscles agglutinated by sera of Groups 2, 3, 4.</span></p>
<p>Group 2. Sera agglutinate corpuscles of Groups 1, 3.<br />
<span class="ml4em">Corpuscles agglutinated by sera of Groups 3, 4.</span></p>
<p>Group 3. Sera agglutinate corpuscles of Groups 1, 2.<br />
<span class="ml4em">Corpuscles agglutinated by sera of Groups 2, 4.</span></p>
<p>Group 4. Sera agglutinate corpuscles of Groups 1, 2, 3.<br />
<span class="ml4em">Corpuscles agglutinated by no serum.</span></p>
</div>
<p>The relative frequency of the four groups follows from the following
figures. Of one hundred bloods tested by Moss in series of twenty there
were found:</p>
<div class="blockquot">
<p>10 belonging to Group 1.<br />
40 belonging to Group 2.<br />
 7 belonging to Group 3.<br />
43 belonging to Group 4.<br /></p>
</div>
<p>Groups 2 and 4 are in the majority and in overwhelming numbers, which
indicates that, as a rule, the<span class="pagenum" title="68"><a name="Page_68" id="Page_68"></a></span> sera agglutinate the blood corpuscles
of individuals of the other groups, but not those of individuals
belonging to the same group. The phenomenon that a serum agglutinates
no corpuscles (Group 1), or that the corpuscles are agglutinated by
no serum (Group 4), are the exceptions. It is obvious that, as far as
our problem is concerned, only Groups 2 and 3 are to be considered.
There is no Mendelian character which refers only to one half of the
individuals except sex. Since nothing is said about a relation of
Groups 2 and 3 to sex such a relation probably does not exist.</p>
<p>8. The facts thus far reported imply the suggestion that the heredity
of the genus is determined by proteins of a definite constitution
differing from the proteins of other genera. This constitution of the
proteins would therefore be responsible for the genus heredity. The
different species of a genus have all the same genus proteins, but the
proteins of each species of the same genus are apparently different
again in chemical constitution and hence may give rise to the specific
biological or immunity reactions.</p>
<p>We may consider it as established by the work of McClung, Sutton, E. B.
Wilson, Miss Stevens, Morgan, and many others, that the chromosomes
are the carriers of the Mendelian characters. These chromosomes occur
in the nucleus of the egg and in the head of the sperm. Now the latter
consists, in certain fish, of lipoids and a combination of nucleinic
acid and pro<span class="pagenum" title="69"><a name="Page_69" id="Page_69"></a></span>tamine or histone, the latter a non-coagulable protein,
more resembling a split product of one of the larger coagulable
proteins.</p>
<p>A. E. <span class="nowrap">Taylor<a name="FNanchor_57_57" id="FNanchor_57_57"></a><a href="#Footnote_57_57" class="fnanchor">57</a></span> found that if the
spermatozoa of the salmon are injected into a rabbit, the blood of the
animal acquires the power of causing cytolysis of salmon spermatozoa.
When, however, the isolated protamines or nucleinic acid or the lipoids
prepared from the same sperm were injected into a rabbit no results of
this kind were observed. H. G. Wells more recently tested the relative
efficiency of the constituents of the testes of the cod (which in
addition to the constituents of the sperm contained the proteins of the
testicle). From the testicle he prepared a histone (the protein body
of the sperm nucleus), a sodium nucleinate, and from the sperm-free
aqueous extract of the testicles a protein resembling albumin was
separated by <span class="nowrap">precipitation.<a name="FNanchor_58_58" id="FNanchor_58_58"></a><a href="#Footnote_58_58" class="fnanchor">58</a></span></p>
<div class="blockquot">
<p>The albumin behaved like ordinary serum albumin or egg albumin,
producing typical and fatal anaphylactic reactions and being
specific when tried against mammalian sera. The nucleinate did not
produce any reactions when guinea-pigs were given small sensitizing
and larger intoxicating doses (0.1 gm.) in a three weeks’
interval; a result to be expected, since no protein is present in
the preparation. The histone was so toxic that its anaphylactic
properties could not be studied.</p>
</div>
<p><span class="pagenum" title="70"><a name="Page_70" id="Page_70"></a></span></p>
<p>It is not impossible that protamines and histones might be found
to act as specific antigens if they were not so toxic. The positive
results which Taylor observed after injection of the sperm might have
been due to the proteins contained in the tail of the spermatozoa,
which in certain animals at least does not enter the egg and hence can
have no influence on heredity.</p>
<p>It is thus doubtful whether or not any of the constituents of the
nucleus contribute to the determination of the species. This in its
ultimate consequences might lead to the idea that the Mendelian
characters which are equally transmitted by egg and spermatozoön,
determine the individual or variety heredity, but not the genus
or species heredity. It is, in our present state of knowledge,
impossible to cause a spermatozoön to develop into an <span
class="nowrap">embryo,<a name="FNanchor_59_59" id="FNanchor_59_59"></a><a href="#Footnote_59_59" class="fnanchor">59</a></span> while we can induce the egg to
develop into an embryo without a spermatozoön. This may mean that the
protoplasm of the egg is the future embryo, while the chromosomes of
both egg and sperm nuclei furnish only the individual characters. </p>
<hr class="chap" />
<p><span class="pagenum" title="71"><a name="Page_71" id="Page_71"></a></span></p>
<h2>CHAPTER IV</h2>
<h3>SPECIFICITY IN FERTILIZATION</h3>
<p>1. We have become acquainted with two characteristics of living
matter: the specificity due to the specific proteins characteristic
for each genus and possibly species and the synthesis of living matter
from the split products of their main constituents instead of from
a supersaturated solution of their own substance, as is the case in
crystals. We are about to discuss in this and the next chapter a third
characteristic, namely, the phenomenon of fertilization. While this
is not found in all organisms it is found in an overwhelming majority
and especially the higher organisms, and of all the mysteries of
animated nature that of fertilization and sex seems to be the most
captivating, to judge from the space it occupies in folklore, theology,
and “literature.” Bacteria, when furnished the proper nutritive medium,
will synthetize the specific material of their own body, will grow
and divide, and this process will be repeated indefinitely as long
as the food lasts and the temperature and other outside conditions
are<span class="pagenum" title="72"><a name="Page_72" id="Page_72"></a></span> normal. It is purely due to limitation of food that bacteria
or certain species of them do not cover the whole planet. But, as
every layman knows, the majority of organisms grow only to a certain
size, then die, and the propagation takes place through sex cells or
gametes: a female cell—the egg—containing a large bulk of protoplasm
(the future embryo) and reserve material; and the male cell which in
the case of the spermatozoön contains only nuclear material and no
cytoplasmic material except that contained in the tail which in some
and possibly many species does not enter the egg. The male element—the
spermatozoön—enters the female gamete—the egg—and this starts the
development. In the case of most animals the egg cannot develop unless
the spermatozoön enters. The question arises: How does the spermatozoön
activate the egg? And also how does it happen that the spermatozoön
enters the egg? We will first consider the latter question. These
problems can be answered best from experiments on forms in which the
egg and the sperm are fertilized in sea water. Many marine animals,
from fishes down to lower forms, shed their eggs and sperm into the sea
water where the fertilization of the egg takes place, outside the body
of the female.</p>
<p>The first phenomenon which strikes us in this connection is again a
phenomenon of specificity. The spermatozoön can, as a rule, only enter
an egg of the same or a closely related species, but not that of one
more<span class="pagenum" title="73"><a name="Page_73" id="Page_73"></a></span> distantly related. What is the character of this specificity?
The writer was under the impression that a clue might be obtained if
artificial means could be found by which the egg of one species might
be fertilized with a distant species for which this egg is naturally
immune. Such an experiment would mean that the lack of specificity
had been compensated by the artificial means. It is well known that
the egg of the sea urchin cannot as a rule be fertilized with the
sperm of a starfish in normal sea water. The writer tried whether this
hybridization could not be accomplished provided the constitution of
the sea water were changed. He succeeded in causing the fertilization
of a large percentage of the eggs of the Californian sea urchin,
<i class="taxonomic">Strongylocentrotus purpuratus</i>, with the sperm of various starfish
(<i>e. g.</i>, <i class="taxonomic">Asterias ochracea</i>) and <i class="taxonomic">Holothurians</i> by slightly
raising the alkalinity of the sea water, through the addition of some
base (NaOH or tetraethylammoniumhydroxide or various amines), the
optimum being reached when 0.6 c.c. N/10 NaOH is added to 50 c.c. of
sea water. It is a peculiar fact that this solution is efficient only
if both egg and sperm are together in the hyperalkaline sea water.
If the eggs and sperm are treated separately with the hyperalkaline
sea water and are then brought together in normal sea water no
fertilization takes place as a rule, while with the same sperm and
eggs the fertilization is successful again if both are mixed in the
hyperalkaline solution. From<span class="pagenum" title="74"><a name="Page_74" id="Page_74"></a></span> this the writer concluded that the
fertilizing power depends on a rapidly reversible action of the alkali
on the surface of the two gametes. It was found that an increase of the
concentration of calcium in the sea water also favoured the entrance of
the <i class="taxonomic">Asterias</i> sperm into the egg of <i class="taxonomic">purpuratus</i>; and that if C<sub>Ca</sub>
was increased it was not necessary to add as much NaOH.</p>
<p>The spermatozoön enters the egg through the so-called fertilization
cone, <i>i. e.</i>, a protoplasmic process comparable to the
pseudopodium of an amœboid cell. The analogy of the process of
phagocytosis—<i>i. e.</i>, the taking up of particles by an amœboid
cell—and that of the engulfing of the spermatozoön by the egg presents
itself. We do not know definitely the nature of the forces which act
in the case of phagocytosis—although surface tension forces and
agglutination have been suggested; both are surface phenomena and are
rapidly reversible.</p>
<p>We should then say that the specificity in the process of fertilization
consists in a peculiarity of the surface of the egg and spermatozoön
which in the case of <i class="taxonomic">S. purpuratus</i> ♀ and <i class="taxonomic">Asterias</i> ♂ can be supplied
by a slight increase in the C<sub>OH</sub> or C<sub>Ca</sub>.</p>
<p>By this method fifty per cent. or more of the eggs of <i class="taxonomic">purpuratus</i>
could be fertilized with the sperm of the starfish <i>Asterias ochracea,
capitata</i>, Ophiurians, and Holothurians, while with the sperm of
another starfish, <i class="taxonomic">Pycnopodia spuria</i>, only five per cent., and
with the<span class="pagenum" title="75"><a name="Page_75" id="Page_75"></a></span> sperm of <i class="taxonomic">Asterina</i> only one per cent. could be <span
class="nowrap">fertilized.<a name="FNanchor_60_60" id="FNanchor_60_60"></a><a href="#Footnote_60_60" class="fnanchor">60</a></span> Godlewski succeeded by the same
method in fertilizing the eggs of a Naples starfish with the sperm of
a <span class="nowrap">crinoid.<a name="FNanchor_61_61" id="FNanchor_61_61"></a><a href="#Footnote_61_61" class="fnanchor">61</a></span> The writer did not succeed
in bringing about the fertilization of the egg of another sea urchin
in California, <i class="taxonomic">Strongylocentrotus franciscanus</i>, with the sperm of
a starfish. Although these eggs formed a membrane in contact with
the sperm, the latter did not enter the egg; nor has the writer as
yet succeeded in causing the sperm of <i class="taxonomic">Asterias</i> to enter the egg of
<i class="taxonomic">Arbacia</i>.</p>
<p><span class="nowrap">Kupelwieser<a name="FNanchor_62_62" id="FNanchor_62_62"></a><a href="#Footnote_62_62" class="fnanchor">62</a></span> observed that the
spermatozoön of molluscs may occasionally enter into the egg of <i class="taxonomic">S.
purpuratus</i> in normal sea water and later, at Naples, he observed the
same for the sperm of annelids. In these cases no development took
place. In teleost fishes the spermatozoön can enter the eggs of widely
different species but with rare exceptions all the embryos will die in
an early stage of <span class="nowrap">development.<a name="FNanchor_63_63" id="FNanchor_63_63"></a><a href="#Footnote_63_63" class="fnanchor">63</a></span></p>
<p>2. The fact that an increase in the alkalinity or in the concentration
of calcium allowed foreign sperm to enter the egg of the sea urchin,
suggested the idea that a diminution of alkalinity or calcium in the
sea water<span class="pagenum" title="76"><a name="Page_76" id="Page_76"></a></span> might block the entrance of the sperm of sea urchin into
eggs of their own species. This was found to be correct; when we put
eggs and sperm of the same species of sea urchin into solutions whose
concentration of Ca or of OH is too small, the sperm, although it may
be intensely active, cannot enter the egg.</p>
<p>For the purpose of these experiments the ovaries and testes of the
sea urchins were not put into sea water, but instead into pure m/2
NaCl and after several washings in this solution were kept in it (they
remain alive for several days in pure m/2 NaCl). Several drops of such
sperm and one drop of eggs were in one series of experiments put into
2.5 c.c. of a neutral mixture of m/2 NaCl and <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub> in the
proportion in which these two salts exist in the sea water. In such a
neutral solution eggs of <i class="taxonomic">Arbacia</i> or <i class="taxonomic">purpuratus</i> are not fertilized
no matter how long they remain in it, although the spermatozoa swim
around the eggs very actively. That no spermatozoön enters the eggs
can be shown by the fact that the eggs do not divide (although they
can segment in such a solution if previously fertilized in sea water
or some other efficient solution). When, however, eggs and sperm are
put into 2.5 c.c. of the same solution of NaCl+MgCl<sub>2</sub>, containing in
addition one drop of a N/100 solution of NaOH (or NH<sub>3</sub> or benzylamine
or butylamine) or eight drops of m/100 NaHCO<sub>3</sub>, most, and often
practically all of the eggs at once form fertilization membranes
and segment at<span class="pagenum" title="77"><a name="Page_77" id="Page_77"></a></span> the proper time, indicating that fertilization has
been accomplished. The same result can be obtained if the eggs are
transferred into a neutral mixture of NaCl+MgCl<sub>2</sub>+CaCl<sub>2</sub> (in
the proportion in which these salts exist in the sea water) or into
a neutral mixture of NaCl+MgCl<sub>2</sub>+KCl+CaCl<sub>2</sub>. In such neutral
mixtures the eggs form fertilization membranes and begin to segment.
The eggs are not fertilized in a neutral solution of NaCl or of <span
class="nowrap">NaCl+KCl.<a name="FNanchor_64_64" id="FNanchor_64_64"></a><a href="#Footnote_64_64" class="fnanchor">64</a></span></p>
<p>It is, therefore, obvious that if we diminish the alkalinity of the
solution surrounding the egg and deprive this solution of CaCl<sub>2</sub>
we establish the same block to the entrance of the spermatozoön of
<i class="taxonomic">Arbacia</i> into the egg of the same species as exists in normal sea
water for the entrance of the sperm of the starfish into the egg of
<i class="taxonomic">purpuratus</i>.</p>
<p>The “block” created in this way, to the entrance of the sperm of
<i class="taxonomic">Arbacia</i> into the egg of the same species is also rapidly reversible.</p>
<p>We reach the conclusion, therefore, that the specificity which allows
the sperm to enter an egg is a surface effect which can be increased
or diminished by an increase or diminution in the concentration of
OH as well as of Ca. The writer has shown that an increase in the
concentration of both substances may cause an agglutination of the
spermatozoa of starfish to the<span class="pagenum" title="78"><a name="Page_78" id="Page_78"></a></span> jelly which surrounds the egg of <span
class="nowrap"><i class="taxonomic">purpuratus</i>.<a name="FNanchor_65_65" id="FNanchor_65_65"></a><a href="#Footnote_65_65" class="fnanchor">65</a></span> It is thus not impossible that
the specificity which favours the entrance of a spermatozoön into
an egg of its own species may consist in an agglutination between
spermatozoön and egg protoplasm (or its fertilization cone); and that
this agglutination is favoured if the C<sub>OH</sub> or C<sub>Ca</sub> or both are
increased within certain limits.</p>
<p>Godlewski discovered a very interesting form of block to the entrance
of the spermatozoön into the egg which takes place if two different
types of sperm are mixed. He had found that the sperm of the annelid
<i class="taxonomic">Chætopterus</i> is able to enter the egg of the sea urchin and that in so
doing it causes membrane formation. The egg, however, does not develop
but dies rapidly, as is the case when we induce artificial membrane
formation, as we shall see in the next chapter.</p>
<p>Godlewski found that if the sperm of <i class="taxonomic">Chætopterus</i> and the sperm of
sea urchins are mixed the mixture is not able to induce development or
membrane formation, since now neither spermatozoön can enter; blood has
the same inhibiting effect as the foreign sperm. The mixture does not
interfere with the development of the eggs if they are previously <span
class="nowrap">fertilized.<a name="FNanchor_66_66" id="FNanchor_66_66"></a><a href="#Footnote_66_66" class="fnanchor">66</a></span></p>
<p>The phenomenon was further investigated by <span
class="nowrap">Herlant<a name="FNanchor_67_67" id="FNanchor_67_67"></a><a href="#Footnote_67_67" class="fnanchor">67</a></span> who found that if the sperm of a sea
urchin is<span class="pagenum" title="79"><a name="Page_79" id="Page_79"></a></span> mixed with the sperm of certain annelids (<i class="taxonomic">Chætopterus</i>)
or molluscs, and if after some time the eggs of the sea urchin are
added to the mixture of the two kinds of sperm no egg is fertilized.
If, however, the solution is subsequently diluted with sea water or
if the egg that was in this mixture is washed in sea water, the same
sperm mixture in which the egg previously remained unfertilized will
now fertilize the egg. From these and similar observations Herlant
draws the conclusion that the block existed at the surface of the
egg, inasmuch as a reaction product of the two types of sperm is
formed after some time which alters the surface of the egg and thereby
prevents the sperm from entering. This view is supported not only
by all the experiments but also by the observation of the writer
that foreign sperm or blood is able to cause a real agglutination
after some time if mixed with the sperm of a sea urchin or a <span
class="nowrap">starfish.<a name="FNanchor_68_68" id="FNanchor_68_68"></a><a href="#Footnote_68_68" class="fnanchor">68</a></span> We can imagine that the precipitate
forms a film around the egg and acts as a block for the agglutination
between egg and spermatozoön. The block can be removed mechanically by
washing.</p>
<p>3. The fact has been mentioned that the most motile sperm will not be
able to enter into the egg if certain other conditions (specificity
or C<sub>OH</sub> or C<sub>Ca</sub>) are not fulfilled. On the other hand, living but
immobile sperm cannot enter the egg under any conditions.<span class="pagenum" title="80"><a name="Page_80" id="Page_80"></a></span> If we add a
trace of KCN to the sperm of <i class="taxonomic">Arbacia</i> so that the spermatozoön becomes
immobile no egg is fertilized even if the eggs and the sperm are
thoroughly shaken together; while the same spermatozoa will fertilize
these eggs as soon as the HCN has evaporated and they again become
motile. It was formerly thought that the spermatozoön had to bore
itself into the egg, being propelled by the movements of the flagellum.
It is, however, more probable that only a certain energy of vibration
is needed on the part of the spermatozoön to make the latter stick
to the surface of the egg and agglutinate and that later forces of a
different character bring the spermatozoön into the egg. The fact that
under normal conditions a very slight degree of motility on the part of
the spermatozoön allows it to enter the egg of its own species seems to
favour such a view.</p>
<p>It is a common experience that spermatozoa become very active
when they reach the neighbourhood of an egg. v. Dungern assumed
that only foreign sperm became thus active, but F. R. <span
class="nowrap">Lillie<a name="FNanchor_69_69" id="FNanchor_69_69"></a><a href="#Footnote_69_69" class="fnanchor">69</a></span> has pointed out that this may be
a specific effect. The writer tested this idea on the sperm and
eggs of two species of starfish and of sea urchins. It should be
mentioned that the eggs of the starfish used in this experiment were
completely immature and could not be fertilized, while the eggs of
the sea urchins were mature. The testicles<span class="pagenum" title="81"><a name="Page_81" id="Page_81"></a></span> and ovaries had been kept
in NaCl and all the sperm was immotile. Eggs and sperm were mixed
together in a pure m/2 NaCl solution where the sperm was only rendered
motile by the proximity of eggs. The following table gives the <span
class="nowrap">result.<a name="FNanchor_70_70" id="FNanchor_70_70"></a><a href="#Footnote_70_70" class="fnanchor">70</a></span></p>
<p class="tac">TABLE V</p>
<p class="tac"><span class="smcap">Specificity of Activation of Sperm by Eggs</span></p>
<table width="90%" cellpadding="3" summary="Specificity of activation of sperm by eggs from species of starfish and sea urchins">
<col width="16%" /><col width="21%" /><col width="21%" /><col width="21%" /><col width="21%" />
<tr><th class="btr"></th><th class="ball"><i>Asterias</i>♂</th><th class="ball"><i>Asterina</i>♂</th><th class="ball"><i>Franciscanus</i>♂</th><th class="btl"><i>Purpuratus</i>♂</th></tr>
<tr><td class="tal btr plhi vat"><i>Asterias</i>♀<br />(immature)</td><td class="plhi vat"><i>Immediately very motile.</i></td><td class="brl vat">No activation.</td><td class="plhi vat">Moderately active.</td><td class="btl plhi vat">Slight effect in immediate contact with egg.</td></tr>
<tr><td class="tal br plhi vat"><i>Asterina</i>♀<br />(immature)</td><td class="plhi vat">Not motile.</td><td class="brl plhi vat"><i>Violent activity.</i></td><td class="plhi vat"><i>Violent activity.</i></td><td class="bl plhi vat">Slight effect only near the egg.</td></tr>
<tr><td class="tal br plhi vat"><i>Franciscanus</i>♀<br />(mature)</td><td class="plhi vat">Slightly motile.</td><td class="brl plhi vat">No motility.</td><td class="plhi vat"><i>Immediately active.</i></td><td class="bl plhi vat"><i>Immediately active.</i></td></tr>
<tr><td class="tal bbr plhi vat"><i>Purpuratus</i>♀<br />(mature)</td><td class="bb plhi vat">Slightly motile after some time.</td><td class="bbrl plhi vat">Slight effect in immediate contact with eggs.</td><td class="bb plhi vat"><i>Immediately active.</i></td><td class="bbl plhi vat"><i>Immediately active.</i></td></tr>
</table>
<p>The spermatozoa of starfish show a marked specificity inasmuch as they
are strongly activated only by the eggs of their own species, although
in this experiment these were immature, and to a slight degree only
by the eggs of the sea urchin <i class="taxonomic">purpuratus</i>. But it is also obvious
that the specificity is far from exclusive since the immature eggs
of <i class="taxonomic">Asterina</i> activate the sperm of the sea urchin <i class="taxonomic">franciscanus</i>
as powerfully as is done<span class="pagenum" title="82"><a name="Page_82" id="Page_82"></a></span> by the mature eggs of the sea urchin
<i class="taxonomic">purpuratus</i> and <i class="taxonomic">franciscanus</i>. In studying these results the reader
must keep in mind first that all these experiments were made in a NaCl
solution and second that it requires a stronger influence to activate
the spermatozoa of the starfish, which are not motile at first even in
sea water, than the sea urchin spermatozoa which are from the first
very active in such sea water, and which may therefore be considered as
being at the threshold of activity in pure NaCl solution.</p>
<p>Wasteneys and the writer (in experiments not yet published) did not
succeed in demonstrating an activating effect of the eggs of various
marine teleosts upon sperm of the same species.</p>
<p>4. F. R. <span class="nowrap">Lillie<a name="FNanchor_71_71" id="FNanchor_71_71"></a><a href="#Footnote_71_71" class="fnanchor">71</a></span> has studied the very
striking phenomenon of transitory sperm agglutination which takes place
when the sperm of a sea urchin or of certain annelids is put into the
supernatant sea water of eggs of the same species. If we put one or
more drops of a very thick sperm suspension of the Californian sea
urchin <i class="taxonomic">S. purpuratus</i> carefully into the centre of a dish containing 3 c.c.
of ordinary sea water and let the drop stand for one-half to one
minute and then by gentle agitation mix the sperm with the sea water
the mass of thick sperm which is at first rather viscous is distributed
equally in sea water in a few<span class="pagenum" title="83"><a name="Page_83" id="Page_83"></a></span> seconds and the result is a homogeneous
sperm suspension. When, however, the same experiment is made with the
sea water which has been standing for a short time over a large mass
of eggs of the same species, the thick drop of sperm seems to be less
miscible and instead of a homogeneous suspension we get, as a result,
the formation of a large number of distinct clusters which are visible
to the naked eye and which may possess a diameter of 1 or 2 mm.
The rest of the sea water is almost free from sperm. These clusters of
spermatozoa may last for from two to ten minutes and then dissolve by
the gradual detachment of the spermatozoa from the periphery of the
cluster.</p>
<p>This phenomenon seems to occur in sea urchins and annelids. The writer
has vainly looked for it in different forms of the Californian starfish
or molluscs and in fish at Woods Hole. Lillie failed to find it in the
starfish at Woods Hole.</p>
<p>The writer found that the sperm of the Californian sea urchin
<i class="taxonomic">Strongylocentrotus purpuratus</i> will form clusters with the egg sea
water of <i class="taxonomic">purpuratus</i> but not with that of <i class="taxonomic">franciscanus</i>; while the
sperm of <i class="taxonomic">franciscanus</i> will agglutinate with the egg sea water of both
species, but the clusters last a little longer with the eggs of its own
species.</p>
<p>He also found that the clusters are more durable in a neutral than in
a slightly alkaline solution and that the agglutination disappears the
more rapidly the<span class="pagenum" title="84"><a name="Page_84" id="Page_84"></a></span> more alkaline the solution. The presence of bivalent
cations, especially Ca, also favours the agglutination.</p>
<p>It was also found that this agglutination occurs only when the
spermatozoa are very motile; thus if a trace of KCN is added to a mass
of thick sea-urchin sperm so that the spermatozoa become immotile a
drop of this sperm will not agglutinate when put in egg sea water of
the same species; while later, after the HCN has evaporated, the same
sperm will agglutinate when put into such sea water.</p>
<p>The writer suggests the following explanation of the phenomenon. The
egg sea water contains a substance which forms a precipitate with
a substance on the surface of the spermatozoön whereby the latter
becomes slightly sticky. This precipitate is slowly soluble in sea
water and the more rapidly the more alkaline (within certain limits).
Only when the spermatozoa run against each other with a certain
impact will they stick together, as Lillie suggested. Lillie assumes
that this agglutinating substance contained in egg sea water is
required to bring about fertilization and he therefore calls it <span
class="nowrap">“fertilizin.”<a name="FNanchor_72_72" id="FNanchor_72_72"></a><a href="#Footnote_72_72" class="fnanchor">72</a></span> But this assumption seems to
go beyond the facts inasmuch as the existence of such an agglutinating
substance can only be proved in a few species of animals (sea urchins
and annelids); and as, moreover, sea-urchin sperm can fertilize eggs
which will not cause the sperm to agglu<span class="pagenum" title="85"><a name="Page_85" id="Page_85"></a></span>tinate, <i>e. g.</i>, the egg
of <i class="taxonomic">franciscanus</i> can be fertilized by sperm of <i class="taxonomic">purpuratus</i>, although
the egg sea water of <i class="taxonomic">franciscanus</i> causes no agglutination of the
sperm of <i class="taxonomic">purpuratus</i>. When the jelly surrounding the egg of the
Californian sea urchin <i class="taxonomic">S. purpuratus</i> is dissolved with acid and the
eggs are washed, the eggs will not cause any more sperm agglutination;
and yet one hundred per cent. of such eggs can be fertilized by <span
class="nowrap">sperm.<a name="FNanchor_73_73" id="FNanchor_73_73"></a><a href="#Footnote_73_73" class="fnanchor">73</a></span></p>
<p>5. It is well known that if an egg is once fertilized it becomes
impermeable for other spermatozoa. This cannot well be due to the fact
that the egg develops; for the writer found some time ago that eggs of
<i class="taxonomic">Strongylocentrotus purpuratus</i> which are induced to develop by means
of artificial parthenogenesis can be fertilized by sperm. The following
observation leaves no doubts in this respect. When the unfertilized
eggs of <i class="taxonomic">purpuratus</i> are put for two hours into hypertonic sea water
(50 c.c. of sea water+8 c.c. 2<sup>1</sup>⁄<sub>2</sub> m NaCl) and then transferred
into sea water it occasionally happens that a certain percentage of
the eggs will begin to divide into 2, 4, 8 or more cells, without
developing any further. When to such eggs after they have remained
in the resting stage for a number of hours or a day, sperm is added,
some or all of the blastomeres form a fertilization membrane and
now begin to develop into larvæ; and if the spermatozoön gets into
a blastomere of the<span class="pagenum" title="86"><a name="Page_86" id="Page_86"></a></span> 2- or 4-cell stage normal plutei will result.
When the sperm is added while the eggs are in active parthenogenetic
cell division the individual blastomeres into which a spermatozoön
enters will also form a fertilization membrane, but such blastomeres
perish very rapidly. It is not yet possible to state why it should
make such a difference for the possibility of development whether the
spermatozoön enters into a blastomere when at rest or when it is in
active nuclear division, although the idea presents itself that in
the latter case an abnormal mix-up and separation of chromosomes and
other constituents may be responsible for the fatal result. Whatever
may be the explanation of this phenomenon it proves to us that it is
not the process of development in itself which acts as a block to
the entrance of a spermatozoön into an egg which is already <span
class="nowrap">fertilized.<a name="FNanchor_74_74" id="FNanchor_74_74"></a><a href="#Footnote_74_74" class="fnanchor">74</a></span></p>
<p>When the spermatozoön enters the egg of the sea urchin it calls forth
the formation of a membrane—the fertilization membrane. It might be
considered possible that this membrane formation or the alteration
underlying or accompanying it is responsible for the fact that an egg
once fertilized becomes immune against a spermatozoön. We shall see
in the next chapter that it is possible to call forth the membrane
in an unfertilized sea-urchin egg by treating it with butyric<span class="pagenum" title="87"><a name="Page_87" id="Page_87"></a></span> acid.
This membrane is so tough in the egg of <i class="taxonomic">Strongylocentrotus</i> that
no spermatozoön can get through it; in the egg of <i class="taxonomic">Arbacia</i> the
membrane is occasionally replaced by a soft gelatinous film. If no
second treatment is given to such eggs they will disintegrate in a
comparatively short time, but when sperm is added some or most of
the eggs will develop in the way characteristic of fertilized <span
class="nowrap">eggs.<a name="FNanchor_75_75" id="FNanchor_75_75"></a><a href="#Footnote_75_75" class="fnanchor">75</a></span> When the membrane is too tough to allow
the spermatozoön to enter the egg it can be shown that if the membrane
is torn mechanically the egg can still be fertilized by sperm.</p>
<p>Should it be possible that the spermatozoön can no longer agglutinate
with the fertilized egg or that those phagocytotic reactions which we
suppose to play a rôle in the entrance of the spermatozoön into the egg
are no longer possible after a spermatozoön has entered? The mere fact
of development is apparently not the cause which bars a spermatozoön
from entering an egg already fertilized by sperm.</p>
<p>Lillie assumes that the egg loses its “fertilizin” in the process of
membrane formation since the sea water containing such eggs no longer
gives the agglutinin reaction with sperm, and he believes that the lack
of “fertilizin” in the fertilized egg or in the egg after membrane
formation is the cause of the block in the fertilized egg. But we have
seen that the artificial<span class="pagenum" title="88"><a name="Page_88" id="Page_88"></a></span> membrane formation does not create such a
block although it puts an end to the “fertilizin” reaction. In the
egg of <i class="taxonomic">purpuratus</i> the “fertilizin” reaction ceases when the jelly
surrounding the egg is dissolved by an acid and the eggs are repeatedly
washed; yet such eggs can easily be fertilized by sperm.</p>
<p>Lillie does not assume that the “fertilizin” causes an agglutination
between egg and spermatozoön—we should assent to such an
assumption—but that the “fertilizin” acts like an “amboceptor”
between egg and spermatozoön, the latter being the complement, the
former the antigen. The pathologist would probably object to this
interpretation since no “amboceptor” is needed for agglutination. The
writer has had some doubts concerning the value of Ehrlich’s side-chain
theory which, besides, can only be applied in a metaphorical sense
to the mechanism of the entrance of the spermatozoön into the <span
class="nowrap">egg.<a name="FNanchor_76_76" id="FNanchor_76_76"></a><a href="#Footnote_76_76" class="fnanchor">76</a></span> </p>
<p><span class="pagenum" title="89"><a name="Page_89" id="Page_89"></a></span></p>
<p>6. The reason that an egg once fertilized with sperm cannot be
fertilized again may be found in a group of facts which we will now
discuss, namely, the self-sterility of many hermaphrodites. The fact
that hermaphrodites are often self-sterile, while their eggs can be
fertilized with sperm from a different individual of the same species
has played a great rôle in the theories of evolution. We are here only
concerned with the mechanism which determines the block to the entrance
of a spermatozoön into an egg of the same hermaphroditic individual.</p>
<p><span class="nowrap">Castle<a name="FNanchor_77_77" id="FNanchor_77_77"></a><a href="#Footnote_77_77" class="fnanchor">77</a></span> observed and studied the
phenomenon of self-sterility in an Ascidian, <i class="taxonomic">Ciona intestinalis</i>,
which is hermaphroditic. Animals which were kept isolated discharged
both eggs and sperm into the surrounding sea water. Often no egg was
fertilized, but in some cases five, ten, or as many as fifty per cent.
of the eggs could be successfully fertilized with sperm from the same
individual; while if several individuals were put into the same dish
as a rule one hundred per cent. of the eggs which were discharged
segmented. <span class="nowrap">Morgan<a name="FNanchor_78_78" id="FNanchor_78_78"></a><a href="#Footnote_78_78" class="fnanchor">78</a></span> found that the eggs
of various females differ in their power of being fertilized by sperm
of the same individual while one hundred per cent. could usually be
fertilized with sperm of a different individual. He<span class="pagenum" title="90"><a name="Page_90" id="Page_90"></a></span> found in addition
that if the eggs of <i class="taxonomic">Ciona</i> are put for about ten minutes into a
two per cent. ether solution in sea water in a number of cases the
percentage of eggs fertilized by sperm of the same individual shows a
slight increase. <span class="nowrap">Fuchs<a name="FNanchor_79_79" id="FNanchor_79_79"></a><a href="#Footnote_79_79" class="fnanchor">79</a></span> has reported
results similar to those of Castle and Morgan.</p>
<p>A new point of attack has been introduced into the work of
self-sterility in plants by the consideration of heredity. Darwin
found that in <i class="taxonomic">Reseda</i> which is monœcious (or hermaphroditic)
certain individuals are either completely self-sterile or completely
self-fertile; and Compton showed that apparently self-fertility is a
Mendelian dominant to <span class="nowrap">self-sterility.<a name="FNanchor_80_80" id="FNanchor_80_80"></a><a href="#Footnote_80_80" class="fnanchor">80</a></span></p>
<p>According to Jost this self-sterility in hermaphroditic plants is
due to the fact that if pollen of the same plant is used the normal
growth of the pollen tube is inhibited, while this inhibition does
not exist for pollen from a different individual. Correns calls these
substances which prevent the adequate growth of pollen, “inhibitory”
substances, and finds that they can apparently be transmitted to the
offspring. He made experiments on <i class="taxonomic">Cardamine pratensis</i> which is <span
class="nowrap">self-sterile.<a name="FNanchor_81_81" id="FNanchor_81_81"></a><a href="#Footnote_81_81" class="fnanchor">81</a></span> He fertilized two individuals
of <i class="taxonomic">Cardamine</i> crosswise and raised sixty plants of the first
generation. He compared the fertility of these F<sub>1</sub> plants toward
(<i>a</i>) their parents, and<span class="pagenum" title="91"><a name="Page_91" id="Page_91"></a></span> (<i>b</i>) foreign plants. All the fertilizations
with the foreign plants were successful, but the fertilizations with
the parents were only partly successful. According to their reaction
they could be divided into four groups:</p>
<div class="blockquot">
<p>(<i>A</i>) fertile with both parents. Type bg<br />
(<i>B</i>) fertile with one (B), sterile with the other parent (G).<br />
  (<i>a</i>) fertile with B, sterile with G. Type bG<br />
  (<i>b</i>) fertile with G, sterile with B. Type Bg<br />
(<i>C</i>) sterile with both parents. Type BG</p>
</div>
<p>It was found that approximately fifteen of the sixty children belonged
to each of the four groups. This should be expected if the inhibitory
substance to each parent is transmitted to the children independently.
Half of the children will thus inherit the inhibitory substance of one
parent and the other half will inherit the inhibitory substance of the
other parent. This agrees with the assumption that there are definite
determiners for the inhibitory substances in the children which will be
transmitted to half of the children. Rather complicated assumptions are
needed to explain all the facts observed by Correns on this basis and
since the subject is still under investigation we need not go further
into the details.</p>
<p>To us the assumption and experimental support of the idea that
self-sterility is caused by the presence of a substance inhibitory to
the entrance of a spermatozoön is important. Should it be possible
that the block<span class="pagenum" title="92"><a name="Page_92" id="Page_92"></a></span> created by the entrance of a spermatozoön into the egg
is also due to an inhibitory substance carried by a spermatozoön into
the egg; and furthermore that the effect of the inhibitory substance
should be the prevention of further agglutination of the spermatozoön
with the egg or of the growth of the pollen tube in plants? On such
an assumption self-sterility would be due to a lack of agglutination
between the egg of a hermaphrodite and a spermatozoön of the same
individual. The experiments on the agglutinins have shown that while
isoagglutinins (<i>i. e.</i>, agglutinins for other individuals of the
same species) are common auto-agglutinins (<i>i. e.</i>, agglutinins
for cells of the same individual) rarely if ever occur.</p>
<p>7. A positive chemotropism of the spermatozoa toward an egg of the same
species has been demonstrated in a few cases, but it seems that this
phenomenon is not determined by that type of substances which give
rise to species specificity. The famous experiment of Pfeffer on the
spermatozoa of ferns inaugurates this line of investigation. He found
that such spermatozoa when moving in a straight line through the water
will be deviated in their course if they come near an archegonium;
they will then turn toward it, enter it, and enter the egg. Pfeffer
showed that 0.01 per cent. malic acid if put into a capillary tube will
attract the spermatozoa of ferns.</p>
<p><span class="pagenum" title="93"><a name="Page_93" id="Page_93"></a></span></p>
<div class="blockquot">
<p>When the liquid in the tube contains only 0.01 per cent. malic
acid the spermatozoa of ferns very soon move toward the opening
of the capillary tube and within from five to ten minutes many
hundreds of spermatozoa may accumulate in the tube. The malic acid
acts as well in the form of a free acid as in the form of <span
class="nowrap">salts.<a name="FNanchor_82_82" id="FNanchor_82_82"></a><a href="#Footnote_82_82" class="fnanchor">82</a></span></p>
</div>
<p>These experiments were continued and amplified by Shibata. <span
class="nowrap">Bruchmann<a name="FNanchor_83_83" id="FNanchor_83_83"></a><a href="#Footnote_83_83" class="fnanchor">83</a></span> found that the spermatozoa of
<i class="taxonomic">Lycopodium</i> are positively chemotactic to citric acid and salts of
this acid, although no citric acid could be shown in the contents of
the archegonia. They are also positively chemotactic to the watery
extract from archegonia.</p>
<p>Dewitz, Buller, and the writer have vainly tried to prove the existence
of a positive chemotropism of spermatozoa to eggs of the same species.
Lillie claims to have proved a positive chemotropism of the sperm of
sea urchins to “fertilizin,” but such a conclusion is only justified
if a method similar to that of Pfeffer’s with capillary tubes, gives
positive results; such a method was not used in Lillie’s experiments.
It seems that the fertilization of the egg by sperm is rendered
possible by two facts; first that where fertilization takes place
outside the body egg and sperm are shed simultaneously by the two
sexes. This can be easily ob<span class="pagenum" title="94"><a name="Page_94" id="Page_94"></a></span>served in the case of fish. But it is also
the case in invertebrates. Thus the writer has observed that the sea
urchins <i class="taxonomic">Strongylocentrotus purpuratus</i> at the shore of Pacific Grove
all spawn simultaneously. The examination extended over several miles
of shore. At such spawning seasons the sea water becomes a suspension
of sperm.</p>
<p>The second fact guaranteeing the fertilization of the eggs is the
overwhelming excess of spermatozoa over eggs. The enormous waste in
animated nature is in agreement with the idea of a lack of purpose;
since in this case the laws of chance must play a great rôle; and the
origin of durable organisms by laws of chance is only comprehensible
on the basis of an enormous wastefulness, for which evidence is not
lacking.</p>
<hr class="chap" />
<p><span class="pagenum" title="95"><a name="Page_95" id="Page_95"></a></span></p>
<h2>CHAPTER V</h2>
<h3>ARTIFICIAL PARTHENOGENESIS</h3>
<p>1. The majority of eggs cannot develop unless they are fertilized,
that is to say, unless a spermatozoön enters into the egg. The
question arises: How does the spermatozoön cause the egg to develop
into a new organism? The spermatozoön is a living organism with a
complicated structure and it is impossible to explain the causation of
the development of the egg from the structure of the spermatozoön. No
progress was possible in this field until ways were found to replace
the action of the living spermatozoön by well-known physicochemical
<span class="nowrap">agencies.<a name="FNanchor_84_84" id="FNanchor_84_84"></a><a href="#Footnote_84_84" class="fnanchor">84</a></span> Various observers such as
Tichomiroff, R. Hertwig, and T. H. Morgan had found that unfertilized
eggs may begin to segment under certain conditions, but such eggs
always disintegrated in their experiments without giving rise to
larvæ. In 1899 the writer succeeded in causing the<span class="pagenum" title="96"><a name="Page_96" id="Page_96"></a></span> unfertilized eggs
of the sea urchin <i class="taxonomic">Arbacia</i> to develop into swimming larvæ, blastulæ,
gastrulæ, and plutei, by treating them with hypertonic sea water of a
definite osmotic pressure for about two hours. When such eggs were then
put back into normal sea water many segmented and a certain percentage
developed into perfectly normal larvæ, blastulæ, gastrulæ, and <span
class="nowrap">plutei.<a name="FNanchor_85_85" id="FNanchor_85_85"></a><a href="#Footnote_85_85" class="fnanchor">85</a></span> Soon afterward this was accomplished
by other methods for the unfertilized eggs of a large number of marine
animals, such as starfish, molluscs, and annelids. None of these eggs
can develop under normal conditions unless a spermatozoön enters.
These experiments furnished proof that the activating effect of the
spermatozoön upon the egg can be replaced by a purely physicochemical
<span class="nowrap">agency.<a name="FNanchor_86_86" id="FNanchor_86_86"></a><a href="#Footnote_86_86" class="fnanchor">86</a></span></p>
<p>The first method used in the production of larvæ from the unfertilized
eggs did not lend itself to an analysis of the activating effect of the
spermatozoön upon the egg, since nothing was known about the action of
a hypertonic solution, except that it withdraws water from the egg; and
there was no indication that the entrance of the spermatozoön causes
the egg to lose water. No further progress was possible until another
method of artificial parthenogenesis was found. When a spermatozoön
enters the egg of a sea urchin or starfish<span class="pagenum" title="97"><a name="Page_97" id="Page_97"></a></span> or certain annelids,
the surface of the egg undergoes a change which is called membrane
formation; and which consists in the appearance of a fine membrane
around the egg, separated from the latter by a liquid (Figs. 4 and
5). O. and R. Hertwig and Herbst had observed that such a membrane
could be produced in an unfertilized egg if the latter was put into
chloroform or xylol, but such eggs perished at once. It was generally
assumed, moreover, that the process of membrane formation was of no
significance in the phenomenon of fertilization, except perhaps that
the fertilization membrane guarded the fertilized egg against a further
invasion by sperm. However, since the fertilized egg is protected
against this possibility by other means the membrane is hardly needed
for such a purpose.</p>
<table width="390" summary="figures 4-5">
<tr><td><div class="figleft" style="width: 175px;">
<img src="images/fig_004.png" width="175" height="165" alt="" /></div></td>
<td><div class="figright" style="width: 175px;">
<img src="images/fig_005.png" width="175" height="174" alt="" /></div></td></tr>
<tr><td class="tac fs90"><span class="smcap">Fig. 4  </span></td>
<td class="tac fs90"><span class="smcap">  Fig. 5</span></td></tr>
<tr><td class="fs90 plhi taj" colspan="2" style="width: 350px;"><span class="smcap">Fig. 4.</span> Unfertilized egg surrounded by
spermatozoa (whose flagellum is omitted in the drawing).</td></tr>
<tr><td class="fs90 plhi taj" colspan="2" style="width: 350px;"><span class="smcap">Fig. 5.</span> The same egg after a spermatozoön
has entered. The fertilization membrane is separated from the egg by a
clear space.</td></tr>
</table>
<p><span class="pagenum" title="98"><a name="Page_98" id="Page_98"></a></span></p>
<p>In 1905 the writer found that membrane formation, or rather the change
of the surface of the egg underlying the membrane formation, is the
essential feature in the activation of the egg by a spermatozoön. He
observed that when unfertilized eggs of the Californian sea urchin
<i class="taxonomic">Strongylocentrotus purpuratus</i> are put for from one and a half to
three minutes into a mixture of 50 c.c. of sea water+2.6 c.c. N/10
acetic or propionic or butyric or valerianic acid and are then put
into normal sea water all or the majority of the eggs form membranes;
and that such eggs when the temperature is very low will segment once
or repeatedly and may even—if the temperature is as low as 4°C. or
less—develop into swimming <span class="nowrap">blastulæ<a name="FNanchor_87_87" id="FNanchor_87_87"></a><a href="#Footnote_87_87" class="fnanchor">87</a></span>;
but they will then disintegrate. On the other hand, if they are kept at
room temperature they will develop only as far as the aster formation
and nuclear division and then begin to disintegrate. It should be
mentioned that the time which elapses between artificial membrane
formation and nuclear division is greater than that between the
entrance of a spermatozoön and nuclear division.</p>
<p>It was obvious, therefore, that artificial membrane formation induced
by butyric acid initiates the processes underlying development of the
egg but that for some reason the egg is sickly and perishes rapidly.</p>
<p>When, however, such eggs were given a short treat<span class="pagenum" title="99"><a name="Page_99" id="Page_99"></a></span>ment with hypertonic
sea water or with lack of oxygen or with KCN they developed into normal
larvæ. This new or improved method of artificial parthenogenesis is as
follows: The eggs are put for from two to four minutes into 50 c.c.
sea water containing a certain amount of N/10 butyric acid (2.6 c.c.
in the case of S. <i class="taxonomic">purpuratus</i> in California and 2.0 c.c. in the case
of <i class="taxonomic">Arbacia</i> in Woods Hole). Ten or fifteen minutes later the eggs are
put into hypertonic sea water (50 c.c. sea water+8 c.c. 2<sup>1</sup>⁄<sub>2</sub> m NaCl
or Ringer solution or cane sugar) in which they remain, at 15° C. from
thirty-five to sixty minutes in the case of <i class="taxonomic">purpuratus</i>, and from
17<sup>1</sup>⁄<sub>2</sub> minutes to 22<sup>1</sup>⁄<sub>2</sub> minutes at 23° in the case of <i class="taxonomic">Arbacia</i> at
Woods Hole. If the eggs are then transferred to normal sea water they
will develop. In making these experiments, which have been repeated and
confirmed by numerous investigators, it should be remembered that this
effect of the hypertonic solution has a high temperature coefficient
(about two for 10° C.) and that a slight overexposure to the hypertonic
sea water injures the eggs so that development is abnormal. By this
method it is possible to imitate the activating effect of the living
spermatozoön upon the egg in every detail and eggs treated in this way
will develop in large numbers into perfectly normal larvæ. We shall see
later that they can also be raised to the adult state.</p>
<p>2. The next task was to find out the nature of the<span class="pagenum" title="100"><a name="Page_100" id="Page_100"></a></span> action of the
two agencies upon the development of the egg. It soon became obvious
that the membrane formation (or the alteration underlying membrane
formation) was the more important of the two, since in the eggs of
starfish and annelids this was sufficient for the production of
larvæ, and that the second treatment had only the corrective effect,
of overcoming the sickly condition in which mere membrane formation
had left the eggs. It was, therefore, of great interest to ascertain
what substances or agencies caused membrane formation in the egg,
since it now became clear that the spermatozoön could only cause
membrane formation by carrying one such substance into the egg. These
investigations led the writer to the result that all those substances
and agencies which are known to cause cytolysis or hemolysis (see
Chapter III) will also induce membrane formation, and that the
essential feature in the causation of development is a cytolysis of
the superficial or cortical layer of the egg. As soon as this layer is
destroyed the development of the egg can begin.</p>
<p>The substances and agencies which cause cytolysis and hence, if
their action is restricted to the surface of the egg, will induce
development are, besides the fatty acids: (1) saponin or solanin or
bile salts; (2) the solvents of lipoids, benzol, toluol, amylene,
chloroform, aldehyde, ether, alcohols, etc.; (3) bases; (4) hypertonic
or hypotonic solutions; (5) rise in temperature, and (6) certain<span class="pagenum" title="101"><a name="Page_101" id="Page_101"></a></span>
salts, <i>e. g.</i>, BaCl<sub>2</sub> and SrCl<sub>2</sub> in the case of the egg of
<i class="taxonomic">purpuratus</i>, and according to R. Lillie, NaI or NaCNS in the egg of
<i class="taxonomic">Arbacia</i>. Whenever we submit an unfertilized sea-urchin egg to any
of these agencies and restrict the cytolysis to the superficial or
cortical layer of the egg (<i>i. e.</i>, if we transfer the egg to
normal sea water before the cytolytic agent has had time to diffuse
into the main egg) the egg will form a membrane and behave as if the
membrane formation had been called forth by a fatty acid, with this
difference only, that the various agencies are not all equally harmless
for the <span class="nowrap">egg.<a name="FNanchor_88_88" id="FNanchor_88_88"></a><a href="#Footnote_88_88" class="fnanchor">88</a></span></p>
<p>If the idea was correct that the change underlying membrane formation
was essentially a cytolysis of the cortical layer of the egg, it was
to be expected (from the data contained in Chapter III) that the
blood serum or the cell extracts of foreign species would also cause
membrane formation and thus induce the development of the unfertilized
egg, while serum of animals of the same species or genus would have no
such effects. This was found to be correct. In 1907 the writer showed
that the blood serum of a Gephyrean worm, <i class="taxonomic">Dendrostoma</i>, was able to
cause membrane formation in the egg of the sea urchin. When added in a
dilution of 1 c.c. of serum to 500 or 1000 c.c. of sea water to eggs of
<i class="taxonomic">purpuratus</i> a certain number formed fertilization membranes. It was
found later that the serum and tissue<span class="pagenum" title="102"><a name="Page_102" id="Page_102"></a></span> extracts of a large number of
animals, especially of mammals (rabbit, pig, ox, etc.), had the same
effect, though it was necessary to use higher concentrations, one-half
sea water and one-half isotonic blood serum. The eggs of every female
sea urchin, however, did not give the reaction and not all the eggs
even of sensitive females formed membranes. The writer found, however,
that it was possible to increase the susceptibility of the eggs against
foreign blood serum by putting them into a <sup>3</sup>⁄<sub>8</sub> m solution of SrCl<sub>2</sub>
for from five to ten minutes (or possibly a little longer) before
exposing them to the foreign blood serum. BaCl<sub>2</sub> acts similarly. The
fact that SrCl<sub>2</sub> alone can cause membrane formation in unfertilized
eggs if they are left long enough in the solution suggests that the
sensitizing effect of the substance consists in a modification of the
cortical layer similar to that underlying membrane formation; and
that the subliminal effect of a short treatment with SrCl<sub>2</sub> and the
subliminal effect of the foreign serum when combined suffice to bring
about the membrane formation.</p>
<p>Not only the watery extract of foreign cells but also that of foreign
sperm, induces membrane formation in the sea-urchin egg. The watery
extract of sperm of starfish is especially active, but the degree of
activity varies considerably with the species of starfish from which
the sperm is taken. The eggs of different species of sea urchins
also show a different degree of suscepti<span class="pagenum" title="103"><a name="Page_103" id="Page_103"></a></span>bility for the sperm of
foreign species. Thus the eggs of <i class="taxonomic">Strongylocentrotus purpuratus</i>
require a higher concentration of sperm extract than the eggs of <i class="taxonomic">S.
franciscanus</i>. For the latter the amount of foreign cell constituents
which suffices to call forth membrane formation is so small that
contact with almost any foreign living spermatozoön produces this
effect; and as a rule no previous sensitizing action of SrCl<sub>2</sub> is
required. When we bring the unfertilized eggs of <i class="taxonomic">S. franciscanus</i> into
contact with the living sperm of starfish or shark or even of fowl,
the eggs form a fertilization membrane without previous sensitization.
A specific substance from the foreign spermatozoön causes membrane
formation before the spermatozoön has time to enter the egg. The
effect is the same as if artificial membrane formation had been called
forth with butyric acid, <i>i. e.</i>, they begin to develop and then
disintegrate unless they receive a second short treatment.</p>
<p>When, however, we treat the eggs with the watery extracts from the
cells of their own or closely related species we find that these
extracts are utterly inactive, even if used in comparatively strong
concentrations. This agrees with the results given in Chapter III.</p>
<p>These phenomena lead to a very paradoxical result; namely that while
in the case of foreign sperm we can cause membrane formation by both
the living and the dead spermatozoön, only the living spermatozoön
of<span class="pagenum" title="104"><a name="Page_104" id="Page_104"></a></span> the same species can induce membrane formation. This might find
its explanation on the assumption that the active substance contained
in the foreign sperm or serum is water-soluble and a protein, while
the activating or membrane-forming substance in the spermatozoön is
insoluble in water but soluble in the egg (or in lipoids). If this
assumption is correct the two substances are essentially different.</p>
<p><span class="nowrap">Robertson<a name="FNanchor_89_89" id="FNanchor_89_89"></a><a href="#Footnote_89_89" class="fnanchor">89</a></span> has succeeded in extracting
a substance from the sperm of the sea urchin which causes membrane
formation of the sea-urchin egg after the latter has been sensitized by
a treatment with SrCl<sub>2</sub>. It seems to the writer that if the substance
extracted by Robertson were the real fertilizing agent contained
in the spermatozoön it should fertilize the egg without a previous
sensitization of the egg with SrCl<sub>2</sub> being required.</p>
<p>3. The action of acids in the mechanism of artificial parthenogenesis
provides some interesting physiological problems. When unfertilized
sea-urchin eggs are left <em>in</em> sea water containing any of the lower
fatty acids up to capronic, the eggs will form no membranes, while
<em>in</em> such sea water, and they will show no outer signs of cytolysis
(swelling). When, however, the eggs are left in sea water containing
any of the fatty acids from heptylic upward the eggs will form
membranes while <em>in</em> the acid sea water and soon afterward will
cytolyze<span class="pagenum" title="105"><a name="Page_105" id="Page_105"></a></span> completely and swell enormously. In solutions of the mineral
acids no membranes are formed and none are formed as a rule when the
eggs are transferred back to sea water. When both a mineral and a
lower fatty acid, <i>e. g.</i>, butyric, are added to sea water the
mineral acid acts as if it were not present, <i>i. e.</i>, the eggs
form membranes when transferred back to sea water if the concentration
of the butyric acid is high enough. All these data are comprehensible
if we assume that only that part of the acid causes membrane formation
which is lipoid soluble, while the water soluble part is not involved
in the process of membrane formation; and that the cytolysis or
swelling of the whole egg can only take place in the higher fatty acids
(heptylic or above) which are little soluble in water and very soluble
in lipoids, while the lower fatty acids, whose water solubility is
comparatively high, can only bring about a cytolysis and swelling in
the cortical layer but not in the rest of the egg. This makes it appear
as though the part undergoing an alteration in membrane formation was a
lipoid; and this would harmonize with the assumption that the specific
membrane-inducing substance in the spermatozoön is not soluble in
water, but soluble in fat.</p>
<p>4. These and other observations led the writer to the view that the
essential process which causes development might be an alteration
of the surface of the egg, in all probability an alteration of the
superficial<span class="pagenum" title="106"><a name="Page_106" id="Page_106"></a></span> layer probably of the nature of a superficial cytolysis.
The question remains: What could be the physicochemical nature of
this cytolysis? The writer had suggested in former papers that in the
cytolysis underlying membrane formation lipoids were dissolved, and he
supposed that the substance to be dissolved might be a calcium-lipoid
compound which might form a continuous layer under the surface of
the <span class="nowrap">egg.<a name="FNanchor_90_90" id="FNanchor_90_90"></a><a href="#Footnote_90_90" class="fnanchor">90</a></span> v. Knaffl, working on the
cytolysis of eggs in the writer’s laboratory, gave the following idea
of the process:</p>
<div class="blockquot">
<p>Protoplasm is rich in lipoids; probably it is mainly an emulsion
of these and proteins. Any physical or chemical stimulus which
can liquefy the lipoids causes cytolysis of the egg. The protein
of the egg can really only swell or be dissolved if the condition
of aggregation of the lipoid is altered by chemical or physical
agencies. The mechanism of cytolysis consists in the liquefaction
of the lipoids and thereupon the lipoid-free protein swells or
is dissolved by taking up water. . . . Hence this
supports Loeb’s view that membrane formation is induced by the
liquefaction of <span class="nowrap">lipoids.<a name="FNanchor_91_91" id="FNanchor_91_91"></a><a href="#Footnote_91_91" class="fnanchor">91</a></span></p>
</div>
<p>The writer suggested that the destruction of an emulsion in the
cortical layer might possibly be the essential feature of the
alteration leading to membrane formation and development. It had been
long observed that unfertilized starfish eggs may begin to<span class="pagenum" title="107"><a name="Page_107" id="Page_107"></a></span> develop
apparently without any outside “stimulus,” and A. P. Mathews found
that slight mechanical agitation of these eggs in sea water increased
the number which developed. It has been shown in numerous experiments
by Delage, R. S. Lillie, and the writer, that the substances causing
development in the starfish egg are identical or closely related to
those which bring about this effect in the egg of the sea urchin and in
both cases the development is preceded by a membrane formation.</p>
<div class="blockquot">
<p>But how can membrane formation be produced by mere agitation? It
seems to me that this can be understood if we suppose that it
depends upon the destruction of an emulsion in the cortical layer
of the egg. It is conceivable that in the egg of certain forms the
stability of this emulsion is so small that mere shaking would be
enough to destroy it and thus induce membrane formation and <span
class="nowrap">development.<a name="FNanchor_92_92" id="FNanchor_92_92"></a><a href="#Footnote_92_92" class="fnanchor">92</a></span></p>
</div>
<p>The durability of emulsions varies, and where an emulsion is very
durable shaking has no effect, while where it is at the critical point
of separating into two continuous phases a slight shaking will bring
about the separation, and where the emulsion is still less durable we
observe the phenomenon of a “spontaneous” parthenogenesis. Eggs like
those of most sea urchins belong to the former, eggs like those of some
starfish and annelids belong to the second or third type.</p>
<p>It is impossible to state at present whether the fertil<span class="pagenum" title="108"><a name="Page_108" id="Page_108"></a></span>ization
membrane is preformed in the fertilized egg and merely lifted off from
the egg or whether its formation is due to the hardening of a colloidal
substance separated from the emulsion (or excreted) and hardened in
touch with sea water. But we can be sure of one thing, namely, that
the liquid between egg and membrane contains some colloidal substance
which determines the tension and spherical shape of the membrane. The
membrane is obviously permeable not only to water but also to dissolved
crystalloids, while it is impermeable to colloids. When we add some
colloidal solution (<i>e. g.</i>, white of egg, blood serum, or tannic
acid) to the sea water containing fertilized eggs of <i class="taxonomic">purpuratus</i>, the
membrane collapses and lies close around the egg; while if the eggs are
put back into sea water or a sugar solution the membrane soon assumes
its spherical shape. This is intelligible on the assumption that in the
process of membrane formation (or in the destruction of the emulsion
in the cortical layer) a colloidal substance goes into solution which
cannot diffuse into the sea water since the membrane is impermeable to
the colloidal particles. The membrane is, however, permeable to the
constituents of sea water or to sugar. Consequently sea water will
diffuse into the space between membrane and egg until the tension of
the membrane equals the osmotic pressure of the colloid dissolved in
the space between egg and the membrane. If we add enough colloid to the
outside solution so that<span class="pagenum" title="109"><a name="Page_109" id="Page_109"></a></span> its osmotic pressure is higher than that of
the colloidal solution inside the membrane the latter will collapse.</p>
<p>It should also be stated that the unfertilized eggs of many marine
animals are surrounded by a jelly (chorion) which is dissolved when the
egg is <span class="nowrap">fertilized.<a name="FNanchor_93_93" id="FNanchor_93_93"></a><a href="#Footnote_93_93" class="fnanchor">93</a></span> The writer has shown
that the same chemical substances which will induce membrane formation
and artificial parthenogenesis will as a rule also cause a swelling and
liquefaction of the chorion.</p>
<p>We have devoted so much space to the mechanism of membrane formation
since it is likely to give a clearer insight into the physicochemical
nature of physiological processes than the phenomena of muscular
stimulation and contraction or nerve stimulation, upon which the
majority of physiologists base their conclusions concerning the
mechanism of life phenomena.</p>
<p>Before we come to the discussion of the second factor in the
activation of the egg it should be stated more definitely that for
the eggs of some forms the first factor, the process underlying
membrane formation, suffices for the development of the egg into a
larva and that no second factor is required in these cases. This
is true for the eggs of starfish and certain annelids.<span class="pagenum" title="110"><a name="Page_110" id="Page_110"></a></span> Thus in
1901 <span class="nowrap">Loeb<a name="FNanchor_94_94" id="FNanchor_94_94"></a><a href="#Footnote_94_94" class="fnanchor">94</a></span> and Neilson showed that
a short treatment with HCl and HNO<sub>3</sub> sufficed to cause some eggs
of <i class="taxonomic">Asterias</i> in Woods Hole to develop into larvæ without a second
treatment being needed, and <span class="nowrap">Delage<a name="FNanchor_95_95" id="FNanchor_95_95"></a><a href="#Footnote_95_95" class="fnanchor">95</a></span>
showed the same for CO<sub>2</sub>; and in 1905 the writer found that the
eggs of the Californian starfish <i class="taxonomic">Asterina</i> can be induced to form a
membrane by butyric acid treatment and that ten per cent. of these
eggs developed into normal larvæ. Quite recently R. S. Lillie observed
that the eggs of <i class="taxonomic">Asterias</i> at Woods Hole can be caused to form
membranes and develop into larvæ by a treatment with butyric acid and
that the time of exposure required to get a maximal number of larvæ
varies approximately inversely with the concentration of the acid,
within a range of 0.0005 to 0.006 N butyric acid. If the exposure
is too short membrane formation will occur without normal <span
class="nowrap">development.<a name="FNanchor_96_96" id="FNanchor_96_96"></a><a href="#Footnote_96_96" class="fnanchor">96</a></span></p>
<p>All this leads us to the conclusion that the main effect of the
spermatozoön in inducing the development of the egg consists in an
alteration of the surface of the latter which is apparently of the
nature of a cytolysis of the cortical layer. Anything that causes
this alteration without endangering the rest of the egg may induce
its development. The spermatozoön, therefore, causes<span class="pagenum" title="111"><a name="Page_111" id="Page_111"></a></span> the development
of the egg by carrying a substance into the latter which effects an
alteration of its surface layer.</p>
<p>5. We will now discuss the action of the second, corrective factor,
in the inducement of development. When we cause membrane formation in
a sea-urchin egg by the proper treatment with butyric acid it will
commence to develop and segment but will disintegrate rapidly if kept
at room temperature and the more rapidly the higher the temperature.
If, however, the eggs are treated afterward for a certain length of
time (from thirty-five to sixty minutes at 15° C. for <i class="taxonomic">purpuratus</i>
and 17<sup>1</sup>⁄<sub>2</sub> to 22<sup>1</sup>⁄<sub>2</sub> minutes for <i class="taxonomic">Arbacia</i> at 23° C.) in a solution
which is isosmotic with 50 c.c. sea water+8 c.c. 2<sup>1</sup>⁄<sub>2</sub> m <span
class="nowrap">NaCl,<a name="FNanchor_97_97" id="FNanchor_97_97"></a><a href="#Footnote_97_97" class="fnanchor">97</a></span> they will develop into larvæ, many of
which may be normal. Any hypertonic solution of this osmotic pressure,
sea water, sugar, or a single salt, will suffice provided the solution
does not contain substances that are too destructive for living matter.
The hypertonic solution produces its corrective effect only if the egg
contains free oxygen; and in a slightly alkaline medium more rapidly
than in a neutral medium. The time of exposure in the hypertonic
solution dimin<span class="pagenum" title="112"><a name="Page_112" id="Page_112"></a></span>ishes in certain limits with the concentration of OH
ions in the solution.</p>
<p>It is strange that in the eggs of <i class="taxonomic">purpuratus</i> the corrective effect
can also be brought about by exposing the eggs after the artificial
membrane formation for about three hours to normal sea water free from
oxygen; or to sea water in which the oxidations have been retarded by
the addition of KCN. This method is not so reliable as the treatment
with hypertonic solution.</p>
<p>What does the hypertonic solution do to prevent the disintegration of
the egg after the artificial membrane formation? The writer suggested
in 1905 that the artificial membrane formation alone starts the
development but leaves the eggs usually in a sickly condition and that
the hypertonic solution or the lack of oxygen allows them to recuperate
from such a condition. The second factor is, according to this view,
merely a corrective or curative factor. The following observations will
explain the reasons for such an assumption.</p>
<p>The writer found that if we keep the unfertilized eggs after artificial
membrane formation in sea water deprived of oxygen the disintegration
of the egg following artificial membrane formation is prevented for
a day at least. The same result can be obtained by adding ten drops
of <sup>1</sup>⁄<sub>10</sub> per cent. KCN to 50 c.c. of sea water, and certain narcotics,
<i>e. g.</i>, chloral hydrate, act in the same way. Wasteneys and
the writer found that chloral hydrate (and other narcotics) in the
con<span class="pagenum" title="113"><a name="Page_113" id="Page_113"></a></span>centration required do not suppress or even lower the oxidations
in the egg to any considerable <span class="nowrap">extent,<a name="FNanchor_98_98" id="FNanchor_98_98"></a><a href="#Footnote_98_98" class="fnanchor">98</a></span>
but they prevent the processes of cell division. Hence it seems that
the egg disintegrates so rapidly after artificial membrane formation
because it is killed by those processes leading to nuclear division or
cell division which are induced by the artificial membrane formation.
If we suppress these phenomena of development (for not too long a time)
we give the egg a chance to recover and if now the impulse to develop
is still active we notice a perfectly normal development. If the egg is
kept too long without oxygen it suffers for other reasons and cannot
develop; the writer has shown that if eggs fertilized by sperm are kept
for too long a time without oxygen they also will no longer be able
to develop normally. The short treatment with a hypertonic solution
supplies the corrective factor required, so that the egg can then
undergo cell division at room temperature without disintegrating.</p>
<p>The correctness of this interpretation, which is in reality mainly a
statement of observations, is proved by the two following groups of
facts. The older observers had already noticed that the unfertilized
eggs of the sea urchin when lying in sea water will die after a day
or more, and that occasionally such eggs show nuclear division or
even the beginning of cell division<span class="pagenum" title="114"><a name="Page_114" id="Page_114"></a></span> shortly before disintegration
sets in. The writer has studied this phenomenon in the unfertilized
eggs of <i class="taxonomic">purpuratus</i> and found that only the eggs of certain females
show this cell division before disintegration and that the cell
division is preceded by an atypical form of membrane formation; the
eggs surrounding themselves by a fine gelatinous film comparable to
that produced in the egg of <i class="taxonomic">Arbacia</i> by a treatment with butyric
acid. It is difficult to state what induces the alteration of the
surface in the eggs that lie so long in sea water. It may be due to
the CO<sub>2</sub> formed by the eggs—since we know that CO<sub>2</sub> may induce
membrane formation—or it may be due to the alkalinity of the sea
water or to a substance originating from the jelly surrounding the
eggs. It was found that if such eggs are kept without oxygen their
disintegration (and cell division) will be delayed considerably. The
presumable explanation for this is that the lack of oxygen prevents
the internal changes underlying cell division and thus prevents
the disintegration of the egg. The direct proof that an egg in the
process of cell division is more endangered by abnormal solutions
than an egg at rest has been furnished by numerous observations of
the writer. He showed in 1906 that the fertilized egg of <i class="taxonomic">purpuratus</i>
dies rather rapidly in a pure m/2 NaCl or any other abnormal isotonic
solution, while the unfertilized egg can live for days in such <span
class="nowrap">solutions.<a name="FNanchor_99_99" id="FNanchor_99_99"></a><a href="#Footnote_99_99" class="fnanchor">99</a></span> In<span class="pagenum" title="115"><a name="Page_115" id="Page_115"></a></span> a series of papers, beginning
in 1905, he showed that the fertilized egg will live longer in
hypertonic, hypotonic, and otherwise abnormally constituted solutions
when the cell divisions are suppressed by lack of oxygen or by the
addition of KCN or of chloral <span class="nowrap">hydrate.<a name="FNanchor_100_100" id="FNanchor_100_100"></a><a href="#Footnote_100_100" class="fnanchor">100</a></span>
It is thus obvious that coincident with the changes underlying nuclear
division or cell division alterations occur in the sensitiveness of
the egg to salt solutions of abnormal concentration or constitution,
<i>e. g.</i>, NaCl+CaCl<sub>2</sub> isotonic with sea water, hypertonic, or
hypotonic solutions.</p>
<p>We must, therefore, conclude that artificial membrane formation
induces development but that it leaves the egg in a sickly condition
in which the very processes leading to cell division bring about
its destruction; that if it is given time it can recover from this
condition and that the treatment with the hypertonic solution also
brings about this recovery rapidly and reliably.</p>
<p><span class="nowrap">Herlant<a name="FNanchor_101_101" id="FNanchor_101_101"></a><a href="#Footnote_101_101" class="fnanchor">101</a></span> suggested that the corrective
effect of the hypertonic solution consisted in the proper development
of the astrospheres required for cell division. According to this
author mere membrane formation does not lead to the formation of
sufficiently large astrospheres and hence cell division may remain
<span class="pagenum" title="116"><a name="Page_116" id="Page_116"></a></span><span class="nowrap">impossible.<a name="FNanchor_102_102" id="FNanchor_102_102"></a><a href="#Footnote_102_102" class="fnanchor">102</a></span> The writer has no
<i lang="la" xml:lang="la">a priori</i> objection to this suggestion which agrees with earlier
observations by Morgan except that it is at present difficult to
harmonize it with all the facts. Why should it be possible to replace
the treatment with the hypertonic solution by a suspension of the
oxidations in the egg for three hours while we know that lack of oxygen
suppresses the formation of astrospheres in the fertilized eggs? What
becomes of the astrospheres if the treatment with the hypertonic
solution precedes the membrane formation by a number of hours or a day
(which is possible as we shall see), and why do they not induce cell
division, if Herlant’s idea is correct? Nevertheless the suggestion of
Herlant deserves to be taken into serious consideration.</p>
<p>6. How can an alteration of the surface of the egg—<i>e. g.</i>,
a cytolytic or other destruction of the cortical layer—lead to
a beginning of development? The answer is possibly given in the
relation of oxidation to development. The writer found in 1895
that if oxygen is withdrawn from the fertilized sea-urchin egg it
can not segment and this seems to be the case for eggs in <span
class="nowrap">general.<a name="FNanchor_103_103" id="FNanchor_103_103"></a><a href="#Footnote_103_103" class="fnanchor">103</a></span> In 1906 he found that the
rapid disintegration of the eggs of the sea urchin which follows
artificial<span class="pagenum" title="117"><a name="Page_117" id="Page_117"></a></span> membrane formation could be prevented when the eggs were
deprived of oxygen or when the oxidations were suppressed in the
eggs by KCN. This suggested a connection between the disintegration
of the egg after artificial membrane formation and the increase in
the rate of oxidations; and he found further that the formation of
acid is greater in the fertilized than in the unfertilized egg. He,
therefore, expressed the view in 1906 that the essential feature
(or possibly one of the essential features) of the process of
fertilization was the increase of the rate of oxidations in the egg
and that this increase was caused by the membrane formation <span
class="nowrap">alone.<a name="FNanchor_104_104" id="FNanchor_104_104"></a><a href="#Footnote_104_104" class="fnanchor">104</a></span> These conclusions have been since
amply confirmed by the measurements of O. Warburg as well as those of
Loeb and Wasteneys, both showing that the entrance of the spermatozoön
into the egg raises the rate of oxidations from 400 to 600 per cent.,
and that membrane formation alone brings about an increase of similar
magnitude. Loeb and Wasteneys found that the hypertonic solution does
not increase the rate of oxidations in a fertilized egg. It does do so,
however, in an unfertilized egg without membrane formation, but merely
for the reason that in such an egg the hypertonic solution brings about
the cytolytic change in the cortex of the egg underlying membrane
<span class="pagenum" title="118"><a name="Page_118" id="Page_118"></a></span><span class="nowrap">formation.<a name="FNanchor_105_105" id="FNanchor_105_105"></a><a href="#Footnote_105_105" class="fnanchor">105</a></span> According to Warburg it
is probable that the oxidations occur mainly if not exclusively at the
surface of the egg since NaOH, which does not diffuse into the egg,
raises the rate of oxidations more than NH<sub>4</sub>OH which does diffuse
into the egg. And finally, the same author showed that the oxidations
in the sea-urchin egg are due to a catalytic process in which iron acts
as a <span class="nowrap">catalyzer.<a name="FNanchor_106_106" id="FNanchor_106_106"></a><a href="#Footnote_106_106" class="fnanchor">106</a></span> In view of all these
facts and their harmony with the methods of artificial parthenogenesis
the suggestion is justifiable that the alteration or cytolysis of the
cortical layer of the egg is in some way connected with the increased
rate of oxidations.</p>
<p>The question remains then: How can membrane formation or the alteration
of the cortical layer underlying membrane formation cause an increase
in the rate of oxidations? One possibility is that the iron (or
whatever the nature of the catalyzer may be) exists in the cortex of
the egg in a masked condition—or in a condition in which it is not
able to act—while the alteration of the cortical layer makes the iron
active. It might be that either the iron or the oxidizable substrate is
contained in the lipoid layer in the unfertilized condition of the egg
and that the destruction or cytolysis of the cortical layer brings both
the iron and the oxidizable substrate into the watery phase in which
they can interact.</p>
<p><span class="pagenum" title="119"><a name="Page_119" id="Page_119"></a></span></p>
<p>Another possibility is that the act of fertilization increases
the permeability of the egg. This idea, which seems attractive,
was first suggested and discussed by the writer in <span
class="nowrap">1906.<a name="FNanchor_107_107" id="FNanchor_107_107"></a><a href="#Footnote_107_107" class="fnanchor">107</a></span> He had found that when fertilized and
unfertilized eggs were put into abnormal salt solutions, <i>e. g.</i>,
pure solutions of NaCl, the fertilized eggs died more rapidly than
the unfertilized eggs and he pointed out that these experiments
suggested the possibility that fertilization increases the permeability
of the egg for salts. The reason for his hesitation to accept this
interpretation was, that the fertilized egg is also more easily injured
by lack of oxygen than the unfertilized egg and in this case the
greater sensitiveness of the fertilized egg was obviously due to its
greater rate of metabolism. Later experiments by the writer showed
that the fertilized egg can be made more resistant to abnormal salt
solutions if its development is suppressed by lack of oxygen or by KCN
or by certain narcotics. With our present knowledge it does not seem
very probable that lack of oxygen diminishes the permeability of the
egg, but we know that it inhibits the developmental processes. Warburg
has made it appear very probable that the fertilized egg is impermeable
for NaOH and if this is the case it should also be impermeable for
<span class="nowrap">NaCl.<a name="FNanchor_108_108" id="FNanchor_108_108"></a><a href="#Footnote_108_108" class="fnanchor">108</a></span></p>
<p><span class="pagenum" title="120"><a name="Page_120" id="Page_120"></a></span></p>
<p>The idea that fertilization and membrane formation cause an
increase in the permeability of the egg was later accepted and
elaborated by R. Lillie. This author assumes that the unfertilized
egg cannot develop because it contains too much CO<sub>2</sub> but that
the CO<sub>2</sub> can escape from the egg as soon as its permeability is
increased through the destruction of the cortical layer of the <span
class="nowrap">egg.<a name="FNanchor_109_109" id="FNanchor_109_109"></a><a href="#Footnote_109_109" class="fnanchor">109</a></span> After the CO<sub>2</sub> has escaped, the
excessive permeability must be restored to its normal value and this
is the rôle of the hypertonic treatment. It is, however, difficult
to harmonize the assumption of an impermeability of the unfertilized
egg for CO<sub>2</sub> with the fact that if the unfertilized sea-urchin egg
is cut into two, as is done in merogony, no development takes place,
while such pieces will develop when a spermatozoön enters. The cortical
layer is removed along the cut surface and there is no reason why the
CO<sub>2</sub> should not escape. Besides, the experiments of Godlewski and the
writer prove that the cortical layer of the unfertilized sea-urchin
egg is apparently very permeable for CO<sub>2</sub> since the latter causes
membrane formation if contained in the sea water in sufficiently high
concentration.</p>
<p>Lillie assumes that the hypertonic treatment restores the permeability
raised to excess by the butyric acid treatment, but this assumption is
not in harmony with<span class="pagenum" title="121"><a name="Page_121" id="Page_121"></a></span> the following facts. The writer has shown that it
is immaterial whether the eggs are treated first with the hypertonic
solution and then with butyric acid or the reverse, if only the eggs
remain longer in the hypertonic solution when the hypertonic treatment
precedes the butyric acid treatment. It was stated in the beginning
of this chapter that the development of the egg can be induced by
hypertonic sea water, and we know the reason since hypertonic sea
water is a cytolytic agency. The writer found that when we expose
unfertilized eggs of <i class="taxonomic">purpuratus</i> for from two to two and a half-hours
to hypertonic sea water they will often not develop and only a few eggs
will undergo the first cell divisions, then going into a condition of
rest. When these eggs, both the segmented and unsegmented, were treated
twenty-four or thirty-six hours later with butyric acid, so that they
formed a membrane, they all developed into larvæ without further
treatment. It is impossible to apply Lillie’s theory to these facts,
for the simple reason that the treatment with hypertonic sea water was
just long enough to induce development in some eggs and hence according
to Lillie’s ideas must have increased the permeability of these eggs.
Yet these same eggs were induced to develop normally when subsequently
treated with butyric acid, which according to Lillie also acts by
increasing the permeability. Nothing indicates that the treatment of
the eggs with a hypertonic solution diminishes<span class="pagenum" title="122"><a name="Page_122" id="Page_122"></a></span> their permeability; the
reverse would be much more probable.</p>
<p>Lillie’s theory also fails to explain that mere treatment of the eggs
with a hypertonic solution can bring about their development into
larvæ. This, however, is intelligible on the assumption that the
hypertonic solution in this case has two different effects, first a
cytolysis of the cortical layer of the egg and second an entirely
different effect, possibly upon the interior of the egg, which
represents the second or corrective effect.</p>
<p><span class="nowrap">McClendon<a name="FNanchor_110_110" id="FNanchor_110_110"></a><a href="#Footnote_110_110" class="fnanchor">110</a></span> has shown that the
electrical conductivity of the egg is increased after fertilization,
and J. <span class="nowrap">Gray<a name="FNanchor_111_111" id="FNanchor_111_111"></a><a href="#Footnote_111_111" class="fnanchor">111</a></span> has found that this
increase in conductivity is only transitory and disappears in fifteen
minutes. This might indicate that the egg becomes transitorily more
permeable for salts after the entrance of the spermatozoön or after
membrane formation; although an increase in conductivity might be
caused by other changes than a mere increase in permeability of the
egg. The writer is of the opinion that it is necessary to meet all
these and other difficulties before we can state that the alteration of
the cortical layer, which is the essential feature of development, acts
chiefly or exclusively by an increase in the permeability of the <span
class="nowrap">egg.<a name="FNanchor_112_112" id="FNanchor_112_112"></a><a href="#Footnote_112_112" class="fnanchor">112</a></span></p>
<p><span class="pagenum" title="123"><a name="Page_123" id="Page_123"></a></span></p>
<p>7. When the experiments on artificial parthenogenesis were first
published they aroused a good deal of antagonism not only among
reactionaries in general but also among a certain group of biologists.
O. Hertwig had defined fertilization as consisting in the fusion of
two nuclei, the egg nucleus and the sperm nucleus. No such fusion
of two nuclei takes place in artificial parthenogenesis since no
spermatozoön enters the egg, and it became necessary, therefore, to
abandon Hertwig’s definition as wrong. The objection raised that the
phenomena are limited to a few species soon became untenable since
it has been possible to produce artificial parthenogenesis in the
egg of plants (<i class="taxonomic">Fucus</i>, according to Overton) as well as of animals,
from echinoderms up to the frog; and it may possibly one day be
accomplished also in warm-blooded animals. A second objection was that
the eggs caused to develop by the methods of artificial parthenogenesis
could never reach the adult stage and that hence the phenomenon was
merely pathological. There was no basis for such a statement, except
that it is extremely difficult to raise marine invertebrates. <span
class="nowrap">Delage<a name="FNanchor_113_113" id="FNanchor_113_113"></a><a href="#Footnote_113_113" class="fnanchor">113</a></span> was courageous enough<span class="pagenum" title="124"><a name="Page_124" id="Page_124"></a></span> to make an
attempt to raise parthenogenetic larvæ of the sea urchin beyond the
larval stage and he succeeded in one case in carrying the animal to the
mature stage. It proved to be a male.</p>
<p>Better opportunities were offered when a method was discovered which
induced the development of the unfertilized eggs of the frog. In
1907, Guyer made the surprising observation that if he injected
lymph or blood into the unfertilized eggs of frogs he succeeded
in starting development and he even obtained two free-swimming
tadpoles. “Apparently the white rather than the red corpuscles are the
stimulating agents which bring about development, because injections
of lymph which contains only white corpuscles produce the same effects
as injections of blood.” Curiously enough, Guyer thought that probably
the cells which he introduced and not the egg were developing. In
1910, Bataillon showed that a mere puncture of the egg with a needle
could induce development but he believes that for the full development
the introduction of a fragment of a leucocyte is required. Bataillon
has called attention to the analogy with the writer’s results on
lower forms, the puncturing of the egg corresponding to the cytolysis
of the surface layer of the egg and the introduction of a leucocyte
as the analogue of the second or corrective factor. The method of
producing artificial parthenogenesis by puncturing the egg has thus
far been successful only in the egg of<span class="pagenum" title="125"><a name="Page_125" id="Page_125"></a></span> the frog. The writer has tried
it in vain on the eggs of many other forms. He has at present seven
parthenogenetic frogs over a year old, produced by merely puncturing
the eggs with a fine needle (Fig. 6). These frogs have reached over
half the size of the adult frog. They can in no way be distinguished
from the frogs produced by fertilization with a spermatozoön.
This makes the proof conclusive that the methods of artificial
parthenogenesis can result in the production of normal organisms which
can reach the adult stage.</p>
<p>Bancroft and the writer tried to determine the sex of a parthenogenetic
tadpole and of a frog just carried through metamorphosis. Since in
early life the sex glands of both sexes in the frog contain eggs it is
not quite easy to determine the sex, except that in the male the eggs
gradually disappear and from this and other criteria we came to the
conclusion that both parthenogenetic specimens, which were four months
old, were males.</p>
<p>The writer has recently examined the gonads of a ten months
old parthenogenetic frog. Here no doubt concerning the sex was
possible since the gonads were well-developed testicles containing
a large number of spermatozoa of normal appearance, and no <span
class="nowrap">eggs.<a name="FNanchor_114_114" id="FNanchor_114_114"></a><a href="#Footnote_114_114" class="fnanchor">114</a></span> (Figs. 7 and 8.) This would
indicate that the frog belongs to those animals in which the male is
heterozygous for sex. </p>
<p><span class="pagenum" title="126"><a name="Page_126" id="Page_126"></a></span></p>
<p>8. The fact that the egg of so high a form as the frog can be
made to develop into a perfect and normal animal without a
spermatozoön—although normally the egg of this form does not develop
unless a spermatozoön enters—corroborates the idea expressed in
previous chapters that the egg is the future embryo and animal; and
that the spermatozoön, aside from its activating effect, only transmits
Mendelian characters to the egg. The question arises: Is it possible
to cause a spermatozoön to develop into an embryo? The idea has
been expressed that the egg was only the nutritive medium on which
the spermatozoön developed into an embryo, but this idea has been
rendered untenable by the experiments on artificial parthenogenesis.
Nevertheless the question whether or not the spermatozoön can develop
into an embryo on a suitable culture medium remains, and it can only be
decided by direct experiments. It was shown by Boveri, Morgan, Delage,
Godlewski, and others, that if a spermatozoön enters an enucleated egg
or piece of egg it can develop into an embryo, but since the cytoplasm
of the egg is the future embryo this experiment proves only that
the egg nucleus may be replaced by the sperm nucleus; and also that
the sperm nucleus carries into the egg, the substances which induce
development. Incidentally these experiments on merogony also prove that
the mere mechanical tearing of the cortical layer,—which must happen
in the separation of the unfertilized<span class="pagenum" title="127"><a name="Page_127" id="Page_127"></a></span> egg into parts with and without
a nucleus,—by dissection or by shaking, is not sufficient to start
development in the sea-urchin egg.</p>
<p>J. de Meyer put the spermatozoa of sea urchins into sea water
containing an extract of the eggs of the same species but found only
that the spermatozoa swell in such a solution. Loeb and Bancroft made
extensive experiments in cultivating spermatozoa of fowl <i lang="la" xml:lang="la">in vitro</i>
on suitable culture media. In yolk and white of egg the head of the
spermatozoön underwent transformation into a nucleus, but no mitosis or
aster formation was <span class="nowrap">observed.<a name="FNanchor_115_115" id="FNanchor_115_115"></a><a href="#Footnote_115_115" class="fnanchor">115</a></span> These
experiments should be continued. </p>
<hr class="chap" />
<p><span class="pagenum" title="128"><a name="Page_128" id="Page_128"></a></span></p>
<h2>CHAPTER VI</h2>
<h3>DETERMINISM IN THE FORMATION OF AN ORGANISM FROM AN EGG</h3>
<p>1. The writer in a former book (<cite>Dynamics of Living Matter</cite>, 1906, p.
1), defined living organisms as chemical machines consisting chiefly
of colloidal material and possessing the peculiarity of preserving
and reproducing themselves. Some authors like Driesch, and v. Uexküll
seem to find it impossible to account for the development of such
machines from an undifferentiated egg on a purely physicochemical
basis. A study of Driesch’s very interesting and important <span
class="nowrap">book<a name="FNanchor_116_116" id="FNanchor_116_116"></a><a href="#Footnote_116_116" class="fnanchor">116</a></span> shows that he assumes the eggs
of certain animals, <i>e. g.</i>, the sea urchin, to consist of
homogeneous material; and he concludes that nature has solved, in the
formation of highly differentiated organisms from such undifferentiated
material, a problem which does not seem capable of a solution by
physicochemical agencies alone. But the supposition of a structureless
egg is wrong, since Boveri has<span class="pagenum" title="129"><a name="Page_129" id="Page_129"></a></span> demonstrated the existence of a very
simple but definite structure in the unfertilized egg of the sea
urchin; and a similar simple structure has been demonstrated by other
authors, especially Conklin, in the eggs of other forms.</p>
<p>In this chapter we shall attempt the task among others of showing
how, on the basis of the simple physicochemical structure of the
unfertilized egg, the main organ of self-preservation of the organism,
the intestine, is formed through the mere process of cell division and
growth. Cell division is the most general of the specific functions
of living matter and it is the basis underlying the differentiation
of the comparatively simple structure of the egg into a more complex
organism. If cell division and growth were equal in all parts of the
egg no differentiation would be possible, but the different regions of
the unfertilized egg contain different constituents and these, probably
on account of their chemical difference, do not all begin to grow or
divide simultaneously and equally.</p>
<div class="figright" style="width: 295px;">
<img src="images/fig_009.png" width="295" height="285" alt="" />
<p class="tac"><span class="smcap">Fig. 9</span></p></div>
<p><span class="nowrap">Boveri<a name="FNanchor_117_117" id="FNanchor_117_117"></a><a href="#Footnote_117_117" class="fnanchor">117</a></span> found that in the unfertilized
egg of the sea urchin <i class="taxonomic">Strongylocentrotus lividus</i> at Naples a definite
structure is indicated by the fact that the yellowish-red pigment
is not equally distributed over the whole surface of the egg but is
arranged in a wide ring from the equator almost to one of the poles.
Thus three<span class="pagenum" title="130"><a name="Page_130" id="Page_130"></a></span> zones can be recognized in the egg (Fig. 9), a small
clear cap <i>A</i> at one pole, a pigmented ring <i>B</i>, and the rest again
unpigmented <i>C</i>. Observation has shown that each one of these regions
gives rise to a definite constituent of the egg: <i>A</i> furnishes the
mesenchyme from which the skeleton and the connective tissue originate;
<i>B</i> is the material for the formation of the intestine, and <i>C</i> gives
rise to the ectoderm.</p>
<p>The pigment is only at the surface of the egg, and its collection at
<i>B</i> indicates only that the material in <i>B</i> differs physicochemically
from <i>A</i> and <i>C</i>. The real determiners of the three different groups
of organs are three different groups of substances whose distribution
is approximately but probably not wholly identical with the regions
indicated by distribution of pigment. The intestine-forming material is
probably not entirely lacking in <i>C</i> but is contained here in a lower
concen<span class="pagenum" title="131"><a name="Page_131" id="Page_131"></a></span>tration and probably the more so the greater the distance from
<i>B</i>; and the same may probably be said for the substances determining
mesenchyme and ectoderm formation. Hence the unfertilized egg contains
already a rough preformation of the embryo inasmuch as the main axis of
the embryo and the arrangement of its first organs are determined.</p>
<table class="figct" summary="figures 10-11">
<tr><td><div class="figcenter" style="width: 220px; padding-top: 13px;">
<a id="fig010"></a><img src="images/fig_010.png" width="220" height="213" alt="" />
<p class="tac"><span class="smcap">Fig. 10</span></p></div></td>
<td>   </td>
<td><div class="figcenter" style="width: 235px;">
<img src="images/fig_011.png" width="235" height="226" alt="" />
<p class="tac"><span class="smcap">Fig. 11</span></p></div></td></tr>
</table>
<p>After the egg is fertilized the cell divisions begin. The first
division is as a rule at right angles to the stratification of the
egg, each of the two cells contains one-half of the pigment ring (and
of each of <i>A</i> and <i>C</i>) (Fig. 10), and after the next division each
contains one-fourth of the pigmented part. Each of the four cells
is a diminutive whole egg since each contains the three layers in
the normal arrangement (Fig. 11).<span class="pagenum" title="132"><a name="Page_132" id="Page_132"></a></span> The next divisions bring about an
unequal division of the material. Four cells will be formed of ectoderm
material <i>C</i> and only little intestine material <i>B</i>, the other four
cells containing <i>B</i> and <i>A</i>. These latter form at the next division
four very small colourless cells, the so-called micromeres, <i>A</i> (Fig.
12), from which the mesenchyme, skeleton, and connective tissue are
formed, four larger cells, <i>B</i>, from which the intestine is formed, and
eight cells, <i>C</i>, from which the ectoderm will arise. The separation
of the three groups of substances is probably not as complete as our
purely diagrammatic drawing (Fig. 12) indicates.</p>
<div class="figright" style="width: 260px;">
<img src="images/fig_012.png" width="260" height="231" alt="" />
<p class="tac"><span class="smcap">Fig. 12</span></p></div>
<p>The cell division proceeds and the cells become smaller and smaller and
all gather at the surface of the egg, thus forming a hollow sphere.
It is not known what brings about this gathering of the cells at the
surface, whether it is protoplasmic creeping or streaming or whether
the cells are held by a jelly-like layer which covers the surface of
the egg (hyaline membrane) (Fig. 13). Then the cilia are formed at the
external surface<span class="pagenum" title="133"><a name="Page_133" id="Page_133"></a></span> of these cells and the egg begins to swim; we say
it has reached the first larval, the so-called blastula stage. This
happens according to Driesch after the tenth series of cell divisions,
when the number of cells is theoretically 1024, in reality not quite
so many (between 800 and 900). The next step consists in the cells
derived from the material <i>A</i> (mesenchyme and micromeres) gliding into
the hollow sphere, where they form a ring, the physicochemical process
responsible for this gliding being yet unknown. At the opening of this
ring an active growing of the cells of the entoderm into the hollow
sphere takes place and the hollow cylinder formed by this growth is
the intestine (Fig. 14). Why the cells grow into the hollow sphere
and not into the opposite direction is unknown. The next step is the
formation of a<span class="pagenum" title="134"><a name="Page_134" id="Page_134"></a></span> skeleton by the formation of crystals consisting of
the CaCO<sub>3</sub> by the mesenchyme cells surrounding the intestine. For
the establishment of the principle in which we are interested the
description of morphogenesis need not be carried farther.</p>
<table class="figct" summary="figures 13-14">
<tr><td><div class="figcenter" style="width: 215px;">
<img src="images/fig_013.png" width="215" height="226" alt="" />
<p class="tac"><span class="smcap">Fig. 13</span></p>
</div></td>
<td>    </td>
<td><div class="figcenter" style="width: 225px;">
<img src="images/fig_014.png" width="225" height="226" alt="" />
<p class="tac"><span class="smcap">Fig. 14</span></p>
</div></td></tr>
</table>
<p>This principle which is under discussion here is the development of
a purposeful arrangement of organs out of the egg. If we assume that
the egg consists of homogeneous material we are indeed confronted with
a riddle. Since the facts contradict such an assumption but show, as
Boveri has pointed out, a prearrangement which allows us to indicate
in the unfertilized egg already the exact spot where the intestine
will grow into the blastula cavity, we are on solid physicochemical
ground, although many questions of detail cannot yet be answered.
Such a preformation as Boveri has demonstrated is only conceivable if
the material of the egg has not too high a degree of fluidity; we may
consider it as consisting essentially of a semi-solid gel which is not
homogeneous throughout the egg but divided into three strata.</p>
<p>2. <span class="nowrap">Lyon<a name="FNanchor_118_118" id="FNanchor_118_118"></a><a href="#Footnote_118_118" class="fnanchor">118</a></span> tried to ascertain whether by
centrifuging the sea-urchin egg it was possible to modify its structure
and thereby affect the later embryo. He and subsequent experimenters
found that it only is pos<span class="pagenum" title="135"><a name="Page_135" id="Page_135"></a></span>sible to change the position of the nucleus
and the distribution of the pigment in the egg. It follows from
this that the nucleus and the pigment are suspended in rather fluid
material, the former in the centre, the pigment at or near the surface.
The position of the nucleus determines the first plane of segmentation,
since the nuclear division precedes the division of the cytoplasm of
the egg and the plane of nuclear division becomes also the plane of the
division of the whole egg—a point which need not be discussed here.
It was found, however, by Lyon and the subsequent investigators that
the place where the micromeres are formed and where the intestine of
the embryo later originates is little influenced by the centrifuging
of the egg. The localization of this spot must therefore be determined
by a structure sufficiently solid not to be shifted by the centrifugal
force. The intestinal stratum in the egg contains the forerunners of
the tissues which secrete hydrolyzing enzymes, <i>e. g.</i>, trypsin
into the digestive tract.</p>
<p>When the surrounding solution is altered in constitution or when the
temperature is too high, the intestine instead of growing into the
hollow sphere grows outside, we get an evagination instead of an
invagination of the intestine. Such larvæ may live for a few days but
they cannot grow into a living organism. The forces which make the
intestine grow into the hollow sphere are unknown; it may possibly be
only the difference between the tension on the external and internal
surfaces of the<span class="pagenum" title="136"><a name="Page_136" id="Page_136"></a></span> hollow sphere; under normal conditions, the resistance
on the inner surface being smaller, the intestine grows into the hollow
sphere.</p>
<p>The intestine is one of the organs required for the self-preservation
of a more complicated organism, in fact a higher organism without
a digestive tract is not capable of living for any length of time.
In the gastrula—<i>i. e.</i>, the blastula with an intestine—we
have an organism which is durable, but the processes leading up to
the formation of the intestine are so simple that it is difficult to
understand why the assumption of a “supergene” should be required in
this case.</p>
<div class="figright" style="width: 250px;">
<img src="images/fig_015.png" width="250" height="157" alt="" />
<p class="tac"><span class="smcap">Fig. 15</span></p></div>
<p>3. <span class="nowrap">Driesch<a name="FNanchor_119_119" id="FNanchor_119_119"></a><a href="#Footnote_119_119" class="fnanchor">119</a></span> was the first to show
that if we isolate one of the first two cells of a dividing egg
each develops into a whole embryo of half size. This is perfectly
intelligible, since each of the two cells contains all the three
layers in the normal arrangement (Fig. <a href="#fig010">10</a>). The cells divide and
the cells having the tendency to creep to the surface of the mass
arrange themselves in a hollow sphere, the blastula. Since micromeres
and intestine material are present and in their normal position an
intestine will grow into the blastula and a whole organism will result.
All of this is as necessary as is the formation of one embryo from the
whole egg material. Yet the two half-embryos betray their origin from
two cleavage cells of the same egg, in that the two gastrulæ formed
are often if not always symmetrical to each<span class="pagenum" title="137"><a name="Page_137" id="Page_137"></a></span> other (Fig. 15), as the
writer had a chance to observe in the egg of <i class="taxonomic">Strongylocentrotus</i> <span
class="nowrap"><i class="taxonomic">purpuratus</i><a name="FNanchor_120_120" id="FNanchor_120_120"></a><a href="#Footnote_120_120" class="fnanchor">120</a></span> in the following experiment.
The eggs of the sea urchin <i class="taxonomic">Strongylocentrotus purpuratus</i> are put soon
after fertilization into solutions which differ from sea water in two
points; namely that they are neutral or very faintly acid (through the
CO<sub>2</sub> absorbed from the air) instead of being faintly alkaline, and
second, that one of the following three constituents of the sea water
is lacking; namely: K, Na, or Ca. When the eggs are allowed to segment
in such a solution the first two cleavage cells are as a rule in a
large percentage of cases—often as many as ninety per cent.—separated
from each other, and when the eggs are put into normal sea water (about
twenty minutes after the cell division) each cell develops into a
normal embryo. In a number of cases the embryos remained inside the
egg membrane and did not move until after the invagination of the
intestine was far advanced; in such cases it was found quite often that
the invagination began at the plane of cleavage at symmetrical points
of the two embryos, and the growth of the intestine was symmetrical in
both embryos.</p>
<p><span class="pagenum" title="138"><a name="Page_138" id="Page_138"></a></span></p>
<p>This symmetry is probably due to the following fact: the first cleavage
plane goes through that spot where the intestine grows into the
blastula cavity. If the micromere material does not change its position
after the two cleavage cells are separated and the new blastulæ do not
become completely spherical the symmetry which we observed is bound
to occur. The occurrence is a confirmation of Boveri’s observation.
It is natural that Driesch also found that each cell in the four-cell
stage should give rise to a full embryo, since each of these cells is
in reality a diminutive egg containing the three strata in the right
arrangement. When, however, the cells of the eight- or sixteen-cell
stage were isolated Driesch’s results were different. In this case
the isolated cells from the ectoderm material did no longer all form
a gastrula; when such a cell still formed a gastrula it was probably
due to the fact that it contained some entoderm material; while the
cells taken from the entoderm region all formed embryos and therefore
contained ectoderm <span class="nowrap">material.<a name="FNanchor_121_121" id="FNanchor_121_121"></a><a href="#Footnote_121_121" class="fnanchor">121</a></span> The
isolated ectoderm cells of a blastula could no longer form an
intestine; they were lacking the entoderm material. It looks as if a
gradual migration of all the entoderm material from the ectoderm into
the entoderm took place during the blastula formation.</p>
<p>When the contents of the egg are displaced by pressure the
result will be determined by the location of<span class="pagenum" title="139"><a name="Page_139" id="Page_139"></a></span> the main mass of
the intestine-forming material; where the main mass of this body
is located the invagination of the intestine will take place.
In his earlier work Driesch assumed from pressure experiments
that the egg had a great power of “regulation.” In a later <span
class="nowrap">paper<a name="FNanchor_122_122" id="FNanchor_122_122"></a><a href="#Footnote_122_122" class="fnanchor">122</a></span> he expressed to a large extent his
agreement with Boveri who denied this power of “regulation” and showed
that the existence of the structure of the egg—<i>i. e.</i>, a division
into three strata, one forming the ectoderm, the second the entoderm,
and the third the mesoderm—was sufficient to explain the various
phenomena of apparent “regulation.” Driesch’s idea of a regulation in
this case has often been used to insist upon the non-explicability
of the phenomena of development from a purely physicochemical
viewpoint. It is, therefore, only fair to point out that <span
class="nowrap">Boveri<a name="FNanchor_123_123" id="FNanchor_123_123"></a><a href="#Footnote_123_123" class="fnanchor">123</a></span> has furnished the facts for a
simpler explanation, which seems to have escaped the notice of <span
class="nowrap">antimechanists.<a name="FNanchor_124_124" id="FNanchor_124_124"></a><a href="#Footnote_124_124" class="fnanchor">124</a></span></p>
<p>The objection may be raised that in accepting Boveri’s facts and
interpretation we pushed the miracle only one step farther and that we
now have to explain the origin of the structure in the unfertilized
egg. This<span class="pagenum" title="140"><a name="Page_140" id="Page_140"></a></span> Boveri has done by showing that the egg grows from the wall
of the ovary and that that part of the egg which is connected with the
wall of the ovary gives rise to the ectoderm layer, while the opposite
part gives rise to the mesenchyme and the intestine. This shows a
connection between the orientation of the egg in the wall of the ovary
and its stratification. While this does not solve the problem of
stratification in the egg it gives the clue to its solution.</p>
<p>The ultimate origin of stratification probably goes back to the fact
of the presence of watery and water-immiscible substances, such as
fats. The experiments by Beutner and the writer have shown that the
electromotive forces which are observed in living tissues originate
at the boundaries between a watery and a water-immiscible phase, like
oleic acid or <span class="nowrap">lecithin.<a name="FNanchor_125_125" id="FNanchor_125_125"></a><a href="#Footnote_125_125" class="fnanchor">125</a></span> In his earlier
<span class="nowrap">writings<a name="FNanchor_126_126" id="FNanchor_126_126"></a><a href="#Footnote_126_126" class="fnanchor">126</a></span> the writer had thought that
the colloids had special significance and this idea seems to prevail
today; but the actual observations have shown that the phase boundary
fat-water is of greater importance. Needless to say the fats if not
present in the cell from the beginning can be formed in the metabolism.</p>
<p>4. All the “regulation” in the egg is of a purely physicochemical
character; it consists essentially of a flow of material. If this idea
is correct, the apparent<span class="pagenum" title="141"><a name="Page_141" id="Page_141"></a></span> power of “regulation” of the blastomeres
should differ according to the degree of fluidity and the possibility
of different layers separating, and this assumption is apparently
supported by facts. The first plane of segmentation of the egg is
usually the plane of symmetry of the later organism and where the
degree of fluidity is less than in the sea-urchin egg, a separation of
the two first blastomeres should easily result in the formation of two
half-embryos instead of two whole embryos.</p>
<p>This is the case for the frog’s egg as Roux showed in a
classical experiment. Roux destroyed one of the two first
cleavage cells of a frog’s egg with a hot needle and found
that as a rule the surviving cell developed into only a <span
class="nowrap">half-embryo.<a name="FNanchor_127_127" id="FNanchor_127_127"></a><a href="#Footnote_127_127" class="fnanchor">127</a></span> The frog’s egg consists of two
substances, a lighter one which is on top and a heavier one below.
Although viscous, the two substances are not too viscous to prevent
a flow if the egg is turned upside down. O. Schultze found that if
a normal egg is turned upside down in the two-cell stage and held
in that position, two full embryos arise, one from each of the two
blastomeres. Through the flow of the lighter liquid in the egg upwards
the two halves of the protoplasm on top become separated and develop
independently into two whole embryos instead of into two half-embryos.
In Roux’s experiment this flow of protoplasm was avoided. Morgan
showed that<span class="pagenum" title="142"><a name="Page_142" id="Page_142"></a></span> if Roux’s experiment is repeated with the modification
that the egg is put upside down after the destruction of the one cell,
the intact cell will give rise not to a half but to a whole <span
class="nowrap">embryo.<a name="FNanchor_128_128" id="FNanchor_128_128"></a><a href="#Footnote_128_128" class="fnanchor">128</a></span> These experiments prove that each of
the first two cleavage cells of the frog’s egg represents one-half of the
embryo and that a whole embryo can develop from each half only when a
redistribution of material takes place, which in the egg of the frog
can be brought about by gravitation since the egg consists of a lighter
and a heavier mass.</p>
<p>When, therefore, in the egg of the sea urchin each of the first two
blastomeres naturally gives rise to a whole embryo it is due to a
greater degree of fluidity of the protoplasm and not to a lack of
preformation of the embryo in the cytoplasm. This idea is confirmed
by the observations on the egg of <i class="taxonomic">Ctenophores</i> whose cytoplasm seems
to be more solid than that of most other eggs. Chun found that the
isolated blastomere of the first cell division produced a half-larva,
possessing only four instead of the eight locomotor plates of the
normal animal.</p>
<p>It seems that in the egg of molluscs, also, the simple symmetry
relations of the body are already preformed. It is well known that
there are shells of snails which turn to the right while others
turn in the opposite direction. The shells of <i class="taxonomic">Lymnæus</i> turn to the
right, those of <i class="taxonomic">Planorbis</i> to the left. It was observed by<span class="pagenum" title="143"><a name="Page_143" id="Page_143"></a></span> <span
class="nowrap">Crampton<a name="FNanchor_129_129" id="FNanchor_129_129"></a><a href="#Footnote_129_129" class="fnanchor">129</a></span>, Kofoid, and Conklin that the
eggs of right-wound snails do not segment in a symmetrical, but in a
spiral, order, and that in left-handed snails the direction of the
spiral segmentation is the reverse of that of the segmentation in the
right-handed snails. Conklin was able to show that the asymmetrical
spiral structure is already preformed in the egg before cleavage. The
asymmetry of the body in snails is therefore already preformed in the
<span class="nowrap">egg.<a name="FNanchor_130_130" id="FNanchor_130_130"></a><a href="#Footnote_130_130" class="fnanchor">130</a></span></p>
<p>E. B. <span class="nowrap">Wilson<a name="FNanchor_131_131" id="FNanchor_131_131"></a><a href="#Footnote_131_131" class="fnanchor">131</a></span> has found a marked
differentiation in the eggs of some annelids and molluscs. He isolated
the first two blastomeres of the egg of <i class="taxonomic">Lanice</i>, an Annelid. These
two blastomeres are somewhat different in size; from the larger one of
the first two blastomeres, the segmented trunk of the worm originates.
Wilson found that</p>
<div class="blockquot">
<p>when either cell of the two-cell stage is destroyed, the remaining
cell segments as if it still formed a part of an entire <span
class="nowrap">embryo.<a name="FNanchor_132_132" id="FNanchor_132_132"></a><a href="#Footnote_132_132" class="fnanchor">132</a></span> The later development of the
two cells differs in an essential respect, and in accordance with
what we should expect from a study of the normal development. The
posterior cell develops into a segmented larva with a prototroch,
an asymmetrical pre-trochal or head region, and<span class="pagenum" title="144"><a name="Page_144" id="Page_144"></a></span> a nearly typical
metameric seta-bearing trunk region, the active movements of which
show that the muscles are normally developed. The pre-trochal
or head region bears an apical organ, but is more or less
asymmetrical, and, in every case observed, but a single eye was
present, whereas the normal larva has two symmetrically placed
eyes. The development of the anterior cell contrasts sharply with
that of the posterior. This embryo likewise produces a prototroch
and a pre-trochal region, with an apical organ, but produces no
post-trochal region, develops no trunk or setæ, and does not become
metameric. Except for the presence of an apical organ, these
anterior embryos are similar in their general features to the
corresponding ones obtained in <i class="taxonomic">Dentalium</i>. None of the individuals
observed developed a definite eye, though one of them bore a
somewhat vague pigment spot.</p>
<p>This result shows that from the beginning of development the
material for the trunk region is mainly localized in the posterior
cell; and, furthermore, that this material is essential for the
development of the metameric structure. The development of this
animal is, therefore, to this extent, at least, a mosaic work
from the first cleavage onward—a result that is exactly parallel
to that which I earlier reached in <i class="taxonomic">Dentalium</i>, where I was able
to show that the posterior cell contains the material for the
mesoblast, the foot, and the shell; while the anterior cell lacks
this material. I did not succeed in determining whether, as in
<i class="taxonomic">Dentalium</i>, this early localization in <i class="taxonomic">Lanice</i> pre-exists in the
unsegmented egg. The fact that the larva from the posterior cell
develops but a single eye, suggests the possibility that each of
the first two cells may be already specified for the formation of
one eye; but this interpretation remains doubtful from the fact
that the larva from the anterior cell did not, in the five or six
cases observed, produce any eye.</p>
</div>
<p><span class="pagenum" title="145"><a name="Page_145" id="Page_145"></a></span></p>
<p>Conklin has established the existence of a definite structure in the
unfertilized eggs of Ascidians, Amphioxus, and many molluscs. In all
cases the results of the isolation of the first blastomeres seem to
agree with the demonstrable structure of the unfertilized egg.</p>
<p>5. These examples may suffice to show that the egg has from the
beginning a simple structure, and we will now point out by which
means further differentiation may come about. Sachs suggested that
all differentiation and the formation of every organ presupposes
the previous existence of specific substances responsible for the
formation. These substances which are now called internal secretions or
hormones develop gradually during embryonic development. What exists
first is a jelly-like block of protoplasmic material with a varying
degree of viscosity and with just enough differentiation to indicate
head and tail end, a right and left, and a dorsal and ventral side of
the future embryo.</p>
<p>Aside from such simple differences phenomena of protoplasmic streaming
contribute to the further differentiation. Such streaming begins,
according to <span class="nowrap">Conklin,<a name="FNanchor_133_133" id="FNanchor_133_133"></a><a href="#Footnote_133_133" class="fnanchor">133</a></span> in the egg just
before fertilization when the surface layer of the egg protoplasm<span class="pagenum" title="146"><a name="Page_146" id="Page_146"></a></span></p>
<div class="blockquot">
<p>streams to the point of entrance of the sperm, and these movements
may lead to the segregation of different kinds of plasma in different
parts of the egg and to the unequal distribution of these substances in
different regions of the egg.</p>
<p>One of the most striking cases of this is found in the Ascidian Styela
in which there are four or five different kinds of substances in the
egg which differ in colour, so that their distribution to different
regions of the egg and to different cleavage cells may be easily
followed and even photographed while in the living condition. The
peripheral layer of protoplasm is yellow and when it gathers at the
lower pole of the egg where the sperm enters it forms a yellow cap.
This yellow substance then moves following the sperm nucleus, up to
the equator of the egg on the posterior side and there forms a yellow
crescent extending around the posterior side of the egg just below the
equator. On the anterior side of the egg a grey crescent is formed
in a somewhat similar manner and at the lower pole between these two
crescents is a slate-blue substance, while at the upper pole is an area
of colourless protoplasm. The yellow crescent goes into cleavage cells
which become muscle and mesoderm, the grey crescent into cells which
become nervous system and notochord, the slate-blue substance into
endoderm cells, and the colourless substance into ectoderm cells.</p>
<p>Thus within a few minutes after the fertilization of the egg and before
or immediately after the first cleavage, the anterior and posterior,
dorsal and ventral, right and left poles are clearly distinguishable,
and the substances which will give rise to ectoderm, endoderm,
mesoderm, muscles, notochord, and nervous system are plainly visible in
their characteristic <span class="nowrap">positions.<a name="FNanchor_134_134" id="FNanchor_134_134"></a><a href="#Footnote_134_134" class="fnanchor">134</a></span> </p>
</div>
<p><span class="pagenum" title="147"><a name="Page_147" id="Page_147"></a></span></p>
<p>We may finally allude briefly to the fact that when once a number
of tissues are differentiated each one may influence the other
by calling forth tropistic reactions. Thus the writer showed
that in the yolk sac of the fish <i class="taxonomic">Fundulus</i> the pigment cells
lie at first without any definite order but that they gradually
are compelled to creep entirely on the blood-vessels and form
a sheath around them with the result that the yolk sac assumes
a tiger-like <span class="nowrap">marking.<a name="FNanchor_135_135" id="FNanchor_135_135"></a><a href="#Footnote_135_135" class="fnanchor">135</a></span> <span
class="nowrap">Driesch<a name="FNanchor_136_136" id="FNanchor_136_136"></a><a href="#Footnote_136_136" class="fnanchor">136</a></span> has pointed out that the mesenchyme
cells are directed in their migration; and it seems that the direction
of the growth of the axis cylinder is determined by the tissues into
which it grows. The idea of tropistic reactions in the formation of
organs has been discussed by <span class="nowrap">Herbst.<a name="FNanchor_137_137" id="FNanchor_137_137"></a><a href="#Footnote_137_137" class="fnanchor">137</a></span></p>
<p>6. As a consequence of further changes definite anlagen or buds
originate later in the embryo which are destined to give rise to
definite organs. Thus in the tadpole early mesenchyme cells are formed
which are the anlagen for the four legs, which will grow out under the
proper conditions. These anlagen are specific inasmuch as from the
anlage of a foreleg only a foreleg, and from the anlage for a hindleg
only a hindleg, will develop. <span class="nowrap">Braus<a name="FNanchor_138_138" id="FNanchor_138_138"></a><a href="#Footnote_138_138" class="fnanchor">138</a></span>
has proved this by trans<span class="pagenum" title="148"><a name="Page_148" id="Page_148"></a></span>planting the anlage of a foreleg to different
parts of the body. No matter into which part of the body they are
transplanted the mesenchyme cells for the foreleg will give rise to a
foreleg only; even if they are transplanted into the spot from which
the hindlegs grow out under natural conditions. There is therefore
nothing to indicate “regulation.”</p>
<p>The same is true for the formation of the eye and probably in general.
We have to consider the formation of the various organs of the body as
being due to the development of specific cells in definite locations
in the organisms which will grow out into definite organs no matter
into which part of the organism they are transplanted. It is at present
unknown what determines the formation of these specific anlagen. They
may lie dormant for a long time and then begin to grow at definite
periods of development. We shall see later that we know more about the
conditions which cause them to grow.</p>
<p>7. The fact that the egg, and probably every cell, has a definite
structure should determine the limits of the divisibility of living
matter. In most cases the complete destruction of a cell means the
cessation of life phenomena. A brain or kidney which has been ground
to a pulp is no longer able to perform its functions; yet we know
that such pulps can still perform some of the characteristic chemical
processes of the organ; <i>e. g.</i>, the alcoholic fermentation
characteristic<span class="pagenum" title="149"><a name="Page_149" id="Page_149"></a></span> of yeast can be caused by the press juice from yeast;
or characteristic oxidations can be induced by the ground pulp of
organs. The question arises as to how far the divisibility of living
matter can be carried without interfering with the total of its
functions. Are the smallest particles of living matter which still
exhibit all its functions of the order of magnitude of molecules
and atoms, or are they of a different order? The first step toward
obtaining an answer to this question was taken by Moritz <span
class="nowrap">Nussbaum,<a name="FNanchor_139_139" id="FNanchor_139_139"></a><a href="#Footnote_139_139" class="fnanchor">139</a></span> who found that if an infusorian
be divided into two pieces, one with and one without a nucleus, only
the piece with a nucleus will continue to live and perform all the
functions of self-preservation and development which are characteristic
of living organisms. This shows that at least two different structural
elements, nucleus and cytoplasm, are needed for life. We can understand
to a certain extent from this why an organ after being reduced to a
pulp, in which the differentiation into nucleus and protoplasm is
definitely and permanently lost, is unable to accomplish all its <span
class="nowrap">functions.<a name="FNanchor_140_140" id="FNanchor_140_140"></a><a href="#Footnote_140_140" class="fnanchor">140</a></span></p>
<p>The observations of Nussbaum and those who repeated his experiments
showed that although two different structures are required, not the
whole mass of an<span class="pagenum" title="150"><a name="Page_150" id="Page_150"></a></span> infusorian is needed to maintain its life. The
question then arose: How small a fraction of the original cell is
required to permit the full maintenance of life? The writer tried
to decide this question in the egg of the sea urchin. He had found
a simple method by which the eggs of the sea urchin (<i class="taxonomic">Arbacia</i>)
can easily be divided into smaller fragments immediately after
fertilization. When the egg is brought from five to ten minutes
after fertilization (long before the first segmentation occurs) into
sea water which has been diluted by the addition of equal parts of
distilled water, the egg takes up water, swells, and causes the
membrane to burst. Part of the protoplasm then flows out, in one egg
more, in another less. If these eggs are afterward brought back into
normal sea water those fragments which contain a nucleus begin to
divide and <span class="nowrap">develop.<a name="FNanchor_141_141" id="FNanchor_141_141"></a><a href="#Footnote_141_141" class="fnanchor">141</a></span> It was found
that the degree of development which such a fragment reaches is a
function of its mass; the smaller the piece, the sooner as a rule its
development ceases. The smallest fragment which is capable of reaching
the pluteus stage possesses the mass of about one-eighth of the whole
egg. Boveri has since stated that it was about one twenty-seventh of
the whole mass. Inasmuch as only the linear dimensions are directly
measurable, a slight difference in measurement will cause a great
discrepancy in the calculation of the mass. Driesc<span class="pagenum" title="151"><a name="Page_151" id="Page_151"></a></span>h’s results disagree
with the statement of Boveri and support the observation of the writer.</p>
<p>If we raise the question why such a limit exists in regard to the
divisibility of living matter, it seems probable that only those
fragments of an egg are capable of development into a pluteus which
contain a sufficient amount of material of each of the three layers. If
this be correct, it would certainly not suffice to mix the <em>chemical</em>
constituents of the egg in order to produce a normal embryo; this would
require besides the proper chemical substances a definite arrangement
or structure of this material. The limits of divisibility of a cell
seem therefore to depend upon its physical structure and must for this
reason vary for different organisms and cells. The smallest piece of a
sea-urchin egg that can reach the pluteus stage is still visible with
the naked eye, and is therefore considerably larger than bacteria or
many algæ, which also may be capable of further division.</p>
<p>8. The most important fact which we gather from these data is that the
cytoplasm of the unfertilized egg may be considered as the embryo in
the rough and that the nucleus has apparently nothing to do with this
predetermination. This must raise the question suggested already in the
third chapter whether it might not be possible that the cytoplasm of
the eggs is the carrier of the genus or even species heredity, while
the Mendelian heredity which is determined by the nucleus<span class="pagenum" title="152"><a name="Page_152" id="Page_152"></a></span> adds only
the finer details to the rough block. Such a possibility exists, and if
it should turn out to be true we should come to the conclusion that the
unity of the organism is not due to a putting together of a number of
independent Mendelian characters according to a “pre-established plan,”
but to the fact that the organism in the rough existed already in the
cytoplasm of the egg before the egg was fertilized. The influence of
the hereditary Mendelian factors or genes consisted only in impressing
the numerous details upon the rough block and in thus determining its
variety and individuality; and this could be accomplished by substances
circulating in the liquids of the body as we shall see in later
chapters.</p>
<hr class="chap" />
<p><span class="pagenum" title="153"><a name="Page_153" id="Page_153"></a></span></p>
<h2>CHAPTER VII</h2>
<h3>REGENERATION</h3>
<p>1. The action of the organism as a whole seems nowhere more pronounced
than in the phenomena of regeneration, for it is the organism as a
whole which represses the phenomena of regeneration in its parts, and
it is the isolation of the part from the influence of the whole which
sets in action the process of regeneration. The leaf of the Bermuda
“life plant”—<i class="taxonomic">Bryophyllum calycinum</i>—behaves like any other leaf as
long as it is part of a healthy whole plant, while when isolated it
gives rise to new plants. The power of so doing was possessed by the
leaf while a part of the whole, and it was the “whole” which suppressed
the formative forces in the leaf. When a piece is cut from the branch
of a willow it forms roots near the lower end and shoots at the upper
end, so that a tolerably presentable “whole” is restored. How does the
“whole” prevent the basal end of the shoot from forming roots as long
as it is part of the plant? A certain fresh-water flatworm has the
mouth and pharynx in the middle of the body. When a<span class="pagenum" title="154"><a name="Page_154" id="Page_154"></a></span> piece is excised
between the head and the pharynx a new head is formed at the oral end,
a new tail at the opposite end, and in the middle of the remaining old
tissue a new mouth and pharynx is formed. How does the “whole” suppress
all this formative power in the part before the latter is isolated? It
almost seems as if the isolation itself were the emancipation of the
part from the tyranny of the whole. The explanation of this tyranny or
of the correlation of the parts in the whole is to be found, however,
in a different influence. The earlier botanists, Bonnet, Dutrochet,
and especially <span class="nowrap">Sachs,<a name="FNanchor_142_142" id="FNanchor_142_142"></a><a href="#Footnote_142_142" class="fnanchor">142</a></span> pointed out
that the phenomena of correlation are determined by the flow of sap
in the body of a plant. These authors formulated the idea that the
formation of new organs in the plant is determined by the existence of
specific substances which are carried by the ascending or descending
sap. Specific shoot-producing substances are carried to the apex,
while specific root-producing substances are carried to the base of a
plant. When a piece is cut from a branch of willow the root-forming
substances must continue to flow to the basal end of the piece, and
since their further progress is blocked there they induce the formation
of roots at the basal end. <span class="nowrap">Goebel<a name="FNanchor_143_143" id="FNanchor_143_143"></a><a href="#Footnote_143_143" class="fnanchor">143</a></span>
and de Vries have<span class="pagenum" title="155"><a name="Page_155" id="Page_155"></a></span> accepted this view and the writer made use of it
in his first experiments on regeneration and heteromorphosis in <span
class="nowrap">animals.<a name="FNanchor_144_144" id="FNanchor_144_144"></a><a href="#Footnote_144_144" class="fnanchor">144</a></span> At that time the idea of the
existence of such specific organ-forming substances was received with some
scepticism, but since then so many proofs for their existence have been
obtained that the idea is no longer questioned. Such substances are
known now under the name of “internal secretions” or “hormones”; their
connection with the theory of Sachs was forgotten with the introduction
of the new nomenclature.</p>
<p>It may be well to enumerate some of the cases in which the influence
of specific substances circulating in the blood upon phenomena of
growth has been proven. One of the most striking observations in this
direction is the one made by Gudernatsch on the growth of the legs of
tadpoles of frogs and <span class="nowrap">toads.<a name="FNanchor_145_145" id="FNanchor_145_145"></a><a href="#Footnote_145_145" class="fnanchor">145</a></span> The young
tadpoles have no legs, but the mesenchyme cells from which the legs are
to grow out later are present at an early stage. From four months to
a year or more may elapse before the legs begin to grow. Gudernatsch
found that legs can be induced to grow in tadpoles at any time, even in
very young specimens, by feeding them with the thyroid gland (no matter
from what<span class="pagenum" title="156"><a name="Page_156" id="Page_156"></a></span> animal). No other material seems to have such an effect. The
thyroid contains iodine, and <span class="nowrap">Morse<a name="FNanchor_146_146" id="FNanchor_146_146"></a><a href="#Footnote_146_146" class="fnanchor">146</a></span>
states that if instead of the gland, iodized amino acids are fed to the
tadpole the same result can be produced. We must, therefore, draw the
conclusion that the normal outgrowth of legs in a tadpole is due to
the presence in the body of substances similar to the thyroid in their
action (it may possibly be thyroid substance) which are either formed
in the body or taken up in the food.</p>
<p>Thus we see that the mesenchyme cells giving rise to legs may lie
dormant for months or a year but will grow out when a certain type of
substances, <i>e. g.</i>, thyroid, circulates in the blood. There may
exist an analogy between the activating effect of the thyroid substance
and the activating effect of the spermatozoön or butyric acid (or other
parthenogenetic agencies) upon the egg, but we cannot state that the
thyroid substance activates the mesenchyme cells by altering their
cortical layer.</p>
<p>The fact that the substance of the thyroid may induce general growth
in the human is too well known to require more than an allusion in
this connection. When growth stops in children as a consequence of a
degeneration of the thyroid, feeding of the patient with thyroid again
induces growth. It may also suffice merely to call attention to the
connection between acromegaly and the hypophysis.</p>
<p>It was formerly believed that the nervous system<span class="pagenum" title="157"><a name="Page_157" id="Page_157"></a></span> acted as a regulator
of the phenomena of metamorphosis in animals, but it was possible to
show by simple experiments that the central nervous system does not
play this rôle and that the regulator must be the blood or substances
contained therein. In the metamorphosis of the <i class="taxonomic">Amblystoma</i> larva the
gills at the head and tail undergo changes simultaneously, the gills
being absorbed completely. The writer showed that in larvæ in which the
spinal cord was cut in two, no matter at which level,—the sympathetic
nerves were in all probability also cut—the two organs continued to
undergo metamorphosis <span class="nowrap">simultaneously.<a name="FNanchor_147_147" id="FNanchor_147_147"></a><a href="#Footnote_147_147" class="fnanchor">147</a></span>
Uhlenhuth found that if the eye of a salamander larva is
transplanted into another larva the transplanted eye undergoes its
metamorphosis into the typical eye of the adult form, simultaneously
with the normal eyes of the individual into which it was <span
class="nowrap">transplanted.<a name="FNanchor_148_148" id="FNanchor_148_148"></a><a href="#Footnote_148_148" class="fnanchor">148</a></span> These and other observations
of a similar character leave no doubt that substances circulating in
the blood and not the central nervous system are responsible for the
phenomena of growth and metamorphosis.</p>
<p>An interesting observation on the rôle of internal secretion in growth
was made by Leo <span class="nowrap">Loeb.<a name="FNanchor_149_149" id="FNanchor_149_149"></a><a href="#Footnote_149_149" class="fnanchor">149</a></span> When<span class="pagenum" title="158"><a name="Page_158" id="Page_158"></a></span> the
fertilized ovum comes in contact with the wall of the uterus it calls
forth a growth there, namely the formation of the maternal placenta
(decidua). This author showed that the corpus luteum of the ovary
gives off a substance to the blood which alters the tissues in the
uterus in such a way that contact with any foreign body induces this
deciduoma formation. The case is of interest since it indicates that
the substance given off by the corpus luteum does not induce growth
directly, but that it allows mechanical contact with a foreign body to
do so while without the intervention of the corpus luteum substance no
such effect of the mechanical stimulus would be observable. The action
of the substance of the corpus luteum is independent of the nervous
system, since in a uterus which has been cut out and retransplanted the
same phenomenon can be observed.</p>
<p>Bouin and <span class="nowrap">Ancel<a name="FNanchor_150_150" id="FNanchor_150_150"></a><a href="#Footnote_150_150" class="fnanchor">150</a></span> have shown that the
corpus luteum, which in the case of pregnancy continues to exist for a
long time, is responsible for the changes in the mammary gland in the
first half of pregnancy, when an active cell proliferation takes place
in the gland. This process can be interrupted by destroying the corpus
luteum artificially. During the second half of gravidity no further
cell proliferation takes place, but the cells begin to secrete milk
while during the period of cell proliferation such secretions do not
occur. </p>
<p><span class="pagenum" title="159"><a name="Page_159" id="Page_159"></a></span></p>
<p>Claude Bernard and Vitzou had shown that the period of growth and
moulting of the higher crustacea is accompanied by a heaping up
of glycogen in the liver and subdermal connective tissue. <span
class="nowrap">Smith<a name="FNanchor_151_151" id="FNanchor_151_151"></a><a href="#Footnote_151_151" class="fnanchor">151</a></span> found that during the period between
two moultings, when there is no growth, the storage cells are seen
to be filled with large and numerous fat globules instead of with
glycogen. He also found that in the <i class="taxonomic">Cladocera</i> “the period of active
growth is accompanied by glycogen—as opposed to fat—metabolism.”
He observed, moreover, that if <i class="taxonomic">Cladocera</i> are crowded at a low
temperature the fat metabolism (with inhibition to growth) is favoured,
while at high temperatures and with no crowding of individuals
the glycogen metabolism is favoured. In the latter case a purely
parthenogenetic mode of propagation is observed, while in the former
sexual reproduction takes place. The effect of crowding of individuals
is possibly due to products of excretion, which then act on growth and
reproduction indirectly by changing the “glycogen metabolism” to “fat
metabolism.”</p>
<p>All these cases agree in this, that apparently specific substances
induce or favour growth, not in the whole body, but in special parts of
the body. Sachs suggested that there must be in each organism as many
specific organ-forming substances as there are organs in the body.</p>
<p>We will now show that the assumption of the exist<span class="pagenum" title="160"><a name="Page_160" id="Page_160"></a></span>ence of such
“organ-forming” substances (which may or may not be specific) and of
their flow in definite channels explains the inhibitory influence of
the whole on the parts as well as the unbridled regeneration of the
isolated parts.</p>
<p>2. We have seen that the resting egg can be aroused to development and
growth by substances contained in a spermatozoön or by certain other
substances mentioned in the preceding chapter. We will assume that
plants contain a large number of cells or buds which are comparable to
the resting egg cell, but which can be aroused to action by certain
substances circulating in the sap; and that the same is effected for
animal cells by substances in the blood. In plants the cells which can
be aroused to new growth have very often a rather definite location
while in lower animals they are more ubiquitous. For experimental
purposes organisms where these buds have a definite location are more
favourable, since we are better able to study the mechanism underlying
the process of activation and inhibition (correlation). When a leaf
of the plant <i class="taxonomic">Bryophyllum calycinum</i> is cut off and put on moist
sand or into water or even into air saturated with water vapour, new
plants will arise from notches of the leaf. This is the usual way of
propagating the plant and in no other part of the leaf except the
notches will new plants arise. These notches therefore contain cells
comparable to seeds or to unfertilized eggs or to the mesenchyme<span class="pagenum" title="161"><a name="Page_161" id="Page_161"></a></span>
cells which give rise to legs in the tadpole of the frog. The question
arises: Why do notches in the leaf never begin to grow while the
leaf is attached to an intact plant, and why do they grow when the
leaf is isolated? To this we are inclined to give an answer in the
sense of Bonnet, Sachs, de Vries, and Goebel, namely that the flow of
(specific?) substances in the plant determines when and where dormant
buds or anlagen shall begin to grow. Such substances may originate
or may be present in the leaf; but as long as it is connected with a
normal plant they will be carried by the circulation to the growing
points of the stem and of the roots and they cannot reach the notches;
while when we detach the leaf, either a new distribution or a new flow
of liquids will be established whereby the substances reach some of
the notches; and in these notches new roots and a new shoot will be
formed. When we cut off a leaf and put it into moist air, not all but
only a few of the notches will, as a rule, grow out (Fig. 16);<span class="pagenum" title="162"><a name="Page_162" id="Page_162"></a></span> but
when we isolate each notch leaving as much of the rest of the leaf
as possible attached to it, each notch will give rise to a new <span
class="nowrap">plant.<a name="FNanchor_152_152" id="FNanchor_152_152"></a><a href="#Footnote_152_152" class="fnanchor">152</a></span> (Fig. 17.) We see, therefore, that it
does not even require a whole plant to cause inhibition but that we may
observe the tyranny of the whole over the parts in a single leaf. The
explanation is as follows: When we isolate a leaf, some of the notches
will commence to grow into new plants and this growth will arrest the
development of the other notches of the leaf in the same way as their
development was suppressed by the whole plant.</p>
<table class="figct" summary="figures 16-17">
<tr><td class="vat"><div class="figcenter" style="width: 265px; padding-top: 11px;">
<img src="images/fig_016.png" width="265" height="221" alt="" />
<p><span class="smcap">Fig. 16.</span> Growth of roots and
shoots in a few notches of an isolated leaf of <i class="taxonomic">Bryophyllum calycinum</i></p></div></td>
<td>   </td>
<td><div class="figcenter" style="width: 280px;">
<img src="images/fig_017.png" width="280" height="232" alt="" />
<p><span class="smcap">Fig. 17.</span> If all the notches
of a leaf are isolated from each other each notch will give rise to
roots and a shoot, but the growth will be less rapid than in Fig. 16.
Figs. 16 and 17 were two leaves taken from the same node of a plant.</p></div></td></tr>
</table>
<p>The explanation is the same; those notches which begin to grow first
will attract the flow of substances to themselves, thus preventing the
other notches from getting those substances. This idea is supported by
the fact that if all the notches are isolated from the leaf each notch
will give rise to a slowly growing<span class="pagenum" title="163"><a name="Page_163" id="Page_163"></a></span> plant, while if the leaf is not cut
into pieces, and a few notches only grow out, their growth is much more
rapid.</p>
<div class="figright" style="width: 320px;">
<img src="images/fig_018-020.png" width="320" height="436" alt="" />
<p class="tac ml3em"><span class="smcap">Fig. 18</span>     
<span class="smcap">Fig. 19</span>    
<span class="smcap">Fig. 20</span></p></div>
<p>In all these experiments the idea that the “isolation” in itself is
responsible for the growth still presents itself. It can be disposed
of by the following experiment which never fails. Three leaves of
<i class="taxonomic">Bryophyllum calycinum</i> are suspended in an atmosphere saturated with
water vapour but their tips are submersed in water (Figs. 18, 19, 20).
The first leaf, Fig. 20, is entirely separated from its stem, the
second leaf, Fig. 19, remains connected with the adjacent piece of
stem, and the third leaf, Fig. 18, remains also connected with this
piece of stem but the latter still possesses both leaves. The first
leaf, Fig. 20, produces new roots and shoots in the submerged part in
a few days; the second leaf, Fig. 19, produces no roots or shoots for
a long time. This might find its explanation by the assumption that
the first leaf, being more isolated than the second, regenerates more
quickly. But this explanation becomes untenable owing to the fact that
the third leaf, Fig. 18, being less isolated than both (possessing a
second leaf in addition to the stem), forms new roots and shoots also
more quickly than the second leaf. The phenomena become intelligible in
the following way. The fact that in the second leaf shoots and roots
are formed very late, if at all, finds its explanation not in the
lessened isolation of this leaf, but in the fact that the formation
of a new shoot or of a callus in the piece of stem takes place<span class="pagenum" title="164"><a name="Page_164" id="Page_164"></a></span> more
quickly than the formation of roots and shoots in the notches of a
completely isolated leaf. The stem acts therefore as a centre of
suction for the flow of substances from the leaf and this prevents
or retards the formation of roots and shoots in the notches. In the
isolated leaf of <i class="taxonomic">Bryophyllum calycinum</i> no callus formation takes
place and hence no flow of the sap<span class="pagenum" title="165"><a name="Page_165" id="Page_165"></a></span> away from the leaf will occur. This
will allow one or more of the notch buds of this leaf to grow out and
then a flow will be established towards these growing buds.</p>
<p>In the third specimen, Fig. 18, the presence of two leaves suppresses
or, as a rule, retards the growth of a shoot on the stem and possibly
also the flow from one leaf may block to some extent the flow from the
opposite leaf if the piece of stem is very short. This puts the leaves
in a condition not as good as that in leaf Fig. 20, but better than in
leaf Fig. <span class="nowrap">19.<a name="FNanchor_153_153" id="FNanchor_153_153"></a><a href="#Footnote_153_153" class="fnanchor">153</a></span></p>
<p>In the normal plant the buds in the notches of the leaf remain dormant
since the flow of the “stimulating” substances takes place towards the
tips of the stem and root, and because these substances are retained
there in excess. This is probably the real basis of the mysterious
dominance of the “whole” over its “parts” or of the anlagen of the
tip of the stem over those farther below. When a piece of the stem of
<i class="taxonomic">Bryophyllum</i> is cut off and its leaves are removed, the two apical
buds will grow out first. This “dominance” finds its explanation
probably in the anatomical structure and the mechanism of sap flow
which tend to bring the “stimulating” substances first to the anlagen
in the tip. In <i class="taxonomic">Laminaria</i> Setchell has been able to show directly that
regeneration always starts from that tissue which conducts nutritive
material.</p>
<p>When we cut out a piece of a stem of <i class="taxonomic">Bryophyllum</i>,<span class="pagenum" title="166"><a name="Page_166" id="Page_166"></a></span> and remove all the
leaves, new shoots will be formed from the two apical buds of the stem,
and roots will arise from the most basal nodes; provided that the stem
is suspended in air saturated with water vapour. The growth in such a
stem deprived of all leaves is slow. If we remove all the leaves on
such a piece of stem except the two at the apical end, the stem will
form only roots, but these will develop much more rapidly than on a
stem without leaves. If we remove all the leaves except the two at
the basal end, the stem will only form shoots (at the apical end) but
these will develop much more rapidly than in a leafless stem. Hence the
leaves accelerate the growth of roots towards the basal end and inhibit
it towards the apical end; and they favour the growth of shoots towards
the apical end and inhibit it in the nodes located nearer the base.</p>
<p>We thus see that while the stem inhibits the growth of the leaves
connected with it, the latter accelerate the growth in the stem. Both
facts can probably be explained on the same basis; namely, on the
assumption that it is the flow of substances from the leaf to the stem
which inhibits the growth of the notches and accelerates the growth
of the buds in the stem. On this assumption it would also follow
that the leaves send root-forming substances towards the basal and
shoot-forming substances towards the apex of the stem. It also seems
to follow from recent as yet unpublished experiments by the writer
that the root-forming substances<span class="pagenum" title="167"><a name="Page_167" id="Page_167"></a></span> are associated or identical with the
substances which cause geotropic curvature in the stem.</p>
<p>These observations show that the phenomena of correlation or of the
influence of the whole over the parts is due to peculiarities of
circulation or the flow of sap; and that the isolation prevents the sap
from flowing away to other parts of the plant. There is no need for
assuming the existence of a mysterious force which directs the piece to
grow into a whole.</p>
<table class="figct" summary="figures 21-22">
<tr><td><div class="figcenter" style="width: 130px;">
<img src="images/fig_021.png" width="130" height="223" alt="" />
<p class="tac"><span class="smcap">Fig. 21</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 240px;">
<img src="images/fig_022.png" width="240" height="52" alt="" />
<p class="tac"><span class="smcap">Fig. 22</span></p>
</div></td></tr>
</table>
<p>3. Phenomena of inhibition or correlation such as we have described
in <i class="taxonomic">Bryophyllum</i> are not lacking in the regeneration of animals, as
experiments on <i class="taxonomic">Tubularia</i> <span class="nowrap">show.<a name="FNanchor_154_154" id="FNanchor_154_154"></a><a href="#Footnote_154_154" class="fnanchor">154</a></span>
<i class="taxonomic">Tubularia mesembryanthemum</i> (Fig. 21) is a hydroid consisting of a
long stem terminating at one end in a stolon which attaches itself to
solid bodies such as rocks, at the other end in a polyp. The writer
found that if we cut a piece from a stolon and suspend it in an
aquarium it forms as a rule a polyp at either end (Fig. 22),<span class="pagenum" title="168"><a name="Page_168" id="Page_168"></a></span> but the
velocity with which the two polyps are formed is not the same, the
polyp at the oral end of the piece being formed much more rapidly—a
day or one or two weeks sooner—than the aboral polyp. The process of
polyp regeneration at the aboral pole could, however, be accelerated
and its velocity made equal to that of the regeneration of the oral
polyp by suppressing the formation of the latter. This was accomplished
by depriving the oral pole of the oxygen necessary for regeneration,
<i>e. g.</i>, by merely putting the oral end of the piece of stem into
the sand. It was, therefore, obvious that the formation of the oral
polyp retarded the formation of the aboral polyp. This inhibition
might have been due to the fact that a specific organ-forming material
needed for the formation of a polyp existed in sufficient quantity in
the stem for the formation of one polyp only at a time. This idea,
however, was found to be incorrect since when the stem was cut into two
or more pieces each piece formed a polyp at once at its oral pole and
regenerated the aboral polyps also, but again with the usual delay.
It seemed more probable then that the cause of the difference in the
rapidity of polyp formation at both ends lay in the fact that certain
material flowed first to the oral pole and induced polyp formation
here but that this flow was reversed as soon as the polyp at the oral
pole was formed or as soon as the formation of the oral polyp was
inhibited by lack of oxygen. The partial<span class="pagenum" title="169"><a name="Page_169" id="Page_169"></a></span> or full completion of the
formation of the oral polyp acted as an inhibition to the further flow
of material to this pole. This idea was supported by an observation
made independently by Godlewski and the writer that if a piece of stem
be cut out of a <i class="taxonomic">Tubularia</i>, and if the piece be ligatured somewhere
between the two ends, the oral and the aboral polyps are formed
simultaneously. This would be comprehensible on the assumption that
the retarding effect which the formation of the oral has on the aboral
polyp was indeed of the nature of a flow of material towards the oral
pole.</p>
<div class="figright" style="width: 85px;">
<img src="images/fig_023.png" width="85" height="260" alt="" />
<p class="tac"><span class="smcap">Fig. 23</span></p></div>
<p>Miss <span class="nowrap">Bickford<a name="FNanchor_155_155" id="FNanchor_155_155"></a><a href="#Footnote_155_155" class="fnanchor">155</a></span> found that the
difference in time between the formation of the two polyps disappears
also when the piece cut from the stem becomes so small that it is of
the order of magnitude of a single polyp. In that case two incomplete
polyps are formed simultaneously at each end (Fig. 23). The new
head in the regeneration of <i class="taxonomic">Tubularia</i> arises, as Miss Bickford
observed, from the tissue near the wound. At some distance from
the wound in the old tissue two rows of tentacles arise, which are
noticeable as rows of longitudinal lines inside the stem before the
head is formed. Driesch noticed that the newly formed head is the
smaller the smaller the whole<span class="pagenum" title="170"><a name="Page_170" id="Page_170"></a></span> piece. (This is true, however, only in
rather small pieces.) There is, therefore, in small pieces a rough
proportionality between size of head and size of regenerating piece.
<span class="nowrap">Driesch<a name="FNanchor_156_156" id="FNanchor_156_156"></a><a href="#Footnote_156_156" class="fnanchor">156</a></span> uses this interesting fact
to prove the existence of an entelechy, while we are inclined to see in
it an analogue to the observation of Leo Loeb, that the velocity of
the process of healing in the case of a deficiency of the epithelium
decreases when the size of the uncovered area diminishes. While we do
not wish to offer any suggestion concerning the mechanism of these
quantitative phenomena—they may be related in some way with the
velocity of certain chemical reactions—we see no reason for assuming
that they cannot be explained on a purely physicochemical basis.</p>
<p>The writer noticed that certain pigmented cells from the entoderm of
the organism always gather at that end where a new polyp is about to
be formed. These red or yellowish cells always collect first at the
oral end of a piece of stem. It may be that certain substances given
off by the pigmented cells at the cut end are responsible for the polyp
formation, but this is only a surmise.</p>
<p>Another suggestion made by <span class="nowrap">Child,<a name="FNanchor_157_157" id="FNanchor_157_157"></a><a href="#Footnote_157_157" class="fnanchor">157</a></span> is
that there exists an axial gradient in the stem whereby the cells<span class="pagenum" title="171"><a name="Page_171" id="Page_171"></a></span>
regenerate the more quickly the nearer they are to the oral pole.
If this were correct, and we cut a long piece from the stem of a
<i class="taxonomic">Tubularia</i> and bisect the piece, the oral pole of the anterior half
should regenerate more quickly than the oral pole of the posterior
half. According to the writer’s observations on a Tubularian (<i class="taxonomic">T.
crocea</i>) growing in the estuaries near Oakland, California, both oral
ends regenerate equally fast in such cases.</p>
<p>4. The phenomena of regeneration in <i class="taxonomic">Cerianthus membranaceus</i>, a sea
anemone, can be easily understood from the experiments on Tubularians,
if we imagine the body wall of <cite>Cerianthus</cite> to consist of a series of
longitudinal elements running parallel to the axis of symmetry of the
animal from the tentacles to the foot. The number of these elements
may be supposed to correspond to the number of tentacles in the outer
row of the normal animal. Each such element behaves like a Tubularian,
with this difference, however, that the elements in <cite>Cerianthus</cite> are
more strongly polarized than in <cite>Tubularia</cite>, and that each one is able
to form a tentacle at its oral pole only. This fact can be nicely
illustrated in the following way: if a square or oblong piece (<i>a b c d</i>,
Fig. 24) be cut from<span class="pagenum" title="172"><a name="Page_172" id="Page_172"></a></span> the body wall of a <i class="taxonomic">Cerianthus</i> in such a way
that one side, <i>a c</i>, of the oblong is parallel to the longitudinal
axis of the animal, tentacles will grow on one of the four sides only;
namely, on the side <span class="nowrap"><i>a b</i>.<a name="FNanchor_158_158" id="FNanchor_158_158"></a><a href="#Footnote_158_158" class="fnanchor">158</a></span> (Fig. 25.)
The other three free edges are not able to produce tentacles. If an
incision be made in the body wall of a <i class="taxonomic">Cerianthus</i>, tentacles will
grow on the lower edge of the incision (Fig. 26).</p>
<table class="figct" summary="figures 24-26">
<tr><td class="vat"><div class="figcenter" style="width: 140px;">
<img src="images/fig_024.png" width="140" height="257" alt="" />
<p class="tac"><span class="smcap">Fig. 24</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 130px; padding-top: 54px;">
<img src="images/fig_025.png" width="130" height="203" alt="" />
<p class="tac"><span class="smcap">Fig. 25</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 175px; padding-top: 76px;">
<img src="images/fig_026.png" width="175" height="181" alt="" />
<p class="tac"><span class="smcap">Fig. 26</span></p>
</div></td></tr>
</table>
<p>The writer tried whether or not by tying a ligature around the middle
of a piece of an Actinian this polarity could be suppressed; but the
experiments did not succeed, inasmuch as the cells compressed by the
ligature died, and were liquefied through bacterial action so that the
pieces in front and behind the ligature fell apart. It is therefore
impossible to decide whether or not a current or a flow of substances
in a certain direc<span class="pagenum" title="173"><a name="Page_173" id="Page_173"></a></span>tion through these elements is responsible for this
polarity, though this may be possible. The writer found, however, that
one condition is necessary for the growth and regeneration of tentacles
which also plays a rôle in the corresponding phenomena in plants,
namely turgidity. The tentacles of <i class="taxonomic">Cerianthus</i> are hollow cylinders
closed at the tip, and by liquid being pressed into them they can be
stretched and appear turgid. If, however, an incision is made in the
body, the tentacles above the incision can no longer be stretched out.
In one experiment the oral disk of a <i class="taxonomic">Cerianthus</i> was cut off; very
soon new tentacles began to grow at the top, and after having reached
a certain size, an incision was made in the animal. The tentacles
above the incision collapsed in consequence and ceased to grow, while
growth of the others continued. On the lower edge of the incision new
tentacles began to grow.</p>
<table class="figct" summary="figures 27-29">
<tr><td><div class="figcenter" style="width: 99px;">
<img src="images/fig_027.png" width="99" height="275" alt="" />
<p class="tac"><span class="smcap">Fig. 27</span></p>
</div></td>
<td>    </td>
<td><div class="figcenter" style="width: 110px;">
<img src="images/fig_028.png" width="110" height="70" alt="" />
<p class="tac"><span class="smcap">Fig. 28</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 177px;">
<img src="images/fig_029.png" width="177" height="275" alt="" />
<p class="tac"><span class="smcap">Fig. 29</span></p>
</div></td></tr>
</table>
<p>It seems also possible that Morgan’s well-known experiment on
regeneration in <i class="taxonomic">Planaria</i> can be explained by a flow of substances.
<span class="nowrap">He<a name="FNanchor_159_159" id="FNanchor_159_159"></a><a href="#Footnote_159_159" class="fnanchor">159</a></span> found that if a piece <i>a c d b</i> be
cut out of a fresh-water Planarian at right angles to the longitudinal
axis (Fig. 27), at the front end a new normal head, at the back end a
new tail, will be regen<span class="pagenum" title="174"><a name="Page_174" id="Page_174"></a></span>erated (Fig. 28); but that if a piece <i>a c d b</i>
be cut from a Planarian obliquely (Fig. 29) instead of at right angles
to the longitudinal axis a tiny head is formed at the foremost corner
of the piece <i>a</i> and a tiny tail at the hindmost corner <i>b</i> (Fig. <a href="#fig030">30</a>).
Why is it that in the oblique piece the head is formed in the corner
and not all along the cut surface as is the case when the cut is made
at right angles to the longitudinal axis? The writer is inclined to
believe that the right answer to this question has been given by <span
class="nowrap">Bardeen.<a name="FNanchor_160_160" id="FNanchor_160_160"></a><a href="#Footnote_160_160" class="fnanchor">160</a></span> This author has pointed out the
apparent rôle that the circulatory (or so-called digestive) canals in
Planarians play in the localization of the phenomena of regeneration,
inasmuch as the new head always forms symmetrically at the opening of
the circulatory vessel or branch which is situated as much as possible
at the foremost end of the<span class="pagenum" title="175"><a name="Page_175" id="Page_175"></a></span> regenerating piece of worm. He assumes
that through muscular action the liquids of the body are forced to
stream toward this end, and that this fact has some connection with
the formation of a new head. There can be no doubt that the facts
here mentioned agree with Bardeen’s suggestion. The oblique pieces in
Morgan’s experiments which at first have the heads and tails outside
the line of symmetry of the middle piece, gradually assume a normal
position (Figs. 31, 32). The writer is inclined to believe that this is
due to mechanical conditions. The head <i>a e c</i> of such an oblique piece
is asymmetrical, the one side <i>a e</i> being less stretched than the other
<i>e c</i>. The higher tension of the piece <i>e c</i> will have the effect of
bringing <i>e</i> nearer <i>c</i>, since we know that acid formation and hence
energy production increases in proportion to surface, <i>i. e.</i>, it
must be the greater the more it is stretched. The reverse is true for
the tail <i>d f b</i>, and the effect here will be that <i>f</i><span class="pagenum" title="176"><a name="Page_176" id="Page_176"></a></span> will be pulled
nearer <i>d</i>. In this way purely mechanical conditions are responsible
for the fact that the soft tissues of the animal are gradually restored
to their true orientation.</p>
<table class="figct" summary="figures 30-32">
<tr><td class="vat"><div class="figcenter" style="width: 145px; padding-top: 71px;">
<a id="fig030"></a><img src="images/fig_030.png" width="145" height="109" alt="" />
<p class="tac"><span class="smcap">Fig. 30</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 120px; padding-top: 22px;">
<img src="images/fig_031.png" width="120" height="158" alt="" />
<p class="tac"><span class="smcap">Fig. 31</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 120px;">
<img src="images/fig_032.png" width="120" height="180" alt="" />
<p class="tac"><span class="smcap">Fig. 32</span></p>
</div></td></tr>
</table>
<p>As a final possible example of the influence of internal secretion
or substances contained in the blood may be mentioned the following
curious observation of <span class="nowrap">Przibram.<a name="FNanchor_161_161" id="FNanchor_161_161"></a><a href="#Footnote_161_161" class="fnanchor">161</a></span> In
a crustacean, <i class="taxonomic">Alpheus</i>, the two chelæ (pincers) are not equal in
size and form, one being very much larger than the other. Przibram
found that when he cut off the larger pincer in such crustaceans the
remaining pincer assumes in the next moulting the size and shape of
the removed large pincer; while in place of the removed pincer one of
the small type is produced. Hence a reversal of the two pincers is
thus brought about. If later on the large pincer is again cut off the
process is repeated and the original dissymmetry is restored. Przibram
was able to show that the nervous system has no connection with this
phenomenon.</p>
<p>The elements which have entered into the discussion thus far are,
first, the flow of substances in preformed channels; second, the
existence of general or specific substances required for the growing
or regenerating organ. A third element is to be added; namely the
“suction” effect upon these substances of a developing organ. Thus we
see that if one or a few of the notches<span class="pagenum" title="177"><a name="Page_177" id="Page_177"></a></span> in a leaf of <i class="taxonomic">Bryophyllum</i>
grow out the other notches of the leaf are inhibited from growing.
There is enough material present in the leaf for all the notches to
grow into shoots as is proved by the fact that all will grow out if
they are isolated from each other. This was explained on the assumption
that the notches of a whole which happen to develop first, create a
flow of these substances from the rest of the leaf to themselves and
thus prevent any getting to the other notches. We stated that this is
supported by the fact that the few notches growing out in an undivided
leaf grow more rapidly than the many shoots growing from each notch of
a divided leaf. But why should a growing shoot or a growing point in
general produce such a suction? I think this may be possible on the
assumption that the consumption of these substances by the growing
organs causes a low osmotic pressure of these substances in the growing
region and this fall of osmotic potential will act as a cause for the
further flow. This brings about the apparent “suction” effect of the
growing elements upon the flow of substances.</p>
<p>5. We mentioned that when a piece is cut from a <i class="taxonomic">Planaria</i> between
pharynx and head a new mouth is formed in the middle. It should also
be mentioned that according to Child the piece after regeneration is
smaller than it was <span class="nowrap">before.<a name="FNanchor_162_162" id="FNanchor_162_162"></a><a href="#Footnote_162_162" class="fnanchor">162</a></span> This
indicates that material in the old cells has been digested or has
under<span class="pagenum" title="178"><a name="Page_178" id="Page_178"></a></span>gone hydrolysis in order to furnish the nutritive material for
the new head and tail, since the piece cannot take up any food from the
outside before a mouth is formed. These phenomena of autodigestion—the
process itself will be discussed in the last chapter—seem to occur
in many (if not all) phenomena of regeneration. It may be that the
collecting of red cells at the end in a Tubularian where regeneration
is about to begin has to do with the furnishing of material by
self-digestion, since these cells are partly at least destroyed in the
process. It is of interest to look for more examples of autodigestion
accompanying phenomena of regeneration.</p>
<table class="figct" summary="figures 33-34">
<tr><td class="vat"><div class="figcenter" style="width: 250px; padding-top: 49px;">
<img src="images/fig_033.png" width="250" height="198" alt="" />
<p class="tac"><span class="smcap">Fig. 33</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 270px;">
<img src="images/fig_034.png" width="270" height="247" alt="" />
<p class="tac"><span class="smcap">Fig. 34</span></p>
</div></td></tr>
</table>
<div class="figright" style="width: 240px;">
<img src="images/fig_035.png" width="240" height="125" alt="" />
<p class="tac"><span class="smcap">Fig. 35</span></p></div>
<p>The writer has observed more closely the transformation of an organ
into more undifferentiated material in <i class="taxonomic">Campanularia</i> (Fig. 33),
a <span class="nowrap">hydroid.<a name="FNanchor_163_163" id="FNanchor_163_163"></a><a href="#Footnote_163_163" class="fnanchor">163</a></span> This organism shows a
remarkable stereotropism. Its stolons attach themselves to solid
bodies, and the stems appear on the side of the stolon exactly opposite
the point or area of contact with the solid body. The stems<span class="pagenum" title="179"><a name="Page_179" id="Page_179"></a></span> grow,
moreover, exactly at right angles to the solid surface element to
which the stolon is attached. If such a stem be cut and put into a
watch glass with sea water, it can be observed that those polyps which
do not fall off go through a series of changes which make it appear
as if the differentiated material of the polyp were transformed into
undifferentiated material. The tentacles are first put together like
the hairs of a camel’s-hair brush (Fig. 34), and gradually the whole
fuses to a more or less shapeless mass which flows back into the
periderm (Fig. 35). It follows from this that in this process certain
solid constituents of the polyp, <i>e. g.</i>, the cell walls, must be
liquefied. This undifferentiated material formed from the polyp may
afterward flow out again, giving rise to a stolon or a polyp; to the
former where it comes in contact with a solid body, to the latter where
it is surrounded by sea water. These observations suggest the idea of
reversibility of the<span class="pagenum" title="180"><a name="Page_180" id="Page_180"></a></span> process of differentiation of organs and tissues,
in certain forms at least. We have to imagine that some of the cells
or interstitial tissue is digested and that as a consequence the organ
loses its characteristic shape.</p>
<p>Giard and Caullery have found that a regressive metamorphosis occurs
in Synascidians, and that the animals hibernate in this condition.
The muscles of the gills of these animals are decomposed into their
individual cells. The result is the formation of a parenchyma which
consists of single cells and of cell aggregates resembling a <span
class="nowrap">morula.<a name="FNanchor_164_164" id="FNanchor_164_164"></a><a href="#Footnote_164_164" class="fnanchor">164</a></span></p>
<p><span class="nowrap">Driesch,<a name="FNanchor_165_165" id="FNanchor_165_165"></a><a href="#Footnote_165_165" class="fnanchor">165</a></span> experimenting on the
regeneration of an Ascidian, found that when he cut off the gills and
siphons of the animal the portion removed was able to regenerate a
whole animal. The gill-piece excised contained no heart, no intestine,
and no stolon, and all these organs were regenerated from the gills. In
a number of cases the regeneration took place by bud formation at the
edge of the wound, but in other cases the gills were transformed into
an undifferentiated mass of tissue from which the missing parts of the
animals arose by budding and new gills were formed.</p>
<p>It is probable that the two cases are only quantitatively different. In
both, autodigestion of certain cell constituents and possibly of whole
cells must take place in order to obtain material for the formation of
the<span class="pagenum" title="181"><a name="Page_181" id="Page_181"></a></span> lost part of the Ascidian. If an interstitial tissue is digested
it becomes a question of how much of this tissue undergoes hydrolysis.
If there is little destroyed the old shape of the gills remains, if
too much is digested the old gills become a shapeless mass in which a
certain number of the old cells are maintained and give rise to the new
animal by cell division. The material for the new organs must of course
be furnished from old cells which have been digested.</p>
<p>If regeneration takes place in pieces which take up no food the
newly formed organs must originate from material absorbed from
cells of the animal which are hydrolyzed and whose material serves
as food for those cells which grow. Very often this process of
digestion takes place without loss of the total form of the organ
and is overlooked by the pure morphologists. In <i class="taxonomic">Campanularia</i>
also the process of collapse described above is only apparent in
a fraction of the cases as in Driesch’s observations on <span
class="nowrap"><i class="taxonomic">Clavellina</i>.<a name="FNanchor_166_166" id="FNanchor_166_166"></a><a href="#Footnote_166_166" class="fnanchor">166</a></span> It is also possible that the
red and yellow entoderm cells which gather at the end where the new
polyp forms furnish the material which is utilized for the process of
growth of the cells from which the tentacles arise (with or without
giving off specific “hormones” besides). </p>
<p><span class="pagenum" title="182"><a name="Page_182" id="Page_182"></a></span></p>
<p>6. We have mentioned the ideas concerning a design, or “entelechy,”
acting as a guide to the developing egg and have shown that this
revival of Platonic and Aristotelian philosophy in biology was due to a
misconception; namely, that the egg consisted of homogeneous material
which was to be differentiated into an organism. For this supernatural
task supernatural agencies seemed required. But we have seen that
the unfertilized egg is already differentiated in a way which makes
the further differentiation a natural affair. This idea of a quasi
superhuman intelligence presiding over the forces of the living is met
with in the field of regeneration, and here again it is based upon a
misconception. The lens of the eye is formed in the embryo from the
epithelium lying above the so-called optic cup (the primitive retina).
Where this retina touches the epithelium the latter begins to grow into
the cup, the ingrowing piece of epithelium is cut off and forms the
lens, which probably under the influence of substances secreted by the
optic cup becomes transparent. Certain animals like the salamander are
able to form a new lens when the old one has been removed by operation,
but the new lens is formed in an entirely different way; namely, from
the upper edge of the iris. G. Wolf, who observed this regeneration
used it to endow the organism with a knowledge of its needs; the idea
of a Platonic preconceived plan or an Aristotelian purpose suggested
itself. But it can be shown that the<span class="pagenum" title="183"><a name="Page_183" id="Page_183"></a></span> organism does in this case what
it is compelled to do by its physical and chemical structure.</p>
<p><span class="nowrap">Uhlenhuth<a name="FNanchor_167_167" id="FNanchor_167_167"></a><a href="#Footnote_167_167" class="fnanchor">167</a></span> has shown by way of tissue
culture that the cells of the iris cannot grow and divide as long as
they are full of pigment granules as they normally are. When the fine
superficial membrane of the iris is torn the pigment granules fall out
and the cells can now grow and multiply. If the lens is taken out of
the eye of the salamander the fine membrane of the iris is torn and
the pigment cells at the edge (especially the upper edge) lose their
pigment granules which fall down on account of their specific gravity.
As soon as this happens the cells will proliferate. A spherical mass
of cells is formed which become transparent and which will cease to
grow as soon as they reach a certain size. The unanswered question is:
Why does the mass of cells become transparent so that it can serve as
a lens? The answer is that young cells when put into the optic cup
always become transparent no matter what their origin; it looks as if
this were due to a chemical influence exercised by the optic cup or
by the liquid it contains. Lewis has shown that when the optic cup is
transplanted into any other place under the epithelium of a larva of
a frog the epithelium will always grow into the cup where the latter
comes in contact with the epithelium; and that the ingrowing part
will always become transparent. This leaves us then with one puzzle
still: Why is the<span class="pagenum" title="184"><a name="Page_184" id="Page_184"></a></span> growth of the lens limited? The limitation in the
growth of organs is one of the most important problems in growth and
organ formation, though unfortunately our knowledge of this topic is
inadequate.</p>
<p>7. The botanist J. Sachs was the first to definitely state that in
each species the ultimate size of a cell is a constant, and that
two individuals of the same species but of different size differ
in regard to the number, but not in regard to the size of their
<span class="nowrap">cells.<a name="FNanchor_168_168" id="FNanchor_168_168"></a><a href="#Footnote_168_168" class="fnanchor">168</a></span> Amelung, a pupil of Sachs,
determined the correctness of Sachs’s theory by actual counts. Sachs,
in addition, recognized that wherever there were large masses of
protoplasm, <i>e. g.</i>, in siphoneæ and other cœloblasts, many
nuclei were scattered throughout the protoplasm. He inferred from this
that “each nucleus is only able to gather around itself and control
a limited mass of <span class="nowrap">protoplasm.”<a name="FNanchor_169_169" id="FNanchor_169_169"></a><a href="#Footnote_169_169" class="fnanchor">169</a></span> He
points out that in the case of the animal egg the reserve material—fat
granules, proteins, and carbohydrates—are partly transformed into
the chromatin substances of the nuclei, and that the cell division
of the egg results in the cells reaching a final size in which each
nucleus has gathered around itself that mass of protoplasm which
it is able to control. <span class="nowrap">Morgan<a name="FNanchor_170_170" id="FNanchor_170_170"></a><a href="#Footnote_170_170" class="fnanchor">170</a></span> and
<span class="nowrap">Driesch<a name="FNanchor_171_171" id="FNanchor_171_171"></a><a href="#Footnote_171_171" class="fnanchor">171</a></span> tested and confirmed the
idea of Sachs for<span class="pagenum" title="185"><a name="Page_185" id="Page_185"></a></span> the eggs of Echinoderms. We stated in the previous
chapter that Driesch produced artificially larvæ of sea urchins of
one-eighth, one-fourth, and one-half their normal size by isolating a
single cleavage cell in one of the first stages of segmentation of the
fertilized sea-urchin egg. He counted in each of the dwarf gastrulæ
resulting from these partial eggs the number of mesenchyme cells
and found that the larvæ from a one-half blastomere possessed only
one-half, those from a one-fourth blastomere only one-fourth, and those
from a one-eighth blastomere only one-eighth of the number of cells
which a normal larva developing from a whole egg possessed. Moreover,
he could show that when two eggs were caused to fuse so as to produce
a single larva of double size, the gastrulæ of such larvæ had twice
the number of mesenchyme cells. Driesch drew the conclusion from his
observations that each morphogenetic process in an egg reaches its
natural end when the cells formed in the process have reached their
final size.</p>
<p>Since each daughter nucleus of a dividing blastomere has the same
number of chromosomes as the original nucleus of the egg, it is
clear that in a normally fertilized egg each nucleus has twice
the mass of chromosomes that is contained in the nucleus of a
merogonic egg, <i>i. e.</i>, an enucleated fragment of protoplasm
into which a spermatozoön has entered and which is able to develop.
Such a fragment has only the sperm nucleus. This<span class="pagenum" title="186"><a name="Page_186" id="Page_186"></a></span> phenomenon of
merogony was discovered by Boveri and was elaborated by <span
class="nowrap">Delage.<a name="FNanchor_172_172" id="FNanchor_172_172"></a><a href="#Footnote_172_172" class="fnanchor">172</a></span> Boveri, in comparing the final size
of the cells in normal and merogonic eggs after the cell divisions had
come to a standstill, found that this size is always in proportion to
the original mass of the chromatin contained in the egg; the cells of
the merogonic embryo, <i>e. g.</i>, the mesenchyme cells, are only
half the size of the same cells in the normally fertilized embryo.
Driesch furnished a further proof of Boveri’s law, that the final ratio
of the mass of the chromatin substance in a nucleus to the mass of
protoplasm is a constant in a given species. Driesch compared the size
of the mesenchyme cells in a sea-urchin embryo produced by artificial
parthenogenesis with those of a normally fertilized egg and found
them half of the size of the latter. When the fertilized eggs and
the parthenogenetic eggs are equal in size from the start,—which is
practically the case if eggs of the same female are used,—the process
of the formation of mesenchyme cells comes to a standstill when their
number in the normally fertilized eggs is half as large as the final
number in the parthenogenetic <span class="nowrap">egg.<a name="FNanchor_173_173" id="FNanchor_173_173"></a><a href="#Footnote_173_173" class="fnanchor">173</a></span>
Boveri’s results as well as those of Driesch were obtained by counting
the cells formed by eggs of equal size and not by simply measuring
the size of the cells. It is most remarkable that certain apparent
exceptions<span class="pagenum" title="187"><a name="Page_187" id="Page_187"></a></span> to Boveri’s law which Driesch has actually found had been
predicted by Boveri.</p>
<p>These facts show that the growth of an organ comes to a standstill when
a certain size is reached or a certain number of cells are formed. We
cannot yet state why this should be, but we are able to add that the
formation of a lens of normal size in the regeneration of the eye is
in harmony with the phenomena in the embryo. There seems therefore
no reason for stating that the regeneration of the lens cannot be
explained on a purely physicochemical basis. The only justification for
such a statement on the part of Wolf is that he was not in possession
of the more complete set of facts now available through the work of
Fischel and Uhlenhuth.</p>
<p>The healing of a wound is a process essentially similar to the
regeneration of the lens. Normally the cells which begin to proliferate
after a wound is made in the skin lie dormant, inasmuch as they neither
grow nor divide. When a wound is made certain layers of epidermal cells
undergo rapid cell division. Leo <span class="nowrap">Loeb<a name="FNanchor_174_174" id="FNanchor_174_174"></a><a href="#Footnote_174_174" class="fnanchor">174</a></span>
has studied this case extensively. He found that if the skin is removed
anywhere, epidermis cells from the wound edge creep upon the denuded
spot and form a covering. This may be a tropism (stereotropism) or
it may be a mere surface tension phenomenon. Next a rapid process
of cell division begins in the cells adjacent to the wound these
cells having been heretofore dormant.<span class="pagenum" title="188"><a name="Page_188" id="Page_188"></a></span> He is inclined to attribute
this increase in the rate of cell division to the stretching of
the epithelial cells, and he is supported in this reasoning by the
observation that the larger the wound the more rapid the process of
<span class="nowrap">healing.<a name="FNanchor_175_175" id="FNanchor_175_175"></a><a href="#Footnote_175_175" class="fnanchor">175</a></span> During wound healing the
mitoses first increase markedly in the old epithelium. With the closure
of the wound a sudden fall in the mitoses takes place. The closure
of the wound causes an increase in the number of epithelial rows
over the defect. This increase is therefore reached at an earlier
period in the larger wound since the process of mitosis is more rapid
here. Leo Loeb thinks that the pressure of the epithelial cells
upon each other leads to a rapid diminution in the mitotic <span
class="nowrap">proliferation.<a name="FNanchor_176_176" id="FNanchor_176_176"></a><a href="#Footnote_176_176" class="fnanchor">176</a></span></p>
<p><span class="pagenum" title="189"><a name="Page_189" id="Page_189"></a></span></p>
<p>Should it be possible that this is more generally the case,
<i>e. g.</i>, also in the lens after it has reached a certain size? The
conditions limiting growth require further investigation.</p>
<p>It is hardly necessary to point out that in these cases we are
seemingly dealing with cases of the inhibition of growth which cannot
be explained by the tyranny of the whole over the parts, and that there
must be conditions at work other than the mere flow of substances which
can cause a cessation of growth. This can be illustrated by certain
observations on the egg.</p>
<p>8. The history of the egg shows a reversible condition of rest and
of activity. The primordial egg cell multiplies actively until a
large number of eggs are formed in the ovary which may reach into the
millions in the case of sea urchins or certain annelids. These cell
divisions then stop and the egg goes into the resting stage in which
it deposits the reserve material for the development of the embryo.
From this condition it can only be called into activity again by the
spermatozoön or the agencies of artificial parthenogenesis.</p>
<p>It seemed of interest to find out whether or not the development of
the egg may be reversed once more after it has been activated. From
all that has been said in the chapter on artificial parthenogenesis,
such a reversal should take place in the cortical layer. The result of
these experiments seems to be that if a complete destruction or change
in the cortical layer has once<span class="pagenum" title="190"><a name="Page_190" id="Page_190"></a></span> taken place—such as that caused by
the entrance of a spermatozoön into the egg—no reversal is possible;
although the development of the fertilized egg may be suppressed
for a long time by either low temperature or lack of oxygen, or, in
the case of seeds and spores, by lack of water. But as soon as the
conditions for the chemical reactions in the egg are normal again, the
development may go on unless the egg has suffered by the methods used
to prevent development or by the long duration of the suppression. With
an incomplete destruction of the cortical layer both development as
well as reversal of development are possible. Thus the writer has shown
that in the egg of <i class="taxonomic">Arbacia</i> the effect of the cortical alteration
of the egg induced by the butyric acid treatment or by the treatment
with bases can be reversed. When unfertilized eggs of <i class="taxonomic">Arbacia</i> are
put for from two to five minutes into 50 c.c. sea water + 2.0 c.c.
N/10 butyric acid they will all form a gelatinous, somewhat atypical
fertilization membrane; when put back into normal sea water all will
perish in a few hours unless they are submitted to the short treatment
with a hypertonic solution mentioned in the previous chapter, while
if submitted to this treatment they will develop. If, however, these
eggs are transferred from the butyric acid sea water not into normal
sea water but into sea water containing some NaCN (10 drops of <sup>1</sup>⁄<sub>10</sub>
per cent. NaCN or KCN in 50 c.c. sea water), and if they remain here
for some time (<i>e. g.</i> overnight) they will not perish<span class="pagenum" title="191"><a name="Page_191" id="Page_191"></a></span> when
subsequently transferred back to normal sea water. Such eggs will
develop when fertilized with sperm. The activating effect of the
membrane formation has, therefore, been reversed and the eggs have gone
back into the resting <span class="nowrap">stage.<a name="FNanchor_177_177" id="FNanchor_177_177"></a><a href="#Footnote_177_177" class="fnanchor">177</a></span> Wasteneys
has found that the rate of oxidation which was raised considerably by
the artificial membrane formation goes back to the value characteristic
for the resting eggs after the reversal of their developmental <span
class="nowrap">tendency.<a name="FNanchor_178_178" id="FNanchor_178_178"></a><a href="#Footnote_178_178" class="fnanchor">178</a></span> Similar results were obtained in
eggs activated with NH<sub>4</sub>OH. It appears from this as though the change
in the cortical layer which leads to the development of the egg and the
increase in the rate of oxidations were reversible in the egg of <span
class="nowrap"><i class="taxonomic">Arbacia</i>.<a name="FNanchor_179_179" id="FNanchor_179_179"></a><a href="#Footnote_179_179" class="fnanchor">179</a></span></p>
<p>The writer had previously noticed that eggs of <i class="taxonomic">Strongylocentrotus
purpuratus</i>, which had been treated for two hours with hypertonic
sea water, not infrequently began to divide into two, four, or eight
cells (and sometimes more) and then went back into the resting state
(except that they possessed the second factor required for development
as stated in Chapter V). It may be<span class="pagenum" title="192"><a name="Page_192" id="Page_192"></a></span> remarked incidentally that such
eggs at the time of cell division contained the centrosomes and
astrospheres, and yet went back into a resting state, thus showing that
the centrosomes are only transitory organs or organs which are only
active under certain conditions. It is quite possible that in these
phenomena of reversal not the whole of the cortical layer has undergone
alteration.</p>
<p>The writer must leave it undecided whether the changes from the resting
to the active state in body cells can also be explained in analogy with
these experiments.</p>
<p>9. In the formation of the lens we have already noticed an instance
where the adjacent organ influences growth inasmuch as the optic
cup controlled the formation of the lens. Such influences are quite
commonly observed. A piece of <i class="taxonomic">Tubularia</i> when cut out from a stem and
suspended in water will regenerate at the aboral pole not a stolon but
a polyp, so that we have an animal terminating at both ends of its body
in a head. The writer called such cases in which an organ is replaced
by an organ of a different kind heteromorphosis.</p>
<div class="figcenter" style="width: 425px;">
<img src="images/fig_036.png" width="425" height="189" alt="" />
<p class="tac"><span class="smcap">Fig. 36</span></p></div>
<p>Contact with a solid body favours the formation of stolons. Fig. 36
shows a piece of a stem of <i class="taxonomic">Pennaria</i> another hydroid, which was lying
on the bottom of an aquarium and which formed stolons at both ends <i>a</i>
and <i>b</i>. In <i class="taxonomic">Margelis</i>, another hydroid, the writer observed<span class="pagenum" title="193"><a name="Page_193" id="Page_193"></a></span> that
without any operation the apical ends of branches which were in contact
with solid bodies continued to grow as stolons, while those surrounded
by sea water continued to grow as stems.</p>
<p>Herbst discovered a very interesting form of heteromorphosis in certain
crustaceans; namely, that in the place of an eye which was cut off, an
entirely different organ could be formed, namely, an antenna. He showed
that the experimenter has it in his power to determine whether the
crustacean shall regenerate an eye or an antenna in place of the eye.
The latter will take place when the optic ganglion is removed with the
eye, the former when it is not removed. These experiments were carried
out successfully on <i class="taxonomic">Palæmon</i>, <i class="taxonomic">Palæmonetes</i>, <i class="taxonomic">Sicyonia</i>, <i class="taxonomic">Palinurus</i>,
and other crustaceans.</p>
<p>The influence of gravitation is very familiar in plants;<span class="pagenum" title="194"><a name="Page_194" id="Page_194"></a></span> in stems of
<i class="taxonomic">Bryophyllum</i> placed horizontally the roots usually come out from the
lower end of the callus. Such phenomena are not often found in animals
but they exist here too as the following observation shows.</p>
<div class="figright" style="width: 310px;">
<img src="images/fig_037.png" width="310" height="221" alt="" />
<p class="tac"><span class="smcap">Fig. 37</span></p></div>
<div class="figleft" style="width: 150px;">
<img src="images/fig_038.png" width="150" height="766" alt="" />
<p class="tac"><span class="smcap">Fig. 38</span></p></div>
<p>If we cut a piece <i>a b</i> (Fig. 37), from the stem <i>s s</i> of <i class="taxonomic">Antennularia
antennina</i> (Fig. 38), a hydroid, and put it into the water in a
horizontal position, new stems <i>c d</i> (Fig. 37) may arise on its upper
side. The small branches on the under side of the old stem <i>a b</i> begin
suddenly to grow vertically down<span class="nowrap">ward.<a name="FNanchor_180_180" id="FNanchor_180_180"></a><a href="#Footnote_180_180" class="fnanchor">180</a></span>
In appearance and function these downward-growing elements are entirely
different from the branches of the normal <i class="taxonomic">Antennularia</i>; they are
roots. In order to understand better the transformation which thus
occurs in these branches, it may be stated that under normal conditions
they have<span class="pagenum" title="195"><a name="Page_195" id="Page_195"></a></span> a limited growth (see Fig. 38), are directed upward, and
have polyps on their upper side. The parts which grow down (Fig. 37)
have no polyps, but attach themselves like true roots to solid bodies.
Thus the changed position of the stem alone, without any operation,
suffices to transform the lateral branches, whose growth is limited,
into roots with unlimited growth. The lateral branches on the upper
side of the stem do not undergo such a transformation into roots except
in the immediate surroundings of the place where a new stem arises. It
seems that the formation of a new stem also causes an excessive growth
of roots, possibly because the formation of new branches causes the
removal of substances which naturally inhibit the formation of roots.
If a piece from the stem be put vertically into the water with top
downward, the uppermost point may continue to grow as a stem, while the
lowest point may give rise to roots. In this case, therefore, a change
in the orientation of organs has the effect of changing the character
of organs.</p>
<p>There are only two ways by which we can account for these influences of
gravi<span class="pagenum" title="196"><a name="Page_196" id="Page_196"></a></span>tation. Either certain substances flow to the lowest level and
collecting there induce growth and possibly changes in the character
of growth (as in <i class="taxonomic">Antennularia</i>) or if the cells have elements of
different specific gravity the relative position of these elements may
possibly change and influence in this way the conditions for growth.
The influence of gravitation as well as of contact upon life phenomena
are at present little understood.</p>
<p>In all these cases of heteromorphosis the original form is not
restored. It is needless to say that they are incompatible with the
theory of natural selection.</p>
<p>The reader will have noticed that in this chapter one term has
not been mentioned which is commonly met with in the literature,
namely the “wound stimulus.” As the writer had indicated in a former
<span class="nowrap">publication,<a name="FNanchor_181_181" id="FNanchor_181_181"></a><a href="#Footnote_181_181" class="fnanchor">181</a></span> the word “stimulus”
is generally used to disguise our ignorance of (and also our lack
of interest in) the causes which underlie the phenomena which we
investigate. Regeneration very often does not take place near the
wound but at some distance from it. But even when the regeneration
takes place at the edge of the wound the latter only serves to create
conditions for regeneration, and these conditions cannot be expressed
by the word “stimulus.”</p>
<p>While our knowledge of the rôle of the whole in<span class="pagenum" title="197"><a name="Page_197" id="Page_197"></a></span> regeneration is
incomplete in a great many details it seems that the known facts
warrant the statement that the phenomena of regeneration belong as much
to the domain of determinism as those of any of the partial phenomena
of physiology.</p>
<hr class="chap" />
<p><span class="pagenum" title="198"><a name="Page_198" id="Page_198"></a></span></p>
<h2>CHAPTER VIII</h2>
<h3>DETERMINATION OF SEX, SECONDARY SEXUAL CHARACTERS, AND SEXUAL INSTINCTS</h3>
<h4><i>I. The Cytological Basis of Sex Determination</i></h4>
<p>1. It is a general fact that both sexes appear in approximately equal
numbers, provided a sufficiently large number of cases are examined.
This fact has furnished the clue for the discovery of the mechanism
which determines the relative number of the two sexes. The honour of
having pointed the way to the solution of the problem belongs to <span
class="nowrap">McClung.<a name="FNanchor_182_182" id="FNanchor_182_182"></a><a href="#Footnote_182_182" class="fnanchor">182</a></span> It has been known that certain
insects, <i>e. g.</i>, Hemiptera and Orthoptera, possess two kinds of
spermatozoa but only one kind of eggs. The two kinds of spermatozoa
differ in regard to a single chromosome, which is either lacking or
different in one-half of the spermatozoa.</p>
<p>The first one to recognize the existence of two kinds of spermatozoa
was Henking, who stated that in <i class="taxonomic">Pyrrhocoris</i> (a Hemipteran) one-half
of the spermatozoa<span class="pagenum" title="199"><a name="Page_199" id="Page_199"></a></span> of each male possessed a nucleolus, while in
the other half it was lacking. Montgomery afterward showed that
Henking’s nucleolus was an accessory chromosome. McClung was the
first to recognize the importance of this fact for the problem of sex
determination. He observed an accessory chromosome in one-half of the
spermatozoa of two forms of Orthoptera, <i class="taxonomic">Brachystola</i> and <i class="taxonomic">Hippiscus</i>,
and reached the following conclusion:</p>
<div class="blockquot">
<p>A most significant fact, and one upon which almost all
investigators are united in opinion, is that the element is
apportioned to but one-half of the spermatozoa. Assuming it to
be true that the chromatin is the important part of the cell
in the matter of heredity, then it follows that we have two
kinds of spermatozoa that differ from each other in a vital
matter. We expect, therefore, to find in the offspring two sorts
of individuals in approximately equal numbers, under normal
conditions, that exhibit marked differences in structure. A careful
consideration will suggest that nothing but sexual characters thus
divides the members of a species into two well-defined groups,
and we are logically forced to the conclusion that the peculiar
chromosome has some bearing upon the arrangement.</p>
</div>
<p>N. M. Stevens and E. B. <span class="nowrap">Wilson<a name="FNanchor_183_183" id="FNanchor_183_183"></a><a href="#Footnote_183_183" class="fnanchor">183</a></span> have
not only proved the correctness of this idea for a number of animals
but have laid the foundation of our present knowledge of the subject.
Wilson showed that in those cases where there are two types of
spermatozoa, one<span class="pagenum" title="200"><a name="Page_200" id="Page_200"></a></span> with and one without an accessory or as it is now
called an X chromosome, all the cells of the female have one chromosome
more than the cells of the male. From this he concludes correctly that
in such species a female is produced when the egg is fertilized by a
spermatozoön containing an X chromosome, while a male is produced when
a spermatozoön without an X chromosome enters the egg.</p>
<p>Such a form is <i class="taxonomic">Protenor</i>, one of the Hemiptera. Wilson made sure
that all the eggs are alike in the number of chromosomes, each
egg containing an X chromosome in addition to the six chromosomes
characteristic of the species <i class="taxonomic">Protenor</i>. There are two types
of spermatozoa in equal numbers in this species, each with six
chromosomes, but one with, the other without, an X chromosome. The
two possible chromosome combinations between egg and spermatozoa are
therefore as follows (see the diagrammatic Fig. <a href="#fig039">39</a>):</p>
<table class="fs100 ml23em" width="55%" cellpadding="2" summary="Possible chromosome combinations between egg and sperm">
<col width="20%" /><col width="35%" /><col width="45%" />
<tr><td class="tac"><i>Egg</i></td><td class="tac"><i>Spermatozoön</i></td><td class="tac"><i>Result</i></td></tr>
<tr><td>(1) 6 + X</td><td>   + 6</td><td>= 12 + X = Male</td></tr>
<tr><td>(2) 6 + X</td><td>   + 6 + X</td><td>= 12 + 2X = Female</td></tr>
</table>
<p>The egg which receives a spermatozoön without an X chromosome has after
fertilization 12+X chromosomes and develops into a male; while the egg
into which a spermatozoön with an X chromosome enters gives rise to
a female. Since all the body cells arise from the fertilized egg by
nuclear division and the<span class="pagenum" title="201"><a name="Page_201" id="Page_201"></a></span> chromosomes remain constant in number in all
cells, the consequence is that all the cells of a female <i class="taxonomic">Protenor</i>
have two X chromosomes; while all the cells of a male <i class="taxonomic">Protenor</i> have
only one X chromosome.</p>
<div class="figcenter" style="width: 440px;"><a id="fig039"></a>
<img src="images/fig_039.png" width="440" height="396" alt="" />
<p class="tac"><span class="smcap">Fig. 39</span></p></div>
<p>The chromosome situation in <i class="taxonomic">Protenor</i> is a somewhat extreme case,
inasmuch as one X chromosome is entirely lacking in the male. In other
forms of Hemiptera, <i>e. g.</i>, <i class="taxonomic">Lygæus</i>, there are also two types
of spermatozoa appearing in equal numbers differing in regard to<span class="pagenum" title="202"><a name="Page_202" id="Page_202"></a></span> the
X chromosome, but here it is only a difference in size; one-half of
the spermatozoa having a large X chromosome, the other half instead
a smaller chromosome. Calling this latter the Y chromosome, the sex
determination in this form is as follows: leaving aside the chromosomes
which are equal in both egg and spermatozoön we may say that there is
one type of egg containing one large X chromosome; there are two types
of spermatozoa in equal numbers, one possessing a large X chromosome,
the other possessing a small Y chromosome. Wilson showed by a study of
the chromosomes in males and females that when one of the spermatozoa
containing a large X chromosome enters the egg, the egg will develop
into a female; while when one of the spermatozoa containing a small Y
chromosome enters it will give rise to a male. Leaving aside the common
chromosomes of both sexes, a fertilized egg containing XX gives rise
to a female, while one containing XY gives rise to a male. There is
in this case as in that of <i class="taxonomic">Protenor</i> a preponderance of chromosome
material in the female, but this quantitative difference is not
essential for the determination of sex, since in some species the Y
chromosome may be as large as the X chromosome.</p>
<p>The main fact is that the female cells have the chromatin composition
XX, the male cells the composition XY, where Y is apparently
qualitatively different and often, but not necessarily, smaller than X,
or entirely lacking.</p>
<p><span class="pagenum" title="203"><a name="Page_203" id="Page_203"></a></span></p>
<p>It may be mentioned in passing that indirect evidence exists indicating
that in man there are also two kinds of spermatozoa and one kind of
egg, and that sex depends on whether a male determining or a female
determining spermatozoön enters the egg.</p>
<p>2. This mode of sex determination holds only for those animals in which
there is one type of egg and two types of spermatozoa. Experimental
evidence furnished first by Doncaster in 1908 on a moth, <i class="taxonomic">Abraxas</i>,
indicated that a number of other forms exists in which matters are
reversed, inasmuch as there are two types of eggs and one type of
spermatozoa. This condition of affairs exists not only in the moth
<i class="taxonomic">Abraxas</i>, but also in the fowl as shown by Pearl. In these forms it
is assumed that all the spermatozoa have one sex chromosome X, while
there are two types of eggs, one possessing the sex chromosome X,
the other possessing Y. When a spermatozoön enters an egg with an
X chromosome, the egg will give rise to a male, while if it enters
a Y egg, a female will arise. The evidence pointing toward this
result is chiefly contained in experiments on sex-limited or more
correctly sex-linked heredity; <i>i. e.</i>, a form of heredity
which follows the sex in a peculiar way. Thus colour-blindness is
a case of sex-linked inheritance, since this abnormality appears
overwhelmingly in the male offspring of a colour-blind person.
Doncaster crossed two varieties of <i class="taxonomic">Abraxas</i> differing in one character
which was sex-linked, and the<span class="pagenum" title="204"><a name="Page_204" id="Page_204"></a></span> results of his crossings indicated
that in this form there are two types of eggs and one type of <span
class="nowrap">spermatozoa.<a name="FNanchor_184_184" id="FNanchor_184_184"></a><a href="#Footnote_184_184" class="fnanchor">184</a></span></p>
<p>These observations on sex-linked heredity confirm the idea that the
sex chromosomes determine the sex. The most extensive and conclusive
experiments along this line are those by Morgan on the fruit fly
<i class="taxonomic">Drosophila</i>. In this form there are two kinds of spermatozoa and one
kind of eggs; the egg has one X chromosome, while one-half of the
spermatozoa has an X the other a Y chromosome; the entrance of the
latter into an egg gives rise to a male, of the former to a female.</p>
<p>While the eyes of the wild fruit fly <i class="taxonomic">Drosophila ampelophila</i> are
red, <span class="nowrap">Morgan<a name="FNanchor_185_185" id="FNanchor_185_185"></a><a href="#Footnote_185_185" class="fnanchor">185</a></span> noticed in one of his
cultures a male that had white eyes. This white-eyed male was mated to
a red-eyed female. The offspring, the F<sub>1</sub> generation, were all red
eyed, males as well as females. These were inbred and now gave in the
F<sub>2</sub> generation the following three types of offspring:</p>
<table class="fs100 ml23em" cellpadding="1" summary="">
<tr><td colspan="3">(1) 50 per cent. females, all with red eyes.</td></tr>
<tr><td rowspan="2">(2) 50 per cent. males</td><td rowspan="2"><img src="images/35x10brk.png" width="10" height="35" style="padding-top: 5px" alt="" /></td><td> 25 per cent. with red eyes.</td></tr>
<tr><td> 25 per cent. with white eyes.</td></tr>
</table>
<p>The character white eye was therefore transmitted only to half the
grandsons; it was a sex-linked character. It is known from a study of
the pedigrees of colour-blind individuals that if the corresponding
ex<span class="pagenum" title="205"><a name="Page_205" id="Page_205"></a></span>periment had been carried out with them, instead of with white-eyed
flies, the same proportions of normal and colour-blind would have
been found: namely, normal colour vision in the F<sub>1</sub> generation, in
both males and females, and half of the males of the F<sub>2</sub> generation
colour-blind, the other half and all the females with normal vision.
Of course, in man, intermarriage between two different F<sub>1</sub> strains
would have been required in place of the inbreeding of the F<sub>1</sub>
generation, which took place in Morgan’s experiments. Morgan interprets
his experiments as follows. The normal red-eyed <i class="taxonomic">Drosophila</i> has one
kind of eggs, each possessing one X chromosome. This X chromosome has
also the factor for the development of red-eye pigment. The white-eyed
male has two kinds of spermatozoa, one with an X chromosome, the other
with a Y chromosome, both lacking the factor for red-eye pigment. If we
designate the X chromosome with the factor for red-eye pigment by <b>X</b> and
the X and Y chromosomes lacking the factor for redness with X and Y the
following combinations must result if we cross a normal red-eyed female
with a white-eyed male:</p>
<table class="fs100 ml23em" width="45%" cellpadding="1" summary="Result of crossing red-eyed female with white-eyed male">
<col width="20%" /><col width="30%" /><col width="50%" />
<tr><td class="tac"><i>Eggs</i></td><td class="tac"><i>Sperm</i></td><td class="tac"><i>Result</i></td></tr>
<tr><td class="tac"><b>X</b></td><td class="tac">X</td><td class="tal"> <b>X</b>X red-eyed female</td></tr>
<tr><td class="tac"><b>X</b></td><td class="tac">Y</td><td class="tal"> <b>X</b>Y red-eyed male</td></tr>
</table>
<p>It is obvious that all the offspring of the first generation (the F<sub>1</sub>
generation) must be red eyed, since all the<span class="pagenum" title="206"><a name="Page_206" id="Page_206"></a></span> eggs have one <b>X</b>
chromosome with the factor for red. According to the results obtained
from cytological studies which will be explained in the next chapter,
the females with the chromatin constitution <b>X</b>X will form two
types of eggs in equal numbers: namely, eggs with an <b>X</b> and
eggs with an X, <i>i. e.</i>, all eggs have one X chromosome, but
in fifty per cent. of the eggs the <b>X</b> has the factor for red,
in fifty per cent. this factor is lacking (X). The males having the
chromosome constitution <b>X</b>Y form two types of spermatozoa, one
with an <b>X</b> possessing the factor for red pigment and one, the Y
chromosomes, lacking this factor. If inbred the next F<sub>2</sub> generation
will give rise to the following four types of offspring: (1) <b>XX</b>,
(2) <b>X</b>X, (3) <b>X</b>Y, (4) XY, all four types in equal numbers.</p>
<p>(1) and (2) give females, both red eyed, since both contain a
red-factored <b>X</b> chromosome. (3) and (4) give males, (3) giving
rise to red-eyed males, since it contains a red-factored <b>X</b>
chromosome, (4) producing males with white eyes since this X chromosome
is lacking the factor for red eyes. Since all four combinations
must appear in equal numbers (provided the experimental material is
ample enough, which was the case in these experiments), in the F<sub>1</sub>
generation both males and females should have red eyes and in the F<sub>2</sub>
generation all the females should have red eyes and half of the males
should have red, half white eyes. These results were obtained.</p>
<p><span class="pagenum" title="207"><a name="Page_207" id="Page_207"></a></span></p>
<p>The experiments were carried further. No white-eyed females had
appeared thus far. On the same assumptions of the relation of the
<b>X</b>, X, and Y chromosomes to the heredity of sex as well as to eye
colour it was possible to predict under what conditions and in which
proportions white-eyed females should arise. Thus if a red-eyed female
of the F<sub>1</sub> generation (a cross between white-eyed male and normal
female) be mated with a white-eyed male the result should be an equal
number of white-eyed males and white-eyed females if the chromosome
theory of sex determination were correct. The reasoning would be as
follows:</p>
<p>The red-eyed female, having the chromosome constitution <b>X</b>X
should form two kinds of eggs in equal numbers with the constitution
<b>X</b> and X; the white-eyed male having the chromosome constitution
XY should form two kinds of spermatozoa X and Y. The following four
types of individuals must then be produced in equal numbers:</p>
<p class="ml25em">(1) <b>X</b>X, (2) XX, (3) <b>X</b>Y, and (4) XY.</p>
<p>In this case (2) must give rise to white-eyed females and (4) to
white-eyed males, while (1) must give rise to red-eyed females and (3)
to red-eyed males. Hence white-eyed males and females and red-eyed
males and females are to be expected in this case in equal numbers, and
this was actually observed.</p>
<p>The numerical agreement in this and the other<span class="pagenum" title="208"><a name="Page_208" id="Page_208"></a></span> experiments between the
expected and observed result cannot well be an accident. The fact that
the inheritance of sex-linked characters in man follows the same laws
as in <i class="taxonomic">Drosophila</i> is a strong argument in favour of the assumption
that in man, also, sex is determined by two kinds of spermatozoa.</p>
<p>Morgan and his students discovered no less than thirty-six sex-linked
characters in <i class="taxonomic">Drosophila</i>, and each behaved in a similar way to
the red and white eye colour in regard to sex-linked inheritance,
so that the chromosome theory of sex determination rests on a
safe basis. That sex is merely determined by the number of X
chromosomes, not by the Y chromosome, is proved by the facts that
the Y chromosome may be completely absent as in <i class="taxonomic">Protenor</i> and that
<span class="nowrap">Bridges<a name="FNanchor_186_186" id="FNanchor_186_186"></a><a href="#Footnote_186_186" class="fnanchor">186</a></span> has found a type of female
<i class="taxonomic">Drosophila</i> with a chromosome formula <b>X</b>XY whose sex was not affected
by the supernumerary Y.</p>
<p>3. On the basis of all these experiments and theories it is
comparatively easy to explain a number of phenomena concerning sex
ratios which before had been very puzzling. In bees it had been shown
many years ago by Dzierzon that the males develop from unfertilized
eggs while the females, queens and workers, develop from fertilized
eggs. This is intelligible on the assumption that the unfertilized egg
contains only one X chromosome while the spermatozoön carries into the<span class="pagenum" title="209"><a name="Page_209" id="Page_209"></a></span>
egg the second X chromosome. But if the male bee produces two types
of spermatozoa we should expect that only one-half of the fertilized
eggs should be females, the other half males. But it happens that of
the two types of spermatozoa only one is formed since in one of the
cell divisions which lead to the formation of spermatozoa one viable
spermatozoön only is formed while the other one perishes. It is,
therefore, quite possible that it is the female-producing spermatozoön
which survives while the male-producing spermatozoön dies.</p>
<p>It is occasionally observed that an insect shows one sex on one side
of its body and the opposite sex on the other side. Boveri suggested
that this phenomenon of gynandromorphism is due to the fact that
the spermatozoön for some unknown reason does not fuse with the egg
nucleus until after the egg has undergone its first cell division.
In this case it fuses with the nucleus of one of the two cells into
which the egg divides (or in some cases even one of the later cells?).
As a consequence the one-half of the embryo which arises from the
cell which was not fertilized would have only one X chromosome and
in a case like the bee would develop parthenogenetically, while
the other half of the body, developing from the cell into which a
spermatozoön has penetrated, would be fertilized. The latter half of
the body would be female, the former male. In his last paper before
his untimely death, Boveri has given<span class="pagenum" title="210"><a name="Page_210" id="Page_210"></a></span> proof for the correctness of
this interpretation as far as gynandromorphism in the bee is <span
class="nowrap">concerned.<a name="FNanchor_187_187" id="FNanchor_187_187"></a><a href="#Footnote_187_187" class="fnanchor">187</a></span></p>
<p>It seems to be generally true that where sexual reproduction leads
only to the formation of females the case finds its explanation in
the fact that the male-producing spermatozoa perish and only the
female-producing spermatozoa survive. Such an observation was made by
Morgan on a certain species of phylloxerans.</p>
<p>The slight preponderance in the number of one sex which is occasionally
found—an excess of six per cent. males over females in the human
race—may well find its explanation on the assumption of a slightly
greater mortality of the female-determining spermatozoa.</p>
<p>In certain forms parthenogenetic and sexual reproduction may alternate
in a cycle, <i>e. g.</i>, in plant lice, <i class="taxonomic">Daphnia</i>, and rotifers. In
plant lice it has been observed for a long time that when the plant
is normal and the weather warm the aphides remain wingless, reproduce
parthenogenetically, and only females exist, and this may last for
years and for more than fifty generations; but that when the plant is
allowed to dry out both sexes appear.</p>
<p>Here we are dealing with a limited determination of sex inasmuch as the
experimenter has it in his power to prevent or allow the production of
males. The facts do not in all probability contradict the statements<span class="pagenum" title="211"><a name="Page_211" id="Page_211"></a></span>
made concerning the rôle of the X chromosomes in the determination
of sex. We have seen that where sex is determined by two types of
spermatozoa one type of eggs is produced which possesses only one X
chromosome. Such eggs might produce males if not fertilized (as they
do in bees), but they cannot produce females because for that purpose
they must have two X chromosomes. It has been shown for certain
cases, and it may be true generally, that if eggs of this type give
rise to parthenogenetic females they may do so because they have for
some reason two X chromosomes. Usually such an egg loses one of the X
chromosomes in a process of nuclear division (the so-called reduction
division) which usually precedes fertilization. If this reduction
division is omitted the egg has two X chromosomes and if such an egg
develops parthenogenetically it gives rise to a female. These cases do
not, therefore, contradict the connection between X chromosomes and
sex determination established by cytological observations and breeding
experiments, on the contrary, they confirm it. The question remains:
How can external conditions bring it about that the reduction division
is omitted? To this question no definite answer can be given at present.</p>
<p>We may in passing mention the well-known observation that twins which
originate from the same egg always have the same sex; while twins
arising from different eggs show the usual variation as to sex. Twins<span class="pagenum" title="212"><a name="Page_212" id="Page_212"></a></span>
coming from one egg have the same chorion and can thereby be diagnosed
as such. They can be produced as we have stated in Chapter V by a
separation of the first two cleavage cells of the egg, each one giving
rise to a full embryo. It harmonizes with all that has been said above
that the sex of two such individuals must be the same since they have
the same number of X chromosomes, the latter being determined in the
human race by the nature of the spermatozoön which enters the egg.</p>
<p>4. While thus far all the facts agree with the dominating influence
of certain chromosomes upon sex determination, one group of facts has
not yet been explained: namely, hermaphroditism. By hermaphroditism is
meant the existence of complete and separate sets of female and male
gonads in the same individual. This condition exists regularly not only
in definite groups of animals, <i>e. g.</i>, certain snails, leeches,
tape-worms, but also, as everybody knows, in flowering plants. While
in some forms both kinds of sex cells, male and female, are formed
and mature simultaneously, as, <i>e. g.</i>, in the Ascidian <i class="taxonomic">Ciona</i>
(see Chapter IV), in others they are formed successively, very often
the spermatozoa appearing first (protandric hermaphroditism). In the
long tapeworm <i class="taxonomic">Tænia</i> each ring has testes and ovaries, but the young
rings are only male while in the older rings the testes disappear
and the ovaries are formed. The same ring is in succession male and<span class="pagenum" title="213"><a name="Page_213" id="Page_213"></a></span>
female. How can we reconcile the facts of hermaphroditism with the
chromosome theory of sex determination? <i class="taxonomic">Rhabdonema nigrovenosum</i>, a
parasite living in the lungs of the frog, is hermaphroditic, but its
eggs produce not a hermaphroditic generation but one with the two
separate sexes; this generation is not parasitic and lives in the soil.
The generation produced by these separate males and females gives rise
again to a hermaphrodite which migrates into the lungs of the frogs.
According to Boveri and <span class="nowrap">Schleip<a name="FNanchor_188_188" id="FNanchor_188_188"></a><a href="#Footnote_188_188" class="fnanchor">188</a></span>
the cells of the hermaphrodite have twelve chromosomes. It produces
two types of spermatozoa with six and five chromosomes respectively
(one-half of the cells losing one chromosome which is left at the
line of cleavage between the two cells); and one type with six
chromosomes. In this way separate males and females are produced by the
hermaphrodite, females with twelve and males with eleven chromosomes.</p>
<p>The males produce again two kinds of spermatozoa, male and female
producing, but the male-producing spermatozoa become functionless.
This fusion of the other spermatozoön containing six chromosomes with
an egg having six chromosomes leads again to the formation of the
hermaphrodite with twelve chromosomes. It is obvious that in this case
the cause for the hermaphroditism is not disclosed. If chromosomes
have<span class="pagenum" title="214"><a name="Page_214" id="Page_214"></a></span> anything to do with hermaphroditism there must be an undiscovered
element in the chromosomes which may explain why the female as well
as the hermaphrodite have the same chromosome constitution; or we
are forced to look for another determinant outside the X chromosomes
or the chromosomes altogether. This seems to be the only cytological
work on the problem of hermaphroditism. Experimental work has been
begun by <span class="nowrap">Correns<a name="FNanchor_189_189" id="FNanchor_189_189"></a><a href="#Footnote_189_189" class="fnanchor">189</a></span> and by Shull on the
determination of hermaphroditism in plants but lack of space forbids us
to give details.</p>
<h4><i>II. The Physiological Basis of Sex Determination</i></h4>
<p>5. As stated at the beginning of this chapter, the chromosome theory
of sex determination explained only one feature of the problem,
namely, the relative numbers in which both sexes or only one sex, as
the case may be, are produced; and in this respect the evidence is so
complete that we must accept it. But with all this, the problem of
sex determination is not exhausted, since a physiological solution of
the problem of sex determination demands an account of how the sex
chromosomes can induce the formation not only of ovaries and testes
but also of the other sex characters. For the solution of this problem
biology will have to depend largely on experiments in which it is
possible<span class="pagenum" title="215"><a name="Page_215" id="Page_215"></a></span> to influence the formation of sex characters and of the sex
glands themselves.</p>
<p>The most striking observations in this direction were made by Baltzer
on a marine worm, <i class="taxonomic">Bonellia</i>. In this animal the two sexes are very
different, the male being a tiny parasite, a few millimetres in length,
which spends its life in the uterus of the female, whose size is about
five centimetres. A female carries as a rule several and often a large
number of the male parasites in its uterus, which indicates that the
males prevail numerically. The fertilized eggs of the animals are
laid in the sea water where the larvæ hatch. At the time of hatching
all larvæ are alike. The differentiation of the larvæ into the dwarf
males and the giant females can be determined at will. The larvæ have
a tendency to attach themselves to the proboscis of the female as
soon as they hatch. If given a chance to do so and if they stick to
the proboscis for more than three days they will develop into males,
which soon afterwards creep into the female where they continue their
parasitic existence. If, however, no adult female <i class="taxonomic">Bonellia</i> is put
into the aquarium in which the larvæ hatch, about ninety per cent. of
the larvæ will, after a period of rest, develop into females; the rest
develop into males. Those which develop into females will often show a
primary maleness which may manifest itself in the production of sperm
or of other secondary male sexual characters. This tendency is stronger
the longer the<span class="pagenum" title="216"><a name="Page_216" id="Page_216"></a></span> period of rest lasts. If the larvæ are allowed to
settle on the proboscis of the adult female but are removed too early
hermaphrodites are produced having male and female characters mixed.</p>
<p>Baltzer has suggested on the basis of some observations that the larvæ
while on the proboscis of the female absorb some substance secreted by
the proboscis, and this substance accelerates the further development
into a male and suppresses the female tendency. If this substance from
the proboscis does not reach the larvæ the tendency to become males is
gradually suppressed in the majority and only a few develop into pure
males or protandric hermaphrodites, while the female characters are
given a chance to develop. Baltzer assumes, therefore,—as it seems to
us correctly—that in all larvæ the tendency for both sexual characters
is present, that they are, in other words, hermaphrodites, but the
chance for the suppression of one and the development of the other
group of characters can be influenced by certain chemical substances
which the larva may take <span class="nowrap">up.<a name="FNanchor_190_190" id="FNanchor_190_190"></a><a href="#Footnote_190_190" class="fnanchor">190</a></span></p>
<p>Giard has studied the effects of a curious form of castration brought
about by parasites, which is followed by a change in the sexual
character of the castrated animal. The phenomenon is very striking
in certain forms of crabs when they are attacked by a parasitic
crustacean, <i class="taxonomic">Sacculina</i>. The two sexes differ in the crab<span class="pagenum" title="217"><a name="Page_217" id="Page_217"></a></span> <i class="taxonomic">Carcinus
mænas</i> by the form of the abdomen, but when a male is attacked by
the parasite its abdomen assumes the female shape. Smith observed in
another crab that in such cases even the abdominal appendages of the
male may be transformed into those of a female. The transformation is
so complete that the older observers had reached the conclusion that
the parasite attacked only the females, since they overlooked the fact
that the castration by the parasite transformed the secondary sexual
characters of the male into those of a female.</p>
<p>Giard observed that in a diœcious plant, <i class="taxonomic">Lychnis dioica</i>, a parasitic
fungus brings about the transformation of the host into a hermaphrodite.</p>
<p>G. Smith has discovered a fact which shows that chemical changes must
underlie these morphological transformations of primary or secondary
sexual characters. He noticed that in male crabs the presence of the
parasite <i class="taxonomic">Sacculina</i> changes the contents of the fatty constituents
in the blood, making them equal to that of the female. Vaney and
Meignon had previously shown that during the chrysalid stage the female
silkworms have always more glycogen and less fat than the males. The
castration by parasites is paralleled by what Caullery calls the
castration by <span class="nowrap">senility.<a name="FNanchor_191_191" id="FNanchor_191_191"></a><a href="#Footnote_191_191" class="fnanchor">191</a></span> In certain
birds and also in mammals at the time when the sexual glands cease
to function certain secondary<span class="pagenum" title="218"><a name="Page_218" id="Page_218"></a></span> sexual characters of the other sex
make their appearance. The most common case is that certain secondary
male characters appear in the old female (exceptionally also in the
young female with abnormal ovaries) (arrhenoidy). Thus old female
pheasants assume the plumage of the male, and in the human female
after the menopause and especially among sterile women a beard may
begin to grow. The opposite phenomenon, the old male assuming female
characters, is not so common. Very interesting observations on changes
in the plumage of castrated fowl have recently been made by <span
class="nowrap">Goodale.<a name="FNanchor_192_192" id="FNanchor_192_192"></a><a href="#Footnote_192_192" class="fnanchor">192</a></span></p>
<p>It had long been observed by cattle breeders that in the case of twins
of different sex the female—the so-called free-martin—is usually
sterile. F. <span class="nowrap">Lillie<a name="FNanchor_193_193" id="FNanchor_193_193"></a><a href="#Footnote_193_193" class="fnanchor">193</a></span> has recently
discovered the cause of this interesting phenomenon. Such twins
originate from two different eggs since the mother has two corpora
lutea, one in each ovary. In normal single pregnancies in cattle there
is never more than one corpus luteum present. The two eggs begin to
develop separately in each horn of the uterus.</p>
<div class="blockquot">
<p>The rapidly elongating ova meet and fuse in the small body of the
uterus at some time between the 10 mm. and the 20 mm.
stage. The blood-vessels from each side then anastomose in the
connecting part of the chorion; a particularly wide arterial
anastomosis develops, so that either<span class="pagenum" title="219"><a name="Page_219" id="Page_219"></a></span> fetus can be injected from
the other. The arterial circulation of each also overlaps the
venous territory of the other, so that a constant interchange
of blood takes place. If both are males or both are females no
harm results from this; but <i>if one is male and the other female,
the reproductive system of the female is largely suppressed,
and certain male organs even develop in the female. This is
unquestionably to be interpreted as a case of hormone action.</i></p>
<p>The reproductive system of these sterile females is for the most
part of the female type, though greatly reduced. The gonad is the
part most affected; so much so that most authors have interpreted
it as testis.</p>
</div>
<p>It should be added, however, that this result cannot at present be
generalized, since in the hermaphrodites the specific hormones of both
sexes must circulate without suppressing each other’s efficiency.</p>
<p>All these facts indicate that certain substances secreted by the
ovaries or testes may inhibit the development of certain sexual
characters of the opposite sex. When these inhibitions are partly or
entirely removed the secondary sexual characters of the opposite sex
may appear. This fact may also be interpreted as an indication of a
latent hermaphroditism and if this be correct the real and latent
hermaphrodites differ only by the degree of inhibition for one sex,
this inhibition being lacking or less complete in the real than in the
latent hermaphrodite.</p>
<p>In the light of this conclusion the observations on the regeneration
of both ovaries and testicles which Janda observed in a hermaphroditic
worm, <i class="taxonomic">Criodrilus</i><span class="pagenum" title="220"><a name="Page_220" id="Page_220"></a></span> <span class="nowrap"><i class="taxonomic">lacuum</i>,<a name="FNanchor_194_194" id="FNanchor_194_194"></a><a href="#Footnote_194_194" class="fnanchor">194</a></span> is no
longer so mysterious. This worm normally possesses in the segments
near the head a pair of ovaries and several pairs of testes. Janda
found that if the anterior parts containing the gonads of these worms
are cut off a complete regeneration takes place, including both types
of gonads, ovaries as well as testes. As a rule, more than one pair
of ovaries appear in the regenerated piece. This important experiment
shows that in a hermaphrodite both types of sex organs can be produced
from body cells or from latent buds resembling body cells. This
phenomenon would be intelligible on the assumption that in the body of
a hermaphrodite substances circulate which favour the development of
both types of sex organs, while in a diœcian animal probably only one
type of sex organ would be developed; the formation of the other being
inhibited.</p>
<p>Richard Goldschmidt has discovered in his breeding experiments on
the gipsy-moth (<i class="taxonomic">Lymantria dispar</i>) a phenomenon which will probably
throw much light on the physiology of sex determination. He found
that certain crosses between the Japanese and the European gipsy-moth
do not give pure sexes, males or females, but mixtures of the sexual
characters of both sexes, and this mixture is a very definite one for
definite crosses. These differences are such that it is possible to
grade the hybrids according to their mani<span class="pagenum" title="221"><a name="Page_221" id="Page_221"></a></span>festations of maleness or
femaleness, both in morphological characters and instincts. Goldschmidt
calls this peculiar phenomenon intersexualism, and its essential
feature is that the various degrees of intersexualism can be produced
at will by the right combination of races.</p>
<div class="blockquot">
<p>Female intersexualism begins with animals which show feathered
antennæ of medium size (feathered antennæ are a male character),
but which are otherwise entirely female in appearance except
that they produce a smaller number of eggs which are fertilized
normally. In the next stage patches of the brown male pigment
appear on the white female wings in steadily increasing quantity.
The instincts are still female, the males are attracted and
copulate. But the characteristic egg sponge laid by the animal
contains nothing but anal hairs in spite of the fact that the
abdomen is filled with ripe eggs. In the next stage whole sections
of the wings show male colouration, with cuneiform female sectors
between, the abdomen becomes smaller, contains fewer ripe eggs,
the instincts are only slightly female, the males are attracted
very little, and reproduction is impossible. In the next stage the
male pigment covers practically the whole wing, the abdomen is
almost male, but still contains ovaries with a few ripe eggs, the
instincts are intermediate between male and female. Then follow
very male-like animals which still show in different organs their
female origin and have rudimentary ovaries. . . .
The end of the series is formed by males, which show in some minor
characters, such as the shape of wings, still some traces of their
female origin.</p>
<p>The series of the male intersexes starts with males showing
a few white female spots on their wings. These become larger
and larger, the amount of brown pigment<span class="pagenum" title="222"><a name="Page_222" id="Page_222"></a></span> correspondingly
decreasing. . . . Hand in hand with this the abdomen
increases in size, reaching in the most extreme cases two-thirds of
the female size (without containing eggs). The same is true for the
instincts which become more and more female.</p>
</div>
<p>(And also for the copulatory organs which also become more and more
female.)</p>
<p>As stated above, the main fact that every desired degree of
intersexualism can be produced at will by properly combining the races
for breeding, and the intersexual potencies of the different races has
been worked out by <span class="nowrap">Goldschmidt.<a name="FNanchor_195_195" id="FNanchor_195_195"></a><a href="#Footnote_195_195" class="fnanchor">195</a></span></p>
<p>6. The relation between chemical substances circulating in the
body—either derivatives of food taken up from without or of chemical
compounds formed naturally inside the body—and the production of
sexual characters is best shown in the polymorphism found among the
social ants, bees, and wasps. Here we have, as a rule, in addition
to the two sexes a third one, the workers, which are in reality
rudimentary and for that reason sterile females. They differ more
or less markedly from both the typical male and female in their
external form, and, as a rule cannot copulate owing to their deficient
structure. This third sex, the sterile neuters, can be transformed
at desire into sexual females in certain species, as P. Marchal has
demonstrated. He worked with a form of social wasps<span class="pagenum" title="223"><a name="Page_223" id="Page_223"></a></span> in which the
workers are sterile and smaller than the real females. In such a
society of wasps all the males and workers die in the fall and only
the fertilized females survive, each one founding a new nest in the
following spring. From the first eggs laid, workers arise, small in
stature and sterile; these workers are nourished by their mother.
Then these workers take care of the feeding of all those larvæ which
arise from the eggs which their mother continues to lay. Throughout
the spring only workers arise from the eggs. The males appear in the
summer, the real females towards the end of the season when the sexes
copulate.</p>
<p>Marchal isolated a number of the sterile workers, providing them with
food but giving them no larvæ to raise. He found that the workers
which thus far had been sterile became fertile, producing, however,
only males. This latter fact is easily understood from what has been
said regarding the bees, namely, that the female produces only one
type of eggs, hence the unfertilized egg can give rise only to males.
The astonishing or important point is that the ovaries of the workers
begin to develop as soon as they no longer have a chance to nourish
the larvæ, provided the food which would have been given to the larvæ
is now at their disposal. In other words, the development of their
ovaries is the outcome of eating the food which under normal conditions
they would have given to the larvæ. The food must, therefore,
contain a substance<span class="pagenum" title="224"><a name="Page_224" id="Page_224"></a></span> which induces the development of eggs. The
natural sterility of the neuters or workers is, therefore, to use P. Marchal’s
expression, a case of “food castration,” (“castration <span
class="nowrap">nutriciale”).<a name="FNanchor_196_196" id="FNanchor_196_196"></a><a href="#Footnote_196_196" class="fnanchor">196</a></span> The workers originate from
fertilized eggs and are therefore females, but for the full development
of the ovaries and the other sexual characters something else besides
the XX chromosomes is needed and this is supplied in this case by the
quantity or quality of the food. May we not conclude that the same
thing may happen generally, except that these substances are formed by
the body under the normal conditions of nutrition through the influence
of constituents of the second X chromosome?</p>
<p>It is known that the future queens among the bees receive also a
special type of food which the workers do not receive. Again the idea
of “food castration” of the latter is suggested.</p>
<p>In rotifers <span class="nowrap">Whitney<a name="FNanchor_197_197" id="FNanchor_197_197"></a><a href="#Footnote_197_197" class="fnanchor">197</a></span> has shown that the
cycle in the production of males and females can be regulated by the
food. In some species a scanty supply of green flagellates produced
purely female offspring, while a copious diet of the same green
flagellates produced a predominance of male grandchildren, sometimes
as high as ninety-five per cent. This was confirmed by Shull and <span
class="nowrap">Ladoff.<a name="FNanchor_198_198" id="FNanchor_198_198"></a><a href="#Footnote_198_198" class="fnanchor">198</a></span></p>
<p><span class="pagenum" title="225"><a name="Page_225" id="Page_225"></a></span></p>
<p>7. The effects of the removal of the ovaries or testes upon the
development of secondary sexual characters differ for different
species. In insects the secondary sexual characters are not altered
by an operative removal of the sexual glands as in the caterpillar,
<i>e. g.</i>, <i class="taxonomic">Ocneria dispar</i>, according to Oudemans. This result
has been invariably confirmed by all subsequent workers, especially
by Meisenheimer. Crampton grafted the heads of pupæ of butterflies
upon the bodies of other specimens of the opposite sex, but the sexual
characters of the head remained unaltered.</p>
<p>In vertebrates, however, there exists a distinct influence of a
secretion from the sexual glands upon the development of certain of
the secondary sexual characters, which do not develop until sexual
maturity. In a way the observations on arrhenoidy and thelyidy referred
to above are indications of this influence.</p>
<p>Bouin and Ancel had already suggested that the sexual glands of
mammals have two independent constituents, the sexual cells and the
interstitial tissue; and that the latter tissue is responsible for the
development of the secondary sexual character. This has been proved
definitely by <span class="nowrap">Steinach,<a name="FNanchor_199_199" id="FNanchor_199_199"></a><a href="#Footnote_199_199" class="fnanchor">199</a></span> who showed
that when young rats are castrated certain secondary sexual characters
are not fully developed. The seminal vesicles and the prostate remain
rudimentary and<span class="pagenum" title="226"><a name="Page_226" id="Page_226"></a></span> the penis develops incompletely. Such animals when
adult recognize the female and seem to follow it, but do not persist
in their attention and neither erection nor cohabitation occurs.
When, however, the testes are retransplanted into the muscles of the
castrated young animal (so that they are no longer connected with their
nerves) seminal vesicles, prostate, and penis develop normally, and
these animals show normal sexual ardour and cohabitate with a female
although the female cannot become pregnant since the males cannot
ejaculate any sperm. When the retransplanted testes were examined it
was found that all the sperm cells had perished, only the interstitial
tissue of the testes remaining. It was, therefore, proved that the
development of the seminal vesicles, the prostate, the penis, and
the normal sexual instincts and activities depends upon the internal
secretions from this interstitial tissue and not upon the sex cells
proper. This agrees with the conclusions at which Bouin and Ancel had
arrived by ligaturing the vasa deferentia of male animals.</p>
<p>Steinach in another series of experiments castrated young male rats and
transplanted into them the ovaries of young females. These ovaries did
not disintegrate, the eggs remaining, and corpora lutea were formed. In
such feminized individuals the seminal vesicles, prostate, and penis
did not reach their normal development, and it was thereby proved that
the internal secretions from the ovary do not promote the growth of
the<span class="pagenum" title="227"><a name="Page_227" id="Page_227"></a></span> secondary sexual male characters. On the contrary, Steinach was
able to show that the growth of the penis was directly inhibited by the
ovary, since in the feminized males this organ remained smaller than in
the merely castrated animals. On the other hand the infantile uterus
and tube when transplanted into the young male with the ovaries grow
in a normal way, and Steinach thinks that pregnancy in such feminized
males is possible if sperm be injected into the uterus. In some regards
the feminized males showed the morphological habitus of females. Soon
after the transplantation of ovaries into a castrated male the nipples
of its mammary glands begin to grow to the large size which they have
in the female and by which the two sexes can easily be discriminated.
In addition the stronger longitudinal growth of the body in the male
does not occur in the feminized specimens, the body growth becomes
that of a female; and likewise the fat and hair of the feminized male
resemble that of a real female.</p>
<p>While the castrated males show an interest in the females, the
feminized males are absolutely indifferent to females and behave
like them when put together with normal males; and, what is more
interesting, they are treated by normal males like normal females. The
sexual instincts have, therefore, also been reversed in the feminized
males by the substitution of ovaries for testes.</p>
<p><span class="pagenum" title="228"><a name="Page_228" id="Page_228"></a></span></p>
<p>The inhibition of the growth of the penis by the ovary is of
importance; it supports the idea already expressed that in
hermaphrodites this inhibition of the growth of the secondary organs of
the other sex is only feeble or does not exist at all.</p>
<p>We may finally ask whether there is any connection between the
cytological basis of sex determination by special sex chromosomes and
the physiological basis of sex determination by specific substances or
internal secretions. It is possible that the sex chromosomes determine
or favour, in a way as yet unknown, the formation of the specific
internal secretion discussed in the second part of this chapter. In
this way all the facts of sex determination might be harmonized, and
it may become clear that when it is possible to modify secretions by
outside conditions or to feed the body with certain as yet unknown
specific substances the influence of the sex chromosomes upon the
determination of sex may be overcome.</p>
<hr class="chap" />
<p><span class="pagenum" title="229"><a name="Page_229" id="Page_229"></a></span></p>
<h2>CHAPTER IX</h2>
<h3>MENDELIAN HEREDITY AND ITS MECHANISM<a name="FNanchor_200_200" id="FNanchor_200_200"></a><a href="#Footnote_200_200" class="fnanchor">200</a></h3>
<h4 class="tac mtb10em"><i>I</i></h4>
<p>1. The scientific era of the investigation of heredity begins with
Mendel’s paper on plant hybridization which was not appreciated by
his contemporaries. Mendel invented a method for the quantitative
study of heredity which consisted essentially in crossing two forms of
peas differing only in one well-defined hereditary character; and in
following statistically and separately the results of this crossing
and that of the inbreeding of the second and third generations of
hybrids. This led him to the recognition of one essential feature
of heredity; namely, that while the hybrids of the first generation
are all alike, each hybrid produces two types of sex cells in equal
numbers, one for each of the pure breeds which has been used for
the crossing. This takes place not only when the forms used for the
crossing differ in regard to one<span class="pagenum" title="230"><a name="Page_230" id="Page_230"></a></span> character only but also if they
differ for two or more characters. The statement made is Mendel’s law
of heredity, or, more correctly, Mendel’s law of the segregation of
the hereditary characters of the parents in the sex cells of the <span
class="nowrap">hybrids.<a name="FNanchor_201_201" id="FNanchor_201_201"></a><a href="#Footnote_201_201" class="fnanchor">201</a></span> Mendel’s law allows us to tabulate
and calculate beforehand the relative number of different forms which
appear if the offspring of a mating of two varieties are bred among
themselves.</p>
<p>In order to do this it must be remembered also that while in some
cases the hybrid is an intermediate between the two parent forms, in
other cases it cannot be discriminated from one of the two parent
forms. In such cases the character which appears in the hybrid was
called by Mendel the dominant character and the one which disappeared
the recessive character. According to Bateson, who was the first to
systematize the phenomena of Mendelian heredity, recessiveness means
generally the absence of a character which is present in the dominant
type. When, <i>e. g.</i>, the cross between a tall and a dwarf form
of pea gives in the first generation only tall peas, on the basis of
the presence and absence theory the dominant form contains a factor
for growth which is lacking in the dwarf form. While this theory fits
many cases it meets with difficulties in others. Thus the presence of
a factor<span class="pagenum" title="231"><a name="Page_231" id="Page_231"></a></span> for pigment should be dominant over the absence of such a
factor, which is usually the case, inasmuch as the cross of a coloured
rat or rabbit with an albino is black or coloured. There is, however,
also a case where whiteness is dominant over colour, as we shall see
later. This fact does not necessarily contradict the presence and
absence <span class="nowrap">theory.<a name="FNanchor_202_202" id="FNanchor_202_202"></a><a href="#Footnote_202_202" class="fnanchor">202</a></span></p>
<p>When two pure breeds of parents differ in one character, <i>e. g.</i>,
two varieties of beans, one with a violet the other with a white
flower, the cross between the two species (the F<sub>1</sub> generation)
has pale violet flowers, approximately intermediate between the two
parents. If these hybrids are bred among themselves the offspring is
called the F<sub>2</sub> generation. According to Mendel’s law the hybrids of
the first F<sub>1</sub> generation all have two kinds of eggs in equal numbers,
one kind representing the pure breed of the parents with violet, the
other of the pure breed with white flowers. The same is true for the
pollen cells. Hence the following possible combinations must appear in
the offspring when the pale violet hybrids are inbred:</p>
<div class="figcenter" style="width: 262px;">
<img src="images/diag1.png" width="262" height="83" alt="diagram showing possible combinations of characters produced when two hybrids are in-bred" /></div>
<p>The four possible combinations are: (1) violet—violet;<span class="pagenum" title="232"><a name="Page_232" id="Page_232"></a></span> (2)
violet—white; (3) violet—white; (4) white—white. The first will
result in pure violet flowers, the fourth in pure white, and the second
and third in pale violet flowers. Since all four combinations will
appear in equal numbers when the number of crossings is sufficiently
large the numerical result will be:</p>
<p class="ml25em">violet : pale violet : white = 1 : 2 : 1</p>
<p>Fifty per cent. of the F<sub>2</sub> generation will be pale violet, 25 per
cent. violet, and 25 per cent. white. The violets and whites each will
breed true when bred among themselves since they are pure, and produce
only one type of eggs and pollen. The pale violets are hybrids and will
again produce the two types of eggs and pollen, that is, if bred among
themselves will again give violets, pale violets, and whites in the
ratio 1:2:1. This the experiment confirms.</p>
<p>As has been stated, it not infrequently happens that all the hybrids
of the first generation are alike. In such cases the one character
is “recessive,” <i>i. e.</i>, overshadowed or covered by the other
the “dominant” character, which alone appears in the hybrids. Thus
when Mendel crossed peas having round seeds with peas having angular
seeds all the hybrids had round seeds. The round form is dominant, the
angular recessive, <i>i. e.</i>, all the hybrids have round seeds. When
these hybrids were bred among themselves the next genera<span class="pagenum" title="233"><a name="Page_233" id="Page_233"></a></span>tion produced
round and angular seeds in the ratio of 3:1 (5474 round to 1850
angular). The explanation is as follows. Let R denote round, A angular
character; the pure breeds of parents have the gametic constitution
RR and AA respectively. When crossed, all the offsprings have the
constitution RA and since A is recessive this hybrid generation
resembles the pure RR parents. The F<sub>1</sub> generation produces two kinds
of eggs R and A and two kinds of pollen R and A in equal numbers, and
these if inbred give the following four combinations in equal numbers:</p>
<p class="ml25em">RR, RA, AR, AA.</p>
<p>Since RA, AR, and RR all give round seeds the F<sub>2</sub> generation produces
round seeds to angular seeds in the ratio of 3:1. The two organisms
with the gametic constitution RR and RA look alike, yet they are
different in regard to heredity. The gametically pure form RR is called
homozygous, the impure form RA heterozygous.</p>
<p>2. W. S. <span class="nowrap">Sutton<a name="FNanchor_203_203" id="FNanchor_203_203"></a><a href="#Footnote_203_203" class="fnanchor">203</a></span> was the first to
show that the behaviour of the chromosomes furnishes an adequate
basis on which to account for Mendel’s law of the segregation of the
characters in the sex cells of the hybrids. If we disregard the cases
of parthenogenesis and the X chromosomes, we may state that each<span class="pagenum" title="234"><a name="Page_234" id="Page_234"></a></span>
species is characterized by a definite number of chromosomes, <span
class="nowrap"><i>e. g.</i><a name="FNanchor_204_204" id="FNanchor_204_204"></a><a href="#Footnote_204_204" class="fnanchor">204</a></span></p>
<table class="fs100 ml25em" width="60%" summary="numbers of chromosomes in different species">
<col width="40%" /><col width="6%" /><col width="35%" /><col width="10%" />
<tr><td>man (probably)</td><td class="tar">24</td><td class="pl20">corn</td><td class="tar">20</td></tr>
<tr><td>mouse</td><td class="tar">20</td><td class="pl20">evening primrose</td><td class="tar">7</td></tr>
<tr><td>snail (<i class="taxonomic">Helix hortensis</i>)</td><td class="tar">22</td><td class="pl20">nightshade</td><td class="tar">36</td></tr>
<tr><td>potato beetle</td><td class="tar">18</td><td class="pl20">tobacco</td><td class="tar">24</td></tr>
<tr><td>cotton</td><td class="tar">28</td><td class="pl20">tomato</td><td class="tar">12</td></tr>
<tr><td>four o’clock</td><td class="tar">16</td><td class="pl20">wheat</td><td class="tar">8</td></tr>
<tr><td>garden pea</td><td class="tar">7</td></tr>
</table>
<p>In the fertilization of the egg the number of chromosomes is doubled
(if we disregard for the moment the complication caused by the X and
Y chromosomes which was considered in the previous chapter). It was
noticed by Montgomery that each chromosome had a definite size and
individuality, and he suggested that homologous chromosomes existed in
sperm and egg and that in fertilization the homologous chromosomes of
egg and sperm always joined and fused in the special stage designated
as synapsis, which will interest us later. On the basis of this
suggestion Sutton developed the chromosome theory of the mechanism of
Mendelian heredity or segregation.</p>
<p>According to this theory, all the cells of an individual (inclusive of
the egg cells and sperm cells) have two sets of homologous chromosomes,
one from the father, the other from the mother. Before the egg and
sperm<span class="pagenum" title="235"><a name="Page_235" id="Page_235"></a></span> are ready for the production of a new individual, each loses
one set of homologous chromosomes in the so-called reduction division,
but the lost set is made up indiscriminately of maternal as well as
paternal chromosomes, so that while one egg retains the maternal
chromosome <i>A</i> the other will retain the paternal one, and so on.
If before the reduction division all the eggs had the chromosome
constitution <i>AA<sub>1</sub></i>, <i>BB<sub>1</sub></i>, <i>CC<sub>1</sub></i>, <i>DD<sub>1</sub></i>
(where <i>A B C D</i> are the paternal and <i>A<sub>1</sub> B<sub>1</sub> C<sub>1</sub> D<sub>1</sub></i> the maternal
chromosomes), after the reduction division each daughter cell has a
full set of four chromosomes, but maternal and paternal mixed. Thus the
one cell may have <i>AB<sub>1</sub>CD<sub>1</sub></i>, the other <i>A<sub>1</sub>B<sub>1</sub>C<sub>1</sub>D<sub>1</sub></i>,
etc. This, according to Sutton, is the basis of the Mendelian heredity.
Suppose the determiner of a certain character (violet colour of flower
in the bean) is located in a chromosome <i>A</i> of this species. The
homologous chromosome in beans with white colour may be designated
as <i>a</i>. According to the chromosome theory of Mendelian heredity <i>a</i>
differs from <i>A</i> in one point, though this difference is probably only
of a chemical character and not visible.</p>
<p>If an egg with <i>A</i> is fertilized by a pollen with <i>a</i> (or <i lang="la" xml:lang="la">vice
versa</i>), after fertilization the chromosome constitution of the
fertilized egg is <i>Aa</i>. All the other homologous chromosomes are
identical and therefore need not be considered. All the nuclei of the
<span class="pagenum" title="236"><a name="Page_236" id="Page_236"></a></span>F<sub>1</sub> generation have the chromosome constitution <i>Aa</i>. All will form
eggs and pollen with nuclei of the same chromosome constitution <i>Aa</i>,
but all these sex cells will go through the maturation division before
they are fertilized; and this reduction division leads to the existence
of two kinds of eggs in equal numbers, one containing only the <i>A</i>, the
other only the <i>a</i> chromosome; and the same happens in the pollen. When
therefore the hybrids F<sub>1</sub> are mated among themselves, the following
four chromosome combinations will be produced:</p>
<div class="figcenter" style="width: 222px;">
<img src="images/diag2.png" width="222" height="75" alt="diagram showing possible combinations of allelles in fertilized eggs" /></div>
<p class="tac">Possible combinations in fertilized eggs
<i>AA</i>, <i>Aa</i>, <i>aa</i>, in the ratio 1:2:1.</p>
<p>Now this is exactly the ratio of Mendelian heredity in the F<sub>2</sub>
generation. The plant with the chromosome constitution <i>AA</i> will form
violet flowers, those with the chromosome constitution <i>Aa</i> will form
pale violet flowers, and those with the chromosome constitution <i>aa</i>
will form white flowers.</p>
<p>To quote Sutton’s words:</p>
<div class="blockquot">
<p>The result would be expressed by the formula <i>AA: Aa: aa</i> which
is the same as that given for any character in a Mendelian case.
Thus the phenomena of germ cell division and of heredity are
seen to have the same essential features viz., purity of units
(chromosomes, characters) and the independent transmission of the
same; while as a corollary it follows in each case that each of the
two antago<span class="pagenum" title="237"><a name="Page_237" id="Page_237"></a></span>nistic units (chromosomes, characters) is contained by
exactly half the gametes produced.</p>
</div>
<p>It is obvious that Sutton by this idea did for heredity in general what
McClung had done for sex determination or sex heredity, that is, he
showed that the numerical results obtained in Mendelian heredity can
be accounted for on the basis that factors for hereditary characters
are carried by definite chromosomes. The cytological basis of sex
determination becomes only a special case of the cytological basis of
Mendelian heredity. In the examples quoted the plants giving rise to
violet and to white flowers are homozygous for the colour of flower
having the chromosome constitution <i>AA</i> and <i>aa</i> respectively; while
the plants with pale violet flowers are heterozygous, having the
chromosome constitution <i>Aa</i> in their nuclei. The former give rise to
identical sex cells <i>A</i> and <i>A</i> or <i>a</i> and <i>a</i>; while the heterozygous
plants give rise to different sex cells <i>A</i> and <i>a</i>.</p>
<p>From this point of view in <i class="taxonomic">Drosophila</i> (and very probably also in
man) the female is homozygous for sex having in all its cells the
critical chromosome constitution XX and giving rise to one type
of eggs only, each with one X chromosome; while the male in these
forms is heterozygous for sex having in all its cells the chromosome
constitution XY and forming two different types of spermatozoa in
equal numbers<span class="pagenum" title="238"><a name="Page_238" id="Page_238"></a></span> X and Y. In <i class="taxonomic">Abraxas</i> and in the fowl the female is
heterozygous for sex and the male homozygous.</p>
<p>3. If the chromosomes are the vehicle for Mendelian heredity it should
be possible to show that the various hereditary characters which follow
Mendel’s law must be distributed over the various chromosomes; and it
should be possible to find out which characters are contained in the
same chromosome. It has already been stated that sex-linked heredity
is intelligible on the assumption that the X chromosome carries the
sex-linked characters. T. H. Morgan and his pupils have shown with the
greatest degree of probability that corresponding linkages occur in
the other chromosomes and that there are in <i class="taxonomic">Drosophila</i> exactly as
many groups of linkage as there are different chromosomes, namely <span
class="nowrap">four.<a name="FNanchor_205_205" id="FNanchor_205_205"></a><a href="#Footnote_205_205" class="fnanchor">205</a></span></p>
<p>Mendel had found that when he crossed two species of peas differing in
regard to two pairs of characters, he obtained in the F<sub>2</sub> generation
results which he calculated on the assumption that the segregation
of the two pairs of characters in the sex cells of the hybrids took
place independently of each other. To illustrate by an example: When
crossing a yellow round pea with a green wrinkled variety in which the
characters round and yellow are dominant, green and wrinkled recessive,
<span class="pagenum" title="239"><a name="Page_239" id="Page_239"></a></span>all the hybrids of the F<sub>1</sub> generation had the characters round and
yellow. When these were inbred the F<sub>2</sub> generation produced four types
of seed in the ratio 9: 3: 3: 1, namely:</p>
<p class="ml25em">
(1) yellow round (315 seeds)<br />
(2) yellow wrinkled (101 seeds)<br />
(3) green round (108 seeds)<br />
(4) green wrinkled (32 seeds)</p>
<p>The explanation according to Mendel’s theory is as follows: Since the
segregation of each pair of characters occurs independently, there must
be 3 yellow to 1 green and also 3 round to 1 wrinkled in the F<sub>2</sub>
generation. The yellow will, therefore, be round and wrinkled in the
ratio of 3:1, which will give 9 yellow round to 3 yellow wrinkled. The
green will also be round and wrinkled in the ratio of 3:1, which will
give 3 green round to 1 green wrinkled, which is the ratio of 9: 3: 3:
1 found by Mendel.</p>
<p>On the basis of the chromosome theory the following explanation could
be given of this numerical relation. The peas with yellow round
seeds have sex cells with a factor for both yellow and for round
in two different chromosomes; these two different chromosomes we
will designate with Y and R. The peas with green and wrinkled seeds
will have in their sex cells factors for these characters in two
homologous chromosomes g and w, where g is the homologue of Y and w
<span class="pagenum" title="240"><a name="Page_240" id="Page_240"></a></span>of R. The cells of the hybrids of the F<sub>1</sub> generation will have the
chromosome constitution Yg Rw, where Y and g and R and w are homologous
chromosomes which will lie alongside each other <span class="nowrap"><span class="fraction"><span class="fnum">YR</span><span class="fden2">gw</span></span></span>.
In the formation of sex cells a reduction of
these four chromosomes to two takes place whereby, according to the
theory of Sutton, the following two types of separation can take place:
YR and gw, or gR and Yw. (A separation into Yg and Rw is impossible
since the division takes place only between homologous chromosomes.)
Hence there will be four types of eggs, YR, gw, gR, and Yw and the
same four types of pollen cells. The F<sub>2</sub> generation will produce the
sixteen possible combinations in equal numbers: namely,</p>
<p class="ml25em">
YRYR YRgw YRgR YRYw<br />
gwYR gwgw gwgR gwYw<br />
gRYR gRgw gRgR gRYw<br />
YwYR Ywgw YwgR YwYw<br />
</p>
<p>Since w and g are recessives and therefore disappear when in
combination with their respective dominants Y and R the result will
be 9 YR (yellow round), 3 Yw (yellow wrinkled), 3 Rg (round green),
and 1 gw (green wrinkled) as Mendel actually observed and as all
investigators since have confirmed.</p>
<p>Bateson made the discovery that these Mendelian ratios 9: 3: 3: 1 did
not always occur when forms differing in two characters were crossed.
He found typical and very constant deviations from this ratio<span class="pagenum" title="241"><a name="Page_241" id="Page_241"></a></span> in
definite cases and these cases he interpreted as being due to “gametic
coupling.”</p>
<div class="blockquot">
<p>These phenomena demonstrate the existence of a complex
interrelation between the factorial units. This interrelation is
such that certain combinations between factors may be more frequent
than others. The circumstances in which this interrelation is
developed and takes effect we cannot as yet distinguish, still less
can we offer with confidence any positive conception as to the mode
in which it is <span class="nowrap">exerted.<a name="FNanchor_206_206" id="FNanchor_206_206"></a><a href="#Footnote_206_206" class="fnanchor">206</a></span></p>
</div>
<p>Morgan has given an ingenious explanation of these deviations on the
basis of the chromosome theory of Mendelian heredity. He assumes
that they occur in those cases where the two or more characters are
contained in the same chromosome. In that case the two factors lying
in the same chromosome should generally be found together. Such was
the case for instance in the experiments with flies having red eyes
and yellow body colour <i lang="la" xml:lang="la">versus</i> white eyes and grey body colour,
the character for white eyes and yellow body being located in the X
chromosome (see preceding chapter), or in the experiments on <i class="taxonomic">Abraxas</i>.
These phenomena are called linkage, and the numerical results of
linkage were given in the preceding chapter in connection with the
crossing of sex-linked characters.</p>
<p>We have already mentioned that before the maturation division occurs
the homologous maternal and paternal chromosomes fuse—the so-called
synapsis<span class="pagenum" title="242"><a name="Page_242" id="Page_242"></a></span> of the cytologists—and afterward separate again. It had
been observed by Janssens that in this stage of fusion and subsequent
separation a partial twisting and a partial exchange between two
chromosomes may take place. Morgan assumes that this exchange accounts
for certain deviations in the ratio of linkage. If in Fig. 40 the white
and black signify two homologous chromosomes I and I<sub>1</sub> containing the
two pairs of homologous factors AB and ab respectively, the synapsis
state would be as in Fig. 41. If the separation were complete, either
I or its homologue I<sub>1</sub> might be lost in the maturation division of
the egg. If, however, the synapsis is slightly irregular, as in Fig.
42, where the chromosomes are slightly twisted, I and I<sub>1</sub> will not
<span class="pagenum" title="243"><a name="Page_243" id="Page_243"></a></span>separate completely but an exchange will take place, part of I<sub>1</sub> and
I becoming exchanged. This would result in the formation of two mixed
chromosomes Ab and aB (Fig. 42). This partial exchange of homologous
chromosomes, which Morgan calls “crossing over,” occurs, as he found in
<i class="taxonomic">Drosophila</i>, in the egg only, not in the maturation division of the
sperm. He informs me that in the silkworm moth Tanaka found that it
occurs only in the male, while in <i class="taxonomic">Primula</i> it takes place both in the
ovules and in the pollen as shown by Gregory.</p>
<table class="figct" summary="figures 40-42">
<tr class="vat"><td><div class="figcenter" style="width: 94px;">
<img src="images/fig_040.png" width="94" height="255" alt="" />
<p class="tac"><span class="smcap">Fig. 40</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 143px;">
<img src="images/fig_041.png" width="143" height="255" alt="" />
<p class="tac"><span class="smcap">Fig. 41</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 144px; padding-top: 20px;">
<img src="images/fig_042.png" width="144" height="235" alt="" />
<p class="tac"><span class="smcap">Fig. 42</span></p>
</div></td></tr>
</table>
<p>Morgan and his fellow-workers have put this theory to numerous tests
by breeding experiments and the results have fully supported it.
According to the chromosome theory linkage should occur only when
factors lie in the same chromosome. Hence it should be possible,
on the basis of this linkage theory, to foretell how many linkage
groups there may occur in a species; namely, as many as there are
chromosomes. In <i class="taxonomic">Drosophila</i> there are four pairs of chromosomes, and
Morgan and his fellow-workers found only four groups of linked <span
class="nowrap">characters.<a name="FNanchor_207_207" id="FNanchor_207_207"></a><a href="#Footnote_207_207" class="fnanchor">207</a></span> This agreement can be no mere
accident.</p>
<p>Carrying the assumption still farther, these authors were able to
show that each individual character has in all probability a definite
location in the chromosome, so that it seems as if each individual
chromosome<span class="pagenum" title="244"><a name="Page_244" id="Page_244"></a></span> consisted of a series of smaller chromosomes, each of which
may be a factor in the determination of a hereditary character which is
transmitted according to Mendel’s law of segregation. Biology has thus
reached in the chromosome theory of Mendelian heredity an atomistic
conception, according to which independent material determiners for
hereditary characters exist in a linear arrangement in the chromosomes.</p>
<h4 class="tac mtb10em"><i>II</i></h4>
<p>4. We are not concerned in this volume with the many applications of
the theory of heredity to the breeding of plants, animals, and man; the
reader will find a discussion of these topics in the numerous writings
of the special workers on <span class="nowrap">genetics.<a name="FNanchor_208_208" id="FNanchor_208_208"></a><a href="#Footnote_208_208" class="fnanchor">208</a></span> We
are, however, interested in the bearing this work has on the conception
of the organism. Two questions present themselves: Is the organism
nothing but a mosaic of hereditary characters determined essentially
by definite elements located in the chromosomes; and if this be true,
what makes a harmonious whole organism out of this kaleidoscopic
assortment? We call it a kaleidoscopic assortment since a glance at the
list of hereditary characters found in one chromosome, according to
Morgan, shows that there is apparently<span class="pagenum" title="245"><a name="Page_245" id="Page_245"></a></span> no physiological or chemical
connection between them, and second: How can a factor contained in the
chromosome determine a hereditary character of the organism? To the
first question we venture to offer the answer which has been already
suggested in various chapters of this book, that the cytoplasm of the
egg is the future embryo in the rough; and that the factors of heredity
in the sperm only act by impressing the details upon the rough block.
This metaphor will receive a more definite meaning by the answer to
the second question. The characters which follow Mendelian heredity
are morphological features as well as instincts. For the former we
have already had occasion to show in previous chapters to what extent
they depend upon the internal secretions or the existence of specific
compounds in the circulation, and the same is true for the instincts
(Chapters VIII and X). This then leads us to the suggestion that
these determiners contained in the chromosomes give rise each to the
formation of one or more specific substances which influence various
parts of the body. We probably do not notice all the effects in each
case, but when a special organ is affected in a conspicuous way, we
connect the factor with this organ or the special feature of the organ
which is altered, and speak of a determiner or factor for that organ,
or for one of its characters. We also understand in this way why
outside conditions should be able to overcome the hereditary tendency<span class="pagenum" title="246"><a name="Page_246" id="Page_246"></a></span>
in certain cases, for instance why the influence of certain hereditary
factors for pigmentation should depend upon temperature as E. Baur
observed.</p>
<p>The view, according to which the determiners in the chromosomes only
tend to give special characters to the embryo or to the adult while
the cytoplasm of the egg may be considered the real embryo, receives
some support from the fact that the first development of the egg is
purely maternal, even if the egg nucleus has been replaced by sperm
of a different species. If an egg of a sea urchin be cut into two
pieces, one with and one without a nucleus, and the enucleated piece
be fertilized with the sperm of a different species of sea urchin, the
blastula and gastrula stages are purely maternal and only the skeleton
of the pluteus stage begins to betray the influence of the foreign
sperm inasmuch as this skeleton is purely paternal, according to
Boveri. In all experiments on hybridization it has been found that the
rate of cell division of the egg is a purely maternal character. Thus
when fish eggs of a species, in which the rate of first segmentation of
the egg is about eight hours, are fertilized with sperm of a species
for which the same process requires about thirty minutes or less at
the same temperature, the rate of segmentation is again about eight
hours. There is then no chromosome influence noticeable in the early
development.</p>
<p>When two forms of sea urchins, <i class="taxonomic">Strongylocentrotus</i><span class="pagenum" title="247"><a name="Page_247" id="Page_247"></a></span> <i class="taxonomic">franciscanus</i> and
<span class="nowrap"><i class="taxonomic">purpuratus</i>,<a name="FNanchor_209_209" id="FNanchor_209_209"></a><a href="#Footnote_209_209" class="fnanchor">209</a></span> are crossed, certain
features of the skeleton of the embryo, <i>e. g.</i>, the so-called
cross-bars, are a dominant, inasmuch as they are found in <i class="taxonomic">purpuratus</i>
and both the crosses, while they are absent in <i class="taxonomic">franciscanus</i>. The
development prior to the formation of the skeleton is purely maternal.
These observations again lend support to the idea that the Mendelian
factors of heredity must have the embryo to work on and that the
organism is not to be considered a mere mosaic of Mendelian factors.
This is further supported by the idea that the species specificity
resides in the proteins of the unfertilized egg (see Chapter III), and
it is quite likely that this species specificity decides which type of
animal should arise from an egg.</p>
<p>The idea had been suggested that the factors which determine the future
character might be ferments or enzymes, or substances from which such
ferments develop. A. R. <span class="nowrap">Moore<a name="FNanchor_210_210" id="FNanchor_210_210"></a><a href="#Footnote_210_210" class="fnanchor">210</a></span> pointed
out that the cross-bars in the skeleton of the hybrid between <i class="taxonomic">S.
purpuratus</i> and <i class="taxonomic">franciscanus</i> develop more slowly than in the pure
breed and that this should be expected if the determiners were enzymes.
Since the pure <i class="taxonomic">purpuratus</i> has two determiners for the development
of the cross-bars (from both egg and sperm), the hybrids only one
(from either<span class="pagenum" title="248"><a name="Page_248" id="Page_248"></a></span> egg or sperm), the pure <i class="taxonomic">purpuratus</i> should have twice
the enzyme mass of the hybrid. It is known that the velocity of a
chemical reaction increases in proportion with the mass (or in some
cases in proportion with the square root of the mass) of the enzyme;
the cross-bars should therefore develop faster in the pure than in the
hybrid breeds, as was observed by Moore. It was, however, not possible
to obtain quantitative data.</p>
<p>On the other hand, it is obvious that this reasoning would not hold
for all cases. Thus when beans with violet flowers are crossed with
white-flowered beans the hybrids are pale blue, which indicates that
the hybrids have less pigment than the pure violet. Now we know that
the mass of enzyme does not influence the chemical equilibrium but only
the velocity of the reaction. The hybrids and pure violets differ,
however, in the mass of violet pigment formed, that is to say, in
regard to the equilibrium. Hence the idea that the determiners are
enzymes or give rise to enzymes is probably not applicable to cases of
this type.</p>
<p>The experiments on the heredity of pigments are at present almost
the only ones which can be used for an analysis of the chemical
nature of the character and its possible determiner. The important
work of G. <span class="nowrap">Bertrand<a name="FNanchor_211_211" id="FNanchor_211_211"></a><a href="#Footnote_211_211" class="fnanchor">211</a></span> and of <span
class="nowrap">Chodat<a name="FNanchor_212_212" id="FNanchor_212_212"></a><a href="#Footnote_212_212" class="fnanchor">212</a></span> on the production of<span class="pagenum" title="249"><a name="Page_249" id="Page_249"></a></span> black
pigment in the cells of animals and plants with the aid of enzymes
has paved the way for such work. Bertrand has shown that tyrosine
(<i>p</i>-oxyphenylaminopropionic acid) is transformed into a black pigment
by an enzyme tyrosinase which occurs in numerous organisms and is
obviously the cause of pigment and colouration in a great number of
species. This discovery was utilized in the study of the heredity of
pigments by Miss Durham, <span class="nowrap">Gortner,<a name="FNanchor_213_213" id="FNanchor_213_213"></a><a href="#Footnote_213_213" class="fnanchor">213</a></span> and
very recently by <span class="nowrap">Onslow.<a name="FNanchor_214_214" id="FNanchor_214_214"></a><a href="#Footnote_214_214" class="fnanchor">214</a></span> The latter
showed that from the skins of certain coloured rabbits and mice a
peroxidase can be extracted which behaves like a tyrosinase toward
tyrosine in the presence of hydrogen peroxide. This peroxidase was
found in the skins of black agouti, chocolate and blue rabbits, but not
in yellow or orange rabbits. The recessive whiteness in rabbits and
mice according to this author is due to the lack of the peroxydase.
There exists a dominant whiteness in the English rabbit which is due to
a tyrosinase inhibitor which destroys the activity of the tyrosinase
“and the dominant white bellies of yellow and agouti rabbits are due
to the same cause.” “Variations in coat colour are probably due to a
quantitative rather than to a qualitative difference in the pigment
present.”</p>
<p>One point might still be mentioned since it may help to overcome a
difficulty in visualizing the connection<span class="pagenum" title="250"><a name="Page_250" id="Page_250"></a></span> between the localization
of a factor in the chromosome and the production of a comparatively
large quantity of a specific chemical compound, <i>e. g.</i>, a
chromogen or a tyrosinase. We must remember that all the cells of an
organism have identical chromosomes, so that a factor for an enzyme
like tyrosinase is contained in every cell throughout the whole body.
It is likely, however, that the same factor (which we may conceive
to be a definite chemical compound) will find a different chemical
substrate to work on in the cells of different organs of the body,
since the different organs differ in their chemical composition.
Thus it is conceivable that in the production of tyrosinase or of
tyrosine not a single chromomere of one single cell is engaged, but
the sum total of all these individual chromomeres of all the cells in
one or several organs of the body. The writer has added this remark
especially in consideration of the fact that some authors seem to feel
that the chromosome conception of heredity is incompatible with a
physicochemical view of this process.</p>
<p>Since we have mentioned this difficulty which some writers seem to
find in the chromosome theory of Mendelian heredity, it may be added
that a single factor may suffice to determine a series of complicated
reflexes. Thus the heliotropic reactions of animals are due to the
presence of photosensitive substances, and it suffices for the
hereditary transmission of the complicated<span class="pagenum" title="251"><a name="Page_251" id="Page_251"></a></span> purposeful reactions based
on these tropisms that a factor for the formation of the photosensitive
substance should <span class="nowrap">exist.<a name="FNanchor_215_215" id="FNanchor_215_215"></a><a href="#Footnote_215_215" class="fnanchor">215</a></span></p>
<p>5. Another point should be emphasized, namely that for Mendelian
heredity it is immaterial whether the character is introduced by the
spermatozoön or by the egg. This fact which Mendel himself already
recognized is in full harmony with the conclusion that the chromosomes
and not the cytoplasm are the bearers of Mendelian heredity, since only
in respect to the chromosome constitution are egg and sperm alike,
while they differ enormously in regard to the mass of protoplasm they
carry. We can, therefore, be tolerably sure that wherever we deal with
a hereditary factor which is determined by the egg alone the cytoplasm
of the latter is partly or exclusively responsible for the result.</p>
<p>We have already mentioned the fact that the rate of segmentation of
the egg is such a character. Yet this character is as definite as
any Mendelian character, and it would be as easy to discriminate two
species of eggs by the time required from insemination to the beginning
of cell division as it would be by any Mendelian character of their
parents.</p>
<p>The application of our modern knowledge of heredity to human affairs
has been discussed in a very original<span class="pagenum" title="252"><a name="Page_252" id="Page_252"></a></span> way by Bateson in his address
before the British Association in Sydney to which the reader may be
<span class="nowrap">referred.<a name="FNanchor_216_216" id="FNanchor_216_216"></a><a href="#Footnote_216_216" class="fnanchor">216</a></span> </p>
<hr class="chap" />
<p><span class="pagenum" title="253"><a name="Page_253" id="Page_253"></a></span></p>
<h2>CHAPTER X</h2>
<h3>ANIMAL INSTINCTS AND TROPISMS<a name="FNanchor_217_217" id="FNanchor_217_217"></a><a href="#Footnote_217_217" class="fnanchor">217</a></h3>
<p>1. The idea that the organism as a whole cannot be explained from
a physicochemical viewpoint rests most strongly on the existence
of animal instincts and will. Many of the instinctive actions are
“purposeful,” <i>i. e.</i>, assisting to preserve the individual and
the race. This again suggests “design” and a designing “force,” which
we do not find in the realm of physics. We must remember, however,
that there was a time when the same “purposefulness” was believed to
exist in the cosmos where everything seemed to turn literally and
metaphorically around the earth, the abode of man. In the latter
case, the anthropo- or geocentric view came to an end when it was
shown that the motions of the planets were regulated by Newton’s law
and that there was no room left for the<span class="pagenum" title="254"><a name="Page_254" id="Page_254"></a></span> activities of a guiding
power. Likewise, in the realm of instincts when it can be shown that
these instincts may be reduced to elementary physicochemical laws the
assumption of design becomes superfluous.</p>
<p>If we look at the animal instincts purely as observers we might well
get the impression that they cannot be explained in mechanistic terms.
We need only consider what mysticism apparently surrounds all those
instincts by which the two sexes are brought together and by which the
entrance of the spermatozoön into the egg is secured; or the remarkable
instincts which result in providing food and shelter for the young
generation.</p>
<p>We have already had occasion to record some cases of instincts which
suggest the possibility of physicochemical explanation; for example the
curious experiment of Steinach on the reversal of the sexual instincts
of the male whose testes had been exchanged for ovaries. There is
little doubt that in this case the sexual activities of each sex are
determined by specific substances formed in the interstitial tissue of
the ovary and testes. The chemical isolation of the active substances
and an investigation of their action upon the various parts of the body
would seem to promise further progress along this line.</p>
<p>Marchal’s observations on the laying of eggs by the naturally sterile
worker wasps are a similar case. The fact that such workers lay
eggs when the queen is removed or when they are taken away from the
larvæ<span class="pagenum" title="255"><a name="Page_255" id="Page_255"></a></span> may be considered as a manifestation of one of those wonderful
instincts which form the delight of readers of Maeterlinck’s romances
from insect life. Imagine the social foresight of the sterile workers
who when the occasion demands it “raise” eggs to preserve the stock
from extinction! And yet what really happens is that these workers,
when there are no larvæ, can consume the food which would otherwise
have been devoured by the larvæ; and some substance contained in
this food induces the development of eggs in the otherwise dormant
ovaries. What appeared at first sight as a mysterious social instinct
is revealed as an effect comparable to that of thyroid substance upon
the growth of the legs of tadpoles in Gudernatsch’s experiment (Chapter
VII).</p>
<p>2. If we wish to show in an unmistakable way the mechanistic character
of instincts we must be able to reduce them to laws which are also
valid in physics. That instinct, or rather that group of instincts,
for which this has been accomplished are the reactions of organisms
to light. The reader is familiar with the tendency of many insects to
fly into the flame. It can be shown that many species of animals, from
the lowest forms up to the fishes, are at certain stages—very often
the larval stage—of their existence, slaves of the light. When such
animals, <i>e. g.</i>, the larvæ of the barnacle or certain winged
plant lice or the caterpillars of certain butterflies, are put into a
trough or<span class="pagenum" title="256"><a name="Page_256" id="Page_256"></a></span> test-tube illuminated from one side only, they will rush
to the side from which the light comes and will continue to do this
whenever the orientation of the trough or test-tube to the light is
changed; while they will be held at the window side of the vessel
if the light or the position of the vessel remains unchanged. This
instinct to get to the source of light is so strong that, <i>e. g.</i>,
the caterpillars of <i class="taxonomic">Porthesia chrysorrhœa</i> die of starvation on the
window side of the vessel, with plenty of food close behind. This
powerful “instinct” is, as we intend to show, in the last analysis, the
expression of the Bunsen-Roscoe law of photochemical reactions. A large
number of chemical reactions are induced or accelerated by light, and
the Bunsen-Roscoe law shows that the chemical effect is in these cases,
within certain limits, equal to the product of the intensity into the
duration of illumination.</p>
<p>The “attraction” or “repulsion” of animals by the light had been
explained by the biologists in an anthropomorphic way by ascribing to
the animals a “fondness” for light or for darkness. Thus Graber, who
had made the most extensive experiments, gave as a result the statement
that animals which are fond of light are also fond of blue while they
hate the red, and those which are fond of the “dark” are fond of red
and hate the <span class="nowrap">blue.<a name="FNanchor_218_218" id="FNanchor_218_218"></a><a href="#Footnote_218_218" class="fnanchor">218</a></span> In 1888 the writer
published a paper<span class="pagenum" title="257"><a name="Page_257" id="Page_257"></a></span> in which he pointed out that the so-called fondness
of animals for light and blue and for dark and red was simply a case
of an automatic orientation of animals by the light comparable to the
turning of the tips of a plant towards the window of the room in which
the plant is <span class="nowrap">raised.<a name="FNanchor_219_219" id="FNanchor_219_219"></a><a href="#Footnote_219_219" class="fnanchor">219</a></span></p>
<p>The phenomenon of a plant bending or growing to the source of light is
called positive heliotropism (while we speak of negative heliotropism
in all cases in which the plant turns away from the light, as is
observed in many roots). The writer pointed out that animals which go
to the light are positively heliotropic (or phototropic) and do so
because they are compelled automatically by the light to move in this
direction, while he called those animals which move away from the light
negatively heliotropic; they are automatically compelled by the light
to move away from it. What the light does is to direct the motions of
the animals and to explain this the following theory was proposed.
Animals possess photosensitive elements on the surface of their bodies,
in the eyes, or occasionally also in epithelial cells of their skin.
These photosensitive elements are arranged symmetrically in the body
and through nerves are connected with symmetrical groups of muscles.
The light causes chemical changes in the<span class="pagenum" title="258"><a name="Page_258" id="Page_258"></a></span> eyes (or the photosensitive
elements of the skin). The mass of photochemical reaction products
formed in the retina (or its homologues) influences the central
nervous system and through this the tension or energy production of
the muscles. If the rate of photochemical reaction is equal in both
eyes this effect on the symmetrical muscles is equal, and the muscles
of both sides of the body work with equal energy; as a consequence
the animal will not be deviated from the direction in which it was
moving. This happens when the axis or plane of symmetry of the animal
goes through the source of light, provided only one source of light
be present. If, however, the light falls sidewise upon the animal,
the rate of photochemical reaction will be unequal in both eyes and
the rate at which the symmetrical muscles of both sides of the body
work will no longer be equal; as a consequence the direction in which
the animal moves will change. This change will take place in one of
two ways, according as the animal is either positively or negatively
heliotropic; in the positively heliotropic animal the resulting motion
will be toward, in the negatively heliotropic from, the light. Where
we have no central nervous system, as in plants or lower animals,
the tension of the contractile or turgid organs is influenced in a
different way, which we need not discuss here.</p>
<p>The reader will perceive that according to the writer’s theory
two agencies are to be considered in<span class="pagenum" title="259"><a name="Page_259" id="Page_259"></a></span> these reactions: first, the
symmetrical arrangement of the photosensitive and the contractile
organs, and second, the relative masses of the photochemical reaction
products produced in both retinæ or photosensitive organs at the same
time. If a positively heliotropic animal is struck by light from one
side, the effect on tension or energy production of muscles connected
with this eye will be such that an automatic turning of the head and
the whole animal towards the source of light takes place; as soon as
both eyes are illuminated equally the photochemical reaction velocity
will be the same in both eyes, the symmetrical muscles of the body will
work equally, and the animal will continue to move in this direction.
In the case of the negatively heliotropic animal the picture is the
same except that if only one eye is illuminated the muscles connected
with this eye will work less energetically. The theory can be nicely
tested for negatively heliotropic animals in the larvæ of the blowfly
when they are fully grown, and for positively heliotropic animals on
the larvæ of <i class="taxonomic">Balanus</i>, and many other organisms.</p>
<table class="figrt" summary="figures 43-44">
<tr><td><div class="figcenter" style="width: 315px;">
<img src="images/fig_043.png" width="315" height="191" alt="" />
<p class="tac"><span class="smcap">Fig. 43</span></p>
</div></td></tr>
<tr><td><div class="figcenter" style="width: 325px;">
<img src="images/fig_044.png" width="325" height="184" alt="" />
<p class="tac"><span class="smcap">Fig. 44</span></p>
</div></td></tr>
</table>
<p>One of the difficulties in identifying the motions of animals to
or from the light with the positive and negative heliotropism of
plants consisted in the fact that plants are mostly sessile (and
respond to a one-sided illumination with heliotropic curvatures to
or from the light), while most animals are free moving and respond
to the one-sided illumination by being<span class="pagenum" title="260"><a name="Page_260" id="Page_260"></a></span> turned and compelled to
move to or from the light. This difficulty was overcome by the
observation that sessile animals like the hydroid <i class="taxonomic">Eudendrium</i> (Fig.
43) or the tube worm <i class="taxonomic">Spirographis</i> (Fig. 44) react to a one-sided
illumination also with heliotropic curvatures like sessile <span
class="nowrap">plants.<a name="FNanchor_220_220" id="FNanchor_220_220"></a><a href="#Footnote_220_220" class="fnanchor">220</a></span> On the other hand, it had been
found before by Strassburger that free-swimming plant<span class="pagenum" title="261"><a name="Page_261" id="Page_261"></a></span> organisms like
the swarmspores of algæ move to or from the source of light as do
free-swimming animals.</p>
<p>3. The writer suggested in <span class="nowrap">1897<a name="FNanchor_221_221" id="FNanchor_221_221"></a><a href="#Footnote_221_221" class="fnanchor">221</a></span> that
the light acts chemically in the heliotropic reactions and in 1912 that
the heliotropic reactions probably follow the law of Bunsen and <span
class="nowrap">Roscoe,<a name="FNanchor_222_222" id="FNanchor_222_222"></a><a href="#Footnote_222_222" class="fnanchor">222</a></span> and it was possible to confirm this
idea by direct <span class="nowrap">experiments.<a name="FNanchor_223_223" id="FNanchor_223_223"></a><a href="#Footnote_223_223" class="fnanchor">223</a></span> This law
states that the photochemical effect of light equals <i>i t</i> where <i>i</i>
is the intensity of the light and <i>t</i> the duration of illumination.
The experiments were carried out on young regenerating polyps of
<i class="taxonomic">Eudendrium</i> by measuring the time required to cause fifty per cent. of
the polyps to bend to the source of light. The intensity of light was
varied by altering the distance of the source of light from the polyps.
Table VI gives the result.</p>
<p class="tac">TABLE VI</p>
<table width="75%" summary="Phototropic reactions of regenerating polyps">
<col width="33%" /><col width="33%" /><col width="33%" />
<tr><th class="btr" rowspan="2"><i>Distance between Polyps and Source of Light</i></th><th class="btl" colspan="2"><i>Time Required to Cause Fifty Per Cent. of the Polyps to Bend towards the Source of Light</i></th></tr>
<tr><td class="tac ball"><span class="smcap">Observed</span></td><td class="tac btl ptb03"><span class="smcap">Calculated from<br />Bunsen-Roscoe Law</span></td></tr>
<tr><td class="tac btr pt03"><i>Metres</i></td><td class="tac brl pt03"><i>Minutes</i></td><td class="tac btl pt03"><i>Minutes</i></td></tr>
<tr><td class="tac">0.25</td><td class="tac brl"><span class="hide">1</span>10</td><td class="tac"></td></tr>
<tr><td class="tac">0.50</td><td class="tac brl">between 35 and 40</td><td class="tac"><span class="hide">1</span>40</td></tr>
<tr><td class="tac">1.00</td><td class="tac brl">150</td><td class="tac">160</td></tr>
<tr><td class="tac bbr pb03">1.50</td><td class="tac bb pb03">between 360 and 420</td><td class="tac bbl pb03">360</td></tr>
</table>
<p><span class="pagenum" title="262"><a name="Page_262" id="Page_262"></a></span></p>
<p>We must therefore conclude that the heliotropic curvature of the
polyps is determined by a photochemical action of the light. The
light brings about or accelerates a chemical reaction which follows
the Bunsen-Roscoe law. As soon as the product of this reaction on one
side of the polyp exceeds that on the other by a certain quantity,
the bending occurs. When the product <i>i t</i> is the same for symmetrical
spots of the organism no bending can result. This is what our theory
suggested.</p>
<p>It is very difficult to prove directly the applicability of the
Bunsen-Roscoe law for free-moving animals, but it can be shown that
intermittent light is as effective as constant light of the same
intensity, provided that the total duration of the illumination by the
intermittent light is equal to that of the constant light, and the
duration of the intermission is sufficiently small (Talbot’s law).
Talbot’s law is in reality only a modification of the Bunsen-Roscoe
law. Ewald has proved in a very elegant way the applicability
of Talbot’s law to the orientation of the eyestalk of <span
class="nowrap"><i class="taxonomic">Daphnia</i>.<a name="FNanchor_224_224" id="FNanchor_224_224"></a><a href="#Footnote_224_224" class="fnanchor">224</a></span> This makes it probable that the
law of Bunsen-Roscoe underlies generally the heliotropic reaction of
animals.</p>
<p>It is of importance for the theory of the identity of the
heliotropism of animals and plants that in the latter organisms the
law of Bunsen and Roscoe is also applicable. This had been shown
previously by<span class="pagenum" title="263"><a name="Page_263" id="Page_263"></a></span> <span class="nowrap">Fröschel<a name="FNanchor_225_225" id="FNanchor_225_225"></a><a href="#Footnote_225_225" class="fnanchor">225</a></span> and by
<span class="nowrap">Blaauw.<a name="FNanchor_226_226" id="FNanchor_226_226"></a><a href="#Footnote_226_226" class="fnanchor">226</a></span> In the following table
are given the results of Blaauw’s experiments on the applicability
of the Bunsen-Roscoe law for the heliotropic curvature of the
seedlings of oats (<i class="taxonomic">Avena sativa</i>). The time required to cause
heliotropic curvatures for intensities of light varying from 0.00017
to 26520 metre-candles was measured. The product <i>i t</i>, namely
metre-candles-seconds, varies very little (between 16 and 26).</p>
<p class="tac">TABLE VII</p>
<table width="90%" summary="Heliotropic curvature of oat seedlings with various light intensities">
<tr><th class="btr" colspan="2">I<br /><i>Duration of Illumination</i></th><th class="btr">II<br /><i>Metre-Candles</i></th><th class="btrd">III<br /><i>Metre-Candles-Seconds</i></th><th class="btld" colspan="2">I<br /><i>Duration of Illumination</i></th><th class="btl" colspan="2">II<br /><i>Metre-Candles</i></th><th class="btl">III<br /><i>Metre-Candles-Seconds</i></th></tr>
<tr><td class="tar bt pt03">43</td><td class="tal btr pt03"> hours</td><td class="tal btr ptl03">0.00017</td><td class="tac btrd pt03">26.3</td><td class="tar btld pt03">25</td><td class="tal btr pt03"> seconds</td><td class="tar btl pt03">1</td><td class="tal btr pt03">.0998</td><td class="tac btl pt03">27.5</td></tr>
<tr><td class="tar">13</td><td class="tal">  "</td><td class="tal brl pl03">0.000439</td><td class="tac brld">20.6</td><td class="tar">8</td><td class="tal br">  "</td><td class="tar">3</td><td class="tal br">.02813</td><td class="tac">24.2</td></tr>
<tr><td class="tar">10</td><td class="tal">  "</td><td class="tal brl pl03">0.000609</td><td class="tac brld">21.9</td><td class="tar">4</td><td class="tal br">  "</td><td class="tar">5</td><td class="tal br">.456</td><td class="tac">21.8</td></tr>
<tr><td class="tar">6</td><td class="tal">  "</td><td class="tal brl pl03">0.000855</td><td class="tac brld">18.6</td><td class="tar">2</td><td class="tal br">  "</td><td class="tar">8</td><td class="tal br">.453</td><td class="tac">16.9</td></tr>
<tr><td class="tar">3</td><td class="tal">  "</td><td class="tal brl pl03">0.001769</td><td class="tac brld">19.1</td><td class="tar">1</td><td class="tal br">  "</td><td class="tar">18</td><td class="tal br">.94</td><td class="tac">18.9</td></tr>
<tr><td class="tar">100</td><td class="tal"> minutes</td><td class="tal brl pl03">0.002706</td><td class="tac brld">16.2</td><td class="tar"><sup>2</sup>⁄<sub>5</sub></td><td class="tal br">  "</td><td class="tar">45</td><td class="tal br">.05</td><td class="tac">18.0</td></tr>
<tr><td class="tar">60</td><td class="tal">  "</td><td class="tal brl pl03">0.004773</td><td class="tac brld">17.2</td><td class="tar"><sup>2</sup>⁄<sub>25</sub></td><td class="tal br">  "</td><td class="tar">308</td><td class="tal br">.7</td><td class="tac">24.7</td></tr>
<tr><td class="tar">30</td><td class="tal">  "</td><td class="tal brl pl03">0.01018</td><td class="tac brld">18.3</td><td class="tar"><sup>1</sup>⁄<sub>25</sub></td><td class="tal br">  "</td><td class="tar">511</td><td class="tal br">.4</td><td class="tac">20.5</td></tr>
<tr><td class="tar">20</td><td class="tal">  "</td><td class="tal brl pl03">0.01640</td><td class="tac brld">19.7</td><td class="tar"><sup>1</sup>⁄<sub>55</sub></td><td class="tal br">  "</td><td class="tar">1255</td><td class="tal br"></td><td class="tac">22.8</td></tr>
<tr><td class="tar">15</td><td class="tal">  "</td><td class="tal brl pl03">0.0249</td><td class="tac brld">22.4</td><td class="tar"><sup>1</sup>⁄<sub>100</sub></td><td class="tal br">  "</td><td class="tar">1902</td><td class="tal br"></td><td class="tac">19.0</td></tr>
<tr><td class="tar">8</td><td class="tal">  "</td><td class="tal brl pl03">0.0498</td><td class="tac brld">23.9</td><td class="tar"><sup>1</sup>⁄<sub>400</sub></td><td class="tal br">  "</td><td class="tar">7905</td><td class="tal br"></td><td class="tac">19.8</td></tr>
<tr><td class="tar">4</td><td class="tal">  "</td><td class="tal brl pl03">0.0898</td><td class="tac brld">21.6</td><td class="tar"><sup>1</sup>⁄<sub>800</sub></td><td class="tal br">  "</td><td class="tar">13094</td><td class="tal br"></td><td class="tac">16.4</td></tr>
<tr><td class="tar bb pb03">40</td><td class="tal bbr pb03"> seconds</td><td class="tal bbrl pbl03">0.6156</td><td class="tac bbrd pb03">24.8</td><td class="tar bbld pb03"><sup>1</sup>⁄<sub>1000</sub></td><td class="tal bbr">  "</td><td class="tar bbl pb03">26520</td><td class="tal bbr"></td><td class="tac bb pb03">26.5</td></tr>
</table>
<p>It is, therefore, obvious that the blind instinct which forces animals
to go to the light, <i>e. g.</i>, in the case of the moth, is identical
with the instinct which makes<span class="pagenum" title="264"><a name="Page_264" id="Page_264"></a></span> a plant bend to the light and is a
special case of the same law of Bunsen and Roscoe which also explains
the photochemical effects in inanimate nature; or in other words,
the will or tendency of an animal to move towards the light can be
expressed in terms of the Bunsen-Roscoe law of photochemical reactions.</p>
<p>The writer had shown in his early publications on light effects that
aside from the heliotropic reaction of animals, which as we now know
depends upon the product of the intensity and duration of illumination,
there is a second reaction which depends upon the sudden changes in
the intensity of illumination. These latter therefore obey a law of
the form: <span class="nowrap">Effect = f (<span class="fraction"><span class="fnum">di</span><span class="bar">/</span><span class="fden">dt</span></span>).<a name="FNanchor_227_227" id="FNanchor_227_227"></a><a href="#Footnote_227_227" class="fnanchor">227</a></span> Jennings
has maintained that the heliotropic reactions of unicellular organisms
are all of this kind, but investigations by Torrey and by <span
class="nowrap">Bancroft<a name="FNanchor_228_228" id="FNanchor_228_228"></a><a href="#Footnote_228_228" class="fnanchor">228</a></span> on <i class="taxonomic">Euglena</i> have shown that
Jennings’s statements were based on incomplete observations.</p>
<p>4. In these experiments only one source of light was applied.
“When two sources of light of equal intensity and distance act
simultaneously upon a heliotropic animal, the latter puts its median
plane at right angles to the line connecting the two sources of <span
class="nowrap">light.”<a name="FNanchor_229_229" id="FNanchor_229_229"></a><a href="#Footnote_229_229" class="fnanchor">229</a></span> This fact has been amply verified by
Bohn, by Parker and his pupils, and especially by Bradley Patten, who<span class="pagenum" title="265"><a name="Page_265" id="Page_265"></a></span>
used it to compare the relative efficiency of two different lights.</p>
<p>The behaviour of the animals under the influence of two lights is a
confirmation of our theory of heliotropism inasmuch as the animal moves
in such a direction that the symmetrical elements of the surface of
the body are struck by light of the same intensity at the same angle,
so that as a consequence equal masses of photosensitive substances
are produced in symmetrical elements of their eyes or skin in equal
times. The effect on the symmetrical muscles will be identical. As
soon as one of the lights is a little stronger the animal will deviate
towards this light, in case it is positively heliotropic and towards
the weaker light if it is negatively heliotropic. This deviation again
is not the product of chance but follows a definite law as <span
class="nowrap">Patten<a name="FNanchor_230_230" id="FNanchor_230_230"></a><a href="#Footnote_230_230" class="fnanchor">230</a></span> has recently shown. He used the
negatively heliotropic larvæ of the blowfly. These larvæ were made to
record their trail while moving under the influence of the two lights.
The results of the measurements of 2500 trails showing the progressive
increase in angular deviation of the larvæ (from the perpendicular
upon the line connecting the two lights), with increasing differences
between the lights, are given in the following table. Since the
deviation or angular deflection of the larvæ is towards the weaker of
the two lights it is marked negative. </p>
<p><span class="pagenum" title="266"><a name="Page_266" id="Page_266"></a></span></p>
<p class="tac">TABLE VIII</p>
<table width="58%" summary="Heliotropic reactions of blowfly larvae">
<col width="22%" /><col width="22%" /><col width="56%" />
<tr><th class="btr" colspan="2"><i>Percentage Difference in the Intensity of the Two Lights</i></th><th class="btl"><i>Average Angular Deflection of the Two Paths of the Larvæ towards the Weaker Light</i></th></tr>
<tr><td class="tac btr pt03" colspan="2"><i>Per Cent.</i></td><td class="tac btl pt03"><i>Degrees</i></td></tr>
<tr><td class="tar">0</td><td class="tal br"></td><td class="tac"><span class="hide">0</span>-0.09</td></tr>
<tr><td class="tar">8</td><td class="tal br pl01"><sup>1</sup>⁄<sub>3</sub></td><td class="tac"><span class="hide">0</span>-2.77</td></tr>
<tr><td class="tar">16</td><td class="tal br pl01"><sup>2</sup>⁄<sub>3</sub></td><td class="tac"><span class="hide">0</span>-5.75</td></tr>
<tr><td class="tar">25</td><td class="tal br"></td><td class="tac"><span class="hide">0</span>-8.86</td></tr>
<tr><td class="tar">33</td><td class="tal br pl01"><sup>1</sup>⁄<sub>3</sub></td><td class="tac">-11.92</td></tr>
<tr><td class="tar">50</td><td class="tal br"></td><td class="tac">-20.28</td></tr>
<tr><td class="tar">66</td><td class="tal br pl01"><sup>2</sup>⁄<sub>3</sub></td><td class="tac">-30.90</td></tr>
<tr><td class="tar">83</td><td class="tal br pl01"><sup>1</sup>⁄<sub>3</sub></td><td class="tac">-46.81</td></tr>
<tr><td class="tar bb pb03">100</td><td class="tal bbr"></td><td class="tac bbl pb03">-77.56</td></tr>
</table>
<p>Let us assume that the negatively heliotropic animal is at an equal
distance from the two unequal lights and placed so that at the
beginning of the experiment its median plane is at right angles to
the line connecting the two lights, but with its head turned away
from them. In that case the velocity of reaction in the symmetrical
photosensitive elements of the eyeless larvæ is greater on the side of
the stronger light. Since the animal is negatively heliotropic this
will result in a greater relaxation or a diminution of the energy
production of the muscles turning the head of the animal towards the
side of the stronger light. Hence the animal will automatically deviate
from the straight line towards the side of the weaker light. By the
alteration of the position of its body the photosensitive elements
exposed to the stronger of the two lights<span class="pagenum" title="267"><a name="Page_267" id="Page_267"></a></span> will be put at a less
efficient angle and hence the rate of photochemical reaction on this
side will be diminished. The deviation from the perpendicular in which
the animal will ultimately move will be such that as a consequence, the
rate of photochemical reaction in symmetrical elements is again equal.
The ultimate direction of motion will, according to our theory always
be such that the mass of chemical products formed under the influence
of light in symmetrical photosensitive elements during the same time is
equal.</p>
<p>Patten also investigated the question whether the same difference of
percentage between two lights would give the same deviation, regardless
of the absolute intensities of the lights used. The absolute intensity
was varied by using in turn from one to five glowers. The relative
intensity between the two lights varied in succession by 0, 8<sup>1</sup>⁄<sub>3</sub>,
16<sup>2</sup>⁄<sub>3</sub>, 25, 33<sup>1</sup>⁄<sub>3</sub>, and 50 per cent. Yet the angular deflections were
within the limits of error identical for each relative difference of
intensity of the two lights no matter whether, 1, 2, 3, 4, or 5 glowers
were used. The following table shows the result.</p>
<p><span class="pagenum" title="268"><a name="Page_268" id="Page_268"></a></span></p>
<p class="tac">TABLE IX</p>
<p class="tac mrl10"><span class="smcap">A Table Based on the Measurements of 2700
Trails Showing the Angular Deflections at Five Different Absolute
Intensities</span></p>
<table cellpadding="2" summary="Heliotropic reactions of blowfly larvae to different absolute intensities">
<tr><th class="btr" rowspan="2"><i>Number<br />of<br />Glowers</i></th><th class="btl" colspan="6"><i>Difference of Intensity between the Two Lights</i></th></tr>
<tr><td class="tac ball pall">0<br />per cent.</td><td class="tac ball pall">8<sup>1</sup>⁄<sub>3</sub><br />per cent.</td><td class="tac ball pall">16<sup>2</sup>⁄<sub>3</sub><br />per cent.</td><td class="tac ball pall">25<br />per cent.</td><td class="tac ball pall">33<sup>1</sup>⁄<sub>3</sub><br />per cent.</td><td class="tac btl pall">50<br />per cent.</td></tr>
<tr><td class="tac bt"></td><td class="tac brl"></td><td class="tac brl" colspan="4"><i>Deflection in Degrees</i></td><td class="tac btl"></td></tr>
<tr><td class="tac">1</td><td class="tac brl"> -0.55<span class="hide">0</span></td><td class="tac">-2.32</td><td class="tac brl">-5.27<span class="hide">0</span></td><td class="tac">-9.04</td><td class="tac brl">-11.86</td><td class="tac">-19.46</td></tr>
<tr><td class="tac">2</td><td class="tac brl"> -0.10<span class="hide">0</span></td><td class="tac">-3.05</td><td class="tac brl">-6.12<span class="hide">0</span></td><td class="tac">-8.55</td><td class="tac brl">-11.92</td><td class="tac">-22.28</td></tr>
<tr><td class="tac">3</td><td class="tac brl">+0.45<span class="hide">0</span></td><td class="tac">-2.60</td><td class="tac brl">-5.65<span class="hide">0</span></td><td class="tac">-8.73</td><td class="tac brl">-13.15</td><td class="tac">-20.52</td></tr>
<tr><td class="tac">4</td><td class="tac brl"> -0.025</td><td class="tac">-2.98</td><td class="tac brl">-6.60<span class="hide">0</span></td><td class="tac">-9.66</td><td class="tac brl">-11.76</td><td class="tac">-19.88</td></tr>
<tr><td class="tac bbr">5</td><td class="tac brl"> -0.225</td><td class="tac">-2.92</td><td class="tac brl">-5.125</td><td class="tac">-8.30</td><td class="tac brl">-10.92</td><td class="tac bbl">-19.28</td></tr>
<tr><td class="tac bbr ptb03">Average</td><td class="tac ball ptb03"> -0.09<span class="hide">0</span></td><td class="tac ball ptb03">-2.77</td><td class="tac ball ptb03">-5.75<span class="hide">0</span></td><td class="tac ball ptb03">-8.86</td><td class="tac ball ptb03">-11.92</td><td class="tac bbl ptb03">-20.28</td></tr>
</table>
<p>Such constancy of quantitative results is only possible where we are
dealing with purely physicochemical phenomena or where life phenomena
are unequivocally determined by purely physicochemical conditions.</p>
<p>5. It seems difficult for some biologists, even with the validity
of the Bunsen-Roscoe law proven, to imagine that the movements of
the animals under the influence of light are not voluntary (or
not dictated by the mysterious “trial and error” method of <span class="pagenum" title="269"><a name="Page_269" id="Page_269"></a></span><span
class="nowrap">Jennings).<a name="FNanchor_231_231" id="FNanchor_231_231"></a><a href="#Footnote_231_231" class="fnanchor">231</a></span> But one wonders how it is
possible on such an assumption to account for the fact that the angle
of deflection of the larva of the fly when under the influence of two
lights of different intensities should be always the same for a given
difference in intensity; or why the time for curvature in <i class="taxonomic">Eudendrium</i>
should vary inversely with the intensity of illumination. It is,
however, possible to complete the case for the purely physicochemical
analysis of these instincts. John Hays Hammond, Jr., has succeeded in
constructing heliotropic machines which in the dark follow a lantern
very much in the manner of a positively heliotropic animal. The eyes
of this heliotropic machine consist of two lenses in whose focus
is situated the “retina” consisting of selenium wire. The two eyes
are separated from each other by a projecting piece of wood which
represents the nose and allows one eye to receive light while the other
is shaded. The galvanic resistance of selenium is altered by light;
and when one selenium wire is shaded while the other is illuminated,
the electric energy (supplied by batteries inside the machine) which
makes the wheels turn (these take the place of<span class="pagenum" title="270"><a name="Page_270" id="Page_270"></a></span> the legs of the normal
animal) no longer flows symmetrically to the steering wheel, and the
machine turns towards the light. In this way the machine follows
a lantern in a dark room in a way similar to that of a positively
heliotropic animal. Here we have a model of the heliotropic animal
whose purely mechanistic character is beyond suspicion, and we may
be sure that it is not “fondness” for light or for brightness nor
will-power nor a method of “trial and error” which makes the machine
follow the light.</p>
<div class="figright" style="width: 320px;">
<img src="images/fig_045.png" width="320" height="428" alt="" />
<p class="tac"><span class="smcap">Fig. 45</span></p></div>
<p>6. It may also be of interest to know that in heliotropism the motions
of the legs are automatically controlled by the chemical changes taking
place in symmetrical elements of the retina. In order to prove this
point we will turn to the phenomenon of galvanotropism. The galvanic
current forces certain animals to move in the direction of one of the
two electrodes just as the light forces the heliotropic animals to move
towards (or from) the source of light. The change in the concentration
of the ions at the boundary of the various organs, especially the
nerves, determines the galvanotropic reactions. When the shrimp
<i class="taxonomic">Palæmonetes</i> is put into a trough with dilute salt solution through
which a current of a certain intensity flows, the animal is compelled
to move towards the <span class="nowrap">anode.<a name="FNanchor_232_232" id="FNanchor_232_232"></a><a href="#Footnote_232_232" class="fnanchor">232</a></span> It can
walk forwards, backwards, or sidewise. Here we can observe directly<span class="pagenum" title="271"><a name="Page_271" id="Page_271"></a></span>
that the effect of the current consists in altering the tension of the
muscles of the legs in such a way as to make it easy for the animal to
move toward the anode and difficult to move toward the cathode. Thus
if the current be sent sidewise through the animal, say from left to
right (Fig. 45), the legs of the left side assume the flexor position,
those of the right the extensor position. With this position of its
legs the animal can easily move<span class="pagenum" title="272"><a name="Page_272" id="Page_272"></a></span> to the left, <i>i. e.</i>, the anode,
and only with difficulty to the right, <i>i. e.</i>, the cathode. This
change in the position of the legs occurs when the animal is not moving
at all, thus showing that the galvanotropic movements take place not
because the animal intends to go to the anode, but that the animal goes
to the anode because its legs are practically prevented by the galvanic
current from working in any other way. This is exactly what happens in
the heliotropic motions of <span class="nowrap">animals.<a name="FNanchor_233_233" id="FNanchor_233_233"></a><a href="#Footnote_233_233" class="fnanchor">233</a></span></p>
<div class="figright" style="width: 300px;">
<img src="images/fig_046.png" width="300" height="480" alt="" />
<p class="tac"><span class="smcap">Fig. 46</span></p></div>
<p>To understand what happens when the current goes lengthwise through the
body it should be stated that <i class="taxonomic">Palæmonetes</i> uses the third, fourth,
and fifth pairs of legs for its locomotion. The third pair pulls in
the forward movement, and the fifth pair pushes. The fourth pair
generally acts like the fifth, and requires no further attention. If a
current be sent through the animal longitudinally, from tail to head,
and the strength be increased gradually, a change soon takes place in
the position of the legs (Fig. 46). In the third pair the tension of
the flexors predominates, in the fifth the tension of the extensors.
The animal can thus move easily with the pulling of the third and the
pushing of the fifth pairs of legs, that is to say, the current changes
the tension of the muscles in such a way that<span class="pagenum" title="273"><a name="Page_273" id="Page_273"></a></span> the forward motion is
rendered easy, the backward motion is difficult. Hence it can easily
move toward the anode, but only with difficulty toward the cathode. If
a current be sent through the animal in the opposite direction, namely,
from head to tail, the third pair of legs is extended, the fifth pair
bent; that is, the third<span class="pagenum" title="274"><a name="Page_274" id="Page_274"></a></span> pair can push, and the fifth pair pull. The
animal will thus move backward easily and forward with difficulty, and
it is thus driven to the anode again.</p>
<p>The explanation which Loeb and Maxwell proposed for this influence
of the current on the legs assumes that there are three groups
of ganglion cells in the central nervous system of these animals
which are oriented according to the three main axes of the body;
(1) right-left and left-right, (2) backward, and (3) forward. It
depends upon whether the ganglion cells or the nerve elements are in
anelectrotonus, which muscles are bent and which relaxed. It would
lead us too far to recapitulate the theory in this place, and the
reader who is interested in it is referred to Loeb and Maxwell’s <span
class="nowrap">paper.<a name="FNanchor_234_234" id="FNanchor_234_234"></a><a href="#Footnote_234_234" class="fnanchor">234</a></span> The importance of the observations
lies in the fact that they show that any element of will or choice on
the part of the animal in these motions is eliminated, that the animal
moves where its legs carry it, and not that the legs carry the animal
where the latter “wishes” to go.</p>
<p>7. This may be the place to dispel an error which has sometimes crept
into the discussion of the tropistic reactions of animals. It has
been stated occasionally that it is the energy gradient and not the
automatic orientation of the animal by the light which makes the
positively heliotropic animal move towards the source of light and the
negatively heliotropic away<span class="pagenum" title="275"><a name="Page_275" id="Page_275"></a></span> from it. Thus the positively heliotropic
animal would be compelled to move towards the source of light as a
consequence of the fact that the intensity of the light increases the
more the nearer the animal approaches the source of light. If the
source of light be the reflected sky-light the difference of intensity
at both ends of a microscopic organism is so slight that it is beneath
the limit capable of influencing the motions.</p>
<div class="figright" style="width: 260px;">
<img src="images/fig_047.png" width="260" height="304" alt="" />
<p class="tac"><span class="smcap">Fig. 47</span></p></div>
<p>A simple experiment published by the writer in 1889 suffices to
dispel the idea that the energy gradient determines the direction of
the motion of an animal in tropistic reactions. Let direct sunlight
(<i>S</i>, Fig. 47) fall through the upper half of a window (<i>w w</i>) upon
a table, and diffused daylight (<i>D</i>) through the lower half of the
window on the same table. A test-tube <i>a c</i> is placed on the table in
such a way that its long axis is at right angles to the plane of the
window; and one half <i>a b</i> is in the direct sun<span class="pagenum" title="276"><a name="Page_276" id="Page_276"></a></span>light, the other half
in the shade. If at the beginning of the experiment the positively
heliotropic animals are in the direct sunlight at <i>a</i>, they promptly
move toward the window, gathering at the window end <i>c</i> of the
tube, although by so doing they go from the sunshine into the <span
class="nowrap">shade.<a name="FNanchor_235_235" id="FNanchor_235_235"></a><a href="#Footnote_235_235" class="fnanchor">235</a></span> This experiment is in harmony with
our idea that the effect of light consists in turning the head of the
animal and subsequently its whole body toward the source of light. By
going from the strong light into the shade the reaction velocity in
both eyes is diminished equally and hence there is no reason for the
animal to change its orientation, though its progressive motion may
be stopped for an instant by the change. But at the boundary between
sunlight and daylight a sudden change from strong to weak light occurs.
If the energy gradient determined the direction of the positively
heliotropic animal, the motion should stop at the boundary from strong
to weak light, which may happen for an instant but which will not
interfere with the progressive motion of the animal.</p>
<p>8. Graber had found that when animals are put into a trough covered
half with blue and half with red glass, those that are “fond” of light
go under the blue, those that are “fond” of darkness go under the red
glass. The writer pointed out that this result should be expected on
the basis of his theory of heliotropism, if<span class="pagenum" title="277"><a name="Page_277" id="Page_277"></a></span> the assumption be correct
that the red light is considerably less efficient than light which goes
through blue glass (such glass also allows green rays to go through).
The botanists had already shown that red glass is impermeable for the
rays which cause heliotropic reactions of plants, and the writer was
able to show the same for the heliotropic reactions of animals. Red
glass acts, therefore, almost like an opaque body for these animals.</p>
<p>A closer examination of the most efficient rays for the heliotropic
reactions of different organisms has revealed the fact that for
some organisms a region in the blue λ = 460–490 µµ, for others a
region in the yellowish-green, near about λ = 520–530 µµ is the
most <span class="nowrap">efficient.<a name="FNanchor_236_236" id="FNanchor_236_236"></a><a href="#Footnote_236_236" class="fnanchor">236</a></span> For many plants
and for some animals, like <i class="taxonomic">Eudendrium</i> and the larvæ of the worm
<i class="taxonomic">Arenicola</i>, a region in the blue is most efficient; for certain, if
not most, animals a region in the yellow-green is most efficient.
Among unicellular green algæ, <i class="taxonomic">Chlamydomonas</i>, has its maximal
efficiency in the yellowish-green and <i class="taxonomic">Euglena</i> in the blue.
According to observations by Mast, some green unicellular organisms
like <i class="taxonomic">Pandorina</i>, <i class="taxonomic">Eudorina</i>, and <i class="taxonomic">Spondylomorum</i> seem to behave
more like <i class="taxonomic">Chlamydomonas</i>, while certain others behave more like
<span class="nowrap"><i class="taxonomic">Euglena</i>.<a name="FNanchor_237_237" id="FNanchor_237_237"></a><a href="#Footnote_237_237" class="fnanchor">237</a></span> Wasteneys and the writer
suggested<span class="pagenum" title="278"><a name="Page_278" id="Page_278"></a></span> that there are two groups of heliotropic substances, one
with a maximum of photosensitiveness in the blue, the other in the
yellowish-green; and that the latter group may or may not be related
or identical with the visual purple which is most rapidly bleached by
light of a wave length near λ = 520–530 µµ.</p>
<p>The ophthalmologist <span class="nowrap">Hess<a name="FNanchor_238_238" id="FNanchor_238_238"></a><a href="#Footnote_238_238" class="fnanchor">238</a></span> has utilized
the heliotropic reactions of animals in an attempt to prove that all
animals from the lowest invertebrates up to the fishes inclusive
suffer from total colour-blindness. This statement was based on the
observation that for most positively heliotropic animals the region
in the yellowish-green near λ = 520 µµ seems the most efficient.
Since this region of the spectrum appears also as the brightest to
a totally colour-blind man, he concluded that all these animals are
totally colour-blind. There is no reason why heliotropic reactions
should be used as an indicator for colour sensations; if totally
colour-blind human beings were possessed of an irresistible impulse
to run into a flame Hess’s assumption might be considered, but no
such phenomenon exists in colour-blind man. Moreover, v. <span
class="nowrap">Frisch<a name="FNanchor_239_239" id="FNanchor_239_239"></a><a href="#Footnote_239_239" class="fnanchor">239</a></span> has shown by experiments on the
influence of the background on the colouration of fish as well as by
experiments on bees and<span class="pagenum" title="279"><a name="Page_279" id="Page_279"></a></span> on <i class="taxonomic">Daphnia</i> that the reactions of these
animals to light of different wave-lengths indicate different effects
besides those of mere intensity. Thus v. Frisch could train bees to
go to a blue piece of cardboard distributed among many cardboards of
different shades of grey. Bees thus trained would alight on any blue
object even if it contained no food. It would be impossible to do this
with totally colour-blind organisms.</p>
<p>9. Heliotropic reactions play a great rôle in the preservation of
individuals as well as of species. In order to understand this rôle
it must be stated that the photosensitive substances appear often
only under certain conditions and that their effect is inhibited
under other conditions. Thus among ants the winged males and females
alone show positive <span class="nowrap">heliotropism,<a name="FNanchor_240_240" id="FNanchor_240_240"></a><a href="#Footnote_240_240" class="fnanchor">240</a></span>
while the wingless workers are free from this reaction. This positive
heliotropism becomes violent at the time of the nuptial flight and this
phenomenon itself seems to be a heliotropic phenomenon since it takes
place in the direction of the light. When the queen founds her nest
she loses her wings and becomes negatively heliotropic again. <span
class="nowrap">Kellogg<a name="FNanchor_241_241" id="FNanchor_241_241"></a><a href="#Footnote_241_241" class="fnanchor">241</a></span> has shown that the nuptial flight of
the bees is also a purely heliotropic phenomenon. When a part of the
hive remote from the entrance is illuminated the bees rush to the light
and can thus be prevented from swarming. These phenomena suggest<span class="pagenum" title="280"><a name="Page_280" id="Page_280"></a></span> that
the presence of some substance secreted by the sex glands may cause the
intensification of the heliotropism which leads to the nuptial flight.</p>
<p>In certain species of <i class="taxonomic">Daphnia</i>, fresh-water copepods, and
of <i class="taxonomic">Volvox</i>, a trace of CO<sub>2</sub> suffices to make negatively
heliotropic or indifferent specimens violently positively
<span class="nowrap">heliotropic.<a name="FNanchor_242_242" id="FNanchor_242_242"></a><a href="#Footnote_242_242" class="fnanchor">242</a></span> Certain
forms of marine copepods and the larvæ of <i class="taxonomic">Polygordius</i>
can be made positively heliotropic by lowering the <span
class="nowrap">temperature<a name="FNanchor_243_243" id="FNanchor_243_243"></a><a href="#Footnote_243_243" class="fnanchor">243</a></span> and the larvæ of the
barnacle can be made negatively heliotropic by strong <span
class="nowrap">light.<a name="FNanchor_244_244" id="FNanchor_244_244"></a><a href="#Footnote_244_244" class="fnanchor">244</a></span> It is quite possible that a change
in the sense of heliotropism by temperature and light is to some
extent at least responsible for the periodic depth migrations of
heliotropic animals. Many if not all positively heliotropic animals
can be made negatively heliotropic by exposure to ultraviolet <span
class="nowrap">light.<a name="FNanchor_245_245" id="FNanchor_245_245"></a><a href="#Footnote_245_245" class="fnanchor">245</a></span></p>
<p>A most interesting example of the rôle of heliotropism in the
preservation of a species is shown in the caterpillars of <i class="taxonomic">Porthesia
chrysorrhœa</i>. The butterfly lays its eggs upon a shrub. The larvæ
hatch late in the fall and hibernate in a nest on the shrub, as a rule
not far from the ground. As soon as the temperature reaches a certain
height, they leave the nest; under natural<span class="pagenum" title="281"><a name="Page_281" id="Page_281"></a></span> conditions, this happens
in the spring when the first leaves have begun to form on the shrub.
(The larvæ can, however, be induced to leave the nest at any time in
the winter provided the temperature is raised sufficiently.) After
leaving the nest, they crawl directly upward on the shrub where they
find the leaves on which they feed. Should the caterpillars move down
the shrub, they would starve, but this they never do, always crawling
upward to where they find their food. What gives the caterpillar
this never-failing certainty which saves its life, and for which a
human being might envy the little larva? Is it a dim recollection of
experiences of former generations? It can be shown that it is the
light reflected from the sky which guides the animal upward. When we
put these animals into a horizontal test-tube in a room, they all
crawl toward the window, or toward a lamp; the animal is positively
heliotropic. It is this positive heliotropism which makes them move
upward where they find their food, when the mild air of the spring
calls them forth from their nest. At the top of the branch, they come
in contact with a leaf, and chemical or tactile influences set the
mandibles of the young caterpillar into activity. If we put these larvæ
into closed test-tubes which lie with their longitudinal axes at right
angles to the window, they will all migrate to the window end, where
they stay and starve, even if their favourite leaves are close behind
them. They are slaves of the light.</p>
<p><span class="pagenum" title="282"><a name="Page_282" id="Page_282"></a></span></p>
<p>The few young leaves on top of a twig are quickly eaten by the
caterpillar. The light, which saved its life by making it creep upward
where it finds food, would cause it to starve could it not free itself
from the bondage of positive heliotropism. The animal, after having
eaten, is no longer a slave of the light, but can and does creep
downward. It can be shown that a caterpillar, after having been fed,
loses its positive heliotropism almost completely and permanently. If
we submit unfed and fed caterpillars of the same nest contained in
two different test-tubes to the same artificial or natural source of
light, the unfed will creep to the light and stay there until they
die, while those that have eaten will pay little or no attention to
the light. Their sensitiveness to light has disappeared; after having
eaten they become independent of light and can creep in any direction.
The restlessness which accompanies the condition of hunger makes the
animal creep downward—which is the only direction open to it—where it
finds new young leaves on which it can feed. The wonderful hereditary
instinct, upon which the life of the animal depends, is its positive
heliotropism in the unfed condition and its loss of this heliotropism
after having eaten. The latter phenomenon is in harmony with the
experiments which show that the heliotropism of certain species of
<i class="taxonomic">Daphnia</i> disappears when the water becomes neutral.</p>
<p>And finally it may be pointed out that the majority<span class="pagenum" title="283"><a name="Page_283" id="Page_283"></a></span> of green plants
could not exist if their stems were not positively, their roots
negatively, heliotropic. It is the positive heliotropism which makes
the top grow toward the light, which enables the leaves to get the
light necessary for assimilation, and the roots to grow into the soil
where they find the water and nutritive salts.</p>
<p>10. While we do not wish to deal here with the different tropisms it
should be stated that aside from heliotropism, chemotropism as well as
stereotropism play the most essential rôle in the so-called instinctive
actions of animals. It is a problem of orientation by the diffusion
of molecules from a centre when a male butterfly is deviated from its
flight and alights on the wooden box in which is enclosed a female
of the same species. We have already alluded to certain phenomena of
chemotropism in Chapter IV. Certain organisms have a tendency to bring
their bodies as much as possible on all sides in contact with solid
bodies; thus the butterfly <i class="taxonomic">Amphipyra</i>, which is a fast runner, will
come to rest under a glass plate when the plate is put high enough
above the ground so that it touches the back of the butterfly. The
animals which live under stones or underground or in caves are as a
rule both negatively heliotropic and positively stereotropic. Their
tropisms predestine or force them into the life they lead.</p>
<p>The sensitive area which forms the basis of tropisms<span class="pagenum" title="284"><a name="Page_284" id="Page_284"></a></span> is as a rule
developed not in the whole organism but only in certain segments of the
body. Thus the eyes are located in the head. But when the action of one
segment becomes overpowering the whole organism follows the segment.
It has been customary among physiologists to speak of reflexes in such
cases. Thus, <i>e. g.</i>, the arms of the male frog develop a powerful
positive stereotropism on their ventral surface during the spawning
season. It would avoid confusion to realize that there is nothing
gained in applying to this tropism the meaningless term “reflex”;
it is better to call them tropisms since the organism as a whole is
involved. If necessary we might speak of segmental tropisms. The act of
seeking the female as well as that of cohabitation are in many cases
combinations of chemotropism and stereotropism. The development of
these tropisms depends upon the presence of certain specific substances
in the body, a fact emphasized already in the case of heliotropism.
In case of the development of the segmental stereotropism of the male
frog at the time of spawning it has been shown that it depends on an
internal secretion from the testes.</p>
<p>It has been suggested by some authors that the tropistic reactions are
determined by some feeling or emotion on the part of the organism.
We have no means of judging the emotions of lower animals (except
by “intuition”). The writer suggested in 1899 in his book on brain
physiology that emotions may be deter<span class="pagenum" title="285"><a name="Page_285" id="Page_285"></a></span>mined by specific substances
which also determine the tropistic reaction (as well as phenomena
of organ formation, although this latter phenomenon has nothing to
do with the subject of instincts); and the excellent work of <span
class="nowrap">Cannon<a name="FNanchor_246_246" id="FNanchor_246_246"></a><a href="#Footnote_246_246" class="fnanchor">246</a></span> has shown the rôle of adrenalin
in the expression of fear. It is, therefore, both unwarranted and
unnecessary to state that hypothetical emotions determine the tropistic
reactions. </p>
<hr class="chap" />
<p><span class="pagenum" title="286"><a name="Page_286" id="Page_286"></a></span></p>
<h2>CHAPTER XI</h2>
<h3>THE INFLUENCE OF ENVIRONMENT</h3>
<p>1. The term environment in relation to an organism may easily assume
a mystic rôle if we assume that it can modify the organisms so that
they become adapted to its peculiarities. Such ideas are difficult
to comprehend from a physicochemical viewpoint, according to which
environment cannot affect the living organism and non-living matter in
essentially different ways. Of course we know that proteins will as a
rule coagulate at temperatures far below the boiling point of water
and that no life is conceivable for any length of time at temperatures
above 100° C., but heat coagulation of proteins occurs as well in
the test-tube as in the living organism. If we substitute for the
indefinite term environment the individual physical and chemical forces
which constitute environment it is possible to show that the influence
of each of these forces upon the organism finds its expression in
simple physicochemical laws and that there is no need to introduce any
other considerations.</p>
<p><span class="pagenum" title="287"><a name="Page_287" id="Page_287"></a></span></p>
<p>We select for our discussion first the most influential of external
conditions, namely temperature. The reader knows that there is a
lower as well as an upper temperature limit for life. Setchell has
ascertained that in hot springs whose temperature is 43° C., or above,
no animals or green alga are <span class="nowrap">found.<a name="FNanchor_247_247" id="FNanchor_247_247"></a><a href="#Footnote_247_247" class="fnanchor">247</a></span>
In hot springs whose temperature is above 43° he found only the
<i class="taxonomic">Cyanophyceæ</i>, whose structure is more closely related to that of
the bacteria than to that of the algæ, inasmuch as they have neither
definitely differentiated nuclei nor chromophores. The highest
temperature at which <i class="taxonomic">Cyanophyceæ</i> occurred was 63° C. Not all the
<i class="taxonomic">Cyanophyceæ</i> were able to stand temperatures above 43° C., but only
a few species. The other <i class="taxonomic">Cyanophyceæ</i> were found at a temperature
below 40° C., and were no more able to stand higher temperatures than
the real algæ or animals. The <i class="taxonomic">Cyanophyceæ</i> of the hot springs were
as a rule killed by a temperature of 73°. From this we must conclude
that they contain proteins whose coagulation temperature lies above
that of animals and green plants, and may be as high as 73°. Among the
fungi many forms can resist a temperature above 43° or 45°; the spores
can generally stand a higher temperature than the vegetative organs.
Duclaux found that certain bacilli (Tyrothrix) found in cheese are
killed in one minute at a temperature of from 80°<span class="pagenum" title="288"><a name="Page_288" id="Page_288"></a></span> to 90°; while for
the spores of the same bacillus a temperature of from 105° to 120° was
<span class="nowrap">required.<a name="FNanchor_248_248" id="FNanchor_248_248"></a><a href="#Footnote_248_248" class="fnanchor">248</a></span></p>
<p>Duclaux has called attention to a fact which is of importance for
the investigation of the upper temperature limit for the life of
organisms. According to this author it is erroneous to speak of a
definite temperature as a fatal one; instead we must speak of a deadly
temperature zone. This is due to the fact that the length of time
which an organism is exposed to a higher temperature is of importance.
Duclaux quotes as an example a series of experiments by Christen on the
spores of soil and hay bacilli. The spores were exposed to a stream
of steam and the time determined which was required at the various
temperatures to kill the spores.</p>
<table class="fs100 ml23em" summary="Exposure time required to kill spores at high temperatures">
<col width="50%" /><col width="50%" />
<tr><td>It took at 100°</td><td>over sixteen hours</td></tr>
<tr><td> " "  " 105–110°</td><td>two to four hours</td></tr>
<tr><td> " "  " 115°</td><td>thirty to sixty minutes</td></tr>
<tr><td> " "  " 125–130°</td><td>five minutes or more</td></tr>
<tr><td> " "  " 135°</td><td>one to five minutes</td></tr>
<tr><td> " "  " 140°</td><td>one minute</td></tr>
</table>
<p>In warm-blooded animals 45° is generally considered a temperature at
which death occurs in a few minutes; but a temperature of 44°, 43°,
or 42° is also to be considered fatal with this difference only, that
it takes<span class="pagenum" title="289"><a name="Page_289" id="Page_289"></a></span> a longer time to bring about death. This fact is to be
considered in the treatment of fever.</p>
<p>It is generally held that death in these cases is due to an
irreversible heat coagulation of proteins. According to Duclaux, it can
be directly observed in micro-organisms that in the fatal temperature
zone the normally homogeneous, or finely granulated, protoplasm is
filled with thick, irregularly arranged bodies, and this is the optical
expression of coagulation. The fact that the upper temperature limit
differs so widely in different forms is explained by Duclaux through
differences in the coagulation temperature of the various proteins. It
is, <i>e. g.</i> known that the coagulation temperature varies with
the amount of water of the colloid. According to Cramer, the mycelium
of <i class="taxonomic">Penicillium</i> contains 87.6 water to 12.4 dry matter, while the
spores have 38.9 water and 61.1 dry substance. This may explain why the
mycelium is killed at a lower temperature than the spores. According
to Chevreul, with an increase in the amount of water, the coagulation
temperature of albuminoids decreases. The reaction of the protoplasm
influences the temperature of coagulation, inasmuch as it is lower
when the reaction is acid, higher when the reaction is alkaline. The
experiments of Pauli show also a marked influence of salts upon the
temperature of coagulation of colloids.</p>
<p>The process of heat coagulation of colloids is also a function of time.
If the exposure to high temperature<span class="pagenum" title="290"><a name="Page_290" id="Page_290"></a></span> is not sufficiently long, only
part of the colloid coagulates; in this case an organism may again
recover.</p>
<p>Inside of these upper and lower temperature limits we find that life
phenomena are influenced by temperature in such a way that their rate
is about doubled for an increase of the temperature of 10° C., and
that this temperature coefficient for 10°, Q<sub>10</sub>, very often steadily
diminishes from the lower to the higher temperature; so that near the
lower temperature limit it becomes often considerably greater than 2
and near the higher temperature limit it becomes very often less than
<span class="nowrap">2.<a name="FNanchor_249_249" id="FNanchor_249_249"></a><a href="#Footnote_249_249" class="fnanchor">249</a></span> This influence of temperature is
so general that we are bound to associate it with an equally general
feature of life phenomena; and such a feature would be most likely
the chemical reactions. It is known through the work of Berthelot,
van’t Hoff, and Arrhenius that the temperature coefficient for the
velocity of chemical reactions is also generally of about the same
order of magnitude; namely ≧2 for a difference of 10°. In chemical
reactions there is also a tendency for Q<sub>10</sub> to become larger for
lower temperature, and coefficients of Q<sub>10</sub> about 5 or 6 have
repeatedly been found for purely chemical reactions between 0° and
10°, <i>e. g.</i>, for the inversion of cane sugar by the hydrogen
ion. The temperature coefficient for the reaction velocity of ferments
<span class="pagenum" title="291"><a name="Page_291" id="Page_291"></a></span>shows the same diminution of Q<sub>10</sub> with rising temperature which
is also noticed in most life phenomena. Thus Van Slyke and <span
class="nowrap">Cullen<a name="FNanchor_250_250" id="FNanchor_250_250"></a><a href="#Footnote_250_250" class="fnanchor">250</a></span> found that the reaction rate of the
enzyme urease “is nearly doubled by every 10° rise in temperature
between 10° and 50°. Within this range the temperature coefficient is
nearly constant and averages 1.91. From O° to 10° it is 2.80, from 50°
to 60° it is only 1.09. The optimum is at about 55°.” The rapid fall of
the temperature coefficient for enzyme action at the upper temperature
limit has been ascribed by Tammann to a progressive destruction of the
active mass of enzyme by the higher temperature (by hydrolysis). This
will, however, not account for the high value of the coefficient near
the lower limit. But is it not imaginable that at low temperature an
aggregation of the enzyme particles exists which is also equivalent to
a diminution of the active mass of the enzyme and that this aggregation
is gradually dispersed by the rising temperature? This would account
for the fact that at a temperature near 0°C life phenomena stop because
the enzymes are all in a state of aggregation or gelation; that then
more and more are dissolved and the rate of chemical reaction increases
since the mass of enzyme particles increases until all the enzyme
molecules are dissolved or rendered active. Under this assumption
three processes are superposed in the variation of the value<span class="pagenum" title="292"><a name="Page_292" id="Page_292"></a></span> of
Q<sub>10</sub> with temperature: (1) the supposed increase in the number of
available ferment molecules with increasing temperature near the lower
temperature limit; (2) the temperature coefficient of the reaction
velocity which is nearly = 2 for 10°C.; (3) the diminution of the number
of available ferment molecules by hydrolysis or some other action of
the increasing temperature. This latter is noticeable near the upper
temperature limit. The reason that 1 and 3 interfere more strongly in
life phenomena than in the chemical reactions of crystalloid substances
may possibly be accounted for by the fact that the enzymes and most of
the constituents of living matter are colloidal, <i>i. e.</i>, consist
of particles of a considerably greater order of magnitude than the
molecules of <span class="nowrap">crystalloids.<a name="FNanchor_251_251" id="FNanchor_251_251"></a><a href="#Footnote_251_251" class="fnanchor">251</a></span></p>
<p>We will now show the rôle of the temperature coefficient
upon phenomena of development. F. R. Lillie and <span
class="nowrap">Knowlton<a name="FNanchor_252_252" id="FNanchor_252_252"></a><a href="#Footnote_252_252" class="fnanchor">252</a></span> first determined the influence
of temperature upon the development of the egg of the frog and
showed that it was of the same nature as that of a chemical
reaction. These experiments were repeated a year later by O. <span
class="nowrap">Hertwig.<a name="FNanchor_253_253" id="FNanchor_253_253"></a><a href="#Footnote_253_253" class="fnanchor">253</a></span></p>
<p><span class="pagenum" title="293"><a name="Page_293" id="Page_293"></a></span></p>
<p>The time required for the eggs to reach definite stages was measured
for different temperatures and it was found that the temperature
coefficient Q<sub>10</sub> between 2.5° and 6° was equal to 10 or more;
between 6° and 15° it was between 2.6 and 4.5; between 10° and 20°
it was 2.9 to 3.3, and between 20° and 24° it was between 1.4 and
2.0. To anybody who has worked on this problem it is obvious that no
exact figures can be obtained in this way, since the point when a
certain stage of development is reached is not so sharply defined as
to exclude a certain latitude of arbitrariness. The writer found that
very exact figures can be obtained on the influence of temperature
upon development of the sea-urchin egg by measuring the time from
insemination to the first cell division. Such experiments were carried
out in a cold-water form <i class="taxonomic">Strongylocentrotus purpuratus</i> and a form
living in warmer water, <span class="nowrap"><i class="taxonomic">Arbacia</i>.<a name="FNanchor_254_254" id="FNanchor_254_254"></a><a href="#Footnote_254_254" class="fnanchor">254</a></span>
The figures on <i class="taxonomic">Arbacia</i> have been verified by different observers in
different years. </p>
<p><span class="pagenum" title="294"><a name="Page_294" id="Page_294"></a></span></p>
<p class="tac">TABLE X</p>
<p class="tac mrl10"><span class="smcap">Influence of Temperature upon the Time (in Minutes)
Required From Insemination to the First Cell Division</span></p>
<table summary="">
<col width="12%" /><col width="12%" /><col width="13%" /><col width="11%" /><col width="13%" /><col width="11%" /><col width="28%" />
<tr><th class="btr" colspan="2" rowspan="2"><span class="smcap">Temperature</span></th><th class="ball" colspan="4"><i>Arbacia</i></th><th class="btl" rowspan="2"><i>Strongylocentrotus<br />purpuratus</i></th></tr>
<tr><td class="tac ball ptb03" colspan="2"><span class="smcap">Loeb and<br />Wasteneys</span><br />1911</td><td class="tac ball ptb03" colspan="2"><span class="smcap">Loeb and<br />Chamberlain</span><br />1915</td></tr>
<tr><td class="tac btr ptb03" colspan="2">°C.</td><td class="tac br ptb03" colspan="2"><i>Minutes</i></td><td class="tac br ptb03" colspan="2"><i>Minutes</i></td><td class="tac btl ptb03"><i>Minutes</i></td></tr>
<tr><td class="tar">3</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac">532</td></tr>
<tr><td class="tar">4</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac">469</td></tr>
<tr><td class="tar">5</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac">352</td></tr>
<tr><td class="tar">6</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac">275</td></tr>
<tr><td class="tar">7</td><td class="tal br"></td><td class="tar">498</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac">291</td></tr>
<tr><td class="tar">8</td><td class="tal br"></td><td class="tar">410</td><td class="tal br"></td><td class="tar">411</td><td class="tal br"></td><td class="tac">210</td></tr>
<tr><td class="tar">9</td><td class="tal br"></td><td class="tar">308</td><td class="tal br"></td><td class="tar">297</td><td class="tal br">.5</td><td class="tac">159</td></tr>
<tr><td class="tar">10</td><td class="tal br"></td><td class="tar">217</td><td class="tal br"></td><td class="tar">208</td><td class="tal br"></td><td class="tac">143</td></tr>
<tr><td class="tar">11</td><td class="tal br"></td><td class="tar">175</td><td class="tal br"></td><td class="tar">175</td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">12</td><td class="tal br"></td><td class="tar">147</td><td class="tal br"></td><td class="tar">148</td><td class="tal br"></td><td class="tac">131</td></tr>
<tr><td class="tar">13</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">129</td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">14</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">116</td><td class="tal br"></td><td class="tac">121</td></tr>
<tr><td class="tar">15</td><td class="tal br"></td><td class="tar">100</td><td class="tal br"></td><td class="tar">100</td><td class="tal br"></td><td class="tac">100</td></tr>
<tr><td class="tar">16</td><td class="tal br"></td><td class="tar">85</td><td class="tal br">.5</td><td class="tar"></td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">17</td><td class="tal br"></td><td class="tar">70</td><td class="tal br">.5</td><td class="tar"></td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">18</td><td class="tal br"></td><td class="tar">68</td><td class="tal br"></td><td class="tar">68</td><td class="tal br"></td><td class="tac"><span class="hide">1</span>87</td></tr>
<tr><td class="tar">19</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">65</td><td class="tal br"></td><td class="tac"><span class="hide">1</span>78</td></tr>
<tr><td class="tar">20</td><td class="tal br"></td><td class="tar">56</td><td class="tal br"></td><td class="tar">56</td><td class="tal br"></td><td class="tac"><span class="hide">1</span>75</td></tr>
<tr><td class="tar">21</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">53</td><td class="tal br">.3</td><td class="tac"><span class="hide">1</span>78</td></tr>
<tr><td class="tar">22</td><td class="tal br"></td><td class="tar">47</td><td class="tal br"></td><td class="tar">46</td><td class="tal br"></td><td class="tac"><span class="hide">1</span>75</td></tr>
<tr><td class="tar">23</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">45</td><td class="tal br">.5</td><td class="tac" rowspan="2">Upper temperature<br />limit</td></tr>
<tr><td class="tar">24</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tar">42</td><td class="tal br"></td></tr>
<tr><td class="tar">25</td><td class="tal br"></td><td class="tar">40</td><td class="tal br"></td><td class="tar">39</td><td class="tal br">.5</td><td class="tac"></td></tr>
<tr><td class="tar">26</td><td class="tal br"></td><td class="tar">33</td><td class="tal br">.5</td><td class="tar"></td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">27</td><td class="tal br">.5</td><td class="tar">34</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar">30</td><td class="tal br"></td><td class="tar">33</td><td class="tal br"></td><td class="tar"></td><td class="tal br"></td><td class="tac"></td></tr>
<tr><td class="tar bb pb03">31</td><td class="tal bbr"></td><td class="tar bb pb03">37</td><td class="tal bbr"></td><td class="tar bb"></td><td class="tal bbr"></td><td class="tac bb"></td></tr>
</table>
<p>These figures permitted the determination of the temperature
coefficients Q<sub>10</sub> with a sufficient degree of accuracy (see next
table). It seemed of importance<span class="pagenum" title="295"><a name="Page_295" id="Page_295"></a></span> to attempt to decide what the chemical
reaction underlying these reaction velocities is (if it is a chemical
reaction). Loeb and <span class="nowrap">Wasteneys<a name="FNanchor_255_255" id="FNanchor_255_255"></a><a href="#Footnote_255_255" class="fnanchor">255</a></span>
investigated the temperature coefficient for the rate of oxidations in
the newly fertilized egg of <i class="taxonomic">Arbacia</i> and found that the temperature
coefficient Q<sub>10</sub> for that process does not vary in the same way as
the temperature coefficient for cell division.</p>
<p class="tac">TABLE XI</p>
<p class="tac mrl10"><span class="smcap">Temperature Coefficients Q<sub>10</sub> for the Rate of
Segmentation and Oxidations in the Eggs of</span> <i class="taxonomic">Strongylocentrotus</i>
<span class="lowercase smcap">AND</span> <i class="taxonomic">Arbacia</i></p>
<table summary="">
<tr><th class="btr" colspan="2" rowspan="2"><span class="smcap">Temperature</span></th><th class="ball" colspan="2"><span class="smcap">Q<sub>10</sub> for Rate of Segmentation in</span></th><th class="btl" rowspan="2">Q<sub>10</sub> for Rate of<br />Oxidations in<br /><i>Arbacia</i></th></tr>
<tr><td class="tac ball ptb03"><i>Strongylocentrotus</i></td><td class="tac ball ptb03"><i>Arbacia</i></td></tr>
<tr><td class="tac btr pt03" colspan="2">°C.</td><td class="tac brl"></td><td class="tac"></td><td class="tac btl"></td></tr>
<tr><td class="tar">3–</td><td class="tal">13</td><td class="tac brl">3.91</td><td class="tac"></td><td class="tac bl">2.18</td></tr>
<tr><td class="tar">4–</td><td class="tal">14</td><td class="tac brl">3.88</td><td class="tac"></td><td class="tac bl"></td></tr>
<tr><td class="tar">5–</td><td class="tal">15</td><td class="tac brl">3.52</td><td class="tac"></td><td class="tac bl">2.16</td></tr>
<tr><td class="tar">7–</td><td class="tal">17</td><td class="tac brl">3.27</td><td class="tac">7.3</td><td class="tac bl">2.00</td></tr>
<tr><td class="tar">8–</td><td class="tal">18</td><td class="tac brl"></td><td class="tac">6.0</td><td class="tac bl"></td></tr>
<tr><td class="tar">9–</td><td class="tal">19</td><td class="tac brl">2.04</td><td class="tac">4.7</td><td class="tac bl"></td></tr>
<tr><td class="tar">10–</td><td class="tal">20</td><td class="tac brl">1.90</td><td class="tac">3.8</td><td class="tac bl">2.17</td></tr>
<tr><td class="tar">11–</td><td class="tal">21</td><td class="tac brl"></td><td class="tac">3.3</td><td class="tac bl"></td></tr>
<tr><td class="tar">12–</td><td class="tal">22</td><td class="tac brl">1.74</td><td class="tac">3.1</td><td class="tac bl"></td></tr>
<tr><td class="tar">13–</td><td class="tal">23</td><td class="tac brl"></td><td class="tac">2.8</td><td class="tac bl">2.45</td></tr>
<tr><td class="tar">15–</td><td class="tal">25</td><td class="tac brl"></td><td class="tac">2.5</td><td class="tac bl">2.24</td></tr>
<tr><td class="tar">16–</td><td class="tal">26</td><td class="tac brl"></td><td class="tac">2.6</td><td class="tac bl"></td></tr>
<tr><td class="tar">17.5–</td><td class="tal">27.5</td><td class="tac brl"></td><td class="tac">2.2</td><td class="tac bl">2.00</td></tr>
<tr><td class="tar bb pb03">20–</td><td class="tal bbr pb03">30</td><td class="tac bbl"></td><td class="tac bbl pb03">1.7</td><td class="tac bbl pb03">1.96</td></tr>
</table>
<p>It is obvious that the temperature coefficient of the rate of
oxidations is remarkably constant, about 2 for 10°, for various
temperatures and does not show<span class="pagenum" title="296"><a name="Page_296" id="Page_296"></a></span> the variation from 7 or more to 2.2 for
Q<sub>10</sub> for the rate of segmentation.</p>
<p><span class="nowrap">Kanitz<a name="FNanchor_256_256" id="FNanchor_256_256"></a><a href="#Footnote_256_256" class="fnanchor">256</a></span> has shown that in a graph
in which the logarithms of the segmentation velocities are drawn as
ordinates and the temperatures as abscissæ the logarithms form two
straight lines which are joined at an angle. According to the law
of van’t Hoff and Arrhenius concerning the influence of temperature
upon velocities of chemical reactions the logarithms should lie in
a straight line. We are dealing therefore in these cases with two
exponential curves, one representing in <i class="taxonomic">Arbacia</i> the interval 7–13°
and the second from 13–26°; in <i class="taxonomic">Strongylocentrotus</i> between 3–9° and
9–20°.</p>
<p>It was found in these experiments that if measurements of the Q<sub>10</sub>
of later stages of development are attempted the variations due to
unavoidable difficulties become too great to permit an equal degree of
reliability in the determinations.</p>
<p>The vast importance of this influence of temperature upon the rate of
development is seen in the fact that in addition to the food supply the
rate of the maturing of plants and animals depends on this factor.</p>
<p>2. This influence of temperature upon development has been used to find
the conditions determining fluctuating variation. The reader knows that
by this expression are understood the differences between individuals
of a pure strain or breed. These variations<span class="pagenum" title="297"><a name="Page_297" id="Page_297"></a></span> are not inherited, a fact
contrary to the idea of Darwin, who assumed that by the selection of
extreme cases of fluctuating variation new varieties could develop.
What is the basis of this fluctuating variation? The writer concluded
that if fluctuating variations were due to a slight variation in the
quantity of a specific substance—in some cases an enzyme—required for
the formation of a hereditary character, the temperature coefficient
might be used to test the idea. We have just seen that the time
required from insemination until the cell division of the first egg
occurs is very sharply defined for each temperature. If a large
number <i>e. g.</i> one hundred or more eggs are under observation
simultaneously in a microscopic field it can be seen that they do not
all segment at the same time but in succession; this is the expression
of fluctuating variation. Miss Chamberlain and the writer have measured
the time which elapses between the moment the first egg of such a group
segments and the moment the last egg begins its segmentation, and
found that this latitude of variation is also very definite for each
temperature, and that its temperature coefficient is for each interval
of 10° practically identical with the temperature coefficient of the
segmentation for the same <span class="nowrap">interval.<a name="FNanchor_257_257" id="FNanchor_257_257"></a><a href="#Footnote_257_257" class="fnanchor">257</a></span>
The slight deviations are practically all in the same sense and
accounted for by a slight deficiency in the nature of the experiments.
The<span class="pagenum" title="298"><a name="Page_298" id="Page_298"></a></span> two following tables give the latitude of variations for
different temperatures for the first segmentation in <i class="taxonomic">Arbacia</i> and the
temperature coefficient for this latitude and the rate of segmentation.
These two latter coefficients are practically identical.</p>
<p class="tac">TABLE XII</p>
<table summary="Influence of temperature variation on first segmentation of Arbacia eggs">
<tr><th class="btr"><i>Temperature</i></th><th class="btrd"><i>Latitude of<br />Variation</i></th><th class="btld"><i>Temperature</i></th><th class="btl"><i>Latitude of<br />Variation</i></th></tr>
<tr><td class="tac btr ptb03">°C.</td><td class="tac btrd ptb03"><i>Minutes</i></td><td class="tac btld ptb03">°C.</td><td class="tac btl ptb03"><i>Minutes</i></td></tr>
<tr><td class="tac"><span class="hide">1</span>9</td><td class="tac brld">52.5</td><td class="tac">18</td><td class="tac bl">12.0</td></tr>
<tr><td class="tac">10</td><td class="tac brld">39.5</td><td class="tac">19</td><td class="tac bl">12.5</td></tr>
<tr><td class="tac">11</td><td class="tac brld">26.0</td><td class="tac">20</td><td class="tac bl"><span class="hide">1</span>9.6</td></tr>
<tr><td class="tac">12</td><td class="tac brld">22.5</td><td class="tac">21</td><td class="tac bl"><span class="hide">1</span>8.0</td></tr>
<tr><td class="tac">13</td><td class="tac brld">19.2</td><td class="tac">22</td><td class="tac bl"><span class="hide">1</span>7.8</td></tr>
<tr><td class="tac">14</td><td class="tac brld">17.5</td><td class="tac">23</td><td class="tac bl"><span class="hide">1</span>8.0</td></tr>
<tr><td class="tac">15</td><td class="tac brld">13.0</td><td class="tac">24</td><td class="tac bl"><span class="hide">1</span>8.0</td></tr>
<tr><td class="tac bbr"></td><td class="tac bbrd"></td><td class="tac bbld pb03">25</td><td class="tac bbl pb03"><span class="hide">1</span>5.0</td></tr>
</table>
<p class="tac">TABLE XIII</p>
<table summary="Influence of temperature variation on rate of segmentation of Arbacia eggs">
<tr><th class="bt" rowspan="2"><i>Temperature<br />Interval</i></th><th class="btld" colspan="2"><span class="smcap">temperature coefficient of</span></th></tr>
<tr><td class="tac btld pall"><i>Latitude of<br />Variation</i></td><td class="tac btl pall"><i>Segmentation</i></td></tr>
<tr><td class="tac btrd ptb03">°C.</td><td class="tac btld"></td><td class="tac btl"></td></tr>
<tr><td class="tac"><span class="hide">1</span>9–19</td><td class="tac blrd">4.2</td><td class="tac">4.7</td></tr>
<tr><td class="tac">10–20</td><td class="tac blrd">3.9</td><td class="tac">3.8</td></tr>
<tr><td class="tac">11–21</td><td class="tac blrd">3.2</td><td class="tac">3.3</td></tr>
<tr><td class="tac">12–22</td><td class="tac blrd">2.8</td><td class="tac">3.1</td></tr>
<tr><td class="tac">13–23</td><td class="tac blrd">2.4</td><td class="tac">2.8</td></tr>
<tr><td class="tac">14–24</td><td class="tac blrd">2.3</td><td class="tac">2.8</td></tr>
<tr><td class="tac bbrd pb03">15–25</td><td class="tac bbld pb03">2.6</td><td class="tac bbl pb03">2.5</td></tr>
</table>
<p><span class="pagenum" title="299"><a name="Page_299" id="Page_299"></a></span></p>
<p>If we assume that the temperature coefficient for the segmentation
of the egg is that of a chemical reaction (other than oxidation)
underlying the process of segmentation, the fluctuating variation in
the time of the segmentations of the various eggs fertilized at the
same time is due to the fact that the mass of the enzyme controlling
that reaction varies within definite limits in different eggs. The
first egg segmenting at a given temperature has the maximal, the last
egg segmenting has the minimal mass of enzyme. It should be added that
the time of the first segmentation is determined by the cytoplasm and
is not a Mendelian character, as was stated in a previous chapter.</p>
<p>3. The point of importance to us is that the influence of temperature
upon the organism is so constant that if disturbing factors are removed
it would be possible to use the time from insemination to the first
segmentation of an egg of <i class="taxonomic">Arbacia</i> as a thermometer on the basis of
the table on page <a href="#Page_295">295</a>.</p>
<p>Facts of this character should dispose of the idea that the organism
as a whole does not react with that degree of machine-like precision
which we find in the realm of physics and chemistry. Such an idea
could only arise from the fact that biologists have not been in the
habit of looking for quantitative laws, chiefly, perhaps, because
the difficulties due to disturbing secondary factors were too great.
The worker in physics knows that in order to discover the laws of a<span class="pagenum" title="300"><a name="Page_300" id="Page_300"></a></span>
phenomenon all the disturbing factors which might influence the result
must first be removed. When the biologist works with an organism as a
whole he is rarely able to accomplish this since the various disturbing
influences, being inseparable from the life of the organism, can often
not be entirely removed. In this case the biologist must look for an
organism in which by chance this elimination of secondary conditions
is possible. The following example may serve as an illustration of
this rather important point in biological work. Although all normal
human beings have about the same temperature, yet if the heart-beats
of a large number of healthy human beings are measured the rate is
found to vary enormously. Thus v. Körösy found among soldiers under
the most favourable and most constant conditions of observations—the
soldiers were examined early in the morning before rising—variations
in the rate of heart-beat between 42 and 108. In view of this fact,
those opposed to the idea that the organism as a whole obeys purely
physicochemical laws might find it preposterous to imagine that the
rate of heart-beat could be used as a thermometer. Yet if we observe
the influence of temperature on the rate of the heart-beat of a large
number of embryos of the fish <i class="taxonomic">Fundulus</i>, while the embryos are still
in the egg, we find that at the same temperature each heart beats
at the same rate, the deviations being only slight and such as the
fluctuating variations would<span class="pagenum" title="301"><a name="Page_301" id="Page_301"></a></span> <span class="nowrap">demand.<a name="FNanchor_258_258" id="FNanchor_258_258"></a><a href="#Footnote_258_258" class="fnanchor">258</a></span>
This constancy is so great that the rate of heart-beat of these
embryos could in fact be used as a rough thermometer. The influence of
temperature upon the rate of heart-beat is completely reversible so
that when we measure the rate for increasing as well as for decreasing
temperatures we get approximately the same values as the following
table shows.</p>
<p class="tac">TABLE XIV</p>
<table summary="Influence of temperature on heart rate of Fundulus embryos">
<col width="25%" /><col width="37%" /><col width="38%" />
<tr><th class="btr"><i>Temperature</i></th><th class="btl" colspan="2"><i>Time Required for Nineteen Heart-beats<br />in the Embryo of Fundulus</i></th></tr>
<tr><td class="tac btr ptb03">°C.</td><td class="tac btl ptb03" colspan="2"><i>Seconds</i></td></tr>
<tr><td class="tac br">30</td><td class="tar">6.</td><td class="tal">25</td></tr>
<tr><td class="tac br">25</td><td class="tar">8.</td><td class="tal">5</td></tr>
<tr><td class="tac br">20</td><td class="tar">11.</td><td class="tal">5</td></tr>
<tr><td class="tac br">15</td><td class="tar">19.</td><td class="tal">0</td></tr>
<tr><td class="tac br">10</td><td class="tar">32.</td><td class="tal">5</td></tr>
<tr><td class="tac br"><span class="hide">1</span>5</td><td class="tar">61.</td><td class="tal">0</td></tr>
<tr><td class="tac br">10</td><td class="tar">33.</td><td class="tal">5</td></tr>
<tr><td class="tac br">15</td><td class="tar">18.</td><td class="tal">8</td></tr>
<tr><td class="tac br">20</td><td class="tar">12.</td><td class="tal">0</td></tr>
<tr><td class="tac br">25</td><td class="tar">10.</td><td class="tal">0</td></tr>
<tr><td class="tac bbr pb03">30</td><td class="tar bbl pb03">6.</td><td class="tal bb pb03">0</td></tr>
</table>
<p>Why does each embryo have the same rate of heart-beat at the same
temperature in contradistinction to the enormous variability of the
same rate in man? The answer is, on account of the elimination of
all secondary disturbing factors. In the embryo of <i class="taxonomic">Fundulus</i> the
heart-beat is a function almost if not exclu<span class="pagenum" title="302"><a name="Page_302" id="Page_302"></a></span>sively of two variables,
the mass of enzymes for the chemical reactions underlying the
heart-beat and the temperature. By inheritance the mass of enzymes is
approximately the same and in this way all the embryos beat at the
same rate (within the limits of the fluctuating variation) at the same
temperature. This identity exists, however, only as long as the embryo
is relatively quiet in the egg. As soon as the embryo begins to move
this equality disappears since the motion influences the heart-beat and
the motility of different embryos differs.</p>
<p>In man the number of disturbing factors is so great that no equality
of the rate for the same temperature can be expected. Differences
in emotions or the internal secretions following the emotions,
differences in previous diseases and their after-effects, differences
in metabolism, differences in the use of narcotics or drugs, and
differences in activity are only some of the number of variables which
enter.</p>
<p>4. As stated above the temperature influences practically all
life phenomena in a similar characteristic way, <i>e. g.</i>, the
production of CO<sub>2</sub> in <span class="nowrap">seeds<a name="FNanchor_259_259" id="FNanchor_259_259"></a><a href="#Footnote_259_259" class="fnanchor">259</a></span>
and the assimilation of CO<sub>2</sub> by green <span
class="nowrap">plants.<a name="FNanchor_260_260" id="FNanchor_260_260"></a><a href="#Footnote_260_260" class="fnanchor">260</a></span> The writer would not be surprised if
even the aberrations in the colour of butterflies under the influence
of temperature<span class="pagenum" title="303"><a name="Page_303" id="Page_303"></a></span> turned out to be connected with the temperature
coefficient. The experiments of Dorfmeister, Weismann, Merrifield,
Standfuss, and Fischer, on seasonal dimorphism and the aberration
of colour in butterflies have so often been discussed in biological
literature that a short reference to them will suffice. By seasonal
dimorphism is meant the fact that species may appear at different
seasons of the year in a somewhat different form or colour. <i class="taxonomic">Vanessa
prorsa</i> is the summer form, <i class="taxonomic">Vanessa levana</i> the winter form of the
same species. By keeping the pupæ of <i class="taxonomic">Vanessa prorsa</i> several weeks at
a temperature of from 0° to 1° Weismann succeeded in obtaining from
the summer chrysalids specimens which resembled the winter variety,
<i class="taxonomic">Vanessa levana</i>.</p>
<p>If we wish to get a clear understanding of the causes of variation in
the colour and pattern of butterflies, we must direct our attention to
the experiments of Fischer, who worked with more extreme temperatures
than his predecessors, and found that almost identical aberrations
of colour could be produced by both extremely high and extremely low
temperatures. This can be seen clearly from the following tabulated
results of his observations. At the head of each column the reader
finds the temperature to which Fischer submitted the pupæ, and in the
vertical column below are found the varieties that were produced. In
the vertical column A are given the normal forms:</p>
<p><span class="pagenum" title="304"><a name="Page_304" id="Page_304"></a></span></p>
<p class="tac">TABLE XV</p>
<table summary="Influence of temperature extremes on the colouration pattern of butterflies">
<tr><th class="btr vat">0° to<br />-20°C.</th><th class="ball vat">0° to<br />+10°C.</th><th class="ball">A<br />(Normal<br />Forms)</th><th class="ball vat">+35° to<br />+37°C.</th><th class="ball vat">+36° to<br />+41°C.</th><th class="btl vat">+42° to<br />+46°C.</th></tr>
<tr><td class="tal btr ptrl03"><i>ichnusoides<br /> (nigrita)</i></td><td class="tal bl ptrl03 vat"><i>polaris</i></td><td class="tal brl ptrl03 vat"><i>urticæ</i></td><td class="tal ptrl03 vat"><i>ichnusa</i></td><td class="tal brl ptrl03 vat"><i>polaris</i></td><td class="tal btl ptrl03"><i>ichnusoides<br /> (nigrita)</i></td></tr>
<tr><td class="tal prl03"><i>antigone<br /> (iokaste)</i></td><td class="tal bl prl03 vat"><i>fischeri</i></td><td class="tal brl prl03 vat"><i>io</i></td><td class="tac vat">——</td><td class="tal brl prl03 vat"><i>fischeri</i></td><td class="tal pl03"><i>antigone<br /> (iokaste)</i></td></tr>
<tr><td class="tal prl03"><i>testudo</i></td><td class="tal bl prl03"><i>dixeyi</i></td><td class="tal brl prl03"><i>polychloros</i></td><td class="tal prl03"><i>erythromelas</i></td><td class="tal brl prl03"><i>dixeyi</i></td><td class="tal pl03"><i>testudo</i></td></tr>
<tr><td class="tal prl03"><i>hygiæa</i></td><td class="tal bl prl03"><i>artemis</i></td><td class="tal brl prl03"><i>antiopa</i></td><td class="tal prl03"><i>epione</i></td><td class="tal brl prl03"><i>artemis</i></td><td class="tal pl03"><i>hygiæa</i></td></tr>
<tr><td class="tal prl03"><i>elymi</i></td><td class="tal bl prl03"><i>wiskotti</i></td><td class="tal brl prl03"><i>cardui</i></td><td class="tac">——</td><td class="tal brl prl03"><i>wiskotti</i></td><td class="tal pl03"><i>elymi</i></td></tr>
<tr><td class="tal prl03"><i>klymene</i></td><td class="tal bl prl03"><i>merrifieldi</i></td><td class="tal brl prl03"><i>atalanta</i></td><td class="tac">——</td><td class="tal brl prl03"><i>merrifieldi</i></td><td class="tal pl03"><i>klymene</i></td></tr>
<tr><td class="tal bbr pbrl03"><i>weismanni</i></td><td class="tal bbr pbrl03"><i>porima</i></td><td class="tal bbr pbrl03"><i>prorsa</i></td><td class="tac bb pbrl03">——</td><td class="tal bbl pbrl03"><i>porima</i></td><td class="tal bbl pbrl03"><i>weismanni</i></td></tr>
</table>
<p>The reader will notice that the aberrations produced at a very
low temperature (from 0° to -20°C.) are absolutely identical with
the aberrations produced by exposing the pupæ to extremely high
temperatures (42° to 46°C.). Moreover, the aberrations produced by a
moderately low temperature (from 0° to 10°C.) are identical with the
aberrations produced by a moderately high temperature (36° to 41°C.).</p>
<p>From these observations Fischer concludes that it is erroneous to speak
of a specific effect of high and of low temperatures, but that there
must be a common cause for the aberration found at the high as well
as at the low temperature limits. This cause he seems to find in the
inhibiting effects of extreme temperatures upon development.</p>
<p>If we try to analyse such results as Fischer’s from a<span class="pagenum" title="305"><a name="Page_305" id="Page_305"></a></span> physicochemical
point of view, we must realize that what we call life consists of a
series of chemical reactions, which are connected in a catenary way;
inasmuch as one reaction or group of reactions (<i>a</i>) (<i>e. g.</i>,
hydrolyses) causes or furnishes the material for a second reaction or
group of reactions (<i>b</i>) (<i>e. g.</i>, oxidations). We know that the
temperature coefficient for physiological processes varies slightly
at various parts of the scale; as a rule it is higher near 0° and
lower near 30°. But we know also that the temperature coefficients
do not vary equally for the various physiological processes. It is,
therefore, to be expected that the temperature coefficients for the
group of reactions of the type (<i>a</i>) will not be identical through
the whole scale with the temperature coefficients for the reactions
of the type (<i>b</i>). If therefore a certain substance is formed at the
normal temperature of the animal in such quantities as are needed for
the catenary reaction (<i>b</i>), it is not to be expected that this same
perfect balance will be maintained for extremely high or extremely low
temperatures; it is more probable that one group of reactions will
exceed the other and thus produce aberrant chemical effects, which
may underlie the colour aberrations observed by Fischer and other
experimenters.</p>
<p>It is important to notice that Fischer was also able to produce
aberrations through the application of narcotics. Wolfgang Ostwald has
produced experi<span class="pagenum" title="306"><a name="Page_306" id="Page_306"></a></span>mentally, through variation of temperature, dimorphism
of form in <i class="taxonomic">Daphnia</i>.</p>
<p>5. Next or equal in importance with the temperature is the nature of
the medium in which the cells are living.</p>
<p>It has often been pointed out that the marine animals and the cells
of the body of metazoic animals are surrounded by a medium of similar
constitution, the sea water and the blood or lymph, both media being
salt solutions differing in concentration but containing the three
salts NaCl, KCl, and CaCl<sub>2</sub> in about the same relative concentration,
namely 100 molecules NaCl : 2.2 molecules of KCl : 1.5 molecules of
CaCl<sub>2</sub>. This has suggested to some authors the poetical dream
that our home was once the ocean, but we cannot test the idea since
unfortunately we cannot experiment with the past. Plants, unicellular
fresh-water algæ, and bacteria do not demand such a medium for their
existence.</p>
<p>Herbst had shown that when sea-urchin larvæ were raised in a medium
in which only one of the constituents of the sea water was lacking
(not only NaCl, KCl, or CaCl<sub>2</sub>, but also Na<sub>2</sub>SO<sub>4</sub>, NaHCO<sub>3</sub>, or
Na<sub>2</sub>HPO<sub>4</sub>), the eggs could not develop into plutei; from which he
concluded that every constituent of the sea water was necessary. This
would indicate a case of extreme adaptation to all the minutiæ of the
external medium.</p>
<p>Experiments on a much more favourable animal<span class="pagenum" title="307"><a name="Page_307" id="Page_307"></a></span> for this purpose, namely,
the eggs of the marine fish <i class="taxonomic">Fundulus</i>, gave altogether different
results. The eggs of this marine fish develop naturally in sea water
but they develop just as well in fresh or in distilled water, and the
young fish when they are made to hatch in distilled water will continue
to live in this medium. This proves that these eggs require none of the
salts of the sea water for their development. When these eggs are put
immediately after fertilization into a pure solution of NaCl of that
concentration in which this salt exists in the sea water practically
all the eggs die without forming an embryo; but if a small quantity of
CaCl<sub>2</sub> is added every egg is able to form one, and these embryos will
develop into fish and the latter will hatch. This led the writer to
the conclusion that these fish (and perhaps marine animals in general)
need the Ca of the sea water only to counteract the injurious effects
which a pure NaCl solution has if it is present in too high a <span
class="nowrap">concentration.<a name="FNanchor_261_261" id="FNanchor_261_261"></a><a href="#Footnote_261_261" class="fnanchor">261</a></span> When we raise the eggs in a
pure NaCl solution of a concentration ≦m/8 practically every egg will
develop; and even in a m/4 or <sup>3</sup>⁄<sub>8</sub> m many or some eggs will form embryos
without adding Ca; it may be that a trace of Ca present in the membrane
of the egg may suffice to counter-balance the injurious action of a
weak salt solution. </p>
<p><span class="pagenum" title="308"><a name="Page_308" id="Page_308"></a></span></p>
<p>The concentration of the NaCl in the sea water at Woods Hole (where
these experiments were made) is about m/2, and as soon as this
concentration of NaCl is reached the eggs are all killed as a rule
before they can form an embryo, unless a small but definite amount
of Ca is added. It was found that the eggs can be raised in much
higher concentrations of NaCl, but in that case more Ca must be
added. The following table gives the minimal amount of CaCl<sub>2</sub> which
must be added in order to allow fifty per cent. of the eggs to form
embryos. (The eggs were put into the solution an hour or two after
fertilization.)</p>
<p class="tac">TABLE XVI</p>
<table width="40%" summary="Influence of electrolyte concentration on formation of Fundulus embryos">
<tr><th class="btr" colspan="2"><i>Concentration<br />of NaCl</i></th><th class="btl" colspan="2"><i>Cc. m/16 CaCl<sub>2</sub> Required<br />for 50 c.c. NaCl Solution</i></th></tr>
<tr><td class="tac btr ptb03" colspan="2">m. </td><td class="tar btl" colspan="2"></td></tr>
<tr><td class="tar"><sup>3</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">0.</td><td class="tal">1</td></tr>
<tr><td class="tar"><sup>4</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">0.</td><td class="tal">3</td></tr>
<tr><td class="tar"><sup>5</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">0.</td><td class="tal">5</td></tr>
<tr><td class="tar"><sup>6</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">0.</td><td class="tal">6</td></tr>
<tr><td class="tar"><sup>7</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">0.</td><td class="tal">9</td></tr>
<tr><td class="tar"><sup>8</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">1.2–</td><td class="tal">1.4</td></tr>
<tr><td class="tar"><sup>9</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">1.8–</td><td class="tal">2.0</td></tr>
<tr><td class="tar"><sup>10</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">2.0–</td><td class="tal">2.5</td></tr>
<tr><td class="tar"><sup>11</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">2.</td><td class="tal">0?</td></tr>
<tr><td class="tar"><sup>12</sup>⁄</td><td class="tal br"><sub>8</sub>  </td><td class="tar">3.0–</td><td class="tal">3.5</td></tr>
<tr><td class="tar bb pb03"><sup>13</sup>⁄</td><td class="tal bbr pb03"><sub>8</sub>  </td><td class="tar bb pb03">6.</td><td class="tal bb pb03">0</td></tr>
</table>
<p>This indicates that the quantity of CaCl<sub>2</sub> required to counteract the
injurious effects of a pure solution of NaCl increases approximately
in proportion to the<span class="pagenum" title="309"><a name="Page_309" id="Page_309"></a></span> square of the concentration of the NaCl <span
class="nowrap">solution.<a name="FNanchor_262_262" id="FNanchor_262_262"></a><a href="#Footnote_262_262" class="fnanchor">262</a></span> The reader will notice that
the eggs can survive and develop in a solution of three times the
concentration of sea water, provided enough Ca is added.</p>
<p>It was found also that not only Ca but a large number of other
bivalent metals were able to counteract the injurious action of an
excessive NaCl solution; namely Mg, Sr, Ba, Mn, Co, Zn, Pb, and <span
class="nowrap">Fe;<a name="FNanchor_263_263" id="FNanchor_263_263"></a><a href="#Footnote_263_263" class="fnanchor">263</a></span> only Hg and Cu could not be used since
they are themselves too toxic. The antagonistic efficiency of the
bivalent cations other than Ca was, however, smaller than that of Ca.
The following table gives the highest concentration of NaCl solution in
which the newly fertilized eggs of <i class="taxonomic">Fundulus</i> can still form an <span
class="nowrap">embryo.<a name="FNanchor_264_264" id="FNanchor_264_264"></a><a href="#Footnote_264_264" class="fnanchor">264</a></span></p>
<p class="ml25em">50 c.c. <sup>10</sup>⁄<sub>8</sub> m NaCl+4 c.c. m/1 MgCl<sub>2</sub><br />
50 c.c. <sup>14</sup>⁄<sub>8</sub> m NaCl+1 c.c. m/1 CaCl<sub>2</sub><br />
50 c.c. <sup>11</sup>⁄<sub>8</sub> m NaCl+1 c.c. m/1 SrCl<sub>2</sub><br />
50 c.c. <sup>7</sup>⁄<sub>8</sub> m NaCl+1 c.c. m/1 BaCl<sub>2</sub></p>
<p>On the other hand it was seen that in all the chlorides with a
univalent cation, LiCl, KCl, RbCl, CsCl, NH<sub>4</sub>Cl, the eggs could
form embryos up to a certain concentration of the salt; but that this
concentration could be raised by the addition of Ca.</p>
<p><span class="pagenum" title="310"><a name="Page_310" id="Page_310"></a></span></p>
<p class="tac">TABLE XVII</p>
<p class="tac mrl10"><span class="smcap">Concentrations at which the Eggs no longer Are Able
to Form Embryos</span></p>
<table summary="Electrolyte concentrations that prevent Fundulus embryo formation">
<tr><th class="btr" colspan="3"><i>In the Pure Salts</i></th><th class="btl" colspan="2"><i>In the Same Salts<br />with the Addition of 1 c.c. m CaCl<sub>2</sub><br />to 50 c.c. Solution</i></th></tr>
<tr><td class="tal bt ptl03">LiCl  </td><td class="tar bt pt03">about 6/</td><td class="tal btr ptr03">32 m</td><td class="tar btl pt03">>5/</td><td class="tal bt pt03 pr06">8 m</td></tr>
<tr><td class="tal pl03">NaCl</td><td class="tar">m/</td><td class="tal br pr03">2</td><td class="tar">>14/</td><td class="tal">8 m</td></tr>
<tr><td class="tal pl03">KCl</td><td class="tar">>11/</td><td class="tal br pr03">16 m</td><td class="tar">>8/</td><td class="tal">8 m</td></tr>
<tr><td class="tal"></td><td class="tar"><6/</td><td class="tal br pr03">8 m</td><td class="tar"></td><td class="tal"></td></tr>
<tr><td class="tal pl03">RbCl</td><td class="tar">>8/</td><td class="tal br pr03">8 m</td><td class="tar">>9/</td><td class="tal">8 m</td></tr>
<tr><td class="tal"></td><td class="tar"><7/</td><td class="tal br pr03">8 m</td><td class="tar"></td><td class="tal"></td></tr>
<tr><td class="tal pl03">CsCl</td><td class="tar">>3/</td><td class="tal br pr03">8 m</td><td class="tar">>8/</td><td class="tal">8 m</td></tr>
<tr><td class="tal bb"></td><td class="tar bb"><4/</td><td class="tal bbr pb03">8 m</td><td class="tar bbl"></td><td class="tal bb"></td></tr>
</table>
<p>In short it turned out that the injurious action of the pure solution
of any chloride (or any other anion) with a univalent metal could
be counteracted to a considerable extent by the addition of small
quantities of a salt with a bivalent metal. It was also found in the
early experiments of the writer <em>that the bivalent or polyvalent anions
had no such antagonistic effect</em> upon the injurious action of the salts
with a univalent cation.</p>
<p>We therefore see that what at first sight appeared in the experiments
of Herbst a necessity, namely, the presence of each constituent of the
sea water, turns out as a special case of a more general law; the salts
with univalent ions are injurious if their concentration exceeds a
certain limit and this injurious action is diminished by a trace of a
salt with a bivalent cation.</p>
<p>Why was it not possible to prove this fact for the<span class="pagenum" title="311"><a name="Page_311" id="Page_311"></a></span> eggs of the sea
urchin? Before we answer this question, we wish to enter upon the
discussion of the nature of the injurious action of a pure NaCl
solution of a certain concentration and of the annihilation of this
action by the addition of a small quantity of Ca. The writer suggested
in 1905 that the injurious action of a pure NaCl solution consisted
in rendering the membrane of the egg permeable for NaCl, whereby the
germ inside the membrane is killed; while the addition of a small
amount of Ca (or any other bivalent metal) prevents the diffusion of
Na into the <span class="nowrap">egg,<a name="FNanchor_265_265" id="FNanchor_265_265"></a><a href="#Footnote_265_265" class="fnanchor">265</a></span> possibly, as T. B.
<span class="nowrap">Robertson<a name="FNanchor_266_266" id="FNanchor_266_266"></a><a href="#Footnote_266_266" class="fnanchor">266</a></span> suggested, by forming
a precipitate with some constituent of the membrane, whereby the
latter becomes more impermeable. The correctness of this idea can be
demonstrated in the following way. When eggs of <i class="taxonomic">Fundulus</i>, which are
three or four days old and contain an embryo, are put into a test-tube
containing 3 m NaCl they will float on this solution for about three
or four hours; after that they will sink to the bottom. Before this
happens the egg will shrink and when it ceases to float the embryo is
usually dead. This is intelligible on the assumption that the NaCl
solution entered the egg, increased its specific gravity so that it
could not float any longer and killed the embryo. When we add, however,
1 c.c. <sup>10</sup>⁄<sub>8</sub> m CaCl<sub>2</sub> to 50 c.c. 3 m NaCl the eggs will float, the<span class="pagenum" title="312"><a name="Page_312" id="Page_312"></a></span>
heart will continue to beat normally and the embryo will continue to
develop for three days or more, because the calcium prevents the NaCl
from entering into the <span class="nowrap">egg.<a name="FNanchor_267_267" id="FNanchor_267_267"></a><a href="#Footnote_267_267" class="fnanchor">267</a></span> For if we
put a newly hatched embryo into 50 c.c. NaCl+1 c.c. <sup>10</sup>⁄<sub>8</sub> m CaCl<sub>2</sub> it
will die almost instantly; hence the membrane must have acted for three
or more days as a shield which prevented the NaCl from diffusing into
the egg in the presence of CaCl<sub>2</sub>.</p>
<p>The same experiments cannot be demonstrated in the sea-urchin egg,
first, because it can live neither in distilled water nor in very
dilute nor very concentrated solutions; and second, because it is not
separated as is the germ of the <i class="taxonomic">Fundulus</i> egg from the surrounding
solution by a membrane which is under proper conditions practically
impermeable for water and salts.</p>
<p>Nevertheless it can be shown that the results at which we arrived in
our experiments on <i class="taxonomic">Fundulus</i> are of a general application. <span
class="nowrap">Osterhout<a name="FNanchor_268_268" id="FNanchor_268_268"></a><a href="#Footnote_268_268" class="fnanchor">268</a></span> has shown that plants which
grow in the soil or in fresh water are readily killed by a pure
NaCl solution of a certain concentration, while they can resist
the same concentration of NaCl if some CaCl<sub>2</sub> is added. Wo. <span
class="nowrap">Ostwald<a name="FNanchor_269_269" id="FNanchor_269_269"></a><a href="#Footnote_269_269" class="fnanchor">269</a></span> has shown the same for a species of
<i class="taxonomic">Daphnia</i>. We, therefore, come to the conclusion that the injurious<span class="pagenum" title="313"><a name="Page_313" id="Page_313"></a></span>
action following an alteration in the constitution of the sea water
is in some of the cases due to an increase in the permeability of the
membranes of the cell, whereby substances can diffuse into the cell
which when the proper balance prevails cannot diffuse. For this balance
the ratio of the concentration of the salts with univalent cation Na
and K over those with bivalent cation Ca and Mg <span class="fs140"><span class="fraction"><span class="fnum">C<sub>Na+K salts</sub></span><span class="bar">/</span><span class="fden">C<sub>Ca+Mg salts</sub></span></span></span>
is of the greatest importance.</p>
<p>6. The importance of this quotient appears in the so-called “behaviour”
of marine animals. We have mentioned the newly hatched larvæ of
the barnacle in connection with heliotropism. These larvæ swim in
a trough of normal sea water at the surface, being either strongly
positively or negatively heliotropic. They collect as a rule in two
dense clusters, one at the window and one at the room side of the
dish. If such animals are put into a solution of NaCl+KCl (in the
proportion in which these salts exist in the sea water), they will
fall to the bottom unable to rise to the surface. They will, however,
rise to the surface and swim energetically to or from the window if
a certain quantity of any of the chlorides of a bivalent metal, Mg,
Ca, or Sr, is added, but these movements will last only a few minutes
when only one of these three salts is added; and then the animals
will fall to the bottom again. If, however, two salts, <i>e. g.</i>,
<span class="pagenum" title="314"><a name="Page_314" id="Page_314"></a></span>MgCl<sub>2</sub> and CaCl<sub>2</sub>, are added the animals will stay permanently at
the surface and react to light as they would have done in normal sea
water. These animals also can resist comparatively large changes in the
concentration of the sea water, and it seemed of interest to find out
whether the quotient <span class="fs140"><span class="fraction"><span class="fnum">C<sub>NaCl+KCl</sub></span><span class="bar">/</span><span class="fden">C<sub>MgCl<sub>2</sub>+CaCl<sub>2</sub></sub></span></span></span>, which just
allowed all the animals to swim at the surface, had a constant value.
The MgCl<sub>2</sub>+CaCl<sub>2</sub> solution was <sup>3</sup>⁄<sub>8</sub> m and contained the two metals
in the proportion in which they exist in the sea water; namely, 11.8
molecules MgCl<sub>2</sub> to 1.5 molecules CaCl<sub>2</sub>. The next table gives the
<span class="nowrap">result.<a name="FNanchor_270_270" id="FNanchor_270_270"></a><a href="#Footnote_270_270" class="fnanchor">270</a></span> Since these experiments lasted
a day or more each, usually two different concentrations of NaCl+KCl of
the ratio 1 : 2 or 1 : 4 were compared in one experiment.</p>
<p class="tac">TABLE XVIII</p>
<table summary="Influence of electrolyte balance on movement of barnacle larvae">
<tr><th class="btr"><i>Number<br />of<br />Experiment</i></th><th class="btr" colspan="2"><i>Concentration<br />of<br />NaCl+KCl</i></th><th class="btr" colspan="2"><i>C.c.<br />3/8 m CaCl<sub>2</sub>+MgCl<sub>2</sub><br />Required</i></th><th class="btl"><i>Value of<br /><span class="fs140"><span class="fraction"><span class="fnum">C<sub>Na+K</sub></span><span class="bar">/</span><span class="fden">C<sub>Mg+Ca</sub></span></span></span></i></th></tr>
<tr><td class="tac btr ptb03" rowspan="2">1</td><td class="tar bt pt03" rowspan="2">  <img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal btr pt03">m/16</td><td class="tar btl pt03">0.</td><td class="tal btr pt03">3</td><td class="tac btl pt03">27.8</td></tr>
<tr><td class="tal br pb06">m/8</td><td class="tar pb06">0.4–</td><td class="tal pb06">0.5</td><td class="tac bl pb06">37.0</td></tr>
<tr><td class="tac br pb03" rowspan="2">2</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">m/8</td><td class="tar">0.</td><td class="tal">5</td><td class="tac bl">33.3</td></tr>
<tr><td class="tal br pb06">m/4</td><td class="tar pb06">0.9–</td><td class="tal pb06">1.0</td><td class="tac bl pb06">35.1</td></tr>
<tr><td class="tac br pb03" rowspan="2">3</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">3/16 m</td><td class="tar">0.</td><td class="tal">7</td><td class="tac bl">35.7</td></tr>
<tr><td class="tal br pb06">3/8 m</td><td class="tar pb06">1.</td><td class="tal pb06">3</td><td class="tac bl pb06">38.5<span class="pagenum" title="315"><a name="Page_315" id="Page_315"></a></span></td></tr>
<tr><td class="tac br pb03" rowspan="2">4</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">m/8</td><td class="tar">0.</td><td class="tal">5</td><td class="tac bl">36.0</td></tr>
<tr><td class="tal br pb06">m/2</td><td class="tar pb06">1.8–</td><td class="tal pb06">1.9</td><td class="tac bl pb06">39.2</td></tr>
<tr><td class="tac br pb03" rowspan="2">5</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">m/4</td><td class="tar">0.8–</td><td class="tal">0.9</td><td class="tac bl">39.2</td></tr>
<tr><td class="tal br pb06">m/2</td><td class="tar pb06">1.6–</td><td class="tal pb06">1.7</td><td class="tac bl pb06">40.3</td></tr>
<tr><td class="tac br pb06" rowspan="2">6</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">5/16 m</td><td class="tar">0.</td><td class="tal">9</td><td class="tac bl">46.3</td></tr>
<tr><td class="tal br pb06">5/8 m</td><td class="tar pb06">1.</td><td class="tal pb06">7</td><td class="tac bl pb06">49.0</td></tr>
<tr><td class="tac bbr pb03" rowspan="2">7</td><td class="tar bb" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" alt="curly bracket" /></td><td class="tal br">3/16 m</td><td class="tar">0.</td><td class="tal">6</td><td class="tac bl">41.7</td></tr>
<tr><td class="tal bbr pb03">6/8 m</td><td class="tar bb pb03">2.</td><td class="tal bbr pb03">4</td><td class="tac bbl pb03">41.7</td></tr>
</table>
<p>These experiments indicate that the ratio of <span class="fs140"><span class="fraction"><span class="fnum">C<sub>Na+K</sub></span><span class="bar">/</span><span class="fden">C<sub>Ca+Mg</sub></span></span></span> remains
very nearly constant with varying concentrations of C<sub>Na+K</sub>.</p>
<p>In former experiments on jellyfish the writer had shown
that there exists an antagonism between Mg and <span
class="nowrap">Ca<a name="FNanchor_271_271" id="FNanchor_271_271"></a><a href="#Footnote_271_271" class="fnanchor">271</a></span>, and this observation was subsequently
confirmed by Meltzer and <span class="nowrap">Auer<a name="FNanchor_272_272" id="FNanchor_272_272"></a><a href="#Footnote_272_272" class="fnanchor">272</a></span> for
mammals. It was observed that in a solution of NaCl+KCl+MgCl<sub>2</sub> the
larvæ of the barnacle were also not able to remain at the surface
for more than a few minutes, while an addition of some CaCl<sub>2</sub> made
them swim permanently at the surface. Various quantities of MgCl<sub>2</sub>
were added to a mixture of m/4 or m/2 NaCl+KCl, to find<span class="pagenum" title="316"><a name="Page_316" id="Page_316"></a></span> out how much
CaCl<sub>2</sub>, was required to allow them to swim permanently at the surface.</p>
<p class="tac">TABLE XIX</p>
<table summary="Influence of electrolyte balance on movement of barnacle larvae">
<tr><th class="btr" rowspan="2"></th><th class="btl" colspan="4"><i>C.c. of m/16 CaCl<sub>2</sub> Necessary<br />to Induce the Majority of<br />the Larvæ to Swim in</i></th></tr>
<tr><td class="tac btr pall" colspan="2">m/2 (Na+K)</td><td class="tac btl pall" colspan="2">m/4 (Na+K)</td></tr>
<tr><td class="tal btr ptr03">50 c.c. NaCl+KCl+0.75 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar btl"></td><td class="tal btr"></td><td class="tar btl pt03">0.</td><td class="tal bt pt03">2</td></tr>
<tr><td class="tal br">50 c.c. NaCl+KCl+ 1.5 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar">0.</td><td class="tal br">4</td><td class="tar">0.</td><td class="tal">3</td></tr>
<tr><td class="tal br">50 c.c. NaCl+KCl+ 2.5 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar">0.</td><td class="tal br">4</td><td class="tar">0.</td><td class="tal">4</td></tr>
<tr><td class="tal br">50 c.c. NaCl+KCl+ 5.0 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar">0.7–</td><td class="tal br">0.8</td><td class="tar">0.7–</td><td class="tal">0.8</td></tr>
<tr><td class="tal br">50 c.c. NaCl+KCl+10.0 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar">1.</td><td class="tal br">6</td><td class="tar">1.</td><td class="tal">6</td></tr>
<tr><td class="tal br">50 c.c. NaCl+KCl+15.0 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar">1.</td><td class="tal br">8</td><td class="tar"></td><td class="tal"></td></tr>
<tr><td class="tal bbr pb03">50 c.c. NaCl+KCl+20.0 c.c. <sup>3</sup>⁄<sub>8</sub> m MgCl<sub>2</sub></td><td class="tar bbl pb03">1.</td><td class="tal bbr pb03">8</td><td class="tar bbl"></td><td class="tal bb"></td></tr>
</table>
<p>In order to interpret these figures correctly we must remember that
we are dealing with two different antagonisms, one between the salts
with univalent and bivalent metals and the other between Mg and Ca.
The former antagonism is satisfied by the addition of Mg, inasmuch
as enough Mg was present for this purpose in all solutions. What was
lacking was the balance between Mg and Ca. The experiments in Table XIX
therefore answer the question of the ratio between Mg and Ca. If we
consider only the concentrations of Mg between 2.5 and 10.0 c.c. <sup>3</sup>⁄<sub>8</sub> m
MgCl<sub>2</sub>—which are those closest to the normal concentration of Mg in
the sea water—we notice that C<sub>Ca</sub> must vary in proportion to C<sub>Mg</sub>.
If we now combine the results of this and the previous paragraph
we may<span class="pagenum" title="317"><a name="Page_317" id="Page_317"></a></span> express them in the form of the <cite>theory of physiologically
balanced salt solutions, by which we mean that in the ocean (and in
the blood or lymph) the salts exist in such ratio that they mutually
antagonize the injurious action which one or several of them would
have if they were alone in</cite> <span class="nowrap"><cite>solution.</cite><a name="FNanchor_273_273" id="FNanchor_273_273"></a><a href="#Footnote_273_273" class="fnanchor">273</a></span>
This law of physiologically balanced solutions seems to be the general
expression of the effect of changes in the constitution of the salt
solutions for marine or all aquatic organisms.</p>
<p>This chapter would not be complete without an intimation of the rôle of
buffers in the sea water and the blood, by which the reaction of these
media is prevented from changing in a way injurious to the organism.
These buffers are the carbonates and phosphates. Instead of saying that
the organisms are adapted to the medium, L. Henderson has pointed out
the fitness of the environment for the development of organisms and
one of these elements of fitness are the buffers against alterations
of the hydrogen ion <span class="nowrap">concentration.<a name="FNanchor_274_274" id="FNanchor_274_274"></a><a href="#Footnote_274_274" class="fnanchor">274</a></span>
The ratio in which the salts of the different metals exist in the sea
water is another. It is obvious that the quantitative laws prevailing
in the effect of environment upon organisms leave no more room for the
interference of a “directing force” of the vitalist than do the laws of
the motion of the solar system. </p>
<hr class="chap" />
<p><span class="pagenum" title="318"><a name="Page_318" id="Page_318"></a></span></p>
<h2>CHAPTER XII</h2>
<h3>ADAPTATION TO ENVIRONMENT</h3>
<p>1. It is assumed by certain biologists that the environment influences
the organism in such a way as to increase its adaptation. Were this
correct it would not contradict a purely physicochemical conception
of life; it would only call for an explanation of the mechanism by
which the adaptation is brought about. There are striking cases on
record which warn us against the universal correctness of the view
that the environment causes an adaptive modification of the organism.
Thus the writer pointed out in 1889 that positive heliotropism
occurs in organisms which have no opportunity to make use of <span
class="nowrap">it,<a name="FNanchor_275_275" id="FNanchor_275_275"></a><a href="#Footnote_275_275" class="fnanchor">275</a></span> <i>e. g.</i>, <i class="taxonomic">Cuma rathkii</i>, a
crustacean living in the mud, and the caterpillars of the willow
borer living under the bark of the trees. We understand today why
this should be so, since heliotropism depends upon the presence of
photosensitive substances, and it can readily be seen<span class="pagenum" title="319"><a name="Page_319" id="Page_319"></a></span> that the
question of use or disuse has nothing to do with the production of
certain harmless chemical compounds in the body. A much more striking
example is offered in the case of galvanotropism. Many organisms
show the phenomenon of galvanotropism, yet, as the writer pointed
out years ago, galvanotropism is purely a laboratory product and no
animal has ever had a chance or will ever have a chance to be exposed
to a constant current except in the laboratory of a scientist. This
fact is as much of a puzzle to the selectionist and to the Lamarckian
(who would be at a loss to explain how outside conditions could have
developed this tropism) as to the vitalist who would have to admit
that the genes and supergenes indulge occasionally in queer freaks
and lapses. The only consistent attitude is that of the physicist who
assumes that the reactions and structures of animals are consequences
of the chemical and physical forces, which no more serve a purpose than
those forces responsible for the solar systems. From this viewpoint it
is comprehensible why utterly useless tropisms or structures should
occur in organisms.</p>
<p>2. A famous case for the apparent adaptation of animals to environment
has been the blind cave animals. It is known that in caves blind
salamanders, blind fishes, and blind insects are common, while such
forms are comparatively rare in the open. This fact has suggested the
idea that the darkness of the cave<span class="pagenum" title="320"><a name="Page_320" id="Page_320"></a></span> was the cause of the degeneration
of the eyes. A closer investigation leads, however, to a different
explanation. Eigenmann has shown that of the species of salamanders
living habitually in North American caves, two have apparently
quite normal eyes. They are <i class="taxonomic">Spelerpes maculicauda</i> and <i class="taxonomic">Spelerpes
stejnegeri</i>. Two others living in caves have quite degenerate eyes,
<i class="taxonomic">Typhlotriton spelæus</i> and <i class="taxonomic">Typhlomolge rathbuni</i>. If disuse is the
direct cause of blindness we must inquire why <i class="taxonomic">Spelerpes</i> is not blind.</p>
<p>Another difficulty arises from the fact that a blind fish
<i class="taxonomic">Typhlogobius</i> is found in the open (on the coast of southern
California) in shallow water, where it lives under rocks in holes
occupied by shrimps. The question must again be raised: How can it
happen that in spite of exposure to light <i class="taxonomic">Typhlogobius</i> is blind?</p>
<p>The most important fact is perhaps the one found by Eigenmann in the
fishes of the family of Amblyopsidæ. Six species of this group live
permanently in caves, are not found in the open, and have abnormal
eyes, while one lives permanently in the open, is never found in caves,
and one comes from subterranean springs. The one form which is found
only in the open, <i class="taxonomic">Chologaster cornutus</i>, has a simplified retina as
well as a comparatively small eye, in other words, its eye is not
normal. This indicates the possibility that the other representatives
which are found only in<span class="pagenum" title="321"><a name="Page_321" id="Page_321"></a></span> caves also might have abnormal eyes even if
they had never lived in caves.</p>
<p>Through these facts the old idea becomes questionable, namely, that the
cave animals had originally been animals with normal eyes which owing
to disuse had undergone a gradual hereditary degeneration.</p>
<p>Recent experiments made on the embryos of the fish <i class="taxonomic">Fundulus</i>
have yielded the result that it is possible to produce
blindness in fish by various means other than lack of <span
class="nowrap">light.<a name="FNanchor_276_276" id="FNanchor_276_276"></a><a href="#Footnote_276_276" class="fnanchor">276</a></span> Thus the writer found that by
crossing the egg of <i class="taxonomic">Fundulus</i> with the sperm of a widely different
species, namely, <i class="taxonomic">Menidia</i>, blind embryos were produced very
frequently; that is to say such embryos had the degenerate eyes
characteristic of blind cave fishes. Very often no other external
trace of an eye, except a gathering of pigment, could be found, while
a close histological examination would possibly have resulted in the
demonstration of rudiments of a lens and other tissues of the eye.</p>
<p>Another method of producing blind fish embryos consists in exposing the
egg immediately, or soon after fertilization, to a temperature between
0° and 2° C. for a number of hours. Many embryos are killed by this
treatment, but those which survive behave very much like the hybrids
between <i class="taxonomic">Fundulus</i> and <i class="taxonomic">Menidia</i>, <i>i. e.</i>, a number of them have
quite degenerated eyes. If the eggs have once formed an embryo they can
be<span class="pagenum" title="322"><a name="Page_322" id="Page_322"></a></span> kept at the temperature of 0° for a month or more without giving
rise to blind animals. Occasionally such rudimentary eyes were also
observed when eggs were kept in a solution containing a trace of KCN.
Stockard has succeeded in producing cyclopean eyes in <i class="taxonomic">Fundulus</i> by
adding an excess of magnesium salt to the sea water in which the eggs
developed or by adding alcohol, and McClendon has confirmed and added
to these results.</p>
<p>The writer tried repeatedly, but in vain, to produce <i class="taxonomic">Fundulus</i> with
deficient eyes by keeping the embryos in the dark. Sperm and egg
were not allowed to be exposed to the light yet the embryos without
exception had normal eyes.</p>
<p>F. Payne raised sixty-nine successive generations of a fly <i class="taxonomic">Drosophila</i>
in the dark, but the eyes and the reaction of the insects to light
remained perfectly normal.</p>
<p>Uhlenhuth has recently demonstrated in a very striking way that the
development of the eyes does not depend upon the influence of light
or upon the eyes functioning. He transplanted the eyes of young
salamanders into different parts of their bodies where they were no
longer connected with the optic nerves. The eyes after transplantation
underwent a degeneration which was followed by a complete regeneration.
He showed that this regeneration took place in complete darkness and
that the transplanted eyes remained normal in salamanders kept in
the dark for fifteen<span class="pagenum" title="323"><a name="Page_323" id="Page_323"></a></span> months. Hence the eyes which were no longer in
connection with the central nervous system, which had received no
light, and could not have functioned, regenerated and remained normal.
The degeneration which took place in the eyes immediately after being
transplanted was apparently due to the interruption of the circulation
in the eye, and the regeneration commenced in all probability with the
re-establishment of the circulation in the transplanted organ.</p>
<p>In our own experiments it can be shown that the circulation in the
embryo was deficient in all cases where the eyes degenerated. The
hybrids between <i class="taxonomic">Fundulus</i> and <i class="taxonomic">Menidia</i> have often a beating heart
but rarely a circulation (although they form blood); and the same
phenomenon occurred in the embryos which were exposed to a low
temperature at an early period of their lives. Hence all the facts
agree that conditions which lead to an abnormal circulation (and
consequently also to an abnormal or inadequate nutrition of the
embryonic eye) may prevent development and lead to the formation of
blind fishes. Eigenmann states that no blood-vessels enter the eye of
the blind cave salamander <i class="taxonomic">Typhlotriton</i>. The presence or absence of
light does not usually interfere with the circulation or nutrition of
the embryonic eye, and hence does not as a rule lead to the formation
of degenerated eyes.</p>
<p>This would lead us to the assumption that the blind<span class="pagenum" title="324"><a name="Page_324" id="Page_324"></a></span> fish owe their
deficiency not to lack of light but to a condition which interferes
with the circulation in the embryonic eye. Such a condition might be
brought about by an anomaly in the germ plasm or in one chromosome,
the nature and cause of which we are not able to determine at present;
but which, since it occurs in the germ plasm or the chromosomes, must
be hereditary. This would explain why it is, that animals with perfect
eyes may occur in caves and why perfectly blind animals may occur
in the open. It leaves, however, one point unexplained; namely, the
greater frequency of blind species in caves or in the dark and the
relative scarcity of such forms in the open.</p>
<p>Eigenmann has shown that all those forms which live in caves
were adapted to life in the dark before they entered the <span
class="nowrap">cave.<a name="FNanchor_277_277" id="FNanchor_277_277"></a><a href="#Footnote_277_277" class="fnanchor">277</a></span> These animals are all negatively
heliotropic and positively stereotropic, and with these tropisms they
would be forced to enter a cave whenever they are put at the entrance.
Even those among the Amblyopsidæ which live in the open have the
tropisms of the cave dweller. This eliminates the idea that the cave
adapted the animals for the life in the dark.</p>
<p>Only those animals can thrive in caves which for their feeding and
mating do not depend upon visual mechan<span class="pagenum" title="325"><a name="Page_325" id="Page_325"></a></span>isms; and conversely, animals
which are not provided with visual mechanisms can hold their own in the
open, where they meet the competition of animals which can see, only
under exceptional conditions. This seems to account for the fact that
in caves blind species are comparatively more prevalent than in the
open.</p>
<p>In other words, the adaptation of blind animals to the cave is only
apparent; they were adapted to cave life before they entered the cave.
Many animals are obviously burdened with a germinal abnormality giving
rise to imperfection and smallness of the eye—the hereditary factor
involved may have to do with the development of the blood-vessels and
lymphatics of the eye. Such mutants can survive more easily in the
cave, where they do not have to meet the competition of seeing forms,
than in the open. In man also an hereditary form of blindness is known,
the so-called hereditary glaucoma. It has nothing to do with light, but
the disease seems to be due to an hereditary anomaly of the circulation
in the eye.</p>
<p><span class="nowrap">Kammerer<a name="FNanchor_278_278" id="FNanchor_278_278"></a><a href="#Footnote_278_278" class="fnanchor">278</a></span> has recently reported that
by keeping the blind European cave salamander <i class="taxonomic">Proteus anguinus</i> under
certain conditions of illumination he succeeded in producing two
specimens with larger eyes. According to him the eyes of <i class="taxonomic">Proteus</i> may
develop to a certain point and then retrogress again. He states that by
keeping young salamanders alternately for a<span class="pagenum" title="326"><a name="Page_326" id="Page_326"></a></span> week or two in sunlight
and in a dark room where they were exposed to red incandescent light,
two males formed somewhat larger eyes. The first year no alteration
was visible. In the second year a slight increase in the size of the
eyes was noticeable under the skin. In the third year the eye protruded
slightly and this increased somewhat in the fourth year.</p>
<p>There is thus far only one case on record in animal biology in which
the light influences the formation of organs. The writer found that
the regeneration of the polyps of the hydroid <i class="taxonomic">Eudendrium</i> does not
take place if the animals are kept in the dark, while the polyps will
regenerate if exposed to the <span class="nowrap">light;<a name="FNanchor_279_279" id="FNanchor_279_279"></a><a href="#Footnote_279_279" class="fnanchor">279</a></span>
and the time of exposure may be rather short according to <span
class="nowrap">Goldfarb.<a name="FNanchor_280_280" id="FNanchor_280_280"></a><a href="#Footnote_280_280" class="fnanchor">280</a></span> It is possible that <i class="taxonomic">Proteus</i>
resembles in this respect <i class="taxonomic">Eudendrium</i>; it should be stated, however,
that of many different forms tried by the writer over a number of
years, <i class="taxonomic">Eudendrium</i> was the only one which gave evidence of such an
influence of light. Of course it is not impossible that the light might
influence reflexly the development of blood-vessels in the eyes of
certain animals, <i>e. g.</i>, <i class="taxonomic">Proteus</i>, and thus allow the eyes of
<i class="taxonomic">Proteus</i> to grow a little larger.</p>
<p>We therefore come to the conclusion that it is not the cave that made
animals blind but that animals with a hereditary tendency towards a
degeneration of the<span class="pagenum" title="327"><a name="Page_327" id="Page_327"></a></span> eyes can survive in a cave while they can only
exceptionally survive in the open. The cause of the degeneration is a
disturbance in the circulation and nutrition of the eye, which is as a
rule independent of the presence or absence of light.</p>
<p>We may by way of a digression stop for a moment to consider the most
astonishing and uncanny case of adaptation; namely, the formation of
the transparent refractive media, especially the lens in front of the
retina. It is due to these media that the rays which are sent out
by a luminous point can be united to an image point on the retina.
One part of this process is understood; namely, the formation of a
lens. Wherever the optic cup of the embryo is transplanted under the
epithelium the latter will be transformed into a transparent lens.
When the upper edge of the iris is injured in the salamander so that
the cells can multiply, the mass of newly formed cells also becomes
transparent and a lens is formed. This indicates the existence
of a substance in the optic cup which makes the epithelial cells
transparent; and which also limits the size of the lens which is
formed. The lens is not always a perfect optical instrument, on the
contrary, it is as a rule somewhat defective. Of course, a great many
details concerning the process of lens regeneration have still to be
worked out.</p>
<p>3. It is well known that most marine animals die if put into
fresh water and <i lang="la" xml:lang="la">vice versa</i>; and in salt lakes or<span class="pagenum" title="328"><a name="Page_328" id="Page_328"></a></span> ponds with a
concentration of salt so high that most marine animals would succumb
if suddenly transferred to such a solution we have a limited fauna
and flora. The common idea is that marine animals become adapted to
fresh water or <i lang="la" xml:lang="la">vice versa</i>; or to the conditions in salt lakes;
especially if the changes take place gradually. Yet it can be shown
that the existence of these different faunas can be explained without
the assumption of an adaptive effect of the environment. The writer
has worked with a marine fish <i class="taxonomic">Fundulus</i> whose eggs develop naturally
in sea water which, however, will develop just as well in distilled
water; and the young fish hatching in distilled water live and grow in
this medium. Most of the adult fish die after several days, when put
suddenly into distilled water, but they can live in fresh water which
contains only a trace of salt. They can also live in very concentrated
sea water, <i>e. g.</i>, twice the normal concentration. Suppose that a
bay of the ocean containing such fish should suddenly become landlocked
and the concentration of the sea water be thus raised to twice its
natural amount; the majority of forms would die and only <i class="taxonomic">Fundulus</i>
and possibly a few other species with the same degree of resistance
would survive. An investigator examining the salinity of the water
and not knowing the natural resistance of <i class="taxonomic">Fundulus</i> to changes in
concentration would be inclined to assume that he had before him an
instance of a gradual adaptation of the<span class="pagenum" title="329"><a name="Page_329" id="Page_329"></a></span> fish to a higher concentration
of the sea water; whereas the fish was already immune to this high
concentration before coming in contact with it.</p>
<p>This fish seemed a favourable object from which to find out how far
an adaptation to the environment really existed; and the result was
surprising. By changing the concentration of the sea water gradually it
is possible to raise the natural resistance of the fish only a trifle,
not much over ten per cent. The concentration of the natural sea water
is a little over that of a m/2 solution of NaCl+KCl+CaCl<sub>2</sub> in the
proportion in which these three salts exist in the sea water. When
adult <i class="taxonomic">Fundulus</i> are put into a <sup>10</sup>⁄<sub>8</sub> m solution of NaCl+KCl+CaCl<sub>2</sub>
in the proportion in which these salts occur in sea water they die
in less than a day, but when put from sea water directly into a
<sup>8</sup>⁄<sub>8</sub> m or <sup>9</sup>⁄<sub>8</sub> m solution they can live indefinitely. It was <span
class="nowrap">found<a name="FNanchor_281_281" id="FNanchor_281_281"></a><a href="#Footnote_281_281" class="fnanchor">281</a></span> that if the concentration of the
sea water was raised gradually (by m/8 a day) the fish on the fifth
day could resist a <sup>10</sup>⁄<sub>8</sub> m solution of NaCl+KCl+CaCl<sub>2</sub> for a month
(or possibly indefinitely; the experiment was discontinued after
that period). When a <sup>10</sup>⁄<sub>8</sub> m solution was allowed to become more
concentrated slowly by evaporation (at room temperature) all the fish
died rapidly when the concentration was <sup>12</sup>⁄<sub>8</sub> m or even below. In higher
concentrations they can live only a day or two. These experiments show
<span class="pagenum" title="330"><a name="Page_330" id="Page_330"></a></span>that while the fish is naturally immune to a <sup>9</sup>⁄<sub>8</sub> m NaCl+KCl+CaCl<sub>2</sub>
solution, by the method of slowly raising the concentration it may be
made to tolerate a <sup>10</sup>⁄<sub>8</sub> m or <sup>11</sup>⁄<sub>8</sub> m solution, but not more. These fish
when once adapted to a <sup>10</sup>⁄<sub>8</sub> m solution can be put suddenly into a very
weak solution, <i>e. g.</i>, a m/80 NaCl, without suffering and when
brought back into a <sup>10</sup>⁄<sub>8</sub> m solution of NaCl+KCl+CaCl<sub>2</sub> they will
continue to live. If they remain for several days in the weak solution
their power of resistance to <sup>10</sup>⁄<sub>8</sub> m NaCl+KCl+CaCl<sub>2</sub> solution is
weakened.</p>
<p>What change takes place when the fish is made more resistant and why
is its normal resistance so great? The answer based on the writer’s
experiments seems to be as follows: <i class="taxonomic">Fundulus</i> is comparatively
resistant to sudden changes in the concentration of the sea water
between m/80 and <sup>9</sup>⁄<sub>8</sub> m because it possesses a comparatively
impermeable skin whose permeability is not seriously altered by
sudden changes within these limits of concentration; while if these
limits are exceeded and the fish are brought suddenly into too high
a concentration the skin becomes permeable and the fish dies, the
gills becoming unfit for use or nerves being injured by the salt which
diffuses into the fish.</p>
<p>The fact, that by slowly raising the concentration to <sup>10</sup>⁄<sub>8</sub> m the fish
may resist this limit, is in reality no adaptation. There is no sharp
limit between the injurious and non-injurious concentration. We have<span class="pagenum" title="331"><a name="Page_331" id="Page_331"></a></span>
seen that the fish is naturally immune to a <sup>9</sup>⁄<sub>8</sub> m solution. It is also
naturally immune to a <sup>10</sup>⁄<sub>8</sub> m or <sup>11</sup>⁄<sub>8</sub> m solution if we give it time to
compensate the injurious effects of a <sup>10</sup>⁄<sub>8</sub> m solution by the repairing
action of its blood or kidneys. Beyond this no rise is possible. In
reality adaptation does not exist in this case.</p>
<p>In former experiments the writer had shown that a pure NaCl solution
of that concentration in which this fish naturally lives kills it very
rapidly, while it lives in such a solution indefinitely if a little
CaCl<sub>2</sub> is added. The explanation of this fact is that the pure NaCl
solution is able to diffuse into the tissues of the animal while the
addition of a trace of CaCl<sub>2</sub> renders the membrane practically
impermeable to NaCl. The question then arose whether it was possible to
make the fish more resistant to a pure NaCl solution of sufficiently
high concentration and how this could be done. On the basis of the
idea of an adaptive effect of the environment we should expect that
by gradually raising the concentration of a pure NaCl solution the
latter would gradually alter the animal and make it more resistant. The
method of procedure suggested was therefore to put the fish first in
low and gradually into increasing concentrations of NaCl. This method
was tried and found futile for the purpose. <i class="taxonomic">Fundulus</i> when put from
sea water (after having been washed) into a <sup>6</sup>⁄<sub>8</sub> m NaCl solution die in
about four hours. When kept previously in a weaker NaCl solution they
die if anything<span class="pagenum" title="332"><a name="Page_332" id="Page_332"></a></span> more quickly. But it is possible to make them live
longer in a <sup>6</sup>⁄<sub>8</sub> m solution of NaCl; we have to proceed, however, by a
method which is in contrast with the ideas of the adaptive influence
of the environment. When the fish are first treated with sea water
(or with a mixture of NaCl+KCl+CaCl<sub>2</sub>) of a higher concentration so
that they become adapted to a <sup>10</sup>⁄<sub>8</sub> m solution of NaCl+KCl+CaCl<sub>2</sub> or
to <sup>10</sup>⁄<sub>8</sub> m sea water, they become also more resistant to an otherwise
toxic solution of NaCl. Fish taken directly from sea water were killed
in less than four hours when put into a <sup>6</sup>⁄<sub>8</sub> m NaCl solution, while
fish of the same lot previously adapted to <sup>10</sup>⁄<sub>8</sub> m sea water in the
manner described above lived two or three days in a <sup>6</sup>⁄<sub>8</sub> m NaCl <span
class="nowrap">solution.<a name="FNanchor_282_282" id="FNanchor_282_282"></a><a href="#Footnote_282_282" class="fnanchor">282</a></span></p>
<p>It is not impossible that it was the high concentration of calcium
in the <sup>10</sup>⁄<sub>8</sub> m sea water which rendered the fish more immune to a
subsequent treatment with NaCl. We know why a pure NaCl solution kills
them and we also know why the addition of CaCl<sub>2</sub> protects them against
this pernicious effect. It is rather strange that where the conditions
of the experiments are clear we find nothing to indicate an adaptive
effect of the environment.</p>
<p>4. Ehrlich’s work on trypanosomes seems to indicate a remarkable
power of adaptation on the part of organisms to certain poisons. If
the writer understands these experiments correctly they consisted
in infecting<span class="pagenum" title="333"><a name="Page_333" id="Page_333"></a></span> a mouse with a certain strain of trypanosomes, and
treating it with a certain arsenic compound, which inhibited somewhat
the propagation of the parasites but did not kill them all. Four or
five days later trypanosomes from this mouse were transmitted to
another mouse and after twenty-four hours this mouse was treated with
a stronger dose of the same arsenic compound; and this process was
repeated. After the third transmission or later, the trypanosomes can
resist considerably higher doses of the same poison than at first and
this resistance is retained for years. Ehrlich seems to have taken
it for granted that he had succeeded in transforming the surviving
trypanosomes into a type which is permanently more resistant to the
arsenic compound than was the original strain.</p>
<p>The writer is not entirely convinced that in these experiments
a possibility was sufficiently considered which is suggested by
Johannsen’s experiments on the importance of pure lines in work on
heredity. According to this author a strain of trypanosomes taken at
random should, in all likelihood, contain a population consisting of
strains with different degrees of resistance. If a high but not the
maximal concentration of an arsenic compound is repeatedly injected
into the infected mice the weaker populations of trypanosomes are
killed and only the more resistant survive. These of course continue to
retain their resistance if transplanted to hosts of the same species.
According to this<span class="pagenum" title="334"><a name="Page_334" id="Page_334"></a></span> interpretation the arsenic-fast strain may possibly
have existed before the experiments were made, and Ehrlich’s treatment
consisted only in eliminating the less resistant strains.</p>
<p>On the other hand, it has been shown that if an arsenic-fast strain
of trypanosomes is carried through a tsetse fly it loses its
arsenic-fastness. This fact may possibly eliminate the applicability
of the pure line theory to a discussion of the nature of the
arsenic-fastness, but it seems that further experiments are desirable.</p>
<p>5. Dallinger stated that he succeeded in adapting certain protozoans to
a temperature of 70° C. by gradually raising their temperature during
several years. It is desirable that this statement be verified; until
this is done doubts are justified. Schottelius found that colonies of
<i class="taxonomic">Micrococcus prodigiosus</i> when transferred from a temperature of 22°
to that of 38° no longer formed pigment and trimethylamine. After the
cocci had been cultivated for ten or fifteen generations at 38° they
failed to form pigment even when transferred back to 22° C. <span
class="nowrap">Dieudonné<a name="FNanchor_283_283" id="FNanchor_283_283"></a><a href="#Footnote_283_283" class="fnanchor">283</a></span> used <i class="taxonomic">Bacillus fluorescens</i>
for similar purposes. At 22° it forms a fluorescing pigment and
trimethylamine, but not at 35°. By constantly cultivating this bacillus
at 35° Dieudonné found that after the fifteenth generation had been
cultivated at 35° the bacillus produced<span class="pagenum" title="335"><a name="Page_335" id="Page_335"></a></span> pigment and trimethylamine
at 35°. Davenport and <span class="nowrap">Castle<a name="FNanchor_284_284" id="FNanchor_284_284"></a><a href="#Footnote_284_284" class="fnanchor">284</a></span> found
that tadpoles of a frog kept at 15° went into heat rigour at 40.3° C.,
while those kept for twenty-eight days at 25° were not affected by
this temperature but went into heat rigour at 43.5°. When the latter
tadpoles were put back for seventeen days to a temperature of 15°
they had lost their resistance to high temperature partially, but not
completely, since they went into heat rigour at 41.6°. The authors
suggest that this adaptation to a higher temperature is due to a
loss of water on the part of protoplasm, whereby the latter becomes
more resistant to an increase in temperature. This idea was put to
a test by <span class="nowrap">Kryž<a name="FNanchor_285_285" id="FNanchor_285_285"></a><a href="#Footnote_285_285" class="fnanchor">285</a></span>, who found that the
coagulation temperature of their muscle plasm is not altered by keeping
cold-blooded animals at different temperatures.</p>
<p>Loeb and <span class="nowrap">Wasteneys<a name="FNanchor_286_286" id="FNanchor_286_286"></a><a href="#Footnote_286_286" class="fnanchor">286</a></span> found that
<i class="taxonomic">Fundulus</i> taken from a low temperature of 10° C. die in less than two
hours when suddenly transferred to sea water of 29° C.; and in a few
minutes if suddenly transferred to a temperature of 35° C. If, however,
the fish were transferred to a temperature of 27° C. for forty hours
they could live indefinitely in sea water of 35°. By exposing the fish
each day two hours to a gradually rising tem<span class="pagenum" title="336"><a name="Page_336" id="Page_336"></a></span>perature they could render
them resistant to a temperature of 39°. The remarkable fact was that
fish if once made resistant to a high temperature (35°) did not lose
this resistance when kept for four weeks at from 10° to 14° C. Control
fish taken from the same temperature died in from two to four minutes;
immunized fish taken from 10° and put directly to 35° C. lived for many
hours or indefinitely. They will even retain this immunity when kept
for two weeks at a temperature of 0.4° C.</p>
<p>Why is it that an animal can in general resist a high temperature
better if the latter is raised gradually than when it is raised
suddenly? Physics offers us an analogy to this phenomenon in the
experience that glass vessels which burst easily when their temperature
is raised suddenly, remain intact when the temperature is raised
gradually. Glass is a poor conductor of heat and when the temperature
is raised suddenly inside a glass cylinder the inner layer of the
cylinder expands while the outer layer on account of the slowness of
conduction of heat does not expand equally and the cylinder may burst.
We might assume that the sudden increase in temperature brings about
certain changes in the cells (<i>e. g.</i>, an increase in permeability
or destruction of the surface layer?). If the rise of temperature
occurs gradually the blood or lymph or the cell sap may have time to
repair the damage, and this repair seems to be irreversible, at least
for some time, as the<span class="pagenum" title="337"><a name="Page_337" id="Page_337"></a></span> experiments on <i class="taxonomic">Fundulus</i> seem to indicate. If
the temperature rises too rapidly the damage cannot be repaired quickly
enough by the cell or body liquids.</p>
<p>It is also to be considered that substances might be formed in the body
at a higher temperature which do not exist at a lower temperature, and
<i lang="la" xml:lang="la">vice versa</i>, and this might explain results like those of Schottelius
or Dieudonné and many others.</p>
<p>6. The theory of an adapting effect of the environment has often been
linked with the assumption of the inheritance of acquired characters.
The older claims of the hereditary transmission of acquired characters,
such as Brown-Séquard’s epilepsy in guinea pigs after the cutting of
the sciatic nerve, have been shown to be unjustified or have found
a different and more rational explanation. Recently P. Kammerer has
claimed to have proven by new experiments that by environmental
changes, hereditary changes can be produced.</p>
<p>It has been mentioned already that the mature male frogs and toads
possess during the breeding season lumps on the thumbs or arms which
are pigmented and which bear numerous minute horny black spines; these
secondary sexual characters serve the male frog in holding the females
in the water during copulation. There is one species which does not
possess this sexual character, namely the male of the so-called midwife
toad (<i class="taxonomic">Alytes obstetricans</i>). In this species the animals copulate on
land, and it is natural to connect the lack of this secon<span class="pagenum" title="338"><a name="Page_338" id="Page_338"></a></span>dary sexual
character in the male with its different breeding habit. Kammerer
now forced such toads to copulate in water instead of on land (by
keeping the animals in a terrarium with a high temperature). He makes
the statement that by forcing the parents to lay their eggs during
successive spawning periods in water he finally obtained offspring
which under normal temperature conditions lay their eggs naturally
in water; in other words, they have changed their habits. We will
not discuss this part of his statement since the breeding habits of
animals in captivity are liable to be abnormal. But Kammerer makes the
further important <span class="nowrap">statement<a name="FNanchor_287_287" id="FNanchor_287_287"></a><a href="#Footnote_287_287" class="fnanchor">287</a></span> that the
male offspring of such couples will in the third generation produce
the swelling on the thumb and the usual roughness, and in the fourth
generation black pads and hypertrophy of the muscles of the forearm
will appear. In other words, he reports having succeeded in producing
an inheritance of an acquired morphological character which has never
been known to occur in this species. Bateson, on account of the
importance of the case, wished to examine it more closely and I will
quote his report.</p>
<div class="blockquot">
<p>The systematists who have made a special study of <i class="taxonomic">Batrachia</i>
appear to be agreed that <i class="taxonomic">Alytes</i> in nature does not have these
structures; and when individuals possessing them can be produced
for inspection it will, I think, be time<span class="pagenum" title="339"><a name="Page_339" id="Page_339"></a></span> to examine the evidence
for the inheritance of acquired characters more seriously. I wrote
to Dr. Kammerer in July, 1910, asking him for the loan of such
a specimen and on visiting the Biologische Versuchsanstalt in
September of the same year I made the same request, but hitherto
none has been produced. In matters of this kind much generally
depends on interpretations made at the time of observation; here,
however, is an example which could readily be attested by preserved
<span class="nowrap">material.<a name="FNanchor_288_288" id="FNanchor_288_288"></a><a href="#Footnote_288_288" class="fnanchor">288</a></span></p>
</div>
<p>More recently the same author has reported another hereditary
morphological change brought about by outside <span
class="nowrap">conditions.<a name="FNanchor_289_289" id="FNanchor_289_289"></a><a href="#Footnote_289_289" class="fnanchor">289</a></span> A certain salamander
(<i class="taxonomic">Salamandra maculosa</i>) has yellow spots on a generally dark skin.
Kammerer states that if such salamanders are kept on a yellow ground
they become more yellow, not by an extension of the chromatophores
(which would not be surprising) but by actual multiplication and
growth of the yellow pigment cells; while the black skin is inhibited
in its growth. The reverse is true if these salamanders are kept on
black soil; in this case according to Kammerer the growth of the
yellow cells of the skin is inhibited while the black part of the
skin grows. Curiously enough, according to him, these induced changes
are hereditary. Here again we are dealing with the inheritance of an
acquired morphological character. </p>
<p><span class="pagenum" title="340"><a name="Page_340" id="Page_340"></a></span></p>
<p><span class="nowrap">Megusar<a name="FNanchor_290_290" id="FNanchor_290_290"></a><a href="#Footnote_290_290" class="fnanchor">290</a></span> has repeated Kammerer’s
experiments on salamanders but contradicts him by stating that the
colour of the soil has no influence on the colouration of salamanders.
Of course, we know the phenomenon of colour adaptation in which the
animal changes its colour pattern according to the environment. This is
an effect of the retina image on the skin and has been interpreted by
the writer as a case of colour telephotography, for which no physical
explanation has yet been <span class="nowrap">found.<a name="FNanchor_291_291" id="FNanchor_291_291"></a><a href="#Footnote_291_291" class="fnanchor">291</a></span> This
phenomenon, however, does not lead to any hereditary change of colour.</p>
<p>Kammerer makes many statements on the heredity of acquired
modifications of instinct; indeed he claims that an interest in music
on the part of parents produces offspring with musical talent. In such
claims much depends upon the subjective interpretation of the observer.</p>
<p>The writer is not aware that there is at present on record a single
adequate proof of the heredity of an acquired character. We have
records of changes in the offspring by poisoning the germ plasm by
alcohol given to parents—as in Stockard’s well-known experiments—or
by exposing butterflies to extreme temperatures, but in these cases
the germ cells were poisoned or altered by the alcohol or by chemical
compounds produced at very low or very high temperatures. This<span class="pagenum" title="341"><a name="Page_341" id="Page_341"></a></span> is of
course an entirely different thing from stating that by inducing the
midwife toad to lay its eggs in the water the male offspring acquires
the pads and horns of other species of frogs on its thumb; or that by
keeping black salamanders on yellow paper the offspring is more yellow.
Yet if there is an inheritance of acquired characters which can in
any way throw light on the so-called phenomena of adaptation it must
consist in results such as Kammerer claims to have obtained.</p>
<p>While the writer does not decline to accept Ehrlich’s interpretation
of the arsenic-fast strains of trypanosomes or Kammerer’s statements
in regard to the inheritance of acquired character, he feels that more
work should be done before they can be used for our problem.</p>
<p>7. This attitude leaves us in a quandary. The whole animated world is
seemingly a symphony of adaptation. We have mentioned already the eye
with its refractive media so well curved and placed that a more or
less perfect image of the outside objects is focussed exactly on the
retina; and this in spite of the fact that lens and retina develop
independently; we have mentioned and discussed the cases of instincts
or automatic arrangements which are required to perpetuate life—the
attraction of the two sexes and the automatic mechanisms by which sperm
and egg are brought together; the maternal instincts by which the
young are taken care of; and all those adaptations by<span class="pagenum" title="342"><a name="Page_342" id="Page_342"></a></span> which animals
get their food and the suitable conditions of preservation. Can we
understand all these adaptations, without a belief in the heredity
of acquired characters? As a matter of fact the tenacity with which
some authors cling to such a belief is dictated by the idea that
this is the only alternative to the supra-naturalistic or vitalistic
ideas. The writer is of the opinion that we do not need to depend
upon the assumption of the heredity of acquired characters, but that
physiological chemistry is adequate for this purpose.</p>
<p>The earlier writers explained the growth of the legs in the tadpole of
the frog or toad as a case of an adaptation to life on land. We know
through Gudernatsch that the growth of the legs can be produced at
any time even in the youngest tadpole, which is unable to live on the
land, by feeding the animal with the thyroid gland. As we have stated
in Chapter VII, it is quite possible that in nature the legs of the
tadpole begin to grow when enough of the thyroid or a similar compound
has been formed or is circulating in the animal.</p>
<p>It might justly be claimed as a case of adaptation that the egg
attaches itself to the wall of the uterus and calls forth the formation
of the decidua. We have mentioned the observation of Leo Loeb that the
corpus luteum of the ovary gives off a substance to the blood which
alters the tissues in the uterus in such a way that contact with any
foreign body (<i>e. g.</i>, the egg) induces this decidua formation.
Again what appeared<span class="pagenum" title="343"><a name="Page_343" id="Page_343"></a></span> as adaptation when unknown turns out to be a
result of the action of a definite chemical substance circulating in
the body.</p>
<p>It appears as a case of adaptation that the eggs of the majority of
animals cannot develop without a spermatozoön, and yet we can imitate
the activating effect of a spermatozoön on the egg by definite chemical
compounds, which leads to the suggestion that the activating effect of
the spermatozoön on the egg might be due to the fact that it carries
such a compound.</p>
<p>The wonderful adaptations exhibited in the mating instincts seem to be
due to definite substances secreted by the sex glands, as was shown
by Steinach (Chapter VII). Here, again, the process as popularly
conceived, is the reverse of the truth; those survive that have the
equipment,—they did not acquire the equipment under the influence of
environment.</p>
<p>It is absolutely imperative for green plants that their stems and
leaves be exposed to the light since only in this way are they able
to form carbohydrates; and it is equally essential that the roots
should grow into the soil so that the plant may get the nitrates and
phosphates required to build up its proteins and nucleins. This result
is, in the language of adaptationists, brought about by an adaptive
response of the plant to the light. In reality this adaptive response
is due (Chapter X) to the presence of a photosensitive substance
present in almost all green plants.</p>
<p><span class="pagenum" title="344"><a name="Page_344" id="Page_344"></a></span></p>
<p>Lewis has shown that if the optic cup is transplanted under the skin of
a young larva into any part of the body the skin in contact with the
optic cup will form a lens; it looks as if a chemical substance from
the optic cup were responsible for the formation of the lens.</p>
<p>These examples might be multiplied indefinitely. They all indicate that
apparent morphological and instinctive adaptations are merely caused
by chemical substances formed in the organism and that there is no
reason for postulating the inheritance of acquired characters. We must
not forget that there are just as many cases where chemical substances
circulating in the body lead to indifferent or harmful results. As an
example of the first type, we may mention the existence of heliotropism
in animals living in the dark, of the latter type, the inheritance of
deficiencies like colour-blindness or glaucoma.</p>
<p>While it is possible for forms with moderate disharmonies to survive,
those with gross disharmonies cannot exist and we are not reminded
of their possible existence. As a consequence the cases of apparent
adaptation prevail in nature.</p>
<p>The following observation may serve to give an idea how small is
the number of existing or durable forms compared with the number of
forms incapable of existence. We have mentioned the fact observed by
Moenkhouse, the writer, and Newman, that it is possible to fertilize
the eggs of each marine bony fish with the<span class="pagenum" title="345"><a name="Page_345" id="Page_345"></a></span> sperm of practically every
other marine bony fish. The number of teleosts at present in existence
is about ten thousand. If we accomplish all possible hybridizations,
one hundred million different crosses will result. Of these only a
small fraction of one per cent. can live (see Chapter I), and it is
generally the lack of a proper circulation which inhibits them from
reaching maturity. It is, therefore, no exaggeration to state that the
number of species existing today is only an extremely small fraction of
those which can and possibly do originate, but which escape our notice
and disappear because they cannot live or reproduce. If we consider
these facts we realize that the mere laws of chance are adequate to
account for the fact of the apparently purposeful adaptations; as they
are adequate to account for the Mendelian numbers.</p>
<hr class="chap" />
<p><span class="pagenum" title="346"><a name="Page_346" id="Page_346"></a></span></p>
<h2>CHAPTER XIII</h2>
<h3>EVOLUTION</h3>
<p>Darwin’s work has been compared to that of Copernicus and Galileo
inasmuch as all these men freed the mind from the incubus of
Aristotelian philosophy which, with the efficient co-operation of the
church and the predatory system of economics, caused the stagnation,
squalor, immorality, and misery of the Middle Ages. Copernicus and
Galileo were the first to deliver the intellect from the idea of
a universe created for the purpose of man; and Darwin rendered a
similar service by his insistence that accidental and not purposeful
variations gave rise to the variety of organisms. In this struggle for
intellectual freedom the names of Huxley and Haeckel must be gratefully
remembered, since without them Darwin’s idea would not have conquered
humanity.</p>
<p>Darwin assumed that the small fluctuating variations could accumulate
to larger variations and thus cause new forms to originate.</p>
<p><span class="pagenum" title="347"><a name="Page_347" id="Page_347"></a></span></p>
<p>It was the merit of de <span class="nowrap">Vries<a name="FNanchor_292_292" id="FNanchor_292_292"></a><a href="#Footnote_292_292" class="fnanchor">292</a></span> to have
pointed out that fluctuating variations are not hereditary and hence
could not have played the rôle assigned to them by Darwin, while
discontinuous variations as they appear in the so-called “sports” or
mutations are inherited. This was an important step in the history of
the theory of evolution. It did not touch the foundation of Darwin’s
work, namely the substitution of the idea of an accidental evolution
for that of a purposeful creation; it only modified the conception of
the possible mechanism of evolution. According to de Vries, there are
special species or groups of species which are in a state of mutation.
He considers the evening primrose on which he made his observations
as one of these forms. Morgan and his pupils have observed over 130
mutations in a fly <i class="taxonomic">Drosophila</i>. From our present limited knowledge we
must admit the possibility that the tendency toward the production of
mutants is not equally strong in different forms. Whether this part
of de Vries’s idea is or is not correct there can be no doubt that
variations occur which consist in the loss and apparently, though in
rarer cases, in the gain or a modification of a Mendelian factor. If we
wish to visualize the basis of such a change we may do so by imagining
well-defined chemical constituents in one or more of the chromomeres
undergoing a chemical change. </p>
<p><span class="pagenum" title="348"><a name="Page_348" id="Page_348"></a></span></p>
<p>This way of looking at the origin of variation has had the effect of
putting an end to the vague speculations concerning the evolution of
one form from another. We demand today the experimental test when such
a statement is made and as a consequence the amount of mere speculation
in this field has diminished considerably.</p>
<p>It is possible that any further progress concerning evolution must come
by experimental attempts to bring about at will definite mutations.
Such attempts have been reported but they are not all beyond the
possibility of <span class="nowrap">error.<a name="FNanchor_293_293" id="FNanchor_293_293"></a><a href="#Footnote_293_293" class="fnanchor">293</a></span> The most
remarkable among them are those by Tower who by a very complicated
combination of effects of temperature and moisture claims to have
produced definite mutations in the potato beetle. The conditions for
these experiments are so expensive and complicated that a repetition by
other investigators has not yet been possible.</p>
<p>It is, however, still uncertain whether the mere addition or loss of
Mendelian characters can lead to the origin of new species. Species
specificity is determined by specific proteins (Chapter III.), while
some Mendelian characters at least seem to be determined by hormones or
substances which need neither be proteins nor specific for the species.</p>
<hr class="chap" />
<p><span class="pagenum" title="349"><a name="Page_349" id="Page_349"></a></span></p>
<h2>CHAPTER XIV</h2>
<h3>DEATH AND DISSOLUTION OF THE ORGANISM</h3>
<p>1. It is an old saying that we cannot understand life unless we
understand death. The dead body, if its temperature is not too low
and if it contains enough water, undergoes rapid disintegration. It
was natural to argue that life is that which resists this tendency to
disintegration. The older observers thought that the forces of nature
determined the decay, while the vital force resisted it. This idea
found its tersest expression in the definition of Bichat, that “life
is the sum total of the forces which resist death.” Science is not the
field of definitions, but of prediction and control. The problem is:
first, how does it happen that as soon as respiration has ceased only
for a few minutes the human body is dead, that is to say, will commence
to undergo disintegration, and second, what protects the body against
this decay while the respiration goes on, although temperature and
moisture are such as to favour decay?</p>
<p>The earlier biologists had already raised the question<span class="pagenum" title="350"><a name="Page_350" id="Page_350"></a></span> why it was that
the stomach and intestine did not digest themselves. The hydrochloric
acid and the pepsin in the stomach and the trypsin in the intestine
digest proteins taken in in the form of food; why do they not digest
the proteins of the cells of the stomach and the intestine? They will
promptly digest the stomach as soon as the individual is dead, but
not during life. A self-digestion may also be caused if the arteries
of the stomach are ligatured. Claude Bernard and others suggested
that the layer of mucus protected the cells of the stomach and of the
intestine from the digestive enzymes; or that the epithelial layer
had a protective effect. Pavy suggested that the alkali of the blood
had a protective action. All these theories became untenable when
Fermi showed that all kinds of living organisms, protozoans, worms,
arthropods, are not digested in solutions of trypsin as long as they
are alive, while they are promptly digested in the same solution when
<span class="nowrap">dead.<a name="FNanchor_294_294" id="FNanchor_294_294"></a><a href="#Footnote_294_294" class="fnanchor">294</a></span> This is in harmony with the fact
that many parasites live in the intestine without being digested as
long as they are alive. Fermi concluded that the living cell cannot be
attacked by the digestive ferments, while with death a change occurs
by which they can be attacked. But what is this change? Fermi seems
to be inclined to think that the “living molecule” of protein is not
hydrolysable (perhaps because the enzyme cannot attach itself to it?),<span class="pagenum" title="351"><a name="Page_351" id="Page_351"></a></span>
while a change in the constitution or configuration of the proteins
takes place after respiration has ceased. The fact that the living
cell resists the digestive action of trypsin and pepsin has found two
other modes of explanation, first, that the cells are surrounded by
a membrane or envelope through which the enzyme cannot diffuse, and
second, that the living cells possess antiferments. But the so-called
antiferments are also said to exist after the death of the cell,
whereas after death the cell is promptly digested. Frédéricq, as well
as Klug, has shown that worms which are not attacked by trypsin are
digested by this enzyme when they are cut into small pieces; although
the pieces of course contain the antienzyme. The other suggestion that
a membrane impermeable for trypsin protects the cells would explain why
living protozoa are not digested by trypsin, but it leaves another fact
unexplained, namely, the autodigestion of all the cells after death by
enzymes contained in the cells themselves.</p>
<p>2. The disintegration of the body after death is not caused exclusively
or even chiefly by the digestive enzymes of the intestinal tract or the
micro-organisms entering the dead body from the outside, but by the
enzymes contained in the cells themselves. This phenomenon of <span
class="nowrap">autolysis<a name="FNanchor_295_295" id="FNanchor_295_295"></a><a href="#Footnote_295_295" class="fnanchor">295</a></span> was first characterized by <span class="pagenum" title="352"><a name="Page_352" id="Page_352"></a></span><span
class="nowrap">Hoppe-Seyler.<a name="FNanchor_296_296" id="FNanchor_296_296"></a><a href="#Footnote_296_296" class="fnanchor">296</a></span></p>
<div class="blockquot">
<p>All organs suffering death within the organism, in the absence of
oxygen, undergo softening and dissolution in a manner resembling
that of putrefaction. In the course of that process, albuminous
matter gives rise to leucin and tyrosin, fat to free acids and
soaps. This maceration, identical with the pathological conception
of softening, is accomplished without giving rise to ill odour and
is a process similar to the one resulting from the action of water,
acids, and digestive enzymes.</p>
</div>
<p>In work of this kind, rigid asepsis is required to exclude the
possibility of bacterial infection and this was first done by
Salkowski, who showed that in aseptically kept tissues like liver and
muscle the amount of substances that can be extracted with hot water
increases considerably. By the work of others, especially Martin Jacoby
and Levene, it was established that the power of self-digestion is
shared by all organs. Analysis of the products of the autodigestion of
tissues shows that, <i>e. g.</i>, the amino acids, which constitute
the proteins, are produced. Dakin, Jones, and Levene demonstrated the
hydrolytic products of the nucleins, in the case of the self-digestion
of <span class="nowrap">tissues.<a name="FNanchor_297_297" id="FNanchor_297_297"></a><a href="#Footnote_297_297" class="fnanchor">297</a></span></p>
<p>Again the question arises: Why do the tissues not undergo autolysis
during lifetime and what protects them, and the answer is that
self-digestion is a consequence of the lack of oxidations. The
presence of antiferments must continue after death and cannot
be the cause which prevents the self-digestion during<span class="pagenum" title="353"><a name="Page_353" id="Page_353"></a></span> life,
since nothing indicates the destruction of the hypothetical
antidigestive enzymes through lack of oxygen. The recent work of
Bradley and <span class="nowrap">Morse<a name="FNanchor_298_298" id="FNanchor_298_298"></a><a href="#Footnote_298_298" class="fnanchor">298</a></span> and of <span
class="nowrap">Bradley<a name="FNanchor_299_299" id="FNanchor_299_299"></a><a href="#Footnote_299_299" class="fnanchor">299</a></span> has thrown some light on the
problem. These authors found that proteins of the liver which are
indigestible can be made digestible by the liver enzymes if an acid
salt or a trace of acid is added to the mixture. A m/200 HCl solution
gives marked acceleration of the autodigestion of the liver. This would
explain why autodigestion takes place after oxidations cease. In many
if not all the cells, acids are constantly formed during lifetime,
<i>e. g.</i>, lactic acid, which through oxidation are turned to CO<sub>2</sub>,
and this diffuses into the blood so that the H ion concentration in
the cells does not rise materially. If, however, the oxidations cease,
as is the case after death, the formation of lactic acid continues,
but the acid is not oxidized to CO<sub>2</sub> and thus removed, and as a
consequence the H ion concentration increases in the cells and the
self-digestion of proteins, which the digestive enzymes contained in
the cells themselves could not attack formerly, becomes possible. Acid
increases the digestibility of a protein, probably by salt formation.
Theoretically we should not be surprised that while in the liver an
increase in the C<sub>H</sub> favours autolysis in other tissues the
same result is produced by the reverse effect. We<span class="pagenum" title="354"><a name="Page_354" id="Page_354"></a></span> might say that the
preservation of a certain C<sub>H</sub> probably at or near the point
of neutrality during life prevents self-digestion, while the gross
alteration of the C<sub>H</sub> in either direction after death (or
after the cessation of oxidations in the tissues) induces autolysis.
Bradley indeed suggests that many of the phenomena of autolysis during
lifetime, such as atrophy, necrosis, involution, might be due to an
increase in the C<sub>H</sub> in the tissues.</p>
<p>These facts agree with the suggestion of Fermi that in the living
cell the proteins cannot be attacked by the digestive enzymes but
relieves us of the necessity of making the monstrous assumption of
a “living molecule” of proteins as distinct from a “dead” molecule.
The difference between life and death is not one between living and
dead molecules, but more likely between the excess of synthetic over
hydrolytic processes.</p>
<p>In the second chapter we mentioned the interesting idea of
Armstrong that when a synthesis is brought about by a digestive
enzyme (<i>e. g.</i>, maltase) not the original substrate is formed
(<i>e. g.</i>, maltose) but an isomer, in this case isomaltose; and
this isomer is not attacked by the enzyme maltase. We thus get a
rational understanding of the statement which Claude Bernard used to
make but which remained at his time mysterious: <i>la vie, c’est la
création</i>. During life, when nutritive material is abundant, through
the<span class="pagenum" title="355"><a name="Page_355" id="Page_355"></a></span> reversible action of certain enzymes, synthetic compounds
are formed from the building stones furnished by the blood. These
synthetic isomers cannot be hydrolyzed by the enzymes by which they
are formed and hence on account of the isomeric structure are immune
against destruction. It is not impossible that the increase of the
concentration of acid in the cells after death transforms the isomers
into that form in which they can be digested by the enzymes contained
in the cell. Another possibility is that the increase in digestibility
brought about by an increase in C<sub>H</sub> in the cell is due to
the hydrating effect of acids on proteins with a subsequent increase
in digestibility. Whatever the answer may be, the work done since
Claude Bernard has removed that cloud of obscurity which in his days
surrounded the prevalence of synthetic action in the living and of
disintegration in the dead tissues.</p>
<p>3. We have already referred to the connection between the lack of
oxygen and the onset of autolysis and disintegration of tissues
in the body. It is of interest that there are cells in which the
disintegration under the influence of lack of oxygen is so rapid that
it can be followed under the microscope. The writer has observed
that certain cells undergo complete irreversible dissolution in a
very short time under the influence of lack of oxygen, <i>e. g.</i>,
the first segmentation cells of the egg of a teleost fish <span
class="nowrap"><i class="taxonomic">Ctenolabrus</i>.<a name="FNanchor_300_300" id="FNanchor_300_300"></a><a href="#Footnote_300_300" class="fnanchor">300</a></span> </p>
<p><span class="pagenum" title="356"><a name="Page_356" id="Page_356"></a></span></p>
<div class="blockquot">
<table class="figrt" summary="figures 48-51">
<tr class="vat"><td><div class="figcenter" style="width: 140px; padding-top: 8px;">
<img src="images/fig_048.png" width="140" height="136" alt="" />
<p class="tac"><span class="smcap">Fig. 48</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 110px;">
<img src="images/fig_049.png" width="110" height="144" alt="" />
<p class="tac"><span class="smcap">Fig. 49</span></p>
</div></td></tr>
<tr class="vat"><td><div class="figcenter" style="width: 95px;">
<img src="images/fig_050.png" width="95" height="128" alt="" />
<p class="tac"><span class="smcap">Fig. 50</span></p>
</div></td>
<td>   </td>
<td><div class="figcenter" style="width: 115px; padding-top: 51px;">
<img src="images/fig_051.png" width="115" height="77" alt="" />
<p class="tac"><span class="smcap">Fig. 51</span></p>
</div></td></tr>
</table>
<p>When these eggs are deprived of oxygen at the time they reach the
eight- or sixteen-cell stage, it can be noticed that the membranes
of the blastomeres are transformed into small droplets within half
an hour or more, according to the temperature. These droplets
begin to flow together, forming larger drops. [Figures 48 to 51
show the successive stages of this process.] When the eggs are
exposed to the air in time, segmentation can begin again; but if
a slightly longer time is allowed to elapse, the process becomes
irreversible and life becomes extinct. Such clear structural
changes cannot often be observed in the eggs of other animals under
the same conditions. Are these changes of structure (apparently
liquefaction of solid elements) responsible for death under such
conditions? In order to obtain an answer to this question, the
writer investigated the<span class="pagenum" title="357"><a name="Page_357" id="Page_357"></a></span> effect of the lack of oxygen upon the
heart-beat of the embryo of the same fish <i class="taxonomic">Ctenolabrus</i>. This egg
is perfectly transparent and the heart-beat can easily be watched.
When these eggs are put into an Engelmann gas chamber and a current
of pure hydrogen is sent through, the heart may cease to beat in
fifteen or twenty minutes; it stops beating suddenly, before the
number of heart-beats has diminished noticeably, and ceases beating
before all the free oxygen can have had time to diffuse from the
egg. In one case the heart beat ninety times per minute before
the hydrogen was sent through; four minutes after the current
of hydrogen had passed through the gas chamber, the rate of the
heart-beat was eighty-seven per minute, three minutes later it was
seventy-seven, and then the beats stopped suddenly. It is hard
to believe that this cessation could have been caused by lack of
energy. Hydrolytic processes alone could furnish sufficient energy
to maintain the heart-beat for some time, even if all the oxygen
had been used up. The suddenness of the standstill at a time when
the rate had hardly diminished seems to be more easily explained by
a sudden collapse of the machine; it might be that liquefaction or
some other change of structure occurs in the heart or its ganglion
cells, comparable to that which we mentioned before. In another
fish <i class="taxonomic">Fundulus</i>, where the cleavage cells undergo no visible
changes in the case of lack of oxygen, the heart of the embryo can
continue to beat for about twelve hours in a current of hydrogen.
In this case the rate of the heart-beat sinks during the first hour
in the hydrogen current from about one hundred to twenty or ten
per minute; then it continues to beat at this rate for ten hours
or more. In this case one might believe that during the period of
steady diminution of the tension of oxygen in the heart (during the
first hour), the heart-beat sinks steadily while it keeps up at a
low but steady rate as long as the energy for the<span class="pagenum" title="358"><a name="Page_358" id="Page_358"></a></span> beat is supplied
solely by hydrolytic processes; but there is certainly no change in
the physical structure of the cells noticeable in <i class="taxonomic">Fundulus</i>, and
consequently there is no sudden standstill of the heart.</p>
<p>Budgett has observed that in many infusorians visible
changes of structure occur in the case of lack of <span
class="nowrap">oxygen<a name="FNanchor_301_301" id="FNanchor_301_301"></a><a href="#Footnote_301_301" class="fnanchor">301</a></span>; as a rule the membrane of the
infusorian bursts or breaks at one point, whereby the liquid
contents flow out. Hardesty and the writer found that Paramœcium
becomes more strongly vacuolized when deprived of oxygen, and at
last bursts. Amœbæ likewise become vacuolized and burst under
these conditions. Budgett found that a number of poisons, such
as potassium cyanide, morphine, quinine, antipyrine, nicotine,
and atropine, produce structural changes of the same character as
those described for lack of oxygen. As far as KCN is concerned,
Schoenbein had already observed that it retards the oxidation
in the tissues, and Claude Bernard and Geppert confirmed this
observation. For the alkaloids, W. S. Young has shown that they
are capable of retarding certain processes of autoxidation. This
accounts for the fact that the above-mentioned poisons produce
changes similar to those observed in the case of lack of <span
class="nowrap">oxygen.<a name="FNanchor_302_302" id="FNanchor_302_302"></a><a href="#Footnote_302_302" class="fnanchor">302</a></span></p>
</div>
<p>The phenomenon of rapid disintegration when deprived of oxygen
(or in the presence of KCN) seems to be general as <span
class="nowrap">Child<a name="FNanchor_303_303" id="FNanchor_303_303"></a><a href="#Footnote_303_303" class="fnanchor">303</a></span> has shown in extensive experiments.
Child has used it to show that younger animals disintegrate more
rapidly than older or larger ones, and he uses this fact for a theory
of senescence. He connects<span class="pagenum" title="359"><a name="Page_359" id="Page_359"></a></span> the more rapid disintegration of the young
animal with a greater <span class="nowrap">metabolism.<a name="FNanchor_304_304" id="FNanchor_304_304"></a><a href="#Footnote_304_304" class="fnanchor">304</a></span>
Without wishing to doubt Child’s interesting observations the writer
is not quite certain whether the more rapid disintegration of the
younger forms is not a result of the fact that the walls of membranes
in the young are softer than those of the older animals, and hence
are more readily liquefied. Such a difference could be due to mere
chemical constitution, <i>e. g.</i>, the increase in Ca in the membrane
with the increase in age. In old age in man the deposit of Ca in the
blood-vessels is a frequent occurrence.</p>
<p>These facts may help us to understand the nature of death and
dissolution of the body in higher animals. Death in these animals is
due to cessation of oxidations, but the surprising fact is that if
the oxidations have been interrupted but a few minutes life cannot
be restored even by artificial respiration. This suggests that the
respiratory ganglia in the medulla oblongata suffer an irreparable
injury or an irreversible change (comparable to that just described in
the cells of <i class="taxonomic">Ctenolabrus</i>) even when deprived of oxygen for only a
short time. As a consequence of the irreversible injury to the medulla
the respirations cease permanently, the<span class="pagenum" title="360"><a name="Page_360" id="Page_360"></a></span> heart-beat must also cease,
and gradually the different tissues must undergo the dissolution
characteristic of death. While all the cells may be immortal they are
only so in the presence of oxygen and the nutritive solution which the
circulating blood furnishes. With the proper supply of oxygen cut off
they can no longer live.</p>
<p>4. It is an unquestionable fact that each form has a quite definite
duration of life. Unicellular organisms are immortal; but for the
higher organisms with sexual reproduction the duration of life is
almost as characteristic as any morphological peculiarity of a species.
No species can exist unless the natural life of its individuals
outlasts the period of sexual maturity; and unless the average duration
of life is long enough to allow as many offspring to be brought into
the world as will compensate for loss by death. The male bee dies
before it is a year old, while the queen may live several years. In
a certain species of butterflies, the Psychidæ, the parthenogenetic
female lays its eggs while still in the cocoon and then dies without
ever leaving the cocoon. The imago of the ephemera leaves the water
in the evening, copulates, lets its eggs fall into the water, and is
dead the next morning. The imperfect condition of their mandibles and
alimentary canal makes them unfit for a long duration of life. The
males of the rotifers which are devoid of organs of digestion live but
a few days.</p>
<p><span class="pagenum" title="361"><a name="Page_361" id="Page_361"></a></span></p>
<p>In the Zoölogical Station at Naples in 1906, an actinian, <i class="taxonomic">Actinia
equina</i>, was alive after having been in captivity fifteen years, and
another one, <i class="taxonomic">Cerianthus</i>, had been observed for twenty-four years.
Korschelt kept earthworms for as long as ten years. The fresh-water
mussel may reach the age of sixty years or more and crayfish may live
for over twenty years. The differences in the duration of life of
mammals are too well known to need discussion. If the cells and tissues
are immortal, how does it happen that the duration of life is so
characteristic for each species?</p>
<p><span class="nowrap">Metchnikoff<a name="FNanchor_305_305" id="FNanchor_305_305"></a><a href="#Footnote_305_305" class="fnanchor">305</a></span> has recently investigated
the cause of “natural” death in the butterfly of the silkworm. The
butterfly in this species lacks the organs necessary for taking up
food, like the male rotifer or the ephemeridæ and hence is already, by
this fact, condemned to a short life. Metchnikoff observed that these
butterflies could live twenty-three days, but the average duration of
life was 15.6 for the males and 16.6 days for the females; and that
seventy-five per cent. of them contained no parasitic fauna or flora in
their intestine. They lose considerably in weight during their lives,
but the males still contain the fat body at the time of death. None of
the changes accompanying “old age” in man are found in the tissues of
these butterflies before death. Metchnikoff is inclined to believe that
the animal is poisoned by some excretion retained in<span class="pagenum" title="362"><a name="Page_362" id="Page_362"></a></span> the body; namely,
the urine, and that this poison also causes the symptoms of weakness
which characterize the animal. He could prove the toxic character of
their urine on other animals. This combined with starvation could
sufficiently account for the short duration of life. The facts of the
case show that it is due to an imperfection in the construction of the
organism such as one would expect to find more or less in each animal
if one discards the idea of purposefulness and divine wisdom in nature.
Only a slight, perhaps an infinitesimal, fraction, of those species
which are theoretically possible and which at one time or another arise
can survive. Those which are durable show all transitions from the
grossest disharmonies to an apparent lack of such shortcomings.</p>
<p>5. Minot had tried to prove that the death of metazoa is due to the
greater differentiation and specialization of their tissues. Admitting
the immortality of the unicellular organisms he argues that death is
the price metazoa pay for the higher differentiation of their cells.
This is of course purely metaphorical, but we may put it into a form in
which it is capable of discussion in physicochemical terms, by assuming
that death is a necessary stage in the development of a species. We
are inclined, however, to follow Metchnikoff and suspect some poison
accidentally or unavoidably formed in the body or some structural
shortcoming as the cause of “natural” death.</p>
<p><span class="pagenum" title="363"><a name="Page_363" id="Page_363"></a></span></p>
<p>An unusually favourable object for the study of natural death is the
animal egg. The egg of the starfish <i class="taxonomic">Asterias forbesii</i> when taken out
of the body is usually immature, but in the spawning season it ripens
in sea water. The <span class="nowrap">writer<a name="FNanchor_306_306" id="FNanchor_306_306"></a><a href="#Footnote_306_306" class="fnanchor">306</a></span> observed that
eggs which ripen disintegrate very rapidly when not fertilized. This
disintegration may be due to a process of autolysis, which sets in
only after the egg has extruded the two polar bodies. The writer found
that by preventing the maturation of the egg either by withdrawing the
oxygen or by replacing the alkaline sea water by a neutral solution
or by exposing the eggs for some time to acidulated sea water, the
disintegration could also be prevented.</p>
<p>Further experiments showed that even in the mature egg rapid
disintegration could be prevented by lack of oxygen, and similar
results were obtained by Mathews. When the egg is fertilized it does
not disintegrate in the presence of oxygen but it gradually dies in
the absence of oxygen. One is almost tempted to say that while the
fertilized egg is a strict aërobe the mature unfertilized egg is an
anaërobe. This latter statement, however, becomes doubtful since the
presence of oxygen may help the disintegration only indirectly by
allowing certain changes to go on in the egg. The important points
for us are that duration of life in the mature unfertilized egg is
comparatively<span class="pagenum" title="364"><a name="Page_364" id="Page_364"></a></span> short and that the entrance of a spermatozoön or the
process of artificial parthenogenesis saves the life of the egg. Loeb
and Lewis found that the life of the unfertilized sea-urchin egg (which
is usually mature when removed from the ovaries) can also be prolonged
when its oxidations are suppressed. The decay of the unfertilized egg
seems to be due to the fact that those alterations in the cortical
layer which underlie the membrane formation and which are responsible
for the starting of development gradually take place. In such a
condition the egg will die quickly unless deprived of oxygen. This view
is supported by the observation of Wasteneys that unfertilized eggs of
<i class="taxonomic">Arbacia</i> show an increased rate of oxidations when allowed to remain
for some time in sea water; we have seen in Chapter V that such an
increase also accompanies artificial membrane formation.</p>
<p>6. If the limited duration of life of an organism is determined by
one or more definite harmful chemical processes, we should expect to
find a temperature coefficient for the duration of life or at least be
able to show that if all other conditions are the same the duration
of life is for a given organism a function of temperature. The <span
class="nowrap">writer<a name="FNanchor_307_307" id="FNanchor_307_307"></a><a href="#Footnote_307_307" class="fnanchor">307</a></span> investigated the duration of life of
fertilized and unfertilized eggs of <i class="taxonomic">Strongylocentrotus purpuratus</i> for
the upper temperature limits. </p>
<p><span class="pagenum" title="365"><a name="Page_365" id="Page_365"></a></span></p>
<p class="tac">TABLE XX</p>
<table summary="Life span of Strongylocentrotus larvae at various temperatures">
<tr><th class="btr" rowspan="2"><i>Temperature</i></th><th class="btl" colspan="4">Duration of life of the eggs of <i>S. purpuratus</i></th></tr>
<tr><td class="tac btl pall" colspan="2"><i>Unfertilized</i></td><td class="tac btl pall" colspan="2"><i>Fertilized</i></td></tr>
<tr><td class="tac btr ptb03">°C.</td><td class="tac btl ptb03" colspan="2"><i>Minutes</i></td><td class="tac btl ptb03" colspan="2"><i>Minutes</i></td></tr>
<tr><td class="tac br pb06" rowspan="2">32</td><td class="tar pl17" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 1<sup>1</sup>⁄<sub>6</sub></td><td class="tar bl"></td><td class="tal pb06" rowspan="2"> 1<sup>1</sup>⁄<sub>2</sub></td></tr>
<tr><td class="tal pb06"> < 2</td><td class="tar bl pb06"></td></tr>
<tr><td class="tac br pb06" rowspan="2">31</td><td class="tar" colspan="2"></td><td class="tar bl pl16" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 2<sup>1</sup>⁄<sub>4</sub></td></tr>
<tr><td class="tar"></td><td class="tar"></td><td class="tal pb06"> < 3</td></tr>
<tr><td class="tac br pb06" rowspan="2">30</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 3 </td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 4</td></tr>
<tr><td class="tal pb06"> < 5 </td><td class="tal pb06"> < 5</td></tr>
<tr><td class="tac br pb06" rowspan="2">29</td><td class="tar" colspan="2"></td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 6</td></tr>
<tr><td class="tar"></td><td class="tar"></td><td class="tal pb06"> < 7</td></tr>
<tr><td class="tac br pb06" rowspan="2">28</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 8 </td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 11</td></tr>
<tr><td class="tal pb06"> < 10 </td><td class="tal pb06"> < 13</td></tr>
<tr><td class="tac br pb06" rowspan="2">27</td><td class="tac pb06" rowspan="2" colspan="2">about 18</td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 20</td></tr>
<tr><td class="tal pb06"> < 22</td></tr>
<tr><td class="tac br pb06" rowspan="2">26</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 35 </td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 35</td></tr>
<tr><td class="tal pb06"> < 40 </td><td class="tal pb06"> < 40</td></tr>
<tr><td class="tac br pb06" rowspan="2">25</td><td class="tar" colspan="2"></td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal"> > 76</td></tr>
<tr><td class="tar"></td><td class="tar"></td><td class="tal pb06"> < 81</td></tr>
<tr><td class="tac br pb06" rowspan="2">24</td><td class="tar" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal" >> 168 </td><td class="tar bl" rowspan="2"><img src="images/30x6brkl.png" width="6" height="30" style="padding-bottom: 4px;" alt="curly bracket" /></td><td class="tal">> 192</td></tr>
<tr><td class="tal pb06">< 200 </td><td class="tal pb06">< 209</td></tr>
<tr><td class="tac br"></td><td class="tar"></td><td class="tar"></td><td class="tac bl pb06" colspan="2"><i>Hours</i></td></tr>
<tr><td class="tac br pb06">22</td><td class="tar" colspan="2"></td><td class="tar bl"></td><td class="tal pb06"> 10<sup>1</sup>⁄<sub>5</sub></td></tr>
<tr><td class="tac br pb06">21</td><td class="tar" colspan="2"></td><td class="tar bl"></td><td class="tal pb06"> 24</td></tr>
<tr><td class="tac bbr pb03">20</td><td class="tar bbl" colspan="2"></td><td class="tar bbl"></td><td class="tal bb pb03"> 72</td></tr>
</table>
<p>These observations show a very high temperature coefficient near the
upper temperature limit, and this<span class="pagenum" title="366"><a name="Page_366" id="Page_366"></a></span> may account at least partly for the
fact that in tropical seas the pelagic fauna is so much more limited
than in polar <span class="nowrap">seas.<a name="FNanchor_308_308" id="FNanchor_308_308"></a><a href="#Footnote_308_308" class="fnanchor">308</a></span> It is quite
probable that the high temperature coefficients at the utmost limits
are only an expression of the coagulation time of certain proteins.</p>
<p>P. and N. Rau state that in the cold certain butterflies live longer,
and similar statements exist for the silkworm, but these statements are
not based on exact experiments, which are difficult. Dr. Northrop and
the writer have started experiments on the influence of temperature on
the duration of life of the fly <i class="taxonomic">Drosophila</i>. Newly hatched flies were
kept first without food except water and air at 34°, 28°, 24°, 19°,
14°, and 10°, and second with cane sugar. The average duration of life
was as follows:</p>
<table summary="Influence of temperature and sugar feeding on life span of Drosophila flies">
<tr><td class="tal"></td><td class="tac prl10"><i>With water</i></td><td class="tac">days</td><td class="tac prl10"><i>With cane sugar</i></td><td class="tac">days</td></tr>
<tr><td class="tal">34°</td><td class="tar ls05">.......</td><td class="tar pr03">2.1</td><td class="tar ls05">..........</td><td class="tar pr03">6.2</td></tr>
<tr><td class="tal">28°</td><td class="tar ls05">.......</td><td class="tar pr03">2.4</td><td class="tar ls05">..........</td><td class="tar pr03">7.2</td></tr>
<tr><td class="tal">24°</td><td class="tar ls05">.......</td><td class="tar pr03">2.4</td><td class="tar ls05">..........</td><td class="tar pr03">9.4</td></tr>
<tr><td class="tal">19°</td><td class="tar ls05">.......</td><td class="tar pr03">4.1</td><td class="tar ls05">..........</td><td class="tar pr03">12.3</td></tr>
<tr><td class="tal">14°</td><td class="tar ls05">.......</td><td class="tar pr03">8.3</td><td class="tac"></td><td class="tar"></td></tr>
<tr><td class="tal">10°</td><td class="tar ls05">.......</td><td class="tar pr03">11.9</td><td class="tac"></td><td class="tar"></td></tr>
</table>
<p><span class="pagenum" title="367"><a name="Page_367" id="Page_367"></a></span></p>
<p>These experiments show that there is a definite temperature coefficient
for the duration of life and that this coefficient is of the order
of magnitude of that of a chemical reaction. We are continuing these
experiments with animals in the presence of food. It should, however,
be remembered that the fly carries with it a good deal of reserve
material from the larval period. We have carried on simultaneously
determinations of the temperature coefficients of the duration of the
larval and pupa stage of these organisms at the same temperatures and
found ratios similar to those given above for the duration of life with
water only.</p>
<p>7. <span class="nowrap">Metchnikoff<a name="FNanchor_309_309" id="FNanchor_309_309"></a><a href="#Footnote_309_309" class="fnanchor">309</a></span> has furnished
the scientific facts for our understanding of senescence. He has
demonstrated that the changes in tissue which give rise to phenomena
of senility are due to the action of phagocytes. Thus the ganglion
cells are altered (digested?) and destroyed by “neuronophags” and
this is the main cause of mental senility. Definite phagocytic cells,
the osteoclasts, slowly dissolve the bones (by the excretion of an
acid?) and this leads to the known fragility of the bones in old age.
The whiteness of the hair is due to the action of phagocytes; in the
muscles in old age the contractile elements are destroyed by the
sarcoplasm, and so on. It agrees with these facts that where organs are
absorbed in the embryonic development of an animal, as <i>e. g.</i>,
the tail of the tad<span class="pagenum" title="368"><a name="Page_368" id="Page_368"></a></span>pole in metamorphosis, the phenomenon is due to a
process of phagocytosis (and autolysis). We have mentioned the fact
that in the larva of the <i class="taxonomic">Amblystoma</i> the absorption of the gills
and of the tail occurs simultaneously and that both must be caused
by a constituent of the blood. Such a constituent may be responsible
for phagocytosis and autolysis in the organs undergoing absorption.
Metchnikoff calls attention to the fact that certain infectious
diseases, <i>e. g.</i>, syphilis, may bring about precocious senility;
and he mentions also the senile appearance of young cretins which
is due to the diseased thyroid. “It is no mere analogy to suppose
that human senescence is the result of a slow but chronic poisoning
of the organism.” He assumes that in man this poisoning is caused
by the products of fermentation in the large intestine and that the
micro-organisms responsible for these fermentations may therefore
be regarded as the real cause of senility in man. Parrots which are
long-lived birds have a limited flora of microbes in their intestine,
while cows and horses which are short-lived in comparison with man
possess an extraordinary richness of the intestinal flora. But,
needless to say, it is not the quantity of microbes alone which is to
be considered, the nature of the microbes is of much greater importance.</p>
<p>Certain plants like the Californian <i class="taxonomic">Sequoia gigantea</i> may be
considered as practically immortal since they live several thousands
of years; other plants, the an<span class="pagenum" title="369"><a name="Page_369" id="Page_369"></a></span>nuals, die after fructification.
Metchnikoff quotes from a letter by de Vries that this author prolonged
the life of <i class="taxonomic">Œnotheras</i> by cutting the flowers before fertilization.</p>
<div class="blockquot">
<p>Under ordinary conditions the stem dies after producing from forty
to fifty flowers, but if cutting be practised new flowers are
produced until the winter cold intervenes. By cutting the stem
sufficiently early the plants are induced to develop new buds at
the base and these buds survive winter and resume growth in the
following spring.</p>
</div>
<p>Metchnikoff suggests that it is a poison formed in the plant (in
connection with fructification?) which kills the annuals, while it
is not formed or is less harmful in the perennials. He compares the
situation to the death of the lactic acid bacilli if the lactic acid
is allowed to accumulate. This hypothesis is certainly worthy of
consideration, and it is quite possible that in addition to structural
shortcomings poisons formed by certain organs of the body as well as
poisons formed by bacteria account for the phenomenon of death in
metazoa.</p>
<hr class="chap" />
<p><span class="pagenum" title="371"><a name="Page_371" id="Page_371"></a></span></p>
<h2>INDEX</h2>
<p>
<span style="margin-left: 1em;"><i class="taxonomic">Abraxas</i>, <a href="#Page_203">203</a>, <a href="#Page_238">238</a>, <a href="#Page_241">241</a></span><br />
<span style="margin-left: 1em;">Acquired characters, inheritance of, <a href="#Page_337">337</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Actinia equina</i>, <a href="#Page_361">361</a></span><br />
<span style="margin-left: 1em;">Adaptation, <a href="#Page_12">12</a>, <a href="#Page_318">318</a> ff.;</span><br />
<span style="margin-left: 2em;">to life in caves, <a href="#Page_319">319</a> ff.;</span><br />
<span style="margin-left: 2em;">fresh and salt water, <a href="#Page_327">327</a> ff.;</span><br />
<span style="margin-left: 2em;">poisons, <a href="#Page_332">332</a> ff.;</span><br />
<span style="margin-left: 2em;">temperature, <a href="#Page_334">334</a> ff.;</span><br />
<span style="margin-left: 2em;">caused by hormones, <a href="#Page_342">342</a></span><br />
<span style="margin-left: 1em;">Addison, W. H. F., <a href="#Page_188">188</a></span><br />
<span style="margin-left: 1em;">Agglutination, of corpuscles by sera, <a href="#Page_67">67</a> ff.;</span><br />
<span style="margin-left: 2em;">of sperm, <a href="#Page_78">78</a>, <a href="#Page_82">82</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Allolobophora terrestris</i>, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Alpheus</i>, <a href="#Page_176">176</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Alytes obstetricans</i>, <a href="#Page_337">337</a>, <a href="#Page_338">338</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Amanita phalloides</i>, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Amblystoma</i>, <a href="#Page_157">157</a>, <a href="#Page_368">368</a></span><br />
<span style="margin-left: 1em;">Amelung, <a href="#Page_184">184</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Amphipyra</i>, <a href="#Page_283">283</a></span><br />
<span style="margin-left: 1em;">Analogies between living and dead matter, <a href="#Page_14">14</a> ff.</span><br />
<span style="margin-left: 1em;">Anaphylaxis reaction, <a href="#Page_61">61</a> ff.</span><br />
<span style="margin-left: 1em;">Ancel, <a href="#Page_158">158</a>, <a href="#Page_225">225</a> ff.</span><br />
<span style="margin-left: 1em;">Antagonistic salt action. <em>See</em> Balanced salt solutions.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Antennularia antennina</i>, <a href="#Page_194">194</a>, <a href="#Page_196">196</a></span><br />
<span style="margin-left: 1em;">Apes, blood relationship to man, <a href="#Page_54">54</a>, <a href="#Page_56">56</a> ff.</span><br />
<span style="margin-left: 1em;">Apolant, <a href="#Page_45">45</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Arbacia</i>, <a href="#Page_75">75</a> ff., <a href="#Page_96">96</a>, <a href="#Page_99">99</a>, <a href="#Page_101">101</a>, <a href="#Page_111">111</a>, <a href="#Page_114">114</a>, <a href="#Page_150">150</a>, <a href="#Page_190">190</a> ff., <a href="#Page_293">293</a> ff., <a href="#Page_298">298</a>, <a href="#Page_299">299</a>, <a href="#Page_364">364</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Arenicola</i>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Armstrong, E. F., <a href="#Page_26">26</a>, <a href="#Page_28">28</a>, <a href="#Page_354">354</a></span><br />
<span style="margin-left: 1em;">Arrhenius, S., <a href="#Page_33">33</a> ff., <a href="#Page_88">88</a>, <a href="#Page_290">290</a>, <a href="#Page_296">296</a></span><br />
<span style="margin-left: 1em;">Arrhenoidy, <a href="#Page_218">218</a>, <a href="#Page_225">225</a></span><br />
<span style="margin-left: 1em;">Artificial parthenogenesis, <a href="#Page_95">95</a> ff.;</span><br />
<span style="margin-left: 2em;">in sea urchins, <a href="#Page_95">95</a> ff.;</span><br />
<span style="margin-left: 2em;">new method of, <a href="#Page_98">98</a>, <a href="#Page_99">99</a>;</span><br />
<span style="margin-left: 2em;">by blood, <a href="#Page_101">101</a> ff.;</span><br />
<span style="margin-left: 2em;">by sperm extract, <a href="#Page_103">103</a>;</span><br />
<span style="margin-left: 2em;">by acids, <a href="#Page_105">105</a>;</span><br />
<span style="margin-left: 2em;">by mechanical agitation, <a href="#Page_107">107</a>;</span><br />
<span style="margin-left: 2em;">in starfish, <a href="#Page_110">110</a>;</span><br />
<span style="margin-left: 2em;">rôle of hypertonic solution, <a href="#Page_112">112</a>, <a href="#Page_115">115</a>, <a href="#Page_116">116</a>;</span><br />
<span style="margin-left: 2em;">and oxidation, <a href="#Page_116">116</a>, <a href="#Page_117">117</a>, <a href="#Page_118">118</a>;</span><br />
<span style="margin-left: 2em;">and permeability, <a href="#Page_119">119</a> ff.;</span><br />
<span style="margin-left: 2em;">in frogs, <a href="#Page_124">124</a>;</span><br />
<span style="margin-left: 2em;">and determination of sex, <a href="#Page_125">125</a></span><br />
<span style="margin-left: 1em;">Artificial production of life, <a href="#Page_38">38</a>–<a href="#Page_39">39</a></span><br />
<span style="margin-left: 1em;">Assimilation of CO<sub>2</sub> without chlorophyll, <a href="#Page_17">17</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Asterias</i>, <a href="#Page_49">49</a>, <a href="#Page_81">81</a>, <a href="#Page_110">110</a>, <a href="#Page_363">363</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">ochracea</i>, <a href="#Page_73">73</a> ff.;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">capitata</i>, <a href="#Page_74">74</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Asterina</i>, <a href="#Page_75">75</a>, <a href="#Page_81">81</a>, <a href="#Page_110">110</a></span><br />
<span style="margin-left: 1em;">Astrospheres, <a href="#Page_115">115</a> ff., <a href="#Page_192">192</a></span><br />
<span style="margin-left: 1em;">Auer, J., <a href="#Page_315">315</a></span><br />
<span style="margin-left: 1em;">Autolysis, <a href="#Page_351">351</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Avena</i>, <a href="#Page_263">263</a></span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">B. coli communis</i>, <a href="#Page_36">36</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">typhosus</i>, <a href="#Page_36">36</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">fluorescens</i>, <a href="#Page_334">334</a></span><br />
<span style="margin-left: 1em;">Bacteria, growth of, <a href="#Page_15">15</a> ff., <a href="#Page_29">29</a>, <a href="#Page_71">71</a> ff.;</span><br />
<span style="margin-left: 2em;">specificity in, <a href="#Page_41">41</a> ff.</span><br />
<span style="margin-left: 1em;">“<i>Bacterio-purpurin</i>,” 41</span><br />
<span style="margin-left: 1em;">Balanced salt solutions, <a href="#Page_307">307</a>–<a href="#Page_317">317</a>;</span><br />
<span style="margin-left: 2em;">theory of, <a href="#Page_317">317</a>;</span><br />
<span style="margin-left: 2em;">and adaptation, <a href="#Page_331">331</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Balanus</i>, <a href="#Page_259">259</a></span><br />
<span style="margin-left: 1em;">Baltzer, F., <a href="#Page_215">215</a> ff.</span><br />
<span style="margin-left: 1em;">Bancroft, F. W., <a href="#Page_70">70</a>, <a href="#Page_125">125</a>, <a href="#Page_127">127</a>, <a href="#Page_264">264</a>, <a href="#Page_269">269</a> ff.</span><br />
<span style="margin-left: 1em;">Bang, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;">Bardeen, C. R., <a href="#Page_174">174</a> ff.</span><br />
<span style="margin-left: 1em;">Barnacle, larvæ of, <a href="#Page_313">313</a> ff.</span><br />
<span style="margin-left: 1em;">Bataillon, <a href="#Page_124">124</a></span><br />
<span style="margin-left: 1em;">Bateson, W., <a href="#Page_230">230</a>, <a href="#Page_240">240</a> ff., <a href="#Page_338">338</a>, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Batrachia</i>, <a href="#Page_338">338</a></span><br />
<span style="margin-left: 1em;">Baur, E., <a href="#Page_48">48</a>, <a href="#Page_246">246</a></span><br />
<span style="margin-left: 1em;">Bayliss, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;">Becquerel, P., <a href="#Page_36">36</a> ff.</span><br />
<span class="pagenum" title="372"><a name="Page_372" id="Page_372"></a></span><span style="margin-left: 1em;"><i class="taxonomic">Beggiatoa</i>, <a href="#Page_19">19</a></span><br />
<span style="margin-left: 1em;">Beijerinck, M., <a href="#Page_20">20</a></span><br />
<span style="margin-left: 1em;">Berkeley, Lord, <a href="#Page_111">111</a></span><br />
<span style="margin-left: 1em;">Bernard, Claude, <a href="#Page_2">2</a> ff., <a href="#Page_26">26</a>, <a href="#Page_159">159</a>, <a href="#Page_350">350</a>, <a href="#Page_354">354</a>, <a href="#Page_355">355</a>, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;">Berthelot, <a href="#Page_290">290</a></span><br />
<span style="margin-left: 1em;">Bertrand, G., <a href="#Page_248">248</a> ff.</span><br />
<span style="margin-left: 1em;">Beutner, R., <a href="#Page_140">140</a></span><br />
<span style="margin-left: 1em;">Bichat, <a href="#Page_2">2</a>, <a href="#Page_349">349</a></span><br />
<span style="margin-left: 1em;">Bickford, E. E., <a href="#Page_169">169</a></span><br />
<span style="margin-left: 1em;">Blaauw, H. A., <a href="#Page_263">263</a></span><br />
<span style="margin-left: 1em;">Blackman, F. F., <a href="#Page_302">302</a></span><br />
<span style="margin-left: 1em;">Blastomeres, <a href="#Page_141">141</a> ff.</span><br />
<span style="margin-left: 1em;">Blind animals, <a href="#Page_319">319</a> ff.</span><br />
<span style="margin-left: 1em;">Blood, transfusion of, <a href="#Page_53">53</a> ff.</span><br />
<span style="margin-left: 1em;">Blood relationship, established by transfusion, <a href="#Page_53">53</a>, <a href="#Page_54">54</a> ff.;</span><br />
<span style="margin-left: 2em;">precipitin reaction, <a href="#Page_55">55</a> ff.;</span><br />
<span style="margin-left: 2em;">anaphylaxis reaction, <a href="#Page_61">61</a> ff.;</span><br />
<span style="margin-left: 2em;">hemoglobin crystals, <a href="#Page_64">64</a> ff.</span><br />
<span style="margin-left: 1em;">Blood serum, precipitin reaction of, <a href="#Page_54">54</a> ff.;</span><br />
<span style="margin-left: 2em;">effect of, on unfertilized eggs, <a href="#Page_101">101</a> ff., <a href="#Page_124">124</a></span><br />
<span style="margin-left: 1em;">Blowfly, heliotropism of larvæ of, <a href="#Page_265">265</a> ff.</span><br />
<span style="margin-left: 1em;">Bohn, G., <a href="#Page_253">253</a>, <a href="#Page_264">264</a>, <a href="#Page_269">269</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Bombinator igneus</i>, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Bonellia</i>, <a href="#Page_215">215</a></span><br />
<span style="margin-left: 1em;">Bonnet, <a href="#Page_154">154</a>, <a href="#Page_161">161</a></span><br />
<span style="margin-left: 1em;">Bordet, <a href="#Page_54">54</a> ff., <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;">Bouin, <a href="#Page_158">158</a>, <a href="#Page_225">225</a> ff.</span><br />
<span style="margin-left: 1em;">Boveri, Th., <a href="#Page_8">8</a>, <a href="#Page_126">126</a>, <a href="#Page_128">128</a> ff., <a href="#Page_134">134</a>, <a href="#Page_138">138</a> ff., <a href="#Page_150">150</a> ff., <a href="#Page_186">186</a> ff., <a href="#Page_209">209</a> ff., <a href="#Page_246">246</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Brachystola</i>, <a href="#Page_199">199</a></span><br />
<span style="margin-left: 1em;">Bradley, H. C., <a href="#Page_27">27</a>, <a href="#Page_64">64</a>, <a href="#Page_353">353</a>, <a href="#Page_354">354</a></span><br />
<span style="margin-left: 1em;">Brandt, <a href="#Page_366">366</a></span><br />
<span style="margin-left: 1em;">Braus, H., <a href="#Page_147">147</a></span><br />
<span style="margin-left: 1em;">Bridges, C. B., <a href="#Page_208">208</a>, <a href="#Page_229">229</a>, <a href="#Page_231">231</a> ff.</span><br />
<span style="margin-left: 1em;">Brown, A. P., <a href="#Page_64">64</a> ff.</span><br />
<span style="margin-left: 1em;">Bruchmann, H., <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Bryophyllum calycinum</i>, <a href="#Page_153">153</a>, <a href="#Page_160">160</a> ff., <a href="#Page_177">177</a></span><br />
<span style="margin-left: 1em;">Buchner, <a href="#Page_24">24</a></span><br />
<span style="margin-left: 1em;">Budgett, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;">Buller, <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;"><a id="Bunsen-Roscoe"></a>Bunsen-Roscoe, law of, <a href="#Page_11">11</a>, <a href="#Page_256">256</a> ff., <a href="#Page_261">261</a>, <a href="#Page_263">263</a>, <a href="#Page_264">264</a></span><br />
<span style="margin-left: 1em;">Burrows, <a href="#Page_31">31</a></span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Campanularia</i>, <a href="#Page_178">178</a>, <a href="#Page_181">181</a></span><br />
<span style="margin-left: 1em;">Cannon, W. B., <a href="#Page_285">285</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Carcinus mænas</i>, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cardamine pratensis</i>, <a href="#Page_90">90</a></span><br />
<span style="margin-left: 1em;">Carrel, <a href="#Page_31">31</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cassia bicapsularis</i>, <a href="#Page_37">37</a></span><br />
<span style="margin-left: 1em;">Castle, W. E., <a href="#Page_89">89</a> ff., <a href="#Page_335">335</a></span><br />
<span style="margin-left: 1em;">Caullery, M., <a href="#Page_158">158</a>, <a href="#Page_180">180</a>, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;">Cave animals, <a href="#Page_319">319</a> ff.</span><br />
<span style="margin-left: 1em;">Cell division, <a href="#Page_15">15</a>, <a href="#Page_29">29</a>, <a href="#Page_129">129</a> ff.;</span><br />
<span style="margin-left: 2em;">suppression of, <a href="#Page_113">113</a> ff.</span><br />
<span style="margin-left: 1em;">Cells, nutritive media of, <a href="#Page_15">15</a> ff;</span><br />
<span style="margin-left: 2em;">immortality of, <a href="#Page_30">30</a> ff.;</span><br />
<span style="margin-left: 2em;">migrating, <a href="#Page_44">44</a>;</span><br />
<span style="margin-left: 2em;">mesenchyme, <a href="#Page_51">51</a> ff., <a href="#Page_130">130</a> ff., <a href="#Page_147">147</a>, <a href="#Page_155">155</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cerianthus membranaceus</i>, <a href="#Page_171">171</a> ff., <a href="#Page_188">188</a>, <a href="#Page_361">361</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Chætopterus</i>, <a href="#Page_78">78</a> ff.</span><br />
<span style="margin-left: 1em;">Chamberlain, M. M., <a href="#Page_293">293</a>, <a href="#Page_297">297</a></span><br />
<span style="margin-left: 1em;">Chapman, H. G., <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;">Chemotropism of spermatozoa, <a href="#Page_92">92</a> ff.</span><br />
<span style="margin-left: 1em;">Chevreul, <a href="#Page_289">289</a></span><br />
<span style="margin-left: 1em;">Child, C. M., <a href="#Page_7">7</a>, <a href="#Page_170">170</a>, <a href="#Page_177">177</a>, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Chlamydomonas</i>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Chodat, R., <a href="#Page_248">248</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Chologaster</i>, <a href="#Page_320">320</a></span><br />
<span style="margin-left: 1em;">Christen, <a href="#Page_288">288</a></span><br />
<span style="margin-left: 1em;">Chromosomes, rôle of, in sex determination, <a href="#Page_198">198</a> ff.;</span><br />
<span style="margin-left: 2em;">theory of Mendelian heredity, <a href="#Page_233">233</a></span><br />
<span style="margin-left: 1em;">Chun, <a href="#Page_142">142</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Ciona intestinalis</i>, <a href="#Page_89">89</a> ff., <a href="#Page_212">212</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cladocera</i>, <a href="#Page_159">159</a></span><br />
<span style="margin-left: 1em;">Clausen, H., <a href="#Page_302">302</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Clavellina</i>, <a href="#Page_181">181</a></span><br />
<span style="margin-left: 1em;">Cohen, E., <a href="#Page_292">292</a></span><br />
<span style="margin-left: 1em;">Cohn, <a href="#Page_41">41</a> ff.</span><br />
<span style="margin-left: 1em;">Compton, <a href="#Page_90">90</a></span><br />
<span style="margin-left: 1em;">Conklin, E. G., <a href="#Page_129">129</a>, <a href="#Page_134">134</a>, <a href="#Page_143">143</a>, <a href="#Page_145">145</a> ff.</span><br />
<span style="margin-left: 1em;">Constancy of species, <a href="#Page_40">40</a>–<a href="#Page_43">43</a></span><br />
<span style="margin-left: 1em;">Copernicus, <a href="#Page_346">346</a></span><br />
<span style="margin-left: 1em;">Corpus luteum, action of, <a href="#Page_157">157</a>–<a href="#Page_158">158</a></span><br />
<span style="margin-left: 1em;">Correlation, <a href="#Page_154">154</a>, <a href="#Page_167">167</a></span><br />
<span style="margin-left: 1em;">Correns, C., <a href="#Page_90">90</a> ff., <a href="#Page_214">214</a></span><br />
<span style="margin-left: 1em;">Cramer, <a href="#Page_289">289</a></span><br />
<span style="margin-left: 1em;">Crampton, H. E., <a href="#Page_143">143</a>, <a href="#Page_225">225</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Criodrilus lacuum</i>, <a href="#Page_219">219</a>–<a href="#Page_220">220</a></span><br />
<span style="margin-left: 1em;">Crossing over of chromosomes, <a href="#Page_241">241</a> ff.</span><br />
<span style="margin-left: 1em;">Crystals, differences between living organisms and, <a href="#Page_14">14</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Ctenolabrus</i>, <a href="#Page_355">355</a>, <a href="#Page_357">357</a>, <a href="#Page_359">359</a></span><br />
<span class="pagenum" title="373"><a name="Page_373" id="Page_373"></a></span><span style="margin-left: 1em;"><i class="taxonomic">Ctenophores</i>, <a href="#Page_142">142</a></span><br />
<span style="margin-left: 1em;">Cuénot, L., <a href="#Page_12">12</a>, <a href="#Page_324">324</a></span><br />
<span style="margin-left: 1em;">Cullen, G. E., <a href="#Page_24">24</a>, <a href="#Page_291">291</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cuma rathkii</i>, <a href="#Page_318">318</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cyanophyceæ</i>, <a href="#Page_287">287</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Cytisus biflorus</i>, <a href="#Page_37">37</a></span><br />
<span style="margin-left: 1em;">Cytoplasm of eggs as future embryo, <a href="#Page_8">8</a>, <a href="#Page_9">9</a>, <a href="#Page_70">70</a>, <a href="#Page_126">126</a>, <a href="#Page_151">151</a> ff.</span><br />
<br />
<span style="margin-left: 1em;">Dakin, <a href="#Page_352">352</a></span><br />
<span style="margin-left: 1em;">Dallinger, <a href="#Page_334">334</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Daphnia</i>, <a href="#Page_210">210</a>, <a href="#Page_262">262</a>, <a href="#Page_279">279</a>, <a href="#Page_280">280</a>, <a href="#Page_282">282</a>, <a href="#Page_306">306</a>, <a href="#Page_312">312</a></span><br />
<span style="margin-left: 1em;">Darbishire, A. D., <a href="#Page_347">347</a></span><br />
<span style="margin-left: 1em;">Darwin, <a href="#Page_90">90</a>, <a href="#Page_297">297</a>, <a href="#Page_346">346</a> ff.</span><br />
<span style="margin-left: 1em;">Darwinian theory, <a href="#Page_5">5</a> ff.</span><br />
<span style="margin-left: 1em;">Davenport, C. B., <a href="#Page_244">244</a>, <a href="#Page_335">335</a></span><br />
<span style="margin-left: 1em;">Death, <a href="#Page_349">349</a> ff.;</span><br />
<span style="margin-left: 2em;">natural, cause of, <a href="#Page_364">364</a>, <a href="#Page_369">369</a></span><br />
<span style="margin-left: 1em;">Decidua formation induced by corpus luteum, <a href="#Page_157">157</a>–<a href="#Page_158">158</a></span><br />
<span style="margin-left: 1em;">Delage, Y., <a href="#Page_107">107</a>, <a href="#Page_110">110</a>, <a href="#Page_111">111</a>, <a href="#Page_123">123</a>, <a href="#Page_126">126</a>, <a href="#Page_186">186</a></span><br />
<span style="margin-left: 1em;">de la Rive, <a href="#Page_24">24</a></span><br />
<span style="margin-left: 1em;">de Meyer, J., <a href="#Page_127">127</a></span><br />
<span style="margin-left: 1em;"><cite>Dendrostoma</cite>, <a href="#Page_101">101</a></span><br />
<span style="margin-left: 1em;"><cite>Dentalium</cite>, <a href="#Page_144">144</a></span><br />
<span style="margin-left: 1em;">Design, <a href="#Page_4">4</a>, <a href="#Page_5">5</a></span><br />
<span style="margin-left: 1em;">Determination of sex, in bees, <a href="#Page_208">208</a> ff.;</span><br />
<span style="margin-left: 2em;">in phylloxerans, <a href="#Page_210">210</a>;</span><br />
<span style="margin-left: 2em;">in <cite>Bonellia</cite>, <a href="#Page_215">215</a></span><br />
<span style="margin-left: 1em;">Development of egg, <a href="#Page_127">127</a> ff.</span><br />
<span style="margin-left: 1em;">de Vries, H., <a href="#Page_6">6</a>, <a href="#Page_42">42</a>, <a href="#Page_154">154</a>, <a href="#Page_161">161</a>, <a href="#Page_347">347</a>, <a href="#Page_369">369</a></span><br />
<span style="margin-left: 1em;">Dewitz, <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;">Dieudonné, C., <a href="#Page_334">334</a>, <a href="#Page_337">337</a></span><br />
<span style="margin-left: 1em;">“Directive force,” 2</span><br />
<span style="margin-left: 1em;">Disharmonies, <a href="#Page_7">7</a></span><br />
<span style="margin-left: 1em;">Divisibility of living matter, limits of, <a href="#Page_148">148</a>–<a href="#Page_151">151</a></span><br />
<span style="margin-left: 1em;">Dominance, <a href="#Page_230">230</a></span><br />
<span style="margin-left: 1em;">Doncaster, L., <a href="#Page_203">203</a></span><br />
<span style="margin-left: 1em;">Dorfmeister, <a href="#Page_303">303</a></span><br />
<span style="margin-left: 1em;">Driesch, H., <a href="#Page_4">4</a> ff., <a href="#Page_128">128</a>, <a href="#Page_133">133</a>, <a href="#Page_136">136</a>, <a href="#Page_138">138</a> ff., <a href="#Page_147">147</a>, <a href="#Page_150">150</a>, <a href="#Page_169">169</a> ff., <a href="#Page_180">180</a> ff., <a href="#Page_184">184</a> ff.</span><br />
<span style="margin-left: 1em;"><cite>Drosophila ampelophila</cite>, <a href="#Page_204">204</a> ff., <a href="#Page_237">237</a>, <a href="#Page_243">243</a>, <a href="#Page_322">322</a>, <a href="#Page_347">347</a>, <a href="#Page_366">366</a></span><br />
<span style="margin-left: 1em;">Duclaux, E., <a href="#Page_288">288</a>, <a href="#Page_289">289</a></span><br />
<span style="margin-left: 1em;">v. Dungern, <a href="#Page_80">80</a></span><br />
<span style="margin-left: 1em;">Duration of life, <a href="#Page_360">360</a> ff.</span><br />
<span style="margin-left: 1em;">Durham, <a href="#Page_249">249</a></span><br />
<span style="margin-left: 1em;">Dutrochet, <a href="#Page_154">154</a></span><br />
<span style="margin-left: 1em;">Dzierzon, <a href="#Page_208">208</a></span><br />
<br />
<span style="margin-left: 1em;">Ectoderm formation, <a href="#Page_130">130</a> ff.</span><br />
<span style="margin-left: 1em;">Egg, as the future embryo, <a href="#Page_8">8</a>, <a href="#Page_9">9</a>, <a href="#Page_70">70</a>, <a href="#Page_126">126</a>, <a href="#Page_151">151</a>;</span><br />
<span style="margin-left: 2em;">artificial parthenogenesis of, <a href="#Page_95">95</a> ff.;</span><br />
<span style="margin-left: 2em;">organisms from, <a href="#Page_128">128</a> ff.;</span><br />
<span style="margin-left: 2em;">determining unity of organism, <a href="#Page_151">151</a>–<a href="#Page_152">152</a>;</span><br />
<span style="margin-left: 2em;">chromosomes in, <a href="#Page_198">198</a> ff.</span><br />
<span style="margin-left: 1em;">Egg structure, <a href="#Page_129">129</a> ff.;</span><br />
<span style="margin-left: 2em;">influence of centrifugal force on, <a href="#Page_135">135</a>;</span><br />
<span style="margin-left: 2em;">and regulation, <a href="#Page_139">139</a>, <a href="#Page_140">140</a>, <a href="#Page_141">141</a>;</span><br />
<span style="margin-left: 2em;">and fluidity of protoplasm, <a href="#Page_141">141</a></span><br />
<span style="margin-left: 1em;">Ehrlich, <a href="#Page_45">45</a>, <a href="#Page_322">322</a>, <a href="#Page_332">332</a> ff., <a href="#Page_341">341</a>;</span><br />
<span style="margin-left: 2em;">side-chain theory of, <a href="#Page_88">88</a>, <a href="#Page_188">188</a></span><br />
<span style="margin-left: 1em;">Eigenmann, <a href="#Page_320">320</a>, <a href="#Page_323">323</a> ff.</span><br />
<span style="margin-left: 1em;">Electromotive forces, origin in living organs, <a href="#Page_140">140</a></span><br />
<span style="margin-left: 1em;">Engelmann, <a href="#Page_357">357</a></span><br />
<span style="margin-left: 1em;">Engler, <a href="#Page_24">24</a></span><br />
<span style="margin-left: 1em;">Entelechy, <a href="#Page_4">4</a>, <a href="#Page_170">170</a>, <a href="#Page_182">182</a></span><br />
<span style="margin-left: 1em;">Environment, influence of, <a href="#Page_286">286</a> ff.;</span><br />
<span style="margin-left: 2em;">temperature, <a href="#Page_288">288</a> ff., <a href="#Page_344">344</a> ff.;</span><br />
<span style="margin-left: 2em;">salinity, <a href="#Page_306">306</a>;</span><br />
<span style="margin-left: 2em;">adaptation to, <a href="#Page_319">319</a></span><br />
<span style="margin-left: 1em;">Enzyme action, <a href="#Page_23">23</a> ff., <a href="#Page_297">297</a>, <a href="#Page_302">302</a></span><br />
<span style="margin-left: 1em;">Ernst, A., <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Eternity of life, <a href="#Page_34">34</a> ff., <a href="#Page_360">360</a></span><br />
<span style="margin-left: 1em;"><cite>Eudendrium</cite>, <a href="#Page_260">260</a>, <a href="#Page_261">261</a>, <a href="#Page_269">269</a>, <a href="#Page_277">277</a>, <a href="#Page_278">278</a>, <a href="#Page_326">326</a></span><br />
<span style="margin-left: 1em;"><cite>Eudorina</cite>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;"><cite>Euglena</cite>, <a href="#Page_264">264</a>, <a href="#Page_269">269</a>, <a href="#Page_272">272</a>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Euler, H., <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Evolution, <a href="#Page_346">346</a> ff.;</span><br />
<span style="margin-left: 2em;">and mutation, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;">Ewald, W. F., <a href="#Page_261">261</a> ff., <a href="#Page_269">269</a>, <a href="#Page_280">280</a>, <a href="#Page_301">301</a></span><br />
<br />
<span style="margin-left: 1em;">Farmer, J. B., <a href="#Page_347">347</a></span><br />
<span style="margin-left: 1em;">Fermi, <a href="#Page_350">350</a>, <a href="#Page_354">354</a></span><br />
<span style="margin-left: 1em;">Fertilization, heterogeneous, <a href="#Page_48">48</a> ff., <a href="#Page_51">51</a>, <a href="#Page_73">73</a> ff.;</span><br />
<span style="margin-left: 2em;">specificity in, <a href="#Page_71">71</a> ff.;</span><br />
<span style="margin-left: 2em;">and oxidation, <a href="#Page_117">117</a> ff.;</span><br />
<span style="margin-left: 2em;">and permeability, <a href="#Page_119">119</a> ff.</span><br />
<span style="margin-left: 1em;">“Fertilizin,” 84, <a href="#Page_87">87</a> ff., <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;">Fischel, <a href="#Page_187">187</a></span><br />
<span style="margin-left: 1em;">Fischer, <a href="#Page_303">303</a> ff.</span><br />
<span style="margin-left: 1em;">Fish, <a href="#Page_55">55</a></span><br />
<span style="margin-left: 1em;">Fitness of environment, <a href="#Page_317">317</a></span><br />
<span style="margin-left: 1em;">Fitzgerald, J. G., <a href="#Page_63">63</a></span><br />
<span class="pagenum" title="374"><a name="Page_374" id="Page_374"></a></span><span style="margin-left: 1em;">Flow of substances and regeneration in <cite>Bryophyllum</cite>, <a href="#Page_161">161</a> ff.</span><br />
<span style="margin-left: 1em;">Fluctuating variations, <a href="#Page_6">6</a>, <a href="#Page_297">297</a> ff., <a href="#Page_346">346</a> ff.</span><br />
<span style="margin-left: 1em;">Folin, <a href="#Page_22">22</a></span><br />
<span style="margin-left: 1em;">Food, influence on polymorphism in wasps, <a href="#Page_222">222</a> ff.</span><br />
<span style="margin-left: 1em;">Food castration, <a href="#Page_224">224</a>;</span><br />
<span style="margin-left: 2em;">influence on sexual cycle in rotifers, <a href="#Page_224">224</a>;</span><br />
<span style="margin-left: 2em;">on metamorphosis in tadpoles, <a href="#Page_155">155</a></span><br />
<span style="margin-left: 1em;">Ford, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;">Forssmann, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;">Frédéricq, <a href="#Page_351">351</a></span><br />
<span style="margin-left: 1em;">Free-martin, cause of sterility, <a href="#Page_218">218</a>–<a href="#Page_219">219</a></span><br />
<span style="margin-left: 1em;">Friedenthal, H., <a href="#Page_53">53</a> ff., <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;">Frisch, K., <a href="#Page_278">278</a>, <a href="#Page_279">279</a></span><br />
<span style="margin-left: 1em;">Fröschel, P., <a href="#Page_263">263</a></span><br />
<span style="margin-left: 1em;">Fuchs, H. M., <a href="#Page_90">90</a></span><br />
<span style="margin-left: 1em;"><cite>Fucus</cite>, <a href="#Page_123">123</a></span><br />
<span style="margin-left: 1em;"><cite>Fundulus heteroclitus</cite>, <a href="#Page_51">51</a>, <a href="#Page_116">116</a>, <a href="#Page_147">147</a>, <a href="#Page_300">300</a>, <a href="#Page_301">301</a>, <a href="#Page_302">302</a>, <a href="#Page_307">307</a> ff., <a href="#Page_321">321</a> ff., <a href="#Page_328">328</a> ff., <a href="#Page_335">335</a>, <a href="#Page_337">337</a>, <a href="#Page_357">357</a> ff.</span><br />
<br />
<span style="margin-left: 1em;">Galileo, <a href="#Page_346">346</a></span><br />
<span style="margin-left: 1em;">Galvanotropism, <a href="#Page_11">11</a>, <a href="#Page_270">270</a> ff., <a href="#Page_319">319</a></span><br />
<span style="margin-left: 1em;">Gay, F. P., <a href="#Page_62">62</a> ff.</span><br />
<span style="margin-left: 1em;">Generation, spontaneous, <a href="#Page_14">14</a> ff., <a href="#Page_34">34</a></span><br />
<span style="margin-left: 1em;">Genes, <a href="#Page_4">4</a> ff., <a href="#Page_152">152</a>, <a href="#Page_319">319</a></span><br />
<span style="margin-left: 1em;">Genus and species, chemical basis of, <a href="#Page_40">40</a> ff.</span><br />
<span style="margin-left: 1em;">Geppert, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;">Germination in seeds, <a href="#Page_35">35</a> ff.</span><br />
<span style="margin-left: 1em;">Giard, <a href="#Page_180">180</a>, <a href="#Page_216">216</a> ff.</span><br />
<span style="margin-left: 1em;">Godlewski, E., <a href="#Page_48">48</a>, <a href="#Page_75">75</a>, <a href="#Page_78">78</a>, <a href="#Page_120">120</a>, <a href="#Page_126">126</a>, <a href="#Page_169">169</a></span><br />
<span style="margin-left: 1em;">Godlewski, E., Sr., <a href="#Page_18">18</a></span><br />
<span style="margin-left: 1em;">Goebel, K., <a href="#Page_154">154</a>, <a href="#Page_161">161</a></span><br />
<span style="margin-left: 1em;">Goldfarb, A. J., <a href="#Page_326">326</a></span><br />
<span style="margin-left: 1em;">Goldschmidt, R., <a href="#Page_220">220</a> ff.</span><br />
<span style="margin-left: 1em;">Goodale, H. D., <a href="#Page_218">218</a></span><br />
<span style="margin-left: 1em;">Gortner, R., <a href="#Page_249">249</a></span><br />
<span style="margin-left: 1em;">Graber, V., <a href="#Page_256">256</a>, <a href="#Page_276">276</a></span><br />
<span style="margin-left: 1em;">Grafting, heteroplastic, in animals, <a href="#Page_46">46</a>;</span><br />
<span style="margin-left: 2em;">in plants, <a href="#Page_47">47</a></span><br />
<span style="margin-left: 1em;">Gravitation, influence on organ formation in <cite>Antennularia</cite>, <a href="#Page_194">194</a> ff.;</span><br />
<span style="margin-left: 2em;">on the egg of the frog, <a href="#Page_141">141</a></span><br />
<span style="margin-left: 1em;">Gray, J., <a href="#Page_122">122</a></span><br />
<span style="margin-left: 1em;">Gregory, <a href="#Page_243">243</a></span><br />
<span style="margin-left: 1em;">Groom, T. T., <a href="#Page_280">280</a></span><br />
<span style="margin-left: 1em;">Growth, termination of, <a href="#Page_184">184</a>;</span><br />
<span style="margin-left: 2em;">influence of cell size, <a href="#Page_187">187</a></span><br />
<span style="margin-left: 1em;">Gudernatsch, J. F., <a href="#Page_155">155</a>, <a href="#Page_255">255</a>, <a href="#Page_342">342</a></span><br />
<span style="margin-left: 1em;">Guyer, <a href="#Page_124">124</a></span><br />
<span style="margin-left: 1em;">Gynandromorphism, <a href="#Page_209">209</a></span><br />
<br />
<span style="margin-left: 1em;">Haeckel, <a href="#Page_346">346</a></span><br />
<span style="margin-left: 1em;">Half-embryos and whole embryos, <a href="#Page_141">141</a>, <a href="#Page_142">142</a></span><br />
<span style="margin-left: 1em;">Hammond, J. H., Jr., <a href="#Page_269">269</a></span><br />
<span style="margin-left: 1em;">Harden, <a href="#Page_16">16</a></span><br />
<span style="margin-left: 1em;">Hardesty, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;">Harmonious character of organism, <a href="#Page_5">5</a>, <a href="#Page_6">6</a>, <a href="#Page_318">318</a> ff., <a href="#Page_341">341</a> ff.</span><br />
<span style="margin-left: 1em;">Harrison, <a href="#Page_31">31</a></span><br />
<span style="margin-left: 1em;">Hartley, <a href="#Page_111">111</a></span><br />
<span style="margin-left: 1em;">Healing of wound, <a href="#Page_187">187</a></span><br />
<span style="margin-left: 1em;">Hektoen, <a href="#Page_66">66</a></span><br />
<span style="margin-left: 1em;"><a id="Heliotropism"></a>Heliotropism, <a href="#Page_11">11</a> ff., <a href="#Page_257">257</a> ff., <a href="#Page_318">318</a>;</span><br />
<span style="margin-left: 2em;">heredity of, <a href="#Page_250">250</a> ff.;</span><br />
<span style="margin-left: 2em;">change of, <a href="#Page_279">279</a>, <a href="#Page_280">280</a> ff.;</span><br />
<span style="margin-left: 2em;">and adaptation, <a href="#Page_318">318</a></span><br />
<span style="margin-left: 1em;">Helmholtz, <a href="#Page_34">34</a></span><br />
<span style="margin-left: 1em;">Hemoglobins, crystallographic measurements of, <a href="#Page_64">64</a> ff.</span><br />
<span style="margin-left: 1em;">Henderson, L., <a href="#Page_317">317</a></span><br />
<span style="margin-left: 1em;">Henking, <a href="#Page_198">198</a> ff.</span><br />
<span style="margin-left: 1em;">Herbst, C., <a href="#Page_97">97</a>, <a href="#Page_147">147</a>, <a href="#Page_193">193</a>, <a href="#Page_306">306</a>, <a href="#Page_310">310</a></span><br />
<span style="margin-left: 1em;">Heredity, of genus and species, <a href="#Page_40">40</a> ff., <a href="#Page_70">70</a>, <a href="#Page_151">151</a>, <a href="#Page_152">152</a>;</span><br />
<span style="margin-left: 2em;">Mendelian, <a href="#Page_70">70</a>, <a href="#Page_151">151</a> ff., <a href="#Page_229">229</a> ff., <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">of sex, <a href="#Page_198">198</a>;</span><br />
<span style="margin-left: 2em;">sex-linked, <a href="#Page_203">203</a> ff., <a href="#Page_238">238</a> ff.;</span><br />
<span style="margin-left: 2em;">and evolution, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;">Herlant, M., <a href="#Page_78">78</a> ff., <a href="#Page_115">115</a> ff.</span><br />
<span style="margin-left: 1em;">Hermaphroditism, <a href="#Page_89">89</a> ff., <a href="#Page_212">212</a> ff., <a href="#Page_216">216</a>, <a href="#Page_219">219</a> ff.</span><br />
<span style="margin-left: 2em;"><em>See also</em> <a href="#hermaphrodites">Inhibition</a> <em>and</em> <a href="#Regeneration">Regeneration</a>.</span><br />
<span style="margin-left: 1em;">Hertwig, O., <a href="#Page_97">97</a>, <a href="#Page_123">123</a>, <a href="#Page_292">292</a></span><br />
<span style="margin-left: 1em;">Hertwig, R., <a href="#Page_95">95</a>, <a href="#Page_97">97</a></span><br />
<span style="margin-left: 1em;">Hess, C., <a href="#Page_278">278</a></span><br />
<span style="margin-left: 1em;">Heterogeneous hybrids, purely maternal, <a href="#Page_49">49</a>, <a href="#Page_50">50</a></span><br />
<span style="margin-left: 1em;">Heterogeneous transplantation, Murphy’s experiments on, <a href="#Page_44">44</a> ff.;</span><br />
<span style="margin-left: 2em;">limitation of, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;">Heteromorphosis, <a href="#Page_155">155</a>, <a href="#Page_193">193</a>–<a href="#Page_196">196</a></span><br />
<span style="margin-left: 1em;">Hill, C., <a href="#Page_25">25</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Hippiscus</i>, <a href="#Page_199">199</a></span><br />
<span style="margin-left: 1em;">Holmes, S. J., <a href="#Page_269">269</a></span><br />
<span style="margin-left: 1em;">Hoppe-Seyler, <a href="#Page_351">351</a></span><br />
<span style="margin-left: 1em;">Hormones, <a href="#Page_145">145</a>, <a href="#Page_155">155</a>, <a href="#Page_181">181</a>, <a href="#Page_219">219</a>;</span><br />
<span style="margin-left: 2em;">and Mendelian heredity, <a href="#Page_245">245</a> ff., <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">and adaptation, <a href="#Page_342">342</a>.</span><br />
<span class="pagenum" title="375"><a name="Page_375" id="Page_375"></a></span><span style="margin-left: 2em;"><em>See also</em> <a href="#Organ-forming_substances">Organ-forming substances</a>.</span><br />
<span style="margin-left: 1em;">Huxley, <a href="#Page_346">346</a></span><br />
<span style="margin-left: 1em;">Hybridization, heterogeneous, in sea urchins, <a href="#Page_48">48</a> ff., <a href="#Page_73">73</a> ff.;</span><br />
<span style="margin-left: 2em;">in fishes, <a href="#Page_51">51</a>;</span><br />
<span style="margin-left: 2em;">in plants (Mendel’s), <a href="#Page_230">230</a> ff.</span><br />
<span style="margin-left: 1em;">Hydrolytic enzymes, action of, <a href="#Page_24">24</a>;</span><br />
<span style="margin-left: 2em;">reversible action of, <a href="#Page_24">24</a> ff.</span><br />
<span style="margin-left: 1em;">Hypertonic solution, <a href="#Page_99">99</a>, <a href="#Page_111">111</a> ff.</span><br />
<br />
<span style="margin-left: 1em;">Imitation of cell structures by colloids, <a href="#Page_39">39</a></span><br />
<span style="margin-left: 1em;">Immortality, of cancer cells, <a href="#Page_30">30</a>;</span><br />
<span style="margin-left: 2em;">of somatic cells, <a href="#Page_30">30</a> ff.;</span><br />
<span style="margin-left: 2em;">of life in general, <a href="#Page_34">34</a> ff.</span><br />
<span style="margin-left: 1em;">Inheritance, of colour-blindness, <a href="#Page_203">203</a>, <a href="#Page_204">204</a>, <a href="#Page_205">205</a>;</span><br />
<span style="margin-left: 2em;">of eye pigment in <i class="taxonomic">Drosophila</i>, <a href="#Page_204">204</a> ff.;</span><br />
<span style="margin-left: 2em;">of pigments, <a href="#Page_248">248</a> ff.;</span><br />
<span style="margin-left: 2em;">of acquired characters, <a href="#Page_337">337</a> ff.</span><br />
<span style="margin-left: 1em;">Inhibition of regeneration in <i class="taxonomic">Bryophyllum</i>, <a href="#Page_162">162</a> ff.</span><br />
<span style="margin-left: 1em;">Inhibition of sexual characters of opposite sex, in pheasants, <a href="#Page_218">218</a>;</span><br />
<span style="margin-left: 2em;">lack of in <a id="hermaphrodites"></a>hermaphrodites, <a href="#Page_219">219</a>;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Bonellia</i>, <a href="#Page_226">226</a></span><br />
<span style="margin-left: 1em;">Instincts, <a href="#Page_10">10</a> ff., <a href="#Page_253">253</a> ff.;</span><br />
<span style="margin-left: 2em;">sexual, <a href="#Page_198">198</a> ff.</span><br />
<span style="margin-left: 1em;">Intersexualism, <a href="#Page_221">221</a></span><br />
<span style="margin-left: 1em;">Intestine, formation of, <a href="#Page_130">130</a> ff.</span><br />
<span style="margin-left: 1em;">Isoagglutinins, <a href="#Page_66">66</a> ff., <a href="#Page_92">92</a></span><br />
<span style="margin-left: 1em;">Isolation of blastomeres, <a href="#Page_136">136</a> ff.</span><br />
<br />
<span style="margin-left: 1em;">Jacoby, <a href="#Page_352">352</a></span><br />
<span style="margin-left: 1em;">Janda, V., <a href="#Page_219">219</a> ff.</span><br />
<span style="margin-left: 1em;">Jansky, <a href="#Page_67">67</a></span><br />
<span style="margin-left: 1em;">Janssens, <a href="#Page_242">242</a></span><br />
<span style="margin-left: 1em;">Jennings, H. S., <a href="#Page_264">264</a> ff.</span><br />
<span style="margin-left: 1em;">Jensen, <a href="#Page_45">45</a></span><br />
<span style="margin-left: 1em;">Joest, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;">Johannsen, W., <a href="#Page_42">42</a>, <a href="#Page_333">333</a></span><br />
<span style="margin-left: 1em;">Jones, <a href="#Page_352">352</a></span><br />
<span style="margin-left: 1em;">Jost, <a href="#Page_90">90</a></span><br />
<br />
<span style="margin-left: 1em;">Kammerer, P., <a href="#Page_325">325</a>, <a href="#Page_337">337</a> ff.</span><br />
<span style="margin-left: 1em;">Kanitz, A., <a href="#Page_290">290</a>, <a href="#Page_292">292</a>, <a href="#Page_296">296</a></span><br />
<span style="margin-left: 1em;">Kastle, J. H., <a href="#Page_26">26</a> ff.</span><br />
<span style="margin-left: 1em;">Kellogg, V. L., <a href="#Page_279">279</a></span><br />
<span style="margin-left: 1em;">Kelvin, <a href="#Page_34">34</a></span><br />
<span style="margin-left: 1em;">King, W. O. R., <a href="#Page_50">50</a>, <a href="#Page_247">247</a></span><br />
<span style="margin-left: 1em;">Klug, <a href="#Page_351">351</a></span><br />
<span style="margin-left: 1em;">v. Knaffl, E., <a href="#Page_106">106</a></span><br />
<span style="margin-left: 1em;">Knowlton, E. P., <a href="#Page_292">292</a></span><br />
<span style="margin-left: 1em;">Kofoid, C. A., <a href="#Page_143">143</a></span><br />
<span style="margin-left: 1em;">v. Körösy, <a href="#Page_300">300</a></span><br />
<span style="margin-left: 1em;">Korschelt, <a href="#Page_361">361</a></span><br />
<span style="margin-left: 1em;">Krakatau, <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Kraus, <a href="#Page_54">54</a> ff.</span><br />
<span style="margin-left: 1em;">Krogh, <a href="#Page_292">292</a></span><br />
<span style="margin-left: 1em;">Kryž, F., <a href="#Page_335">335</a></span><br />
<span style="margin-left: 1em;">Kupelwieser, H., <a href="#Page_75">75</a></span><br />
<br />
<span style="margin-left: 1em;">Lack of oxygen, influence on disintegration of tissue, <a href="#Page_355">355</a> ff.</span><br />
<span style="margin-left: 1em;">Ladoff, S., <a href="#Page_224">224</a></span><br />
<span style="margin-left: 1em;">Lamarck, <a href="#Page_6">6</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Laminaria</i>, <a href="#Page_165">165</a></span><br />
<span style="margin-left: 1em;">Landois, L., <a href="#Page_53">53</a></span><br />
<span style="margin-left: 1em;">Landsteiner, <a href="#Page_66">66</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lanice</i>, <a href="#Page_143">143</a> ff.</span><br />
<span style="margin-left: 1em;">Lankester, E. R., <a href="#Page_41">41</a></span><br />
<span style="margin-left: 1em;">Leathes, J. B., <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Leucæna leucocephala</i>, <a href="#Page_37">37</a></span><br />
<span style="margin-left: 1em;">Levene, <a href="#Page_351">351</a>, <a href="#Page_352">352</a></span><br />
<span style="margin-left: 1em;">Lewis, <a href="#Page_183">183</a>, <a href="#Page_344">344</a>, <a href="#Page_364">364</a></span><br />
<span style="margin-left: 1em;">Light, influence on organ formation, in cave animals, <a href="#Page_319">319</a> ff.;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Proteus</i>, <a href="#Page_325">325</a>;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Eudendrium</i>, <a href="#Page_326">326</a>.</span><br />
<span style="margin-left: 2em;"><em>See also</em> <a href="#Heliotropism">Heliotropism</a>.</span><br />
<span style="margin-left: 1em;">Lillie, F. R., <a href="#Page_80">80</a>, <a href="#Page_82">82</a> ff., <a href="#Page_87">87</a> ff., <a href="#Page_93">93</a>, <a href="#Page_134">134</a>, <a href="#Page_191">191</a>, <a href="#Page_218">218</a>, <a href="#Page_292">292</a></span><br />
<span style="margin-left: 1em;">Lillie, R. S., <a href="#Page_101">101</a>, <a href="#Page_107">107</a>, <a href="#Page_110">110</a>, <a href="#Page_120">120</a> ff.</span><br />
<span style="margin-left: 1em;">Lipase, synthetic action of, <a href="#Page_26">26</a></span><br />
<span style="margin-left: 1em;">Living and dead matter, specific differences between, <a href="#Page_14">14</a> ff.</span><br />
<span style="margin-left: 1em;">Lloyd, D. J., <a href="#Page_111">111</a></span><br />
<span style="margin-left: 1em;">Localization of Mendelian characters in individual chromosomes, <a href="#Page_243">243</a>, <a href="#Page_244">244</a></span><br />
<span style="margin-left: 1em;">Loeb, Leo, <a href="#Page_30">30</a> ff., <a href="#Page_45">45</a>, <a href="#Page_157">157</a>, <a href="#Page_170">170</a>, <a href="#Page_187">187</a> ff., <a href="#Page_342">342</a></span><br />
<span style="margin-left: 1em;">Loevenhart, A. S., <a href="#Page_26">26</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lumbricus rubellus</i>, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lychnis dioica</i>, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lycopodium</i>, <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lygæus</i>, <a href="#Page_201">201</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lymantria dispar</i>, <a href="#Page_220">220</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Lymnæus</i>, <a href="#Page_142">142</a></span><br />
<span style="margin-left: 1em;">Lymphocytes, rôle of, <a href="#Page_45">45</a> ff.</span><br />
<span style="margin-left: 1em;">Lyon, E. P., <a href="#Page_134">134</a> ff.</span><br />
<br />
<span style="margin-left: 1em;">Macfadyen, A., <a href="#Page_36">36</a></span><br />
<span style="margin-left: 1em;">Maeterlinck, <a href="#Page_255">255</a></span><br />
<span style="margin-left: 1em;">Magnus, W., <a href="#Page_60">60</a></span><br />
<span class="pagenum" title="376"><a name="Page_376" id="Page_376"></a></span><span style="margin-left: 1em;">Maltase, synthetic action of, <a href="#Page_25">25</a></span><br />
<span style="margin-left: 1em;">Marchal, P., <a href="#Page_222">222</a> ff., <a href="#Page_254">254</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Margelis</i>, <a href="#Page_192">192</a></span><br />
<span style="margin-left: 1em;">Mass of chromatin and of cytoplasm, <a href="#Page_186">186</a></span><br />
<span style="margin-left: 1em;">Mast, <a href="#Page_269">269</a>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Mathews, A. P., <a href="#Page_107">107</a>, <a href="#Page_363">363</a></span><br />
<span style="margin-left: 1em;">Matthaei, G. L. C., <a href="#Page_302">302</a></span><br />
<span style="margin-left: 1em;">Maxwell, S. S., <a href="#Page_270">270</a>, <a href="#Page_274">274</a>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">McClendon, J. F., <a href="#Page_122">122</a>, <a href="#Page_322">322</a></span><br />
<span style="margin-left: 1em;">McClung, C. E., <a href="#Page_68">68</a>, <a href="#Page_198">198</a> ff., <a href="#Page_237">237</a></span><br />
<span style="margin-left: 1em;">Megusar, <a href="#Page_340">340</a></span><br />
<span style="margin-left: 1em;">Meignon, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;">Meisenheimer, <a href="#Page_225">225</a></span><br />
<span style="margin-left: 1em;">Meltzer, S.J., <a href="#Page_315">315</a></span><br />
<span style="margin-left: 1em;">Membrane formation, <a href="#Page_86">86</a> ff.;</span><br />
<span style="margin-left: 2em;">artificial, <a href="#Page_98">98</a> ff.</span><br />
<span style="margin-left: 1em;">Mendel, G., <a href="#Page_23">23</a>, <a href="#Page_229">229</a> ff.</span><br />
<span style="margin-left: 1em;">Mendelian characters, and evolution, <a href="#Page_70">70</a>, <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">and internal secretions, <a href="#Page_243">243</a>, <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">and enzymes, <a href="#Page_247">247</a>, <a href="#Page_248">248</a>, <a href="#Page_249">249</a></span><br />
<span style="margin-left: 1em;">Mendelian, factors of heredity, <a href="#Page_4">4</a> ff., <a href="#Page_68">68</a>, <a href="#Page_151">151</a> ff.;</span><br />
<span style="margin-left: 2em;">mutation, <a href="#Page_66">66</a>;</span><br />
<span style="margin-left: 2em;">dominant, <a href="#Page_90">90</a>;</span><br />
<span style="margin-left: 2em;">segregation, <a href="#Page_229">229</a> ff.</span><br />
<span style="margin-left: 2em;"><em>See also</em> <a href="#Non-Mendelian_inheritance">Non-Mendelian inheritance</a>.</span><br />
<span style="margin-left: 1em;">Mendelian heredity, mechanism of, <a href="#Page_229">229</a> ff.;</span><br />
<span style="margin-left: 2em;">and chromosomes, <a href="#Page_233">233</a> ff.;</span><br />
<span style="margin-left: 2em;">and hormones, <a href="#Page_245">245</a> ff., <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">and enzymes, <a href="#Page_247">247</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Menidia</i>, <a href="#Page_51">51</a>, <a href="#Page_321">321</a>, <a href="#Page_323">323</a></span><br />
<span style="margin-left: 1em;">Merogony, <a href="#Page_120">120</a>, <a href="#Page_126">126</a>, <a href="#Page_186">186</a></span><br />
<span style="margin-left: 1em;">Merrifield, <a href="#Page_303">303</a></span><br />
<span style="margin-left: 1em;">Mesenchyme formation, <a href="#Page_130">130</a> ff.</span><br />
<span style="margin-left: 1em;">Metamorphosis of tadpoles induced by thyroid, <a href="#Page_155">155</a>, <a href="#Page_156">156</a></span><br />
<span style="margin-left: 1em;">Metchnikoff, <a href="#Page_361">361</a> ff., <a href="#Page_367">367</a> ff.</span><br />
<span style="margin-left: 1em;">Michaelis, L., <a href="#Page_62">62</a>, <a href="#Page_317">317</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Micrococcus prodigiosus</i>, <a href="#Page_334">334</a></span><br />
<span style="margin-left: 1em;">Micromeres, <a href="#Page_132">132</a> ff.</span><br />
<span style="margin-left: 1em;">Minot, <a href="#Page_362">362</a></span><br />
<span style="margin-left: 1em;">Moenkhaus, W. J., <a href="#Page_51">51</a>, <a href="#Page_344">344</a></span><br />
<span style="margin-left: 1em;">Molisch, <a href="#Page_20">20</a></span><br />
<span style="margin-left: 1em;">Montgomery, <a href="#Page_199">199</a>, <a href="#Page_234">234</a></span><br />
<span style="margin-left: 1em;">Moore, A. R., <a href="#Page_50">50</a>, <a href="#Page_247">247</a> ff., <a href="#Page_280">280</a></span><br />
<span style="margin-left: 1em;">Morgan, T. H., <a href="#Page_46">46</a>, <a href="#Page_68">68</a>, <a href="#Page_89">89</a> ff., <a href="#Page_95">95</a>, <a href="#Page_116">116</a>, <a href="#Page_126">126</a>, <a href="#Page_134">134</a>, <a href="#Page_141">141</a> ff., <a href="#Page_173">173</a>, <a href="#Page_175">175</a>, <a href="#Page_184">184</a>, <a href="#Page_204">204</a> ff., <a href="#Page_229">229</a> ff., <a href="#Page_241">241</a> ff., <a href="#Page_244">244</a>, <a href="#Page_347">347</a></span><br />
<span style="margin-left: 1em;">Morse, M., <a href="#Page_156">156</a>, <a href="#Page_353">353</a></span><br />
<span style="margin-left: 1em;">Morton, J. J., <a href="#Page_44">44</a></span><br />
<span style="margin-left: 1em;">Moss, W. L., <a href="#Page_67">67</a></span><br />
<span style="margin-left: 1em;">Muller, H. J., <a href="#Page_229">229</a>, <a href="#Page_231">231</a> ff.</span><br />
<span style="margin-left: 1em;">Murphy, J. B., <a href="#Page_44">44</a> ff.</span><br />
<span style="margin-left: 1em;">Mutation, <a href="#Page_6">6</a>, <a href="#Page_42">42</a>, <a href="#Page_243">243</a>; and evolution, <a href="#Page_347">347</a>, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;">Myers, <a href="#Page_55">55</a></span><br />
<br />
<span style="margin-left: 1em;">Nathanson, <a href="#Page_19">19</a></span><br />
<span style="margin-left: 1em;">Natural death, <a href="#Page_361">361</a> ff.</span><br />
<span style="margin-left: 1em;">Neilson, <a href="#Page_110">110</a></span><br />
<span style="margin-left: 1em;">Newman, <a href="#Page_344">344</a></span><br />
<span style="margin-left: 1em;">Newton’s Law, <a href="#Page_253">253</a></span><br />
<span style="margin-left: 1em;">Nitrifying bacteria, <a href="#Page_16">16</a> ff.</span><br />
<span style="margin-left: 1em;"><a id="Non-Mendelian_inheritance"></a>Non-Mendelian inheritance, genus and species characters, <a href="#Page_70">70</a>, <a href="#Page_151">151</a>, <a href="#Page_251">251</a>;</span><br />
<span style="margin-left: 2em;">rate of segmentation, <a href="#Page_246">246</a>;</span><br />
<span style="margin-left: 2em;">first development, <a href="#Page_247">247</a></span><br />
<span style="margin-left: 1em;">Northrop, <a href="#Page_366">366</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Nostocaceæ</i>, <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Nussbaum, M., <a href="#Page_149">149</a></span><br />
<span style="margin-left: 1em;">Nuttall, G. H. F., <a href="#Page_56">56</a> ff.</span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Ocneria dispar</i>, <a href="#Page_225">225</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Œnotherus</i>, <a href="#Page_369">369</a></span><br />
<span style="margin-left: 1em;">Onslow, H., <a href="#Page_249">249</a></span><br />
<span style="margin-left: 1em;"><a id="Organ-forming_substances"></a>Organ-forming substances or hormones in regeneration, <a href="#Page_154">154</a> ff.;</span><br />
<span style="margin-left: 2em;">causing metamorphosis in tadpoles, <a href="#Page_155">155</a>–<a href="#Page_157">157</a>;</span><br />
<span style="margin-left: 2em;">decidua formation, <a href="#Page_158">158</a>;</span><br />
<span style="margin-left: 2em;">development of milk glands, <a href="#Page_158">158</a>;</span><br />
<span style="margin-left: 2em;">Sachs’s theory of, <a href="#Page_159">159</a></span><br />
<span style="margin-left: 1em;">Organisms from eggs, <a href="#Page_128">128</a> ff.</span><br />
<span style="margin-left: 1em;">Origin of life, <a href="#Page_14">14</a> ff., <a href="#Page_33">33</a> ff.</span><br />
<span style="margin-left: 1em;">Osborne, <a href="#Page_23">23</a></span><br />
<span style="margin-left: 1em;">Osterhout, W. J. V., <a href="#Page_312">312</a></span><br />
<span style="margin-left: 1em;">Ostwald, Wo., <a href="#Page_29">29</a>, <a href="#Page_305">305</a>, <a href="#Page_312">312</a></span><br />
<span style="margin-left: 1em;">Oudemans, <a href="#Page_225">225</a></span><br />
<span style="margin-left: 1em;">Overton, <a href="#Page_123">123</a></span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Palæmon</i>, <a href="#Page_193">193</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Palæmonetas</i>, <a href="#Page_193">193</a>;</span><br />
<span style="margin-left: 2em;">geotropism of, <a href="#Page_270">270</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Palinurus</i>, <a href="#Page_193">193</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Pandorina</i>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Parker, G. H., <a href="#Page_264">264</a>, <a href="#Page_269">269</a></span><br />
<span style="margin-left: 1em;">Parthenogenesis, artificial, <a href="#Page_95">95</a> ff.;</span><br />
<span style="margin-left: 2em;">“spontaneous,” <a href="#Page_107">107</a></span><br />
<span style="margin-left: 1em;">Pasteur, <a href="#Page_14">14</a> ff., <a href="#Page_24">24</a>, <a href="#Page_33">33</a>, <a href="#Page_38">38</a></span><br />
<span style="margin-left: 1em;">Patten, B., <a href="#Page_264">264</a> ff</span><br />
<span style="margin-left: 1em;">Pauli, W., <a href="#Page_289">289</a></span><br />
<span style="margin-left: 1em;">Pavy, <a href="#Page_350">350</a></span><br />
<span class="pagenum" title="377"><a name="Page_377" id="Page_377"></a></span><span style="margin-left: 1em;">Payne, F., <a href="#Page_322">322</a></span><br />
<span style="margin-left: 1em;">Pearl, R., <a href="#Page_203">203</a>, <a href="#Page_244">244</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Penicillium</i>, <a href="#Page_289">289</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Pennaria</i>, <a href="#Page_192">192</a></span><br />
<span style="margin-left: 1em;">Pepsin, synthetic action of, <a href="#Page_28">28</a>, <a href="#Page_62">62</a>, <a href="#Page_63">63</a></span><br />
<span style="margin-left: 1em;">Pfeffer, <a href="#Page_92">92</a> ff.</span><br />
<span style="margin-left: 1em;">Phagocytosis, <a href="#Page_367">367</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Planaria</i>, <a href="#Page_173">173</a> ff., <a href="#Page_177">177</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Planorbis</i>, <a href="#Page_142">142</a></span><br />
<span style="margin-left: 1em;">Plants, heteroplastic grafting in, <a href="#Page_47">47</a> ff.;</span><br />
<span style="margin-left: 2em;">regeneration in, <a href="#Page_160">160</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Polygordius</i>, <a href="#Page_280">280</a></span><br />
<span style="margin-left: 1em;">Polymorphism, <a href="#Page_222">222</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Porthesia</i>, <a href="#Page_256">256</a>, <a href="#Page_280">280</a> ff.</span><br />
<span style="margin-left: 1em;">Preadaptation, <a href="#Page_12">12</a>, <a href="#Page_324">324</a></span><br />
<span style="margin-left: 1em;">Precipitin reaction, <a href="#Page_54">54</a> ff.</span><br />
<span style="margin-left: 1em;">Preformation of organism in egg, <a href="#Page_128">128</a> ff., <a href="#Page_142">142</a>–<a href="#Page_145">145</a></span><br />
<span style="margin-left: 1em;">Presence and absence theory, <a href="#Page_230">230</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Primula</i>, <a href="#Page_243">243</a></span><br />
<span style="margin-left: 1em;">Proteins, specific reactions of, <a href="#Page_54">54</a> ff.;</span><br />
<span style="margin-left: 2em;">and species specificity, <a href="#Page_68">68</a>;</span><br />
<span style="margin-left: 2em;">and evolution, <a href="#Page_70">70</a>, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Protenor</i>, <a href="#Page_200">200</a> ff., <a href="#Page_208">208</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Proteus</i>, <a href="#Page_325">325</a> ff.</span><br />
<span style="margin-left: 1em;">Przibram, H., <a href="#Page_176">176</a></span><br />
<span style="margin-left: 1em;">Pure lines, <a href="#Page_333">333</a>, <a href="#Page_334">334</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Pycnopodia spuria</i>, <a href="#Page_74">74</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Pyrrhocoris</i>, <a href="#Page_198">198</a></span><br />
<br />
<span style="margin-left: 1em;">Radiation pressure, rôle in transmission of spores through interstellar space, <a href="#Page_34">34</a> ff.</span><br />
<span style="margin-left: 1em;"><i>Rana, esculenta</i>, <a href="#Page_46">46</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">palustris</i>, <a href="#Page_46">46</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">virescens</i>, <a href="#Page_46">46</a></span><br />
<span style="margin-left: 1em;">Rate of segmentation, a non-Mendelian hereditary character, <a href="#Page_246">246</a></span><br />
<span style="margin-left: 1em;">Rau, <a href="#Page_366">366</a></span><br />
<span style="margin-left: 1em;">Reaction, tropistic, <a href="#Page_11">11</a> ff., <a href="#Page_92">92</a> ff., <a href="#Page_147">147</a>, <a href="#Page_178">178</a>, <a href="#Page_187">187</a>, <a href="#Page_255">255</a> ff.;</span><br />
<span style="margin-left: 2em;">precipitin, <a href="#Page_54">54</a> ff.;</span><br />
<span style="margin-left: 2em;">anaphylaxis, <a href="#Page_61">61</a> ff.</span><br />
<span style="margin-left: 1em;"><a id="Regeneration"></a>Regeneration, <a href="#Page_9">9</a> ff., <a href="#Page_153">153</a> ff.;</span><br />
<span style="margin-left: 2em;">in plants, <a href="#Page_160">160</a> ff.;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Bryophyllum</i>, <a href="#Page_161">161</a>–<a href="#Page_167">167</a>;</span><br />
<span style="margin-left: 2em;">in animals, <a href="#Page_167">167</a> ff.;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Tubularia</i>, <a href="#Page_167">167</a>–<a href="#Page_170">170</a>;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Cerianthus</i>, <a href="#Page_171">171</a> ff.;</span><br />
<span style="margin-left: 2em;">in Planarians, <a href="#Page_173">173</a>–<a href="#Page_176">176</a>;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Alpheus</i>, <a href="#Page_176">176</a>;</span><br />
<span style="margin-left: 2em;">and autolysis, <a href="#Page_178">178</a>–<a href="#Page_181">181</a>;</span><br />
<span style="margin-left: 2em;">of lens, <a href="#Page_182">182</a>, <a href="#Page_183">183</a>;</span><br />
<span style="margin-left: 2em;">external influences on, <a href="#Page_192">192</a> ff.;</span><br />
<span style="margin-left: 2em;">of gonads in hermaphrodites, <a href="#Page_219">219</a></span><br />
<span style="margin-left: 1em;">Regulation, <a href="#Page_139">139</a>, <a href="#Page_140">140</a>, <a href="#Page_141">141</a>;</span><br />
<span style="margin-left: 2em;">in regeneration, <em>see</em> Regeneration.</span><br />
<span style="margin-left: 1em;">Reichert, E. T., <a href="#Page_64">64</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Reseda</i>, <a href="#Page_90">90</a></span><br />
<span style="margin-left: 1em;">Resistance of spores, <a href="#Page_36">36</a>;</span><br />
<span style="margin-left: 2em;">seeds, <a href="#Page_36">36</a> ff.</span><br />
<span style="margin-left: 1em;">Reversibility of development, in <i class="taxonomic">Campanularia</i>, <a href="#Page_178">178</a> ff.;</span><br />
<span style="margin-left: 2em;">in Ascidians, <a href="#Page_180">180</a>;</span><br />
<span style="margin-left: 2em;">in egg, <a href="#Page_189">189</a> ff.;</span><br />
<span style="margin-left: 2em;">in <i class="taxonomic">Antennularia</i>, <a href="#Page_194">194</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Rhabdonema nigrovenosum</i>, <a href="#Page_213">213</a></span><br />
<span style="margin-left: 1em;">Richet, C., <a href="#Page_61">61</a></span><br />
<span style="margin-left: 1em;">Richter, <a href="#Page_34">34</a></span><br />
<span style="margin-left: 1em;">Ringer solution, <a href="#Page_99">99</a></span><br />
<span style="margin-left: 1em;">Robertson, T. B., <a href="#Page_28">28</a> ff., <a href="#Page_62">62</a> ff., <a href="#Page_104">104</a>, <a href="#Page_311">311</a></span><br />
<span style="margin-left: 1em;">Roentgen rays, <a href="#Page_45">45</a></span><br />
<span style="margin-left: 1em;">Roscoe, <em>see</em> <a href="#Bunsen-Roscoe">Bunsen</a></span><br />
<span style="margin-left: 1em;">Rotifers, determination of sexual cycle by food, <a href="#Page_224">224</a></span><br />
<span style="margin-left: 1em;">Roux, W., <a href="#Page_141">141</a> ff.</span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Saccharomyces</i>, <a href="#Page_36">36</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">cerevisiæ</i>, <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Sacculina</i>, <a href="#Page_216">216</a> ff.</span><br />
<span style="margin-left: 1em;">Sachs, <a href="#Page_88">88</a></span><br />
<span style="margin-left: 1em;">v. Sachs, J., <a href="#Page_145">145</a>, <a href="#Page_154">154</a> ff., <a href="#Page_159">159</a>, <a href="#Page_161">161</a>, <a href="#Page_184">184</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Salamandra maculosa</i>, <a href="#Page_339">339</a></span><br />
<span style="margin-left: 1em;">Salkowski, <a href="#Page_352">352</a></span><br />
<span style="margin-left: 1em;">Salts required for life, <a href="#Page_306">306</a> ff.</span><br />
<span style="margin-left: 1em;">Sansum, W. D., <a href="#Page_64">64</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Schizophyceæ</i>, <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Schleip, W., <a href="#Page_213">213</a></span><br />
<span style="margin-left: 1em;">Schoenbein, <a href="#Page_358">358</a></span><br />
<span style="margin-left: 1em;">Schottelius, <a href="#Page_334">334</a>, <a href="#Page_337">337</a></span><br />
<span style="margin-left: 1em;">Schroeder, <a href="#Page_14">14</a>, <a href="#Page_33">33</a></span><br />
<span style="margin-left: 1em;">Schultze, O., <a href="#Page_141">141</a></span><br />
<span style="margin-left: 1em;">Schütze, <a href="#Page_55">55</a></span><br />
<span style="margin-left: 1em;">Schwann, <a href="#Page_33">33</a></span><br />
<span style="margin-left: 1em;">Schwarzschild, <a href="#Page_34">34</a></span><br />
<span style="margin-left: 1em;">Secretions, internal, <a href="#Page_145">145</a>, <a href="#Page_155">155</a>, <a href="#Page_157">157</a></span><br />
<span style="margin-left: 1em;">Self-digestion, <a href="#Page_350">350</a> ff.</span><br />
<span style="margin-left: 1em;">Self-sterility, <a href="#Page_89">89</a> ff.</span><br />
<span style="margin-left: 1em;">Senescence, <a href="#Page_367">367</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Sequoia</i>, <a href="#Page_31">31</a>, <a href="#Page_368">368</a></span><br />
<span style="margin-left: 1em;">Setchell, W. A., <a href="#Page_165">165</a>, <a href="#Page_287">287</a></span><br />
<span style="margin-left: 1em;">Sex, of parthenogenetic frogs, <a href="#Page_125">125</a>;</span><br />
<span style="margin-left: 2em;">of twins, <a href="#Page_211">211</a></span><br />
<span style="margin-left: 1em;">Sex chromosome, <a href="#Page_199">199</a> ff.</span><br />
<span style="margin-left: 1em;">Sex determination, cytological basis of, <a href="#Page_198">198</a> ff.;</span><br />
<span class="pagenum" title="378"><a name="Page_378" id="Page_378"></a></span><span style="margin-left: 2em;">physiological basis of, <a href="#Page_214">214</a> ff.</span><br />
<span style="margin-left: 1em;">Sexual characters, <a href="#Page_198">198</a> ff.</span><br />
<span style="margin-left: 1em;">Shibata, <a href="#Page_93">93</a></span><br />
<span style="margin-left: 1em;">Shull, A. F., <a href="#Page_214">214</a>, <a href="#Page_224">224</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Sicyonia</i>, <a href="#Page_193">193</a></span><br />
<span style="margin-left: 1em;">Side-chain theory, <a href="#Page_88">88</a>, <a href="#Page_188">188</a></span><br />
<span style="margin-left: 1em;">Smith, Geoffrey, <a href="#Page_159">159</a>, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;">Smith, Graham, <a href="#Page_58">58</a></span><br />
<span style="margin-left: 1em;">Spain, K. C., <a href="#Page_188">188</a></span><br />
<span style="margin-left: 1em;">Spallanzani, <a href="#Page_33">33</a></span><br />
<span style="margin-left: 1em;">Species, chemical basis of, <a href="#Page_40">40</a> ff.;</span><br />
<span style="margin-left: 2em;">specificity of, <a href="#Page_41">41</a> ff.;</span><br />
<span style="margin-left: 2em;">incompatibility of, not closely related, <a href="#Page_44">44</a> ff.</span><br />
<span style="margin-left: 1em;">Species specificity, determined by proteins, <a href="#Page_63">63</a>, <a href="#Page_68">68</a>, <a href="#Page_348">348</a>;</span><br />
<span style="margin-left: 2em;">apparently not by nucleins, <a href="#Page_69">69</a></span><br />
<span style="margin-left: 1em;">Specificity, of grafted tissues, <a href="#Page_47">47</a>;</span><br />
<span style="margin-left: 2em;">of spermatozoa, <a href="#Page_48">48</a>;</span><br />
<span style="margin-left: 2em;">of blood sera, <a href="#Page_53">53</a> ff.;</span><br />
<span style="margin-left: 2em;">in fertilization, <a href="#Page_71">71</a> ff.;</span><br />
<span style="margin-left: 2em;">of activation of sperm by eggs, <a href="#Page_80">80</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Spelerpes</i>, <a href="#Page_320">320</a></span><br />
<span style="margin-left: 1em;">Spermatozoa, fertilization of eggs by, <a href="#Page_72">72</a> ff.;</span><br />
<span style="margin-left: 2em;">activation by eggs of, <a href="#Page_80">80</a> ff.;</span><br />
<span style="margin-left: 2em;">agglutination of, <a href="#Page_82">82</a> ff.;</span><br />
<span style="margin-left: 2em;">cluster formation of, <a href="#Page_83">83</a>;</span><br />
<span style="margin-left: 2em;">chemotropism of, <a href="#Page_92">92</a> ff.;</span><br />
<span style="margin-left: 2em;">cultivating of, <a href="#Page_126">126</a> ff.;</span><br />
<span style="margin-left: 2em;">chromosomes of, <a href="#Page_198">198</a> ff.</span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Spirographis</i>, <a href="#Page_260">260</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Spondylomorum</i>, <a href="#Page_277">277</a></span><br />
<span style="margin-left: 1em;">Spontaneous generation, <a href="#Page_33">33</a>, <a href="#Page_38">38</a></span><br />
<span style="margin-left: 1em;">Spooner, G. B., <a href="#Page_134">134</a></span><br />
<span style="margin-left: 1em;">Standfuss, <a href="#Page_303">303</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Staphylococcus pyogenes aureus</i>, <a href="#Page_36">36</a></span><br />
<span style="margin-left: 1em;">Steffenhagen, K., <a href="#Page_55">55</a></span><br />
<span style="margin-left: 1em;">Steinach, E., <a href="#Page_225">225</a> ff., <a href="#Page_254">254</a>, <a href="#Page_343">343</a></span><br />
<span style="margin-left: 1em;">Stereotropism, <a href="#Page_178">178</a>, <a href="#Page_187">187</a>, <a href="#Page_283">283</a></span><br />
<span style="margin-left: 1em;">Stevens, Miss, <a href="#Page_68">68</a>, <a href="#Page_199">199</a></span><br />
<span style="margin-left: 1em;">Stimulus, <a href="#Page_196">196</a></span><br />
<span style="margin-left: 1em;">Stockard, <a href="#Page_322">322</a>, <a href="#Page_340">340</a></span><br />
<span style="margin-left: 1em;">Strassburger, <a href="#Page_260">260</a></span><br />
<span style="margin-left: 1em;">Streaming as means of egg differentiation, <a href="#Page_145">145</a>, <a href="#Page_146">146</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Strongylocentrotus franciscanus</i>, <a href="#Page_50">50</a>, <a href="#Page_52">52</a>, <a href="#Page_75">75</a>, <a href="#Page_81">81</a> ff., <a href="#Page_103">103</a>, <a href="#Page_247">247</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Strongylocentrotus lividus</i>, <a href="#Page_129">129</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Strongylocentrotus purpuratus</i>, <a href="#Page_52">52</a>, <a href="#Page_73">73</a> ff., <a href="#Page_81">81</a> ff., <a href="#Page_94">94</a>, <a href="#Page_98">98</a> ff., <a href="#Page_103">103</a>, <a href="#Page_108">108</a>, <a href="#Page_109">109</a>, <a href="#Page_111">111</a> ff., <a href="#Page_137">137</a>, <a href="#Page_191">191</a>, <a href="#Page_246">246</a> ff., <a href="#Page_293">293</a> ff., <a href="#Page_364">364</a>;</span><br />
<span style="margin-left: 2em;">larvæ of, <a href="#Page_49">49</a> ff.</span><br />
<span style="margin-left: 1em;">Sturtevant, A. H., <a href="#Page_229">229</a> ff.</span><br />
<span style="margin-left: 1em;">Styela, <a href="#Page_146">146</a></span><br />
<span style="margin-left: 1em;">Sulphur bacteria, <a href="#Page_19">19</a> ff.</span><br />
<span style="margin-left: 1em;">Supergenes, <a href="#Page_5">5</a>, <a href="#Page_9">9</a>, <a href="#Page_136">136</a>, <a href="#Page_319">319</a></span><br />
<span style="margin-left: 1em;">Sutton, W. S., <a href="#Page_68">68</a>, <a href="#Page_233">233</a> ff.</span><br />
<span style="margin-left: 1em;">Synthesis of living matter, by micro-organisms, <a href="#Page_15">15</a> ff.;</span><br />
<span style="margin-left: 2em;">by enzymes, <a href="#Page_24">24</a> ff.</span><br />
<span style="margin-left: 1em;">Synthetic action of enzymes, <a href="#Page_23">23</a> ff., <a href="#Page_38">38</a></span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Tænia</i>, <a href="#Page_212">212</a></span><br />
<span style="margin-left: 1em;">Talbot, <a href="#Page_262">262</a></span><br />
<span style="margin-left: 1em;">Tammann, <a href="#Page_291">291</a></span><br />
<span style="margin-left: 1em;">Tanaka, <a href="#Page_243">243</a></span><br />
<span style="margin-left: 1em;">Taylor, A. E., <a href="#Page_27">27</a>, <a href="#Page_69">69</a> ff.</span><br />
<span style="margin-left: 1em;">Tchistowitch, <a href="#Page_54">54</a> ff.</span><br />
<span style="margin-left: 1em;">Teleost fish, crosses of, <a href="#Page_6">6</a> ff., <a href="#Page_345">345</a></span><br />
<span style="margin-left: 1em;">Temperature, effect on heliotropism, <a href="#Page_280">280</a>;</span><br />
<span style="margin-left: 2em;">upper limit for organisms, <a href="#Page_287">287</a> ff.;</span><br />
<span style="margin-left: 2em;">effect on life, <a href="#Page_288">288</a> ff.;</span><br />
<span style="margin-left: 2em;">on butterflies, <a href="#Page_303">303</a> ff.;</span><br />
<span style="margin-left: 2em;">adaptation to, <a href="#Page_334">334</a> ff.</span><br />
<span style="margin-left: 1em;">Temperature coefficient, <a href="#Page_290">290</a> ff., <a href="#Page_305">305</a>;</span><br />
<span style="margin-left: 2em;">for enzyme, <a href="#Page_291">291</a>;</span><br />
<span style="margin-left: 2em;">for development, <a href="#Page_292">292</a> ff.;</span><br />
<span style="margin-left: 2em;">for oxidations, <a href="#Page_295">295</a>;</span><br />
<span style="margin-left: 2em;">and fluctuating variation, <a href="#Page_296">296</a> ff.;</span><br />
<span style="margin-left: 2em;">for heart-beat, <a href="#Page_300">300</a> ff.;</span><br />
<span style="margin-left: 2em;">for duration of life, <a href="#Page_366">366</a></span><br />
<span style="margin-left: 1em;">Thatcher, Miss, <a href="#Page_181">181</a></span><br />
<span style="margin-left: 1em;">Thyroid inducing metamorphosis in tadpoles, <a href="#Page_155">155</a>, <a href="#Page_156">156</a></span><br />
<span style="margin-left: 1em;">Tichomiroff, <a href="#Page_95">95</a></span><br />
<span style="margin-left: 1em;">Tissue culture of spermatozoa, <a href="#Page_127">127</a></span><br />
<span style="margin-left: 1em;">Tissues, transplantation of, <a href="#Page_30">30</a> ff., <a href="#Page_44">44</a> ff.;</span><br />
<span style="margin-left: 2em;">cultivation of, <a href="#Page_31">31</a> ff.;</span><br />
<span style="margin-left: 2em;">specificity of, <a href="#Page_44">44</a> ff.</span><br />
<span style="margin-left: 1em;">Torrey, H. B., <a href="#Page_264">264</a>, <a href="#Page_269">269</a></span><br />
<span style="margin-left: 1em;">Tower, <a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;">Transfusion of blood, <a href="#Page_53">53</a></span><br />
<span style="margin-left: 1em;">Transplantation, of tissues, <a href="#Page_30">30</a> ff., <a href="#Page_44">44</a> ff.;</span><br />
<span style="margin-left: 2em;">of cancers, <a href="#Page_45">45</a>;</span><br />
<span style="margin-left: 2em;">of anlagen, <a href="#Page_148">148</a>;</span><br />
<span style="margin-left: 2em;">of eye of salamander, <a href="#Page_157">157</a>;</span><br />
<span style="margin-left: 2em;">of testes, <a href="#Page_226">226</a>;</span><br />
<span style="margin-left: 2em;">of ovaries, <a href="#Page_227">227</a></span><br />
<span style="margin-left: 1em;">Traube, <a href="#Page_28">28</a></span><br />
<span style="margin-left: 1em;">Treub, <a href="#Page_21">21</a></span><br />
<span style="margin-left: 1em;">Trial and error, <a href="#Page_268">268</a>, <a href="#Page_270">270</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Trifolium arvense</i>, <a href="#Page_37">37</a></span><br />
<span style="margin-left: 1em;">Tropisms, <a href="#Page_11">11</a> ff., <a href="#Page_92">92</a> ff., <a href="#Page_147">147</a>, <a href="#Page_178">178</a>, <a href="#Page_187">187</a>, <a href="#Page_253">253</a> ff.;</span><br />
<span style="margin-left: 2em;">and instincts, <a href="#Page_253">253</a>;</span><br />
<span style="margin-left: 2em;">theory of, <a href="#Page_257">257</a> ff.</span><br />
<span style="margin-left: 1em;">Tropisms, in embryonic development, <a href="#Page_147">147</a>;</span><br />
<span class="pagenum" title="379"><a name="Page_379" id="Page_379"></a></span><span style="margin-left: 2em;">of cave animals, <a href="#Page_324">324</a></span><br />
<span style="margin-left: 1em;">Trypanosomes, <a href="#Page_332">332</a> ff.</span><br />
<span style="margin-left: 1em;">Trypsin, synthetic action of, <a href="#Page_27">27</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Tuber brumale</i>, <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Tubularia crocea</i>, <a href="#Page_171">171</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Tubularia mesembryanthemum</i>, <a href="#Page_167">167</a>, <a href="#Page_169">169</a>, <a href="#Page_192">192</a></span><br />
<span style="margin-left: 1em;">Twins, origin of, <a href="#Page_136">136</a> ff.;</span><br />
<span style="margin-left: 2em;">sex of, <a href="#Page_211">211</a></span><br />
<span style="margin-left: 1em;">Tyndall, <a href="#Page_33">33</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Typhlogobius</i>, <a href="#Page_320">320</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Typhlomolge</i>, <a href="#Page_320">320</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Typhlotriton</i>, <a href="#Page_320">320</a>, <a href="#Page_323">323</a></span><br />
<span style="margin-left: 1em;">Tyrosinase, <a href="#Page_249">249</a>, <a href="#Page_250">250</a></span><br />
<span style="margin-left: 1em;">Tyrosine, <a href="#Page_249">249</a>, <a href="#Page_250">250</a></span><br />
<br />
<span style="margin-left: 1em;">v. Uexküll, J., <a href="#Page_4">4</a> ff., <a href="#Page_128">128</a>, <a href="#Page_139">139</a></span><br />
<span style="margin-left: 1em;">Uhlenhuth, E., <a href="#Page_157">157</a>, <a href="#Page_183">183</a>, <a href="#Page_187">187</a></span><br />
<span style="margin-left: 1em;">Uhlenhuth, P., <a href="#Page_55">55</a>, <a href="#Page_58">58</a>, <a href="#Page_66">66</a>, <a href="#Page_322">322</a></span><br />
<span style="margin-left: 1em;">Underhill, F. P., <a href="#Page_23">23</a></span><br />
<br />
<span style="margin-left: 1em;"><i class="taxonomic">Vanessa, prorsa</i>, <a href="#Page_303">303</a>;</span><br />
<span style="margin-left: 2em;"><i class="taxonomic">levana</i>, <a href="#Page_303">303</a></span><br />
<span style="margin-left: 1em;">Vaney, <a href="#Page_217">217</a></span><br />
<span style="margin-left: 1em;">Van Slyke, D. D., <a href="#Page_22">22</a>, <a href="#Page_24">24</a>, <a href="#Page_291">291</a></span><br />
<span style="margin-left: 1em;">van’t Hoff, <a href="#Page_24">24</a> ff., <a href="#Page_290">290</a>, <a href="#Page_292">292</a>, <a href="#Page_296">296</a></span><br />
<span style="margin-left: 1em;">Variation, <a href="#Page_6">6</a>, <a href="#Page_297">297</a> ff., <a href="#Page_346">346</a>–<a href="#Page_348">348</a></span><br />
<span style="margin-left: 1em;">Vitzou, <a href="#Page_159">159</a></span><br />
<span style="margin-left: 1em;"><i class="taxonomic">Volvox</i>, <a href="#Page_280">280</a></span><br />
<br />
<span style="margin-left: 1em;">Walcott, <a href="#Page_42">42</a>, <a href="#Page_61">61</a></span><br />
<span style="margin-left: 1em;">Warburg, O., <a href="#Page_117">117</a> ff.</span><br />
<span style="margin-left: 1em;">Warming, <a href="#Page_41">41</a></span><br />
<span style="margin-left: 1em;">Wasps, polymorphism in, <a href="#Page_222">222</a>–<a href="#Page_224">224</a>;</span><br />
<span style="margin-left: 2em;">sex determination, <a href="#Page_255">255</a> ff.</span><br />
<span style="margin-left: 1em;">Wassermann, <a href="#Page_55">55</a></span><br />
<span style="margin-left: 1em;">Wasteneys, H., <a href="#Page_29">29</a>, <a href="#Page_82">82</a>, <a href="#Page_87">87</a>, <a href="#Page_112">112</a>, <a href="#Page_113">113</a>, <a href="#Page_117">117</a>, <a href="#Page_191">191</a>, <a href="#Page_277">277</a>, <a href="#Page_293">293</a>, <a href="#Page_295">295</a>, <a href="#Page_335">335</a>, <a href="#Page_364">364</a></span><br />
<span style="margin-left: 1em;">Weiggert, <a href="#Page_188">188</a></span><br />
<span style="margin-left: 1em;">Weismann, <a href="#Page_7">7</a>, <a href="#Page_30">30</a>, <a href="#Page_303">303</a></span><br />
<span style="margin-left: 1em;">Wells, H. G., <a href="#Page_62">62</a>, <a href="#Page_69">69</a></span><br />
<span style="margin-left: 1em;">Welsh, D. A., <a href="#Page_60">60</a></span><br />
<span style="margin-left: 1em;">Werner, F., <a href="#Page_340">340</a></span><br />
<span style="margin-left: 1em;">Wheeler, W. M., <a href="#Page_43">43</a></span><br />
<span style="margin-left: 1em;">White, J., <a href="#Page_36">36</a></span><br />
<span style="margin-left: 1em;">Whitney, D. D., <a href="#Page_224">224</a></span><br />
<span style="margin-left: 1em;">Wilson, E. B., <a href="#Page_68">68</a>, <a href="#Page_143">143</a>, <a href="#Page_199">199</a> ff.</span><br />
<span style="margin-left: 1em;">Winkler, <a href="#Page_47">47</a></span><br />
<span style="margin-left: 1em;">Winogradsky, S., <a href="#Page_16">16</a> ff., <a href="#Page_42">42</a></span><br />
<span style="margin-left: 1em;">Wolf, G., <a href="#Page_182">182</a>, <a href="#Page_187">187</a></span><br />
<br />
<span style="margin-left: 1em;">Yeast cells, cultivation of, <a href="#Page_15">15</a> ff.</span><br />
<span style="margin-left: 1em;">Young, <a href="#Page_16">16</a>, <a href="#Page_358">358</a></span><br />
</p>
<hr class="chap" />
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Science. By <span class="smcap">E. W. Scripture</span>, Ph.D., M.D.,
Assistant Neurologist Columbia University, formerly Director of the
Psychological Laboratory at Yale University. 189 Illustrations. 2d
Edition, Revised and Enlarged. 8<sup>o</sup>.</p>
<div class="blockquot fs90">
<p>“The chapters on Time and Action, Reaction Time, Thinking Time,
Rhythmic Action, and Power and Will are most interesting. This book
should be carefully read by every one who desires to be familiar
with the advances made in the study of the mind, which advances,
in the last twenty-five years, have been quite as striking and
epoch-making as the strides made in the more material lines of
knowledge.”—<i>Jour. Amer. Med. Ass’n.</i>, Feb. 22, 1908.</p>
</div>
<p><b>25.</b>—<b>The World’s Gold.</b> By <span class="smcap">L. de
Launay</span>, Professor at the École Supérieure des Mines. Translated
by Orlando Cyprian Williams. With an Introduction by Charles A. Conant,
author of “History of Modern Banks of Issue,” etc. 8<sup>o</sup>.</p>
<div class="blockquot fs90">
<p>M. de Launay is a professor of considerable repute not only in
France, but among scientists throughout the world. In this work
he traces the various uses and phases of gold; first its geology;
secondly, its extraction; thirdly, its economic value.</p>
</div>
<p><b>26.</b>—<b>The Interpretation of Radium.</b> By <span
class="smcap">Frederick Soddy</span>, Lecturer in Physical Chemistry in
the University of Glasgow. Third Edition, rewritten, with data brought
down to 1912. 8<sup>o</sup> With 33 Diagrams and Illustrations.</p>
<div class="blockquot fs90">
<p>As the application of the present-day interpretation of Radium
(that it is an element undergoing spontaneous disintegration) is
not confined to the physical sciences, but has a wide and general
bearing upon our whole outlook on Nature, Mr. Soddy has presented
the subject in non-technical language, so that the ideas involved
are within reach of the lay reader. No effort has been spared to
get to the root of the matter and to secure accuracy, so that
the book should prove serviceable to other fields of science and
investigation, as well as to the general public.</p>
</div>
<p><b>27.</b>—<b>The Social Evil.</b> With Special Reference to
Conditions Existing in the City of New York. A Report Prepared in
1902 under the Direction of the Committee of Fifteen. Second Edition,
Revised, with New Material Covering the Years 1902–1911. Edited by
<span class="smcap">Edwin R. A. Seligman</span>, LL.D., McVickar
Professor of Political Economy in Columbia University. 8vo.</p>
<div class="blockquot fs90">
<p>A study that is far from being of merely local interest and
application. The problem is considered in all its aspects and, for
this purpose, reference has been made to conditions prevailing in
other communities and to the different attempts foreign cities have
made to regulate vice.</p>
</div>
<p><b>28.</b>—<b>Microbes and Toxins.</b> By <span class="smcap">Etienne
Burnet</span>, of the Pasteur Institute, Paris. With an Introduction by
Élie Metchnikoff, Sub-Director of the Pasteur Institute, Paris. With
about 71 Illustrations.</p>
<div class="blockquot fs90">
<p>A well-known English authority said in recommending the volume:
“Incomparably the best book there is on this tremendously important
subject. In fact, I am assured that nothing exists which gives
anything like so full a study of microbiology.” In the volume are
considered the general functions of microbes, the microbes of the
human system, the form and structure of microbes, the physiology of
microbes, the pathogenic protozoa, toxins, tuberculin and mallein,
immunity, applications of bacteriology, vaccines and serums,
chemical remedies, etc.</p>
</div>
<p><b>29.</b>—<b>Problems of Life and Reproduction.</b> By <span
class="smcap">Marcus Hartog</span>, D. Sc., Professor of Zoology in
University College, Cork. 8vo.</p>
<div class="blockquot fs90">
<p>The author uses all the legitimate arms of scientific controversy
in assailing certain views that have been widely pressed on
the general public with an assurance that must have given
many the impression that they were protected by the universal
consensus of biologists. Among the subjects considered are: “The
Cellular Pedigree and the Problem of Heredity”; “The Relation
of Brood-Formation to Ordinary Cell-Division”; “The New Force,
Mitokinetism”; “Nuclear Reduction and the Function of Chroism”;
“Fertilization”; “The Transmission of Acquired Characters”;
“Mechanism and Life”; “The Biological Writings of Samuel Butler”;
“Interpolation in Memory”; “The Teaching of Nature Study.”</p>
</div>
<p><b>30.</b>—<b>Problems of the Sexes.</b> By <span class="smcap">Jean
Finot</span>, Author of “The Science of Happiness,” etc. Translated
under authority by Mary J. Safford. 8vo.</p>
<div class="blockquot fs90">
<p>A masterly presentation of the attitude of the ages toward women
and an eloquent plea for her further enfranchisement from imposed
and unnatural limitations. The range of scholarship that has been
enlisted in the writing may well excite one’s wonder, but the tone
of the book is popular and its appeal is not to any small section
of the reading public but to all the classes and degrees of an age
that, from present indications, will go down in history as the
century of Woman.</p>
</div>
<p><b>31.</b>—<b>The Positive Evolution of Religion.</b> Its Moral and
Social Reaction. By <span class="smcap">Frederic Harrison</span>. 8vo.</p>
<div class="blockquot fs90">
<p>The author has undertaken to estimate the moral and social reaction
of various forms of Religion—beginning with Nature Worship,
Polytheism, Catholicism, Protestantism, and Deism. The volume may
be looked upon as the final word, the summary of the celebrated
author’s philosophy—a systematic study of the entire religious
problem.</p>
</div>
<p><b>32.</b>—<b>The Science of Happiness.</b> By <span
class="smcap">Jean Finot</span>, Author of “Problems of the Sexes,”
etc. Translated from the French by Mary J. Safford. 8<sup>o</sup>.</p>
<div class="blockquot fs90">
<p>In this work, which was crowned by the Academy, the author
considers a subject, the solution of which offers more enticement
to the well-wisher of the race than the gold of the Incas did to
the treasure-seekers of Spain, who themselves doubtless looked
upon the coveted yellow metal, however mistakenly, as a key to the
happiness which all are trying to find. “Amid the noisy tumult of
life, amid the dissonance that divides man from man,” remarks M. Finot,
“the Science of Happiness tries to discover the divine link
which binds humanity to happiness through the soul and through the
union of souls.” The author considers the nature of happiness and
the means of its attainment, as well as many allied questions.</p>
</div>
<p><b>33.</b>—<b>Genetic Theory of Reality.</b> Being the Outcome of
Genetic Logic as Issuing in the Æsthetic Theory of Reality Called
Pancalism. By <span class="smcap">James Mark Baldwin</span>, Ph.D.,
D.Sc., LL.D., Foreign Correspondent of the Institute of France, Author
of “History of Psychology,” etc.</p>
<div class="blockquot fs90">
<p>The author here states the general results of the extended studies
in genetic and social science and anthropology made by him and
others, and gives a critical account of the history of the
interpretation of nature and man, both racial and philosophical.</p>
<p>The book offers an <i>Introduction to Philosophy</i> from a new point of
view. It contains, also, a valuable glossary of the terms employed
in these and similar discussions.</p>
</div>
<p><b>34.</b>—<b>Mosquito Control in Panama.</b> The Eradication of
Malaria and Yellow Fever in Cuba and Panama. By <span class="smcap">J. A.
Le Prince</span>, C.E., A. M., Chief Sanitary Inspector,
Isthmian Canal Commission, 1904–1914, and <span class="smcap">A. J.
Orenstein</span>, M.D., Assistant Chief Sanitary Inspector, Isthmian
Canal Commission. With an introduction by <span class="smcap">L. O.
Howard</span>, Ph.D., Entomologist and Chief, Bureau of Entomology,
United States Department of Agriculture. 8<sup>o</sup>. 95 illustrations.</p>
<div class="blockquot fs90">
<p>Mr. Le Prince’s books will be not only of great practical
importance as a guide to future work of the same character,
especially in the Tropics, but also of permanent historic value.</p>
</div>
<p><b>35.</b>—<b>The Organism as a Whole.</b> From a Physico-Chemical
Viewpoint. By <span class="smcap">Jacques Loeb</span>, Author of
“Comparative Physiology of the Brain.” 8<sup>o</sup>.</p>
<div class="blockquot fs90">
<p>The author accounts for the harmonious character of the organism on
a purely physico-chemical basis, without the assumption of design
on the one hand, and without the formulation of too definite a
theory of evolution on the other. The book contains, in addition to
the text, all the necessary illustrations.</p>
</div>
<div class="footnotes mt3em"><h3>FOOTNOTES:</h3>
<div class="footnote">
<p><a name="Footnote_1_1" id="Footnote_1_1"></a><a href="#FNanchor_1_1"><span class="label">1</span></a> Bernard C., <i>Leçons sur les Phénomènes de la Vie</i>. Paris,
1885, i., 22–64.</p></div>
<div class="footnote">
<p><a name="Footnote_2_2" id="Footnote_2_2"></a><a href="#FNanchor_2_2"><span class="label">2</span></a> Driesch, H., <i>The Science and Philosophy of the Organism</i>.
2 vols. The Gifford Lectures, 1907 and 1908.</p></div>
<div class="footnote">
<p><a name="Footnote_3_3" id="Footnote_3_3"></a><a href="#FNanchor_3_3"><span class="label">3</span></a> v. Uexküll, J., <i>Bausteine zu einer biologischen
Weltanschauung</i>. München, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_4_4" id="Footnote_4_4"></a><a href="#FNanchor_4_4"><span class="label">4</span></a> v. Uexküll, J., <i>Bausteine zu einer biologischen
Weltanschauung</i>. München, 1913, p. 216.</p></div>
<div class="footnote">
<p><a name="Footnote_5_5" id="Footnote_5_5"></a><a href="#FNanchor_5_5"><span class="label">5</span></a> de Vries, H., <i>Die Mutationstheorie</i>. Leipzig, 1901.</p></div>
<div class="footnote">
<p><a name="Footnote_6_6" id="Footnote_6_6"></a><a href="#FNanchor_6_6"><span class="label">6</span></a> This difficulty is also felt by mechanistic writers
like Child, who on page 12 of his recent book on <i>Senescence and
Rejuvenescence</i> (Chicago, 1915) makes the following remarks: “These
theories of Weismann do not account satisfactorily for the peculiarly
constant course and character of development and morphogenesis. If we
follow them to their logical conclusion, which their authors have not
done, we find ourselves forced to assume the existence of some sort of
controlling and co-ordinating principle outside the units themselves
and superior to them. If the units constitute the physicochemical
basis of life, as their authors maintain, then this controlling
principle, since it is an essential feature of life, must of necessity
be something which is not physicochemical in nature. In short these
theories lead us in the final analysis to the same conclusion as that
reached by the neovitalists. If we are not content to accept this
conclusion we must reject the theories.” These last sentences do not
exhaust all the possibilities, since the writer is trying to show
in this book that the widest acceptance of the chromosome theory of
heredity is compatible with a consistent physicochemical conception of
the organism as a whole.</p></div>
<div class="footnote">
<p><a name="Footnote_7_7" id="Footnote_7_7"></a><a href="#FNanchor_7_7"><span class="label">7</span></a> Pasteur, L., <i>Annal. d. Chim. et d. Physique</i>, 1862, 3
sér., lxiv., 1.</p></div>
<div class="footnote">
<p><a name="Footnote_8_8" id="Footnote_8_8"></a><a href="#FNanchor_8_8"><span class="label">8</span></a> Winogradsky, S., “Die Nitrification,” <i>Handb. d. tech.
Mykol.</i>, 1904–06, iii., 132.</p></div>
<div class="footnote">
<p><a name="Footnote_9_9" id="Footnote_9_9"></a><a href="#FNanchor_9_9"><span class="label">9</span></a> Winogradsky, <i>loc. cit.</i>, p. 163 and ff.</p></div>
<div class="footnote">
<p><a name="Footnote_10_10" id="Footnote_10_10"></a><a href="#FNanchor_10_10"><span class="label">10</span></a> Godlewski, E., <i>Anz. d. Akad. d. Wissensch. in Krakau</i>,
1892, 408; 1895, 178.</p></div>
<div class="footnote">
<p><a name="Footnote_11_11" id="Footnote_11_11"></a><a href="#FNanchor_11_11"><span class="label">11</span></a> Nathanson, <i>Mitteil. d. zool. Station</i>, Neapel, 1902.</p></div>
<div class="footnote">
<p><a name="Footnote_12_12" id="Footnote_12_12"></a><a href="#FNanchor_12_12"><span class="label">12</span></a> Beijerinck, M., <i>Folia Microbiologica</i>, 1914, iii., 91.</p></div>
<div class="footnote">
<p><a name="Footnote_13_13" id="Footnote_13_13"></a><a href="#FNanchor_13_13"><span class="label">13</span></a> Ernst, A., <i>The New Flora of the Volcanic Island of
Krakatau</i>, Cambridge, 1908.</p></div>
<div class="footnote">
<p><a name="Footnote_14_14" id="Footnote_14_14"></a><a href="#FNanchor_14_14"><span class="label">14</span></a> Euler, H., <i>Pflanzenchemie</i>, 1909, ii. and iii., 140.</p></div>
<div class="footnote">
<p><a name="Footnote_15_15" id="Footnote_15_15"></a><a href="#FNanchor_15_15"><span class="label">15</span></a> This fact was thoroughly established by Mendel and
Osborne. A summary of their work is given in Underhill, F. P.,
<i>Physiology of the Amino Acids</i>, 1916.</p></div>
<div class="footnote">
<p><a name="Footnote_16_16" id="Footnote_16_16"></a><a href="#FNanchor_16_16"><span class="label">16</span></a> Van Slyke, D. D., and Cullen, G. E., <i>Jour. Biol. Chem.</i>,
1914, xix., 141.</p></div>
<div class="footnote">
<p><a name="Footnote_17_17" id="Footnote_17_17"></a><a href="#FNanchor_17_17"><span class="label">17</span></a> Hill, C., <i>Jour. Chem. Soc.</i>, 1898, lxxiii., 634.</p></div>
<div class="footnote">
<p><a name="Footnote_18_18" id="Footnote_18_18"></a><a href="#FNanchor_18_18"><span class="label">18</span></a> Armstrong, E. F., <i>Proc. Royal Soc.</i>, 1905, B. lxxvi.,
592.</p></div>
<div class="footnote">
<p><a name="Footnote_19_19" id="Footnote_19_19"></a><a href="#FNanchor_19_19"><span class="label">19</span></a> Kastle, J. H., and Loevenhart, A. S., <i>Am. Chem. Jour.</i>,
1900, xxiv., 491.</p></div>
<div class="footnote">
<p><a name="Footnote_20_20" id="Footnote_20_20"></a><a href="#FNanchor_20_20"><span class="label">20</span></a> Taylor, A. E., <i>Univ. Cal. Pub.</i>, 1904, <i>Pathology</i>, i.,
33; <i>Jour. Biol. Chem.</i>, 1906, ii., 87.</p></div>
<div class="footnote">
<p><a name="Footnote_21_21" id="Footnote_21_21"></a><a href="#FNanchor_21_21"><span class="label">21</span></a> Bradley, H. C., <i>Jour. Biol. Chem.</i>, 1913, xiii., 407.</p></div>
<div class="footnote">
<p><a name="Footnote_22_22" id="Footnote_22_22"></a><a href="#FNanchor_22_22"><span class="label">22</span></a> This would lead to the idea that the enzymes in the cell
also synthetize molecules of their own kind, or that, in other words,
the synthetic processes in the cell are of the nature of autocatalysis.
Loeb, <i>Der chemische Character des Befruchtungsvorgangs</i>, Leipzig,
1908. Robertson, T. B., <i>Arch. f. Entwicklngsmech.</i>, 1908, xxv., 581;
xxvi., 108; 1913, xxxvii., 497; <i>Am. Jour. Physiol.</i>, 1915, xxxvii.,
1; Robertson and Wasteneys, H., <i>Arch. f. Entwicklngsmech.</i>, 1913,
xxxvii., 485. Ostwald, Wo., <i>Über die zeitlichen Eigenschaften der
Entwicklungsvorgänge</i>, Leipzig, 1908.</p></div>
<div class="footnote">
<p><a name="Footnote_23_23" id="Footnote_23_23"></a><a href="#FNanchor_23_23"><span class="label">23</span></a> Loeb, Leo, <i>Jour. Med. Res.</i>, 1901, vi., 28; <i>Arch. f.
Entwicklngsmech.</i>, 1907, xxiv., 655.</p></div>
<div class="footnote">
<p><a name="Footnote_24_24" id="Footnote_24_24"></a><a href="#FNanchor_24_24"><span class="label">24</span></a> Loeb, Leo, <i>Über die Entstehung von Bindegewebe,
Leucocyten und rothen Blutkörperchen aus Epithel und über eine Methode
isolierte Gewebsteile zu züchten</i>. Chicago, 1897.</p></div>
<div class="footnote">
<p><a name="Footnote_25_25" id="Footnote_25_25"></a><a href="#FNanchor_25_25"><span class="label">25</span></a> While this has been demonstrated thus far only for
connective-tissue cells it may be true also for other cells.</p></div>
<div class="footnote">
<p><a name="Footnote_26_26" id="Footnote_26_26"></a><a href="#FNanchor_26_26"><span class="label">26</span></a> Arrhenius, S., <i>Worlds in the Making</i>, London and New
York, 1908, p. 212.</p></div>
<div class="footnote">
<p><a name="Footnote_27_27" id="Footnote_27_27"></a><a href="#FNanchor_27_27"><span class="label">27</span></a> White, J., <i>Proc. Roy. Soc.</i>, 1909, B, lxxxi., 417.</p></div>
<div class="footnote">
<p><a name="Footnote_28_28" id="Footnote_28_28"></a><a href="#FNanchor_28_28"><span class="label">28</span></a> Macfadyen, A., <i>Proc. Roy. Soc.</i>, 1903, lxxi., 76.</p></div>
<div class="footnote">
<p><a name="Footnote_29_29" id="Footnote_29_29"></a><a href="#FNanchor_29_29"><span class="label">29</span></a> Becquerel, P., <i>Revue générale des Sciences</i>, 1914, xxv.,
559.</p></div>
<div class="footnote">
<p><a name="Footnote_30_30" id="Footnote_30_30"></a><a href="#FNanchor_30_30"><span class="label">30</span></a> Winogradsky, S., <i>Beiträge zur Morphologie und
Physiologie der Bacterien</i>. Leipzig, 1888.</p></div>
<div class="footnote">
<p><a name="Footnote_31_31" id="Footnote_31_31"></a><a href="#FNanchor_31_31"><span class="label">31</span></a> Johannsen, W., <i>Elemente der exacten Erblichkeitslehre</i>.
2d ed., 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_32_32" id="Footnote_32_32"></a><a href="#FNanchor_32_32"><span class="label">32</span></a> Murphy, J. B., <i>Jour. Exper. Med.</i>, 1913, xvii., 482;
1914, xix., 181; xix., 513; Murphy and Morton, J. J., <i>Jour. Exper.
Med.</i>, 1915, xxii., 204.</p></div>
<div class="footnote">
<p><a name="Footnote_33_33" id="Footnote_33_33"></a><a href="#FNanchor_33_33"><span class="label">33</span></a> The reader is referred to Morgan’s book on <i>Regeneration</i>
(New York, 1901), for the literature on this subject.</p></div>
<div class="footnote">
<p><a name="Footnote_34_34" id="Footnote_34_34"></a><a href="#FNanchor_34_34"><span class="label">34</span></a> Baur, E., <i>Einführung in die experimentelle
Vererbungslehre</i>. Berlin, 1911, p. 232.</p></div>
<div class="footnote">
<p><a name="Footnote_35_35" id="Footnote_35_35"></a><a href="#FNanchor_35_35"><span class="label">35</span></a> Literature on this subject in Chapter IV.</p></div>
<div class="footnote">
<p><a name="Footnote_36_36" id="Footnote_36_36"></a><a href="#FNanchor_36_36"><span class="label">36</span></a> Loeb, J., King, W. O. R., and Moore, A. R., <i>Arch. f.
Entwicklngsmech.</i>, 1910, xxix., 354.</p></div>
<div class="footnote">
<p><a name="Footnote_37_37" id="Footnote_37_37"></a><a href="#FNanchor_37_37"><span class="label">37</span></a> Moenkhaus, W. J., <i>Am. Jour. Anat.</i>, 1904, iii., 29.</p></div>
<div class="footnote">
<p><a name="Footnote_38_38" id="Footnote_38_38"></a><a href="#FNanchor_38_38"><span class="label">38</span></a> Loeb, J., <i>Jour. Morphol.</i>, 1912, xxiii., 1.</p></div>
<div class="footnote">
<p><a name="Footnote_39_39" id="Footnote_39_39"></a><a href="#FNanchor_39_39"><span class="label">39</span></a> Landois, L., <i>Zur Lehre von der Bluttransfusion</i>.
Leipzig, 1875.</p></div>
<div class="footnote">
<p><a name="Footnote_40_40" id="Footnote_40_40"></a><a href="#FNanchor_40_40"><span class="label">40</span></a> This is probably true only within the limits of exactness
used in these experiments.</p></div>
<div class="footnote">
<p><a name="Footnote_41_41" id="Footnote_41_41"></a><a href="#FNanchor_41_41"><span class="label">41</span></a> Friedenthal, H., “Experimenteller Nachweis der
Blutverwandtschaft.” <i>Arch. f. Physiol.</i>, 1900, 494.</p></div>
<div class="footnote">
<p><a name="Footnote_42_42" id="Footnote_42_42"></a><a href="#FNanchor_42_42"><span class="label">42</span></a> Uhlenhuth, P., and Steffenhagen, K., Kolle-Wassermann,
<i>Handb. d. pathol. Mikroorg.</i>, 2nd Ed., 1913, iii., 257.</p></div>
<div class="footnote">
<p><a name="Footnote_43_43" id="Footnote_43_43"></a><a href="#FNanchor_43_43"><span class="label">43</span></a> Nuttall, George H. F., <i>Blood Immunity and Blood
Relationship</i>, Cambridge Univ. Press, 1904.</p></div>
<div class="footnote">
<p><a name="Footnote_44_44" id="Footnote_44_44"></a><a href="#FNanchor_44_44"><span class="label">44</span></a> Nuttall, <i>Blood Immunity and Blood Relationship</i>, pp. 319
and 320.</p></div>
<div class="footnote">
<p><a name="Footnote_45_45" id="Footnote_45_45"></a><a href="#FNanchor_45_45"><span class="label">45</span></a> Nuttall, pp. 345 and 346.</p></div>
<div class="footnote">
<p><a name="Footnote_46_46" id="Footnote_46_46"></a><a href="#FNanchor_46_46"><span class="label">46</span></a> Welsh, D. A., and Chapman, H. G., <i>Jour. Hygiene</i>, 1910,
x., 177.</p></div>
<div class="footnote">
<p><a name="Footnote_47_47" id="Footnote_47_47"></a><a href="#FNanchor_47_47"><span class="label">47</span></a> Magnus, W., and Friedenthal, H., <i>Ber. d. deutsch. bot.
Gesellsch.</i>, 1906, xxiv., 601.</p></div>
<div class="footnote">
<p><a name="Footnote_48_48" id="Footnote_48_48"></a><a href="#FNanchor_48_48"><span class="label">48</span></a> Richet, C., <i>L’anaphylaxie</i>. Paris, 1912.</p></div>
<div class="footnote">
<p><a name="Footnote_49_49" id="Footnote_49_49"></a><a href="#FNanchor_49_49"><span class="label">49</span></a> Quoted from Wells, H. G., <i>Jour. Infect. Diseases</i>, 1908,
v., 449.</p></div>
<div class="footnote">
<p><a name="Footnote_50_50" id="Footnote_50_50"></a><a href="#FNanchor_50_50"><span class="label">50</span></a> <i>Ibid.</i>, 1911, ix., 147.</p></div>
<div class="footnote">
<p><a name="Footnote_51_51" id="Footnote_51_51"></a><a href="#FNanchor_51_51"><span class="label">51</span></a> Gay, F. P., and Robertson, T. B., <i>Jour. Biol. Chem.</i>,
1912, xii., 233.</p></div>
<div class="footnote">
<p><a name="Footnote_52_52" id="Footnote_52_52"></a><a href="#FNanchor_52_52"><span class="label">52</span></a> Fitzgerald, J. G., and Leathes, J. B., <i>Univ. Cal. Pub.</i>,
1912, “Pathology,” ii., 39.</p></div>
<div class="footnote">
<p><a name="Footnote_53_53" id="Footnote_53_53"></a><a href="#FNanchor_53_53"><span class="label">53</span></a> Bradley, H. C., and Sansum, W. D., <i>Jour. Biol. Chem.</i>,
1914, xviii., 497.</p></div>
<div class="footnote">
<p><a name="Footnote_54_54" id="Footnote_54_54"></a><a href="#FNanchor_54_54"><span class="label">54</span></a> Reichert, E. T., and Brown, A. P., “The Differentiation
and Specificity of Corresponding Proteins and other Vital Substances in
Relation to Biological Classification and Organic Evolution.” Carnegie
Institution Publication No. 116, Washington, 1909.</p></div>
<div class="footnote">
<p><a name="Footnote_55_55" id="Footnote_55_55"></a><a href="#FNanchor_55_55"><span class="label">55</span></a> Uhlenhuth, <i>Das biologische Verfahren zur Erkennung und
Unterscheidung von Menschen und Tierblut</i>, Jena, 1905, p. 102.</p></div>
<div class="footnote">
<p><a name="Footnote_56_56" id="Footnote_56_56"></a><a href="#FNanchor_56_56"><span class="label">56</span></a> Moss, W. L., <i>Johns Hopkins Hospital Bulletin</i>, 1910,
xxi., 62.</p></div>
<div class="footnote">
<p><a name="Footnote_57_57" id="Footnote_57_57"></a><a href="#FNanchor_57_57"><span class="label">57</span></a> Taylor, A. E., <i>Jour. Biol. Chem.</i>, 1908, v., 311.</p></div>
<div class="footnote">
<p><a name="Footnote_58_58" id="Footnote_58_58"></a><a href="#FNanchor_58_58"><span class="label">58</span></a> Wells, H. G., <i>Jour. Infect. Diseases</i>, 1911, ix., 166.</p></div>
<div class="footnote">
<p><a name="Footnote_59_59" id="Footnote_59_59"></a><a href="#FNanchor_59_59"><span class="label">59</span></a> Loeb, J., and Bancroft, F. W., <i>Jour. Exper. Zoöl.</i>,
1912, xii., 381.</p></div>
<div class="footnote">
<p><a name="Footnote_60_60" id="Footnote_60_60"></a><a href="#FNanchor_60_60"><span class="label">60</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1903, xcix., 323;
1904, civ., 325; <i>Arch. f. Entwcklngsmech.</i>, 1910, xxx., II., 44; 1914,
xl., 310; <i>Science</i>, 1914, xl., 316.</p></div>
<div class="footnote">
<p><a name="Footnote_61_61" id="Footnote_61_61"></a><a href="#FNanchor_61_61"><span class="label">61</span></a> Godlewski, E., <i>Arch. f. Entwcklngsmech.</i>, 1906, xx.,
579.</p></div>
<div class="footnote">
<p><a name="Footnote_62_62" id="Footnote_62_62"></a><a href="#FNanchor_62_62"><span class="label">62</span></a> Kupelwieser, H., <i>Arch. f. Entwcklngsmech.</i>, 1909,
xxvii., 434; <i>Arch. f. Zellforsch.</i>, 1912, viii., 352.</p></div>
<div class="footnote">
<p><a name="Footnote_63_63" id="Footnote_63_63"></a><a href="#FNanchor_63_63"><span class="label">63</span></a> See Chapter II.</p></div>
<div class="footnote">
<p><a name="Footnote_64_64" id="Footnote_64_64"></a><a href="#FNanchor_64_64"><span class="label">64</span></a> Loeb, J., <i>Science</i>, 1914, xl., 316; <i>Am. Naturalist</i>,
1915, xlix., 257.</p></div>
<div class="footnote">
<p><a name="Footnote_65_65" id="Footnote_65_65"></a><a href="#FNanchor_65_65"><span class="label">65</span></a> Loeb, <i>Arch. f. Entwcklngsmech.</i>, 1914, xl., 310.</p></div>
<div class="footnote">
<p><a name="Footnote_66_66" id="Footnote_66_66"></a><a href="#FNanchor_66_66"><span class="label">66</span></a> Godlewski, E., <i>Arch. f. Entwcklngsmech.</i>, 1911, xxxiii.,
196.</p></div>
<div class="footnote">
<p><a name="Footnote_67_67" id="Footnote_67_67"></a><a href="#FNanchor_67_67"><span class="label">67</span></a> Herlant, M., <i>Anat. Anzeiger</i>, 1912, xlii., 563.</p></div>
<div class="footnote">
<p><a name="Footnote_68_68" id="Footnote_68_68"></a><a href="#FNanchor_68_68"><span class="label">68</span></a> Loeb, J., <i>Jour. Exper. Zoöl.</i>, 1914, xvii., 123.</p></div>
<div class="footnote">
<p><a name="Footnote_69_69" id="Footnote_69_69"></a><a href="#FNanchor_69_69"><span class="label">69</span></a> Lillie, F. R., <i>Jour. Exper. Zoöl.</i>, 1914, xvi., 523.</p></div>
<div class="footnote">
<p><a name="Footnote_70_70" id="Footnote_70_70"></a><a href="#FNanchor_70_70"><span class="label">70</span></a> Loeb, J., <i>Am. Naturalist</i>, 1915, xlix., 257.</p></div>
<div class="footnote">
<p><a name="Footnote_71_71" id="Footnote_71_71"></a><a href="#FNanchor_71_71"><span class="label">71</span></a> Lillie, F. R., <i>Science</i>, 1913, xxxviii., 524; <i>Jour.
Exper. Zoöl.</i>, 1914, xvi., 523; <i>Biol. Bull.</i>, 1915, xxviii., 18.</p></div>
<div class="footnote">
<p><a name="Footnote_72_72" id="Footnote_72_72"></a><a href="#FNanchor_72_72"><span class="label">72</span></a> Lillie, F. R., <i>loc. cit.</i></p></div>
<div class="footnote">
<p><a name="Footnote_73_73" id="Footnote_73_73"></a><a href="#FNanchor_73_73"><span class="label">73</span></a> Loeb, J., <i>Jour. Exper. Zoöl</i>., 1914, xvii., 123; <i>Am.
Naturalist</i>, 1915, xlix., 257.</p></div>
<div class="footnote">
<p><a name="Footnote_74_74" id="Footnote_74_74"></a><a href="#FNanchor_74_74"><span class="label">74</span></a> Loeb, J., <i>Arch. f. Entwcklngsmech.</i>, 1907, xxii., 479;
<i>Artificial Parthenogenesis and Fertilization</i>, Chicago, 1913, p. 240.</p></div>
<div class="footnote">
<p><a name="Footnote_75_75" id="Footnote_75_75"></a><a href="#FNanchor_75_75"><span class="label">75</span></a> Loeb, J., <i>Science</i>, 1913, xxxviii., 749; <i>Arch. f.
Entwcklngsmech.</i>, 1914, xxxviii., 277; Wasteneys, H., <i>Jour. Biol.
Chem.</i>, 1916, xxiv., 281.</p></div>
<div class="footnote">
<p><a name="Footnote_76_76" id="Footnote_76_76"></a><a href="#FNanchor_76_76"><span class="label">76</span></a> Loeb, J., <i>Am. Naturalist</i>, 1915, xlix., 257.</p>
<p>The writer may be permitted to illustrate by a special case his reason
for declining to accept Ehrlich’s side-chain theory. Ehrlich and Sachs
found that if to a given mass of toxin small quantities of antitoxin
are added successively the first fraction added neutralized more
than the later fractions; and on the basis of this reasoning Ehrlich
concluded that ten different toxins were contained in the diphtheria
toxin. Arrhenius showed that the same phenomenon can be obtained when
a weak base like NH<sub>4</sub>OH is neutralized by a weak acid (<i>e. g.</i>,
boric acid); hence we should assume that NH<sub>4</sub>OH consists of ten
different forms of ammonia. Both cases, the saturation of toxin with
antitoxin and ammonia with boric acid are equilibrium phenomena.
(Arrhenius, S., <i>Quantitative Laws in Biological Chemistry</i>, London,
1915.)</p></div>
<div class="footnote">
<p><a name="Footnote_77_77" id="Footnote_77_77"></a><a href="#FNanchor_77_77"><span class="label">77</span></a> Castle, W. E., <i>Bull. Mus. Comp. Zoöl.</i>, Harvard, 1896,
xxvii., 203.</p></div>
<div class="footnote">
<p><a name="Footnote_78_78" id="Footnote_78_78"></a><a href="#FNanchor_78_78"><span class="label">78</span></a> Morgan, T. H., <i>Jour. Exper. Zoöl.</i>, 1904, i., 135;
<i>Arch. f. Entwcklngsmech.</i>, 1910, xxx., 206.</p></div>
<div class="footnote">
<p><a name="Footnote_79_79" id="Footnote_79_79"></a><a href="#FNanchor_79_79"><span class="label">79</span></a> Fuchs, H. M., <i>Jour. Genet.</i>, 1915, iv., 215.</p></div>
<div class="footnote">
<p><a name="Footnote_80_80" id="Footnote_80_80"></a><a href="#FNanchor_80_80"><span class="label">80</span></a> Quoted from Fuchs.</p></div>
<div class="footnote">
<p><a name="Footnote_81_81" id="Footnote_81_81"></a><a href="#FNanchor_81_81"><span class="label">81</span></a> Correns, C., <i>Biol. Centralbl.</i>, 1913, xxxiii., 389.</p></div>
<div class="footnote">
<p><a name="Footnote_82_82" id="Footnote_82_82"></a><a href="#FNanchor_82_82"><span class="label">82</span></a> Pfeffer, <i>Untersuchungen aus dem botanischen Institut zu
Tübingen</i>, 1881–1885, i., 363.</p></div>
<div class="footnote">
<p><a name="Footnote_83_83" id="Footnote_83_83"></a><a href="#FNanchor_83_83"><span class="label">83</span></a> Bruchmann, H., <i>Flora</i>, 1909, ic., 193.</p></div>
<div class="footnote">
<p><a name="Footnote_84_84" id="Footnote_84_84"></a><a href="#FNanchor_84_84"><span class="label">84</span></a> The substitution of well-known physicochemical agencies
for the mysterious action of the spermatozoön was the task the
writer set himself in this work and not the explanation of natural
parthenogenesis, as the author of a recent text-book seems to assume.</p></div>
<div class="footnote">
<p><a name="Footnote_85_85" id="Footnote_85_85"></a><a href="#FNanchor_85_85"><span class="label">85</span></a> Loeb, J., <i>Am. Jour. Physiol.</i>, 1899, iii., 135; 1900,
iii., 434.</p></div>
<div class="footnote">
<p><a name="Footnote_86_86" id="Footnote_86_86"></a><a href="#FNanchor_86_86"><span class="label">86</span></a> Loeb, J., <i>Artificial Parthenogenesis and Fertilization</i>,
Chicago, 1913. The reader is referred to this book for the literature
on the subject.</p></div>
<div class="footnote">
<p><a name="Footnote_87_87" id="Footnote_87_87"></a><a href="#FNanchor_87_87"><span class="label">87</span></a> The reader will find a description of the development of
this egg in the next chapter.</p></div>
<div class="footnote">
<p><a name="Footnote_88_88" id="Footnote_88_88"></a><a href="#FNanchor_88_88"><span class="label">88</span></a> The reader is referred for details to the writer’s book
on the subject.</p></div>
<div class="footnote">
<p><a name="Footnote_89_89" id="Footnote_89_89"></a><a href="#FNanchor_89_89"><span class="label">89</span></a> Robertson, T. B., <i>Arch. f. Entwcklngsmech.</i>, 1912,
xxxv., 64.</p></div>
<div class="footnote">
<p><a name="Footnote_90_90" id="Footnote_90_90"></a><a href="#FNanchor_90_90"><span class="label">90</span></a> Loeb, J., <i>Über den chemischen Charakter des
Befruchtungsvorgangs</i>, etc., Leipzig, 1908.</p></div>
<div class="footnote">
<p><a name="Footnote_91_91" id="Footnote_91_91"></a><a href="#FNanchor_91_91"><span class="label">91</span></a> v. Knaffl, E., <i>Arch. f. d. ges. Physiol.</i>, 1908,
cxxiii., 279.</p></div>
<div class="footnote">
<p><a name="Footnote_92_92" id="Footnote_92_92"></a><a href="#FNanchor_92_92"><span class="label">92</span></a> Loeb, J., <i>Artificial Parthenogenesis and Fertilization</i>,
p. 255.</p></div>
<div class="footnote">
<p><a name="Footnote_93_93" id="Footnote_93_93"></a><a href="#FNanchor_93_93"><span class="label">93</span></a> It has been stated by several writers that the eggs of
the sea urchin can no longer form the fertilization membrane when the
jelly surrounding the egg is dissolved. The writer has found that if
the jelly surrounding the eggs of <i>Strongylocentrotus purpuratus</i> is
dissolved by acid the eggs still form a fertilization membrane upon the
entrance of a spermatozoön.</p></div>
<div class="footnote">
<p><a name="Footnote_94_94" id="Footnote_94_94"></a><a href="#FNanchor_94_94"><span class="label">94</span></a> Loeb, J., <i>Artificial Parthenogenesis and Fertilization</i>,
1913, p. 250 and ff.</p></div>
<div class="footnote">
<p><a name="Footnote_95_95" id="Footnote_95_95"></a><a href="#FNanchor_95_95"><span class="label">95</span></a> Delage, Y., <i>Arch. d. Zoöl. expér. et gén.</i>, 1902, x.,
213; 1904, ii., 27; 1905, iii., 104.</p></div>
<div class="footnote">
<p><a name="Footnote_96_96" id="Footnote_96_96"></a><a href="#FNanchor_96_96"><span class="label">96</span></a> Lillie, R. S., <i>Jour. Biol. Chem.</i>, 1916, xxiv., 233.</p></div>
<div class="footnote">
<p><a name="Footnote_97_97" id="Footnote_97_97"></a><a href="#FNanchor_97_97"><span class="label">97</span></a> It is necessary to call attention to the fact that
sugar solutions of a high concentration (<i>e. g.</i>, m solutions)
have a much higher osmotic pressure than that which they should have
theoretically (Lord Berkeley and Hartley). Delage by ignoring this fact
has misinterpreted his experiments with sugar solutions. See Lloyd, D. J.,
<i>Arch. f. Entwcklngsmech.</i>, 1914, xxxviii., 402.</p></div>
<div class="footnote">
<p><a name="Footnote_98_98" id="Footnote_98_98"></a><a href="#FNanchor_98_98"><span class="label">98</span></a> Loeb, J., and Wasteneys, H., <i>Jour. Biol. Chem.</i>, 1913,
xiv., 517; <i>Biochem. Ztschr.</i>, 1913, lvi., 295.</p></div>
<div class="footnote">
<p><a name="Footnote_99_99" id="Footnote_99_99"></a><a href="#FNanchor_99_99"><span class="label">99</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1906, ii., 81.</p></div>
<div class="footnote">
<p><a name="Footnote_100_100" id="Footnote_100_100"></a><a href="#FNanchor_100_100"><span class="label">100</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1906, cxiii.,
487; <i>Biochem. Ztschr.</i>, 1910, xxvi., 279, 289; xxvii., 304; xxix., 80;
<i>Arch. f. Entwcklngsmech.</i>, 1914, xl., 322.</p></div>
<div class="footnote">
<p><a name="Footnote_101_101" id="Footnote_101_101"></a><a href="#FNanchor_101_101"><span class="label">101</span></a> Herlant, M., <i>Arch. de Biol.</i>, 1913, xxviii., 505.</p></div>
<div class="footnote">
<p><a name="Footnote_102_102" id="Footnote_102_102"></a><a href="#FNanchor_102_102"><span class="label">102</span></a> It is also important to remember that the formation of
astrospheres after mere membrane formation occurs considerably more
slowly than if the egg has also received a treatment with a hypertonic
solution.</p></div>
<div class="footnote">
<p><a name="Footnote_103_103" id="Footnote_103_103"></a><a href="#FNanchor_103_103"><span class="label">103</span></a> The writer found that the eggs of <i>Fundulus</i> will
segment a number of times even if all the oxygen has apparently been
removed.</p></div>
<div class="footnote">
<p><a name="Footnote_104_104" id="Footnote_104_104"></a><a href="#FNanchor_104_104"><span class="label">104</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1906, ii., 183.</p></div>
<div class="footnote">
<p><a name="Footnote_105_105" id="Footnote_105_105"></a><a href="#FNanchor_105_105"><span class="label">105</span></a> Thus the treatment of an unfertilized egg without
membrane with a hypertonic solution combines two effects, first the
general cytolytic alteration of the cortical layer of the membrane and
the corrective effect of the hypertonic solution. The former effect
raises the rate of oxidations in the egg, the latter does not.</p></div>
<div class="footnote">
<p><a name="Footnote_106_106" id="Footnote_106_106"></a><a href="#FNanchor_106_106"><span class="label">106</span></a> Warburg, O., <i>Sitzungsber. d. Heidelberger Akad. d.
Wissnsch.</i>, B. 1914.</p></div>
<div class="footnote">
<p><a name="Footnote_107_107" id="Footnote_107_107"></a><a href="#FNanchor_107_107"><span class="label">107</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1906, ii., 87.</p></div>
<div class="footnote">
<p><a name="Footnote_108_108" id="Footnote_108_108"></a><a href="#FNanchor_108_108"><span class="label">108</span></a> Unless the egg is left so long in the pure NaCl solution
that its permeability is increased.</p></div>
<div class="footnote">
<p><a name="Footnote_109_109" id="Footnote_109_109"></a><a href="#FNanchor_109_109"><span class="label">109</span></a> Lillie, R. S., <i>Jour. Morphol.</i>, 1911, xxii., 695; <i>Am.
Jour. Physiol.</i>, 1911, xxvii., 289.</p></div>
<div class="footnote">
<p><a name="Footnote_110_110" id="Footnote_110_110"></a><a href="#FNanchor_110_110"><span class="label">110</span></a> McClendon, J. F., Publications of the Carnegie
Institution, No. 183, 125; <i>Am. Jour. Physiol.</i>, 1910, xxvii., 240.</p></div>
<div class="footnote">
<p><a name="Footnote_111_111" id="Footnote_111_111"></a><a href="#FNanchor_111_111"><span class="label">111</span></a> Gray, J., <i>Proc. Cambridge Philosophical Society</i>, 1913,
xvii., 1.</p></div>
<div class="footnote">
<p><a name="Footnote_112_112" id="Footnote_112_112"></a><a href="#FNanchor_112_112"><span class="label">112</span></a> R. Lillie has recently shown that in a hypotonic
solution water diffuses more rapidly into a fertilized than into an
unfertilized egg. This is exactly what one should expect since the
unfertilized egg is not only surrounded by the cortical layer but also
by a thick layer of jelly both of which are lacking in the fertilized
egg. It is difficult to understand how this observation can throw any
light on the mechanism of development, since water diffuses rapidly
enough into the unfertilized egg.</p></div>
<div class="footnote">
<p><a name="Footnote_113_113" id="Footnote_113_113"></a><a href="#FNanchor_113_113"><span class="label">113</span></a> Delage, Y., <i>Compt. rend. Acad. Sc.</i>, 1909, cxlviii.,
453.</p></div>
<div class="footnote">
<p><a name="Footnote_114_114" id="Footnote_114_114"></a><a href="#FNanchor_114_114"><span class="label">114</span></a> Since this was written, two more of the parthenogenetic
frogs over a year old died. Both were males.</p></div>
<div class="footnote">
<p><a name="Footnote_115_115" id="Footnote_115_115"></a><a href="#FNanchor_115_115"><span class="label">115</span></a> Loeb, J., <i>Artificial Parthenogenesis and
Fertilization</i>, Chicago, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_116_116" id="Footnote_116_116"></a><a href="#FNanchor_116_116"><span class="label">116</span></a> Driesch, H., <i>Science and Philosophy of the Organism</i>.
London, 1908 and 1909.</p></div>
<div class="footnote">
<p><a name="Footnote_117_117" id="Footnote_117_117"></a><a href="#FNanchor_117_117"><span class="label">117</span></a> Boveri, Th., <i>Verhandl. d. physik.-med. Gesellsch.</i>,
Würzburg, 1901, xxxiv., 145.</p></div>
<div class="footnote">
<p><a name="Footnote_118_118" id="Footnote_118_118"></a><a href="#FNanchor_118_118"><span class="label">118</span></a> Lyon, E. P., <i>Arch. f. Entwcklngsmech.</i>, 1907, xxiii.,
151; Morgan, T. H., and Spooner, G. B., <i>ibid.</i>, 1909, xxviii., 104;
Morgan, <i>Jour. Exper. Zoöl.</i>, 1910, ix., 594; Conklin, E. G., <i>ibid.</i>,
1910, ix., 417; Lillie, F. R., <i>Biol. Bull.</i>, 1909, xvi., 54.</p></div>
<div class="footnote">
<p><a name="Footnote_119_119" id="Footnote_119_119"></a><a href="#FNanchor_119_119"><span class="label">119</span></a> Driesch, H., <i>Ztschr. f. wissnsch. Zoöl.</i>, 1891, liii.,
160.</p></div>
<div class="footnote">
<p><a name="Footnote_120_120" id="Footnote_120_120"></a><a href="#FNanchor_120_120"><span class="label">120</span></a> Loeb, J., <i>Arch. f. Entwcklngsmech.</i>, 1909, xxvii., 119.</p></div>
<div class="footnote">
<p><a name="Footnote_121_121" id="Footnote_121_121"></a><a href="#FNanchor_121_121"><span class="label">121</span></a> Driesch, H., <i>Arch. f. Entwcklngsmech.</i>, 1900, x., 361.</p></div>
<div class="footnote">
<p><a name="Footnote_122_122" id="Footnote_122_122"></a><a href="#FNanchor_122_122"><span class="label">122</span></a> Driesch, H., <i>Arch. f. Entswcklngsmech.</i>, 1902, xiv.,
500.</p></div>
<div class="footnote">
<p><a name="Footnote_123_123" id="Footnote_123_123"></a><a href="#FNanchor_123_123"><span class="label">123</span></a> Boveri, Th., <i>Verhandl. d. physik. med. Gesellsch.</i>,
Würzburg, N.F., 1901, xxxiv., 145.</p></div>
<div class="footnote">
<p><a name="Footnote_124_124" id="Footnote_124_124"></a><a href="#FNanchor_124_124"><span class="label">124</span></a> v. Uexküll makes in his last book (<i>Bausteine zu einer
biologischen Weltanschauung</i>, München, 1913, p. 24) the following
statement: “Driesch succeeded in showing that the germ cell has no
trace of a machine-like structure but consists entirely of equivalent
parts.” This is not correct.</p></div>
<div class="footnote">
<p><a name="Footnote_125_125" id="Footnote_125_125"></a><a href="#FNanchor_125_125"><span class="label">125</span></a> Loeb, J., and Beutner, R., <i>Biochem. Ztschr.</i>, 1912,
xli., 1; xliv., 303; 1913, li., 288; li., 300; 1914, lix., 195.</p></div>
<div class="footnote">
<p><a name="Footnote_126_126" id="Footnote_126_126"></a><a href="#FNanchor_126_126"><span class="label">126</span></a> Loeb, J., <i>The Dynamics of Living Matter</i>. New York,
1906. Introductory Remarks.</p></div>
<div class="footnote">
<p><a name="Footnote_127_127" id="Footnote_127_127"></a><a href="#FNanchor_127_127"><span class="label">127</span></a> Roux, W., <i>Virchow’s Archiv</i>, 1888, cxiv., 113.</p></div>
<div class="footnote">
<p><a name="Footnote_128_128" id="Footnote_128_128"></a><a href="#FNanchor_128_128"><span class="label">128</span></a> Morgan, T. H., <i>Embryology of the Frog</i>. New York.</p></div>
<div class="footnote">
<p><a name="Footnote_129_129" id="Footnote_129_129"></a><a href="#FNanchor_129_129"><span class="label">129</span></a> Crampton, H. E., <i>New York Academy of Sciences</i>, 1894;
Kofoid, C. A., <i>Proc. Am. Acad. Arts and Sciences</i>, 1894, xxix.</p></div>
<div class="footnote">
<p><a name="Footnote_130_130" id="Footnote_130_130"></a><a href="#FNanchor_130_130"><span class="label">130</span></a> Conklin, E. G., <i>Anat. Anzeig.</i>, 1903, xxiii., 577;
<i>Heredity and Environment in the Development of Man</i>. Princeton, 1915,
p. 171.</p></div>
<div class="footnote">
<p><a name="Footnote_131_131" id="Footnote_131_131"></a><a href="#FNanchor_131_131"><span class="label">131</span></a> Wilson, E. B., <i>Science</i>, 1904, xx., 748; <i>Jour. Exper.
Zoöl.</i>, 1904, i., 1, 197.</p></div>
<div class="footnote">
<p><a name="Footnote_132_132" id="Footnote_132_132"></a><a href="#FNanchor_132_132"><span class="label">132</span></a> The reader will notice the absence of “regulation.”</p></div>
<div class="footnote">
<p><a name="Footnote_133_133" id="Footnote_133_133"></a><a href="#FNanchor_133_133"><span class="label">133</span></a> Conklin, E. G., <i>Heredity and Environment in the
Development of Man</i>. Princeton University Press, 1915. The reader
is referred to this book for the literature and main facts on the
structure of the egg; it should also be stated that Conklin’s book
is one of the best introductions to modern biology in the English
literature.</p></div>
<div class="footnote">
<p><a name="Footnote_134_134" id="Footnote_134_134"></a><a href="#FNanchor_134_134"><span class="label">134</span></a> Conklin, E. G., <i>loc. cit.</i>, p. 117.</p></div>
<div class="footnote">
<p><a name="Footnote_135_135" id="Footnote_135_135"></a><a href="#FNanchor_135_135"><span class="label">135</span></a> Loeb, J., <i>Jour. Morphol.</i>, 1893, xiii., 161; <i>The
Mechanistic Conception of Life</i>. Chicago, 1912, p. 106.</p></div>
<div class="footnote">
<p><a name="Footnote_136_136" id="Footnote_136_136"></a><a href="#FNanchor_136_136"><span class="label">136</span></a> Driesch, H., <i>Science and Philosophy of the Organism</i>,
i., p. 104.</p></div>
<div class="footnote">
<p><a name="Footnote_137_137" id="Footnote_137_137"></a><a href="#FNanchor_137_137"><span class="label">137</span></a> Herbst, C., <i>Formative Reize in der tierischen
Ontogenese</i>. Leipzig, 1901.</p></div>
<div class="footnote">
<p><a name="Footnote_138_138" id="Footnote_138_138"></a><a href="#FNanchor_138_138"><span class="label">138</span></a> Braus, H., <i>Münchener Med. Wochnschr.</i>, 1903, 1 (II.),
No. 47, p. 2076.</p></div>
<div class="footnote">
<p><a name="Footnote_139_139" id="Footnote_139_139"></a><a href="#FNanchor_139_139"><span class="label">139</span></a> Nussbaum, M., <i>Arch. f. mikroscop. Anat.</i>, 1886, xxvi.,
485.</p></div>
<div class="footnote">
<p><a name="Footnote_140_140" id="Footnote_140_140"></a><a href="#FNanchor_140_140"><span class="label">140</span></a> It must not be overlooked that in bacteria and the
blue algæ no distinct differentiation into nucleus and protoplasm can
be shown. To these organisms, therefore, the experiments of Nussbaum
cannot be applied.</p></div>
<div class="footnote">
<p><a name="Footnote_141_141" id="Footnote_141_141"></a><a href="#FNanchor_141_141"><span class="label">141</span></a> Loeb, J., <i>Arch. d. f. ges. Physiol.</i>, 1893, lv., 525.</p></div>
<div class="footnote">
<p><a name="Footnote_142_142" id="Footnote_142_142"></a><a href="#FNanchor_142_142"><span class="label">142</span></a> v. Sachs, J., “Stoff und Form der Pflanzenorgane,”
<i>Gesammelte Abhandlungen</i>, 1892, ii., 1160. Arbeiten a. d. bot. Inst.
Würzburg, 1880–82.</p></div>
<div class="footnote">
<p><a name="Footnote_143_143" id="Footnote_143_143"></a><a href="#FNanchor_143_143"><span class="label">143</span></a> Goebel, K., <i>Einleitung in die experimentelle
Morphologie der Pflanzen</i>, 1908.</p></div>
<div class="footnote">
<p><a name="Footnote_144_144" id="Footnote_144_144"></a><a href="#FNanchor_144_144"><span class="label">144</span></a> Loeb, J., Untersuchungen zur physiologischen Morphologie
der Tiere. I. Heteromorphose. Würzburg, 1891. II. Organbildung und
Wachsthum. 1892. Reprinted in <i>Studies in General Physiology</i>. Chicago,
1906.</p></div>
<div class="footnote">
<p><a name="Footnote_145_145" id="Footnote_145_145"></a><a href="#FNanchor_145_145"><span class="label">145</span></a> Gudernatsch, J. F., <i>Zentralbl. f. Physiol.</i>, 1912,
xxvi., 323; <i>Arch. f. Entwcklngsmech.</i>, 1912, xxxv., 457; <i>Am. Jour.
Anat.</i>, 1914, xv., 431.</p></div>
<div class="footnote">
<p><a name="Footnote_146_146" id="Footnote_146_146"></a><a href="#FNanchor_146_146"><span class="label">146</span></a> Morse, M., <i>Jour. Biol. Chem.</i>, 1914, xix., 421.</p></div>
<div class="footnote">
<p><a name="Footnote_147_147" id="Footnote_147_147"></a><a href="#FNanchor_147_147"><span class="label">147</span></a> Loeb, J., <i>Arch. f. Entwcklngsmech.</i>, 1897, iv., 502.</p></div>
<div class="footnote">
<p><a name="Footnote_148_148" id="Footnote_148_148"></a><a href="#FNanchor_148_148"><span class="label">148</span></a> Uhlenhuth, E., <i>ibid.</i>, 1913, xxxvi., 211.</p></div>
<div class="footnote">
<p><a name="Footnote_149_149" id="Footnote_149_149"></a><a href="#FNanchor_149_149"><span class="label">149</span></a> Loeb, Leo, <i>Zentralbl. f. allg. Path. u. path. Anat.</i>,
1907, xviii., 563; <i>Zentralbl. f. Physiol.</i>, 1908, xxii., 498; 1909,
xxiii., 73; 1910, xxiv., 203; <i>Arch. f. Entwcklngsmech.</i>, 1909, xxvii.,
89, 463; <i>Jour. Am. Med. Assoc.</i>, 1908, l., 1897; 1909, liii., 1471.</p></div>
<div class="footnote">
<p><a name="Footnote_150_150" id="Footnote_150_150"></a><a href="#FNanchor_150_150"><span class="label">150</span></a> Quoted from M. Caullery, <i>Les Problèmes de la
Sexualité</i>, Paris, 1913, p. 126.</p></div>
<div class="footnote">
<p><a name="Footnote_151_151" id="Footnote_151_151"></a><a href="#FNanchor_151_151"><span class="label">151</span></a> Smith, Geoffrey, <i>Proc. Roy. Soc.</i>, B. 1915, lxxxviii.,
418.</p></div>
<div class="footnote">
<p><a name="Footnote_152_152" id="Footnote_152_152"></a><a href="#FNanchor_152_152"><span class="label">152</span></a> Loeb, J., <i>Bot. Gazette</i>, 1915, lx., 249.</p></div>
<div class="footnote">
<p><a name="Footnote_153_153" id="Footnote_153_153"></a><a href="#FNanchor_153_153"><span class="label">153</span></a> With larger leaves the experiment may also succeed in
moist air.</p></div>
<div class="footnote">
<p><a name="Footnote_154_154" id="Footnote_154_154"></a><a href="#FNanchor_154_154"><span class="label">154</span></a> Loeb, J., Untersuchungen zur physiologischen
Morphologie. I. Heteromorphose. 1891. II. Organbildung und Wachsthum.
Würzburg, 1892.</p></div>
<div class="footnote">
<p><a name="Footnote_155_155" id="Footnote_155_155"></a><a href="#FNanchor_155_155"><span class="label">155</span></a> Bickford, E. E., <i>Jour. Morphol.</i>, 1894, ix., 417.</p></div>
<div class="footnote">
<p><a name="Footnote_156_156" id="Footnote_156_156"></a><a href="#FNanchor_156_156"><span class="label">156</span></a> Driesch, H., <i>Science and Philosophy of the Organism</i>,
i., 127.</p></div>
<div class="footnote">
<p><a name="Footnote_157_157" id="Footnote_157_157"></a><a href="#FNanchor_157_157"><span class="label">157</span></a> Child, C. M., “Die physiologische Isolation von Teilen
des Organismus,” Roux’s <i>Vorträge und Aufsätze</i>, Leipzig, 1911.</p></div>
<div class="footnote">
<p><a name="Footnote_158_158" id="Footnote_158_158"></a><a href="#FNanchor_158_158"><span class="label">158</span></a> Loeb, J., “Untersuchungen zur physiologischen
Morphologie der Tiere.”</p></div>
<div class="footnote">
<p><a name="Footnote_159_159" id="Footnote_159_159"></a><a href="#FNanchor_159_159"><span class="label">159</span></a> Morgan, T. H., <i>Regeneration</i>, New York, 1901.</p></div>
<div class="footnote">
<p><a name="Footnote_160_160" id="Footnote_160_160"></a><a href="#FNanchor_160_160"><span class="label">160</span></a> Bardeen, C. R., <i>Am. Jour. Physiol.</i>, 1901, v., 1;
<i>Arch. f. Entwcklngsmech.</i>, 1903, xvi., 1.</p></div>
<div class="footnote">
<p><a name="Footnote_161_161" id="Footnote_161_161"></a><a href="#FNanchor_161_161"><span class="label">161</span></a> Przibram, H., <i>Arch. f. Entwcklngsmech.</i>, 1901, xi.,
329.</p></div>
<div class="footnote">
<p><a name="Footnote_162_162" id="Footnote_162_162"></a><a href="#FNanchor_162_162"><span class="label">162</span></a> Child, C. M., <i>Senescence and Rejuvenescence</i>. Chicago,
1915.</p></div>
<div class="footnote">
<p><a name="Footnote_163_163" id="Footnote_163_163"></a><a href="#FNanchor_163_163"><span class="label">163</span></a> Loeb, J., <i>Am. Jour. Physiol.</i>, 1900, iv., 60.</p></div>
<div class="footnote">
<p><a name="Footnote_164_164" id="Footnote_164_164"></a><a href="#FNanchor_164_164"><span class="label">164</span></a> The writer quotes this after Driesch.</p></div>
<div class="footnote">
<p><a name="Footnote_165_165" id="Footnote_165_165"></a><a href="#FNanchor_165_165"><span class="label">165</span></a> Driesch, H., <i>Arch. f. Entwcklngsmech.</i>, 1902, xiv.,
247.</p></div>
<div class="footnote">
<p><a name="Footnote_166_166" id="Footnote_166_166"></a><a href="#FNanchor_166_166"><span class="label">166</span></a> One author, Miss Thatcher, in trying to repeat these
observations, did not notice the total collapse of the tissues and
concluded that my observations must have been wrong. The writer is
fairly certain that his observations were correct.</p></div>
<div class="footnote">
<p><a name="Footnote_167_167" id="Footnote_167_167"></a><a href="#FNanchor_167_167"><span class="label">167</span></a> Not yet published.</p></div>
<div class="footnote">
<p><a name="Footnote_168_168" id="Footnote_168_168"></a><a href="#FNanchor_168_168"><span class="label">168</span></a> v. Sachs, J., “Physiologische Notizen,” vi., <i>Flora</i>,
1893.</p></div>
<div class="footnote">
<p><a name="Footnote_169_169" id="Footnote_169_169"></a><a href="#FNanchor_169_169"><span class="label">169</span></a> <i>Ibid.</i>, ix., 425, <i>Flora</i>, 1895.</p></div>
<div class="footnote">
<p><a name="Footnote_170_170" id="Footnote_170_170"></a><a href="#FNanchor_170_170"><span class="label">170</span></a> Morgan, T. H., <i>Arch. f. Entwcklngsmech.</i>, 1895, ii.,
81; 1901, xiii., 416; 1903, xvi., 117.</p></div>
<div class="footnote">
<p><a name="Footnote_171_171" id="Footnote_171_171"></a><a href="#FNanchor_171_171"><span class="label">171</span></a> Driesch, H., <i>Arch. f. Entwcklngsmech.</i>, 1898, vi., 198;
1900, x., 361.</p></div>
<div class="footnote">
<p><a name="Footnote_172_172" id="Footnote_172_172"></a><a href="#FNanchor_172_172"><span class="label">172</span></a> Delage, Y., <i>Arch. Zoöl. expér.</i>, 1899, vii., 383.</p></div>
<div class="footnote">
<p><a name="Footnote_173_173" id="Footnote_173_173"></a><a href="#FNanchor_173_173"><span class="label">173</span></a> Driesch, H., <i>Arch. f. Entwcklngsmech.</i>, 1905, xix.,
648.</p></div>
<div class="footnote">
<p><a name="Footnote_174_174" id="Footnote_174_174"></a><a href="#FNanchor_174_174"><span class="label">174</span></a> Loeb, Leo, <i>Arch. f. Entwcklngsmech.</i>, 1898, vi., 297.</p></div>
<div class="footnote">
<p><a name="Footnote_175_175" id="Footnote_175_175"></a><a href="#FNanchor_175_175"><span class="label">175</span></a> Spain, K. C., and Loeb, Leo, <i>Jour. Exper. Med.</i>,
1916, xxiii., 107; Loeb, L., and Addison, W. H. F., <i>Arch. f.
Entwcklngsmech.</i>, 1911, xxxii., 44; 1913, xxxvii., 635.</p></div>
<div class="footnote">
<p><a name="Footnote_176_176" id="Footnote_176_176"></a><a href="#FNanchor_176_176"><span class="label">176</span></a> The excessive formation of epithelial cells in the
healing of wounds has led the older pathologists to the generalization
that if something is removed in the body an excessive compensation will
take place. The formation of antibodies has even been explained on this
basis by Weiggert and Ehrlich in their side-chain theory. As a matter
of fact, this generalization is entirely incorrect and in regeneration
of starfish, actinians, flatworms, annelids, and possibly in all
forms the reverse is true; <i>e. g.</i>, if we cut off the anterior
half of the body in <i>Cerianthus</i> less is reproduced than was cut away
namely only tentacles and the mouth, but not the missing piece of the
body. Weiggert’s conception of regeneration was probably based on the
phenomenon of the healing of wounds, but the excessive epithelium
formation in this case is not the expression of a general law of
regeneration but of the peculiar mechanical conditions which lead to
mitoses. It would be a very strange coincidence indeed if a theory of
antibody formation based on such an erroneous generalization should be
correct.</p></div>
<div class="footnote">
<p><a name="Footnote_177_177" id="Footnote_177_177"></a><a href="#FNanchor_177_177"><span class="label">177</span></a> Loeb, <i>Arch. f. Entwcklngsmech.</i>, 1914, xxxviii., 277.</p></div>
<div class="footnote">
<p><a name="Footnote_178_178" id="Footnote_178_178"></a><a href="#FNanchor_178_178"><span class="label">178</span></a> Wasteneys, H., <i>Jour. Biol. Chem.</i>, 1916, xxiv., 281.</p></div>
<div class="footnote">
<p><a name="Footnote_179_179" id="Footnote_179_179"></a><a href="#FNanchor_179_179"><span class="label">179</span></a> F. Lillie thinks that the KCN in this experiment merely
inhibits the change of the cortical layer necessary for development.
This is contradicted by two facts: first, the writer has shown in 1906
that KCN does not inhibit the membrane formation, and, second, the eggs
will not return to the resting stage when put back into sea water too
soon; in that case they will disintegrate. This shows that in the KCN
something more happens than the mere block to disintegration.</p></div>
<div class="footnote">
<p><a name="Footnote_180_180" id="Footnote_180_180"></a><a href="#FNanchor_180_180"><span class="label">180</span></a> Loeb, J., Untersuchungen zur physiologischen Morphologie
der Tiere. II. Organbildung und Wachsthum. Würzburg, 1892.</p></div>
<div class="footnote">
<p><a name="Footnote_181_181" id="Footnote_181_181"></a><a href="#FNanchor_181_181"><span class="label">181</span></a> Loeb, J., <i>Die chemische Entwicklungserregung des
tierischen Eies</i>. Berlin, 1909.</p></div>
<div class="footnote">
<p><a name="Footnote_182_182" id="Footnote_182_182"></a><a href="#FNanchor_182_182"><span class="label">182</span></a> McClung, C. E., “The Accessory Chromosome—Sex
Determinant?” <i>Biol. Bull.</i>, 1902, iii., 43.</p></div>
<div class="footnote">
<p><a name="Footnote_183_183" id="Footnote_183_183"></a><a href="#FNanchor_183_183"><span class="label">183</span></a> Wilson, E. B., “Studies on Chromosomes,” <i>Jour. Exper.
Zoöl.</i>, 1905, ii., 371, 507; 1906, iii., 1; 1909, vi., 69, 147; 1910,
ix., 53; 1912, xiii., 345. “Croonian Lecture,” 1914, <i>Proc. Roy. Soc.</i>,
B. lxxxviii., 333.</p></div>
<div class="footnote">
<p><a name="Footnote_184_184" id="Footnote_184_184"></a><a href="#FNanchor_184_184"><span class="label">184</span></a> Doncaster, L., <i>The Determination of Sex</i>. Cambridge,
1914.</p></div>
<div class="footnote">
<p><a name="Footnote_185_185" id="Footnote_185_185"></a><a href="#FNanchor_185_185"><span class="label">185</span></a> Morgan, T. H., <i>Heredity and Sex</i>. New York, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_186_186" id="Footnote_186_186"></a><a href="#FNanchor_186_186"><span class="label">186</span></a> Bridges, C. B., <i>Genetics</i>, 1916, i., 1.</p></div>
<div class="footnote">
<p><a name="Footnote_187_187" id="Footnote_187_187"></a><a href="#FNanchor_187_187"><span class="label">187</span></a> Boveri, Th., <i>Arch. f. Entwcklngsmech.</i>, 1915, xlii.,
264.</p></div>
<div class="footnote">
<p><a name="Footnote_188_188" id="Footnote_188_188"></a><a href="#FNanchor_188_188"><span class="label">188</span></a> Boveri, Th., <i>Verhand. d. phys.-med. Gesellsch.</i>
Würzburg, 1911, xli., 85. Schleip, W., <i>Ber. d. naturf. Gesellsch.</i>,
Freiburg i. Br., 1911, xix.</p></div>
<div class="footnote">
<p><a name="Footnote_189_189" id="Footnote_189_189"></a><a href="#FNanchor_189_189"><span class="label">189</span></a> Correns, C., <i>Biol. Centralbl.</i>, 1916, xxxvi., 12.</p></div>
<div class="footnote">
<p><a name="Footnote_190_190" id="Footnote_190_190"></a><a href="#FNanchor_190_190"><span class="label">190</span></a> Baltzer, F., <i>Mitteil. d. zoölog. Station</i>, Neapel,
1914, xxii.</p></div>
<div class="footnote">
<p><a name="Footnote_191_191" id="Footnote_191_191"></a><a href="#FNanchor_191_191"><span class="label">191</span></a> Caullery, M., <i>Les Problèmes de la Sexualité</i>. Paris,
1913.</p></div>
<div class="footnote">
<p><a name="Footnote_192_192" id="Footnote_192_192"></a><a href="#FNanchor_192_192"><span class="label">192</span></a> Goodale, H. D., <i>Biol. Bull.</i>, 1916, xxx., 286.</p></div>
<div class="footnote">
<p><a name="Footnote_193_193" id="Footnote_193_193"></a><a href="#FNanchor_193_193"><span class="label">193</span></a> Lillie, F., <i>Science</i>, 1916, xliii., 611.</p></div>
<div class="footnote">
<p><a name="Footnote_194_194" id="Footnote_194_194"></a><a href="#FNanchor_194_194"><span class="label">194</span></a> Janda, V., <i>Arch. f. Entwcklngsmech.</i>, 1912, xxxiii.,
345; xxxiv., 557.</p></div>
<div class="footnote">
<p><a name="Footnote_195_195" id="Footnote_195_195"></a><a href="#FNanchor_195_195"><span class="label">195</span></a> Goldschmidt, R., <i>Proc. Nat. Acad. Sc.</i>, 1916, ii., 53;
<i>Ztschr. induct. Abstammungslehre</i>, 1912, vii., and 1914, xi.</p></div>
<div class="footnote">
<p><a name="Footnote_196_196" id="Footnote_196_196"></a><a href="#FNanchor_196_196"><span class="label">196</span></a> This account of Marchal’s beautiful experiments is taken
from Caullery, M., <i>Les Problèmes de la Sexualité</i>. Paris, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_197_197" id="Footnote_197_197"></a><a href="#FNanchor_197_197"><span class="label">197</span></a> Whitney, D. D., <i>Science</i>, 1916, xliii., 176.</p></div>
<div class="footnote">
<p><a name="Footnote_198_198" id="Footnote_198_198"></a><a href="#FNanchor_198_198"><span class="label">198</span></a> Shull, A. F., and Ladoff, S., <i>Science</i>, 1916, xliii.,
177.</p></div>
<div class="footnote">
<p><a name="Footnote_199_199" id="Footnote_199_199"></a><a href="#FNanchor_199_199"><span class="label">199</span></a> Steinach, E., <i>Zentralbl. f. Physiol.</i>, 1910, xxiv.,
551; <i>Arch. f. d. ges. Physiol.</i>, 1912, cxliv., 72.</p></div>
<div class="footnote">
<p><a name="Footnote_200_200" id="Footnote_200_200"></a><a href="#FNanchor_200_200"><span class="label">200</span></a> For the literature on the subject the reader is referred
to Morgan, T. H., Sturtevant, A. H., Muller, H. J., and Bridges, C. B.,
<i>The Mechanism of Mendelian Heredity</i>. New York, 1915.</p></div>
<div class="footnote">
<p><a name="Footnote_201_201" id="Footnote_201_201"></a><a href="#FNanchor_201_201"><span class="label">201</span></a> Mendel, G., “Experiment in Plant-Hybridization,”
translated in W. Bateson’s classical book on Mendel’s <i>Principles of
Heredity</i>. Cambridge, 1909.</p></div>
<div class="footnote">
<p><a name="Footnote_202_202" id="Footnote_202_202"></a><a href="#FNanchor_202_202"><span class="label">202</span></a> The reader will find a critical discussion of the
presence and absence theory on page 220 of Morgan, Sturtevant, Muller,
and Bridges, <i>The Mechanism of Mendelian Heredity</i>. New York, 1915.</p></div>
<div class="footnote">
<p><a name="Footnote_203_203" id="Footnote_203_203"></a><a href="#FNanchor_203_203"><span class="label">203</span></a> Sutton, W. S., “The Chromosomes in Heredity,” <i>Biol.
Bull.</i>, 1904, iv., 231.</p></div>
<div class="footnote">
<p><a name="Footnote_204_204" id="Footnote_204_204"></a><a href="#FNanchor_204_204"><span class="label">204</span></a> Morgan, T. H., Sturtevant, A. H., Muller, H. J., and
Bridges, C. B., <i>Mechanism of Mendelian Heredity</i>. New York, 1915, p.
26.</p></div>
<div class="footnote">
<p><a name="Footnote_205_205" id="Footnote_205_205"></a><a href="#FNanchor_205_205"><span class="label">205</span></a> Morgan, T. H., Sturtevant, A. H., Muller, H. J., and
Bridges, C. B., <i>The Mechanism of Mendelian Heredity</i>. New York, 1915.</p></div>
<div class="footnote">
<p><a name="Footnote_206_206" id="Footnote_206_206"></a><a href="#FNanchor_206_206"><span class="label">206</span></a> Bateson, W., <i>loc. cit.</i>, p. 157.</p></div>
<div class="footnote">
<p><a name="Footnote_207_207" id="Footnote_207_207"></a><a href="#FNanchor_207_207"><span class="label">207</span></a> The number of hereditary characters examined to test the
theory was over 130.</p></div>
<div class="footnote">
<p><a name="Footnote_208_208" id="Footnote_208_208"></a><a href="#FNanchor_208_208"><span class="label">208</span></a> Bateson, W., <i>Mendel’s Principles of Heredity</i>, 3d ed.,
1913; Davenport, Chas. B., <i>Heredity in Relation to Eugenics</i>, 1911.
Pearl, R., <i>Modes of Research in Genetics</i>.</p></div>
<div class="footnote">
<p><a name="Footnote_209_209" id="Footnote_209_209"></a><a href="#FNanchor_209_209"><span class="label">209</span></a> Loeb, J., King, W. O. R., and Moore, A. R., <i>Arch.
f. Entwcklngsmech.</i>, 1910, xxix., 354. These experiments have been
repeated at different seasons of the year and in different years and
have been found to be constant.</p></div>
<div class="footnote">
<p><a name="Footnote_210_210" id="Footnote_210_210"></a><a href="#FNanchor_210_210"><span class="label">210</span></a> Moore, A. R., <i>Arch. f. Entwcklngsmech.</i>, 1912, xxxiv.,
168.</p></div>
<div class="footnote">
<p><a name="Footnote_211_211" id="Footnote_211_211"></a><a href="#FNanchor_211_211"><span class="label">211</span></a> Bertrand, G., <i>Ann. d. l’Inst. Pasteur</i>, 1908, xxii.,
381; <i>Bull. Soc. Chim.</i>, 1896, xv., 791.</p></div>
<div class="footnote">
<p><a name="Footnote_212_212" id="Footnote_212_212"></a><a href="#FNanchor_212_212"><span class="label">212</span></a> Chodat, R., <i>Arch. d. Sc. phys. et nat.</i>, 1915, xxxix.,
327.</p></div>
<div class="footnote">
<p><a name="Footnote_213_213" id="Footnote_213_213"></a><a href="#FNanchor_213_213"><span class="label">213</span></a> Gortner, R. A., <i>Trans. Chem. Soc.</i>, 1910, xcvii., 110.</p></div>
<div class="footnote">
<p><a name="Footnote_214_214" id="Footnote_214_214"></a><a href="#FNanchor_214_214"><span class="label">214</span></a> Onslow, H., <i>Proc. Roy. Soc.</i>, 1915, B. lxxxix., 36.</p></div>
<div class="footnote">
<p><a name="Footnote_215_215" id="Footnote_215_215"></a><a href="#FNanchor_215_215"><span class="label">215</span></a> Loeb, J., “Egg Structure and the Heredity of Instincts,”
<i>The Monist</i>, 1897, vii., 481.</p></div>
<div class="footnote">
<p><a name="Footnote_216_216" id="Footnote_216_216"></a><a href="#FNanchor_216_216"><span class="label">216</span></a> Bateson, W., <i>Nature</i>, 1916, xciii., 674.</p></div>
<div class="footnote">
<p><a name="Footnote_217_217" id="Footnote_217_217"></a><a href="#FNanchor_217_217"><span class="label">217</span></a> Ideas similar to those expressed in this chapter may be
found in the writer’s former book <i>Comparative Physiology of the Brain
and Comparative Psychology</i>, New York, 1900, and in the books by George
Bohn, <i>La Naissance de l’Intelligence</i>, Paris, 1909, and <i>La nouvelle
Psychologie animale</i>, Paris, 1911.</p></div>
<div class="footnote">
<p><a name="Footnote_218_218" id="Footnote_218_218"></a><a href="#FNanchor_218_218"><span class="label">218</span></a> Graber, V., <i>Grundlinien zur Erforschung des
Helligkeits- und Farbensinnes der Tiere</i>. Prag, 1884.</p></div>
<div class="footnote">
<p><a name="Footnote_219_219" id="Footnote_219_219"></a><a href="#FNanchor_219_219"><span class="label">219</span></a> Loeb, J., <i>Sitzungsber. d. physik.-med. Gesellsch</i>.
Würzburg, 1888. <i>Der Heliotropismus der Tiere und seine Übereinstimmung
mit dem Heliotropismus der Pflanzen.</i> Würzburg, 1889. <i>Arch. f. d. ges.
Physiol.</i>, 1897, lxvi., 439.</p></div>
<div class="footnote">
<p><a name="Footnote_220_220" id="Footnote_220_220"></a><a href="#FNanchor_220_220"><span class="label">220</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1890, xlvii.,
391; 1896, lxiii., 273.</p></div>
<div class="footnote">
<p><a name="Footnote_221_221" id="Footnote_221_221"></a><a href="#FNanchor_221_221"><span class="label">221</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1897, lxvi., 439.</p></div>
<div class="footnote">
<p><a name="Footnote_222_222" id="Footnote_222_222"></a><a href="#FNanchor_222_222"><span class="label">222</span></a> Loeb, J., <i>The Mechanistic Conception of Life</i>, Chicago,
1912, p. 27.</p></div>
<div class="footnote">
<p><a name="Footnote_223_223" id="Footnote_223_223"></a><a href="#FNanchor_223_223"><span class="label">223</span></a> Loeb, J., and Ewald, W. F., <i>Zentralbl. f. Physiol.</i>,
1914, xxvii., 1165.</p></div>
<div class="footnote">
<p><a name="Footnote_224_224" id="Footnote_224_224"></a><a href="#FNanchor_224_224"><span class="label">224</span></a> Ewald, W. F., <i>Science</i>, 1913, xxxviii., 236.</p></div>
<div class="footnote">
<p><a name="Footnote_225_225" id="Footnote_225_225"></a><a href="#FNanchor_225_225"><span class="label">225</span></a> Fröschel, P., <i>Sitzungsber. d. k. Akad. d. Wissensch.</i>,
Wien, 1908, cxvii.</p></div>
<div class="footnote">
<p><a name="Footnote_226_226" id="Footnote_226_226"></a><a href="#FNanchor_226_226"><span class="label">226</span></a> Blaauw, H. A., <i>Rec. d. travaux botaniques Neérlandais</i>,
1909, v., 209.</p></div>
<div class="footnote">
<p><a name="Footnote_227_227" id="Footnote_227_227"></a><a href="#FNanchor_227_227"><span class="label">227</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1893, liv., 81;
<i>Jour. Exper. Zoöl.</i>, 1907, iv., 151.</p></div>
<div class="footnote">
<p><a name="Footnote_228_228" id="Footnote_228_228"></a><a href="#FNanchor_228_228"><span class="label">228</span></a> Bancroft, F. W., <i>Jour. Exper. Zoöl.</i>, 1913, xv., 383.</p></div>
<div class="footnote">
<p><a name="Footnote_229_229" id="Footnote_229_229"></a><a href="#FNanchor_229_229"><span class="label">229</span></a> Loeb, J., <i>Studies in General Physiology</i>, Chicago,
1905, p. 2.</p></div>
<div class="footnote">
<p><a name="Footnote_230_230" id="Footnote_230_230"></a><a href="#FNanchor_230_230"><span class="label">230</span></a> Patten, Bradley M., <i>Am. Jour. Physiol.</i>, 1915,
xxxviii., 313.</p></div>
<div class="footnote">
<p><a name="Footnote_231_231" id="Footnote_231_231"></a><a href="#FNanchor_231_231"><span class="label">231</span></a> According to this theory the animal is not directly
oriented by the outside force, <i>e. g.</i> the light, but selects
among its random movements the one which is most “suited” and keeps
on moving in this direction. This idea is untenable for most if not
all the cases of tropisms and has been refuted by practically all the
workers in this field, <i>e. g.</i>, Parker and his pupils, Bohn, H. B.
Torrey, Holmes, Bancroft, Ewald, and others. It is only upheld by
Jennings and Mast; and is accepted among those to whom the idea of a
physicochemical explanation of life phenomena does not appeal. Torrey
and Bancroft (for the literature the reader is referred to Bancroft’s
paper, <i>Jour. Exper. Zoöl.</i>, 1913, xv., 383) have shown directly that
the theory of trial and error is not even correct for the organism for
which Jennings has developed this idea; namely <i>Euglena</i>.</p></div>
<div class="footnote">
<p><a name="Footnote_232_232" id="Footnote_232_232"></a><a href="#FNanchor_232_232"><span class="label">232</span></a> Loeb, J., and Maxwell, S. S., <i>Arch. f. d. ges.
Physiol.</i>, 1896, lxiii., 121.</p></div>
<div class="footnote">
<p><a name="Footnote_233_233" id="Footnote_233_233"></a><a href="#FNanchor_233_233"><span class="label">233</span></a> That the mechanisms by which heliotropic and
galvanotropic orientation is brought about are identical was shown by
Bancroft in <i>Euglena</i> (Bancroft, <i>loc. cit.</i>).</p></div>
<div class="footnote">
<p><a name="Footnote_234_234" id="Footnote_234_234"></a><a href="#FNanchor_234_234"><span class="label">234</span></a> Loeb, J., and Maxwell, S. S., <i>Arch. f. d. ges.
Physiol.</i>, 1896, lxiii., 121.</p></div>
<div class="footnote">
<p><a name="Footnote_235_235" id="Footnote_235_235"></a><a href="#FNanchor_235_235"><span class="label">235</span></a> Loeb, J., <i>Dynamics of Living Matter</i>, p. 126.</p></div>
<div class="footnote">
<p><a name="Footnote_236_236" id="Footnote_236_236"></a><a href="#FNanchor_236_236"><span class="label">236</span></a> Loeb, J., and Maxwell, S. S., <i>Univ. Cal. Pub.</i>, 1910,
<i>Physiol.</i>, iii., 195; Loeb and Wasteneys, <i>Proc. Nat. Acad. Sc.</i>,
1915, i., 44; <i>Science</i>, 1915, xli., 328; <i>Jour. Exper. Zoöl.</i>, 1915,
xix., 23; 1916, xx., 217.</p></div>
<div class="footnote">
<p><a name="Footnote_237_237" id="Footnote_237_237"></a><a href="#FNanchor_237_237"><span class="label">237</span></a> Mast, S. O., <i>Proc. Nat. Acad. Sc.</i>, 1915, i., 622.</p></div>
<div class="footnote">
<p><a name="Footnote_238_238" id="Footnote_238_238"></a><a href="#FNanchor_238_238"><span class="label">238</span></a> Hess, C., “Gesichtssinn,” <i>Winterstein’s Handb. d.
vergl. Physiol.</i>, 1913, iv.</p></div>
<div class="footnote">
<p><a name="Footnote_239_239" id="Footnote_239_239"></a><a href="#FNanchor_239_239"><span class="label">239</span></a> v. Frisch, K., “Der Farbensinn und Formensinn der
Biene,” <i>Zoöl. Jahrb. Abt. f. allg. Zoöl. u. Physiol.</i>, 1914, xxxv. See
also Ewald, W. F., <i>Ztschr. f. Sinnesphysiol.</i>, 1914, xlviii., 285.</p></div>
<div class="footnote">
<p><a name="Footnote_240_240" id="Footnote_240_240"></a><a href="#FNanchor_240_240"><span class="label">240</span></a> Loeb, J., <i>Der Heliotropismus der Tiere</i>, 1889.</p></div>
<div class="footnote">
<p><a name="Footnote_241_241" id="Footnote_241_241"></a><a href="#FNanchor_241_241"><span class="label">241</span></a> Kellogg, V. L., <i>Science</i>, 1903, xviii., 693.</p></div>
<div class="footnote">
<p><a name="Footnote_242_242" id="Footnote_242_242"></a><a href="#FNanchor_242_242"><span class="label">242</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1906, cxv., 564.</p></div>
<div class="footnote">
<p><a name="Footnote_243_243" id="Footnote_243_243"></a><a href="#FNanchor_243_243"><span class="label">243</span></a> <i>Ibid.</i>, 1893, liv., 81.</p></div>
<div class="footnote">
<p><a name="Footnote_244_244" id="Footnote_244_244"></a><a href="#FNanchor_244_244"><span class="label">244</span></a> Groom, Theo. T., and Loeb, J., <i>Biol. Centralbl.</i>, 1890,
x., 160; Ewald, W. F., <i>Jour. Exper. Zoöl.</i>, 1912, xiii., 591.</p></div>
<div class="footnote">
<p><a name="Footnote_245_245" id="Footnote_245_245"></a><a href="#FNanchor_245_245"><span class="label">245</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1906, cxv., 564;
Moore, A. R., <i>Jour. Exper. Zoöl.</i>, 1912, xiii., 573.</p></div>
<div class="footnote">
<p><a name="Footnote_246_246" id="Footnote_246_246"></a><a href="#FNanchor_246_246"><span class="label">246</span></a> Cannon, W. B., <i>Bodily Changes in Pain, Hunger, Fear,
and Rage</i>, New York, 1915.</p></div>
<div class="footnote">
<p><a name="Footnote_247_247" id="Footnote_247_247"></a><a href="#FNanchor_247_247"><span class="label">247</span></a> Setchell, W. A., <i>Science</i>, 1903, xxvii., 934.</p></div>
<div class="footnote">
<p><a name="Footnote_248_248" id="Footnote_248_248"></a><a href="#FNanchor_248_248"><span class="label">248</span></a> Duclaux, E., <i>Traité de microbiol.</i>, 1898, i., 280.</p></div>
<div class="footnote">
<p><a name="Footnote_249_249" id="Footnote_249_249"></a><a href="#FNanchor_249_249"><span class="label">249</span></a> A full discussion of the literature on temperature
coefficients is given in A. Kanitz’s book on <i>Temperatur and
Lebensvorgänge</i>, Berlin, 1915.</p></div>
<div class="footnote">
<p><a name="Footnote_250_250" id="Footnote_250_250"></a><a href="#FNanchor_250_250"><span class="label">250</span></a> Van Slyke, D. D., and Cullen, G. E., <i>Jour. Biol.
Chem.</i>, 1914, xix., 141.</p></div>
<div class="footnote">
<p><a name="Footnote_251_251" id="Footnote_251_251"></a><a href="#FNanchor_251_251"><span class="label">251</span></a> These considerations may meet the objections of Krogh
to the application of the van’t Hoff rule of temperature effect on
reaction velocity to life phenomena. See also the discussion of this
subject in Kanitz’s book.</p></div>
<div class="footnote">
<p><a name="Footnote_252_252" id="Footnote_252_252"></a><a href="#FNanchor_252_252"><span class="label">252</span></a> Lillie, F. R., and Knowlton, E. P., <i>Zoöl. Bull.</i>, 1897,
i.</p></div>
<div class="footnote">
<p><a name="Footnote_253_253" id="Footnote_253_253"></a><a href="#FNanchor_253_253"><span class="label">253</span></a> Hertwig, O., <i>Arch. mikrosk. Anat.</i>, 1898, li., 319. See
also E. Cohen, <i>Vorträge für Aerste über physikalische Chemie.</i> 2d ed.
Leipzig, 1907.</p></div>
<div class="footnote">
<p><a name="Footnote_254_254" id="Footnote_254_254"></a><a href="#FNanchor_254_254"><span class="label">254</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1908, cxxiv.,
411; Loeb J., and Wasteneys, H., <i>Biochem. Ztschr.</i>, 1911, xxxvi., 345;
Loeb J., and Chamberlain, M. M., <i>Jour. Exper. Zoöl.</i>, 1915, xix., 559.</p></div>
<div class="footnote">
<p><a name="Footnote_255_255" id="Footnote_255_255"></a><a href="#FNanchor_255_255"><span class="label">255</span></a> <i>Loc. cit.</i></p></div>
<div class="footnote">
<p><a name="Footnote_256_256" id="Footnote_256_256"></a><a href="#FNanchor_256_256"><span class="label">256</span></a> Kanitz, A., <i>loc. cit.</i>, p. 123.</p></div>
<div class="footnote">
<p><a name="Footnote_257_257" id="Footnote_257_257"></a><a href="#FNanchor_257_257"><span class="label">257</span></a> Loeb, J., and Chamberlain, M. M., <i>Jour. Exper. Zoöl.</i>,
1915, xix., 559.</p></div>
<div class="footnote">
<p><a name="Footnote_258_258" id="Footnote_258_258"></a><a href="#FNanchor_258_258"><span class="label">258</span></a> Loeb, J., and Ewald, W. F., <i>Biochem. Ztschr.</i>, 1913,
lviii., 179.</p></div>
<div class="footnote">
<p><a name="Footnote_259_259" id="Footnote_259_259"></a><a href="#FNanchor_259_259"><span class="label">259</span></a> Clausen, H., <i>Landwirtschaftl. Jahrb.</i>, 1890, xix., 893.</p></div>
<div class="footnote">
<p><a name="Footnote_260_260" id="Footnote_260_260"></a><a href="#FNanchor_260_260"><span class="label">260</span></a> Matthaei, G. L. C., <i>Trans. Philosoph. Soc.</i>, 1904,
cxcvii., 47; Blackman, F. F., <i>Ann. of Bot.</i>, 1905, xix., 281.</p></div>
<div class="footnote">
<p><a name="Footnote_261_261" id="Footnote_261_261"></a><a href="#FNanchor_261_261"><span class="label">261</span></a> Loeb, J., “The Poisonous Character of a Pure NaCl
Solution.” <i>Am. Jour. Physiol.</i>, 1900, iii., 329; <i>Arch. f. d. ges.
Physiol.</i>, 1901, lxxxviii., 68; <i>Am. Jour. Physiol.</i>, 1902, vi., 411;
<i>Biochem. Zischr.</i>, 1906, ii., 81.</p></div>
<div class="footnote">
<p><a name="Footnote_262_262" id="Footnote_262_262"></a><a href="#FNanchor_262_262"><span class="label">262</span></a> Loeb, J., <i>Jour. Biol. Chem.</i>, 1915, xxiii., 423.</p></div>
<div class="footnote">
<p><a name="Footnote_263_263" id="Footnote_263_263"></a><a href="#FNanchor_263_263"><span class="label">263</span></a> Loeb, J., “On the Physiological Effects of the Valency
and Possibly the Electrical Charges of Ions,” <i>Am. Jour. Physiol.</i>,
1902, vi., 411.</p></div>
<div class="footnote">
<p><a name="Footnote_264_264" id="Footnote_264_264"></a><a href="#FNanchor_264_264"><span class="label">264</span></a> Loeb, J., <i>Jour. Biol. Chem.</i>, 1914, xix., 431.</p></div>
<div class="footnote">
<p><a name="Footnote_265_265" id="Footnote_265_265"></a><a href="#FNanchor_265_265"><span class="label">265</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1905, cvii., 252.</p></div>
<div class="footnote">
<p><a name="Footnote_266_266" id="Footnote_266_266"></a><a href="#FNanchor_266_266"><span class="label">266</span></a> Robertson, T. B., <i>Ergeb. d. Physiol.</i>, 1910, x., 216.</p></div>
<div class="footnote">
<p><a name="Footnote_267_267" id="Footnote_267_267"></a><a href="#FNanchor_267_267"><span class="label">267</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1912, xlvii., 127.</p></div>
<div class="footnote">
<p><a name="Footnote_268_268" id="Footnote_268_268"></a><a href="#FNanchor_268_268"><span class="label">268</span></a> Osterhout, W. J. V., <i>Bot. Gazette</i>, 1906, xlii., 127;
1907, xliv., 257; <i>Jour. Biol., Chem.</i>, 1906, i., 363.</p></div>
<div class="footnote">
<p><a name="Footnote_269_269" id="Footnote_269_269"></a><a href="#FNanchor_269_269"><span class="label">269</span></a> Ostwald, Wo., <i>Arch. f. d. ges. Physiol.</i>, 1905, cvi.,
568.</p></div>
<div class="footnote">
<p><a name="Footnote_270_270" id="Footnote_270_270"></a><a href="#FNanchor_270_270"><span class="label">270</span></a> Loeb, J., <i>Jour. Biol. Chem.</i>, 1915, xxiii., 423.</p></div>
<div class="footnote">
<p><a name="Footnote_271_271" id="Footnote_271_271"></a><a href="#FNanchor_271_271"><span class="label">271</span></a> Loeb, J., <i>Jour. Biol. Chem.</i>, 1905–06, i., 427.</p></div>
<div class="footnote">
<p><a name="Footnote_272_272" id="Footnote_272_272"></a><a href="#FNanchor_272_272"><span class="label">272</span></a> Meltzer, S. J., and Auer, J., <i>Am. Jour. Physiol.</i>,
1908, xxi., 400.</p></div>
<div class="footnote">
<p><a name="Footnote_273_273" id="Footnote_273_273"></a><a href="#FNanchor_273_273"><span class="label">273</span></a> This theory was first expressed by the writer in <i>Am.
Jour. Physiol.</i>, 1900, iii., 434.</p></div>
<div class="footnote">
<p><a name="Footnote_274_274" id="Footnote_274_274"></a><a href="#FNanchor_274_274"><span class="label">274</span></a> Henderson, L., <i>The Fitness of the Environment</i>. See
also Michaelis, L., <i>Die Wasserstoffionenconzentration</i>. Berlin. 1914.</p></div>
<div class="footnote">
<p><a name="Footnote_275_275" id="Footnote_275_275"></a><a href="#FNanchor_275_275"><span class="label">275</span></a> Loeb, J., <i>Der Heliotropismus der Tiere and seine
Übereinstimmung mit dem Heliotropismus der Pflanzen</i>. Würzburg, 1890
(appeared in 1889).</p></div>
<div class="footnote">
<p><a name="Footnote_276_276" id="Footnote_276_276"></a><a href="#FNanchor_276_276"><span class="label">276</span></a> Loeb, J., <i>Biol. Bull.</i>, 1915, xxix., 50.</p></div>
<div class="footnote">
<p><a name="Footnote_277_277" id="Footnote_277_277"></a><a href="#FNanchor_277_277"><span class="label">277</span></a> Cuénot has proposed the term preadaptation for such
cases and this term expresses the situation correctly. Cuénot, L., <i>La
Génèse des Espèces animales</i>. Paris, 1911.</p></div>
<div class="footnote">
<p><a name="Footnote_278_278" id="Footnote_278_278"></a><a href="#FNanchor_278_278"><span class="label">278</span></a> Kammerer, P., <i>Arch. f. Entwcklngsmech.</i>, 1912, xxxiii.,
349.</p></div>
<div class="footnote">
<p><a name="Footnote_279_279" id="Footnote_279_279"></a><a href="#FNanchor_279_279"><span class="label">279</span></a> Loeb, J., <i>Arch. d. f. ges. Physiol.</i>, 1896, lxiii.,
273.</p></div>
<div class="footnote">
<p><a name="Footnote_280_280" id="Footnote_280_280"></a><a href="#FNanchor_280_280"><span class="label">280</span></a> Goldfarb, A. J., <i>Jour. Exper. Zoöl.</i>, 1906, iii., 129;
1910, viii., 133.</p></div>
<div class="footnote">
<p><a name="Footnote_281_281" id="Footnote_281_281"></a><a href="#FNanchor_281_281"><span class="label">281</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1913, liii., 391.</p></div>
<div class="footnote">
<p><a name="Footnote_282_282" id="Footnote_282_282"></a><a href="#FNanchor_282_282"><span class="label">282</span></a> Loeb, J., <i>Biochem. Ztschr.</i>, 1913, liii., 391.</p></div>
<div class="footnote">
<p><a name="Footnote_283_283" id="Footnote_283_283"></a><a href="#FNanchor_283_283"><span class="label">283</span></a> Dieudonné, A., <i>Arb. a. d. kais. Gesndhtsmt.</i>, 1894,
ix., 492.</p></div>
<div class="footnote">
<p><a name="Footnote_284_284" id="Footnote_284_284"></a><a href="#FNanchor_284_284"><span class="label">284</span></a> Davenport, C. B., and Castle, W. E., <i>Arch. f.
Entwcklngsmech.</i>, 1896, ii., 227.</p></div>
<div class="footnote">
<p><a name="Footnote_285_285" id="Footnote_285_285"></a><a href="#FNanchor_285_285"><span class="label">285</span></a> Kryž, F., <i>Arch. f. Entwcklngsmech.</i>, 1907, xxiii., 560.</p></div>
<div class="footnote">
<p><a name="Footnote_286_286" id="Footnote_286_286"></a><a href="#FNanchor_286_286"><span class="label">286</span></a> Loeb, J., and Wasteneys, H., <i>Jour. Exper. Zoöl.</i>, 1912,
xii., 543.</p></div>
<div class="footnote">
<p><a name="Footnote_287_287" id="Footnote_287_287"></a><a href="#FNanchor_287_287"><span class="label">287</span></a> Kammerer, P., <i>Arch. f. Entwcklngsmech.</i>, 1909, xxviii.,
448.</p></div>
<div class="footnote">
<p><a name="Footnote_288_288" id="Footnote_288_288"></a><a href="#FNanchor_288_288"><span class="label">288</span></a> Bateson, W., <i>Problems of Genetics</i>, pp. 201–202. Yale
University Press, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_289_289" id="Footnote_289_289"></a><a href="#FNanchor_289_289"><span class="label">289</span></a> Kammerer, P., <i>Arch. f. Entwcklngsmech.</i>, 1913, xxxvi.,
4.</p></div>
<div class="footnote">
<p><a name="Footnote_290_290" id="Footnote_290_290"></a><a href="#FNanchor_290_290"><span class="label">290</span></a> Werner, F., <i>Biol. Centralbl.</i>, 1915, xxxv., 176.</p></div>
<div class="footnote">
<p><a name="Footnote_291_291" id="Footnote_291_291"></a><a href="#FNanchor_291_291"><span class="label">291</span></a> Loeb, J., <i>The Mechanistic Conception of Life</i>. Chicago,
1912.</p></div>
<div class="footnote">
<p><a name="Footnote_292_292" id="Footnote_292_292"></a><a href="#FNanchor_292_292"><span class="label">292</span></a> de Vries, H., <i>The Mutation Theory</i>, translated by
Farmer, J. B., and Darbishire, A. D., Chicago, 1909. <i>Species and
Varieties</i>. Chicago, 1906. <i>Gruppenweise Artbildung</i>. Berlin, 1913.</p></div>
<div class="footnote">
<p><a name="Footnote_293_293" id="Footnote_293_293"></a><a href="#FNanchor_293_293"><span class="label">293</span></a> For a critical discussion of the details, see Bateson,
W., <i>Problems of Genetics</i>, New Haven, 1913, Chapter X.</p></div>
<div class="footnote">
<p><a name="Footnote_294_294" id="Footnote_294_294"></a><a href="#FNanchor_294_294"><span class="label">294</span></a> Fermi, C., <i>Centralbl. f. Bacteriologie</i>, Abt. 1, 1910,
lvi., 55.</p></div>
<div class="footnote">
<p><a name="Footnote_295_295" id="Footnote_295_295"></a><a href="#FNanchor_295_295"><span class="label">295</span></a> Levene, P. A., <i>Autolysis</i>. The Harvey Lectures,
1905–1906, p. 73, gives a full account of the work on this subject up
to 1905.</p></div>
<div class="footnote">
<p><a name="Footnote_296_296" id="Footnote_296_296"></a><a href="#FNanchor_296_296"><span class="label">296</span></a> Hoppe-Seyler, F., <i>Tübinger med.-chem. Untersuchungen</i>,
1871, P. 499.</p></div>
<div class="footnote">
<p><a name="Footnote_297_297" id="Footnote_297_297"></a><a href="#FNanchor_297_297"><span class="label">297</span></a> Levene, P. A., <i>Am. Jour. Physiol.</i>, 1904, xii., 276.</p></div>
<div class="footnote">
<p><a name="Footnote_298_298" id="Footnote_298_298"></a><a href="#FNanchor_298_298"><span class="label">298</span></a> Bradley, H. C., and Morse, M., <i>Jour. Biol. Chem.</i>,
1915, xxi., 209.</p></div>
<div class="footnote">
<p><a name="Footnote_299_299" id="Footnote_299_299"></a><a href="#FNanchor_299_299"><span class="label">299</span></a> Bradley, H. C., <i>ibid.</i>, 1915, xxii., 113.</p></div>
<div class="footnote">
<p><a name="Footnote_300_300" id="Footnote_300_300"></a><a href="#FNanchor_300_300"><span class="label">300</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1895, lxii., 249.</p></div>
<div class="footnote">
<p><a name="Footnote_301_301" id="Footnote_301_301"></a><a href="#FNanchor_301_301"><span class="label">301</span></a> Budgett, S. P., <i>Am. Jour. Physiol.</i>, 1898, i., 210.</p></div>
<div class="footnote">
<p><a name="Footnote_302_302" id="Footnote_302_302"></a><a href="#FNanchor_302_302"><span class="label">302</span></a> Loeb, J., <i>The Dynamics of Living Matter</i>, New York,
1906, pp. 19–21.</p></div>
<div class="footnote">
<p><a name="Footnote_303_303" id="Footnote_303_303"></a><a href="#FNanchor_303_303"><span class="label">303</span></a> Child, C. M., <i>Senescence and Rejuvenescence</i>, Chicago,
1915.</p></div>
<div class="footnote">
<p><a name="Footnote_304_304" id="Footnote_304_304"></a><a href="#FNanchor_304_304"><span class="label">304</span></a> It is a fact that in the early cells of <i>Ctenolabrus</i>
the dissolution of the cell walls through lack of O precedes death,
since when oxygen is admitted early enough the cells recover again.
In infusorians the bursting of the animal due to lack of O occurs
suddenly, while the animal is still moving, and this bursting is the
cause of death, and not the reverse.</p></div>
<div class="footnote">
<p><a name="Footnote_305_305" id="Footnote_305_305"></a><a href="#FNanchor_305_305"><span class="label">305</span></a> Metchnikoff, E., <i>Ann. d. l’Inst. Pasteur</i>, 1915, xxix.,
477.</p></div>
<div class="footnote">
<p><a name="Footnote_306_306" id="Footnote_306_306"></a><a href="#FNanchor_306_306"><span class="label">306</span></a> Loeb, J., <i>Biol. Bull.</i>, 1902, iii., 295.</p></div>
<div class="footnote">
<p><a name="Footnote_307_307" id="Footnote_307_307"></a><a href="#FNanchor_307_307"><span class="label">307</span></a> Loeb, J., <i>Arch. f. d. ges. Physiol.</i>, 1908, cxxiv.,
411.</p></div>
<div class="footnote">
<p><a name="Footnote_308_308" id="Footnote_308_308"></a><a href="#FNanchor_308_308"><span class="label">308</span></a> K. Brandt (“Über den Nitratgehalt des Ozeanwassers and
seine biologische Bedeutung,” <i>Abh. d. kais. Leop. Carol. deutsch.
Akad. d. Naturfoscher.</i>, 1915) accounts for this fact by the assumption
that through the greater activity of the denitrifying bacteria in the
tropical waters the amount of available nitrates is here comparatively
smaller than in the polar oceans. The writer fully appreciates the
importance of this fact but nevertheless is inclined also to see a
limiting factor in the enormously rapid decline of the duration of life
at the upper temperature limits.</p></div>
<div class="footnote">
<p><a name="Footnote_309_309" id="Footnote_309_309"></a><a href="#FNanchor_309_309"><span class="label">309</span></a> Metchnikoff, E., <i>The Prolongation of Life</i>. New York,
1907.</p></div></div>
<p> </p>
<p> </p>
<hr />
<p> </p>
<div class="transnote"><p><b><a id="Transcribers_notes"></a>Transcriber’s note</b>:</p>
<p>A small number of spelling anomalies were noted and these have mostly
been corrected, but a few that possibly represent authentic contemporary
alternatives have been left unchanged. A <a href="#Spelling_anomalies">list
of anomalies</a> is given below.</p>
<p class="mt3em"><a id="Spelling_anomalies"></a><b><a href="#Transcribers_notes">Spelling anomalies</a></b></p>
<p><i>Corrections</i><br />
spermatozoon —> spermatozoön<br />
i.e. —> i. e.<br />
e.g. —> e. g.<br />
nermaphrodite —> hermaphrodite<br />
suceeded —> succeeded<br />
ôf —> of<br />
tryosinase —> tyrosinase<br />
in-as-much —> inasmuch<br />
ultra-violet —> ultraviolet<br />
view-point —> viewpoint<br />
Fredericq —> Frédéricq<br />
Korösy —> Körösy<br />
Sitzngsber —> Sitzungsber<br />
negaceros —> megaceros<br />
<br />
<i>Variants</i><br />
clew/clue<br />
Entswcklngsmech/Entwcklngsmech/Entwicklngsmech<br />
peroxidase/peroxydase (latter spelling in quoted text.)<br />
20° C/20°C (spaced and unspaced temperature specifications)<br />
8vo/8^o (octavo paper size in the publications listed in the end matter)</p>
</div>
<div>*** END OF THE PROJECT GUTENBERG EBOOK 45962 ***</div>
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