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 Miylogenetic Association 
 _.i Relation to Certain 
 Medical Problems 
 
 Ether Day Address 
 1910 
 
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Phylogenetic Association 
 in Relation to Certain 
 Medical Problems 
 
 GEORGE W. CRILE, M.D. 
 
 Cleveland, Ohio 
 
 Ether Day Address 
 1910 
 
Digitized by the Internet Archive 
 
 in 2010 with funding from 
 
 Open Knowledge Commons 
 
 
 http://www.archive.org/details/phylogeneticassoOOcril 
 
PHYLOGENETIC ASSOCIATION IN RELA- 
 TION TO CERTAIN MEDICAL 
 PROBLEMS.* 
 
 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 first pause 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 grati- 
 tude for the blessings of anesthesia. Two years ago 
 an historical appreciation of the discovery of ether 
 was here presented by Professor Welch, and last 
 year an address on medical research was given by 
 President Eliot. I, therefore, will not attempt a gen- 
 eral address, but will present an experimental and 
 clinical research. 
 
 Time will permit the presentation of only the sum- 
 maries of the large amount of data. The great 
 assistance rendered by my associates, Dr. D. H. 
 Dolley, Dr. H. G. Sloan, Dr. J. B. Austin and 
 Dr. M. L. Mentenf, I acknowledge with gratitude. 
 
 ♦Address delivered at the Massachusetts General Hospital on the 
 sixty-fourth anniversary of Ether Day, Oct. 15, 1910. 
 
 +From H. K. Cushing Laboratory of Experimental Medicine, Western 
 Reserve University, Cleveland. 
 
 3 
 
The scope of the title of this paper may be ex- 
 plained by a concrete example. 
 
 When a barefoot boy steps on a sharp stone there is 
 an immediate discharge of nervous energy in his effort 
 at escape from the wounding stone. This is not a vol- 
 untary act. It is not due to his own personal experience 
 (i.e., his ontogeny), but is due to the experience of 
 his progenitors during the vast periods of time re- 
 quired 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 appro- 
 priate discharge of nervous energy automatically 
 followed. If the sole of the foot is repeatedly bruised 
 or crushed by the stone, shock may be produced. If 
 the stone be only lightly applied, then there is also a 
 discharge of nervous energy from the sensation of 
 tickling. The body has had implanted within it in a 
 similar manner other mechanisms of ancestral or phy- 
 logenetic 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 including 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 set up by a 
 surgical operation still reach the brain. We know 
 that not every portion of the brain is fully anesthe- 
 tized, since surgical anesthesia does not kill. The 
 
 4 
 
question then is, What effect has trauma under surgi- 
 cal anesthesia upon the part of the brain that remains 
 awake ? If, in surgical anesthesia, the traumatic 
 impulses cause an excitation of those wide-awake 
 cells, are the remainder of the cells of the brain, 
 despite anesthesia, influenced in any way? If influ- 
 enced, they are prevented by the anesthesia from 
 expressing the same in conscious perception or in 
 muscular action. Whether the anesthetized cells are 
 influenced or not must be determined by noting the 
 physiologic function 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 anesthe- 
 sia. If the trauma is sufficient, exhaustion of the 
 entire brain is observed after the effect of the anes- 
 thetic is worn off ; that is to say, despite the complete 
 paralysis of voluntary motion and the loss of conscious- 
 ness 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. As 
 to 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 answered by the following experi- 
 ments, viz : the circulation of animals was first ren- 
 dered static by over-transfusion, and was controlled by 
 a continuous blood-pressure record on a drum, the 
 factor of anemia was thereby wholly excluded during 
 the application of the trauma and during the removal 
 of a specimen of brain tissue for histologic study. In 
 every such instance morphologic changes in the cells 
 
 5 
 
of all parts of the brain were found, but it required 
 more trauma to produce equal morphologic changes 
 in animals protected against low blood pressure than 
 in animals whose blood pressure gradually declined in 
 the course of the experiments. 
 
 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 are prevented from reaching 
 the brain by cocaine blocking, then, despite the inten- 
 sity 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. A still further 
 negative evidence that inhalation anesthesia offers 
 little or no protection to the brain cells from trauma is 
 derived from the following experiment : A dog whose 
 spinal cord had been divided at the level of the first 
 dorsal segment, and then kept in good condition for 
 two months, showed a recovery of the spinal reflexes, 
 such as the scratch reflex, etc. This animal is known 
 as a "spinal' 1 dog. Now, in this animal the abdo- 
 men and hind extremities have no direct nerve con- 
 nection with the brain. In such a dog a continuous 
 severe trauma of the abdominal viscera and of the 
 hind extremities lasting four hours was accompanied 
 by but slight change in either the circulation or in the 
 respiration, and no microscopical alteration of the 
 brain cells. Judging from a large number of experi- 
 ments on normal dogs under ether, such an amount 
 
 6 
 
of trauma would have caused not only a complete 
 physiologic exhaustion of the brain, but also morpho- 
 logic alterations of all of the brain cells and physical 
 destruction of many. We must, therefore, conclude 
 that, although ether anesthesia produces unconscious- 
 ness, 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 
 oxide anesthesia there is approximately only one- 
 fourth the exhaustion on equal trauma as under ether ; 
 either nitrous oxide protects or ether predisposes to 
 exhaustion under trauma. With this as a point of 
 departure we will inquire into the cause of this ex- 
 haustion of the brain cells. 
 
 On the Cause of the Exhaustion of the Brain Cells 
 
 from Trauma of Various Parts of the Body Under 
 
 Inhalation Anesthesia. 
 
 Numerous experiments on animals upon the effect 
 of ether anesthesia per se, i.e., ether anesthesia with- 
 out trauma, showed that although certain changes 
 were seen there was neither the characteristic physio- 
 logic exhaustion after the anesthesia had worn off nor 
 were there seen the characteristic changes in the 
 brain cells. Turning to trauma, in a study of the 
 behavior of individuals as a whole under deep and 
 under light anesthesia, we at once found the cue to 
 the discharge of energy, — the consequent physiologic 
 exhaustion and the morphologic changes in the brain 
 cells. 
 
 If, in the course of abdominal operations, rough 
 manipulation of the parietal peritoneum is made, there 
 is frequently observed a marked increase in the res- 
 piratory rate and an increase in the expiratory force, 
 
 7 
 
even to the extent of an audible expiratory groan. 
 Under light ether anesthesia severe manipulation of 
 the peritoneum often causes such vigorous contrac- 
 tions of the abdominal muscles that the operator may 
 be greatly hindered in his work. 
 
 Among the unconscious responses to trauma under 
 ether anesthesia are purposeless moving, withdrawing 
 of the injured part, and if the anesthesia is sufficiently 
 light and the trauma sufficiently strong, there may be 
 an effort directed toward escape from the injury. In 
 injury under ether anesthesia every grade of response 
 may be seen, from the slightest change in the respira- 
 tion 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 at escape from the injury. 
 
 Can anyone picture the actual result of a formi- 
 dable abdominal operation extending over a period of 
 half an hour or more in an unanesthetized human 
 patient if extensive adhesions are broken up, or if a 
 large tumor is 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 the patient not suffer complete exhaustion ? If 
 the traumata, under inhalation anesthesia, be suffi- 
 ciently strong and repeated in sufficient numbers, the 
 brain cells will finally be deprived of their discharge- 
 able nervous energy and become exhausted just as 
 exhaustion follows a strenuous and too prolonged 
 muscular exertion, for example, such as is seen in 
 endurance tests. Whether the nerve energy of the 
 brain is discharged by injury under anesthesia, or 
 whether by ordinary muscular exertion, identical mor- 
 phologic changes are seen in the nerve cells. In 
 
 8 
 
shock from injury, in exhaustion from overwork 
 (Hodge and Dolley) and in exhaustion from pure 
 fear, the general functional weakness is similar, — in 
 each a certain length of time is required to effect re- 
 covery, 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, viz : what de- 
 termines the discharge of energy from trauma with or 
 without inhalation anesthesia ? 
 
 On the Cause of the Discharge of Nervous Energy 
 
 from Trauma in Animals Under Inhalation 
 
 Anesthesia as Well as in the Normal 
 
 State with Special Reference to 
 
 Medical Problems. 
 
 I looked into this problem from many view-points 
 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. There is, of 
 course, no direct final proof of the truth of even the 
 doctrine of evolution. It is idle to consider any ex- 
 perimental research into the cause of phenomena that 
 have by natural selection required millions of years to 
 develop. Nature has made the experiments on a 
 world-wide scale ; the data are before us for interpre- 
 tation. Darwin could do no more than collect all 
 available facts and then frame an hypothesis that best 
 harmonized the facts. Sherrington, that masterly 
 physiologist, in his volume entitled " The Integrative 
 
 9 
 
Action of the Nervous System," shows clearly how 
 the central nervous system was built up in the proc- 
 ess 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 anatomical forms. I 
 will assume, therefore, that the discharge of nervous 
 energy is accomplished by the application of the law 
 of inheritance and association, and that this hypothesis 
 will explain many clinical phenomena. I shall 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 on this 
 hypothesis. 
 
 According to the doctrine of evolution, every func- 
 tion owes its origin to natural selection in the struggle 
 for existence. In the lower and simpler animal life, 
 indeed, in our human progenitors as well, existence 
 depended principally upon the success with which 
 three great purposes were achieved, viz : (l) 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 bio- 
 logic sense this statement holds for man of to-day. 
 Disregarding for the present the expenditure of energy 
 for procuring food and for procreation, we will consider 
 the discharge of energy in self-preservation. The 
 mechanisms for self-defense which we now possess 
 were developed in the course of vast periods of time 
 from the lowest forms through all the intermediary 
 stages to our present estate. One would expect, 
 therefore, that we are now in possession of mechan- 
 isms which still may discharge energy on adequate 
 
stimulation but are not suited to our present needs. 
 We shall point out such examples. As Sherrington 
 has stated, there is interposed between ourselves and 
 the environment in which we are immersed, our skin, 
 in which are implanted many receptors for receiving 
 specific stimuli which are transmitted to the brain. 
 When these stimuli reach the brain, there is a specific 
 response principally in the form of muscular action. 
 Now, each receptor can only be adequately stimulated 
 by the particular factor or factors in the environment 
 which created the necessity for the receptor in ques- 
 tion. Thus there have arisen receptors for touch, for 
 temperature, for pain, etc. The receptors for pain 
 have been designated noci-ceptors (nocuous or harmful 
 influences) by Sherrington. 
 
 On the basis of natural selection, only the regions 
 of the body that have been during long periods of time 
 exposed to injury could have developed noci-ceptors. 
 On this ground the finger, because it is exposed, should 
 have many noci-ceptors, while the brain, though the 
 most important organ of the body, because it has been 
 during a vast period of time protected by a skull, should 
 have no noci-ceptors. 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 removal of the skull and dura under ether 
 anesthesia and under local anesthesia. Then various 
 portions of the hemispheres were slowly but completely 
 destroyed by rubbing with a piece of gauze. In some 
 instances the hemisphere was destroyed by burning. 
 In no instance was there more than a slight response 
 of the centers governing circulation and respiration, 
 and there was no morphologic change noted in a histo- 
 logic study of the brain cells of the uninjured hemis- 
 
phere. The experiment was as completely negative 
 as the experiments on the "spinal" dog. Clinically 
 I have confirmed the experimental findings in the 
 course of explorations for brain tumor with a probe in 
 conscious patients. Such explorations elicited neither 
 pain nor evidence of altered physiologic functions. 
 The brain, therefore, contains no mechanism, — no 
 noci-ceptors, — the direct stimulation of which could 
 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 purposive nerve mus- 
 cular 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 dis- 
 charge of nervous energy on receiving trauma. The 
 various tissues and organs of the body are differently 
 endowed with injury receptors, or the noci-ceptors of 
 Sherrington. The abdomen and chest when trauma- 
 tized stand first in their facility for causing the dis- 
 charge 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 that this physical 
 type or that physical type of trauma elicits different 
 responses as to the discharge of energy. Because it is 
 such a commonplace, one scarcelv realizes the impor- 
 tance of the fact that clean-cut wounds with a razor- 
 like knife cause the least reaction, while a tearing, 
 crushing trauma causes the greatest response. It is 
 a suggestive fact that the technic of the carnivora in 
 fighting each other and in killing their prey is probably 
 the most efficient shock-producing trauma known. In 
 the course of evolution this may well liave been the pre- 
 dominating type of trauma to which our progenitors were 
 subjected. 
 
 12 
 
The discharge of energy caused by an adequate me- 
 chanical stimulation of the noci-ceptors is best ex- 
 plained in accordance with the law of phylogeny and 
 association. That is, injuries awaken such reflex 
 actions as have by natural selection been developed 
 for the purpose of self-protection. Adequate stimu- 
 lation of the noci-ceptors for pain is not the only means 
 of causing a discharge of nervous energy. Nervous 
 energy may also be discharged by adequate stimula- 
 tion of the various ticklish regions of the body. The 
 entire skin surface of the body contains delicate tick- 
 lish receptors. These receptors are closely related 
 to the noci-ceptors for pain, and their adequate stimu- 
 lation by an insect-like touch causes a discharge of 
 energy — a nerve muscular reaction — resembling 
 that of brushing off insects. This reflex is similar to 
 the scratch reflex elicited in the dog. This 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 im- 
 portance to the safety of the animal. A similar tick- 
 lish zone guards the nasal chambers. The discharge 
 of energy here takes such form as effectively to dis- 
 lodge the foreign body. The larynx is exquisitely 
 ticklish, and in response to adequate stimulus, energy 
 is discharged in the production of a vigorous cough. 
 The mouth and pharynx have active receptors which 
 cause the rejection of nocuous substances. The con- 
 
 13 
 
junctival reflex, though not classed as ticklish, is a 
 most efficient self-protective reflex. I assume that 
 there is no doubt as to the meaning of the adequate 
 stimuli and the nerve-muscular response of the 
 various ticklish receptors of the surface of the skin, 
 of the ear, the nose, and the eye, and the larynx. 
 These mechanisms were developed by natural selec- 
 tion as protective measures against the intrusion of 
 insects and foreign bodies into regions of great im- 
 portance. The discharge of energy in these instances 
 is in accordance with the law of inheritance and asso- 
 ciation. 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 estab- 
 lished 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 
 that of a tooth-shaped body. The response to tick- 
 ling 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 acquired through vast periods of fight- 
 ing, with teeth and claws. Even puppies at play bite 
 each other in their ticklish points and thus give a reca- 
 pitulation of their ancestral battles and of the real battles 
 to come. The mere fact that animals fight effectively 
 
 14 
 
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 is no 
 book of rules governing the conduct of a fight between 
 animals. The sequences of events follow each other 
 with such kaleidoscopic rapidity that the process is 
 but a series of automatic stimulations and physiologic 
 reactions. Whatever the significance, 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 
 possess 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 com- 
 pletely exhausted as though he had experienced a 
 major surgical operation or as if he had run a Mara- 
 thon 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 
 these two distinct groups of receptors, the noci and 
 the sexual, cause 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 forcibly to obstruct 
 the mouth and the nose, threatening asphyxia. 
 Neither friend nor foe is trusted, and a desperate 
 struggle for air ensues. It will be readily granted 
 that the efforts 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 of self-preservation. No patient views with 
 equanimity the application of shackles preparatory to 
 anesthesia for an operation. 
 
 We have now considered some of the causes of the 
 discharge of nervous energy due to various types of 
 harmful physical contact, and have suggested analo- 
 gous though antithetical sexual receptors. The re- 
 sponse to the adequate stimuli of each of the several 
 receptors is a discharge of nerve muscular energy of 
 a specific type : One type 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 in 
 response to sexual and to painful stimuli. 
 
 According to Sherrington, a given receptor has a 
 low threshold for only one, its own — hence a specific 
 stimulus and a high threshold for all others ; that is, 
 the doors that guard the nerve paths to the brain are 
 opened only on receiving the proper password. 
 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 per- 
 form acts, 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 re- 
 ceptors 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 success- 
 fully compete for the final common path, with the 
 stimulus of a noci-ceptor. The stimulus of a fly on 
 
 16 
 
the nose would be at once superseded by the crushing 
 of a finger. In quick succession do the various re- 
 ceptors (Sherrington) occupy the final common path, 
 but each stimulus is for the time always the sole pos- 
 sessor, hence the nervous system is integrated (con- 
 nected up) to act as a whole. Each individual at 
 every moment of its life has a limited amount of dis- 
 chargeable nervous energy. This energy is at the 
 disposal of any stimulus that obtains possession of the 
 final common path, i.e., the performance of acts. Each 
 discharge of energy is subtracted from the sum total, 
 and whether the subtractions are made by the excita- 
 tion of noci-ceptors by trauma, by tickling, by fighting, 
 by fear, by flight or by the excitation of sexual re- 
 ceptors, singly or in combination, the sum total of 
 expenditure of energy, if large enough, produces 
 exhaustion. Apparently there is no distinction be- 
 tween 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 dis- 
 charge of energy is specific for each type of stimula- 
 tion. 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 Receiptors, or Through Representation 
 
 of Injury {Psychic) . 
 
 We will now turn from the discussion of the dis- 
 charge of nervous energy by mechanical stimuli to the 
 discharge of energy through mental perception. 
 Phylogenetic association may arise through the distance 
 receptors as well as through physical contact, viz : 
 through sight, hearing, smell, or by a repre- 
 
 17 
 
sentation of physical experiences. 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 dis- 
 tributed as injury. Animals under the stimulus of 
 fear, according to W. T. Hornaday, not only may 
 exhibit preternatural strength, but also show strategy 
 of the highest order, a strategy not seen under 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 can- 
 not fly and so becomes an easy victim. The phe- 
 nomena 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 fear, we see in the marvelous and 
 inexplicable manner in which perspiration immediately 
 exudes from it. This exudation is all the more re- 
 markable as the surface is then cold, and hence the 
 
 term, ' a cold sweat ' ; whereas the sudorific glands 
 
 18 
 
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 be- 
 comes husky and indistinct, or altogether may 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 ensue ; there 
 is a death-like pallor ; the breathing is labored ; the 
 wings of the nostrils are dilated ; there is a gasping 
 and convulsive motion of the lips, a tremor on the 
 hollowed 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 become rigid, or may be 
 thrown into convulsive movements. The hands are 
 alternately clenched and opened, often with a twitch- 
 ing movement. The arms may be protruded, as if 
 they were 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 soldier may be 
 seized with a sudden panic. As fear arises 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 
 
 *9 
 
soon follows, and the mental powers fail. The intes- 
 tines 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 
 violently, the breathing to be hurried, and the chest 
 to heave, and the nostrils to be dilated. As these ex- 
 ertions 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 emo- 
 tion of fear is strongly felt, though it may not be from 
 any exertion, the same results tend to reappear, 
 through the force of inheritance and association." 
 (Danvin.) 
 
 In an experimental research, we found evidence 
 that the physiologic phenomena of /ewhave a physical 
 basis. This evidence is morphologic alterations in the 
 brain cells, similar to certain stages of surgical shock 
 and in fatigue from muscular exertion. For the pres- 
 ent we will 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 
 on 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, so far as can 
 be determined, all of the functions of the body re- 
 quiring the expenditure of energv and which are of 
 no direct assistance in the effort toward self-preser- 
 
 20 
 
vation are suspended. In voluntary expenditure of 
 muscular energy, such as in the chase, the suspension 
 of other functions is by no means so complete. Fear, 
 hence trauma, may, therefore, drain to the last dreg 
 the dischargeable nervous energy ; therefore, the 
 greatest possible exhaustion may be produced by fear 
 and trauma. This is a distinction between fear and 
 desire. 
 
 There is a factor, however, that influences the dis- 
 charge of energy which I must discuss briefly. I 
 refer to summation. 
 
 Summation. 
 
 In the discharge of energy, summation plays an 
 important role. Summation is attained by the repeti- 
 tion of stimuli at such a rate that each succeeding stim- 
 ulus 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 until it becomes unbearable. This is sum- 
 mation. When a patient requires for a long time 
 frequent painful wound dressings, there is a gradual 
 increase in the acuteness of the pain receptors. This 
 is summation. In a larger sense the behavior of the 
 entire individual gives considerable evidence of sum- 
 mation, 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 nervous energy of man may be dis- 
 charged. The integrative action of the nervous system 
 and the discharge of nervous energy by phylogenetic 
 association may be illustrated by the analogy of an 
 electric automobile. The electric automobile is com- 
 posed of three 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) ; and the controller which is 
 connected with the cells by wiring (the receptors and 
 the nerve fibers) ; and an accelerator button for in- 
 creasing the electrical 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 pur- 
 pose 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, the 
 machine is by this adequate stimulus 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 ex- 
 hausted, 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 top speed 
 
ahead (trauma and fear) , and if the accelerator is on 
 as well (thyroid secretion?), though the machine will 
 not move, the battery will not only soon be exhausted, 
 but the battery elements themselves will be seriously 
 damaged (exhaustion, — surgical shock). 
 
 We have now presented some evidence that nerv- 
 ous 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 the specific purpose of 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 noci-ceptors. The effect of 
 the adequate stimulus of a noci-ceptor is like that of 
 pressing an electric button that sets in motion great 
 machinery. 
 
 With this conception, the human body is 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 " Ro- 
 setta Stone " which furnishes the key. 
 
 Anoci- Association . 
 
 We are now prepared on the law of phylogenetic 
 association 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 cocaine, there will be no 
 discharge of energv due to the operation; hence, there 
 
 2 3 
 
can be no shock, no exhaustion. Under these condi- 
 tions of operation the nervous system is protected 
 against noci-association whether by noci-perception or 
 by an adequate stimulation of noci-ceptors. The 
 state of the patient in whom all noci-associations are 
 excluded can be described only by coming a new 
 word. That word is " anon- association.'''' 
 
 The difference between anesthesia and anoci-asso- 
 ciation 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 hence does 
 not prevent surgical shock nor the train of later nerv- 
 ous impairments so well described by Mumford. 
 Anoci- association excludes fear. pain, shock and post- 
 operative neuroses. Anoci-association is accomplished 
 bv a combination of special management of patients 
 (applied psychology), morphine, inhalation anesthe- 
 sia 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, viz : 
 that the discharge of nervous energy is accomplished 
 bv the law of phvlogenetic association. If this point 
 seems to have been labored, it is because we expect 
 to rear upon this foundation a clinical structure. How 
 does this hvpothesis 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, viz : operation during the state of 
 anoci-association. Assuming there is no unfavorable 
 
 -4 
 
effect of the anesthetic, and no hemorrhage, the nerve 
 cells of the brain cannot be exhausted in the course of 
 a surgical operation except by fear, or trauma, or by 
 both. Fear mav be excluded by narcotics and spe- 
 cial consideration until the patient is rendered uncon- 
 scious bv inhalation anesthesia. Then in addition to 
 inhalation anesthesia, blocking with cocaine the nerve 
 paths between the brain and the field of operation will 
 place the patient in the beneficent state of anoci-asso- 
 ciation, and at the completion of the operation the pa- 
 tient will be as free from shock as at the beginning. 
 In so-called '* fair risks such precautions mav not 
 be necessary, but in cases handicapped bv infections, 
 by anemia, by previous shock and by Graves' disease, 
 etc.. anoci-association mav become vitally important. 
 
 Graves Disease. 
 
 Applying the principle of the discharge of nervous 
 energy bv phylogenetic association, and on the addi- 
 tional hypothesis that in the discharge of nervous 
 energy the thvroid gland is. through the nervous sys- 
 tem, stimulated, we can explain many phenomena of 
 Graves' disease and possibly supply some of the factors 
 to explain both the genesis and the cure of the disease. 
 
 In the wild state of animal life in which only the 
 fittest survive in the struggle for existence, every 
 point of advantage mav have selection value. An an- 
 imal engaged in battle or in a desperate effort at es- 
 cape will be able to give a better account of itself if 
 it has some means of accelerating the discharge of 
 energy, some influence like that of oil upon the kin- 
 dling fire. There is evidence, though perhaps not 
 conclusive, that such an influence is exerted by the 
 thvroid °;land. This evidence is as follows : In mvxe- 
 
dema, a condition characterized by a lack of thyroid 
 secretion, there is a dulness of reflexes, and of intel- 
 lect, 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 greatly sharpened, 
 energy is discharged with very greatly increased facil- 
 ity, and metabolism is at a maximum. The same 
 holds true in the administration of thyroid extract in 
 large doses in normal subjects. In the course of 
 sexual activities there is an increased action of the 
 thyroid as indicated by an increased size and vascu- 
 larity of the thyroid. In fear and in injury in cases 
 of Graves' disease the thyroid is probably stimulated to 
 increased activity as indicated by the increased activity 
 of the thyroid circulation, by an increase in the size of 
 the gland, by presenting the histologic appearance of 
 activity in the nucleus 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, especially depressive influences, such as nerv- 
 ous shocks, worry and nervous strain, disappointment 
 in love, business reverses, illness and death of rela- 
 tives and friends. The association of activity of the 
 thyroid with procreation is well known, hence the in- 
 cidence of the double strain of overwork or of fear 
 and the sexual evolution in maturing girls is obviously 
 favorable to the development of Graves' disease. 
 The presence of a colloid goiter is a suitable soil for 
 the development of Graves' disease. I fully recog- 
 nize the evidence that infection or auto-intoxication 
 
 26 
 
may be contributing factors and must be assigned 
 their role. 
 
 I have never known a case of Graves' disease to 
 develop from success or from happiness alone, nor 
 from hard physical labor, unattended by strain, nor 
 from the results of energy voluntarily discharged. 
 Some cases seem to have had their origin in over-do- 
 sage of thyroid extract in too vigorous an attempt to 
 cure a colloid goiter. In Graves' disease one of the 
 most striking characteristics is the patient's loss of 
 control and an increased susceptibility to stimuli, espe- 
 cially to trauma and to fear and to the administration 
 of thyroid extract. It has been shown that the vari- 
 ous 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. This is clearly demonstrated in the brains 
 of rabbits subjected to fear alone. Of special interest 
 is the effect of daily fright. In this case the brain 
 cells show a distinct change, although the animal is 
 subjected to no fear for twenty-four hours before it is 
 killed. Now, a great distinction between man and 
 the lower animals is the greater control man has ac- 
 quired over his actions. This quality of control, hav- 
 ing 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 
 Graves' disease there has been demonstrated in a 
 typical case a marked morphologic change in the 
 brain cells. As previously stated, the origin of many 
 cases of Graves' disease is associated in a broad sense 
 with some noci-influence. If this influence causes 
 stimulation of both the brain and the thyroid, its ex- 
 
 27 
 
cessive action may cause impairment of the brain and 
 hyperplasia of the thyroid as well. As self-control is 
 impaired, fear obtains ascendency and, pari passu, 
 would stimulate the thyroid still more actively. Finally, 
 the fear of the disease itself becomes a noci-stimulus. 
 As the thyroid secretion causes an increase in the 
 facility for the discharge of nervous energy, there is 
 established a pathologic reciprocal interaction between 
 the brain and the thyroid. The effect of the con- 
 stantly 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. 
 Cure may be greatly facilitated by a complete rest cure. 
 A cure implies the return of the brain cells to their 
 normal state, with the re-establishment of the normal 
 self-control, and the restoration of the thyroid to its 
 normal state. Then the impulses of daily life will 
 once more have possession of the final common path 
 and the noci-influence be dispossessed. The discov- 
 ery of the real cause of a given case of Graves' dis- 
 ease is frequently difficult because the exciting cause 
 may be personal and is "painful. Of extreme interest 
 is the fact that the patient in the acute stage may be 
 unable to refer to the real cause without exhibiting an 
 exacerbation of the symptoms of the disease. I pre- 
 sume no case should be regarded as cured until refer- 
 ence can be made to the cause without an abnormal 
 reaction. It has been established that in Graves' dis- 
 ease injury to any part of the body even under inhala- 
 tion anesthesia causes an exacerbation of the disease. 
 
 28 
 
Fear alone may cause an acute exacerbation. These 
 acute exacerbations are frequently designated " hyper- 
 thyroidism " and are the special hazard of operation. 
 
 In operating on subjects of Graves' disease on the 
 principle of anoci-association, there is scarcely a change 
 in the pulse, in the respiration or in the nervous state 
 at the close of the operation. Against the effect of 
 the inflowing stimuli from the wound after the cocaine 
 has worn off I know no remedy. It is necessary, 
 therefore, in the serious cases not to venture too far. 
 Since the adoption of this new method (anoci-associa- 
 tion) my operative results have been so vastly improved 
 that I now regard no case of Graves' disease as in- 
 operable, at least to the extent of making a double 
 ligation. 
 
 If we believe that a continuous stimulation of both 
 the brain and the thyroid gland, on the law of phylo- 
 genetic association, 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 is severed, or if the lobe is excised 
 and the patient is reinforced by a sojourn in a sanato- 
 rium, or some environment free from former noci-asso- 
 ciation, the patient will, providing the brain cells, 
 the heart or other essential organs have not suffered 
 irreparable damage, be restored to normal health. 
 There are still many missing links, and the foregoing 
 is not offered as a final solution, although many of the 
 phenomena from the view-point of the surgeon are 
 
 explicable. 
 
 Sexual JVeur asthenia. 
 
 The state of sexual neurasthenia is in many re- 
 spects analogous to that of Graves' disease. In the 
 
 29 
 
sexual reflexes summation leads to hyper-excitability 
 to psychic and mechanical stimuli of a specific tvpe 
 analogous to the hyper-excitability in Graves' disease 
 to trauma and fear ; both are based on the law 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 other 
 agencies and thus exclude the associational stimuli 
 until the nervous mechanism has again become re- 
 stored to the normal. 
 
 Interpretation of Some of the Phenomena of Certain 
 
 Diseases of the Abdomen on the Hypothesis of 
 
 Phylogenetic Association. 
 
 On the law of phylogenetic association, it is prob- 
 able that many of the phenomena of certain lesions in 
 the abdominal cavity become explicable. The noci- 
 ceptors in the abdomen, like noci-ceptors elsewhere, 
 have been established by some kind of injury to which 
 this region has been frequently exposed over vast 
 periods of time. On this premise, we could at once 
 predict that there are no noci-ceptors for heat within 
 the abdomen because during countless years the in- 
 tra-abdominal region has not come in contact with 
 heat. That this inference is correct is shown by the 
 fact that the application of a thermocautery to the in- 
 testines when completing a colostomy in a conscious 
 patient is absolutely painless. One could also pre- 
 dict the fact that there are no touch receptors in the 
 abdominal viscera, hence 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 noci-ceptors which are adapted 
 
 30 
 
for their specific protective purposes, and when ade- 
 quately stimulated respond in a specific manner on 
 the law of phylogenetic association, so the abdominal 
 viscera have developed equally specific noci-ceptors as 
 a protection against specific nocuous influences. The 
 principal harmful influences to which the abdominal 
 viscera may have been long exposed are deep tearing 
 injuries by teeth and claws in the course of the in- 
 numerable struggles of our progenitors with each 
 other and with their enemies ; the perforation of the 
 intestinal tract from ulcers, injuries, appendicitis, 
 gallstones, etc., causing peritonitis ; and over-disten- 
 tion of the hollow viscera from various forms of ob- 
 struction. Whatever may be the connection, it is a 
 fact that the type of trauma from fighting corresponds 
 nicely to that which in the experimental laboratory 
 causes the most shock. Division of the intestines 
 with a sharp knife causes no pain, but pulling on the 
 mesentery elicits pain. Likewise, ligature of 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 
 intestines causes great pain, but sharp cutting or 
 burning causes none. In the abdominal viscera, like 
 the superficial parts, noci-ceptors have been pre- 
 sumedly developed by specific harmful influences, and 
 each noci-ceptor is open to stimulation only by the 
 particular type that produced it. 
 
 As we have just stated, pain is associated with the 
 excitation of noci-ceptors, and these may take prece- 
 dence over and dispossess the routine functions, such 
 as peristalsis, secretion and absorption, of their occu- 
 pancy of their respective nervous mechanisms, just as 
 
 31 
 
fear does. Hence, the loss of weight, the lassitude, 
 the indigestion, the constipation and the many altera- 
 tions in the function of the various glands and organs 
 of the digestive system in chronic appendicitis, chronic 
 gall-bladder disease, may be explained. This hy- 
 pothesis readily explains the extraordinary improve- 
 ment in the digestive functions and the general health 
 following the removal of an appendix so slightly al- 
 tered physically that only the clinical results in many 
 cases could persuade one that this change could be an 
 adequate cause for such far-reaching and important 
 symptoms. It would equally explain certain gall- 
 bladder phenomena — the indigestion, loss of weight, 
 disturbed functions, etc. This hypothesis may supply 
 the explanation of the disturbance from an active anal 
 fissure, which is a potent noci-associator, and the con- 
 sequent disproportionate relief after the trivial opera- 
 tion for its cure. Noci-association would well explain 
 the great functional disturbances of the viscera imme- 
 diately following abdominal operations. 
 
 Post-operative and traumatic neuroses are at once 
 explained on the ground of noci-association, with the 
 resulting strain upon the brain cells, causing 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 he must not be afraid be- 
 cause in nine chances out of ten 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. 
 Yet this is much the same position in which some 
 surgical patients are placed. In railway wrecks we 
 can readily understand the striking difference between 
 the conscious passenger and the sleeping or drunken 
 
 3 2 
 
one. In the latter persons the noci-ceptors and re- 
 ceptors were not aroused, hence their immunity. In 
 the functional disturbances of the pelvic organs asso- 
 ciation and summation may play a large role. On 
 this hypothesis many cases of neurasthenia may well 
 be explained. In the behavior of the individual as a 
 whole summation may well be a scientific expression 
 for "nagging." Many other pathologic phenomena 
 may be explained in a similar manner. Thus we can 
 better understand the variation of a gastric analysis in 
 a timid patient alarmed over his condition and afraid 
 of the hospital. He is integrated by fear, and fear 
 taking precedence over all other impulses, no organ 
 functionates normally. On the same ground, 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 is 
 equal 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, in- 
 spires, 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 on 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, are helpful. On the contrary, any 
 fragment of associational evidence of despair or mis- 
 fortune, whether it be the corrugated brow, the 
 gloomy silence of despair, a doubtful word, is equally 
 depressing, and so could one add indefinitely to the 
 symbolism that governs our daily lives. Thus, we 
 see that through the law of inheritance and noci-asso- 
 
 33 
 
ciation, we are able to read into the behavior of 
 various diseases a new meaning. 
 
 Observations on Patients Whose Associational Centers 
 
 Are Dulled, and on Diseases and Injuries of 
 
 Regions not Endowed with JVoci-ceptors. 
 
 Reversing the order, let us 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 man with associational centers 
 keen and man with these centers dulled or lost is the 
 contrast between life and death. On the behavior of 
 the individual without associational power much might 
 be said. 
 
 On the laws of adaptation through natural selection, 
 phylogeny and association, one should 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 
 noci-ceptors for cancer, and active noci-ceptors for the 
 acute infections, because against cancer nature has no 
 helpful response to offer and in certain of the acute 
 pyogenic infections the noci-ceptors give the benefi- 
 cent physiologic rest. 
 
 Could we dispossess ourselves of the shackles of 
 psychology, and 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. 
 
 34 
 
Natural Selection and Chemical JVoci-association in 
 the Infections. 
 
 Heretofore we have considered the behavior of the 
 individual as a whole in response to a certain type of 
 noci-influences. We have been thinking in terms of 
 physical escape from gross physical dangers, or grap- 
 pling with gross nerve-muscular enemies of the same 
 or of other species, as related to some problems in 
 medicine. To explain these phenomena we have 
 invoked the aid of the laws of natural selection and 
 phylogenetic association. If our conclusions are cor- 
 rect, then it should follow that in the same laws we 
 can find the explanation of immunity, which, of 
 course, means a defensive response to our microscopic 
 enemies. There should be no more difficulty in 
 building up by natural selection an efficient army of 
 phagocytes, or specific chemical reactions against 
 microscopic enemies, than the building up of the various 
 noci-ceptors for our muscular defense against our 
 gross enemies. That immunity is a chemical reaction 
 is no hindrance to the application of the law of natural 
 selection nor of association. What essential differ- 
 ence 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 ade- 
 quate stimuli by phylogenetic association of a chem- 
 ical nature whereby immune bodies are produced. 
 
 While mentioning this subject I will only raise the 
 question whether or not the specific character of the 
 inaugural symptoms of some infectious diseases may 
 not be due to phylogenetic association. These in- 
 augural symptoms are measurably a recapitulation of 
 
 35 
 
the leading phenomena of the disease in its completed 
 clinical picture. Thus the furious immediate phe- 
 nomena of pneumonia, of peritonitis, of erysipelas, of 
 the exanthemata, show phenomena of exaggeration 
 which are analogous to the phenomena of physical 
 injury and of fear of physical violence. Just as the 
 acute phenomena of fear or the adequate stimulus of 
 noci-ceptors are a recapitulation of phylogenetic 
 struggles, so may the inaugural symptoms of infec- 
 tions be a similar phylogenetic recapitulation of the 
 course of the disease. A certain amount of negative 
 evidence is supplied by the difference between the 
 response of a dose of toxins as compared with a dose 
 of a standard drug. No drug in therapeutic dosage 
 except the iodine compounds causes a febrile re- 
 sponse ; no drug causes a chill ; all specific toxins cause 
 febrile responses, and many cause chills. If a species 
 of animal had been poisoned by a drug over vast 
 periods of time, and if natural selection had success- 
 fully established a self-defensive response, then the 
 administration of that drug would cause the noci- 
 association (chemical) , and a specific reaction analo- 
 gous to that following Coley's toxins might be 
 expected. Bacterial noci-association probably operates 
 through the same law as the physical contact of en- 
 vironment does. But natural selection is impartial. 
 It must be supposed that it acts upon the microscopic 
 invader just as well as upon the host. On this 
 ground one would infer that the bacteria of acute in- 
 fections must have met by natural selection each ad- 
 vance of the immunity of the host by the same law of 
 natural selection. Hence, the fast and furious strug- 
 gle between man and his microscopic enemies merely 
 indicates to what extent natural selection has de- 
 
 36 
 
veloped the attack and the defense respectively. This 
 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 char- 
 acteristics of being ancient enemies. On this hypoth- 
 esis one might understand the high mortality of 
 measles when introduced into a new country. The 
 infecting agency of measles by natural selection has 
 become a powerful enemy of the human race, but the 
 particular race to whom this infection is newly intro- 
 duced has not had the equal advantage of building up 
 its defense by the same law — natural selection. The 
 variation in the effect of auto- and iso-pollution of 
 water may be explained in a similar manner. Im- 
 munity and food assimilation are, therefore, on equal 
 footing. May not the phenomena of anaphylaxis be 
 studied on associational lines ? Then, too, there may- 
 be chemical noci-associations of 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 infec- 
 tions to the laws of natural selection and specific 
 chemical noci-association has been made as a sugges- 
 tion. Since the doctrine of evolution is all or nothing, 
 I have included many phenomena to see how reason- 
 able or unreasonable such an explanation might be. 
 
 Recapitulation. 
 
 The following are the principal points presented : 
 In operations under inhalation anesthesia the nerve im- 
 
 37 
 
pulses 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 path- 
 ologic change in the nerve cells. Under ether anes- 
 thesia the damage is at least four times greater than 
 under nitrous oxide. Inhalation anesthesia is, there- 
 fore, but a veneer, a mask that "covers the deep 
 suffering of the patient." The cause of the exhaus- 
 tion of the brain is the discharge of nervous energy in 
 a futile effort to energize the paralyzed muscles in an 
 effort at escape from the injury just as if no anesthetic 
 had been given. The exhaustion is, therefore, of the 
 same nature as that from over-exertion. 
 
 But if the nerve paths connecting the field of opera- 
 tion and the brain be blocked, then there is no discharge 
 of nervous energy from the trauma, and consequently 
 no exhaustion however severe or prolonged the opera- 
 tion. 
 
 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 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 morphine and 
 scopolamine, which so impair the associational function 
 of the brain cells that immunity to fear is established. 
 Animals whose natural defense is muscular exertion, 
 among which is man, mav have their dischargeable 
 
 38 
 
nervous energy used up by fear alone, by trauma alone, 
 but most effectively by the combination of both. 
 What is the mechanism of this discharge of energy ? 
 It is the adequate stimulus of the noci-ceptors — the 
 electric buttons — and the physiologic response for the 
 purpose of self-preservation. According to Sherring- 
 ton, 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 strong, under other 
 phylogenetic associations, such as the chase and pro- 
 creation. When adequate stimuli are repeated in such 
 a rhythm that the new stimulus is received before the 
 effect of the previous one has worn off, a higher maxi- 
 mum is reached than is possible under a single stimu- 
 lus, however powerful. 
 
 Sexual receptors are implanted into 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 stimulus of 
 the noci-ceptors. The specific response of either the 
 sexual receptors or the noci-ceptors is at the expense 
 of the total amount of nervous energy available at the 
 moment. Likewise, daily labor, which, in the lan- 
 guage of evolution, is the chase, expends nervous 
 energy. However, under the dominance of fear or 
 injury the integration is most nearly absolute and prob- 
 ably every expenditure of nervous energy not required 
 for efforts at self-preservation is arrested ; hence fear 
 and injury drain the cup to the dregs. This is the 
 potential difference between fear and desire, between 
 injury and conjugation. 
 
 What is the practical application of this ? In opera- 
 tive surgery there is introduced a new principle, which 
 
 39 
 
removes from surgery much of the immediate risk 
 from its trauma by establishing anoci-association ; it 
 places on a physical basis certain of the phenomena of 
 fear ; it explains to us the physical basis for the im- 
 pairment of the entire individual under worry or mis- 
 fortune ; the daily noci-associations of the individual 
 as a social unit ; or a noci-influence of a part of the 
 body ; on the other hand, it explains the power of 
 therapeutic suggestion and other influences which serve 
 for the time to change the noci- integration, the physi- 
 cal 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 the 
 genesis of the common cold, the principle is probably 
 equally applicable to the acute infections whose chem- 
 ical noci-association gives rise to many of the phenomena 
 of the disease and explains their cure by natural im- 
 munity and by vaccines ; it 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 during eons of time 
 and amid the vicissitudes of change with perhaps less 
 alteration than the crust of the earth. Whether 
 lodged in man or in the lower animals, they are related 
 to and obey the same general biological laws, thus 
 binding them, that is, ourselves, to the entire past and 
 perform their function on the law of phylogenetic 
 association. 
 
 So long have we directed our attention upon tumors, 
 
 40 
 
infections and injuries that we have not sufficiently 
 considered the vital force itself. We have viewed 
 each anatomical and pathologic part as an entity, and 
 man as an isolated phenomenon in nature. May 
 we not find in the law of adaptation under natural se- 
 lection, and the law of phylogenetic association, the 
 master key that will open to us the explanation of 
 many of the pathologic phenomena as they have al- 
 ready explained many normal phenomena ? 
 
 And may medicine not correlate the pathologic phe- 
 nomena of the sick man with the forces of evolution, 
 as the naturalists have correlated the phenomena of 
 the sound man, — and disease as well as health be 
 given its evolutionary setting ? 
 
 41 
 

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