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 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.