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+**The Project Gutenberg Etext of Origin and Nature of Emotions**
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+The Origin and Nature of Emotions
+
+by George W. Crile
+
+March, 1998  [Etext #1233]
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+
+
+
+THE ORIGIN AND NATURE
+
+of the
+
+EMOTIONS
+
+Miscellaneous Papers
+
+BY
+
+GEORGE W. CRILE, M.D.
+
+PROFESSOR OF SURGERY, SCHOOL OF MEDICINE, WESTERN RESERVE UNIVERSITY
+VISITING SURGEON TO THE LAKESIDE HOSPITAL, CLEVELAND
+
+EDITED BY
+AMY F. ROWLAND, B. S.
+
+
+
+
+PREFACE
+
+
+IN response to numerous requests I have brought together into this volume
+eight papers which may serve as a supplement to the volumes previously
+published[*] and as a preface to monographs now in preparation.
+
+
+[*] Surgical Shock, 1899; Surgery of the Respiratory System, 1899;
+Problems Relating to Surgical Operations, 1901; Blood Pressure
+in Surgery, 1903; Hemorrhage and Transfusion, 1909;
+Anemia and Resuscitation, 1914; and Anoci-association, 1914
+(with Dr. W. E. Lower).
+
+
+In the first of these addresses, the Ether Day Address, delivered at
+the Massachusetts General Hospital in October, 1910, I first
+enunciated the Kinetic Theory of Shock, the key to which was found
+in laboratory researches and in a study of Darwin's "Expression
+of the Emotions in Man and in Animals," whereby the phylogenetic
+origin of the emotions was made manifest and the pathologic
+identity of surgical and emotional shock was established.
+Since 1910 my associates and I have continued our researches through--
+(a) Histologic studies of all the organs and tissues of the body;
+(b) Estimation of the H-ion concentration of the blood in the emotions
+of anger and fear and after the application of many other forms of stimuli;
+(c) Functional tests of the adrenals, and (d) Clinical observations.
+
+It would seem that if the striking changes produced by fear
+and anger and by physical trauma in the master organ of the body--
+the brain--were due to WORK, then we should expect to find
+corresponding histologic changes in other organs of the body as well.
+We therefore examined every organ and tissue of the bodies of animals
+which had been subjected to intense fear and anger and to infection and
+to the action of foreign proteins, some animals being killed immediately;
+some several hours after the immediate effects of the stimuli had passed;
+some after seances of strong emotion had been repeated several
+times during a week or longer.
+
+The examination of all the tissues and organs of these animals
+showed changes in three organs only, and with few exceptions in all
+three of these organs--the brain, the adrenals, and the liver.
+The extent of these changes is well shown by the photomicrographs
+which illustrate the paper on "The Kinetic System" which is included
+in this volume.  This paper describes many experiments which show
+that the brain, the adrenal, and the liver play together constantly
+and that no one of these organs--as far at least as is indicated
+by the histologic studies--can act without the co-operation
+of the other two.
+
+Another striking fact which has been experimentally established
+is that the deterioration of these three organs caused by emotion,
+by exertion, and by other causes is largely counteracted,
+if not exclusively, during sleep.  If animals exhausted by the continued
+application of a stimulus are allowed complete rest for a certain
+number of hours, _*without sleep_, the characteristic histologic
+appearance of exhaustion in the brain, adrenals, and liver is not
+altered notably, whereas in animals allowed to sleep for the same
+number of hours the histologic changes in these organs are lessened--
+in some cases obliterated even.
+
+This significant phenomenon and its relation will be dealt with in
+a later monograph.
+
+Many of the arguments and illustrations by which the primary
+premises were established are repeated--a few in all--many in
+more than one of these addresses.  It will be observed, however,
+that the APPLICATION of these premises varies, and that their
+SIGNIFICANCE broadens progressively.
+
+In the Ether Day Address the phylogenetic key supplied by Darwin was
+utilized to formulate the principle that the organism reacts as a unit
+to the stimuli of physical injury, of emotion, of infection, etc.
+To the study of these reactions (transformations of energy)
+the epoch-making work of Sherrington, "The Integrative Action
+of the Nervous System," gave an added key by which the dominating
+role of the brain was determined.  Later the original work
+of Cannon on the adrenal glands gave facts, and an experimental
+method by which Darwin's phylogenetic theory of the emotions
+was further elaborated in other papers, especially in the one
+entitled "Phylogenetic Association in Relation to the Emotions,"
+read before The American Philosophical Society in April, 1911.
+GEORGE W. CRILE.  CLEVELAND, OHIO, _February, 1915_.
+
+
+
+CONTENTS PAGE PHYLOGENETIC ASSOCIATION IN RELATION TO CERTAIN MEDICAL
+PROBLEMS. . . . . . . . . . . . . . . . . . . . . . . . . . .1
+
+PHYLOGENETIC ASSOCIATION IN RELATION TO THE EMOTIONS . . . .
+55 PAIN, LAUGHTER, AND CRYING. . . . . . . . . . . . . . . . . 77
+
+THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND
+BRAIN FUNCTIONS-EXPERIMENTAL AND CLINICAL . . . .111
+
+A MECHANISTIC VIEW OF PSYCHOLOGY . . . . . . . . . . . . . .127
+
+A MECHANISTIC THEORY OF DISEASE. . . . . . . . . . . . . . .157
+
+THE KINETIC SYSTEM . . . . . . . . . . . . . . . . . . . . .173
+
+ALKALESCENCE, ACIDITY, ANESTHESIA--A THEORY OF ANESTHESIA.  .227
+
+INDEX. . . . . . . . . . . . . . . . . . . . . . . . . . . .237
+THE ORIGIN AND NATURE OF THE EMOTIONS
+
+PHYLOGENETIC ASSOCIATION IN RELATION TO CERTAIN MEDICAL PROBLEMS[*]
+
+
+[*] Address delivered at the Massachusetts General Hospital on
+the sixty-fourth anniversary of Ether Day, Oct. 15, 1910.
+
+
+The discovery of the anesthetic properties of ether and its practical
+application to surgery must always stand as one of the great
+achievements of medicine.  It is eminently fitting that the anniversary
+of that notable day, when the possibilities of ether were first
+made known to the world, should be celebrated within these walls,
+and whatever the topic of your Ether Day orator, he must fittingly
+pause first to pay tribute to that great event and to the master
+surgeons of the Massachusetts General Hospital.  On this occasion,
+on behalf of the dumb animals as well as on behalf of suffering humanity,
+I express a deep sense of gratitude for the blessings of anesthesia.
+
+Two years ago, an historic appreciation of the discovery of ether
+was presented here by Professor Welch, and last year an address
+on medical research was given by President Eliot.  I, therefore,
+will not attempt a general address, but will invite your
+attention to an experimental and clinical study.  In presenting
+the summaries of the large amount of data in these researches,
+I acknowledge with gratitude the great assistance rendered by
+my associates, Dr. D. H. Dolley, Dr. H. G. Sloan, Dr. J. B. Austin,
+and Dr. M. L. Menten.[*]
+
+
+[*] From the H. K. Cushing Laboratory of Experimental Medicine,
+Western Reserve University, Cleveland.
+
+
+The scope of this paper may be explained by a concrete example.
+When a barefoot boy steps on a sharp stone there is an immediate discharge
+of nervous energy in his effort to escape from the wounding stone.
+This is not a voluntary act.  It is not due to his own personal experience--
+his ontogeny--but is due to the experience of his progenitors
+during the vast periods of time required for the evolution
+of the species to which he belongs, _i.  e_., his phylogeny.
+The wounding stone made an impression upon the nerve receptors
+in the foot similar to the innumerable injuries which gave origin
+to this nerve mechanism itself during the boy's vast phylogenetic or
+ancestral experience.  The stone supplied the phylogenetic association,
+and the appropriate discharge of nervous energy automatically followed.
+If the sole of the foot be repeatedly bruised or crushed by a stone,
+shock may be produced; if the stone be only lightly applied,
+then the consequent sensation of tickling causes a discharge of
+nervous energy.  In like manner there have been implanted in the body
+other mechanisms of ancestral or phylogenetic origin whose purpose
+is the discharge of nervous energy for the good of the individual.
+In this paper I shall discuss the origin and mode of action of some
+of these mechanisms and their relation to certain phases of anesthesia.
+
+The word anesthesia--meaning WITHOUT FEELING--describes accurately
+the effect of ether in anesthetic dosage.  Although no pain
+is felt in operations under inhalation anesthesia, the _*nerve
+impulses excited by a surgical operation still reach the brain_.
+We know that not every portion of the brain is fully anesthetized,
+since surgical anesthesia does not kill.  The question then is:
+What effect has trauma under surgical anesthesia upon the part
+of the brain THAT REMAINS AWAKE?  If, in surgical anesthesia,
+the traumatic impulses cause an excitation of the wide-awake cells,
+are the remainder of the cells of the brain, despite anesthesia,
+affected in any way?  If so, they are prevented by the anesthesia from
+expressing that influence in conscious perception or in muscular action.
+Whether the ANESTHETIZED cells are influenced or not must be determined
+by noting the physiologic functions of the body after anesthesia has
+worn off, and in animals by an examination of the brain-cells as well.
+It has long been known that the vasomotor, the cardiac, and the respiratory
+centers discharge energy in response to traumatic stimuli applied
+to various sensitive regions of the body during surgical anesthesia.
+If the trauma be sufficient, exhaustion of the entire brain
+will be observed after the effect of the anesthesia has worn off;
+that is to say, despite the complete paralysis of voluntary
+motion and the loss of consciousness due to ether, the traumatic
+impulses that are known to reach the AWAKE centers in the medulla
+also reach and influence every other part of the brain.
+Whether or not the consequent functional depression and the morphologic
+alterations seen in the brain-cells may be due to the low blood-pressure
+which follows excessive trauma is shown by the following experiments:
+The circulation of animals was first rendered STATIC by over-transfusion,
+and was controlled by a continuous blood-pressure record on a drum,
+the factor of anemia being thereby wholly excluded during the application
+of the trauma and during the removal of a specimen of brain tissue
+for histologic study.  In each instance, morphologic changes
+in the cells of all parts of the brain were found, but it required
+much more trauma to produce brain-cell changes in animals whose
+blood-pressure was kept at the normal level than in the animals
+whose blood-pressure was allowed to take a downward course.
+In the cortex and in the cerebellum, the changes in the brain-cells
+were in every instance more marked than in the medulla.
+
+There is also strong NEGATIVE evidence that traumatic impulses
+are not excluded by ether anesthesia from the part of the brain
+that is apparently asleep.  This evidence is as follows:
+If the factor of fear be excluded, and if in addition the traumatic
+impulses be prevented from reaching the brain by cocain[*] blocking,
+then, despite the intensity or the duration of the trauma within
+the zone so blocked, there follows no exhaustion after the effect
+of the anesthetic disappears, and no morphologic changes are noted
+in the brain-cells.
+
+
+[*] Since the presentation of this paper, novocain has been
+substituted for cocain in operations under anoci-association.
+
+
+Still further negative evidence that inhalation anesthesia offers
+little or no protection to the brain-cells against trauma is derived
+from the following experiment:  A dog whose spinal cord had been
+divided at the level of the first dorsal segment, and which had
+then been kept in good condition for two months, showed a recovery
+of the spinal reflexes, such as the scratch reflex, etc.  Such an
+animal is known as a "spinal dog."  Now, in this animal, the abdomen
+and hind extremities had no direct nerve connection with the brain.
+In this dog, continuous severe trauma of the abdominal viscera and of
+the hind extremities lasting for four <p 5-7> hours was accompanied
+by but slight change in either the circulation or in the respiration,
+and by no microscopic alteration of the brain-cells (Fig. 1). Judging
+from a large number of experiments on NORMAL dogs under ether,
+such an amount of trauma would have caused not only complete
+physiologic exhaustion of the brain, but also morphologic alterations
+of all of the brain-cells and the physical destruction of many
+(Fig. 2). We must, therefore, conclude that, although ether anesthesia
+produces unconsciousness, it APPARENTLY PROTECTS NONE OF THE BRAIN-CELLS
+against exhaustion from the trauma of surgical operations; ether is,
+so to speak, but a veneer.  Under nitrous oxid anesthesia there is
+approximately only one-fourth as much exhaustion as is produced by equal
+trauma under ether (Fig. 3). We must conclude, therefore, either that
+nitrous oxid protects the brain-cells against trauma or that ether
+predisposes the brain-cells to exhaustion as a result of trauma.
+With these premises let us now inquire into the cause of this
+exhaustion of the brain-cells.
+
+
+The Cause of the Exhaustion of the Brain-cells as a Result of Trauma
+of Various Parts of the Body under Inhalation Anesthesia
+
+
+Numerous experiments on animals to determine the effect of ether
+anesthesia _per se_, _i.  e_., ether anesthesia without trauma,
+showed that, although certain changes were produced, these included
+neither the physiologic exhaustion nor the alterations in the
+brain-cells which are characteristic of the effects of trauma.
+On turning to the study of trauma, we at once found in the behavior
+of individuals as a whole under deep and under light anesthesia
+the clue to the cause of the discharge of energy, of the consequent
+physiologic exhaustion, and of the morphologic changes in the brain-cells.
+
+If, in the course of abdominal operations, rough manipulations
+of the parietal peritoneum be made, there will be frequently
+observed a marked increase in the respiratory rate and an increase
+in the expiratory force which may be marked by the production
+of an audible expiratory groan.  Under light ether anesthesia,
+severe manipulations of the peritoneum often cause such vigorous
+contractions of the abdominal muscles that the operator is greatly
+hindered in his work.
+
+Among the unconscious responses to trauma under ether anesthesia
+are purposeless moving, the withdrawal of the injured part, and,
+if the anesthesia be sufficiently light and the trauma sufficiently
+strong, there may be an effort toward escape from the injury.
+In injury under ether anesthesia every grade of response may be seen,
+from the slightest change in the respiration or in the blood-pressure
+to a vigorous defensive struggle.  As to the purpose of these
+subconscious movements in response to injury, there can be no doubt--
+THEY ARE EFFORTS TO ESCAPE FROM THE INJURY.
+
+Picture what would be the result of a formidable abdominal operation
+extending over a period of half an hour or more on an unanesthetized
+human patient, during which extensive adhesions had been broken up,
+or a large tumor dislodged from its bed!  In such a case,
+would not the nervous system discharge its energy to the utmost
+in efforts to escape from the injury, and would not the patient suffer
+complete exhaustion?  If the traumata under inhalation anesthesia
+are sufficiently strong and are repeated in sufficient numbers,
+the brain-cells are finally deprived of their dischargeable nervous
+energy and become exhausted just as exhaustion follows such strenuous
+and prolonged muscular exertion as is seen in endurance tests.
+Whether the energy of the brain be discharged by injury under anesthesia
+or by ordinary muscular exertion, identical morphologic changes are
+seen in the nerve-cells. In shock from injury (Fig. 2), in exhaustion
+from overwork (Hodge and Dolley) (Fig. 4), and in exhaustion from pure fear
+(Fig. 5), the resultant general functional weakness is similar--
+in each case a certain length of time is required to effect recovery,
+and in each there are morphologic changes in the brain-cells. It
+is quite clear that in each of these cases the altered function
+and form of the brain-cells are due to an _*excessive discharge
+of nervous energy_.  This brings us to the next question:
+What determines the discharge of energy as a result of trauma
+with or without inhalation anesthesia?
+
+
+The Cause of the Discharge of Nervous Energy as a Result of Trauma
+under Inhalation Anesthesia and under Normal Conditions
+
+
+I looked into this problem from many viewpoints and there seemed
+to be no solution until it occurred to me to seek the explanation
+in certain of the postulates which make up the doctrine of evolution.
+I realize fully the difficulty and the danger in attempting
+to reach the generalization which I shall make later and in
+the hypothesis I shall propose, for there is, of course, no direct
+final proof of the truth of even the doctrine of evolution.
+It is idle to consider any experimental research into the cause
+of phenomena that have developed by natural selection during
+millions of years.  Nature herself has made the experiments on
+a world-wide scale and the data are before us for interpretation.
+Darwin could do no more than to collect all available facts and then
+to frame the hypothesis by which the facts were best harmonized.
+Sherrington, that masterly physiologist, in his volume entitled
+"The Integrative Action of the Nervous System," shows clearly how
+the central nervous system was built up in the process of evolution.
+Sherrington has made free use of Darwin's doctrine in explaining
+physiologic functions, just as anatomists have extensively
+utilized it in the explanation of the genesis of anatomic forms.
+I shall assume, therefore, that the discharge of nervous energy is
+accomplished by the application of the laws of inheritance and association,
+and I conclude that this hypothesis will explain many clinical phenomena.
+I shall now present such evidence in favor of this hypothesis as time
+and my limitations will admit, after which I shall point out certain
+clinical facts that may be explained by this hypothesis.
+
+According to the doctrine of evolution, every function owes
+its origin to natural selection in the struggle for existence.
+In the lower and simpler forms of animal life, indeed, in our
+human progenitors as well, existence depended principally upon
+the success with which three great purposes were achieved:
+(1) Self-defense against or escape from enemies; (2) the acquisition
+of food; and (3) procreation; and these were virtually the only purposes
+for which nervous energy was discharged.  In its last analysis,
+in a biologic sense, this statement holds true of man today.
+Disregarding for the present the expenditure of energy for procuring
+food and for procreation, let us consider the discharge of energy
+for self-preservation. The mechanisms for self-defense which we
+now possess were developed in the course of vast periods of time
+through innumerable intermediary stages from those possessed by
+the lowest forms of life.  One would suppose, therefore, that we must
+now be in possession of mechanisms which still discharge energy on
+adequate stimulation, but which are not suited to our present needs.
+We shall point out some examples of such unnecessary mechanisms.
+As Sherrington has stated, our skin, in which are implanted many
+receptors for receiving specific stimuli which are transmitted
+to the brain, is interposed between ourselves and the environment
+in which we are immersed.  When these stimuli reach the brain,
+there is a specific response, principally in the form of
+muscular action.  Now, each receptor can be adequately stimulated
+only by the particular factor or factors in the environment
+which created the necessity for the existence of that receptor.
+Thus there have arisen receptors for touch, for temperature,
+for pain, etc.  The receptors for pain have been designated _nociceptors_
+(nocuous or harmful) by Sherrington.
+
+On the basis of natural selection, nociceptors could have developed
+in only those regions of the body which have been exposed to injury
+during long periods of time.  On this ground the finger, because it
+is exposed, should have many nociceptors, while the brain, though the
+most important organ of the body, should have no nociceptors because,
+during a vast period of time, it has been protected by a skull.
+Realizing that this point is a crucial one, Dr. Sloan and I made a series
+of careful experiments.  The cerebral hemispheres of dogs were exposed
+by removing the skull and dura under ether and local anesthesia.
+Then various portions of the hemispheres were slowly but
+completely destroyed by rubbing them with pieces of gauze.
+In some instances a hemisphere was destroyed by burning.
+In no case was there more than a slight response of the centers governing
+circulation and respiration, and no morphologic change was noted
+in an histologic study of the brain-cells of the uninjured hemisphere.
+The experiment was as completely negative as were the experiments
+on the "spinal dog."  Clinically I have confirmed these experimental
+findings when I have explored the brains of conscious patients
+with a probe to determine the presence of brain tumors.
+Such explorations elicited neither pain nor any evidence of altered
+physiologic functions.  The brain, therefore, contains no mechanism--
+no nociceptors--the direct stimulation of which can cause
+a discharge of nervous energy in a self-defensive action.
+That is to say, direct injury of the brain can cause no purposeful
+nerve-muscular action, while direct injury of the finger does cause
+purposeful nerve-muscular action.  In like manner, the deeper portions
+of the spinal region have been sheltered from trauma and they, too,
+show but little power of causing a discharge of nervous energy
+on receiving trauma.  The various tissues and organs of the body
+are differently endowed with injury receptors--the nociceptors
+of Sherrington.  The abdomen and chest when traumatized stand first
+in their facility for causing the discharge of nervous energy, _i.
+e_., THEY STAND FIRST IN SHOCK PRODUCTION.  Then follow the extremities,
+the neck, and the back.  It is an interesting fact also that different
+types of trauma elicit different responses as far as the consequent
+discharge of energy is concerned.
+
+Because it is such a commonplace observation, one scarcely realizes
+the importance of the fact that clean-cut wounds inflicted
+by a razor-like knife cause the least reaction, while a tearing,
+crushing trauma causes the greatest response.  It is a suggestive fact
+that the greatest shock is produced by any technic which imitates
+the methods of attack and of slaughter used by the carnivora.
+_*In the course of evolution, injuries thus produced may well have
+been the predominating type of traumata to which our progenitors
+were subjected_.  In one particular respect there is an analogy between
+the response to trauma of some parts of the body of the individuals
+of a species susceptible to shock and the response to trauma of the
+individuals in certain other great divisions of the animal kingdom.
+Natural selection has protected the crustaceans against their
+enemies by protective armor, _e.  g_., the turtle and the armadillo;
+to the birds, it has given sharp eyes and wings, as, for instance,
+the wild goose to another species--the skunk--it has given a noisome odor
+for its protection.  The turtle, protected by its armor against trauma,
+is in a very similar position to that of the sheltered brain
+of man and, like the brain, the turtle does not respond to trauma
+by an especially active self-protective nerve-muscular response,
+but merely withdraws its head and legs within the armored protection.
+It is proverbially difficult to exhaust or to kill this animal by trauma.
+The brain and other phylogenetically sheltered parts likewise give no
+exhausting self-protective nerve-muscular response to trauma.  The skunk
+is quite effectively protected from violence by its peculiar odor.
+This is indicated not only by the protective value of the odor itself,
+but also by the fact that the skunk has no efficient nerve-muscular
+mechanism for escape or defense; it can neither run fast nor can it
+climb a tree.  Moreover, in encounters it shows no fear and backs
+rather than runs.  The armadillo rolls itself into a ball for defense.
+On these premises we should conclude that the turtle,
+the armadillo, and the skunk have fewer nociceptors than has
+a dog or man, and that they would show less response to trauma.
+In two carefully conducted experiments on skunks and two on armadillos
+(an insufficient number) the energy discharged in response to severe
+and protracted trauma of the abdominal viscera was very much less than
+in similar experiments on dogs, opossums, pigs, sheep, and rabbits.
+It was indeed relatively difficult to exhaust the skunks and armadillos
+by trauma.  These experiments are too few to be conclusive,
+but they are of some value and furnish an excellent lead.
+It seems more than a coincidence that proneness to fear,
+distribution of nociceptors, and susceptibility to shock go
+hand-in-hand in these comparative observations (Figs. 6, 7, and 8).
+
+The discharge of energy caused by an adequate mechanical stimulation
+of the nociceptors is best explained in accordance with the law
+of phylogenetic association.  That is, injuries awaken those reflex
+actions which by natural selection have been developed for the purpose
+of self-protection. Adequate stimulation of the nociceptors for pain
+is not the only means by which a discharge of nervous energy is caused.
+Nervous energy may be discharged also by adequate stimulation
+of the various ticklish regions of the body; the entire skin
+surface of the body contains delicate ticklish receptors.
+These receptors are closely related to the nociceptors for pain,
+and their adequate stimulation by an insect-like touch
+causes a discharge of energy,--a nerve-muscular reaction,--
+resembling that developed for the purpose of brushing off insects.
+This reflex is similar to the scratch reflex in the dog.
+The discharge of energy is almost wholly independent of the will
+and is a self-protective action in the same sense as is the response
+to pain stimuli.  The ear in man and in animals is acutely ticklish,
+the adequate stimulus being any foreign body, especially a buzzing,
+insect-like contact.  The discharge of nervous energy in horses
+and in cattle on adequate stimulation of the ticklish receptors
+of the ear is so extraordinary that in the course of evolution it
+must have been of great importance to the safety of the animal.
+A similar ticklish zone guards the nasal chambers, the discharge of energy
+here taking a form which effectively dislodges the foreign body.
+The larynx is exquisitely ticklish, and, in response to any adequate
+stimulus, energy is discharged in the production of a vigorous cough.
+The mouth and pharynx have active receptors which cause the rejection
+of noxious substances.  The conjunctival reflex, though not
+classed as ticklish, is a most efficient self-protective reflex.
+I assume that there is no doubt as to the relation between
+the adequate stimuli and the nerve-muscular response of the various
+ticklish receptors of the surface of the skin, of the ear,
+the nose, the eye, and the larynx.  These mechanisms were developed
+by natural selection as protective measures against the intrusion
+of insects and foreign bodies into regions of great importance.
+The discharge of energy in these instances is in accordance
+with the laws of inheritance and association.  The other ticklish
+points which are capable of discharging vast amounts of energy
+are the lateral chest-wall, the abdomen, the loins, the neck,
+and the soles of the feet.  The type of adequate stimuli of the soles
+of the feet, the distribution of the ticklish points upon them,
+and the associated response, leave no doubt that these ticklish points
+were long ago established as a means of protection from injury.
+Under present conditions they are of little value to man.
+
+The adequate stimulus for the ticklish points of the ribs,
+the loins, the abdomen, and the neck is deep isolated pressure,
+probably the most adequate being pressure by a tooth-shaped body.
+The response to tickling in these regions is actively and obviously
+self-defensive. The horse discharges energy in the form of a kick;
+the dog wriggles and makes a counter-bite; the man makes efforts
+at defense and escape.
+
+There is strong evidence that the deep ticklish points of the body
+were developed through vast periods of fighting with teeth and claws
+(Fig. 9). Even puppies at play bite each other in their ticklish
+points and thus give a recapitulation of their ancestral battles
+and of the real battles to come (Fig. 10). The mere fact that animals
+fight effectively in the dark and always according to the habit
+of their species supports the belief that the fighting of animals
+is not an intellectual but a reflex process.  There are no rules
+which govern the conduct of a fight between animals.  The events
+follow each other with such kaleidoscopic rapidity that the process
+is but a series of automatic stimulations and physiologic reactions.
+Whatever their significance, therefore, it is certain that man did
+not come either accidentally or without purpose into possession
+of the deep ticklish regions of his chest and abdomen.
+Should any one doubt the vast power that adequate stimulation
+of these regions possesses in causing the discharge of energy,
+let him be bound hand and foot and vigorously tickled for an hour.
+What would happen?  He would be as completely exhausted as though he had
+experienced a major surgical operation or had run a Marathon race.
+
+A close analogy to the reflex process in the fighting of animals
+is shown in the role played by the sexual receptors in conjugation.
+Adequate stimulation of either of these two distinct groups
+of receptors, the sexual and the noci, causes specific behavior--
+the one toward embrace, the other toward repulsion.  Again, one of
+the most peremptory causes of the discharge of energy is that due
+to an attempt to obstruct forcibly the mouth and the nose so that
+asphyxia is threatened.  Under such conditions neither friend
+nor foe is trusted, and a desperate struggle for air ensues.
+It will be readily granted that the reactions to prevent suffocation
+were established for the purpose of self-preservation, but the discharge
+of nerve-muscular energy to this particular end is no more specific
+and no more shows adaptive qualities than do the preceding examples.
+Even the proposal to bind one down hand and foot excites resentment,
+a feeling originally suggested by the need for self-preservation.
+No patient views with equanimity the application of shackles
+as a preparation for anesthesia.
+
+We have now considered some of the causes of those discharges of nervous
+energy which result from various types of harmful physical contact,
+and have referred to the analogous, though antithetical,
+response to the stimulation of the sexual receptors.
+The response to the adequate stimuli of each of the several receptors
+is a discharge of nerve-muscular energy of a specific type; that is,
+there is one type of response for the ear, one for the larynx,
+one for the pharynx, another for the nose, another for the eye,
+another for the deep ticklish points of the chest and the abdomen,
+quite another for the delicate tickling of the skin, and still
+another type of response to sexual stimuli.
+
+According to Sherrington, a given receptor has a low threshold
+for only one, its own specific stimulus, and a high threshold
+for all others; that is, the doors that guard the nerve-paths
+to the brain are opened only when the proper password is received.
+According to Sherrington's law, the individual as a whole responds
+to but one stimulus at a time, that is, only one stimulus
+occupies the nerve-paths which carry the impulses as a result
+of which acts are performed, _i.  e_., the final common path.
+As soon as a stronger stimulus reaches the brain it dispossesses
+whatever other stimulus is then occupying the final common path--
+the path of action.  The various receptors have a definite order
+of precedence over each other (Sherrington). For example, the impulse
+from the delicate ticklish points of the skin, whose adequate
+stimulus is an insect-like contact, could not successfully compete
+for the final common path with the stimulus of a nociceptor.
+The stimulus of a fly on the nose would be at once superseded by
+the crushing of a finger.  In quick succession do the various receptors
+(Sherrington) occupy the final common path, but each stimulus is for
+the time the sole possessor, hence the nervous system is integrated
+(connected) to act as a whole.  Each individual at every moment
+of life has a limited amount of dischargeable nervous energy.
+This energy is at the disposal of any stimulus that obtains possession
+of the final common path, and results in the performance of an act.
+Each discharge of energy is subtracted from the sum total of stored
+energy and, whether the subtractions are made by the excitation
+of nociceptors by trauma, by tickling, by fighting, by fear,
+by flight, or by the excitation of sexual receptors, by any
+of these singly or in combination with others, the sum total of
+the expenditure of energy, if large enough, produces exhaustion.
+Apparently there is no distinction between that state of exhaustion
+which is due to the discharge of nervous energy in response
+to trauma and that due to other causes.  The manner of the
+discharge of energy is specific for each type of stimulation.
+On this conception, traumatic shock takes its place as a natural
+phenomenon and is divested of its mask of mystery.
+
+
+The Discharge of Energy through Stimulation of the Distance Receptors,
+or through Representation of Injury (Psychic)
+
+
+We will now turn from the discussion of the discharge of nervous energy by
+mechanical stimuli to the discharge of energy through mental perception.
+_Phylogenetic_ association may result from stimulation of the distance
+receptors through sight, hearing, smell, or by a representation
+of physical experiences, as well as from physical contact.
+The effect upon the organism of the representation of injury
+or of the perception of danger through the distance receptors is
+designated FEAR.  Fear is as widely distributed in nature as is its cause,
+that is, fear is as widely distributed as injury.  Animals under
+the stimulus of fear, according to W. T. Hornaday, not only may exhibit
+preternatural strength, but also may show strategy of the highest order,
+a strategy not seen under the influence of a lesser stimulus.
+In some animals fear is so intense that it defeats escape; this is
+especially true in the case of birds in the presence of snakes.
+The power of flight has endowed the bird with an easy means of escape
+from snakes, especially when the encounter is in the tops of trees.
+Here the snake must move cautiously, else he will lose his equilibrium;
+his method of attack is by stealth.  When the snake has stalked
+its prey, the bird is often so overcome by fear that it cannot fly
+and so becomes an easy victim (Fig. 11). The phenomena of fear
+are described by Darwin as follows:
+
+"Fear is often preceded by astonishment, and is so near akin to it that
+both lead to the senses of sight and hearing being instantly aroused.
+In both cases the eyes and mouth are widely opened and the
+eyebrows raised.  The frightened man at first stands like a statue,
+motionless and breathless, or crouches down as if instinctively
+to escape observation.  The heart beats quickly and violently,
+so that it palpitates or knocks against the ribs.  * * * That the skin
+is much affected under the sense of great fear we see in the marvelous
+and inexplicable manner in which perspiration immediately exudes from it.
+This exudation is all the more remarkable as the surface is then cold,
+and hence the term, `a cold sweat'; whereas the sudorific glands
+are properly excited into action when the surface is heated.
+The hairs also on the skin stand erect, and the superficial
+muscles shiver.  In connection with the disturbed action of the heart,
+the breathing is hurried.  The salivary glands act imperfectly;
+the mouth becomes dry, and is often opened and shut.  I have also
+noticed that under slight fear there is a strong tendency to yawn.
+One of the best-marked symptoms is the trembling of all the
+muscles of the body; and this is often first seen in the lips.
+From this cause, and from the dryness of the mouth, the voice
+becomes husky and indistinct, or may altogether fail.
+* * * As fear increases into agony of terror, we behold, as under
+all violent emotions, diversified results.  The heart beats wildly,
+or may fail to act and faintness ensues; there is death-like pallor;
+the breathing is labored; the wings of the nostrils are widely dilated;
+`there is a gasping and convulsive motion of the lips, a tremor
+on the hollow cheek, a gulping and catching of the throat';
+the uncovered and protruding eyeballs are fixed on the object of terror;
+or they may roll restlessly from side to side.  * * * The pupils
+are said to be enormously dilated.  All the muscles of the body
+may become rigid, or may be thrown into convulsive movements.
+The hands are alternately clenched and opened, often with a
+twitching movement.  The arms may be protruded, as if to avert
+some dreadful danger, or may be thrown wildly over the head.
+* * * In other cases there is a sudden and uncontrollable tendency
+to headlong flight; and so strong is this that the boldest soldiers
+may be seized with a sudden panic.  As fear rises to an extreme pitch,
+the dreadful scream of terror is heard.  Great beads of sweat
+stand on the skin.  All the muscles of the body are relaxed.
+Utter prostration soon follows, and the mental powers fail.
+The intestines are affected.  The sphincter muscles cease
+to act and no longer retain the contents of the body.
+* * * Men, during numberless generations, have endeavored
+to escape from their enemies or danger by headlong flight,
+or by violently struggling with them; and such great exertions
+will have caused the heart to beat rapidly, the breathing to
+be hurried, the chest to heave, and the nostrils to be dilated.
+As these exertions have often been prolonged to the last extremity,
+the final result will have been utter prostration, pallor, perspiration,
+trembling of all the muscles, or their complete relaxation.
+And now, whenever the emotion of fear is strongly felt, though it
+may not lead to any exertion, the same results tend to reappear,
+through the force of inheritance and association"[*] (Fig. 12).
+
+
+[*] Darwin:  Expression of the Emotions in Man and Animals.
+
+
+In an experimental research, we found evidence that the physiologic
+phenomena of fear have a physical basis.  This evidence is found
+in the morphologic alterations in the brain-cells, which are similar
+to those observed in certain stages of surgical shock and in fatigue
+from muscular exertion (Figs. 2, 4, 5, and 13). For the present,
+we shall assume that fear is a REPRESENTATION of trauma.
+Because fear was created by trauma, fear causes a discharge of the energy
+of the nervous system by the law of phylogenetic association.
+The almost universal fear of snakes, of blood, and of death
+and dead bodies may have such a phylogenetic origin.
+It was previously stated that under the stimulus of fear animals
+show preternatural strength.  An analysis of the phenomena of fear
+shows that, as far as can be determined, all the functions of the body
+requiring the expenditure of energy, and which are of no direct
+assistance in the effort toward self-preservation, are suspended.
+In the voluntary expenditure of muscular energy, as in the chase,
+the suspension of other functions is by no means so complete.
+Fear and trauma may drain to the last dreg the dischargeable
+nervous energy, and, therefore, the greatest possible exhaustion
+may be produced by fear and trauma.
+
+
+Summation
+
+In the discharge of energy, summation plays an important role.
+Summation is attained by the repetition of stimuli at such a rate
+that each succeeding stimulus is applied before the nerve-cells
+have returned to the resting stage from the preceding stimulus.
+If drops of water fall upon the skin from a sufficient height to cause
+the slightest unpleasant sensation, and at such a rate that before
+the effect of the stimulus of one drop has passed another drop
+falls in precisely the same spot, there will be felt a gradually
+increasing painful sensation which finally becomes unbearable.
+This is summation of stimuli.  When, for a long time, a patient
+requires frequent painful wound dressings, there is a gradual
+increase in the acuteness of the pain of the receptors.
+This is caused by summation.  In a larger sense, the entire behavior
+of the individual gives considerable evidence of summation, _e.
+g_., in the training of athletes, the rhythmic discharge of muscular
+energy at such intervals that the resting stage is not reached
+before a new exercise is given results in a gradual ascent
+in efficiency until the maximum is reached.  This is summation,
+and summation plays a large role in the development of both normal
+and pathologic phenomena.
+
+We have now pointed out the manner in which at least
+a part of the nervous energy of man may be discharged.
+The integrative action of the nervous system and the discharge
+of nervous energy by phylogenetic association may be illustrated
+by their analogy to the action of an electric automobile.
+The electric automobile is composed of four principal parts:
+The motor and the wheels (the muscular system and the skeleton);
+the cells of the battery containing stored electricity
+(brain-cells, nervous energy); the controller, which is connected
+with the cells by wiring (the receptors and the nerve-fibers);
+and an accelerator for increasing the electric discharge
+(thyroid gland?). The machine is so constructed that it acts
+as a whole for the accomplishment of a single purpose.
+When the controller is adjusted for going ahead (adequate stimulus
+of a receptor), then the conducting paths (the final common path)
+for the accomplishment of that purpose are all open to the flow of
+the current from the battery, and the vehicle is integrated to go ahead.
+It spends its energy to that end and is closed to all other impulses.
+When the controller is set for reverse, by this adequate stimulus
+the machine is integrated to back, and the battery is closed to all
+other impulses.  Whether integrated for going forward or backward,
+if the battery be discharged at a proper rate until exhausted,
+the cells, though possessing no more power (fatigue), have sustained
+no further impairment of their elements than that of normal wear
+and tear.  Furthermore, they may be restored to normal activity
+by recharging (rest). If the vehicle be placed against a stone wall,
+and the controller be placed at high-speed (trauma and fear),
+and if the accelerator be used as well (thyroid secretion?), though
+the machine will not move, not only will the battery soon be exhausted,
+but the battery elements themselves will be seriously damaged
+(exhaustion--surgical shock).
+
+We have now presented some evidence that nervous energy is
+discharged by the adequate stimulation of one or more of the various
+receptors that have been developed in the course of evolution.
+In response to an adequate stimulus, the nervous system is
+integrated for a specific purpose by the stimulated receptor,
+and but one stimulus at a time has possession of the final common path--
+the nerve mechanisms for action.  The most numerous receptors
+are those for harmful contact; these are the nociceptors.
+The effect of the adequate stimulus of a nociceptor is like that of
+pressing an electric button that sets great machinery in motion.
+
+With this conception, the human body may be likened to a
+musical instrument--an organ--the keyboard of which is composed
+of the various receptors, upon which environment plays the many
+tunes of life; and written within ourselves in symbolic language
+is the history of our evolution.  The skin may be the "Rosetta Stone"
+which furnishes the key.
+
+
+Anoci-association
+
+
+By the law of phylogenetic association, we are now prepared
+to make a practical application of the principles of the discharge
+of nervous energy.  In the case of a surgical operation, if fear
+be excluded and if the nerve-paths between the field of operation
+and the brain be blocked with cocain,[*] no discharge of energy will be
+caused by the operation; hence no shock, no exhaustion, can result.
+Under such conditions the nervous system is protected against
+noci-association, resulting from noci-perception or from an adequate
+stimulation of nociceptors.  The state of the patient in whom all
+noci-associations are excluded can be described only by coining
+a new word.  That word is "anoci-association" (Fig. 14).
+
+
+[*] See footnote, page 4.@@@
+
+
+The difference between anesthesia and anoci-association is that,
+although _inhalation anesthesia_ confers the beneficent loss of
+consciousness and freedom from pain, it does not prevent the nerve
+impulses from reaching and influencing the brain, and therefore does
+not prevent surgical shock nor the train of later nervous impairments
+so well described by Mumford.  _Anoci-association_ excludes fear,
+pain, shock, and postoperative neuroses.  _Anoci-association_ is
+accomplished by combining the special management of patients
+(applied psychology), morphin, inhalation anesthesia,
+and local anesthesia.
+
+We have now presented in summary much of the mass of experimental
+and clinical evidence we have accumulated in support of our
+principal theme, which is that the discharge of nervous energy is
+accomplished in accordance with the law of phylogenetic association.
+If this point seems to have been emphasized unduly, it is because
+we expect to rear upon this foundation a clinical structure.
+How does this hypothesis apply to surgical operations?
+
+
+Prevention of Shock by the Application of the Principle of
+Anoci-association
+
+
+
+Upon this hypothesis a new principle in operative surgery is founded, _i.
+e_., operation during the state of _anoci-association_. Assuming that
+no unfavorable effect is produced by the anesthetic and that there is
+no hemorrhage, the cells of the brain cannot be exhausted in the course
+of a surgical operation except by fear or by trauma, or by both.
+Fear may be excluded by narcotics and special management until
+the patient is rendered unconscious by inhalation anesthesia.
+Then if, in addition to inhalation anesthesia, the nerve-paths
+between the brain and the field of operation are blocked with
+cocain,[*] the patient will be placed in the beneficent state of
+_anoci-association_, and at the completion of the operation will be
+as free from shock as at the beginning.  In so-called "fair risks"
+such precautions may not be necessary, but in cases handicapped
+by infections, by anemia, by previous shock, and by Graves'
+disease, etc., anoci-association may become vitally important.
+
+
+[*] See footnote, page 4.@@@
+
+
+Graves' Disease
+
+
+By applying the principle of the discharge of nervous energy by
+phylogenetic association, and by making the additional hypothesis
+that in the discharge of nervous energy the thyroid gland is stimulated
+through the nervous system, we can explain many of the phenomena
+of Graves' disease and may possibly discover some of the factors
+which explain both its genesis and its cure.
+
+In the wild state of animal life in which only the fittest
+survive in the struggle for existence, every point of advantage
+has its value.  An animal engaged in battle or in a desperate
+effort to escape will be able to give a better account of itself
+if it have some means of accelerating the discharge of energy--
+some influence like that of pouring oil upon the kindling fire.
+There is evidence, though perhaps it is not conclusive,
+that such an influence is exerted by the thyroid gland.
+In myxedema, a condition characterized by a lack of thyroid secretion,
+there is dulness of the reflexes and of the intellect, a lowered
+muscular power, and generally a sluggish discharge of energy.
+In Graves' disease there is an excessive production of thyroid secretion.
+In this disease the reflexes are increased, the discharge of
+energy is greatly facilitated, and metabolism is at a maximum.
+The same phenomena occur also after the administration of thyroid
+extract in large doses to normal subjects.  In the course of
+sexual activities there is an increased action of the thyroid,
+which is indicated by an increase in its size and vascularity.
+That in fear and in injury the thyroid, in cases of Graves'
+disease, is probably stimulated to increased activity is indicated
+by the increased activity of the thyroid circulation, by an increase
+in the size of the gland, by the histologic appearance of activity
+in the nuclei of the cells, and by an increase of the toxic symptoms.
+Finally, Asher has stated that electric stimulation of the nerve supply
+of the thyroid causes an increased secretion.  The origin of many cases
+of Graves' disease is closely associated with some of the causes
+of the discharge of nervous energy, depressive influences especially,
+such as nervous shocks, worry and nervous strain, disappointment in love,
+business reverses, illness and death of relatives and friends.
+The association of thyroid activity with procreation is well known,
+hence the coincidence of a strain of overwork or of fear with
+the sexual development of maturing girls is obviously favorable
+to the incidence of Graves' disease.  The presence of a colloid goiter
+is a suitable soil for the development of Graves' disease, and I
+fully recognize also the evidence that infection or auto-intoxication
+may be contributing factors and must be assigned their role.
+
+I have never known a case of Graves' disease to be caused by success
+or happiness alone, or by hard physical labor unattended by
+psychic strain, or to be the result of energy voluntarily discharged.
+Some cases seem to have had their origin in overdosage with thyroid
+extract in too vigorous an attempt to cure a colloid goiter.
+One of the most striking characteristics of Graves' disease is
+the patient's loss of control and his increased susceptibility
+to stimuli, especially to trauma and to fear and to the administration
+of thyroid extract.  It has been shown that the various causes
+of the discharge of nervous energy produce alterations in the nervous
+system and probably in the thyroid gland.  This is especially
+true of the fear stimulus, and has been clearly demonstrated
+in the brains of rabbits which had been subjected to fear alone
+(Fig. 13). Of special interest was the effect of daily fright.
+In this case the brain-cells showed a distinct change, although the animal
+had been subjected to no fear for twenty-four hours before it was killed
+(Fig. 13 C. Now, a great distinction between man and the lower
+animals is the greater control man has acquired over his actions.
+This quality of control, having been phylogenetically most recently
+acquired, is the most vulnerable to various NOCUOUS influences.
+The result of a constant noci-integration may be a wearing-out
+of the control cells of the brain.  In a typical case of Graves'
+disease a marked morphologic change in the brain-cells has
+been demonstrated (Fig. 15). As has been previously stated,
+the origin of many cases of Graves' disease is associated
+with some noci-influence. If this influence causes stimulation
+of both the brain and the thyroid, its excessive action may cause
+impairment of the brain and also hyperplasia of the thyroid.
+As self-control is impaired, fear obtains an ascendency and,
+_pari passu_, stimulates the thyroid still more actively (Fig. 16).
+Finally, the fear of the disease itself becomes a noci-stimulus.
+As the thyroid secretion causes an increase in the facility
+with which nervous energy is discharged, a pathologic reciprocal
+interaction is established between the brain and the thyroid.
+The effect of the constantly recurring stimulus of the noci-influence
+is heightened by summation.  This reciprocal goading may
+continue until either the brain or the thyroid is destroyed.
+If the original noci-stimulus is withdrawn before the fear of the
+disease becomes too strong, and before too much injury to the brain
+and the thyroid has been inflicted, a spontaneous cure may result.
+Recovery may be greatly facilitated by complete therapeutic rest.
+A cure implies the return of the brain-cells to their normal state,
+with the reestablishment of the normal self-control and the
+restoration of the thyroid to its normal state, when the impulses
+of daily life will once more have possession of the final
+common path and the noci-influence will be dispossessed.
+The discovery of the real cause of a given case of Graves' disease is
+frequently difficult because it may be of a painful personal nature.
+Of extreme interest is the fact that, in the acute stage,
+the patient may be unable to refer to the exciting cause without
+exhibiting an exacerbation of the symptoms of the disease.
+I presume no case should be regarded as cured until reference
+can be made to its cause without an abnormal reaction.
+It has been established that in Graves' disease injury to any part
+of the body, even under inhalation anesthesia, causes an exacerbation
+of the disease.  Fear alone may cause an acute exacerbation.
+These acute exacerbations are frequently designated "hyperthyroidism"
+and are the special hazard of operation.
+
+In applying the principle of anoci-association in operations on
+patients with Graves' disease there is scarcely a change in the pulse,
+in the respiration, or in the nervous state at the close of the operation.
+I know no remedy which can obviate the effect of the inflowing
+stimuli from the wound after the cocain[*] has worn off.[t] It
+is necessary, therefore,
+
+
+Beats 70 80 90 100 110 120
+
+
+
+Ether ******* ******** ******** ******** ********
+
+
+
+N2O ******* ******** ******** ******** *
+
+
+
+Anoci.  ******* ******** ******** ** not to venture too far
+in serious cases.  Since the adoption of this new method
+(anoci-association) my operative results have been so vastly improved
+that I now rarely regard any case of Graves' disease as inoperable,
+at least to the extent of contraindicating a double ligation (Fig. 17).
+
+
+[*] See footnote, page 4.@@@
+
+[t] In later papers and in "Anoci-association" (Crile and Lower)
+methods of combating postoperative hyperthyroidism are fully discussed.
+
+
+If we believe that, in accordance with the law of phylogenetic association,
+a continuous stimulation of both the brain and the thyroid gland,
+accelerated by summation, plays a role in the establishment
+of the pathologic interaction seen in Graves' disease, then it
+is but the next step to assume that if the nerve connection between
+the brain and the thyroid be severed, or if the lobe be excised
+and the patient reinforced by a sojourn in a sanatorium or in some
+environment free from former noci-associations, he may be restored
+to normal health, provided that the brain-cells, the heart,
+or other essential organs have not suffered irreparable damage.
+There are still many missing links in the solution of this problem,
+and the foregoing hypotheses are not offered as final, although from
+the viewpoint of the surgeon many of the phenomena of this
+disease are explicable.
+
+
+Sexual-Neurasthenia
+
+
+The state of sexual neurasthenia is in many respects analogous
+to that of Graves' disease.  In the sexual reflexes, summation leads
+to a hyperexcitability by psychic and mechanical stimuli of a
+specific type which is analogous to the hyperexcitability in Graves'
+disease under trauma and fear; the explanation of both conditions
+is based on the laws of the discharge of energy by phylogenetic
+association and summation.  It would be interesting to observe
+the effect of interrupting the nerve impulses from the field of
+the sexual receptors by injections of alcohol, or by other agencies,
+so as to exclude the associational stimuli until the nervous
+mechanism has again become restored to its normal condition.
+Interpretation of Some of the Phenomena of Certain Diseases of the
+Abdomen in Accordance with the Hypothesis of Phylogenetic Association
+
+
+The law of phylogenetic association seems to explain many
+of the phenomena of certain lesions in the abdominal cavity.
+The nociceptors in the abdomen, like nociceptors elsewhere, have been
+established as a result of some kind of injury to which during
+vast periods of time this region has been frequently exposed.
+On this premise, we should at once conclude that there are no
+nociceptors for heat within the abdomen because, during countless years,
+the intra-abdominal region never came into contact with heat.
+That this inference is correct is shown by the fact that the
+application of a thermocautery to the intestines when completing
+a colostomy in a conscious patient is absolutely painless.
+One would conclude also that there are no touch receptors in the
+abdominal viscera, and therefore no sense of touch in the peritoneum.
+Just as the larynx, the ear, the nose, the sole of the foot,
+and the skin have all developed the specific type of nociceptors
+which are adapted for their specific protective purposes, and which,
+when adequately stimulated, respond in a specific manner in accordance
+with the law of phylogenetic association, so, the abdominal viscera
+have developed equally specific nociceptors as a protection against
+specific nocuous influences.  The principal harmful influences
+to which the abdominal viscera have been exposed during vast periods
+of time are deep tearing injuries by teeth and claws in the innumerable
+struggles of our progenitors with each other and with their enemies
+(Fig. 9); peritonitis caused by perforations of the intestinal
+tract from ulcers, injuries, appendicitis, gall-stones, etc.;
+and overdistention of the hollow viscera by various forms of obstruction.
+Whatever may be the explanation, it is a fact that the type
+of trauma which results from fighting corresponds closely with
+that which causes the most shock in the experimental laboratory.
+Division of the intestines with a sharp knife causes no pain,
+but pulling on the mesentery elicits pain.  Ligating the stump
+of the appendix causes sharp, cramp-like pains.  Sharp division
+of the gall-bladder causes no pain, but distention, which is
+the gall-bladder's most common pathologic state, produces pain.
+Distention of the intestine causes great pain, but sharp cutting or burning
+causes none.  In the abdominal viscera, as in the superficial parts,
+nociceptors have presumably been developed by specific harmful
+influences and each nociceptor is open to stimulation only by a
+stimulus of the particular type that produced it.
+
+As a result of the excitation of nociceptors, with which pain
+is associated, the routine functions, such as peristalsis, secretion,
+and absorption are dispossessed from the control of their respective
+nervous mechanisms, just as they are inhibited by fear.  This hypothesis
+explains the loss of weight, the lassitude, the indigestion,
+the constipation, and the many alterations in the functions of the various
+glands and organs of the digestive system in chronic appendicitis.
+It readily explains also the extraordinary improvement in the digestive
+functions and the general health which follows the removal
+of an appendix which is so slightly altered physically that only
+the clinical results could persuade one that this slight change could
+be an adequate cause for such far-reaching and important symptoms.
+This hypothesis explains certain gall-bladder phenomena likewise,--
+indigestion, loss of weight, disturbed functions, etc.,--and it
+may supply the explanation of the disturbance caused by an active
+anal fissure, which is a potent noci-associator, and the consequent
+disproportionate relief after the trivial operation for its cure.
+Noci-association would well explain also the great functional disturbances
+of the viscera which immediately follow abdominal operations.
+
+Postoperative and traumatic neuroses are at once explained on
+the ground of noci-association, the resulting strain from which,
+upon the brain-cells, causes in them physical lesions.
+If one were placed against a wall and were looking into the gun muzzles
+of a squad of soldiers, and were told that there were nine chances
+out of ten that he would not be killed outright when the volley
+was fired, would it help him to be told that he must not be afraid?
+Such an experience would be written indelibly on his brain.
+This corresponds closely to the position in which some surgical patients
+are placed.  In railway wrecks, we can readily understand the striking
+difference between the after-effects in the passengers who were conscious
+at the time of the accident and those who were asleep or drunk.
+In the latter the noci-perceptors and receptors were not aroused,
+hence their immunity to the nervous shock.  In the functional disturbances
+of the pelvic organs, association and summation may play a large role.
+On this hypothesis many cases of neurasthenia may well be explained.
+From the behavior of the individual as a whole we may well conclude
+that summation is but a scientific expression for "nagging."
+Many other pathologic phenomena may be explained in a similar manner.
+Thus we can understand the variations in the gastric analyses in a
+timid patient alarmed over his condition and afraid of the hospital.
+He is integrated by fear, and as fear takes precedence over all
+other impulses, no organ functionates normally.  For the same reason,
+one sees animals in captivity pine away under the dominance of fear.
+The exposure of a sensitive brain to the naked possibility of death from
+a surgical operation may be compared to uncovering a photographic plate
+in the bright sunlight to inspect it before putting it in the camera.
+This principle explains, too, the physical influence of the physician
+or surgeon, who, by his PERSONALITY, inspires, like a Kocher,
+absolute confidence in his patient.  The brain, through its power
+of phylogenetic association, controls many processes that have wholly
+escaped from the notice of the "practical man."  It is in accordance
+with the law of association that a flower, a word, a touch, a cool breeze,
+or even the thought of a fishing rod or of a gun, is helpful.
+On the contrary, all suggestions of despair or misfortune--
+a corrugated brow, the gloomy silence of despair, or a doubtful word--
+are equally depressing.  In like manner, one could add many
+illustrations of the symbolism that governs our daily lives.
+Thus we see that through the laws of inheritance and noci-association,
+we are able to read a new meaning into the clinical phenomena
+of various diseases.
+
+
+Observations on Patients whose Associational Centers are Dulled,
+and on Diseases and Injuries of Regions not Endowed with Nociceptors
+
+
+Reversing the order of our reasoning, let us now glance at the patient
+who is unconscious and who, therefore, has lost much of the power
+of association.  His mouth is usually dry, the digestive processes
+are at a low ebb, the aroma of food causes no secretion of saliva,
+tickling the nose causes no sneezing; he catches no cold.
+The laryngeal reflex is lost and food may be quietly inhaled;
+the entire process of metabolism is low.  The contrast between a man
+whose associational centers are keen and a man in whom these centers
+are dulled or lost is the contrast between life and death.
+
+In accordance with the law of adaptation through natural selection,
+phylogeny, and association, one would expect no pain in abscess
+of the brain, in abscess of the liver, in pylephlebitis,
+in infection of the hepatic vessels, in endocarditis.
+This law explains why there are no nociceptors for cancer,
+while there are active nociceptors for the acute infections.
+It is because nature has no helpful response to offer against cancer,
+while in certain of the acute pyogenic infections the nociceptors
+force the beneficent physiologic rest.
+
+Could we dispossess ourselves of the shackles of psychology,
+forget its confusing nomenclature, and view the human brain,
+as Sherrington has said, "as the organ of, and for the adaptation
+of nervous reaction," many clinical phenomena would appear in
+a clearer light.
+
+
+Natural Selection and Chemical Noci-association in the Infections
+
+
+Thus far we have considered the behavior of the individual as a whole
+in his response to a certain type of noci-influences. We have been voicing
+our argument in terms of physical escape from GROSS physical dangers,
+or of grappling with GROSS NERVE-MUSCULAR enemies of the same or of
+other species.  To explain these phenomena we have invoked the aid
+of the laws of natural selection and phylogenetic association.
+If our conclusions be correct, then it should follow that in the same
+laws we may find the explanation of immunity, which, of course,
+means a defensive response to our MICROSCOPIC enemies.  There should
+be no more difficulty in evolving an efficient army of phagocytes
+by natural selection, or in developing specific chemical reactions
+against _*microscopic enemies_, than there was in evolving the various
+nociceptors for our nerve-muscular defense against our _*gross enemies_.
+That immunity is a chemical reaction is no argument against
+the application of the law of natural selection or of association.
+What essential difference is there between the chemical defense of
+the skunk against its NERVE-MUSCULAR enemies and its chemical defense
+(immunity) against its MICROSCOPIC ENEMIES?
+
+The administration of vaccines becomes the adequate stimulus which
+awakens phylogenetic association of a chemical nature as a result
+of which immune bodies are produced.
+
+In discussing this subject I will raise only the question whether
+or not the specific character of the inaugural symptoms of some
+infectious diseases may be due to phylogenetic association.
+These inaugural symptoms are measurably a recapitulation of the leading
+phenomena of the disease in its completed clinical picture.
+Thus, the furious initiative symptoms of pneumonia, of peritonitis,
+or erysipelas, of the exanthemata, are exaggerations of phenomena
+which are analogous to the phenomena accompanying physical injury
+and fear of physical violence.  Just as the acute phenomena of fear,
+or those which accompany the adequate stimulation of nociceptors,
+are recapitulations of phylogenetic struggles, so may the inaugural
+symptoms of an infection be a similar phylogenetic recapitulation
+of the course of the disease.  A certain amount of negative
+evidence is supplied by a comparison of the response to a dose
+of toxins with the response to a dose of a standard drug.
+No drug in therapeutic dosage except the iodin compounds causes
+a febrile response; no drug causes a chill; on the other hand,
+all specific toxins cause febrile responses and many cause chills.
+If a species of animal had been poisoned by a drug during vast periods
+of time, and if natural selection had successfully established
+a self-defensive response, then the administration of that drug would
+cause a noci-association (chemical), and a specific reaction analogous
+to that following the administration of Coley's toxins might be expected.
+Bacterial noci-association probably operates through the same
+law as that through which physical noci-association operates.
+Natural selection is impartial, however.  It must be supposed that it
+acts impartially upon the microscopic invader and upon the host.
+On this ground one must infer that, in accordance with the same law
+of natural selection, the bacteria of acute infections have met
+by natural selection each advance in the struggle of the host
+for immunity.  Hence the fast and furious struggle between man
+and his microscopic enemies merely indicates to what extent natural
+selection has developed the ATTACK and the DEFENSE respectively.
+This struggle is analogous to the quick and decisive battles
+of the carnivora when fighting among themselves or when contending
+against their ancient enemies.  But when phylogenetically strange
+animals meet each other, they do not understand how to conduct a fight:
+natural selection has not had the opportunity of teaching them.
+The acute infections have the characteristics of being ancient enemies.
+On this hypothesis one can understand the high mortality of measles
+when it is introduced into a new country.  By natural selection,
+measles has become a powerful enemy of the human race, and a race
+to which this infection is newly introduced has not had the advantage
+of building up a defense against it by the law of natural selection.
+May not the phenomena of anaphylaxis be studied on associational lines?
+Then, too, there may be chemical noci-associations with enemies
+now extinct, which, like the ticklish points, may still be active
+on adequate stimulation.  This brief reference to the possible
+relation of the phenomena of the acute infections to the laws
+of natural selection and of specific chemical noci-association has
+been made as a suggestion.  Since the doctrine of evolution explains
+all or nothing, I have included many phenomena to see how reasonable
+or unreasonable such an explanation might be.
+
+
+Recapitulation
+
+
+The following are the principal points presented:  In operations
+under inhalation anesthesia the nerve impulses from the trauma
+reach every part of the brain--the cerebrum that is apparently
+anesthetized as well as the medulla that is known to remain awake--
+the proof being the PHYSIOLOGIC exhaustion of and the PATHOLOGIC
+change in the nerve-cells. Under ether anesthesia the damage
+to the nerve-cells is at least four times greater than under
+nitrous oxid.  Inhalation anesthesia is, therefore, but a veneer--
+a mask that "covers the deep suffering of the patient."  The cause
+of the exhaustion of the brain is the discharge of nervous energy
+in a futile effort to energize the paralyzed muscles in an attempt
+to escape from the injury just as if no anesthetic had been given.
+The exhaustion is, therefore, of the same nature as that from overexertion,
+but if the nerve-paths connecting the field of operation
+and the brain be blocked, then there is no discharge of nervous
+energy from the trauma, and consequently there is no exhaustion,
+however severe or prolonged the operation may be.
+
+Fear is a factor in many injuries and operations.  The phenomena
+of fear probably are exhibited only by animals whose natural defense
+is nerve-muscular. The skunk, the porcupine, the turtle, have little
+or no fear.  Fear is born of the innumerable injuries which have
+been inflicted in the course of evolution.  Fear, like trauma,
+may cause physiologic exhaustion of and morphologic changes
+in the brain-cells. The representation of injury, which is fear,
+being elicited by phylogenetic association, may be prevented
+by the exclusion of the noci-association or by the administration
+of drugs like morphin and scopolamin, which so impair the associational
+function of the brain-cells that immunity to fear is established.
+Animals whose natural defense is in muscular exertion, among which is man,
+may have their dischargeable nervous energy exhausted by fear alone,
+or by trauma alone, but most effectively by the combination of both.
+What is the mechanism of this discharge of energy?  It is the adequate
+stimulation of the nociceptors and the physiologic response for the purpose
+of self-preservation. According to Sherrington, the nervous system
+responds in action as a whole and to but one stimulus at a time.
+The integration of the individual as a whole occurs not alone in injury
+and fear, but also, though not so markedly, as a result of other
+phylogenetic associations, such as those of the chase and procreation.
+When adequate stimuli are repeated with such rapidity that the new
+stimulus is received before the effect of the previous one has
+worn off, a higher maximum effect is produced than is possible
+under a single stimulus, however powerful.
+
+Sexual receptors are implanted in the body by natural selection,
+and the adequate stimuli excite the nerve-muscular reactions
+of conjugation in a manner analogous to the action of the adequate
+stimuli of the nociceptors.  The specific response of either
+the sexual receptors or the nociceptors is at the expense
+of the total amount of nervous energy available at the moment.
+Likewise in daily labor, which, in the language of evolution,
+is the chase, nervous energy is expended.  Under the dominance
+of fear or injury, however, the integration is most nearly
+absolute and probably every expenditure of nervous energy which is
+not required for efforts toward self-preservation is arrested;
+hence fear and injury drain the cup of energy to the dregs.
+This is the potential difference between fear and desire,
+between injury and conjugation.
+
+What is the practical application of this?  In operative surgery
+there is introduced a new principle, which removes from surgery much
+of the immediate risk from its trauma by establishing ANOCI-ASSOCIATION;
+it places certain of the phenomena of fear on a physical basis;
+it explains to us the physical basis for the impairment of the entire
+individual under worry or misfortune; it makes evident the physical
+results of the daily noci-associations experienced by the individual
+as a social unit.  On the other hand, it explains the power
+of therapeutic suggestion and of other influences which serve
+for the time to change the noci-integration; it shows the physical
+basis for the difference between hope and despair; it explains
+some of the phenomena of Graves' disease, of sexual neurasthenia,
+possibly of hay-fever and of the common cold.  The principle is probably
+equally applicable to the acute infections, in each of which chemical
+noci-association gives rise to many of the phenomena of the disease
+and it explains their cure by natural immunity and by vaccines.
+This hypothesis should teach us to view our patients as a whole;
+and especially should it teach the surgeon gentleness.  It should
+teach us that there is something more in surgery than mechanics,
+and something more in medicine than physical diagnosis and drugs.
+
+
+Conclusion
+
+
+The brain-cells have existed for eons and, amid the vicissitudes
+of change, they have persisted with perhaps less alteration than has
+the crust of the earth.  Whether in man or in the lower animals,
+they are related to and obey the same general biologic laws,
+thus being bound to the entire past and performing their function
+in accordance with the law of phylogenetic association.
+
+For so long a time have we directed our attention to tumors,
+infections, and injuries that we have not sufficiently considered
+the vital force itself.  We have viewed each anatomic and pathologic
+part as an entity and man as an isolated phenomenon in nature.
+May we not find in the laws of adaptation under natural selection,
+and of phylogenetic association, the master key that will disclose
+to us the explanation of many pathologic phenomena as they have
+already explained many normal phenomena?
+
+And may medicine not correlate the pathologic phenomena of the sick
+man with the forces of evolution, as the naturalists have correlated
+the phenomena of the sound man, and thus may not disease, as well
+as health, be given its evolutionary setting?
+
+
+
+PHYLOGENETIC ASSOCIATION IN RELATION TO THE EMOTIONS[*]
+
+
+[*] Address before the American Philosophical Society, Philadelphia,
+April 22, 1911.
+
+
+The surgeon is familiar with the manifestations of every variety
+of the human emotions in the various stations of life, from infancy
+to senility, in health and in disease.  Not only does he come
+into intimate contact with the emotions displayed by the victims
+of disease and of accidents, but he also observes those manifested
+by the relatives and friends of the families of his patients.
+Moreover, he is unhappily forced to notice the emotional effect
+upon himself when he is waging an unequal battle against death--
+the strain and worry at a crisis, when a life is in the balance
+and a single false move may be fatal, is an experience known only
+to the operating surgeon.
+
+For the data for this paper, therefore, in which I shall for the most
+part limit my discussion to the strongest of all emotions--FEAR--I have
+drawn largely from my personal experience as a surgeon, as well
+as from an experimental research in which I have had the valuable
+assistance of my associates, Dr. H. G. Sloan, Dr. J. B. Austin,
+and Dr. M. L. Menten.
+
+I believe it can be shown that it is possible to elicit the emotion
+of fear only in those animals that utilize a motor mechanism
+in defense against danger or in escape from it.  For example,
+the defense of the skunk is a diabolic odor which repels its enemies;
+the skunk has no adequate equipment for defense or escape by
+muscular exertion, and the skunk therefore shows little or no fear.
+Again, certain species of snakes are protected by venom;
+they possess no other means of defense nor have they adequate
+motor mechanisms for escape and they show no fear.  Because of
+their strength other animals, such as the lion, the grizzly bear,
+and the elephant, show but little fear (Fig. 6). Animals which have
+an armored protection, such as the turtle, show little fear.
+It is, therefore, obvious that fear is not universal and that the
+emotion of fear is felt only by those animals whose self-preservation
+is dependent upon an uncertain adequacy of their power of muscular
+exertion either for defense or for flight (Fig. 7).
+
+What are the principal phenomena of fear?  They are palpitation
+of the heart, acceleration of the rate and alteration of the rhythm
+of the respiration, cold sweat, rise in body temperature,
+tremor, pallor, erection of the hair, suspension of the principal
+functions of digestion, muscular relaxation, and staring of the eyes
+(Fig. 12). The functions of the brain are wholly suspended except those
+which relate to the self-protective response against the feared object.
+Neither the brain nor any other organ of the body can respond
+to any other lesser stimulus during the dominance of fear.
+
+From these premises it would appear that under the influence
+of fear, most, perhaps all, of the organs of the body are divided
+sharply into two classes:  First, those that are stimulated,
+and, second, those that are inhibited.  Those that are stimulated
+are the entire muscular system, the vasomotor and locomotor systems,
+the senses of perception, the respiration, the mechanism for erecting
+the hair, the sweat-glands, the thyroid gland, the adrenal gland
+(Cannon), and the special senses.  On the other hand,
+all the digestive and procreative functions are inhibited.
+What is the significance of this stimulation of some and inhibition
+of other organs?  As far as we know, the stimulated organs
+increase the efficiency of the animal for fight or for flight.
+It is through skeletal muscles that the physical attack or escape
+is effected; these muscles alone energize the claws, the teeth,
+the hoofs, and the means for flight.  The increased action of the
+muscles of the heart and the blood-vessels increases the efficiency
+of the circulation; the secretion of the adrenal gland causes a rise
+in the blood-pressure; the increased action of the thyroid gland causes
+an increased metabolic activity; there is evidence that glycogen
+is actively called out, this being the most immediately available
+substance for the production of energy; the increased activity
+of the respiration is needed to supply the greater need of oxygen
+and the elimination of the increased amount of waste products;
+the dilatation of the nostrils affords a freer intake of air;
+the increased activity of the sweat-glands is needed to regulate
+the temperature of the body which the increased metabolism causes to rise.
+The activity of all the organs of perception--sight, hearing, smell--
+is increased in order that the danger may be more accurately perceived.
+It cannot be a mere coincidence that the organs and the tissues
+that are stimulated in the emotion of fear are precisely those that
+are actually utilized in a physical struggle for self-preservation.
+
+Are any other organs stimulated by fear except those that can
+or that do assist in making a defensive struggle?  I know of none.
+On the other hand, if an animal could dispense with his bulky
+digestive organs, whose functions are suspended by fear, if he could,
+so to speak, clear his decks for battle, it would be to his advantage.
+Although the marvelous versatility of natural selection apparently
+could devise no means of affording this advantage, it nevertheless shut
+off the nervous current and saved the vital force which is ordinarily
+consumed by these non-combatants in the performance of their functions.
+Whatever may be the origin of fear, its phenomena are due to a
+stimulation of all the organs and tissues that add to the efficiency
+of the physical struggle for self-preservation and an inhibition
+of the func-
+
+
+{illust. caption = FIG.  19--THE BROAD JUMP.  Note the similarity
+of the expression to the facial expression of fear and of anger
+(Figs. 12 and 21). (Wm. J. Brownlow, drawn from photo.)
+tions of the leading organs that do not participate in that struggle--
+the non-combatants, so to speak.  Fear arose from injury,
+and is one of the oldest and surely the strongest emotion.
+By the slow process of vast empiricism nature has evolved the
+wonderful defensive motor me-chanism of many animals and of man.
+The stimulation of this mechanism leading to a physical struggle is action,
+and the stimulation of this mechanism without action is emotion.
+We may say, therefore, that fear is a PHYLOGENETIC FIGHT OR FLIGHT (Fig.
+18). On this hypothesis all the organs and parts {illust. caption
+= FIG.  20.-FINISH OF RELAY RACE.
+
+Compare the facial expression of the runners with those in Figs.
+12, 19, 22.  These pictures illustrate the fact that the same
+mechanism is stimulated in emotion as in physical action.
+(Photo by Underwood and Underwood, N. Y.)}
+
+
+of the body are integrated, connected, or correlated for the
+self-preservation of the individual by the activity of his motor mechanism
+(Figs. 12, 19, and 20). We fear not in our hearts alone, not in our
+brains alone, not in our viscera alone--fear influences every organ
+and tissue; each organ or tissue is stimulated or inhibited according
+to its use or hindrance in the physical struggle for existence.
+By thus concentrating all or most of the nerve force on the nerve-muscular
+mechanism for defense, a greater physical power is developed.
+Hence it is that under the stimulus of fear animals are able to perform
+preternatural feats of strength.  For the same reason, the exhaustion
+following fear will be increased as the powerful stimulus of fear drains
+the cup of nervous energy even though no visible action may result.
+An animal under the stimulus of fear may be likened to an automobile
+with the clutch thrown out but whose engine is racing at full speed.
+The gasoline is being consumed, the machinery is being worn,
+but the machine as a whole does not move, though the power of its
+engine may cause it to tremble.
+
+When this conception is applied to the human beings of today,
+certain mysterious phenomena are at once elucidated.  It must be borne
+in mind that man has not been presented with any new organs to meet
+the requirements of his present state of civilization; indeed, not only
+does he possess organs of the same type as those of his savage fellows,
+but of the same type also as those possessed by the lower animals even.
+In fact, man has reached his present status of civilization with
+the primary equipment of brutish organs.  Perhaps the most striking
+difference between man and animals lies in the greater control
+which man has gained over his primitive instinctive reactions.
+As compared with the entire duration of organic evolution,
+man came down from his arboreal abode and assumed his new role
+of increased domination over the physical world but a moment ago.
+And now, though sitting at his desk in command of the complicated
+machinery of civilization, when he fears a business catastrophe
+his fear is manifested in the terms of his ancestral physical battle
+in the struggle for existence.  He cannot fear intellectually,
+he cannot fear dispassionately, he fears with all his organs,
+and the same organs are stimulated and inhibited as if, instead of it
+being a battle of credit, of position, or of honor, it were a physical
+battle with teeth and claws.  Whether the cause of acute fear
+be moral, financial, social, or stage fright, the heart beats wildly,
+the respirations are accelerated, perspiration is increased,
+there are pallor, trembling, indigestion, dry mouth, etc.
+The phenomena are those which accompany physical exertion
+in self-defense or escape.  There is not one group of phenomena
+for the acute fear of the president of a bank in a financial
+crash and another for the hitherto trusted official who suddenly
+and unexpectedly faces the imminent probability of the penitentiary;
+or one for a patient who unexpectedly finds he has a cancer
+and another for the hunter when he shoots his first big game.
+Nature has but one means of response to fear, and whatever its cause
+the phenomena are always the same--always physical.
+
+If the stimulus of fear be repeated from day to day, whether in
+the case of a mother anxious on account of the illness of a child;
+a business man struggling against failure; a politician under contest
+for appointment; a broker in the daily hazard of his fortune;
+litigants in legal battle, or a jealous lover who fears a rival;
+the countless real as well as the baseless fears in daily life,
+in fact, all forms of fear, as it seems to me, express themselves
+in like terms of ancestral physical contests.  On this law,
+fear dominates the various organs and parts of the body.
+
+Anger and fear express opposite emotional states.  Fear is the
+expression of a strong desire to escape from danger; anger, of a
+strong desire to attack physically and to vanquish opposition.
+This hypothesis is strongly supported by the outward expressions
+of fear and of anger.  When the business man is conducting a struggle
+for existence against his rivals, and when the contest is at
+its height, he may clench his fists, pound the table, perhaps show
+his teeth, and exhibit every expression of physical combat.
+Fixing the jaw and showing the teeth in anger merely emphasize
+the remarkable tenacity of phylogeny.  Although the development
+of the wonderful efficiency of the hands has led to a modification
+of the once powerful canines of our progenitors, the ancestral use
+of the teeth for attack and defense is attested in the display of anger.
+In all stations of life differences of opinion may lead to argument
+and argument to physical combats, even to the point of killing.
+The physical violence of the savage and of the brute still lies
+surprisingly near the surface (Fig. 21).
+
+We have now presented some of the reasons based largely on gross animal
+behavior why fear is to be regarded as a response to phylogenetic
+association with physical danger.  In further support of this hypothesis,
+I shall now present some clinical and experimental evidence.
+Although there is not convincing proof, yet there is evidence that
+the effect of the stimulus of fear upon the body when unaccompanied
+by physical activity is more injurious than is an actual physical
+contest which results in fatigue without gross physical injury.
+It is well known that the soldier who, while under fire,
+waits in vain for orders to charge, suffers more than the soldier
+who flings himself into the fray; and that a wild animal endeavoring
+to avoid capture suffers less than one cowering in captivity.
+An unexpressed smouldering emotion is measurably relieved by action.
+It is probable that the various energizing substances needed in
+physical combat, such as the secretions of the thyroid, the adrenals
+(Cannon), etc., may cause physical injury to the body when they
+are not consumed by action (Fig. 22).
+
+That the brain is definitely influenced--damaged even--
+by fear has been proved by the following experiments:
+Rabbits were frightened by a dog but were neither injured nor chased.
+After various periods of time the animals were killed and their
+brain-cells compared with the brain-cells of normal animals--
+wide-spread changes were seen (Fig. 13). The principal clinical phenomena
+expressed by the rabbit were rapid heart, accelerated respiration,
+prostration, tremors, and a rise in temperature.  The dog showed
+similar phenomena, excepting that, instead of such muscular relaxation
+as was shown by the rabbit, it exhibited aggressive muscular action.
+Both the dog and the rabbit were exhausted but, although the dog
+exerted himself actively and the rabbit remained physically passive,
+the rabbit was much more exhausted.
+
+Further observations were made upon the brain of a fox
+which had been chased for two hours by members of a hunt club,
+and had been finally overtaken by the hounds and killed.
+Most of the brain-cells of this fox, as compared with those of a
+normal fox, showed extensive physical changes (Fig. 4).
+
+The next line of evidence is offered with some reservation,
+but it has seemed to me to be more than mere idle speculation.
+It relates to the phenomena of one of the most interesting diseases
+in the entire category of human ailments--I refer to exophthalmic goiter,
+or Graves' disease, a disease primarily involving the emotions.
+This disease is frequently the direct sequence of severe
+mental shock or of a long and intensely worrying strain.
+The following case is typical:  A broker was in his usual health up
+to the panic of 1907; during this panic his fortune and that of others
+were for almost a year in jeopardy, failure finally occurring.
+During this heavy strain he became increasingly nervous and by
+imperceptible degrees there developed a pulsating enlargement of
+the thyroid gland, an increased prominence of the eyes, marked increase
+in perspiration--profuse sweating even--palpitation of the heart,
+increased respiration with frequent sighing, increase in blood-pressure;
+there were tremor of many muscles, rapid loss of weight and strength,
+frequent gastro-intestinal disturbances, loss of normal control
+of his emotions, and marked impairment of his mental faculties.
+He was as completely broken in health as in fortune.
+These phenomena resembled closely those of fear and followed
+in the wake of a strain which was due to fear.
+
+In young women exophthalmic goiter often follows in the wake
+of a disappointment in love; in women, too, it frequently follows
+the illnesses of children or parents during which they have had
+to endure the double strain of worry and of constant care.
+Since such strains usually fall most heavily upon women, they are
+the most frequent victims of this disease.  Now, whatever the exciting
+cause of exophthalmic goiter, whether it be unusual business worry,
+disappointment in love, a tragedy, or the illness of a loved one,
+the symptoms are alike and closely resemble the phenomena of one
+of the great primitive emotions.  How could disappointment in love
+play a role in the causation of Graves' disease?  If the hypothesis
+which has been presented as an explanation of the genesis and
+the phenomena of fear be correct, then that hypothesis explains
+also the emotion of love.  If fear be a phylogenetic physical
+defense or escape which does not result in muscular action,
+then love is a phylogenetic conjugation without physical action.
+The quickened pulse, the leaping heart, the accelerated respiration,
+the sighing, the glowing eye, the crimson cheek, and many other
+phenomena are merely phylogenetic recapitulations of ancestral acts.
+The thyroid gland is believed to participate in such physical activities.
+Hence it may well follow that the disappointed maiden who is intensely
+integrated for a youth will, at every thought of him, be subjected
+by phylogenetic association to a specific stimulation analogous
+to that which attended the ancestral consummation.  Moreover, a happy
+marriage has many times been followed by a cure of the exophthalmic
+goiter which appeared in the wake of such an experience.
+
+The victims of Graves' disease present a counterpart of
+emotional exhaustion.  That the emotions in Graves' disease are
+abnormally acute is illustrated by my personal observation
+of the death of a subject of this disease from fear alone.
+Whatever the exciting cause of this disease, the symptoms are the same;
+just as in fear, the phenomena are the same whatever the exciting cause.
+
+Figures 12 and 16 show the resemblance between the outward appearances
+of a patient with Graves' disease and of a person obsessed by fear.
+Fear and Graves' disease have the following phenomena in common:
+Increased heart-beat, increased respiration, rising temperature,
+muscular tremors, protruding eyes, loss in weight; Cannon has found
+an increased amount of adrenalin in the blood in fear and Frankel
+in Graves' disease; increased blood-pressure; muscular weakness;
+digestive disturbances; impaired nervous control; hypersusceptibility
+to stimuli; in protracted intense fear the brain-cells show marked
+physical changes, and in Graves' disease analogous changes are seen
+(Figs. 13 C and 15). In Graves' disease there seems to be a composite
+picture of an intense expression of the great primitive emotions.
+If Graves' disease be a disease of the great primitive emotions,
+or rather of the whole motor mechanism, how is the constant flow
+of stimulation of this complicated mechanism supplied?  It would
+seem that there must be secreted in excessive amount some substance
+that activates the motor mechanism.  The nervous system in Graves'
+disease is hypersusceptible to stimuli and to thyroid extract.
+It might follow that even a normal amount of thyroid secretion would
+lead to excessive stimulation of the hypersusceptible motor mechanism.
+
+This condition of excessive motor activity and hyperexcitability may
+endure for years.  What is the source of this pathologic excitation?
+The following facts may give a clue.  In suitable cases of Graves'
+disease, if the thyroid secretion is sufficiently diminished by a removal
+of a part of the gland or by interrupting the nerve and the blood supply,
+the phenomena of the disease are diminished immediately, and in favorable
+cases the patient is restored to approximately the normal condition.
+The heart action slows, the respiratory rate falls, the restlessness
+diminishes, digestive disturbances disappear, tremors decrease,
+there is a rapid increase in the body weight, and the patient gradually
+resumes his normal state.  On the other hand, if for a period
+of time extract of the thyroid gland is administered to a normal
+individual in excessive dosage, there will develop nervousness,
+palpitation of the heart, sweating, loss of weight, slight protrusion
+of the eyes, indigestion; in short, most of the phenomena of Graves'
+disease and of the strong emotions will be produced artificially
+(Figs. 15 and 23). When the administration of the thyroid extract
+is discontinued, these phenomena may disappear.  On the other hand,
+when there is too little or no thyroid gland, the individual
+becomes dull, stupid, and emotionless, though he may be irritable;
+while if a sufficient amount of thyroid extract be given to such
+a patient he may be brought back to his normal condition.
+
+Hence we see that the phenomena of the emotions may within certain
+limits be increased, diminished, or abolished by increasing,
+diminishing, or totally excluding the secretion of the thyroid gland.
+
+Graves' disease may be increased by giving thyroid extract and by fear.
+It may be diminished by removing a part of the gland, or by
+interrupting the blood and nerve supply, or by complete rest.
+In addition, at some stage of Graves' disease there is an
+increase in the size and in the number of the secreting cells.
+These facts regarding the normal and the pathologic supply of thyroid
+secretion point to this gland as one of the sources of the energizing
+substance or substances, by means of which the motor phenomena
+of animals are executed and their emotions expressed.
+
+Anger is similar to fear in origin and, like fear, is an integration
+and stimulation of the motor mechanism and its accessories.
+Animals which have no natural weapons for attack experience neither
+fear nor anger, while the animals which have weapons for attack
+express anger principally by energizing the muscles used in attack.
+Although, as has already been stated, the efficiency of the hands
+of man has largely supplanted the use of the teeth, he still shows
+his teeth in anger and so gives support to the theory that this
+emotion is of remote ancestral origin and proves the great persistence
+of phylogenetic association.  On this conception we can understand
+why it is that a patient consumed by worry--which to me signifies
+interrupted stimulation, a state of alternation between hope
+and fear--suffers so many bodily impairments and diseases even.
+This hypothesis explains the slow dying of animals in captivity.
+It explains the grave digestive and metabolic disturbances which
+appear under any nerve strain, especially under the strain of fear,
+and the great benefits of confidence and hope; it explains the nervousness,
+loss of weight, indigestion--in short, the comprehensive physical
+changes that are wrought by fear and by sexual love and hate.
+On this hypothesis we can understand the physical influence
+of one individual over the body and personality of another;
+and of the infinite factors in environment that, through phylogenetic
+association, play a role in the functions of many of our organs.
+It is because under the uncompromising law of survival of the fittest
+we were evolved as motor beings that we do not possess any organs or
+faculties which have not served our progenitors in accomplishing their
+survival in the relentless struggle of organic forms with one another.
+We are now, as we were then, essentially motor beings, and the only way in
+which we can meet the dangers in our environment is by a motor response.
+Such a motor response implies the integration of our entire being
+for action, this integration involving the activity of certain glands,
+such as the adrenals (Cannon), the thyroid, the liver, etc., which throw
+into the blood-stream substances which help to form energy, but which,
+if no muscular action ensues, are harmful elements in the blood.
+While this motor preparation is going on, the entire digestive
+tract is inhibited.  It thus becomes clear why an emotion is more
+harmful than action.
+
+Any agency that can sufficiently inspire faith,--dispel worry,--
+whether that agency be mystical, human, or divine, will at once
+stop the body-wide stimulations and inhibitions which cause
+lesions which are as truly physical as is a fracture.
+The striking benefits of good luck, success, and happiness;
+of a change of scene; of hunting and fishing; of optimistic
+and helpful friends, are at once explained by this hypothesis.
+One can also understand the difference between the broken body
+and spirits of an animal in captivity and its buoyant return to its
+normal condition when freed.
+
+But time will not permit me to follow this tempting lead, which has
+been introduced for another purpose--the proposal of a remedy.
+
+Worries either are or are not groundless.  Of those that have
+a basis, many are exaggerated.  It has occurred to me to utilize
+as an antidote an appeal to the same great law that originally
+excited the instinctive involuntary reaction known as fear--
+the law of self-preservation.
+
+I have found that if an intelligent patient who is suffering from
+fear can be made to see so plainly as to become firmly convinced
+that his brain, his various organs, indeed his whole being,
+could be physically damaged by fear, that this same instinct of
+self-preservation will, to the extent of his conviction, banish fear.
+It is hurling a threatened active militant danger, whose injurious
+influences are both certain and known, against an uncertain,
+perhaps a fancied, one.  In other words, fear itself is an injury
+which when recognized is instinctively avoided.  In a similar manner
+anger may be softened or banished by an appeal to the stronger
+self-preserving instinct aroused by the fear of physical damage,
+such as the physical injury of brain-cells. This playing of one
+primitive instinct against another is comparable to the effect
+produced upon two men who are quarreling when a more powerful enemy
+of both comes threateningly on the scene.
+
+The acute fear of a surgical operation may be banished by the use
+of certain drugs that depress the associational power of the brain and
+so minimize the effect of the preparations that usually inspire fear.
+If, in addition, the entire field of operation is blocked by local
+anesthesia so that the associational centers are not awakened,
+the patient will pass through the operation unscathed.
+
+The phylogenetic origin of fear is injury, hence injury and fear cause
+the same phenomena.  In their quality and in their phenomena psychic
+shock and traumatic shock are the same.  The perception of danger
+by the special senses in the sound of the opening gun of a battle,
+or in the sight of a venomous snake, is phylogenetically the same
+and causes the same effects upon the entire body as an operation under
+anesthesia or a physical combat in that each drives the motor mechanism.
+The use of local anesthetics in the operative field prevents
+nerve-currents from the seat of injury from reaching the brain and there
+integrating the entire body for a self-defensive struggle.  The result,
+even though a part of the brain is asleep and the muscles paralyzed,
+is the same as that produced by the interception of the terrifying
+sound of the gun, or of the sight of the dangerous reptile,
+since the stimulation of the motor mechanism is prevented.
+
+By both the positive and the negative evidence we are forced
+to believe that the emotions are primitive instinctive reactions
+which represent ancestral acts; and that they therefore utilize
+the complicated motor mechanism which has been developed by the forces
+of evolution as that best adapted to fit the individual for his
+struggle with his environment or for procreation.
+
+The mechanism by which the motor acts are performed and the mechanism
+by which the emotions are expressed are one and the same.
+These acts in their infinite complexity are suggested by association--
+phylogenetic association.  When our progenitors came in contact
+with any exciting element in their environment, action ensued then
+and there.  There was much action--little restraint or emotion.
+Civilized man is really in auto-captivity. He is subjected
+to innumerable stimulations, but custom and convention frequently
+prevent physical action.  When these stimulations are sufficiently
+strong but no action ensues, the reaction constitutes an emotion.
+A phylogenetic fight is anger; a phylogenetic flight is fear;
+a phylogenetic copulation is sexual love, and so one finds in this
+conception an underlying principle which may be the key to an
+understanding of the emotions and of certain diseases.
+
+
+
+PAIN, LAUGHTER, AND CRYING[*]
+
+[*] Address delivered before the John Ashhurst, Jr.. Surgical Society
+of the University of Pennsylvania, May 3, 1912.
+
+PAIN
+
+
+Pain, like other phenomena, was probably evolved for a particular purpose--
+surely for the good of the individual; like fear and worry,
+it frequently is injurious.  What then may be its purpose?
+
+We postulate that pain is one of the phenomena which result
+from a stimulation to motor action.  When a barefoot boy steps
+on a sharp stone it is important that the injuring contact be
+released as quickly as possible; and therefore physical injury pain
+results and impels the required action.  Anemia of the soft parts
+at the points of pressure results from prolonged sitting or lying
+in one position, and as a result pain compels a muscular action
+that shifts the damaging pressure--this is the pain of anemia;
+when the rays of the blazing sun shine directly upon the retina,
+pain immediately causes a protective muscular action--the lid is closed,
+the head turns away--this is light pain; when standing too close
+to a blazing fire the excessive heat causes a pain which results
+in the protective muscular action of moving away--this is heat pain;
+when the urinary bladder is acutely overdistended the resultant
+pain induces voluntary as well as involuntary muscular contraction--
+this is evacuation pain; associated with defecation is a characteristic
+warning pain, and an active pain which induces the required
+muscular action--this, like the pain accompanying micturition,
+is an evacuation pain; in obstruction of the urinary passages
+and of the large and the small intestine the pain is exaggerated,
+as is the accompanying muscular contraction--this is a pathologic
+evacuation pain; when the fetus reaches full term and labor is
+to begin, it is heralded by pain which is associated with rhythmic
+contractions of the uterine muscle; later, many other muscles
+take part in the birth and pain is associated with all these
+muscular contractions--these are labor pains; when a foreign body,
+be it ever so small, falls upon the conjunctiva or cornea there
+results what is perhaps the acutest pain known, and quick and active
+muscular action follows--this is special contact pain.  Special pain
+receptors are placed in certain parts of the nose, the pharynx,
+and the larynx, the stimulation of which causes special motor acts,
+such as sneezing, hawking, coughing.  Curiously vague pains are
+associated with the protective motor act of vomiting and with the sexual
+motor acts--these may be termed nausea pains and pleasure pains.
+We now see, therefore, that against the injurious physical contacts
+of environment, against heat and cold, against damaging sunlight,
+against local anemia when resting or sleeping, the body is protected
+by virtue of the muscular action which results from pain.
+Then, too, for the emptying of the pregnant uterus, for the evacuation
+of the intestine and of the urinary bladder as normal acts,
+and for the overcoming of obstructions in these tracts,
+pain compels the required muscular actions, For passing gall-stones
+and urinary calculi, urgent motor stimuli are awakened by pain.
+For each of these diversified pains the consequent muscular action
+is specific in type, distribution, and intensity.  This statement
+is so commonplace that we are apt to miss the significance and
+the wonder of it.  It is probable that every nerve-ending in the skin
+and every type of stimulation represents a separate motor pattern,
+the adequate stimulation of which causes always the same response.
+
+Let us pass on to the discussion of another and perhaps even
+more interesting type of pain, that associated with infection.
+Not all kinds of infection are painful; and in those infections
+that may be associated with pain there is pain only when certain
+regions of the body are involved.  Among the infections that are not
+associated with pain are scarlet fever, typhoid fever, measles, malaria,
+whooping-cough, typhus fever, and syphilis in its early stages.
+The infections that are usually, though not always, associated with
+pain are the pyogenic infections.  The pyogenic infections
+and the exanthemata constitute the great majority of infections
+and are the basis of the discussion which follows.
+
+I will state one of my principal conclusions first, _i.
+e_., that the only types of infection that are associated with pain
+are those in which the infection may be spread by muscular action
+or those in which the fixation of parts by continued muscular
+rigidity is an advantage; and, further, as a striking corollary,
+that the type of infection that may cause muscular action when it
+attacks one region of the body may cause no such action when it
+attacks another region.
+
+The primary, and perhaps the most striking, difference between
+the painless exanthemata and the painful pyogenic infections is that
+in the case of the exanthemata the protective response of the body
+is a chemical one,--the formation of antibodies in the blood,
+which usually produce permanent immunity,--while the response to the
+pyogenic infections is largely phagocytic.  In the pyogenic infections,
+in order to protect the remainder of the body, which, of course,
+enjoys no immunity, every possible barrier against the spread
+of the infection is thrown about the local point of infection.
+How are these barriers formed?  First, lymph is poured out, then the part
+is fixed by the continuous contraction of the neighboring muscles
+and by the inhibition of those muscles that, in the course of their
+ordinary function, would by their contractions spread the infection.
+Wherever there is protective muscular rigidity there is also pain.
+On the other hand, in pyogenic infections in the substance
+of the liver, in the substance of the kidney, within the brain,
+in the retroperitoneal space, in the lobes of the lung, in the chambers
+of the heart and in the blood-vessels of the chest and the abdomen,
+in all locations in which muscular contractions can in no way assist
+in localizing the disease, pyogenic infections produce no muscular
+rigidity and no pain.  Apparently, therefore, only those infections are
+painful which are associated with a protective muscular contraction.
+This explains why tuberculosis of the hip is painful, while tuberculosis
+of the lung is painless.
+
+There is a third type of pain which modifies muscular action
+in a curious way.  We have already stated that local pain serves
+an adaptive purpose.  In this light let us now consider headache.
+Headache is one of the commonest initiatory symptoms of the
+various infections, especially of those infections which are
+accompanied by no local pain and by no local muscular action.
+In peritonitis, cholecystitis, pleurisy, arthritis, appendicitis,
+salpingitis, child-birth, in obstructions of the intestinal
+and the genito-urinary tract, in short, in those acute processes
+in which the local symptoms are powerful enough to govern
+the individual as a whole,--to make him lie down and keep quiet,
+refuse food and possibly reject what is already in the stomach,--
+in all these conditions there is rarely a headache, but in the diseases
+in which local pain is absent, such as the exanthemata, typhoid fever,
+and auto-intoxication, which have no dominating local disturbances
+to act as policemen to put the individual to bed and to make him
+refuse food that he may be in the most favorable position to combat
+the oncoming disease, in such cases in which these masterful and
+beneficent local influences are absent we postulate that headache
+has been evolved to perform this important service.
+
+On the hypothesis that it is good for the individual who is acutely
+stricken by a disease or who is poisoned by autointoxication to rest
+and fast, and that the muscular system obeys the imperial command
+of pain, and in view of the fact that the brain is not only in constant
+touch with the conditions of every part of the body but that it
+is also the controlling organ of the body, one would expect that in
+these diseases the major pain whose purpose it is to govern general
+muscular action would be located in the head and there we find it.
+How curious and yet how intelligible is the fact that, though a
+headache may be induced by even a slight auto-intoxication,
+an abscess may exist within the brain without causing pain.
+When an obliterative endarteritis is threatening a leg with
+anemic gangrene, or when one lies too long in the same position on
+a hard bed, there is threatening injury from local anemia, and as a
+result there is acute pain, but when the obliterative endarteritis
+threatens anemia of the brain, or when an embolism or thrombosis has
+produced anemia of the brain, there may be no accompanying pain.
+The probable explanation of the pain which results in the first instance
+and the lack of pain in the second is that in the former muscular action
+constitutes a self-protective response, but in the other it does not.
+Diseases and injuries of the brain are notoriously difficult
+to diagnosticate.  This may well be because it has always been so well
+protected by the skull that there have been evolved within it few
+tell-tale self-protective responses, so that in the presence of injury
+and disease within itself the brain remains remarkably silent.
+It should occasion no surprise that there are in the brain no receptors,
+the mechanical stimulation of which can cause pain, because its bony
+covering has always prevented the adaptive implantation within it
+of contact pain receptors.  Dr. Frazier tells me that in the course
+of his operations on the brains of unanesthetized patients
+he is able to explore the entire brain freely and without pain.
+From my own experience I am able to confirm Dr. Frazier's observation.
+In addition, the two-stage operation for the excision of the Gasserian
+ganglion provides an observation of extraordinary interest.
+If at the first seance the ganglion is exposed, but is not disturbed
+except by the iodoform gauze packing, then on the following
+day the gauze may be removed, the ganglion picked up, and its
+branches and root excised without anesthesia and without pain.
+The same statement and explanation may be made regarding the distribution
+of pain receptors for physical contact within the parenchyma of the liver,
+the gall-bladder, the abdominal viscera, the spleen, the heart,
+the lungs, the retroperitoneal tissue, the deep tissue of the back,
+the vertebrae, and in certain portions of the spinal cord.
+Just what is the distribution of the receptors for heat and for cold
+I am unable to state, but this much we do know, that without
+anesthesia the intestines may be cauterized freely without the least
+pain resulting, and in animals the cauterization of the brain causes
+no demonstrable change in the circulatory or respiratory reactions.
+It is probable therefore that the distribution of the pain receptors
+for physical contact and for heat are limited to those parts of the body
+that have been exposed to injurious contacts with environment.
+
+Of special significance is the pain which is due to cold,
+which increases muscular tone and produces shivering.  The general
+increase in muscular tone produces an interesting postural phenomenon:
+the limbs are flexed and the body bent forward, a position which probably
+is due to the fact that the flexors are stronger than the extensors.
+As muscular action is always accompanied by heat production,
+the purpose of the muscular contraction and the shivering
+is quite certainly caused by cold to assist in the maintenance
+of the normal body temperature.
+
+We have now discussed many of the causes of pain and in each instance
+we have found an associated muscular action which apparently
+serves some adaptive purpose (Figs. 24 and 25). If we assume
+that pain exists for the purpose of stimulating muscular reactions,
+we may well inquire what part of the nervous are is the site of
+the sensation of pain--the nerve-endings, the trunk, or the brain?
+Does pain result from physical contact with the nerve-endings, with
+the physical act of transmitting an impression along the nerve trunk,
+or with the process within the brain-cells by which energy is released
+to cause a motor act?
+
+It seems most probable that the site of the pain is in the brain-cells.
+If this be so, then what is the physical process by which the
+phenomena of pain are produced?  The one hypothesis that can be
+tested experimentally is that pain is a phenomenon resulting from
+the rapid discharge of energy in the brain-cells. If this be true,
+then if every pain receptor of the body were equally stimulated
+in such a manner that
+
+
+{illust. caption = FIG.  25.--FEAR AND AGONY.  "Amid this dread
+exuberance of woe ran naked spirits wing'd with horrid fear."--
+Dante's "Inferno," Canto XXIV, lines 89, 90.  all the stimuli
+reached the brain-cells simultaneously, the cells would find
+themselves in equilibrium and no motor act would be performed.
+But if all the pain receptors of the body but one were equally stimulated,
+and this one stimu-lated harder than the rest, then the latter
+would gain possession of the final common path, the sensation
+of pain would be felt, and a muscular contraction would result.
+It is well known that when a greater pain is thrown into
+competition with a lesser one, the lesser is completely submerged.
+In this manner the school-boy initiates the novice into the mystery
+of the painless plucking of hair.  The simultaneous, but severe
+application of the boot to the blindfolded victim takes complete
+and exclusive possession of the final common path and the hair
+is painlessly plucked through the triumph of the boot stimulus over
+the hair stimulus in the struggle for the possession of the final
+common path.  Another argument in favor of this hypothesis that
+pain is an accompaniment of the release of energy in the brain-
+cells is found in the fact that painless stimuli received through
+the special senses may completely submerge the painful stimuli
+of physical injury; for although the stimuli to motor action,
+which are received through the senses of sight, hearing, and smell,
+cause even more powerful motor action than those caused by
+physical contact stimuli, yet they are not accompanied by pain.
+Examples of this triumph of stimulation of the special senses over
+contact stimulation are frequently seen in persons obsessed by anger
+or fear, and to a less degree in those obsessed by sexual emotion.
+In the fury of battle the soldier may not perceive his wound until
+the emotional excitation is wearing away, when the sensation
+of warm blood on the skin may first attract his attention.
+Religious fanatics are said to feel no pain when they subject themselves
+to self-injury. Now, since both psychic and mechanical stimuli cause motor
+action by the excitation ofprecisely the same mechanism in the brain,
+and since the more rapid release of energy from psychic stimuli
+submerges the physical stimuli and prevents pain, it would seem
+that pain must be a phenomenon which is associated with the process
+of releasing energy by the brain-cells. Were physical injury inflicted
+in a quiescent state equal to that inflicted in the emotional state,
+great pain and intense muscular action would be experienced.
+Now the emotions are as purely motor excitants as is pain.
+The dynamic result is the same the principal difference being the greater
+suddenness and the absolute specificity of the pain stimuli as compared
+with the more complex and less peremptory stimuli of the emotions.
+A further evidence that pain is a product of the release of brain-cell
+energy is the probability that if one could pierce the skin at
+many points on a limb in such a manner that antagonistic points
+only were equally and simultaneously stimulated, then an equilibrium
+in the governing brain- cells would be established and neither
+pain nor motion would follow.  An absolute test of this assumption
+cannot be made but it is supported by the obtainable evidence.
+We will now turn to a new viewpoint, a practical as well as a
+fascinating one, which can best be illustrated by two case histories:
+A man, seventy-eight years old, whose chief complaint was obstinate
+constipation, was admitted to the medical ward of the Lakeside Hospital
+several years ago.  The abdomen was but slightly distended;
+there was no fever, no increased leukocytosis, no muscular rigidity,
+and but slight general tenderness.  He claimed to have lost in weight
+and strength during the several months previous to his admission.
+A tentative diagnosis of malignant tumor of the large intestine was made,
+but free movements weresecured rather easily, and we abandoned
+the idea of an exploratory operation.  The patient gradually failed
+and died without a definite diagnosis having been made by either
+the medical or the surgical service.  At autopsy there was found
+a wide-spread peritonitis arising from a perforated appendix.
+A child, several years old, was taken ill with some indefinite disease.
+A number of the ablest medical and surgical consultants of a leading
+medical center thoroughly and repeatedly investigated the case.
+Although they could make no definite diagnosis they all
+agreed that the trouble surely could not be appendicitis
+because there was neither muscular rigidity nor tenderness.
+The autopsy showed a gangrenous appendix and general peritonitis.
+How can these apparently anomalous cases be explained?
+These two cases are illustrations of the same principle that underlies
+the freedom from pain which results from the use of narcotics
+and anesthetics, the same principle that explains the fact that
+cholecystitis may occur in the aged without any other local symptoms
+than the presence of a mass and perhaps very slight tenderness;
+and that accounts in general for the lack of well-expressed disease
+phenomena in senility and in infancy.  The reason why the aged,
+the very young, and the subjects of general paresis show but few
+symptoms of disease is that in senility the brain is deteriorated,
+while in infancy the brain is so undeveloped that the mechanism
+of association is inactive, hence pain and tenderness,
+which are among the oldest of the associations, are wanting.
+Senility and infancy are by nature normally narcotized.
+The senile are passing through the twilight into the night;
+while infants are traversing through the dawn into the day.
+Hence it is that the diagnosis of injury and disease in the extremes
+oflife is beset by especial difficulties, since the entire body
+is as silent as are the brain, the pericardium, the mediastinum,
+and other symptomless areas.  For the same reason, when a patient
+who is seriously ill with a painful disease turns upon the physician
+a glowing eye and an eager face, and remarks how comfortable he feels,
+then the end is near.  This is a brilliant and fateful clinical mirage.
+When one reflects on the vast amount of evidence as to the origin
+and the purpose of pain, he is forced to conclude that pain is
+a phenomenon of motor stimulation, and that its principal role is
+the protection of the individual against the gross and the microscopic
+enemies in his environment.  The benefits of pain are especially
+manifested in the urgent muscular actions by means of which the body
+moves away from physical injury; obstructions of the hollow
+viscera are overcome; rest is compelled in the acute infections--
+the infected points are held rigidly quiet, the muscles of the abdomen
+are fixed, and harmful peristalsis is arrested in peritonitis;
+while there is absolutely no pain in the diseases or injuries
+which affect those regions of the body in which in the course
+of evolution no pain receptors were placed, or in those diseases
+in which muscular inhibition or contraction is of no help.
+In a biologic sense pain is closely associated with the emotional stimuli,
+for both pain and the emotions incite motor activity for the good
+of the individual.  The frequent occurrence of post-operative and
+post- traumatic pain is accounted for by the fact that the operation
+or the injury has lowered the threshold of the brain- cells to trauma;
+the brain and not the local sensitive field is the site of the pain.
+I have found that, by blockingthe field of operation with
+local anesthesia, post-operative pain is diminished; that is,
+since the local anesthesia prevents the strong stimuli of the
+trauma from reaching the brain, its threshold is not lowered.
+There is a close resemblance between the phenomena of pain habit,
+of education, of physical training, of love and of hate.  In education,
+in pain habit, in all emotional relations, a low brain- cell threshold
+is established which facilitates the reception of specific stimuli;
+all these processes are motor acts, or are symbolic of motor acts,
+and we may be trained to perceive misfortune and pain as readily as we
+are trained to perceive mathematical formulae or moral precepts.
+In each and every case, readiness of perception depends, as it seems to me,
+upon a modified state of the brain-cells, their threshold especially,
+the final degree of perception possible in any individual being perhaps
+based on the type of potential molecules of which the brain is built.
+We must believe also that every impression is permanent, as only thus
+could an individual animal or a man be fitted by his own experience
+for life's battles.  LAUGHTER AND CRYING What is laughter?
+What is its probable origin, its distribution, and its purpose?
+Laughter is an involuntary rhythmic contraction of certain
+respiratory muscles, usually accompanied by certain vocal sounds.
+It is a motor act of the respiratory apparatus primarily, although if
+intense it may involve not only the extraordinary muscles of respiration,
+but most of the muscles of the body.  There are many degrees
+of laughter, from the mere brightening of the eyes, a fleeting smile,
+tittering andgiggling, to hysteric and convulsive laughter.
+Under certain circumstances, laughter may be so intense and
+so long continued that it leads to considerable exhaustion.
+The formation of tears is sometimes associated with laughter.
+When integrated with laughter, the nervous system can perform
+no other function.  Crying is closely associated with laughter,
+and in children especially laughter and crying are readily interchanged.
+We postulate that laughter and weeping serve a useful purpose.
+According to Darwin, only man and monkeys laugh (Fig. 26);
+other animals exhibit certain types of facial expression accompanying
+various emotions, but laughter in the sense in which that word
+is commonly used is probably an attribute of the primates only,
+although it is probable that many animals find substitutes for laughter.
+The proneness of man to laughter is modified by age, sex, training,
+mental state, health, and by many other factors.  Healthy, happy children
+are especially prone to laughter, while disease, strong emotions,
+fatigue, and age diminish laughter.  Women laugh more than do men.
+The healthy, happy maturing young woman perhaps laughs most, especially
+when she is slightly embarrassed.  What causes laughter?  Good news,
+high spirits, tickling, hearing and seeing others laugh; droll stories;
+flashes of wit; passages of humor; averted injury; threatened breach
+of the conventions; and numerous other causes might be added.
+It is obvious that laughter may be produced by diverse influences,
+many of which are so unlike each other that it would at first sight
+seem improbable that a single general principle underlies all.
+Before presenting a hypothesis which harmonizes most of the facts,
+and which mayoffer an explanation of the origin and purpose of laughter,
+let us return for a moment to some previous considerations--
+that man is essentially a motor being; that all his responses to
+the physical forces of his environment are motor; {illust. caption
+= FIG.  26.--LAUGHING CHIMPANZEE.  "Mike," the clever chimpanzee
+in the London Zoo, evidently enjoys a joke as well as any one else.
+(Photo by Underwood and Underwood, N. Y.)}
+
+
+that thoughts and words even are symbolic of motor acts;
+that in the emotions of fear, of anger, and of sexual love
+the whole body is integrated for acts which are not performed.
+These integrations stimulate the brain-cells, the ductless glands,
+and other parts, and the energizing secretions, among which are epinephrin,
+thyroid and hypophyseal secretions, are thrown into the blood-stream,
+while that most available fuel, glycogen, is also mobilized in the blood.
+This body-wide preparation for action may be designated kinetic reaction.
+The fact that emotion is more injurious to the body than is
+muscular action is well known, the difference being probably caused
+by the fact that when there is action the above-mentioned products
+of stimulation are consumed, while in stimulation without action
+they are not consumed and must be eliminated as waste products.
+Now these activating substances and the fuel glycogen may be consumed
+by any muscular action as well as by the particular muscular action
+for which the integration and consequent stimulation were made;
+that is, if one were provoked to such anger that he felt impelled
+to attack the object of his anger, one of three things might happen:
+First, he might perform no physical act but give expression to
+the emotion of anger; second, he might engage in a physical struggle
+and completely satisfy his anger; third, he might immediately engage
+in violent gymnastic exercises and thus consume all the motor-producing
+elements mobilized by the anger and thus clarify his body.
+
+In these premises we find our explanation of the origin and purpose
+of laughter and crying, for since they consist almost wholly
+of muscular exertion, they serve precisely such clarifying purposes
+as would be served by the gymnastic exercises of an angry man.
+As it seems to me, the muscular action of laughter clears the system
+of the energizing substances which have been mobilized in various
+parts of the body for the performance of other actions (Figs. 27
+to 29). If this be true, the first question that presents itself is,
+Why is the respiratory system utilized for such a clarifying purpose?
+Why do we not laugh with our feet and hands as well?
+Were laughter expressed with the hands, the monkey might fall
+from the tree and, if by the feet, man might fall to the ground.
+He would at least be ataxic.  In fact, laughter has the great
+advantage of utilizing a group of powerful muscles which can be
+readily spared without seriously interfering with the maintenance
+of posture.  Laughter, however, is only one form of muscular action
+which may consume the fuel thrown into the blood by excitation.
+That these products of excitation are often consumed by other motor
+acts than laughter is frequently seen in public meetings when
+the stamping of feet and the clapping of hands in applause gives
+relief to the excitation (Fig. 30). Why the noise of laughter?
+In order that the products of excitation may be quickly and
+completely consumed, the powerful group of expiratory muscles must
+have some resistance against which they can exert themselves strongly
+and at the same time provide for adequate respiratory exchange.
+The intermittent closure of the epiglottis serves this purpose admirably,
+just as the horizontal bars afford the resistance against which muscles
+may be exercised.  The facial muscles are not in use for other purposes,
+hence their contractions will consume a little of the fuel.
+An audience excited by the words of an impassioned speaker undergoes
+a body-wide stimulation for action, all of which may be eliminated
+by laughter or by applause (Fig. 31).
+
+Let us test this hypothesis by some practical examples.
+The first is an incident that accidentally occurred in our laboratory
+during experiments on fear which were performed as follows:
+A keen, snappy fox terrier was completely muzzled by winding a broad strip
+of adhesive plaster around his jaw so as to include all but the nostrils.
+When this aggressive little terrier and the rabbit found themselves
+in close quarters each animal became completely governed by instinct;
+the rabbit crouched in fear, while the terrier, with all the ancestral
+assurance of seizing his prey, rushed, upon the rabbit, his muzzle
+always glancing off and his attack ending in awkward failure.
+
+This experiment was repeated many times and each time provoked
+the serious-minded scientific visitors who witnessed it
+to laughter.  Why?  Because the spectacle of a savage little terrier
+rushing upon an innocent rabbit as if to mangle it integrated
+the body of the onlooker with a strong desire to exert muscular
+action to prevent the cruelty.  This integration caused a conversion
+of the potential energy in the brain-cells into kinetic energy,
+and there resulted a discharge into the blood-stream of activating
+internal secretions for the purpose of producing muscular action.
+Instantly and unexpectedly the danger passed and the preparation
+for muscular action intended for use in the protection of the rabbit
+was not needed.  This fuel was consumed by the neutral muscular
+action of laughter, which thus afforded relief.
+
+A common example of the same nature is that encountered on the street
+when a pedestrian slips on a banana peel and, just as he is
+about to tumble, recovers his equilibrium.  The onlookers secure
+relief from the integration to run to his rescue by laughing.
+On the other hand, should the same pedestrian fall and fracture
+his skull the motor integration of the onlookers would be consumed
+by rendering physical assistance--hence there would be no laughter.
+In children almost any unexpected phenomenon, such as a sudden "booing"
+from behind a door, is attended by laughter, and in like manner
+the kinetic reaction produced by the innumerable threats of danger
+which are suddenly averted, a breach of the conventions, a sudden
+relief from acute nervous tension; a surprise--indeed, any excitant
+to which there is no predetermined method of giving a physical response--
+may be neutralized by the excitation of the mechanism of laughter.
+
+In the same way the laughter excited by jokes may be explained.
+An analysis of a joke shows that it is composed of two parts--
+the first, in which is presented a subject that acts as a stimulus
+to action, and the second, in which the story turns suddenly
+so that the stimulus to action is unexpectedly withdrawn.
+The subject matter of the joke affects each hearer according
+to the type of stimuli that commonly excites that individual.
+Hence it is that a joke may convulse one person while it bores another,
+and so there are jokes of the classes, bankers' jokes, politicians' jokes,
+the jokes of professional men, of the plebeian, of the artist, etc.
+If the joke fails, the integration products of the excitation may
+be used in physical resentment (Fig. 32).
+
+Another type of laughter is that associated with the ticklish points
+of certain parts of the body, the soles of the feet and certain
+parts of the trunk and of the abdomen.  The excitation of the
+ticklish receptors, like pain, compels self-defensive motor acts.
+This response is of phylogenetic origin, and may be awakened only
+by stimuli which are too light to be painful.  In this connection
+it is of interest to note that a superficial, insect-like contact
+with the skin rarely provokes laughter, and that the tickling
+of the nasal, oral, and pulmonary tracts does not produce laughter.
+The ticklish points that cause laughter are rather deeply placed,
+and a certain type of physical contact is required to constitute
+an adequate stimulus.  That is, the contact must arouse a phylogenetic
+association with a physical struggle or with physical exertion.
+In the foot, the adequate stimuli for laughter are such contacts
+as resemble or suggest piercing by stones or rough objects.. The
+intention of the one who tickles must be known; if his intention
+be playful, laughter results, whereas if injury be intended,
+then an effort toward escape or defense is excited, but no laughter.
+If deep tickling of the ribs is known to be malicious, it will excite
+physical resentment and not laughter.  Self-tickling rarely causes
+laughter for the reason that auto-tickling can cause only a known
+degree of stimulation, so that there results no excessive integration
+which requires relief by the neutral muscular activity of laughter.
+In fact, one never sees purposeful acts and laughter associated.
+According to its severity, an isolated stimulus causes either
+an action or laughter.  The ticklish points in our bodies were
+probably developed as a means of defense against serious attacks
+and of escape from injurious contacts.
+
+Anger, fear, and grief are also strong excitants and, therefore,
+are stimuli to motor activity.  It is obvious that whatever the excitant
+the physico-chemical action of the brain and the ductless glands
+cannot be reversed--the effect of the stimulus cannot be recalled,
+therefore either a purposeful muscular act or a neutralizing act
+must be performed or else the liberated energy must smoulder
+in the various parts of the body.
+
+It is on this hypothesis that the origin and the purpose of laughter
+and crying may be understood.  Even a superficial analysis of the
+phenomena of both laughter and crying show them to be without any
+external motor purpose; the respiratory mechanism is intermittently
+stimulated and inhibited; and the shoulder and arm muscles, indeed,
+many muscles of the trunk and the extremities are, as far as any
+external design is concerned, purposelessly contracted and released
+until the kinetic energy mobilized by excitation is utilized.
+During this time the facial expression gives the index to
+the mental state.
+
+Crying, like laughter, is always preceded by a stimulation
+to some motor action which may or may not be performed
+(Figs. 33 and 34). If a mother is anxiously watching the course
+of a serious illness of her child and if, in caring for it, she is
+stimulated to the utmost to perform motor acts, she will continue
+in a state of motor tenseness until the child recovers or dies.
+If relief is sudden, as in the crisis of pneumonia, and the mother
+is not exhausted, she will easily laugh if tired, she may cry.
+If death occurs, the stimulus to motor acts is suddenly
+withdrawn and she then cries aloud, and performs many motor
+acts as a result of the intense stimulation to motor activity
+which is no longer needed in the physical care of her child.
+With this clue we can find the explanation of many phenomena.  We can
+understand why laughter and crying are so frequently interchangeable;
+why they often blend and why either gives a sense of relief;
+we can understand why either laughter or crying can come only
+when the issue that causes the integration is determined; we can
+understand the extraordinary tendency to laughter that discloses
+the unspoken sentiments of love; we can understand the tears
+of the woman when she receives a proposal of marriage from the man
+she loves; we can understand why any averted circumstance,
+such as a threatened breach of the conventions, which would have led
+to embarrassment or humiliation, leads to a tendency to laughter;
+and why the recital of heroic deeds by association leads to tears,
+On the other hand, under the domination of acute diseases,
+of acute fear, or of great exhaustion, there is usually neither
+laughter nor crying because the nervous system is under the control
+of a dominating influence as a result of which the body is so
+exhausted that the excess of energy which alone can produce laughing
+or crying is lacking.
+
+A remarkable study of the modification of laughter and crying by disease
+is found in that most interesting of diseases--exophthalmic goiter.
+In this disease there is a low threshold to all stimuli.
+That the very motor mechanism of which we have been speaking
+is involved, is shown by an enormous increase in its activity.
+There is also an increase in the size of certain at least of the
+activating glands--the thyroid and the adrenals are enlarged and overactive
+and the glycogen-producing function of the liver is stimulated.
+The most striking phenomenon of this disease, however, is the remarkable
+lowering of the brain thresholds to stimuli.  In other words,
+in Graves' disease the nervous system and the activating glands--
+the entire motor mechanism--are in an exalted state of activity.
+
+If this be true, then these patients should exhibit behavior
+precisely contrary to that of those suffering from acute infection,
+that is, they should be constantly clearing their systems of
+these superabundant energizing materials by crying or laughing,
+and this is precisely what happens--the flood-gates of tears are open
+much of the time in Graves' disease--a disease of the emotions.
+
+We have already interpreted pain as a phenomenon of motor activity.
+When pain does not lead to muscular activity it therefore frequently
+leads to crying or to moaning, just as tickling, which is equally
+an incentive to motor activity, results in laughter if it does
+not find full expression in action.
+
+From the foregoing we infer that pain, the intense motor response
+to tickling, and emotional excitation are all primitive biologic
+reactions for the good of the individual, and that all have
+their origin in the operation of the great laws of evolution.
+If to this inference we add the physiologic dictum that the nervous
+system always acts as a whole, and that it can respond to but one
+stimulus at a time, we can easily understand that while diverse
+causes may integrate the nervous system for a specific action,
+if the cause be suddenly removed, then the result of the
+integration of the nervous system may be, not a specific action,
+but an undesigned muscular action, such as crying or laughter.
+Hence it is that laughter and crying may be evoked by diverse
+exciting causes.  The intensity of the laughter or of the crying
+depends upon the intensity of the stimulus and the dynamic state
+of the individual.
+
+The linking together of these apparently widely separated phenomena
+by the simple law of the discharge of energy by association perhaps
+explains the association of an abnormal tendency to tears with an
+abnormally low threshold for pain (Fig. 36). In the neurasthenic,
+tears and pain are produced with abnormal facility.  Hence it is that,
+if a patient about to undergo a surgical operation is in a state of fear
+and dread before the operation, the threshold to all stimuli is lowered,
+and this lowered threshold will continue throughout the operation,
+even under inhalation anesthesia, because the stimulus produced by
+cutting sensitive tissue is transmitted to the brain just as readily
+as if the patient were not anesthetized.  In like manner, the brain
+may be sensitized by the administration of large doses of thyroid
+extract prior to operation, the threshold to injury in such a case
+continuing to be low to traumatic stimuli even under anesthesia.
+Under the sensitizing influences of thyroid extract or of Graves'
+disease the effect of an injury, of an operation, or of emotional
+excitation is heightened.  The extent to which the threshold to pain
+or to any other excitant is affected by Graves' disease is illustrated
+by the almost fatal reaction which I once saw result from the mere
+pricking with a hypodermic needle of a patient with this disease.
+As the result of a visit from a friend, the pulse-rate of a victim of this
+disease may increase twenty beats and his temperature rise markedly.
+I have seen the mere suggestion of an operation produce collapse.
+As the brain is thus remarkably sensitized in Graves' disease, we find
+that in these patients laughter, crying, emotional disturbances,
+and surgical shock are produced with remarkable facility.
+
+I hope that even this admittedly crude and imperfect consideration
+of this subject will suggest the possibility of establishing
+a practical viewpoint as to the origin and purpose of pain,
+of tickling, and of such expressions of emotion as laughter and crying,
+and that it may help us to understand their significance in health
+and in disease.
+
+
+
+THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND
+BRAIN FUNCTIONS--EXPERIMENTAL AND CLINICAL[*]
+
+[*] Address before The American Philosophical Society, April 18, 1913.
+
+
+The brain in all animals (including man) is but the clearing-house
+for reactions to environment, for animals are essentially motor
+or neuromotor mechanisms, composed of many parts, it is true,
+but integrated by the nervous system.  Throughout the phylogenetic history
+of the race the stimuli of environment have driven this mechanism,
+whose seat of power--the battery--is the brain.
+
+Since all normal life depends upon the response of the brain
+to the daily stimuli, we should expect in health, as well
+as in disease, to find modifications of the functions and the
+physical state of the component parts of this central battery--
+the brain-cells. Although we must believe, then, that every
+reaction to stimuli, however slight, produces a corresponding
+change in the brain-cells, yet there are certain normal, that is,
+non-diseased, conditions which produce especially striking changes.
+The cell changes due to the emotions, for example, are so similar,
+and in extreme conditions approach so closely to the changes produced
+by disease, that it is impossible to say where the normal ceases
+and the abnormal begins.
+
+In view of the similarity of brain-cell changes it is not strange
+that in the clinic as well as in daily life, we are confronted
+constantly by outward manifestations which are so nearly
+identical that the true underlying cause of the condition in
+any individual case is too often overlooked or misunderstood.
+In our laboratory experiments and in our clinical observations
+we have found that exhaustion produced by intense emotion,
+prolonged physical exertion, insomnia, intense fear, certain toxemias,
+hemorrhage, and the condition commonly denominated surgical shock,
+produce similar outward manifestations and identical brain-cell changes.
+
+It is, therefore, the purpose of this paper to present the definite
+results of laboratory researches which show certain relations
+between alterations in brain functions and physical changes
+in the brain-cells.
+
+Fear.--Our experiments have shown that the brain-cell changes due
+to fear may be divided into two stages:  First, that of hyperchromatism--
+stimulation; second, that of hypochromatism--exhaustion (Figs. 5 and
+13). Hyperchromatism was shown only in the presence of the activating
+stimuli or within a very short time after they had been received.
+This state gradually changed until the period of maximum exhaustion
+was reached--about six hours later.  Then a process of reconstruction
+began and continued until the normal state was again reached.
+
+Fatigue.--Fatigue from overexertion produced in the brain-cells
+like changes to those produced by fear, these changes being
+proportional to the amount of exertion (Fig. 4). In the extreme
+stage of exhaustion from this cause we found that the total
+quantity of Nissl substance was enormously reduced.
+When the exertion was too greatly prolonged, it took weeks or
+months for the cells to be restored to their normal condition.
+We have proved, therefore, that in exhaustion resulting from emotion
+or from physical work a certain number of the brain-cells are
+permanently lost.  This is the probable explanation of the fact
+that an athlete or a race-horse trained to the point of highest
+efficiency can reach his maximum record but once in his life.
+Under certain conditions, however, it is possible that, though some
+chromatin is forever lost, the remainder may be so remarkably developed
+that for a time at least it will compensate for that which is gone.
+
+Hemorrhage.--The loss of blood from any cause, if sufficient to reduce
+the blood-pressure, will occasion a change in the brain-cells, provided
+that the period of hypotension lasts for more than five minutes.
+This time limit is a safeguard against permanent injury
+from the temporary hypotension which causes one to faint.
+If the hemorrhage be long continued and the blood-pressure be low,
+there will be a permanent loss of some of the brain-cells. This
+explains why an individual who has suffered from a prolonged
+hemorrhage will never again be restored to his original powers.
+
+Drugs.--According to their effect upon the brain-cells, drugs
+may be divided into three classes:  First, those that stimulate
+the brain-cells to increased activity, as strychnin (Fig. 37);
+second, those that chemically destroy the brain-cells, as alcohol
+and iodoform (Figs. 38 and 39); third, those that suspend the functions
+of the cells without damaging them, as nitrous oxid, ether, morphin.
+Our experiments have shown that the brain-cell changes induced
+by drugs of the first class are precisely the same as the cycle
+of changes produced by the emotions and by physical activity.
+We have found that strychnin, according to the dosage, causes convulsions
+ending in exhaustion and death; excitation followed by lassitude;
+stimulation without notable after-results; or
+
+
+{illust. caption = A, Section of Cerebellum of Normal Dog.  C, Section of
+Cerebellum of Dog after Repeated Doses of Strychnin.  FIG.  37.--
+BRAIN-CELLS SHOWING STAGE OF HYPERCHROMATISM FOLLOWED BY CHROMATOLYSIS
+RESULTING FROM THE CONTINUATION OF THE STIMULUS.  (Camera lucida
+drawings.)increased mental tone; while the brain-cells accurately
+display these physiologic alterations in proportional hyperchromatism
+in the active stages, and proportional chromatolysis in the stages
+of reaction.  The biologic and therapeutic application of this fact
+is as obvious as it is important.
+
+In our experiments, alcohol in large and repeated dosage caused
+marked morphologic changes in the brain-cells which went as far
+even as the destruction of some of the cells (Fig. 39). Ether,
+on the other hand, even after five hours of administration,
+produced no observable destructive changes in the brain-cells.
+
+The effect of iodoform was peculiarly interesting, as it was the only
+drug that produced a rise of temperature.  Its observed effect upon
+the brain-cells was that of wide-spread destruction.
+
+Infections.--In every observation regarding the effect of pyogenic
+infections on dogs and on man we found that they caused definite
+and demonstrable lesions in certain cells of the nervous system,
+the most marked changes being in the cortex and the cerebellum
+(Fig. 40). For example, in fatal infections resulting from
+bowel obstruction, in peritonitis, and in osteomyelitis, the real
+lesion is in the brain-cells. We may, therefore, reasonably conclude
+that the lassitude, the diminished mental power, the excitability,
+irritability, restlessness, delirium, and unconsciousness which may
+be associated with acute infections, are due to physical changes
+in the brain-cells.
+
+Graves' Disease.--In Graves' disease the brain-cells show marked
+changes which are apparently the same as those produced by overwork,
+by the emotions, and by strychnin.  In the postmortem examination
+of one advanced case it was found that a large number of brain-cells
+were disintegrated beyond the power of recuperation, even had
+the patient lived.  This is undoubtedly the reason why a severe case
+of exophthalmic goiter sustains a permanent loss of brain power.
+
+Insomnia.--The brains of rabbits which had been kept awake for one
+hundred hours showed precisely the same changes as those shown
+in physical fatigue, strychnin poisoning, and exhaustion from
+emotional stimulation.  Eight hours of continuous sleep restored
+all the cells except those that had been completely exhausted.
+This will explain the permanent ill effect of long-continued insomnia;
+that is, long-continued insomnia permanently destroys a part
+of the brain-cells just as do too great physical exertion,
+certain drugs, emotional strain, exophthalmic goiter, and hemorrhage.
+We found, however, that if, instead of natural sleep, the rabbits
+were placed for the same number of hours under nitrous oxid anesthesia,
+not only did the brain-cells recover from the physical deterioration,
+but that 90 per cent.  of them became hyperchromatic.
+This gives us a possible clue to the actual chemical effect of sleep.
+For since nitrous oxid owes its anesthetic effect to its influence
+upon oxidation, we may infer that sleep also retards the oxidation
+of the cell contents.  If this be true, then it is probable
+that inhalation anesthetics exert their peculiar influence upon
+that portion of the brain through which sleep itself is produced.
+If nitrous oxid anesthesia and sleep are chemically identical, then we
+have a further clue to one of the primary mechanisms of life itself;
+and as a practical corollary one might be able to produce artificial
+sleep which would closely resemble normal sleep, but which would
+have this advantage, that by using an anesthetic which interferes with
+oxidation the brain-cells might be reconstructed after physical fatigue,
+after emotional strain, or after the depression of disease.
+
+In the case of the rabbit in which nitrous oxid was substituted
+for sleep, the appearance of the brain-cells resembled that in
+but one other group experimentally examined--the brain-cells
+of hibernating woodchucks.
+
+Insanity.--Our researches have shown that in the course of a fatal
+disease and in fatal exhaustion, however produced, death does not
+ensue until there is marked disorganization of the brain tissue.
+In the progress of disease or exhaustion one may see in different
+patients every outward manifestation of mental deterioration,
+manifestations which, in a person who does not show any other sign of
+physical disease, mark him as insane.  Take, for example, the progressive
+mental state of a brilliant scholar suffering from typhoid fever.
+On the first day of the gradual onset of the disease he would
+notice that his mental power was below its maximum efficiency;
+on the second he would notice a further deterioration, and so
+the mental effect of his disease would progress until he would
+find it impossible to express a thought or to make a deduction.
+No one can be philanthropic with jaundice; no one suffering
+from Graves' disease can be generous; no mental process is possible
+in the course of the acute infectious diseases.  Just prior to death
+from any cause every one is in a mental state which, if it could
+be continued, would cause that individual to be judged insane.
+If the delirium that occurs in the course of certain diseases
+should be continued, the patient would be judged insane.
+In severe cases of Graves' disease the patient is insane.
+Individuals under overwhelming emotion may be temporarily insane.
+Every clinician has seen great numbers of cases in which insanity
+is a phase of a disease, of an injury, or of an emotion.
+The stage of excitation in anesthesia is insanity.
+The only difference between what is conventionally called insanity
+and the fleeting insanity of the sick and the injured is that of time.
+We may conclude, therefore, what must be the brain-picture of the person
+who is permanently insane.  This _a priori_ reasoning is all that
+is possible, since the study of the brain in the insane has thus far
+been confined to the brains of those who have died of some disease.
+And it is impossible to say which changes have been produced by the
+fatal disease, and which by the condition which produced the insanity.
+The only logical way by which to investigate the physical basis
+of insanity would be to make use of the very rare opportunities
+of studying the brains of insane persons who have died in accidents.
+
+Our experiments have proved conclusively that whether we call a person
+fatigued or diseased, the brain-cells undergo physical deterioration,
+accompanied by loss of mental power (Figs. 40 to 43). Even to the minutest
+detail we can show a direct relationship between the physical state
+of the brain-cells and the mental power of the individual, that is,
+the physical power of a person goes _pari passu_ with his mental power.
+Indeed, it is impossible to conceive how any mental action,
+however subtle, can occur without a corresponding change in the
+brain-cells. It is possible now to measure only the evidences of
+the effects on the brain-cells of gross and violent mental activity.
+At some future time it will doubtless be possible so to refine
+the technic of brain-cell examinations that more subtle changes
+may be measured.  Nevertheless, with the means at our disposal
+we have shown already that in all the conditions which we
+have studied the cells of the cortex show the greatest changes,
+and that loss of the higher mental functions invariably accompanies
+the cell deterioration.
+
+
+
+
+A MECHANISTIC VIEW OF PSYCHOLOGY[*]
+
+
+[*] Address delivered before Sigma Xi, Case School
+of Science, Cleveland, Ohio, May 27, 1913, and published
+in _Science_, August 29, 1913.
+
+
+Traditional religion, traditional medicine, and traditional psychology
+have insisted upon the existence in man of a triune nature.
+Three "ologies" have been developed for the study of each nature
+as a separate entity--body, soul, and spirit--physiology, psychology,
+theology; physician, psychologist, priest.  To the great minds
+of each class, from the days of Aristotle and Hippocrates on,
+there have come glimmerings of the truth that the phenomena
+studied under these divisions were interrelated.  Always, however,
+the conflict between votaries of these sciences has been sharp,
+and the boundary lines between them have been constantly changing.
+Since the great discoveries of Darwin, the zoologist, biologist,
+and physiologist have joined hands, but still the soul-body-spirit
+chaos has remained.  The physician has endeavored to fight the gross
+maladies which have been the result of disordered conduct;
+the psychologist has reasoned and experimented to find the laws
+governing conduct; and the priest has endeavored by appeals to an
+unknown god to reform conduct.
+
+The great impulse to a deeper and keener study of man's relation,
+not only to man, but to the whole animal creation, which was given
+by Darwin, has opened the way to the study of man on a different basis.
+Psychologists, physicians, and priests are now joining hands as never
+before in the great world-wide movement for the betterment of man.
+The new science of sociology is combining the functions of all three,
+for priest, physician, and psychologist have come to see that man
+is in large measure the product of his environment.
+
+My thesis to-night, however, will go beyond this common agreement,
+for I shall maintain, not that man is in _*large measure_ the product
+of his environment, but that environment has been the actual CREATOR
+of man; that the old division between body, soul, and spirit
+is non-existent; that man is a unified mechanism responding in every
+part to the adequate stimuli given it from without by the environment
+of the present and from within by the environment of the past,
+the record of which is stored in part in cells throughout
+the mechanism, but especially in its central battery--the brain.
+I postulate further that the human body mechanism is equipped, first,
+for such conflict with environment as will tend to the preservation
+of the individual; and, second, for the propagation of the species,
+both of these functions when most efficiently carried out tending
+to the upbuilding and perfection of the race.
+
+Through the long ages of evolution the human mechanism has been
+slowly developed by the constant changes and growth of its parts
+which have resulted from its continual adaptation to its environment.
+In some animals the protection from too rough contact with
+surroundings was secured by the development of an outside armor;
+in others noxious secretions served the purposes of defense,
+but such devices as these were not suitable for the higher animals
+nor for the diverse and important functions of the human race.
+The safety of the higher animals and of man had to be preserved
+by some mechanism by means of which they could become adapted
+to a much wider and more complex environment, the dominance over
+which alone gives them their right to be called "superior beings."
+The mechanism by the progressive development of which living
+beings have been able to react more and more effectually to their
+environment is the central nervous system, which is seen in one
+of its simplest forms in motor plants, such as the sensitive
+plant and the Venus fly-trap, and in its highest development only
+in the sanest, healthiest, happiest, and most useful men.
+
+The essential function of the nervous system was primarily to secure
+some form of motor activity, first as a means of securing food,
+and later as a means of escaping from enemies and to promote procreation.
+Activities for the preservation of the individual and of the species
+were and are the only purposes for which the body energy is expended.
+The central nervous system hag accordingly been developed for the purpose
+of securing such motor activities as will best adapt the individuals
+of a species for their self-preservative conflict with environment.
+
+It is easy to appreciate that the simplest expressions of nerve response--
+the reflexes--are motor in character, but it is difficult to understand
+how such intangible reactions as love, hate, poetic fancy, or moral
+inhibition can be also the result of the adaptation to environment
+of a distinctively motor mechanism.  We expect, however, to prove
+that so-called "psychic" states as well as the reflexes are products
+of adaptation; that they occur automatically in response to adequate
+stimuli in the environment; that, like the reflexes, they are
+expressions of motor activity, which, although intangible and unseen,
+in turn incite to activity the units of the motor mechanism of the body;
+and finally, that any "psychic" condition results in a definite depletion
+of the potential energy in the brain-cells which is proportionate
+to the muscular exertion of which it is the representative.
+
+That this nerve mechanism may effectively carry out its
+twofold function, first, of self-adaptation to meet adequately
+the increasingly complicated stimuli of environment; and second,
+of adapting the motor mechanism to respond adequately to its demands,
+there have been implanted in the body numerous nerve ceptors--
+some for the transmission of stimuli harmful to the mechanism--
+nociceptors some of a beneficial character--beneceptors; and still
+others more highly specialized, which partake of the nature of both
+bene- and nociceptors--the distance ceptors, or special senses.
+
+A convincing proof that environment has been the creator
+of man is seen in the absolute adaptation of the nociceptors
+as manifested in their specific response to adequate stimuli,
+and in their presence in only those parts of the body which throughout
+the history of the race have been most exposed to harmful contacts.
+We find they are most numerous in the face, the neck, the abdomen,
+the hands, and the feet; while in the back they are few in number,
+and within the bony cavities they are lacking.
+
+Instances of the specific responses made by the nociceptors might be
+multiplied indefinitely.  Sneezing, for example, is a specific response
+made by the motor mechanism to stimulation of nociceptors in the nose,
+while stimulation of the larynx does not produce a sneeze, but a cough;
+stimulation of the nociceptors of the stomach does not produce cough,
+but vomiting; stimulation of the nociceptors of the intestine
+does not produce vomiting, but increased peristaltic action.
+There are no nociceptors misplaced; none wasted; none that do not
+make an adequate response to adequate stimulation.
+
+Another most significant proof that the environment of the past
+has been the creator of the man of to-day is seen in the fact
+that man has added to his environment certain factors to which
+adaptation has not as yet been made.  For example, heat is
+a stimulus which has existed since the days of prehistoric man,
+while the _x_-ray is a discovery of to-day; to heat, the nociceptors
+produce an adequate response; to the _x_-ray there is no response.
+There was no weapon in the prehistoric ages which could move at
+the speed of a bullet from the modern rifle, therefore, while slow
+penetration of the tissues produces great pain and muscular response,
+there is no response to the swiftly moving bullet.
+
+The response to contact stimuli then depends always on the presence
+of nociceptors in the affected part of the body and to the type
+of the contact.  Powerful response is made to crushing injury by
+environmental forces; to such injuring contacts as resemble the impacts
+of fighting; to such tearing injuries as resemble those made by teeth
+and claws (Fig. 9). On the other hand, the sharp division of tissue
+by cutting produces no adaptive response; indeed, one might imagine
+that the body could be cut to pieces by a superlatively sharp knife
+applied at tremendous speed without material adaptive response.
+
+These examples indicate how the history of the phylogenetic experiences
+of the human race may be learned by a study of the position
+and the action of the nociceptors, just as truly as the study
+of the arrangement and variations in the strata of the earth's
+crust discloses to us geologic history.
+
+These adaptive responses to stimuli are the result of the action
+of the brain-cells, which are thus continually played upon by
+the stimuli of environment.  The energy stored in the brain-cells
+in turn activates the various organs and parts of the body.
+If the environmental impacts are repeated with such frequency that
+the brain-cells have no time for restoration between them, the energy
+of the cells becomes exhausted and a condition of shock results.
+Every action of the body may thus be analyzed into a stimulation
+of ceptors, a consequent discharge of brain-cell energy,
+and a final adaptive activation of the appropriate part.
+Walking, running, and their modifications constitute an adaptation
+of wonderful perfection, for, as Sherrington has shown,
+the adaptation of locomotion consists of a series of reflexes--
+ceptors in the joints, in the limb, and in the foot being stimulated
+by variations in pressure.
+
+As we have shown, the bene- and nociceptors orientate man to all
+forms of physical contact--the former GUIDE HIM TO the acquisition
+of food and to sexual contact; the latter DIRECT HIM FROM contacts
+of a harmful nature.  The distance ceptors, on the other hand,
+adapt man to his distant environment by means of communication
+through unseen forces--ethereal vibrations produce sight; air waves
+produce sound; microscopic particles of matter produce smell.
+The advantage of the distance ceptors is that they allow time
+for orientation, and because of this great advantage the majority
+of man's actions are responses to their adequate stimuli.
+As Sherrington has stated, the greater part of the brain has been
+developed by means of stimuli received through the special senses,
+especially through the light ceptors, the optic nerves.
+
+We have just stated that by means of the distance ceptors animals
+and man orientate themselves to their distant environment.
+As a result of the stimulation of the special senses chase and escape
+are effected, fight is conducted, food is secured, and mates are found.
+It is obvious, therefore, that the distance ceptors are the primary
+cause of continuous and exhausting expenditures of energy.
+On the other hand, stimuli applied to contact ceptors lead to short,
+quick discharges of nervous energy.  The child puts his hand
+in the fire and there is an immediate and complete response
+to the injuring contact; he sees a pot of jam on the pantry shelf
+and a long train of continued activities are set in motion,
+leading to the acquisition of the desired object.
+
+The contact ceptors do not at all promote the expenditure of energy
+in the chase or in fight, in the search for food or for mates.
+Since the distance ceptors control these activities, one would expect to
+find that they control also those organs whose function is the production
+of energizing internal secretions.  Over these organs--the thyroid,
+the adrenals, the hypophysis--the contact ceptors have no control.
+Prolonged laboratory experimentation seems to prove this postulate.
+According to our observations, no amount of physical trauma inflicted upon
+animals will cause hyperthyroidism or increased adrenalin in the blood,
+while fear and rage do produce hyperthyroidism and increased adrenalin
+(Fig. 44) (Cannon). This is a statement of far-reaching importance
+and is the key to an explanation of many chronic diseases--
+diseases which are associated with the intense stimulation of
+the distance ceptors in human relations.
+
+Stimuli of the contact ceptors differ from stimuli of the distance
+ceptors in still another important particular.  The adequacy of stimuli
+of the contact ceptors depends upon their number and intensity,
+while the adequacy of the stimuli of the distance ceptors depends
+upon the EXPERIENCE of the species and of the individual.
+That is, according to phylogeny and ontogeny this or that sound,
+this or that smell, this or that sight, through association
+recapitulates the experience of the species and of the individual--
+awakens the phylogenetic and ontogenetic memory.  In other words, sights,
+sounds, and odors are symbols which awaken phylogenetic association.
+If a species has become adapted to make a specific response to a
+certain object, then that response will occur automatically in an
+individual of that species when he hears, sees, or smells that object.
+Suppose, for example, that the shadow of a hawk were to fall
+simultaneously on the eyes of a bird, a rabbit, a cow, and a boy.
+That shadow would at once activate the rabbit and the bird to an
+endeavor to escape, each in a specific manner according to its
+phylogenetic adaptation; the cow would be indifferent and neutral;
+while the boy, according to his personal experience or ontogeny,
+might remain neutral, might watch the flight of the hawk with interest
+or might try to shoot it.
+
+Each phylogenetic and each ontogenetic experience by an indirect
+method develops its own mechanism of adaptation in the brain;
+and the brain threshold is raised or lowered to stimuli by
+the strength and frequency of repetition of the experience.
+Thus through the innumerable symbols supplied by environment the distance
+ceptors drive this or that animal according to the type of brain
+pattern and the particular state of threshold which has been developed
+in that animal by its phylogenetic and ontogenetic experiences.
+The brain pattern depends upon his phylogeny, the state of threshold
+upon his ontogeny.  Each BRAIN PATTERN is created by some particular
+element in the environment to which an adaptation has been made
+for the good of the species.  The _*state of threshold_ depends
+upon the effect made upon the individual by his personal contacts
+with that particular element in his environment.  The presence
+of that element produces in the individual an associative recall
+of the adaptation of his species--that is, the brain pattern developed
+by his phylogeny becomes energized to make a specific response.
+The intensity of the response depends upon the state of threshold--
+that is, upon the associative recall of the individual's
+own experience--his ontogeny.
+
+If the full history of the species and of the individual
+could be known in every detail, then every detail of that
+individual's conduct in health and disease could be predicted.
+Reaction to environment is the basis of conduct, of moral standards,
+of manners and conventions, of work and play, of love and hate,
+of protection and murder, of governing and being governed, in fact,
+of all the reactions between human beings--of the entire web of life.
+To quote Sherrington once more:  "Environment drives the brain,
+the brain drives the various organs of the body."
+
+By what means are these adaptations made?  What is the mechanism through
+which adequate responses are made to the stimuli received by the ceptors?
+We postulate that in the brain there are innumerable patterns
+each the mechanism for the performance of a single kind of action,
+and that the brain-cells supply the energy--electric or otherwise--
+by which the act is performed; that the energy stored in the brain-cells
+is in some unknown manner released by the force which activates
+the brain pattern; and that through an unknown property of these brain
+patterns each stimulus causes such a change that the next stimulus
+of the same kind passes with greater facility.
+
+Each separate motor action presumably has its own mechanism--
+brain pattern--which is activated by but one ceptor and by
+that ceptor only when physical force of a certain intensity
+and rate of motion is applied.  This is true both of the visible
+contacts affecting the nociceptors and of the invisible contacts
+by those intangible forces which affect the distance ceptors.
+For example, each variation in speed of the light-producing
+waves of ether causes a specific reaction in the brain.
+For one speed of ether waves the reaction is the perception
+of the color blue; for another, yellow; for another, violet.
+Changes in the speed of air waves meet with specific response
+in the brain patterns tuned to receive impressions through the
+aural nerves, and so we distinguish differences in sound pitch.
+If we can realize the infinite delicacy of the mechanisms adapted
+to these infinitesimal variations in the speed and intensity of
+invisible and intangible stimuli, it will not be difficult to conceive
+the variations of brain patterns which render possible the specific
+responses to the coarser contacts of visible environment.
+
+Each brain pattern is adapted for but one type of motion,
+and so the specific stimuli of the innumerable ceptors play
+each upon its own brain pattern only.  In addition, each brain
+pattern can react to stimuli applied only within certain limits.
+Too bright a light blinds; too loud a sound deafens.  No mechanism
+is adapted for waves of light above or below a certain rate of speed,
+although this range varies in different individuals and in different
+species according to the training of the individual and the need
+of the species.
+
+We have already referred to the fact that there is no receptive
+mechanism adapted to the stimuli from the _x_-ray, from the
+high-speed bullet, from electricity.  So, too, there are innumerable
+forces in nature which can excite in man no adaptive response,
+since there exist in man no brain patterns tuned to their waves,
+as in the case of certain ethereal and radioactive forces.
+
+On this mechanistic basis the emotions may be explained as activations
+of the entire motor mechanism for fighting, for escaping, for copulating.
+The sight of an enemy stimulates in the brain those patterns formed
+by the previous experiences of the individual with that enemy, and also
+the experiences of the race whenever an enemy had to be met and overcome.
+Each of these many brain patterns in turn activates that part of
+the body through which lies the path of its own adaptive response--
+those parts including the special energizing or activating organs.
+Laboratory experiments show that in an animal driven strongly
+by emotion the following changes may be seen:  (1) A mobilization
+of the energy-giving compound in the brain-cells, evidenced by a
+primary increase of the Nissl substance and a later disappearance
+of this substance and the deterioration of the cells (Figs. 5 and 13);
+(2) increased output of adrenalin (Cannon), of thyroid secretion,
+of glycogen, and an increase of the power of oxidation in the muscles;
+(3) accelerated circulation and respiration with increased
+body temperature; (4) altered metabolism.  All these are adaptations
+to increase the motor efficiency of the mechanism.  In addition,
+we find an inhibition of the functions of every organ and tissue that
+consumes energy, but does not contribute directly to motor efficiency.
+The mouth becomes dry; the gastric and pancreatic secretions are
+lessened or are completely inhibited; peristaltic action stops.
+The obvious purpose of all these activations and inhibitions is
+to mass every atom of energy upon the muscles that are conducting
+the defense or attack.
+
+So strong is the influence of phylogenetic experience that though
+an enemy to-day may not be met by actual physical attack,
+yet the decks are cleared for action, as it were, and the weapons
+made ready, the body as a result being shaken and exhausted.
+The type of emotion is plainly declared by the activation
+of the muscles which would be used if the appropriate physical
+action were consummated.  In anger the teeth are set, the fists
+are clenched, the posture is rigid; in fear the muscles collapse,
+the joints tremble, and the running mechanism is activated
+for flight; in sexual excitement the mimicry is as obvious.
+The emotions, then, are the preparations for phylogenetic activities.
+If the activities are consummated, the fuel--glycogen--and the activating
+secretions from the thyroid, the adrenals, the hypophysis are consumed.
+In the activation without action, these products must be eliminated
+as waste products and so a heavy strain is put upon the organs
+of elimination.  It is obvious that the body under emotion might be
+clarified by active muscular exercise, but the subject of the emotion
+is so strongly integrated thereby that it is difficult for him
+to engage in diverting, clarifying exertion.  The person in anger
+does not want to be saved from the ill effects of his own emotion;
+he wants only to fight; the person in fear wants only to escape;
+the person under sexual excitement wants only possession.
+
+All the lesser emotions--worry, jealousy, envy, grief, disappointment,
+expectation--all these influence the body in this manner, the consequences
+depending upon the intensity of the emotion and its protraction.
+Chronic emotional stimulation, therefore, may fatigue or exhaust
+the brain and may cause cardiovascular disease, indigestion, Graves'
+disease, diabetes, and insanity even.
+
+The effect of the emotions upon the body mechanism may be compared
+to that produced upon the mechanism of an automobile if its engines
+are kept running at full speed while the machine is stationary.
+The whole machine will be shaken and weakened, the batteries and weakest
+parts being the first to become impaired and destroyed, the length
+of usefulness of the automobile being correspondingly limited.
+
+We have shown that the effects upon the body mechanism of the action
+of the various ceptors is in relation to the response made by the brain
+to the stimuli received.  What is this power of response on the part
+of the brain but CONSCIOUSNESS?  If this is so, then consciousness
+itself is a reaction to environment, and its intensity must vary
+with the state of the brain and with the environmental stimuli.
+If the brain-cells are in the state of highest efficiency, if their
+energy has not been drawn upon, then consciousness is at its height;
+if the brain is fatigued, that is, if the energy stored in the cells
+has been exhausted to any degree, then the intensity of consciousness
+is diminished.  So degrees of consciousness vary from the height
+maintained by cells in full vigor through the stages of fatigue
+to sleep, to the deeper unconsciousness secured by the administration
+of inhalation anesthetics, to that complete unconsciousness
+of the environment which is secured by blocking the advent to
+the brain of all impressions from both distance and contact ceptors,
+by the use of both local and inhalation anesthetics--the state
+of anoci-association (Fig. 14).
+
+Animals and man may be so exhausted as to be only semi-conscious.
+While a brain perfectly refreshed by a long sleep cannot immediately
+sleep again, the exhausted brain and the refreshed brain when subjected
+to equal stimuli will rise to unequal heights of consciousness.
+The nature of the physical basis of consciousness has been
+sought in experiments on rabbits which were kept awake from
+one hundred to one hundred and nine hours.  At the end of this
+time they were in a state of extreme exhaustion and seemed
+semi-conscious. If the wakefulness had been further prolonged,
+this state of semi-consciousness would have steadily changed
+until it culminated in the permanent unconsciousness of death.
+An examination of the brain-cells of these animals showed physical
+changes identical with those produced by exhaustion from other causes,
+such as prolonged physical exertion or emotional strain (Figs. 45
+and 46). After one hundred hours of wakefulness the rabbits were
+allowed a long period of sleep.  All the brain-cells were restored
+except those that had been in a state of complete exhaustion.
+A single seance of sleep served to restore some of the cells,
+but those which had undergone extreme changes required prolonged rest.
+These experiments give us a definite physical basis for explaining
+the cost to the body mechanism of maintaining the conscious state.
+We have stated that the brain-cell changes produced by prolonged
+consciousness are identical with those produced by physical exertion
+and by emotional strain.  Rest, then, and especially sleep,
+is needed to restore the physical state of the brain-cells which
+have been impaired, and as the brain-cells constitute the central
+battery of the body mechanism, their restoration is essential
+for the maintenance of normal vitality.
+
+In ordinary parlance, by consciousness we mean the activity
+of that part of the brain in which associative memory resides,
+but while associative memory is suspended the activities of the brain
+as a whole are by no means suspended; the respiratory and circulatory
+centers are active, as are those centers which maintain muscular tone.
+This is shown by the muscular response to external stimuli made
+by the normal person in sleep; by the occasional activation of motor
+patterns which may break through into consciousness causing dreams;
+and finally by the responses of the motor mechanism made to the injuring
+stimuli of an operation on a patient under inhalation anesthesia only.
+
+Direct proof of the mechanistic action of many of life's phenomena
+is lacking, but the proof is definite and final of the part
+that the brain-cells play in maintaining consciousness;
+of the fact that the degree of consciousness and mental
+efficiency depends upon the physical state of the brain-cells;
+and finally that efficiency may be restored by sleep,
+provided that exhaustion of the cells has not progressed too far.
+In this greatest phenomenon of life, then, the mechanistic theory
+is in harmony with the facts.
+
+Perhaps no more convincing proof of our thesis that the body is
+a mechanism developed and adapted to its purposes by environment
+can be secured than by a study of that most constant manifestation
+of consciousness--pain.
+
+Like the other phenomena of life, pain was undoubtedly evolved
+for a particular purpose--surely for the good of the individual.
+Like fear and worry, it frequently is injurious.  What then may
+be its purpose?
+
+We postulate that pain is a result of contact ceptor stimulation
+for the purpose of securing protective muscular activity.
+This postulate applies to all kinds of pain, whatever their cause--
+whether physical injury, pyogenic infection, the obstruction
+of hollow viscera, childbirth, etc.
+
+All forms of pain are associated with muscular action, and as in every
+other stimulation of the ceptors, each kind of pain is specific
+to the causative stimuli.  The child puts his hand in the fire;
+physical injury pain results, and the appropriate muscular
+response is elicited.  If pressure is prolonged on some parts
+of the body, anemia of the parts may result, with a corresponding
+discomfort or pain, requiring muscular action for relief.
+When the rays of the sun strike directly upon the retina, light pain
+causes an immediate protective action, so too in the evacuation
+of the intestine and the urinary bladder as normal acts, and in
+overcoming obstruction of these tracts, discomfort or pain compel
+the required muscular actions.  This view of pain as a stimulation
+to motor action explains why only certain types of infection are
+associated with pain; namely, those types in which the infection
+may be spread by muscular action or those in which the fixation
+of parts by continued muscular rigidity is an advantage.
+As a further remarkable proof of the marvelous adaptation
+of the body mechanism to meet varying environmental conditions,
+we find that just as nociceptors have been implanted in only those
+parts of the body which have been subject to nocuous contacts,
+so a type of infection which causes muscular action in one part
+of the body may cause none when it attacks another.
+
+This postulate gives us the key to the pain-muscular phenomena
+of peritonitis, pleurisy, cystitis, cholecystitis, etc., as well as to
+the pain-muscular phenomena in obstructions of the hollow viscera.
+If pain is a part of a muscular response and occurs only
+as a result of contact ceptor stimulation by physical injury,
+infection, anemia, or obstruction, we may well inquire which part
+of the nerve mechanism is the site of the phenomenon of pain.
+Is it the nerve-ending, the nerve-trunk, or the brain?  That is,
+is pain associated with the physical contact with the nerve-ending,
+or with the physical act of transmission along the nerve-trunk,
+or with the change of brain-cell substance by means of which
+the motor-producing energy is released?
+
+We postulate that the pain is associated with the discharge of energy
+from the brain-cells. If this be true, then if every nociceptor in
+the body were equally stimulated in such a manner that all the stimuli
+should reach the brain-cells simultaneously, then the cells would
+find themselves in equilibrium and no motor act would be performed.
+But if all the pain nerve ceptors but one were equally stimulated,
+and this one more strongly stimulated than the rest, then this
+one would gain possession of the final common path--would cause
+a muscular action and the sensation of pain.
+
+It is well known that when a greater pain or stimulus is thrown
+into competition with a lesser one, the lesser is submerged.
+Of this fact the school-boy makes use when he initiates
+the novice into the mystery of the painless pulling of hair.
+The simultaneous but severe application of the boot to the blindfolded
+victim takes complete but exclusive possession of the final common
+path and the hair is painlessly plucked as a result of the triumph
+of the boot stimulus over the pull on the hair in the struggle
+for the final common path.
+
+Persons who have survived a sudden, complete exposure to superheated steam,
+or whose bodies have been enwrapped in flame, testify that they
+have felt no pain.  As this absence of pain may be due to the fact
+that the emotion of fear gained the final common path, to the exclusion
+of all other stimuli, we are trying by experimentation to discover
+the effects of simultaneous painful stimulation of all parts of the body.
+The data already in hand, and the experiments now in progress,
+in which anesthetized animals are subjected to powerful stimuli
+applied to certain parts of the body only, or simultaneously to
+all parts of the body, lead us to believe that in the former case
+the brain-cells become stimulated or hyperchromatic, while in the latter
+case no brain-cell changes occur.  We believe that our experiments
+will prove that an equal and simultaneous stimulation of all parts
+of the body leaves the brain-cells in a state of equilibrium.
+Our theory of pain will then be well sustained, not only by common
+observation, but by experimental proof, and so the mechanistic view
+will be found in complete harmony with another important reaction.
+
+We have stated that when a number of contact stimuli act simultaneously,
+the strongest stimulus will gain possession of the final common path--
+the path of action.  When, however, stimuli of the distance ceptors
+compete with stimuli of the contact ceptors, the contact-ceptor
+stimuli often secure the common path, not because they are stronger
+or more important, but because they are immediate and urgent.
+In many instances, however, the distance-ceptor stimuli are strong,
+have the advantage of a lowered threshold, and therefore compete
+successfully with the immediate and present stimuli of the
+contact ceptors.  In such cases we have the interesting phenomenon
+of physical injury without resultant pain or muscular response.
+The distance-ceptor stimuli which may thus triumph over even powerful
+contact-ceptor stimuli are those causing strong emotions--as great
+anger in fighting; great fear in a battle; intense sexual excitement.
+Dr. Livingstone has testified to his complete unconsciousness
+to pain during his struggle with a lion; although he was torn
+by teeth and claws, his fear overcame all other impressions.
+By frequently repeated stimulation the Dervish secures a low
+threshold to the emotions caused by the thought of God or the devil,
+and his emotional excitement is increased by the presence of others
+under the same stimulation; emotion, therefore, secures the final
+common path and he is unconscious of pain when he lashes, cuts,
+and bruises his body.  The phenomena of hysteria may be explained
+on this basis, as may the unconsciousness of passing events
+in a person in the midst of a great and overwhelming grief.
+By constant practice the student may secure the final common path for
+such impressions as are derived from the stimuli offered by the subject
+of his study, and so he will be oblivious of his surroundings.
+Concentration is but another name for a final common path secured
+by the repetition and summation of certain stimuli.
+
+If our premises are sustained, then we can recognize in man no will,
+no ego, no possibility for spontaneous action, for every action must
+be a response to the stimuli of contact or distance ceptors, or to their
+recall through associative memory.  Memory is awakened by symbols which
+represent any of the objects or forces associated with the act recalled.
+Spoken and written words, pictures, sounds, may stimulate the brain
+patterns formed by previous stimulation of the distance ceptors;
+while touch, pain, temperature, pressure, may recall previous
+contact-ceptor stimuli.  Memory depends in part upon the adequacy
+of the symbol, and in part upon the state of the threshold.
+If one has ever been attacked by a snake, the threshold to any
+symbol which could recall that attack would be low; the later
+recall of anything associated with the bite or its results would
+produce in memory a recapitulation of the whole scene, while even
+harmless snakes would thereafter be greeted with a shudder.
+On the other hand, in a child the threshold is low to the desire
+for the possession of any new and strange object; in a child,
+therefore, to whom a snake is merely an unusual and fascinating object,
+there is aroused only curiosity and the desire for the possession
+of a new plaything.
+
+If we are to attribute to man the possession of a governing
+attribute not possessed by other parts of the animal creation,
+where are we to draw the boundary line, and say "here the ego--
+the will--the reason--emerges"? What attribute, after all, has man
+which in its ultimate analysis is not possessed by the lowest
+animals or by the vegetable creation, even?  From the ameba,
+on through all the stages of animal existence, every action is
+but a response to an adequate stimulus; and as a result of adequate
+stimuli each step has been taken toward the higher and more
+intricate mechanisms which play the higher and more intricate parts
+in the great scheme of nature.
+
+The Venus fly-trap responds to as delicate a stimulus as do
+any of the contact ceptors of animals, and the motor activity
+resulting from the stimulus is as complex.  To an insect-like touch
+the plant responds; to a rough contact there is no response; that is,
+the motor mechanism of the plant has become attuned to only such
+stimuli as simulate the contact of those insects which form its diet.
+It catches flies, eats and digests them, and ejects the refuse
+(Fig. 47). The ameba does no less.  The frog does no more,
+excepting that in its place in creation a few more reactions are
+required for its sustenance and for the propagation of its species.
+Man does no more, excepting that in man's manifold relations
+there are innumerable stimuli, for meeting which adequately,
+innumerable mechanisms have been evolved.  The motor mechanism
+of the fly-trap is perfectly adapted to its purpose.
+The motor mechanism of man is adapted to its manifold uses,
+and as new environmental influences surround him, we must believe
+that new adaptations of the mechanism will be evolved to meet
+the new conditions.
+
+Is not this conception of man's activities infinitely more wonderful,
+and infinitely more comprehensible than is the conception that his
+activities may be accounted for by the existence of an unknown,
+unimaginable, and intangible force called "mind" or "soul"?
+
+We have already shown how the nerve mechanism is so well adapted
+to the innumerable stimuli of environment that it can accurately
+transmit and distinguish between the infinite variations of speed
+in the ether waves producing light, and the air waves producing sound.
+Each rate of vibration energizes only the mechanism which has
+been attuned to it.  With marvelous accuracy the light and sound
+waves gain access to the nerve tissue and are finally interpreted
+in terms of motor responses, each by the brain pattern attuned
+to that particular speed and intensity.  So stimuli and resultant
+actions multiplied by the total number of the motor patterns
+in the brain of man give us the sum total of his life's activities--
+they constitute his life.
+
+As in evolutionary history the permanence of an adaptation of the body
+mechanism depends upon its value in the preservation of the life
+of the individual and upon its power to increase the value of
+the individual to the race, so the importance and truth of these
+postulates and theories may well be judged on the same basis.
+
+The fundamental instincts of all living matter are self-preservation
+and the propagation of the species.  The instinct for self-preservation
+causes a plant to turn away from cold and damaging winds toward
+the life-giving sun; the inert mussel to withdraw within its shell;
+the insect to take flight; the animal to fight or to flee; and man
+to procure food that he may oppose starvation, to shelter himself
+and to provide clothes that he may avoid the dangers of excessive
+cold and heat, to combat death from disease by seeking medical aid,
+to avoid destruction by man or brute by fight or by flight.
+The instinct to propagate the species leads brute man by crude methods,
+and cultured man by methods more refined, to put out of his way sex
+rivals so that his own life may be continued through offspring.
+The life of the species is further assured by the protective
+action exercised over the young by the adults of the species.
+As soon as the youngest offspring is able successfully to carry on his
+own struggle with environment there is no longer need for the parent,
+and the parent enters therefore the stage of disintegration.
+The average length of life in any species is the sum of the years
+of immaturity, plus the years of female fertility, plus the adolescent
+years of the offspring.
+
+The stimuli resulting from these two dominant instincts are now
+so overpowering as compared with all other environmental stimuli
+that the mere possession of adequate knowledge of the damaging effects
+of certain actions as compared with the saving effects of others will
+(other things being equal) lead the individual to choose the right,--
+the self- and species-preservative course of action, instead of the wrong,--
+the self- and species-destructive course of action.
+
+The dissemination of the knowledge of the far-reaching
+deleterious effects of protracted emotional strain, of overwork,
+and of worry will automatically raise man's threshold to
+the damaging activating stimuli causing the strong emotions,
+and will cause him to avoid dangerous strains of every kind.
+The individual thus protected will therefore rise to a plane
+of poise and efficiency far above that of his uncontrolled fellows,
+and by so much will his efficiency, health, and happiness be augmented.
+
+A full acceptance of this theory cannot fail to produce in those
+in whose charge rests the welfare of the young, an overwhelming
+desire to surround children with those environmental stimuli only
+which will tend to their highest ultimate welfare.
+
+Such is the stimulating force of tradition that many who
+have been educated under the tenets of traditional beliefs
+will oppose these hypotheses--even violently, it may be.
+So they have opposed them; so they opposed Darwin; so they
+have opposed all new and apparently revolutionary doctrines.
+Yet these persons themselves are by their very actions proving
+the efficiency of the vital principles which we have enunciated.
+What is the whole social welfare movement but a recognition
+on the part of municipalities, educational boards, and religious
+organizations of the fact that the future welfare of the race
+depends upon the administration to the young of forceful
+uplifting environmental stimuli?
+
+There are now, as there were in Darwin's day, many who feel that man
+is degraded from his high estate by the conception that he is not
+a reasoning, willing being, the result of a special creation.
+But one may wonder indeed what conception of the origin of man can
+be more wonderful or more inspiring than the belief that he has
+been slowly evolved through the ages, and that all creatures
+have had a part in his development; that each form of life has
+contributed and is contributing still to his present welfare
+and to his future advancement.
+
+
+Recapitulation
+
+Psychology,--the science of the human soul and its relations,--
+under the mechanistic theory of life, must receive a new definition.
+It becomes a science of man's activities as determined by the
+environmental stimuli of his phylogeny and of his ontogeny.
+
+On this basis we postulate that throughout the history of the race nothing
+has been lost, but that every experience of the race and of the individual
+has been retained for the guidance of the individual and of the race;
+that for the accomplishment of this end there has been evolved through
+the ages a nerve mechanism of such infinite delicacy and precision
+that in some unknown manner it can register permanently within
+itself every impression received in the phylogenetic and ontogenetic
+experience of the individual; that each of these nerve mechanisms
+or brain patterns has its own connection with the external world,
+and that each is attuned to receive impressions of but one kind,
+as in the apparatus of wireless telegraphy each instrument can
+receive and interpret waves of a certain rate of intensity only;
+that thought, will, ego, personality, perception, imagination,
+reason, emotion, choice, memory, are to be interpreted in terms
+of these brain patterns; that these so-called phenomena of human
+life depend upon the stimuli which can secure the final common path,
+this in turn having been determined by the frequency and the strength
+of the environmental stimuli of the past and of the present.
+
+Finally, as for life's origin and life's ultimate end,
+we are content to say that they are unknown, perhaps unknowable.
+We know only that living matter, like lifeless matter, has its own
+place in the cosmic processes; that the gigantic forces which operated
+to produce a world upon which life could exist, as a logical sequence,
+when the time was ripe, evolved life; and finally that these cosmic
+forces are still active, though none can tell what worlds and what
+races may be the result of their coming activities.
+
+
+
+
+A MECHANISTIC THEORY OF DISEASE[*]
+
+
+[*] Oration in Surgery.  Delivered at the 147th Annual Meeting of the
+Medical Society of New Jersey, at Spring Lake, N. J., June 11, 1913.
+
+In this address the paragraphs which were taken from the preceding
+paper, "A Mechanistic View of Psychology," have been omitted,
+those portions only being republished in which the premises have
+been applied in a discussion of certain medical problems rather
+than of psychological problems.
+
+
+
+The human body is an elaborate mechanism equipped first for such
+conflict with environment as will tend to the preservation
+of the individual, and second for the propagation of the species,
+both of these functions, when most efficiently carried out,
+tending to the upbuilding and perfection of the race.
+From the date of Harvey's discovery of the circulation of the blood,
+to the present day, the human body has been constantly compared
+to a machine, but the time for analogy and comparison is past.
+I postulate that the body is itself a mechanism responding in every
+part to the adequate stimuli given it from without by the environment
+of the present and from within by the environment of the past,
+the memory of which is stored in the central battery of the mechanism--
+the brain.
+ *   *    *    *    *    *    *    *    *    *
+ *   *    *    *    *    *    *    *    *    *
+
+If the full history of the species and of the individual
+could be known in every detail, then every detail of that
+individual's conduct in health and disease could be predicted.
+Reaction to environment is the basis of conduct, of moral standards,
+of manners and conventions, of work and play, of love and hate,
+of protection and murder, of governing and being governed, in fact,
+of all the reactions between human beings--of the entire web of life.
+As Sherrington has stated, "Environment drives the brain, the brain
+drives the various organs of the body," and here we believe we find
+the key to a mechanistic interpretation of all body processes.
+
+On this basis we may see that the activities of life depend upon
+the ability of the parts of the body mechanism to respond adequately
+to adequate stimulation.  This postulate applies not only to stimuli
+from visible forces, but to those received by the invasion of
+the micro-bodies which cause pyogenic or non-pyogenic infections.
+In the case of dangerous assaults by visible or invisible enemies,
+the brain, through the nerves and all parts of the motor mechanism,
+meets the attack by attempts at adaptation.  Recovery, invalidism,
+and death depend upon the degree of success with which the attacking
+or invading enemies are met.  Questions regarding disease become,
+therefore, questions in adaptation, and it is possible that,
+when studied in the light of this conception, the key to many hitherto
+unsolved physical problems may be found.
+
+Perhaps no more convincing proof of our thesis may be secured
+than by a study of that ever-present phenomenon--pain.  In whatever
+part of the body and by whatever apparent cause pain is produced,
+we find that it is invariably a stimulation to motor activity--
+whose ultimate object is protection.  Thus by the muscular action
+resulting from pain we are protected against heat and cold;
+against too powerful light; against local anemia caused by prolonged
+pressure upon any portion of the body.  So, too, pain of greater
+or less intensity compels the required emptying of the pregnant
+uterus and the evacuation of the intestine and the urinary bladder.
+
+It should be noted that in every instance the muscular activity
+resulting from pain is specific in its type, its distribution,
+and its intensity, this specificity being true not only of pain
+which is the result of external stimulation, but also of the pain
+associated with certain types of infection.
+
+Pain, however, is not the only symptom of the invasion of
+the body by pyogenic or parasitic organisms.  Fever, invariably,
+and chills, often, accompany the course of the infections.
+Can these phenomena also be explained as adaptations of the motor
+mechanism for the good of the individual?
+
+As the phenomena of chills and fever are most strikingly exhibited
+in malaria, let us study the course of events in that disease.
+It is known that the malarial parasite develops in the red
+blood-corpuscles, and that the chills and fever appear when
+the cycle of parasitic development is complete and the adults
+are ready to escape from the corpuscles of the blood plasma.
+Bass, of New Orleans, has proved that the favorable temperature
+for the growth of the malarial organism is 98'0, and that at 102'0
+the adult organisms will be killed, though the latter temperature
+is not fatal to the spores.  The adult life of the malarial
+parasite begins after its escape into the blood plasma, and it is
+there that the organism is most susceptible to high temperature.
+We must infer, therefore, that the fever is an adaptation on the part
+of the host for despatching the enemy.
+
+What, then, may be the protective part played by the chill?
+A chill is made up of intermittent contractions of all the external
+muscles of the body.  This activity results in an increase
+of the body heat and in an anemia of the superficial parts
+of the body, so that less heat can be lost by radiation.
+By this means, therefore, the external portions of the body contribute
+measurably to the production of the beneficent and saving fever.
+
+It must be remembered that this power of adaptation is not peculiar
+to man alone, but that it is a quality shared by all living creatures.
+While the human body has been adapting itself for self-protection
+by producing a febrile reaction whereby to kill the invading organisms,
+the invaders on their side have been adapting themselves for a life
+struggle within the body of the host.  In these mortal conflicts
+between invaders and host, therefore, the issue is often in doubt,
+and sometimes one and sometimes the other will emerge victorious.
+
+We must believe that a similar adaptive response exists in all
+parasitic infections--the cycles varying according to the stages in
+the development of the invaders.  If the bacteria develop continuously,
+the fever is constant instead of intermittent, since the adequate
+stimulus is constantly present.
+
+Bacteriology has taught us that both heat and cold are fatal
+to pathogenic infections; for this reason either of the apparently
+contradictory methods of treatment may help, _i.  e_., either hot
+or cold applications.  It should be borne in mind, however, that we have
+to deal not only with the adult organisms, but with the spores also.
+The application of cold may keep the spores from developing,
+while heat may promote their development, and the course of the disease
+may vary, therefore, according to our choice of treatment.
+
+From this viewpoint, we can understand the intermittent temperature
+in a patient who is convalescing from an extreme infection,
+as peritonitis, pylephlebitis, multiple abscess of the liver, etc.
+In these conditions there may occur days of normal temperature,
+followed by an abrupt rise which will last for several days--
+this in turn succeeded by another remittance.  This cycle may be
+repeated several times, and on our hypothesis we may believe it
+is caused by the successive development to maturity of spores
+of varying ages.
+
+If these premises are sound, the wisdom of reducing the temperature
+in case of infection may well be questioned.
+
+On this mechanistic basis the emotions also may be explained
+as activations of the entire motor mechanism for fighting,
+for escaping, for copulating.
+ *   *    *    *    *    *    *    *    *    *
+ *   *    *    *    *    *    *    *    *    *
+
+The emotions, then, are the preparation for phylogenetic activities
+(Fig. 48). If the activities were consummated, the fuel--glycogen--
+and the activating secretions from the thyroid, the adrenals,
+the hypophysis, would be consumed.  In the activation without
+action these products must be eliminated as waste products
+and so a heavy strain is put upon the organs of elimination.
+It is obvious that the body under emotion might be clarified
+by active muscular exercise, but the subject of the emotion is so
+strongly integrated thereby that it is difficult for him to engage
+in diverting, clarifying exertion.
+ *   *    *    *    *    *    *    *    *    *
+ *   *    *    *    *    *    *    *    *    *
+
+So, as we have indicated already, certain deleterious effects are
+produced when the body mechanism is activated without resultant action.
+For example, the output of adrenalin is increased, and, as a consequence,
+arteriosclerosis and cardiovascular disease may occur in persons
+who have been subjected to prolonged emotional strain, since it
+has been proved that the prolonged administration of adrenalin
+will cause these conditions.  We have stated that the emotions cause
+increased output of glycogen.  Glycogen is a step toward diabetes,
+and therefore this disease, too, is prone to appear in persons
+under emotional strain.  It is most common in those races which
+are especially emotional in character, so we are not surprised
+to find it especially prevalent among Jews.  So common is this
+particular result of prolonged emotion that some one has said,
+"When the stocks go down in New York, diabetes goes up."
+Nephritis, also, may result from emotional stress, because of the strain
+put upon the kidneys by the unconsumed activating substances.
+The increased heart action and the presence of these activating
+secretions may cause myocarditis and heart degeneration.
+Claudication also may result from the impaired circulation.
+
+The emotions may cause an inhibition of the digestive secretions
+and of intestinal peristalsis.  This means that the digestive processes
+are arrested, that putrefaction and autointoxication will result,
+and that still further strain will thus be put upon the organs
+of elimination.  Who has not observed in himself and in others when under
+the influence of fear, anger, jealousy, or grief that the digestive
+processes and general well-being are rapidly and materially altered;
+while as tranquillity, peace, and happiness return the physical
+state improves accordingly?
+
+Dentists testify that as a result of continued strong emotion the character
+of the saliva changes, pyorrhea develops, and the teeth decay rapidly.
+Every one knows that strong emotion may cause the hair to fall
+out and to become prematurely gray.
+
+As to the most important organ of all--the brain--every one is
+conscious of its impaired efficiency under emotional strain,
+and laboratory researches show that the deficiency is accounted
+for by actual cell deterioration; so the individual who day by day
+is under heavy emotional strain finds himself losing strength slowly--
+especially do his friends note it.  By summation of stimuli
+his threshold becomes lowered until stimuli, which under normal
+conditions would be of no effect, produce undue responses.
+"The grasshopper becomes a burden," and prolonged rest and change
+of environmental conditions are necessary for restoration.
+
+If in a long emotional strain the brain is beaten down;
+if the number of "low-efficiency" cells increases, the driving
+power of the brain is correspondingly lessened and therefore
+the various organs of the body may escape through the very
+inefficiency of the brain to produce in them forced activity.
+On the other hand, if the brain remains vigorous, the kidneys
+may take the strain and break down; if the kidneys do not break,
+the blood-vessels may harden; if the blood-vessels are not affected,
+the thyroid may become hyperplastic and produce Graves' disease;
+if the thyroid escapes, diabetes may develop; while if the iron
+constitution of the mechanism can successfully bear the strain
+in all its parts, then the individual will break his competitors,
+and their mechanisms will suffer in the struggle.
+
+This whole train of deleterious results of body activation without
+action may be best observed and studied in that most emotional
+of diseases--exophthalmic goiter.  In this disease the constantly
+stimulated distance ceptors dispossess the contact ceptors from
+the common path, and drive the motor mechanism to its own destruction,
+and the patient has the appearance of a person in great terror,
+or of a runner approaching the end of a Marathon race (Figs. 16
+and 48 to 54).
+
+Exophthalmic goiter may result from long emotional or mental stress
+in those cases in which the thyroid takes the brunt of the strain upon
+the mechanism.  As adrenalin increases blood-pressure, so thyroid
+secretion increases brain activity, and increased brain activity
+in turn causes an increased activation of the motor mechanism
+as a whole.
+
+We know that a deficiency or lack of thyroid secretion will inhibit
+sexual emotion and conception, will produce stupidity and inertia;
+will diminish vitality.  On the other hand, excessive thyroid secretion
+drives the entire mechanism at top speed; the emotions are intensified;
+the skin becomes soft and moist, the eyes are brilliant and staring;
+the limbs tremble; the heart pounds loudly and its pulsations often
+are visible; the respiration is rapid; the stimulation of the fear
+mechanism causes the eyes to protrude (Fig. 16); the temperature
+mounts at every slight provoca-tion and may reach the incredible
+height of 110'0 even.  In time, the entire organism is destroyed--
+literally consumed--by the concentration of dynamic energy.
+It is interesting to note that in these patients emotion gains complete
+possession of the final common path; they are wild and delirious--
+but they never have pain.
+
+All the diseases caused by excessive motor activity may be called
+kinetic diseases.  Against the conditions in life which produce
+them man reacts in various ways.  He intro-
+
+
+{illust. caption = FIG.  51.--CROSS-COUNTRY RACE.  Winner of six-mile
+cross-country race showing typical expression of exhaustion.
+(Copyright by Underwood and Underwood, N. Y.) duces restful variety
+into his life by hunting and fishing; by playing golf and tennis;
+by horseback riding; by cultivating hobbies which effectually.
+turn the current of his thoughts{illust. caption = FIG.  52.--{A B
+and C} from the consuming stress and strain of his business
+or professional life.  These diversions are all rational
+attempts to relieve tension by self-preservative reactions.
+For the same reason man attempts to relieve the strain of
+contention with his fellow-man by unions, trusts, corporations.
+In spite of all efforts, however, many constitutions are
+still broken daily in the fierce conflicts of competition.
+We know how often the overdriven individual endeavors to minimize
+the activities of his motor mechanism by the use of agents which diminish
+brain activity, such as alcohol, tobacco, and various narcotics.
+Occasionally also, some person, who can find no respite from his own
+relentless energies, seeks relief in oblivion by suicide.
+
+Most fortunately, two fundamental instincts--self-preservation and
+the propagation of the species--act powerfully to prevent
+this last fatal result, and instead the harassed individual
+seeks from others the aid which is lacking within himself.
+He may turn to the priest who seeks and often secures the final
+common path for faith in an over-ruling Providence, a faith which in
+many incontrovertible instances has proved sufficient in very truth
+to move mountains of lesser stimuli; or he turns to a physician,
+who too often treats the final outcome of the hyperactivity only.
+The physician who accepts the theory of the kinetic diseases,
+however, will not only repair as far as he may the lesions caused
+by the disordered and forced activities, but will, by compelling and
+forceful suggestion, secure the final common path for right conduct,
+that is, for a self- and species-preservative course of action
+as opposed to wrong conduct-a self- and species-destructive
+course of action.
+
+By forcefully imparting to his patient the knowledge of the far-reaching
+effects of protracted emotional strain, of overwork, and of worry,
+the physician will automatically raise his threshold to the damaging
+activating stimuli which have produced the evil results.
+Even though some parts of his organism may have been permanently disabled,
+a patient thus protected may yet rise to a plane of poise and
+efficiency far above that of his uncontrolled fellows.
+
+In extreme cases it does not seem unreasonable to believe that the
+uncontrolled patient might be rescued by the same principle which has
+proved effective in saving patients from the emotional and traumatic strain
+of surgical operations--the principle of anoci-association. That is,
+by disconnecting one or more of the activating organs from the brain,
+the motor mechanism might be saved from its self-destruction.
+
+Under this hypothesis, that man in disease, as in health,
+is the product of his phylogeny as well as of ontogeny, the sphere
+of the physician's activities takes on new aspects of far-reaching
+and inspiring significance.  Prognosis will become definite in proportion
+to the physician's knowledge not only of the ontogenetic history of
+the individual patient, but also of the phylogenetic history of the race.
+As that knowledge increases, as he appreciates more and more keenly
+the significance of environment in its effect upon individual development,
+in so far will the physician be in a position to contribute mightily
+to the welfare of the race.
+
+
+
+THE KINETIC SYSTEM[*]
+
+
+[*] Address delivered before the New York State Medical Society, April 28,
+1914, to which has been added a further note regarding studies
+of hydrogen ion concentration in the blood.
+
+
+In this paper I formulate a theory which I hope will harmonize a large
+number of clinical and experimental data, supply an interpretation
+of certain diseases, and show by what means many diverse causes
+produce the same end effects.
+
+Even should the theory prove ultimately to be true, it will in the mean
+time doubtless be subjected to many alterations.  The specialized
+laboratory worker will, at first, fail to see the broader clinical view,
+and the trained clinician may hesitate to accept the laboratory findings.
+Our viewpoint has been gained from a consideration of both lines
+of evidence on rather a large scale.
+
+The responsibility for the kinetic theory is assumed by myself,
+while the responsibility for the experimental data is shared fully
+by my associates, Dr. J. B. Austin, Dr. F. W. Hitchings, Dr. H. G. Sloan,
+and Dr. M. L. Menten.[t]
+
+
+[t] From H. K. Cushing Laboratory of Experimental Medicine,
+Western Reserve University, Cleveland.
+
+
+Introduction
+
+The self-preservation of man and kindred animals is effected
+through mechanisms which transform latent energy into kinetic energy
+to accomplish adaptive ends.  Man appropriates from environment
+the energy he requires in the form of crude food which is refined
+by the digestive system; oxygen is taken to the blood and carbon
+dioxid is taken from the blood by the respiratory system;
+to and from the myriads of working cells of the body, food and oxygen
+and waste are carried by the circulatory system; the body is cleared
+of waste by the urinary system; procreation is accomplished through
+the genital system; but none of these systems was evolved primarily
+for the purpose of transforming potential energy into kinetic energy
+for specific ends.  Each system transforms such amounts of potential
+into kinetic energy as are required to perform its specific work;
+but no one of them transforms latent into kinetic energy for the purposes
+of escaping, fighting, pursuing, nor for combating infection.
+The stomach, the kidneys, the lungs, the heart strike no physical
+blow-their role is to do certain work to the end that the blow may
+be struck by another system evolved for that purpose.  I propose
+to offer evidence that there is in the body a system evolved primarily
+for the transformation of latent energy into motion and into heat.
+This system I propose to designate "The Kinetic System."
+
+The kinetic system does not directly circulate the blood,
+nor does it exchange oxygen and carbon dioxid; nor does it perform
+the functions of digestion, urinary elimination, and procreation;
+but though the kinetic system does not directly perform these functions,
+it does play indirectly an important role in each, just as the kinetic
+system itself is aided indirectly by the other systems.
+
+The principal organs which comprise the kinetic system are
+the brain, the thyroid, the adrenals, the liver, and the muscles.
+The brain is the great central battery which drives the body;
+the thyroid governs the conditions favoring tissue oxidation;
+the adrenals govern immediate oxidation processes; the liver fabricates
+and stores glycogen; and the muscles are the great converters
+of latent energy into heat and motion.
+
+Adrenalin alone, thyroid extract alone, brain activity alone,
+and muscular activity alone are capable of causing the body temperature
+to rise above the normal.  The functional activity of no other gland
+of the body alone, and the secretion of no other gland alone, can cause
+a comparable rise in body temperature--that is, neither increased
+functional activity nor any active principle derived from the kidney,
+the liver, the stomach, the pancreas, the hypophysis, the parathyroids,
+the spleen, the intestines, the thymus, the lymphatic glands,
+or the bones can, _per se_, cause a rise in the general body
+temperature comparable to the rise that may be caused by the activity
+of the brain or the muscles, or by the injection of adrenalin
+or thyroid extract.  Then, too, when the brain, the thyroid,
+the adrenals, the liver, or the muscles are eliminated, the power
+of the body to convert latent into kinetic energy is impaired or lost.
+I shall offer evidence tending to show that an excess of either
+internal or external environmental stimuli may modify one or more
+organs of the kinetic system, and that this modification may cause
+certain diseases.  For example, alterations in the efficiency
+of the cerebral link may yield neurasthenia, mania, dementia;
+of the thyroid link, Graves' disease, myxedema; of the adrenal link,
+Addison's disease, cardiovascular disease.
+
+This introduction may serve to give the line of our argument.
+We shall now consider briefly certain salient facts which relate to
+the conversion of latent into kinetic energy as an adaptive reaction.
+The experimental data are so many that they will later be published
+in a monograph.
+
+The amount of latent energy which may be converted into kinetic
+energy for adaptive ends varies in different species, in individuals
+of the same species, in the same individual in different seasons;
+in the life cycle of growth, reproduction and decay;
+in the waking and sleeping hours; in disease and in activity.
+We shall here consider briefly the reasons for some of those variations
+and the mechanisms which make them possible.
+
+
+Biologic Consideration of the Adaptive Variation in Amounts
+of Energy Stored in Various Animals
+
+Energy is appropriated from the physical forces of nature
+that constitute the environment.  This energy is stored in
+the body in quantities in excess of the needs of the moment.
+In some animals this excess storage is greater than in other animals.
+Those animals whose self-preservation is dependent on purely
+mechanical or chemical means of defense--such animals as crustaceans,
+porcupines, skunks or cobras--have a relatively small amount
+of convertible (adaptive) energy stored in their bodies.
+On the contrary, the more an animal is dependent on its muscular
+activity for self-preservation, the more surplus available
+(adaptive) energy there is stored in its body.  It may be true that all
+animals have approximately an equal amount per kilo of chemical energy--
+but certainly they have not an equal amount stored in a form
+which is available for immediate conversion for adaptive ends.
+Adaptive Variation in the Rate of Energy Discharge
+
+What chance for survival would a skunk have without odor; a cobra
+without venom; a turtle without carapace; or a porcupine shorn
+of its barbs, in an environment of powerful and hostile carnivora?
+And yet in such an hostile environment many unprotected animals
+survive by their muscular power of flight alone.  It is evident that
+the provision for the storage of "adaptive" energy is not the only
+evolved characteristic which relates to the energy of the body.
+The more the self-preservation of the animal depends on motor activity,
+the greater is the range of variation in the rate of discharge of energy.
+The rate of energy discharge is especially high in animals evolved
+along the line of hunter and hunted, such as the carnivora and
+the herbivora of the great plains.
+
+
+Influences That Cause Variation in the Rate of Output of Energy
+in the Individual
+
+Not only is there a variation in the rate of output of energy among
+various species of animals, but one finds also variations in the rate
+of output of energy among individuals of the same species.
+If our thesis that men and animals are mechanisms responding to
+environmental stimuli be correct, and further, if the speed of energy
+output be due to changes in the activating organs as a result of
+adaptive stimulation, then we should expect to find physical changes
+in the activating glands during the cycles of increased activation.
+What are the facts?  We know that most animals have breeding
+seasons evolved as adaptations to the food supply and weather.
+Hence there is in most animals a mating season in advance of
+the season of maximum food supply so that the young may appear at
+the period when food is most abundant.  In the springtime most birds
+and mammals mate, and in the springtime at least one of the great
+activating glands is enlarged--the thyroid in man and in animals shows
+seasonal enlargement.  The effect of the increased activity is seen
+in the song, the courting, the fighting, in the quickened pulse,
+and in a slightly raised temperature.  Even more activation
+than that connected with the season is seen in the physical state
+of mating, when the thyroid is known to enlarge materially,
+though this increased activity, as we shall show later, is probably
+no greater than the increased activity of other activating glands.
+In the mating season the kinetic activity is speeded up; in short,
+there exists a state--a fleeting state--of mild Graves' disease.
+In the early stages of Graves' disease, before the destructive phenomena
+are felt, the kinetic speed is high, and life is on a sensuous edge.
+Not only is there a seasonal rhythm to the rate of flow of energy,
+but there is a diurnal variation--the ebb is at night,
+and the full tide in the daytime.  This observation is verified
+by the experiments which show that certain organs in the kinetic
+chain are histologically exhausted, the depleted cells being
+for the most part restored by sleep.
+
+We have seen that there are variations in speed in different species,
+and that in the same species speed varies with the season of the year
+and with the time of day.  In addition there are variations also in
+the rate of discharge of energy in the various cycles of the life
+of the individual.  The young are evolved at high speed for growth,
+so that as soon as possible they may attain to their own power
+of self-defense; they must adapt themselves to innumerable bacteria,
+to food, and to all the elements in their external environment.
+Against their gross enemies the young are measurably protected
+by their parents; but the parents--except to a limited extent in
+the case of man--are unable to assist in the protection of the young
+against infectious disease.
+
+The cycle of greatest kinetic energy for physiologic ends is the period
+of reproduction.  In the female especially there is a cycle of increased
+activity just prior to her development into the procreative state.
+During this time secondary sexual characters are developed--
+the pelvis expands, the ovaries and the uterus grow rapidly,
+the mammary glands develop.  Again in this period of increasing
+speed in the expenditure of energy we find the thyroid,
+the adrenals, and the hypophysis also in rapid growth.
+Without the normal development of the ovary, the thyroid,
+and the hypophysis, neither the male nor the female can develop
+the secondary sexual characters, nor do they develop sexual desire
+nor show seasonal cycles of activity, nor can they procreate.
+The secondary sexual characters--sexual desire, fertility--may be
+developed at will, for example, by feeding thyroid products from
+alien species to the individual deprived of the thyroid.
+
+At the close of the child-bearing period there is a permanent
+diminution of the speed of energy discharge, for energy is no
+longer needed as it was for the self-preservation of the offspring
+before adolescence, and for the propagation of the species
+during the procreative period.  Unless other factors intervene,
+this reduction in speed is progressive until senescent death.
+The diminished size of the thyroid of the aged bears testimony
+to the part the activating organs bear in the general decline.
+
+We have now referred to variations in the rate of discharge of
+energy in different species; in individuals of the same species;
+in cycles in the same individual--such as the seasons of food supply,
+the periods of wakefulness and of sleep, the procreative period,
+and we have spoken of those variations caused artificially
+by thyroid feeding, thus far having confined our discussion
+to the conversion for adaptive purposes of latent into kinetic
+energy in muscular and in procreative action.  We shall now consider
+the conversion of latent into kinetic energy in the production of
+heat,[*] and endeavor to answer the questions which arise at once:
+Is there one mechanism for the conversion of latent energy into heat
+and another mechanism for its conversion into muscular action?
+What is the adaptive advantage of fever in infection?
+
+
+[*] We use the terms "heat" and "muscular action" in the popular sense,
+though physicists use them to designate one and the same kind of energy.
+
+The Purpose and the Mechanism of Heat Production in Infections
+
+Vaughan has shown that the presence in the body of any alien protein
+causes an increased production of heat, and that there is no difference
+between the production of fever by foreign proteins and by infections.
+Before the day of the hypodermic needle and of experimental medicine,
+the foreign proteins found in the body outside the alimentary tract
+were brought in by invading microorganisms.  Such organisms interfered
+with and destroyed the host.  The body, therefore, was forced
+to evolve a means of protection against these hostile organisms.
+The increased metabolism and fever in infection might operate
+as a protection in two ways--the increased fever, by interfering
+with bacterial growth, and the increased metabolism, by breaking up
+the bacteria.  Bacteriologists have taught us that bacteria grow best
+at the normal temperature of the body, hence fever must interfere
+with bacterial growth.  With each rise of one degree centigrade
+the chemical activity of the body is increased 10 per cent.
+In acute infections there is aversion to food and frequently there
+is vomiting.  In fever, then, we have diminished intake of energy,
+but an increased output of energy--hence the available potential
+energy in the body is rapidly consumed.  This may be an adaptation
+for the purpose of breaking up the foreign protein molecules
+composing the bacteria.  Thus the body may be purified by a chemical
+combustion so furious that frequently the host itself is destroyed.
+The problems of immunity are not considered here.
+
+As to the mechanism which produces fever, we postulate that it
+is the same mechanism as that which produces muscular activity.
+Muscular activity is produced by the conversion of latent energy
+into motion, and fever is produced largely in the muscles by
+the conversion of latent energy into heat.  We should, therefore,
+find similar changes in the brain, the adrenals, the thyroid,
+and the liver, whatever may be the purpose of the conversion of energy--
+whether for running, for fighting, for the expression of emotion,
+or for combating infection.
+
+We shall first present experimental and clinical evidence which tends
+to show what part is played by the brain in the production of both
+muscular and febrile action, and later we shall discuss the parts
+played by the adrenals, the thyroid, and the liver.  Histologic Changes
+in the Brain-cells in Relation to the Maintenance of Consciousness
+and to the Production of the Emotions, Muscular Activity, and Fever
+
+We have studied the brain-cells in human cases of fever,
+and in animals after prolonged insomnia; after the injection
+of the toxins of gonococci, of streptococci, of staphylococci,
+and of colon, tetanus, diphtheria, and typhoid bacilli; and after
+the injection of foreign proteins, of indol and skatol, of leucin,
+and of peptones.  We have studied the brains of animals which had been
+activated in varying degrees up to the point of complete exhaustion
+by running, by fighting, by rage and fear, by physical injury,
+and by the injection of strychnin (Figs. 2, 4, 5, and 37). We have
+studied the brains of salmon at the mouth of the Columbia River
+and at its headwater (Fig. 55); the brains of electric fish,
+the storage batteries of which had been partially discharged,
+and of those the batteries of which had been completely discharged;
+the brains of woodchucks in hibernation and after fighting;
+the brains of humans who had died from anemia resulting from hemorrhage,
+from acidosis, from eclampsia, from cancer and from other chronic diseases
+(Figs. 40 to 43, 56, 74, and 75). We have studied also the brains
+of animals after the excision of the adrenals, of the pancreas,
+and of the liver (Figs. 57 and 60).
+
+In every instance the loss of vitality--that is, the loss
+of the normal power to convert potential into kinetic energy--
+was accompanied by physical changes in the brain-cells (Figs. 45
+and 46). The converse was also true, that is, the brain-cells
+of animals with normal vital power showed no histologic changes.
+The changes in the brain-cells were identical whatever the cause.
+The crucial question then becomes:  Are these constant changes in
+the brain-cells the result of work done by the brain-cells in running,
+in fighting, in emotion, in fever?  In other words, does the brain
+perform a definite role in the conversion of latent energy into
+fever or into muscular action; or are the brain-cell changes caused
+by the chemical products of metabolism?  Happily, this crucial
+question was definitely answered by the following experiment:
+The circulations of two dogs were crossed in such a manner that the
+circulation of the head of one dog was anastomosed with the circulation
+of the body of another dog, and vice versa.  A cord encircled the neck
+of each so firmly that the anastomosing circulation was blocked
+(Fig. 58). If the brain-cell changes were due to metabolic products,
+then when the body of dog "A" was injured, the brain of dog "A"
+would be normal and the brain of dog "B" would show changes.
+Our experiments showed brain-cell changes in the brain of the dog
+injured and no changes in the brain of the uninjured dog.
+
+The injection of adrenalin causes striking brain-cell changes:
+first, a hyperchromatism, then a chromatolysis.  Now if adrenalin
+caused these changes merely as a metabolic phenomenon and not as a
+"work" phenomenon, then the injection of adrenalin into the carotid
+artery of a crossed circulation dog would cause no change in its
+circulation and its respiration, since the brain thus injected
+is in exclusive vascular connection with the body of another dog.
+In our experiment the blood-pressures of both dogs were recorded
+on a drum when adrenalin was injected into the common carotid.
+The adrenalin caused a rise in blood-pressure, an increase
+in the force of cardiac contraction, increase in respiration,
+and a characteristic adrenalin rise in the blood-pressure of both dogs.
+The rise was seen first in the dog whose brain alone received adrenalin
+and about a minute later in the dog whose body alone received adrenalin
+(Fig. 59). Histologic examinations of the brains of both dogs
+showed marked hyperchromatism in the brain receiving adrenalin,
+while the brain receiving no adrenalin showed no change.
+Here is a clear-cut observation on the action of adrenalin
+on the brain, for both the functional and the histologic
+tests showed that adrenalin causes increased brain action.
+The significance of this affinity of the brain for adrenalin begins
+to be seen when I call attention to the following striking facts:
+
+1.  Adrenalin alone causes hyperchromatism followed by chromatolysis,
+and in overdosage causes the destruction of some brain-cells.
+
+2.  When both adrenal glands are excised and no other factor
+is introduced, the Nissl substance progressively disappears from
+the brain-cells until death.  This far-reaching point will be taken
+up later (Fig. 60).
+
+Here our purpose is to discuss the cause of the brain-cell changes.
+We have seen that in crossed brain and body circulation trauma
+causes changes in the cells of the brain which is disconnected
+from the traumatized body by its circulation, but which is
+connected with the traumatized body by the nervous system.
+We have seen that adrenalin causes activation of the body connected
+with its brain by the nervous system, and histologic changes in
+the brain acted on directly by the adrenalin, but we found no notable
+brain-cell changes in the other brain through which the products
+of metabolism have circulated.
+
+In the foregoing we find direct evidence that the products of
+metabolism are not the principal cause of the brain-cell changes.
+We shall now present evidence to show that for the most part
+the brain-cell changes are "work" changes.  What work?  We postulate
+that it is the work by which the energy stored in the brain-cells is
+converted into electricity or some other form of transmissible energy
+which then activates certain glands and muscles, thus converting latent
+energy into beat and motion.  It has chanced that certain other studies
+have given an analogous and convincing proof of this postulate.
+In the electric fish a part of the muscular mechanism is replaced
+by a specialized structure for storing and discharging electricity.
+We found "work" changes in the brain-cells of electric fish
+after all their electricity had been rapidly discharged
+(Fig. 61). We found further that electric fish could not discharge
+their electricity when under anesthesia, and clinically we
+know that under deep morphin narcosis, and under anesthesia,
+the production both of heat and of muscular action is hindered.
+The action of morphin in lessening fever production is probably
+the result of its depressing influence on the brain-cells, because
+of which a diminished amount of their potential energy is converted
+into electricity and a diminished electric discharge from the brain
+to the muscles should diminish heat production proportionally.
+We found by experiment that under deep morphinization brain-cell
+changes due to toxins could be largely prevented (Fig. 62);
+in human patients deep morphinization diminishes the production
+of muscular action and of fever and conserves life when it is
+threatened by acute infections.  The contribution of the brain-cells
+to the production of heat is either the result of the direct
+conversion of their stored energy into heat, or of the conversion
+of their latent energy into electricity or a similar force,
+which in turn causes certain glands and muscles to convert latent
+energy into heat.
+
+A further support to the postulate that the brain-cells contribute
+to the production of fever by sending impulses to the muscles
+is found in the effect of muscular exertion, or of other forms of
+motor stimulation, in the presence of a fever-producing infection.
+Under such circumstances muscular exertion causes additional fever,
+and causes also added but identical changes in the brain-cells. Thyroid
+extract and iodin have the same effect as muscular exertion and infection
+in the production of fever and the production of brain-cell changes.
+All this evidence is a strong argument in favor of the theory that
+certain constituents of the brain-cells are consumed in the work
+performed by the brain in the production of fever.
+
+That the stimulation of the brain-cells without gross activity
+of the skeletal muscles and without infection can produce heat
+is shown as follows:
+
+(_a_) Fever is produced when animals are subjected to fear without
+any consequent exertion of the skeletal muscles.
+
+(_b_) The temperature of the anxious friends of patients will rise
+while they await the outcome of an operation (Fig. 63).
+
+(_c_) The temperature and pulse of patients will rise as a result
+of the mere anticipation of a surgical operation (Fig. 64).
+
+(_d_) There are innumerable clinical observations as to the effect
+of emotional excitation on the temperature of patients.
+A rise of a degree or more is a common result of a visit from
+a tactless friend.  There is a traditional Sunday increase
+of temperature in hospital wards.  Now the visitor does not bring
+and administer more infection to the patient to cause this rise,
+and the rise of temperature occurs even if the patient does
+not make the least muscular exertion as a result of the visit.
+I once observed an average increase of one and one-eighth degrees
+of temperature in a ward of fifteen children as a result of a Fourth
+of July celebration.
+
+Is the contribution of the brain to the production of heat due
+to the conversion of latent energy directly into heat, or does
+the brain produce heat principally by converting its latent energy
+into electricity or some similar form of transmissible energy which,
+through nerve connections, stimulates other organs and tissues,
+which in turn convert their stores of latent energy into heat?
+
+According to Starling, when the connection between the brain
+and the muscles of an animal is severed by curare, by anesthetics,
+by the division of the cord and nerves, then the heat-producing power
+of the animal so modified is on a level with that of cold-blooded animals.
+With cold the temperature falls, with heat it rises.  Such an animal
+has no more control over the conversion of latent energy into heat
+than it has over the conversion of latent energy into motion.
+
+Electric stimulation done over a period of time causes brain-cell changes,
+and electric stimulation of the muscles causes a rise in temperature.
+
+
+Summary of Brain-cell Studies
+
+In our crossed circulation experiments we found that neither waste
+products nor metabolic poisons could be considered the principal
+cause of the brain-cell changes.  We found that in the production
+both of muscular action and of fever there were brain-cell changes
+which showed a quantita-tive relation to the temperature changes
+or to the muscular work done.  We observed that under deep
+morphinization the febrile response or the muscular work done was
+either diminished or eliminated and that the brain-cell changes were
+correspondingly diminished or eliminated.  We found also that brain-cell
+changes and muscular work followed electric stimulation alone.
+I conclude, therefore, that the brain-cell changes are work changes.
+
+We shall next consider other organs of the kinetic system in their
+relation to muscular activity, to emotion, to consciousness,
+to sleep, to hibernation, and to heat production.
+
+
+The Adrenals
+
+In our extensive study of the brain in its relation to the production
+of energy and the consequent exhaustion caused by fear and rage;
+by the injection of foreign proteins, of bacterial toxins,
+and of strychnin; by anaphylaxis; by the injection of thyroid extract,
+of adrenalin, and of morphin, we found that, with the exception
+of morphin, each of these agents produced identical changes in
+the brain-cells. As we believed that the adrenals were intimately
+associated with the brain in its activities, we concluded that
+the adrenals also must have been affected by each of these agents.
+To prove this relation, we administered the above-mentioned
+stimuli to animals and studied their effects upon the adrenals
+by functional, histologic, and surgical methods, the functional
+tests being made by Cannon's method.
+
+Functional Study of the Adrenals.--Our method of applying
+the Cannon test for adrenalin was as follows:  (_a_) The blood
+of the animals was tested before the application of the stimulus.
+If this test was negative, then (_b_) the stimulus was applied
+and the blood again tested.  If this second test was negative,
+a small amount of adrenalin was added.  If a positive reaction
+was then given, the negative result was accepted as conclusive.
+(_c_) If the control test was negative, then the stimulus was given.
+If the blood after stimulation gave a positive result for adrenalin,
+a second test of the same animal's blood was made twenty-five minutes
+or more later.  If the second test was negative, then the positive
+result of the first test was accepted as conclusive.
+
+We have recorded 66 clear-cut experiments on dogs, which show that
+after fear and rage, after anaphylaxis, after injections of indol
+and skatol, of leucin and creatin, of the toxins of diphtheria and
+colon bacilli, of streptococci and staphylococci, of foreign proteins,
+and of strychnin, the Cannon test for adrenalin was positive.
+The test was negative after trauma under anesthesia, and after
+intravenous injections of thyroid extract, of thyroglobin,
+and of the juices of various organs injected into the same animal from
+which the organs were taken.  Placental extract gave a positive test.
+The test was sometimes positive after electric stimulation
+of the splanchnic nerves.  On the other hand, if the nerve supply
+to the adrenals had been previously divided, or if the adrenals
+had been previously excised, then the Cannon test was negative
+after the administration of each of the foregoing adequate stimuli.
+Blood taken directly from the adrenal vein gave a positive result,
+but under deep morphinization the blood from the adrenal vein
+was negative, and under deep morphinization the foregoing adequate
+stimuli were negative.
+
+In brief, the agencies that in our brain-cell studies were found to
+cause hyperchromatism followed by chromatolysis gave positive results
+in the Cannon test for adrenalin (Fig. 62). The one agent which was
+found to protect the brain against changes in the Nissl substance--
+morphin--gave a negative result in the Cannon test for adrenalin.
+After excision of the adrenals, or after division of their nerve supply,
+all Cannon tests for adrenalin were negative.
+
+Histologic Study of the Adrenals.--Histologic studies of the adrenals
+after the application of the adequate stimuli which gave positive
+results to the Cannon test for adrenalin are now in progress,
+and thus far the histologic studies corroborate the functional tests.
+
+In hibernating woodchucks, the cells of the adrenal cortex were found
+to be vacuolated and shrunken.  In one hundred hours of insomnia,
+in surgical shock, in strong fear, in exhaustion from fighting,
+after peptone injections, in acute infections, the adrenals undergo
+histologic changes characteristic of exhaustion (Figs. 66 to 67).
+
+We have shown that brain and adrenal activity go hand in hand,
+that is, that the adrenal secretion activates the brain, and that
+the brain activates the adrenals.  The fundamental question which now
+arises is this:  Are the brain and the adrenals interdependent?
+A positive answer may be given to this question, for the evidence
+of the dependence of the brain upon the adrenals is as clear as is
+the evidence of the dependence of the adrenals upon the brain.
+(1) After excision of the adrenals, the brain-cells undergo
+continuous histologic and functional deterioration until death.
+During this time the brain progressively loses its power
+to respond to stimuli and there is also a progressive loss
+of muscular power and a diminution of body temperature.
+(2) {illust. caption = FIG.  66.In our crossed circulation experiments
+we found that adrenalin alone could cause increased brain activity,
+while histologically we know that adrenalin alone causes an increase
+of the Nissl substance.  An animal, both of whose adrenals
+had been excised, showed no hyperchromatism in the brain-cells
+after the injection of strychnin, toxins, foreign proteins, etc.
+(3) When the adrenal nerve supply is divided (Cannon-Elliott), then
+there is no increased adrenal activity in response to adequate stimuli.
+
+From these studies we are forced to conclude not only that the brain
+and adrenals are interdependent, but that the brain is actually
+more dependent upon the adrenals than the adrenals upon the brain,
+since the brain deteriorates progressively to death without the adrenals,
+while the adrenal whose connection with the brain has been broken
+by the division of its nerve supply will still produce sufficient
+adrenalin to support life.
+
+From the strong affinity of the brain-cells for adrenalin which was
+manifested in our experiments we may strongly suspect that the Nissl
+substance is a volatile, extremely unstable combination of certain
+elements of the brain-cells and adrenalin, because the adrenals alone
+do not take the Nissl stain and the brain deprived of adrenalin
+also does not take Nissl stain.  The consumption of the Nissl
+substance in the brain-cells is lessened or prevented by morphin,
+as is the output of adrenalin; and the consumption of the Nissl
+substance is also lessened or prevented by nitrous oxid.
+But morphin does not prevent the action of adrenalin injected
+into the circulation, hence the control of morphin over energy
+expenditure is exerted directly on the brain-cells. Apparently morphin
+and nitrous oxid both act through this interference with oxidation
+in the brain.  We, therefore, conclude that within a certain range
+of acidity of the blood adrenalin can unite with the brain-cells
+only through the mediation of oxygen, and that the combination
+of adrenalin, oxygen, and certain brain-cell constituents
+causes the electric discharge that produces heat and motion.
+In this interrelation of the brain and the adrenals we have what is,
+perhaps, the master key to the automatic action of the body.
+Through the special senses environmental stimuli reach the brain
+and cause it to liberate energy, which in turn activates certain
+other organs and tissues, among which are the adrenals.  The increased
+output of adrenalin activates the brain to still greater activity,
+as a result of which again the entire sympathetic nervous system
+is further activated, as is manifested by increased heart action,
+more rapid respiration, raised blood-pressure, increased output
+of glycogen, increased power of the muscles to metabolize glucose, etc.
+
+If this conclusion be well founded, we should find corroborative evidence
+in histologic changes in that great storehouse of potential energy,
+the liver, as a result of the application of each of the adequate
+stimuli which produced brain-cell and adrenal changes.
+
+
+The Liver
+
+Prolonged insomnia, prolonged physical exertion, infections, injections of
+toxins and of strychnin, rage and fear, physical injury under anesthesia,
+in fact, all the adequate stimuli which affected the brain and
+the adrenals, produced constant and identical histologic changes
+in the liver--the cells stained poorly, the cytoplasm was vacuolated,
+the nuclei were crenated, the cell membranes were irregular, the most
+marked changes occurring in the cells of the periphery of the lobules
+(Figs. 69 and 70). In prolonged insomnia the striking changes
+in the liver were repaired by one seance of sleep.
+
+Are the histologic changes in the liver cells due to metabolism or toxic
+products, or are they "work" changes incident to the conversion of latent
+into kinetic energy?  Are the brain, adrenals, and liver interdependent?
+The following facts establish the answers to these queries:
+
+(1) The duration of life after excision of the liver is about
+the same as after adrenalectomy--approximately eighteen hours.
+
+(2) The amount of glycogen in the liver was diminished in all the
+experiments showing brain-adrenal activity; and when the histologic
+changes were repaired, the normal amount of glycogen was again found.
+
+(3) In crossed circulation experiments changes were found in the liver
+of the animal whose brain received the stimulus.
+
+From these premises we must consider that the brain, the adrenals,
+and the liver are mutually dependent on one another for the conversion
+of latent into kinetic energy.  Each is a vital organ, each equally vital.
+It may be said that excision of the brain may apparently cause death
+in less time than excision of the liver or adrenals, but this statement
+must be modified by our definition of death.  If all the brain
+of an animal be removed by decapitation, its body may live on for at
+least eleven hours if its circulation be maintained by transfusion.
+An animal may live for weeks or months after excision of the cerebral
+hemispheres and the cerebellum, while an overtransfused animal may
+live many hours, days even, after the destruction of the medulla.
+It is possible even that the brain actually is a less vital organ
+than either the adrenals or the liver.
+
+In our research to discover whether any other organs should be
+included with the brain, the adrenals, and the liver in this mutually
+interdependent relation, we hit upon an experiment which throws
+light upon this problem.
+
+Groups of rabbits were gently kept awake for one hundred hours
+by relays of students, an experiment which steadily withdrew
+energy but caused not the slightest physical or emotional injury
+to any of them; no drug, toxin, or other agent was given to them;
+they were given sufficient food and drink.  In brief, the internal
+and external environments of these animals were kept otherwise normal
+excepting for the gentle stimuli which insured continued wakefulness.
+This protracted insomnia gradually exhausted the animals completely,
+some to the point of death even.  Some of the survivors were killed
+immediately after the expiration of one hundred hours of wakefulness,
+others after varying intervals.
+
+Histologic studies were made of every tissue and organ in the body.
+Three organs, the brain, the adrenals, and the liver, and these three only,
+showed histologic changes.  In these three organs the histologic changes
+were marked, and were almost wholly repaired by one seance of sleep.
+In each instance these histologic changes were identical with
+those seen after physical exertion, emotions, toxins, etc.[*] It
+would appear, then, that these three organs take the stress of life--
+the brain is the "battery," the adrenals the "oxydizer," and the liver
+the "gasoline tank."  This clear-cut insomnia experiment corresponds
+precisely with our other brain-adrenal observations.
+
+
+[*] Further studies have given evidence that the elimination of the acids
+resulting from energy-transformation as well as the conversion
+of energy stored in the kinetic organs causes histologic changes
+in the liver, the adrenals, and possibly in the brain.
+
+
+With these three kinetic organs we may surely associate also the
+"furnace," the muscles, in which the energy provided by the brain,
+adrenals, and liver, plus oxygen, is fabricated into heat and motion.
+
+Benedict, in his monumental work on metabolism, has demonstrated
+that in the normal state, at least, variations in the heart-beat
+parallel variations in metabolism.  He and others have shown also that
+all the energy of the body, whether evidenced by heat or by motion,
+is produced in the muscles.  In the muscles, then, we find the fourth
+vital link in the kinetic chain.  The muscles move the body,
+circulate the blood, effect respiration, and govern the body temperature.
+They are the passive servants of the brain-adrenal-liver syndrome.
+
+Neither the brain, the adrenals, the liver, nor the muscles, however,
+nor all of these together, have the power to change the rate of
+the expenditure of energy; to make possible the increased expenditure
+in adolescence, in pregnancy, in courting, and mating, in infections.
+No one of these organs, nor all of them together, can act as a
+pace-maker or sensitizer.  The brain acts immediately in response
+to the stimuli of the moment; the adrenals respond instantly
+to the fickle brain and the effects of their actions are fleeting;
+the liver contains fuel only and cannot activate, and the muscles
+in turn act as the great furnace in which the final transformation
+into available energy is made.  The Thyroid
+
+Another organ--the thyroid--has the special power of governing
+the RATE OF DISCHARGE of energy; in other words, the thyroid is the
+pace-maker. Unfortunately, the thyroid cannot be studied to advantage
+either functionally or histologically, for there is as yet no available
+test for thyroid secretion in the blood as there is for adrenalin,
+and thyroid activity is not attended by striking histologic changes.
+Therefore the only laboratory studies which have been satisfactory
+thus far are those by which the iodin content of the thyroid
+has been established.  Iodin is stored in the colloid lacunae
+of the thyroid and, in combination with certain proteins,
+is the active agent of the thyroid.
+
+Beebe has shown that electric stimulation of the nerve supply of
+the thyroid diminishes the amount of iodin which it contains, and it
+is known that in the hyperactive thyroid in Graves' disease the iodin
+content is diminished.  The meagerness of laboratory studies, however,
+is amply compensated by the observations which the surgeon has been
+able to make on a vast scale--observations which are as definite
+as are the results of laboratory experiments.
+
+The brain-cells and the adrenals are securely, concealed from
+the eye of the clinician, hence the changes produced in them
+by different causes escape his notice, but the thyroid has always
+been closely scrutinized by him.  The clinician knows that every
+one of the above-mentioned causes of increased brain-cell, adrenal,
+liver and muscle activity may cause an increase in the activity
+of both the normal or the enlarged thyroid; and lie knows only too
+well that in a given case of exophthalmic goiter the same stimuli
+which excite the brain, the adrenals, the liver, and the muscles
+to increased activity will also aggravate this disease.
+
+The function of the thyroid in the kinetic chain is best evidenced,
+however, by its role in the production of fever.  Fever results
+from the administration of thyroid extract alone in large doses.
+In the hyperactivity of the thyroid in exophthalmic goiter one sees
+a marked tendency to fever, in severe cases there is daily fever.
+In fact, in Graves' disease we find displayed to an extraordinary
+degree an exaggeration of the whole action of the kinetic mechanism.
+
+We have stated that in acute Graves' disease there is a tendency
+to the production of spontaneous fever, and that there is a magnified
+diurnal variation in temperature which is due to an increased output
+of energy in even the normal reaction producing consciousness.  In Graves'
+disease there is, therefore, a state of intensified consciousness, which is
+associated with low brain thresholds to all stimuli--both to stimuli
+that cause muscular action and to stimuli that cause fever.  The intensity
+of the kinetic discharge is seen in the constant fine tremor.
+It is evident that the thresholds of the brain have been sensitized.
+In this hypersensitization we find the following strong evidence as to
+the identity of the various mechanisms for the production of fever.
+In the state of superlative sensitization which is seen in Graves'
+disease we find that the stimuli that produce muscular movement,
+the stimuli that produce emotional phenomena, and the stimuli that
+produce fever are as nearly as can be ascertained equally effective.
+Clinical evidence regarding this point is abundant, for in
+patients with Graves' disease we find that the three types
+of conversion of energy resulting from emotional stimulation,
+from infection stimulation, and from nociceptor stimulation
+(pain), are, as nearly as can be judged, equally exaggerated.
+In the acute cases of Graves' disease the explosive conversion
+of latent energy into heat and motion is unexcelled by any other
+known normal or pathologic phenomenon.  Excessive thyroid secretion,
+as in thyrotoxicosis from functioning adenomata, and excessive
+thyroid feeding, cause all the phenomena of Graves' disease except
+the exophthalmos and the emotional facies (Figs. 15 and 23).
+The ligation of arteries, the division of its nerve supply,
+or the excision of part of the gland, may reverse the foregoing picture
+and restore the normal condition.  The patient notes the effect
+on the second day and often within a week is relatively quiescent.
+On the contrary, if there is thyroid deficiency there results
+the opposite state, a reptilian sluggishness.
+
+At will, then, through diminished, normal, or excessive administration
+of thyroid secretion, we may produce an adynamic, a normal,
+or an excessively dynamic state.  By the thyroid influence,
+the brain thresholds are lowered and life becomes exquisite;
+without its influence the brain becomes a globe of relatively
+inert substance.  Excessive doses of iodin alone cause
+most of the symptoms of Graves' disease.  As we have stated,
+the active constituent of the thyroid is iodin in a special
+protein combination which is stored in the colloidal spaces.
+Hence one would not expect to find changes in the cells of the thyroid
+gland as a result of increased activity unless it be prolonged.
+
+We have thus far considered the normal roles played by the brain,
+the adrenals the liver, the muscles, and the thyroid in transforming
+latent into kinetic energy in the form of heat and motion as an
+adaptive response to environmental stimuli.
+
+The argument may be strengthened, however, by the discussion of
+the effect of the impairment of any of these links in the kinetic
+chain upon the conversion of latent into kinetic energy.
+
+
+Effect Upon the Output of Energy of Impaired or Lost Function
+of Each of the Several Links in the Kinetic Chain
+
+(1) _The Brain_.--In cerebral softening we may find all the organs
+of the body comparatively healthy excepting the brain.
+As the brain is physically impaired it cannot normally stimulate
+other organs to the conversion of latent energy into heat or
+into motion, but, on the contrary, in these cases we find feeble
+muscular and intellectual power.  I believe also that in patients
+with cerebral softening, infections such as pneumonia show a lower
+temperature range than in patients whose brains are normal.
+
+(2) _The Adrenals_.--In such destructive lesions of the adrenals
+as Addison's disease one of the cardinal symptoms is a subnormal
+temperature and impaired muscular power.  Animals upon whom double
+adrenalectomy has been performed show a striking fall in temperature,
+muscular weakness,--after adrenalectomy the animal may not be able
+to stand even,--and progressive chromatolysis.
+
+(3) _The Liver_.--When the function of the liver is impaired
+by tumors, cirrhosis, or degeneration of the liver itself,
+then the entire energy of the body is correspondingly diminished.
+This diminution of energy is evidenced by muscular and mental weakness,
+by diminished response and by gradual loss of efficiency which finally
+reaches the state of asthenia.
+
+(4) _The Muscles_.--It has been observed clinically that if the muscles
+are impaired by long disuse, or by a disease such as myasthenia gravis,
+then the range of production of both heat and motion is below normal.
+This is in agreement with the experimental findings that anesthetics,
+curare, or any break in the muscle-brain connection causes diminished
+muscular and heat production.
+
+(5) _The Thyroid_.--In myxedema one of the cardinal symptoms
+is a persistently subnormal temperature and, though prone
+to infection, subjects of myxedema show but feeble febrile response
+and readily succumb.  This clinical observation is strikingly
+confirmed by laboratory observations; normal rabbits subjected
+to fear showed a rise in temperature of from one to three degrees,
+while two rabbits whose thyroids had been previously removed and who
+had then been subjected to fright showed much less febrile response.
+Myxedema subjects show a loss of physical and mental energy
+which is proportional to the lack of thyroid.  Deficiency in any
+of the organs of the kinetic chain causes alike loss of heat,
+loss of muscular and emotional action, of mental power, and of the power
+of combating infections--the negative evidence thus strongly supports
+the positive.  By accumulating all the evidence we believe we
+are justified in associating the brain, the adrenals, the thyroid,
+the muscles, and the liver as vital links in the kinetic chain.
+Other organs play a role undoubtedly, though a minor one.
+
+
+Studies in Hydrogen Ion Concentration in Activation of the Kinetic System
+
+Having established the identity of some, at least, of the organs
+which constitute the kinetic chain, we endeavored to secure still
+further evidence regarding the energy-transforming function of these
+organs by making studies of the H-ion concentration of the blood,
+as one would expect, _prima facie_, that the normal reaction would
+be altered by kinetic activation.[*]
+
+
+[*] The H-ion observations were made in my laboratory by Dr. M. L. Menten.
+
+
+H-ion concentration tests were made after the application
+of the adequate stimuli by which the function of the kinetic
+organs had been determined, and we studied also the effect upon
+the acidity of the blood of strychnin convulsions after destruction
+of the medulla; of deep narcotization with morphin before anesthesia;
+of deep narcotization with morphin after the H-ion concentration
+had already been increased by fear, by anger, by exertion,
+by injury under anesthesia, or by anesthesia alone.
+
+The complete data of these experiments will be later reported in
+a monograph; here it is sufficient to state that anger, fear, injury,
+muscular exertion, inhalation anesthesia, strychnin, alcohol, in fact,
+all the stimuli which we had already found to produce histologic
+changes in the brain, the adrenals, and the liver-excepting
+bacterial toxins--caused increased H-ion concentration.
+Of striking significance is the fact that morphin alone caused
+no change in the H-ion concentration, while if administered before
+the application of a stimulus which by itself produced increased
+H-ion concentration, the action of that stimulus was neutralized
+or postponed.  If, however, morphin was administered after increased
+acidity had been produced by any stimulus, or by inhalation anesthesia,
+then the time required for the restoration of the normal alkalinity
+was much prolonged, and in some instances the power of acid
+neutralization was permanently lost.
+
+After excision of the liver, the normal H-ion concentration
+was maintained for periods varying from one to several hours,
+after which the concentration (acidity) began to increase as
+the vitality of the animal began to decline, the concentration
+(acidity) increasing rapidly until death.  After excision of
+the adrenals the blood remained normal for from four to six hours,
+when the H-ion concentration increased rather suddenly,
+the increase being synchronous with the incidence of the phenomena
+which immediately preceded death.
+
+In none of these cases was it determined whether the increased
+H-ion concentration was due to other causes of death or whether
+death was due to the increased acidity.
+
+It is also significant that after the application of each of
+the adequate stimuli which increased the H-ion concentration
+of the blood in other parts of the body the blood from the adrenal
+vein showed a slight diminution in acidity, as, in most instances,
+did the blood from the hepatic vein also.
+
+In fact, the H-ion concentration of the blood in the adrenal vein
+was less than in the blood of any other part of the circulation.
+
+
+Kinetic Diseases
+
+If our conclusions are sound, then in the kinetic system we find
+an explanation of many diseases, and having found the explanation,
+we may find new methods of combating them.
+
+When the kinetic system is driven at an overwhelming rate of speed,--
+as by severe physical injury, by intense emotional excitation,
+by perforation of the intestines, by the pointing of an abscess
+into new territory, by the sudden onset of an infectious disease,
+by an overdose of strychnin, by a Marathon race, by a grilling fight,
+by foreign proteins, by anaphylaxis,--the result of these acute
+overwhelming activations of the kinetic system is clinically
+designated shock, and according to the cause is called traumatic shock,
+toxic shock, anaphylactic shock, drug shock, etc.
+
+The essential pathology of shock is identical whatever the cause.
+If, however, instead of an intense overwhelming activation,
+the kinetic system is continuously or intermittently overstimulated
+through a considerable period of time, as long as each of the links
+in the kinetic chain takes the strain equally the result will be
+excessive energy conversion, excessive work done; but usually,
+under stress, some one link in the chain is unable to take the strain
+and then the evenly balanced work of the several organs of the kinetic
+system is disturbed.  If the brain cannot endure the strain,
+then neurasthenia, nerve exhaustion, or even insanity follows.
+If the thyroid cannot endure the strain, it undergoes hyperplasia,
+which in turn may result in a colloid goiter or in exophthalmic goiter.
+If the adrenals cannot endure the strain, cardiovascular disease
+may develop.  If the liver cannot take the strain, then death from
+acute acidosis may follow, or if the neutralizing effect of the liver
+is only partially lost, then the acidity may cause Bright's disease.
+Overactivation of the kinetic system may cause glycosuria and diabetes.
+
+Identical physical and functional changes in the organs of
+the kinetic system may result from intense continued stimulation
+from any of the following causes:  Excessive physical labor,
+athletic exercise, worry or anxiety, intestinal autointoxication,
+chronic infections, such as oral sepsis, tonsillitis, and adenoids;
+chronic appendicitis, chronic cholecystitis, colitis, and skin infections;
+the excessive intake of protein food (foreign protein reaction);
+emotional strain, pregnancy, stress of business or professional life--
+all of which are known to be activators of the kinetic system.
+
+From the foregoing statements we are able to understand
+the muscular weakness following fever; we can understand why
+the senile have neither muscular power nor strong febrile reaction;
+why long-continued infections produce pathologic changes in the organs
+constituting the kinetic chain; why the same pathologic changes
+result from various forms of activation of the kinetic system.
+In this hypothesis we find a reason why cardiovascular disease may
+be caused by chronic infection, by auto-intoxication, by overwork,
+or by emotional excitation.  We now see that the reason why we find
+so much difficulty in differentiating the numerous acute infections
+from each other is because they play upon the same kinetic chain.
+Our postulate harmonizes the pathologic democracy of the kinetic organs,
+for it explains not only why, in many diseases, the pathologic
+changes in these organs are identical, but why the same changes
+are seen as the result of emotional strain and overwork.
+We can thus understand how either emotional strain or acute or chronic
+infection may cause either exophthalmic goiter or cardiovascular disease;
+how chronic intestinal stasis with the resultant absorption of
+toxins may cause cardiovascular disease, neurasthenia, or goiter.
+Here is found an explanation of the phenomena of shock, whether the
+shock be the result of toxins, of infection, of foreign proteins,
+of anaphylaxis, of psychic stimuli, or of a surgical operation
+with its combination of both psychic and traumatic elements.
+
+This conception of the kinetic system has stood a crucial test by making
+possible the shockless operation.  It has offered a plausible explanation
+of the cause and the treatment of Graves' disease.  Will the kinetic
+theory stand also the clinical test of controlling that protean
+disease bred in the midst of the stress of our present-day life?
+Present-day life, in which one must ever have one hand on the sword and
+the other on the throttle, is a constant stimulus of the kinetic system.
+The force of these kinetic stimuli may be lessened at the cerebral
+link by intelligent control--a protective control is empirically
+attained by many of the most successful men.  The force of the kinetic
+stimuli may be broken at the thyroid link by dividing the nerve supply,
+reducing the blood supply, or by partial excision; or if the adrenals
+feel the strain, the stimulating force may be broken by dividing
+their nerve supply, reducing the blood supply, or by partial excision.
+No theory is worth more than its yield in practice, but already we
+have the shockless operation, the surgical treatment of Graves'
+disease, and the control of shock and of the acute infections
+by overwhelming morphinization (Figs. 62, 72, and 73).
+
+
+Conclusions
+
+To become adapted to their environment animals are transformers of energy.
+This adaptation to environment is made by means of a system of organs
+evolved for the purpose of converting potential energy into heat
+and motion.  The principal organs and tissues of this system are
+the brain, the adrenals, the thyroid, the muscles, and the liver.
+Each is a vital link, each plays its particular role, and one cannot
+compensate for the other.  A change in any link of the kinetic
+chain modifies proportionately the entire kinetic system which is
+no stronger than its weakest link.
+
+In this conception we find a possible explanation of many diseases
+one which may point the way to new and more effective therapeutic
+measures than those now at our command.
+
+
+
+ALKALESCENCE, ACIDITY, ANESTHESIA--A THEORY OF ANESTHESIA[*]
+
+
+[*] Paper delivered before the Virginia Medical Association,
+Washington, D. C., October 29, 1914.
+
+
+Alkalis and bases compose the greater part of the food of man
+and animals, the blood in both man and animals under normal conditions
+being slightly alkaline or rather potentially alkaline; that is,
+although in circulating blood the concentration of the OH-ions--
+upon which the degree of alkalinity depends--is but little more
+than in distilled water, yet blood has the power of neutralizing
+a considerable amount of acid (Starling, Wells). At the time of death,
+whatever its cause, the concentration of H-ions in the blood increases,--
+the concentration of H-ions being a measure of acidity,--that is,
+the potential or actual alkalinity decreases and the blood becomes
+actually neutral or acid.
+
+To determine what conditions tend to diminish the normal alkalinity
+of the blood, many observations were made for me in my laboratory
+by Dr. M. L. Menten to determine by electric measurements
+the H-ion concentration of the blood under certain pathologic
+and physiologic conditions.
+
+As a result of these researches we are able to state that the H-ion
+concentration of the blood--its acidity--is increased by excessive
+muscular activity; excessive emotional excitation; surgical shock;
+in the late stages of infection; by asphyxia; by strychnin convulsions;
+by inhalation anesthetics; after excision of the pancreas, and in the late
+stages of life after excision of the liver and excision of the adrenals.
+Morphin and decapitation cause no change in the H-ion concentration.
+Ether, nitrous oxid, and alcohol produce an increased acidity
+of the blood which is proportional to the depth of anesthesia.
+
+Many of the cases studied were near death, as would be expected,
+since it is well known that a certain degree of acidity is
+incompatible with life.
+
+Since alkalis and bases preponderate in ingested food;
+since alkalinity of the blood is diminished by bodily activity;
+and since at the point of death the blood is always acid, we may
+infer that some mechanism or mechanisms of the body were evolved
+for the purpose of changing bases into acids that thus energy
+might be liberated.
+
+These observations lead naturally to the question, May not
+acidity of itself be the actual final cause of death?
+We believe that it may be so from the facts that--(1)
+The intravenous injection of certain acids causes death quickly,
+but that convulsions do not occur, since the voluntary muscles
+lose their power of contraction; and (2) the intravenous injection
+of acids causes extensive histologic changes in the brain,
+the adrenals, and the liver which resemble the changes invariably
+caused by activation of the kinetic system (Figs. 74 and 75). In view
+of these facts may we not find that anesthesia and many instances
+of unconsciousness are merely phenomena of acidity?
+
+As has been stated already, we have found that the H-ion concentration
+of the blood--its acidity--is increased by alcohol, by ether,
+and by nitrous oxid.  In addition our tests have shown that under
+ether the increase of the H-ion concentration--acidity--is more
+gradual than under nitrous oxid, an observation which accords well
+with the fact that nitrous oxid more quickly induces anesthesia
+than does ether.
+
+Further striking testimony in favor of the hypothesis that
+the production of acidity by inhalation anesthetics is the method
+by which anesthesia itself is produced is found in the fact
+that although lethal doses of acid cause muscular paralysis,
+yet this paralysis may be mitigated by adrenalin--which is alkaline.
+This observation may explain in part the remarkable success of
+the method of resuscitation devised by me, in which animals "killed"
+by anesthetics and asphyxia are revived by the use of adrenalin.
+
+In animals under inhalation anesthesia Williams found that no
+nerve-current could be detected by the Einthoven string galvanometer,
+a fact which might be explained by postulating that nerve-currents
+can flow from the brain to the muscles and glands only when there
+is a difference of potential.  Any variation from the normal
+alkalinity of the body must change the difference in potential.
+Since the nerve-currents in animals under anesthesia are not demonstrable
+by any apparatus at our command, and since anesthesia produces acidity,
+then we may infer that acidity reduces the difference in potential.
+As long as there is life, a galvanometer of sufficient delicacy
+would perforce detect, a nerve-current until the acidity increased
+to such a point as to reduce the difference in potential to zero--
+the point of death.  If at this point a suitable alkali--
+adrenalin solution--can be introduced quickly enough, the vital difference
+in potential may be restored and the life processes will be renewed.
+Bearing especially on this point is the fact that if adrenalin
+in sufficient quantities be administered simultaneously with an acid,
+it will not only prevent the fall in blood-pressure usually
+caused by the acid, but will also prevent the histologic changes
+in the brain, adrenals, and liver which are usually caused by
+the intravenous injection of acids.
+
+This hypothesis regarding the cause of anesthesia and unconsciousness
+explains and harmonizes many facts.  It explains how asphyxia,
+overwhelming emotion, and excessive muscular exertion, by causing acidity,
+may produce unconsciousness.  It explains the acidosis which results
+from starvation, from uremia, from diabetes, from Bright's disease,
+and supplies a reason for the use of intravenous infusions of sodium
+bicarbonate to overcome the coma of diabetes and uremia (Fig. 76).
+It may explain the quick death from chloroform and nitrous oxid;
+and may perhaps show why unconsciousness is so commonly the immediate
+precursor of death.
+
+One of the most noticeable immediate effects of the administration
+of an inhalation anesthetic is a marked increase in the rapidity
+and force of the respiration.  The respiratory center has evidently
+been evolved to act with an increase of vigor which is proportional--
+within certain limits--to the increase in the H-ion concentration,
+whereas the centers governing the voluntary muscles are inhibited.
+In this antithetic reaction of the higher cortical centers and the lower
+centers in the medulla to acidity we find a remarkable adaptation
+which prevents the animal from killing itself by the further increase
+in acidity which would be produced by muscular activity.  That is,
+as the acidity produced by muscular action increases and threatens life,
+the respiratory action, by which carbon dioxid is eliminated and
+oxygen supplied, is increased, while the driving power of the brain,
+which produces acidity, is diminished or even inhibited entirely;
+that is, the state of unconsciousness or anesthesia is reached.
+We conclude first that, without this life-saving regulation,
+animals under stress would inevitably commit suicide; and, second,
+that it is probable that the remarkable phenomenon of anesthesia--
+the coincident existence of unconsciousness and life--is due to this
+antithetic action of the cortex and the medulla.
+
+In the human, as in the animal, the degree of acidity parallels
+the depth of inhalation anesthesia.
+
+Within a few seconds after beginning nitrous oxid anesthesia the acidity
+of the blood is increased.  This rapid acidulation is synchronous
+with almost instantaneous unconsciousness and increased respiration.
+If the oxygen in the inhaled mixture be increased, a decrease in
+acidity is again synchronous with lighter anesthesia and a decrease
+in the respiratory rate.
+
+If these premises be sound, we are justified in asserting that the state
+of anesthesia is due to an induced acidity of the blood.  If the acidity
+is slight, then the anesthesia is slight and the force of the nerve
+impulses is lessened, but the patient is still conscious of them.
+As the acidity increases associative memory is lost, and the patient
+is said to be unconscious:  the centers governing the voluntary muscles
+are not inhibited, however, and cutting the skin causes movements.
+If the acidity is further increased, there is loss of muscular tone
+and even the strong contact ceptor stimuli of a surgical operation
+do not cause any muscular response, and, finally, the acidity may be
+increased to the point at which the respiratory and circulatory centers
+can no longer respond by increased effort, and anesthetic death--
+that is, ACID death--follows.
+
+Certain clinical phenomena are clarified by this theory and serve
+to substantiate it.  For example, it is well known that inhalation
+anesthesia precipitates the impending acidosis which results
+from starvation, from extreme Graves' disease, from great exhaustion,
+from surgical shock, and from hemorrhage, and which is present
+when death from any cause is imminent.
+
+We see, therefore, that anesthesia is made possible, first, by the fact
+that inhalation anesthetics cause acidity, and, second, by the antithetic
+adaptation of the higher centers in the brain and of the centers
+governing respiration and circulation.
+
+In deep contrast to the action of inhalation anesthetics is that
+of narcotics.  Deep narcotization with morphin and scopolamin is
+induced slowly; the respiratory and pulse-rate are progressively lessened--
+and there is no acidity.
+
+By our researches we have established in what consists the generic
+difference between inhalation anesthetics and narcotics.
+In our experiments no increase in the H-ion concentration was produced
+by morphin or by scopolamin, no matter how deep the narcotization.
+In animals already narcotized by morphin the production of acid by any
+of the acid-producing stimuli was delayed or prevented.  On the other hand,
+in animals in which an acidity had already been produced by ether,
+by shock, by anger, or by fear, the later administration of morphin
+delayed or inhibited entirely the neutralization of the acidity.
+In other words, morphin interferes with the normal mechanism by
+which acidity is neutralized possibly because its inhibiting action
+on the respiratory center is sufficient to overcome the stimulating
+action of acidity on that center, for, as we have stated,
+the neutralization of acidity is in large measure accomplished
+by the increased respiration induced by the acidity itself.
+
+
+SUMMARY
+
+Acidity inhibits the functions of the cerebral cortex,
+but stimulates those of the medulla.  This antithetic reaction
+to the stimulus of increased H-ion concentration is an adaptation
+to prevent animals from committing suicide by over-activity,
+for the mechanism for the initiation and control of the
+transformation of energy is in the higher centers of the brain,
+while an essential part of the mechanism for the neutralization
+of acidity--the centers governing circulation and respiration--
+is in the medulla.  This explains many clinical phenomena--
+why excessive acidity causes paralysis, why there is great thirst
+after inhalation anesthesia, after excessive muscular activity,
+excessive emotion--after all those activities which we have found
+to be acid-producing, for water, like air, neutralizes acids.
+The excessive use of alcohol, anesthetics, excessive work,
+intense emotion, all produce lesions of the kidney and of the liver.
+The explanation is found in the fact that all these stimuli
+increase the acidity of the blood.  and that, if long continued,
+the neutralizing mechanism must be broken down and so the end-products
+of metabolism are insufficiently prepared for elimination.
+
+In view of these considerations we may well conclude that the maintenance
+of the normal potential alkalinity of the blood is to be estimated
+as the keystone of the foundation of life itself.
+
+
+
+INDEX
+
+ABDOMEN, diseases of, phylogenetic association and, 44 Acidity,
+227 Adaptive energy, 176 variation in rate of energy discharge,
+177 Adrenalin, Cannon's test for, 134, 196 injection of,
+changes in brain-cells from, 186 Adrenals, 196 brain and,
+relation of, 1.98 diseases of, effect of, on output of energy,
+216 functional study of, 196 histologic study of, 198 Alcohol,
+changes in brain-cells from, 116 Alkalescence, 227 Anemia, pain of,
+77 Anesthesia, 2, 227 anoci-association and, differentiation, 34 effect
+of trauma under, upon brain that remains awake, 3 inhalation,
+cause of exhaustion of brain-cells as result of trauma under,
+8 theory of, 227 Anger, 63, 70 Anoci-association, 34 anesthesia
+and, differentiation, 34 Graves' disease and, 36 prevention
+of shock by application of principle of, 36 Aristotle, 127 Asher,
+:37 Associational centers, dulled, 47 Austin, 2, 55, 173
+
+BASS, 159 Beebe, 213 Benedict, 212 Biologic consideration of
+adaptive variation in amounts of energy stored in various animals,
+176 Brain, adrenals and, relation of, 198 diseases of, effect of,
+on output of energy, 216 effect of trauma under anesthesia oil,
+3 functions, physical state of brain-cells and, relation between,
+111 influence of fear on, 64 Brain-cells, cause of exhaustion
+of as result of trauma under inhalation anesthesia, 8 changes in,
+from alcohol, 116 from drugs, 113 from fatigue, 112 from fear,
+112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform,
+116 from strychnin, 113 in Graves' disease, 116 in infections,
+116 in insanity, 120 in insomnia, 119 histologic changes in,
+in relation to maintenance of consciousness and to production
+of emotions, muscular activity, and fever, 182 physical state,
+brain functions and, relation between, 111
+
+CANNON, 57, 64, 68, 73, 133, 138, 196, 202 Cannon's test
+for adrenalin, 134, 196 Cells, brain-, cause of exhaustion of,
+as result of trauma under inhalation anesthesia, 8 changes in,
+from alcohol, 116 from drugs, 113 from fatigue, 112 from fear,
+112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform,
+116 from strychnin, 113 in Graves' disease, 116 in infections,
+116 in insanity, 120 in insomnia, 119 histologic changes in, in relation
+to maintenance of consciousness and to production of emotions,
+muscular activity, and fever, 182 physical state, brain functions and,
+relation between, Ill Chemical noci-association in infections,
+48 Cold pain, 83 sweat, 27 Contact pain, special, 78 Crying,
+90 in exophthalmic goiter, 106
+
+DARWIN, 12, 26, 30, 91, 127, 153 on phenomena of fear, 26 Disease,
+mechanistic theory of, 157 Distance receptors, discharge of energy
+through stimulation of, 25 Dog, spinal, 4 Dolley, 2, 10 Drugs,
+changes in brain-cells from, 113
+
+ELIOT, 1 Elliott, 202 Energy, adaptive, 176 Energy, discharge, rate of,
+adaptive variation in, 177 nervous, cause of discharge of,
+12 as result of trauma under inhalation anesthesia, 12 discharge of,
+role of summation in, 30 through representation of injury,
+25 through stimulation of distance receptors, 25 psychic discharge,
+25 output of, effect of diseases of adrenals on, 216 of brain on,
+216 of liver on, 216 of muscles on, 216 of thyroid on, 217 rate
+of out put, influences that cause variation in, 177 Environment,
+128, 130 Evacuation pain, 77 Exophthalmic goiter, 66 crying in,
+106 fear and, resemblance between, 68 laughing in, 106
+
+FATIGUE, changes in brain-cells from, 112 Fear, 26, 52, 55 changes
+in brain-cells from, 112 Darwin on phenomena of, 26 Graves'
+disease and, resemblance between, 68 influence of, on brain,
+61 phenomena of, 56 Fly-trap, Venus', 151 Frankel, 68 Frazier,
+82 Functional study of adrenals, 196
+
+GOITER, exophthalmic, 66 crying in, 106 Goiter, exophthalmic, fear and,
+resemblance between, 68 laughter in, 106 Graves' disease, 66
+anoci-association and, 36 changes in brain-cells in, 116 crying in,
+106 fear and, resemblance between, 68 laughter in, 106
+
+HARVEY, 1,57 Headache, 80 Heat pain, 77 production in infections,
+purpose and mechanism, 180 Hemorrhage, changes in brain-cells from,
+113 Hippocrates, 127 Histologic changes in liver, 205 study of adrenals,
+198 Hitchings, 173 Hodge, 10 Hornaday, 26 Hydrogen ion concentration
+in activation of kinetic system, 217 Hyperthyroidism, 42
+
+INFECTIONS, changes in brain-Cells in, 116 chemical noci-association in,
+48 heat production in, purpose and mechanism, 180 pain of,
+79 Inhalation anesthesia, cause of exhaustion of brain-cells as result
+of trauma under, 8 trauma under, cause of discharge of nervous energy
+as result of, 12 Insanity, changes in brain-cells in, 120 Insomnia,
+changes in brain-cells in, 119 effect of, 205
+
+Iodoform, changes in brain-cells from, 116
+
+KINETIC diseases, 219 reaction, 93 system, 173
+
+LABOR pains, 79 Laughter, 90 causes of, 91 in exophthalmic goiter,
+106 Law, Sherrington's, 24 Light pain, 77 Liver, diseases of, effect of,
+on output of energy, 216 histologic changes in, 205 Livingstone,
+148 Lower, 42
+
+MALARIA, 159 McKenzie, 162 Mechanistic theory of disease, 157 view
+of psychology, 127 Medical problems, phylogenetic association
+in relation to, 1 Menten, 2, 55, 173, 218, 227 Muscles, diseases of,
+effect of, on output of energy, 216
+
+NAGGING, 46 Nausea pains, 78 Nervous energy, cause of discharge of,
+12 as result of trauma under inhalation anesthesia, 12 discharge of,
+role of summation in, 30 through representation of injury,
+25 through stimulation of distance receptors, 25 psychic discharge,
+25 Neurasthenia, sexual, 43 Neuroses, postoperative, 46 traumatic,
+46 Noci-association, chemical, in infections, 48 Nociceptors,
+14 diseases and injuries of regions not endowed with, 47
+
+PAIN, 77, 107, 144, 158 cold, 83 contact, special, 78 evacuation,
+77 heat, 77 labor, 78 light, 77 nausea, 78 of anemia, 77 of infection,
+79 pleasure, 78 post-operative, 89 site of, 83 traumatic, 89 Personality,
+47 Phylogenetic association, diseases of abdomen and, 44 in relation
+to certain medical problems, 1 to emotions, 55 Pleasure pains,
+78 Postoperative neuroses, 46 pain, 89 Propagation of species,
+152 Psychic discharge of energy, 25 Psychology, mechanistic view, 127
+
+REACTION, kinetic, 93 Receptors, distance, discharge of energy
+through stimulation of, 25 sexual, 53 ticklish, 19
+
+SELF-PRESERVATION, 152 Sexual neurasthenia, 43 Sexual receptors,
+53 Sherrington, 12, 13, 14, 24, 25, 48, 52, 132, 136, 158 Sherrington's
+law, 24 Shock, prevention of, by application of principle of
+anoci-association, 36 Sloan, 2, 14, .55, 173 Spinal dog, 4 Starling,
+195, 227 Strychnin, changes in brain-cells from, 113 Summation,
+role of, in discharge of nervous energy, 30 Sweat, cold, 27
+
+TEST, Cannon's, for adrenalin, 134, 196 Thyroid gland, 213 diseases of,
+effect of, on output of energy, 217 Ticklish receptors,
+19 Trauma, cause of exhaustion of brain-cells as result of,
+under inhalation anesthesia, 8 effect of, under anesthesia,
+upon brain that remains awake, 3 under inhalation anesthesia,
+cause of discharge of nervous energy as result of, 12 Traumatic neuroses,
+46 pain, 89
+
+VAUGHAN, 180 Venus' fly-trap, 149, 151
+
+WEEPING, 90 Welch, 1 Wells, 227 Williams, 231 Worry, 74
+
+
+
+
+
+End of The Project Gutenberg Etext of Origin and Nature of Emotions**
+