Part 4

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[*]

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.