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?