UNIVERSI DEPARTMENT RSItY /F IENTK)|F F F TORONTO 'SYCHOLOGY McA!NSH8cCO THE MACMILLAN COMPANY NEW YORK • BOSTON • CHICAGO • DALLAS ATLANTA • SAN FRANCISCO MACMILLAN & CO., LIMITED LONDON • BOMBAY • CALCUTTA MELBOURNE THE MACMILLAN CO. OF CANADA, LTD. TORONTO MAN-AN ADAPTIVE MECHANISM GEORGE W. CRILE, F.A.C.S. PROFESSOR OF SURGERY, SCHOOL OF MEDICINE, WESTERN RESERVE UNIVERSITY ; VISITING SURGEON TO THE LAKESIDE HOSPITAL, CLEVELAND EDITED BY ANNETTE AUSTIN, A.B. ffotfe THE MACMILLAN COMPANY 1916 All rights reserved C 594890 T~i0 54 COPYEIGHT, 1916, BY THE MACMILLAN COMPANY. Set up and electrotypcd. Published March, 1916. Xortoooti J. 8. Gushing Co. — Berwick & Smith Co. Norwood, Mass., U.S.A. PREFACE FOR more than twenty years, the general theme treated in this volume has been under investigation in my laboratory and my clinic, and the volumes published during that time have recorded the steps by which I have approached the theories here pre- sented. The accumulated experimental and clinical data are so extensive that summaries only are given in the present volume, which is an argument for the main thesis, that man is essentially an energy-trans- 1 forming mechanism, obeying the laws of physics, as do other mechanisms. In presenting this thesis, cer- tain hypotheses have been freely employed where the data were, insufficient that they may furnish a work- ing basis upon which to accumulate additional data. An hypothesis — incomplete or even false — is so easily demolished that it can do little harm ; while the presentation of a " false fact " may produce per- nicious results. To no one are the imperfections and shortcomings of this presentation more apparent than to the author, who lays no claim to expert knowledge in any one of the several sciences involved in attempting a synthesis •of such wide scope. A review of the literature and the details of most of the researches whose conclusions are used in this viii PREFACE volume are not included here, but will be published elsewhere. Our difficulties and the shortcomings in our argument will be obvious enough even when relieved from references to a massive literature. The work of the laboratory, which since the be- ginning of the research has included some 2500 experiments, has as far as possible been checked and illuminated at every step by the clinical observations made by my associates, Dr. Lower and Dr. Sloan, and by myself. The result of this research, as here presented, is the combined outcome of a large amount of work and enthusiasm on the part of many associates. It represents a generous contribution, not only of labor, but of valuable suggestion and criticism from col- leagues and friends, to whom I wish here to express my gratitude. I am deeply sensible of my obligations to Sir Vic- tor Horsley for the opportunity of beginning this research in his laboratory in 1895 ; and for many valuable suggestions and criticisms ; to Professor Sherrington for reading the original manuscript on " Phylogenetic Association " ; and to Professors G. N. Stewart, W. T. Howard, T. Sollman, and J. J. R. MacLeod of the Western Reserve Medical School, all of whom have generously given me the benefit of their wide experience and scientific knowledge. To the following laboratory and clinical associates I acknowledge my gratitude and indebtedness for assuming much of the burden of experimental de- tails : Dr. Guy H. Fitzgerald, Dr. A. Cudell, Dr. Homer H. Heath, Dr. C. H. Lenhart, Dr. Worth Brown, Dr. PREFACE ix Clyde E. Ford, Dr. H. P. Cole, Dr. D. A. Prendergast, Dr. A. B. Eisenbrey, Miss 0. M. Lewis, Dr. A. M. Tweedie, Dr. Lawrence Pomeroy. To Dr. David H. Dolley, Dr. F. W. Hitchings, and Dr. J. B. Austin I wish particularly to express my deep appreciation of their long, painstaking, and en- thusiastic service in the laboratory ; and for bearing the burden of the major portion of the experimental details. I ana indebted to Dr. Dolley • for making for me the histologic studies of the brain in shock and emotion; to Dr. Hitchings for prolonged and extensive work in every branch of the research, par- ticularly for his work on the adrenals ; for a critical review of the literature ; for devising a method of making actual Pnrkinje cell counts ; and for compil- ing, analyzing, and tabulating the large mass of ex- perimental data ; to Dr. Austin for painstaking work on the histologic changes in the organs and tissues of man and animals, and especially for his extensive histologic study of the brain, which has included the counting and classifying of over one hundred thou- sand brain-cells; to Dr. H. G. Sloan for assuming many of the operative details; for the physiological investigation of the adrenals, and for other clinical and research work ; to Dr. Maud L. Menten for her researches upon the adrenals, the electric fish, and the H-ion concentration of the blood, in its relation to the factors causing exhaustion and death. My thanks are due to Dr. Austin and Mr. John E. Olivenbaum for making the photomicrographs ; to Mr. W. J. Brownlow for original drawings and pho- tographic studies; to Miss Amy F. Rowland for x PREFACE collaboration in the research upon the chemical con- stituents of various organs of animals under condi- tions of activation; and to Dr. W. J. Crozier for reading the manuscript and for valuable suggestions. To my associate, Dr. W. E. Lower, I am heavily indebted for the invaluable assistance he has given me throughout the entire research To Miss Annette Austin I wish to express my special appreciation of her great assistance in com- piling the data from my various monographs, manu- scripts, and papers, as well as from the literature ; and of her aid in their presentation in the following pages. GEOKGE W. CEILE. GUSHING LABORATORY OF EXPERIMENTAL MEDICINE, WESTERN RESERVE UNIVERSITY, January 1, 1915. CONTENTS PAGE INTRODUCTION 1 PART I GENERAL CONSIDERATION OF BIOLOGIC ADAPTA- TION AND ASCENT OF MAN CHAPTER I. ADAPTATION TO ENVIRONMENT 17 PART II THE MECHANISMS OF ADAPTATION: RECEPTOR AND EFFECTOR II. THE NERVOUS SYSTEM 43 III. ADAPTATION BY MEANS OF CONTACT CEPTORS . . 67 IV. ADAPTATION BY MEANS OF CHEMICAL, CEPTORS AND CHEMICAL ACTIVITY 95 V. ADAPTATION BY MEANS OF DISTANCE CEPTORS — EMOTIONS — MENTAL STATES 118 VI. THE KINETIC SYSTEM . ... 157 PART III BIOLOGIC INTERPRETATION OF PHENOMENA OF HEALTH AND DISEASE VII. DISEASES OF THE KINETIC SYSTEM .... 211 VIII. KINETIC DISEASES (Continued) 225 IX. ANOCIATION 242 xi xii CONTENTS CHAPTER PAOR X. CERTAIN PHASES OF THE RELATION BETWEEN THE KINETIC SYSTEM AND GROWTH, PROCREATION AND CHEMICAL PURITY 261 XI. A MECHANISTIC INTERPRETATION OF THE ACTION OF CERTAIN DRUGS 285 XII. ACTION PATTERNS ; CONSCIOUSNESS AND SLEEP . 298 XIII. PAIN, LAUGHTER AND WEEPING 318 XIV. TRANSFORMATION OF ENERGY AND ACIDOSIS . . 340 XV. ELECTRO-CHEMICAL PHENOMENA 356 XVI. THE INDIVIDUAL AS AN ADAPTIVE MECHANISM . . 366 LIST OF ILLUSTRATIONS FIGURE PAGB 1. Protective Coloration of the Rocky Mountain White-tailed Ptarmigan 29 2. The Sussex Man 34 3. Positive Heliotropism of a Marine Worm .... 47 4. Comparison of the Embryos of Man and Other Vertebrates 50 5. Venus' Fly-trap 53 6. Contest between Ant-bear and Puma 76 7. Horror and Agony 124 8. Athlete making a Record Broad Jump 126 9. Finish of One-half Mile Intercollegiate Race . . . 127 10. Athlete breaking the Record for Shot Put . . . .128 11. Anger in Male Gorilla 129 12. Exhausted Suffragist 130 13. Cat Terrified by Dog 131 14. Violent Effort ..133 15. Exhaustion 134 16. Tigress and Cubs at Rest . 135 17. Composure 137 18. Photomicrographs showing Effects of Acute and of Chronic Fright on the Brain-cells of a Rabbit .... 139 19. Case of Exophthalmic Goiter 142 20. Tracing showing Effect of Fear on Adrenal Output of a Cat 146 21. Photomicrographs showing the Effect of Fright on the Brain-cells of a Rabbit 149 22. Photomicrographs showing the Effect of Fright on the Ad- renals of a Rabbit 150 23. Photomicrographs showing the Effect of Fright on the Liver of a Rabbit 151 24. Photomicrographs showing the Effect of Insomnia on the Brain-cells of a Rabbit 166 25. Photomicrographs showing the Effect of Insomnia on the Adrenals of a Rabbit 167 26. Photomicrographs showing the Effect of Insomnia on the Liver of a Rabbit 168 27. Photomicrographs showing the Effect of Exertion on the Brain-cells of a Cat ... 169 XIV FIGURB PA "S . . A. B. Section of normal cerebellum Section of cerebellum of dog after of dog. surgical trauma. . FIG. 54. — EFFECT OF SURGICAL TRAUMA ON THE BRAIN-CELLS OF A DOG. Compare the hypochromatic appearance of the Purkinje cells in B with the deeply colored, intact cells in A. (From photomicrographs, X 310.) Since protection of the patient against fear-producing stimuli before the operation depends largely upon the details of his reception at the hospital, no less than upon his reception in the surgeon's own office, and upon 244 MAN --AN ADAPTIVE MECHANISM his preparation for operation, the intelligent • coopera- tion and understanding of every member of the surgi- cal and hospital staff is indispensable to a realization of a perfected anociation. A. Section of normal adrenal of dog. B. Section of adrenal of dog after surgical trauma. FIG. 55. — EFFECT OF SURGICAL TRAUMA ON THE ADRENALS OF A DOG. Compare A and B, noting the marked signs of disintegration in B. (From photomicrographs, X 1640.) If the natural fear of the approaching ordeal, which is felt by every normal individual, be augmented by tactless words in the surgeon's consulting room, by an ANOCIATION 245 Section of normal liver of dog. Section of liver of dog after surgical trauma. FIG. 56. — EFFECT OF SURGICAL TRAUMA ON THE LIVER OF A DOG. Note the vacuolated spaces, the disappearance of nuclei and general dis- integration of cells in B. (From photomicrographs, X 1640.) ungracious reception at the hospital, by inconsiderate treatment on the part of interne, nurse or orderly, by the sound of clanking instruments or by the rough or forced administration of an anesthetic, then the re- 246 MAN — AN ADAPTIVE MECHANISM sistance of the patient, already lowered by his diseased condition, will be still further lowered. No matter how perfect and non-shocking the actual operative technique itself may be, the outcome will be prejudiced by these early adverse factors. (Figs. 57, 58.) If, however, the preoperative environment of the patient be free from all but the most beneficent sug- gestions ; if his nerves be calmed and his consciousness dulled by the preoperative administration of a sedative ; TEMPERATURE 1OO i i i i 105 i i i i UNDER ORDINARY CONDITIONS AFTER FOURTH OPJULY CELEBRATION — FIG. 57. — CHART SHOWING EFFECT OF EMOTIONAL EXCITEMENT ON THE TEMPERATURE. As a result of a Fourth of July celebration, the children in a ward at Lakeside Hospital showed an average increase in temperature of If degrees F. if a non-suffocating, odorless inhalation anesthetic be employed ; if, during the course of the operation, every division of sensitive tissue, be preceded by the injec- tion of a local anesthetic to cut off from the brain all injurious afferent impulses ; and if this be followed by the injection of a second local anesthetic to protect the patient against the painful period of postoperative adjustment; and if gentle manipulation and sharp dissection be used, — if all these measures be employed, the patient will be protected against all damaging fac- tors except those inherent in the diseased or injured condition from which he is seeking relief. ANOCIATION 247 FIG. 58. — CHARTS SHOWING EFFECT OF FEAR UPON THE PULSE. The patient, a foreigner, was brought to the operating room from the accident ward, pulse and temperature normal. When he found himself in the operating room he was greatly disturbed. It was impossible to make him understand that his leg was not to be amputated, but only a plaster cast applied. Under the stimulus of fear his pulse rose to 150, and he soon developed a temperature of 101.2 degrees. 248 MAN --AN ADAPTIVE MECHANISM To secure complete freedom from noxious physical and psychic stimuli throughout the whole course of the operation, no one anesthetic is entirely adequate, any more than one set of rules of conduct is applicable to 15. C. Section of normal cere- Section of cerebellum Section of cerebellum bellum of dog. of dog after continuous of dog after the con- administration of ether tinuous administration for four hours. of nitrous oxid for four hours. FIG. 59. — COMPARATIVE EFFECTS OF ETHER AND OF NITROUS OXID ON THE BRAIN-CELLS OF DOGS. Compare the hypochromatic and disorganized appearance of the Purkinje cells in B with the hyperchromatic Purkinje cells in C. (From photomicrographs, X 310.) the handling of every case. An intelligent selection and careful combination of anesthetics, adjusted to the needs of the individual patient, is the rule. As a general anesthetic in routine cases, nitrous oxid-oxygen is preferred to ether, for many reasons. It ANOCIATION 249 is odorless and non-suffocating ; a few inhalations are sufficient to induce unconsciousness ; it is less likely to produce nausea than is ether ; and laboratory experi- ments and clinical experience have shown that by the A. B. c. Section of normal Section of adrenal of Section of adrenal of adrenal of dog. dog after continuous ad- dog after continuous ad- ministration of ether for ministration of nitrous four hours. oxid for four hours. FIG. 60. — COMPARATIVE EFFECTS OF ETHER AND OF NITROUS OXID ON THE ADRENALS OF DOGS. Note the disappearance of cytoplasm and of some nuclei and the irregular shapes of other nuclei in B as compared with the general conservation of cytoplasm and the well-shaped abundant nuclei in C. (From photomicrographs, X 1640.) use of nitrous oxid the organs of the kinetic system are actually to a large extent protected against exhaustion from the traumatic impulses of the operation. (Figs. 59, 60, 61.) Ether, however skillfully administered, in- duces a period of psychic stress in the earlier stages of 250 MAN — AN ADAPTIVE MECHANISM its administration; it immediately impairs the im- munity of the patient, since it anesthetizes the phagocytes as well as the patient, and leaves the organism in the position of a citadel threatened by Section of the normal liver of a dog. B. Section of liver of a dog after the continuous administration of ether for four hours. C. Section of liver of a dog after the continuous administration of ni- trous oxid for four hours. FIG. 61. — COMPARATIVE EFFECTS OF ETHER AND OF NITROUS OXID ON THE LIVERS OF DOGS. Although the conservative effect of nitrous oxid is not as evident in the liver as in the adrenals or the cerebellum, yet here also the disappearance of cell substance and of nuclei is much more marked in B than in C. (From photomicrographs, X 1640.) attack while its defenders lie drunk in the trenches ; it also extends the coagulation time of the blood and makes the danger from hemorrhage more certain. Being a fat solvent, ether dissolves many of the lipoids in the brain, the renal epithelium, the liver and else- ANOCIATION 251 where, thus increasing the amount of waste products to be eliminated, laying a heavier task upon the kidneys, and incidentally increasing the liability to pneumonia, embolism and nephritis. In addition, prolonged etherization causes striking histologic changes in the brain, the adrenals and the liver. In the choice of the anesthetic, however, it should be emphasized that the patient is the first consideration, not the prejudice of the surgeon for a certain method. If nitrous oxid-oxygen does not fully anesthetize the patient, as may happen in some cases and frequently happens with inebriates, then sufficient ether to attain the desired end should be added. It should also be borne in mind always that while nitrous oxid-oxygen is the safest of all anesthetics in the hands of an expert in the technique of its administration, it is perhaps the most unsafe in the hands of the inexperienced and there- fore should never be administered except by an anesthetist specially trained in its use. In over 14,000 administra- tions of nitrous oxid by the specially trained anesthe- tists on my staff, there has been no death. With the increasing efficiency of the hospital organ- ization and the growing knowledge of the wonderful qualities of nitrous oxid, preoperative sedatives are required less and less. The peace of mind of the patient having been secured by management and, if needed, by sedatives, and uncon- sciousness induced by inhalation anesthesia, the opera- tion proceeds, each division of nerve-bearing tissue being preceded by the injection of a local anesthetic — novocain in 1-400 solution. The infiltrated parts are subjected immediately to a firm but gentle pressure MAN --AN ADAPTIVE MECHANISM with the hand in order that no nerve in the field of operation may be left free to carry an activating im- pulse to the brain. If the operation be abdominal, first the skin, then the subcutaneous tissue, then the fascia and, finally, the remaining muscle or posterior sheath and the peritoneum are in turn novocainized, subjected to momentary pressure to spread the anes- thetic and then divided within the blocked zone. If the blocking has been complete, then, upon opening the abdomen, the intestines will lie within the abdom- inal cavity, and the abdominal muscles will be com- pletely relaxed. Under these conditions the entire abdomen may be explored without awakening the nociceptor sentinels. If the operative procedure is such that activation is inevitable, ether is added in advance. In suitable cases in which no infection is present, an additional guarantee against postoperative discomfort may be given by an injection of quinin and urea hydrochlorid, in a \ to \ per cent solution. This anesthetic is injected at a distance from the line of incision. Its effects last for several days so that by its use the patient is protected from noxious impulses from the operative field until the healing process has well begun. Results of Anociation The result of a systematic employment of anociation in all cases operated by me in Lakeside Hospital has been to decrease the mortality rate to less than one third the mortality rate before the method of anociation was employed. Unless all facts are known, ANOCIATION 253 however, mere mortality statistics may be of little value to one who contemplates the fact that even a mediocre operator, who possesses the liberty and the judgment to operate only upon those cases which pre- sent the required amount of strength to endure his technique and his hospital organization, can show as low a mortality rate as the most expert operator who is sup- ported by the best trained staff but dealing with graver risks. A better clue to the comparative value of methods is to be found in a study of postoperative mor- bidity records. Here anociation has assuredly proved its superiority. In comparison with the past records of patients operated under the same general conditions of hospital organization and mechanical technique, but without the protection of anociation, the records of the anoci-protected cases show a striking diminution in the long train of distressing conditions which are the usual sequelae to operations under ether anesthesia. Shock, gas pain, nausea and vomiting, backache, asep- tic wound fever, pneumonia, nephritis, painful scar, neurasthenia and hyperthyroidism are all diminished or wholly prevented by operation under anociation. In the diminution of each one of these common sequelce to surgical operations, there is to be found a significant corroboration of the kinetic theory. The Kinetic Theory of Peritonitis and Postoperative Gas Pain The occurrence and prevention of postoperative gas pain may be explained on a biologic basis in the fol- lowing manner : Prior to the era of aseptic surgery, it may be believed that most if not all abdominal wounds 254 MAN --AN ADAPTIVE MECHANISM became infected. Had this state of affairs continued long enough, then, by the law of natural selection, some protective mechanism against infection would have been evolved within the abdomen. The peritoneum possesses such a mechanism, and we believe that the phenomena of gas pain and of peritonitis are parts of a self -defensive reaction. Since infection is most readily spread and increased by movement, immobili- zation of the abdominal muscles in the infected region is a prime requirement in overcoming any abdominal infection. Within the abdomen, immobilization is secured (1) by the inhibition of the intestines ; (2) by the distension of the intestines; (3) by the rigid and persistent contraction of the abdominal muscles ; and (4) by the exudation of a sticky, gluelike fluid. The infected point is thus fixed by paralysis ; by disten- sion ; by rigidity of the abdominal wall; and by gluing. On account of the intestinal inhibition, digestion and absorption cease, and anorexia and vomiting fol- low, as self-protective measures against the dangers of poisonous, broken-down food products. Pain and ten- derness play a part by forcing the maintenance of a boxlike rigidity of the abdomen. As the abdominal walls are rigid, respiratory move- ments are confined to the thorax ; and since the lungs are thus but partially filled, the respiratory rate is in- creased to compensate for the diminished volume of exchanged gases. The increased H-ion concentration due to increased energy transformation also tends to increase the respiratory rate. The diminished respira- tory excursion and consequent partial venous stasis in the lungs predispose to pleurisy and pneumonia. ANOCIATION 255 The loss of water by vomiting, the diminished intake of water and the failure of water absorption cause a rapid shrinkage of the soft parts which is especially noted in the face, while the increased blood supply to the intestines, combined with the diminished intake of water causes a rapid diminution of the pulse volume. The loss of water is followed also by a diminished vol- ume of urine. At the same time metabolism is in- creased, and as a result the acid by-products and the H-ion concentration of the blood are increased. The increased H-ion concentration of the blood stimulates the respiratory center. The loss of water and the in- creased H-ion concentration cause thirst. In this pic- ture of the gamut of the phenomena of peritonitis we see that all are logical results of the activity of a local, self-defense mechanism against infection. Every pen- etration of the peritoneum initiates this protective mechanism whether there is infection or not — hence abdominal operations are usually followed by gas pain. If that portion of the brain through which this adaptive response is made be kept in ignorance of the incision into the peritoneum by progressive novocain blocking during the operation and by quinin and urea hydrochlorid blocking to prevent nerve impulses from reaching the brain after the operation, there should be — and there is — diminished or no gas pain. But if, on the other hand, a single nerve pathway escape the blocking and communicate with the brain, there is gas pain, as would be expected. The same principle is illustrated in the effective treatment of peritonitis by large physiologic doses of opium — the Alonzo Clark treatment. This treatment, 256 MAN --AN ADAPTIVE MECHANISM by depressing the activity of the brain, keeps within safe bounds the defensive activity of the kinetic system, which if uncontrolled is prone to exceed the limit of safety. Pain and muscular rigidity are prevented. Metabolism is held practically at a standstill, so there is little need of food ; peristalsis is inhibited, therefore the intestines are immobile ; and phagocytosis has an opportunity to overcome the infection. This treatment does not replace but supplements surgical treatment. Painful Scar The phenomenon of painful scar, which in origin is akin to many pathological as well as normal conditions, may be explained by the fundamental principle of nerve action that any strong traumatic or psychic stimulus produces a change in conductivity somewhere in the cerebral arc, the effect of which is to lower the thresh- old of that arc. Thus, if a man has been held up at the point of a pistol by a highwayman at a certain street corner, for months afterward whenever he passes that corner that circumstance will be vividly recalled, and perhaps the whole train of activity phenomena follow- ing upon the incident may be recapitulated. The effect of traumatic stimuli is similar. The arc receiving strong traumatic stimuli suffers a lowered threshold and from that time on mere trifles become adequate stimuli. Familiar examples of this are the sensitiveness of limbs after fractures, and the painful stumps of amputated limbs ; the apparent location of the pain being often not in the remaining stump, but in the part amputated. The lesion of a painful scar, therefore, is not at the site of the wound, but in the brain. Now, if an operation ANOCIATION 257 be so performed that no strong traumatic stimulus reaches the brain, either during or after operation, then the threshold to the cerebral arc from the wound will not be lowered, and the scar will yield no abnormal pain. Postoperative or Posttraumatic Nervousness A lowered threshold, resulting from some overwhelm- ing stimulus which predisposes the kinetic system to an uncontrollable discharge of energy in response to trifling stimuli, may explain many abnormal conditions, among them postoperative neurasthenia, which is largely prevented by anociation. It is an unhappy reflection upon surgery that the general public has come to expect that a state of nervous derangement, which may last -from several months to a year or more, is an inevitable sequel to operations. When, in the night, one is suddenly awakened by the consciousness of an impending peril, the brain threshold is immediately lowered, apparently as an adaptation for the more swift and accurate perception of the danger. Hearing, sight and sense of touch are ab- normally acute. A similar state of universally lowered threshold exists after the receipt of a crushing physical injury. In this tense state, minor stimuli produce major effects, and the individual, in common parlance, is "nervous." In an operation under inhalation anes- thesia alone, the unconscious brain has been tortured nearly as much as the conscious brain would be under the same amount of injury and the resultant effect upon the brain threshold is the same. It is not strange that from such an ordeal the patient emerges "nervous" 258 MAN --AN ADAPTIVE MECHANISM and "exhausted," to endure a long period of lessened efficiency, of weeping at trifles, of being easily fatigued, of inability to "control" the steady uncalled-for out- flow of energy which escapes like flood water over a low dam — a state that will continue until the threshold is raised again by the gradual return of the brain to its normal threshold. Aseptic Wound Fever and Postoperative " Hyperthyroidism " The production and the prevention of aseptic wound fever are based, as we believe, upon the physical law that any form of energy may be converted into heat, so that the pain stimuli from a wound may cause the production of both heat and motion. Any stimulus which drives the motor mechanism of the body beyond the point of normal expression will cause fever. Anger, athletic contests, fear, physical injuries, all produce a rapid oxidation, increased temperature and increased acid by-products. In operations under general anes- thesia, especially, we expect to see some postoperative rise of temperature as the result of the activation of the kinetic system by the physical and psychic activation of the operation. Since, by the use of anociation, we are able to minimize postoperative fever, we conclude that, barring infection and the absorption of hemoglobin, fever after operations under general anesthesia alone is the result of increased transformation of energy, due to activation of the kinetic system by trauma and psychic stress. In like manner anociation prevents postoperative " hyperthyroidism " by preventing the activating impulses from reaching the brain during ANOCIATION 259 operations on the thyroid in cases of exophthalmic goiter, thus preventing excessive activation with the resultant excessive acid by-products. Postoperative Pneumonia Many theories have been advanced to account for the more frequent occurrence of pneumonia after operations in the upper abdomen, than after operations in the lower abdomen, on the back or on the extremities. That pneumonia is not due to ether alone is proved by its occurrence after operations under local anesthesia. That it is not due to infection alone is shown by the fact that it occurs as frequently in connection with un- infected as with infected wounds. That it is not due to emboli or thrombosis alone is evident from the fact that superficial wounds are rarely followed by pneu- monia. The clue to the real cause is found in a comparison of the postoperative behavior of patients operated upon under anociation with those operated upon without that protection. After the nocuous operation the wound is tender. As the upper abdominal muscles have spe- cially important respiratory functions, in each respiratory movement these powerful muscles pull on the stitches which hold together the divided wall. The exquisite pain produced by this respiratory pull causes the inhi- bition of the muscular contractions on the side of the incision, or on both sides if the wound be median. As a result, the excursion of the lower chest wall is dimin- ished, so that the lower lobes of the lungs cannot be filled completely. That a lessened exchange of air in the lower lobes predisposes to pneumonia is suggested 260 MAN --AN ADAPTIVE MECHANISM by the frequent occurrence of pneumonia in cases of localized pleurisy, in which pain causes an inhibition of free excursion in the part of the chest which is in- volved. The resultant pneumonia usually occurs in that portion of the lungs whose free action is inhibited. After gall bladder operations, pneumonia begins usually not in the left but in the right lobe, whereas were the pneumonia embolic in its origin, the lobes would probably fare alike. The diminution in the number of cases of postopera- tive pneumonia since the adoption of the technique of anociation is final proof of this theory as to its cause. Because of the lack of local tenderness in the field of operation produced by the technique of the operation itself, and by the postoperative nerve blocking with quinin and urea hydrochlorid, there is diminished or no inhibition of the respiratory excursions. This also, without doubt, explains the reduced mortality of opera- tions for umbilical hernia performed with the transverse incision (Mayo). CHAPTER X CERTAIN PHASES OF THE RELATION BETWEEN THE KINETIC SYSTEM AND GROWTH, PROCREATION AND CHEMICAL PURITY IN taking possession of the final common path in the brain, stimuli of the external environment, as has been stated, observe a definite order of precedence, depending upon the phylogenetic and ontogenetic meaning of each stimulus to the particular organism in question. In general, it may be said that self-preservation stimuli take precedence over species-preservation stimuli. We postulate that the same order of precedence may be observed in responses to the chemical and physical stimuli of the internal environment of the body. The stimuli to growth and reproduction, the stimuli of pregnancy, the stimuli to maintenance of the chemi- cal purity of the body, are constantly struggling within the body for the available supply of transformable energy ; and the nature of the stimulus gaining posses- sion of the final common path determines many condi- tions of health and disease in the organism. Some- times the stimuli of the external environment compete with the stimuli of the internal environment — as when the integration of the body in response to the stimulus of fear interferes with the normal action of the stimuli in response to which nutrition is accomplished — and the sum total of health or disease is the net 261 MAN --AN ADAPTIVE MECHANISM result of the balance struck between these competing stimuli of the two environments. The kinetic system, which is strongly driven by the self-preservative stimuli of starvation, of acute or chronic infection, of physical injury or of overwork ; or which is crippled by the deficient functional activity of the brain, thyroid, liver or adrenals, will have a lessened power to respond to the less urgent and more easily deferred stimuli to growth and reproduction. It is known that children grow slowly who suffer from acute and chronic infections, such as oral sepsis, ton- sillitis, adenoids, middle ear infection, caries of the bone and indigestion ; from impure, improper or insufficient food ; from overcrowding, poor ventilation, overwork, cruelty and pain ; from deficient functional activity of the thyroid, hypophysis, liver, brain or heart. It is also known that after the removal of these bur- dens or deficiencies, and the reestablishment of normal internal and external environments, growth is rapid. This is evidenced by the result of feeding thyroid ex- tract to myxcedematous children ; by the rapid growth after the cure of chronic appendicitis, hip joint disease, tonsillitis, adenoids and chronic mastoiditis ; after the substitution of happiness and content for homesick- ness ; and of good hygiene for bad hygiene. Interfer- ence with growth is in direct proportion to the reduction in efficiency of the kinetic system. It does not matter whether this reduction is the result of a decreased effi- ciency of some one link in the system, or of an increased call upon the stored energy for response to contact ceptor, distance ceptor or chemical stimuli, so that less energy is left for other demands. GROWTH AND CHEMICAL PURITY 263 An impairment of the efficiency of the kinetic system by an impairment of the function of one organ in the system is equivalent to an impairment in effi- ciency through excessive driving of this system — by worry, fear, pain, infection, overwork or by insuffi- cient food. The increased rate of growth in a myxce- dematous patient resulting from thyroid feeding is equal to that effected by removing chronically infected tonsils and adenoids, by providing pure milk and good hygiene for the underfed and neglected child or by stopping overwork, pain and worry. Conversion of Energy for Reproduction The causes which prevent the transformation of en- ergy by the kinetic system for growth also prevent the transformation of energy for reproduction. The same internal and external stimuli which make an excessive demand upon the kinetic system for self-preservative reactions (diminishing or inhibiting the response to growth stimuli), when present in the growing or adult organism, may prevent or retard the development of secondary sexual characteristics, sexual desire, concep- tion and pregnancy. It is known that when the thyroid or adrenals are deficient, the development of secondary sexual charac- teristics is retarded. The development of secondary sexual characteristics may be arrested by excision of the sex glands, and may be delayed by acute or chronic infection, by emotional strain, by auto-intoxication, by pyorrhea alveolaris and by defective hygiene. It is probable that secondary sexual characteristics and normal sexual function are in part the result of 264 MAN --AN ADAPTIVE MECHANISM the action of the internal secretions of the ovaries or testicles upon the kinetic system, by which is produced the kinetic activity required to build up the organs and to create the sex function. Therefore, wherever there is a defect in a link of the kinetic system or absence of efficiency in the ovaries or testicles, there will be a correspondingly diminished expression of sex phenomena. Such a conception of the development of the function of reproduction might explain why wild animals, as a rule, do not procreate in captivity. Food may be abundant, shelter secure, the kinetic system active, but the fear integration excludes the procreation stim- ulus and prevents energy from being diverted into normal procreative channels. Animals have been so evolved that their tendency to breed is diminished in the midst of hazardous or hostile environments. In the past, such environments would have led to the destruction of mother and offspring ; death would have followed procreation in times of drouth and famine and in a period of great cold with scarcity of food. This phylogenetic fact may explain why at any time, when the general nutrition is low, the poverty of the kinetic system is such that energy cannot be spared for pro- creation. Maintenance of the Standard of Chemical Purity in the Body In addition to transforming energy for the adaptive reactions of running, fighting, work, emotion, eliminat- ing foreign proteins, combating infection and further- ing growth and procreation, it may be suggested that GROWTH AND CHEMICAL PURITY 265 the kinetic system transforms energy for the purpose of maintaining the body at an optimum chemical standard and at an optimum bulk. Our evidence for this state- ment rests upon the fact that most of the metabolic activities which result in the maintenance of the chemical purity of the body are attended by the same phenomena, the same functional and histological changes in the brain, adrenals and liver that are produced by other activations of the kinetic system. Were not some mechanism in the body adapted to regulate the disposition of food intake, to limit the storage of the digestion products of proteins, carbohy- drates and fats, the normal organism in the midst of an abundant food supply would, like sand dunes, con- tinually increase in bulk. That there is such a regu- lating mechanism, and that this mechanism is the kinetic system, is suggested by the facts about to be presented, which show that intravenous injections of excessive doses of amino acids, of glucose, of alcohol or of fatty acids result in : (1) an increased meta- bolic activity, i.e., increase in output of calories; (2) an increased activity of the organs of the kinetic system, resulting in functional and histologic changes identical with those produced by running, fighting, emotion or infection (Figs. 62, 63, 64) ; and (3) a di- minished power of the kinetic system to respond to other adequate stimuli. (1) Metabolism: Rubner, Benedict, Lusk, Du Bois and others have shown, by calorimetric methods, that protein injection is followed by an increased pro- duction of calories. This is the so-called mass action 266 MAN --AN ADAPTIVE MECHANISM of proteins. Lusk has shown that the mass action of a protein injection is greater than could be accounted for by the calories of the protein itself. This is expli- cable on the hypothesis that protein, in excess of the cellular needs, is an adequate stimulus for the kinetic A. B. Section of normal cerebellum Section of cerebellum of cat after °f cat. injections of leucin. FIG. 62. — EFFECT OF LEUCIN ON THE BRAIN-CELLS OF A CAT. Note the loss of chromatic material in all and the evidences of disintegra- tion in many of the cells of B. (From photomicrographs, X 310.) system. (Figs. 65, 66, 67.) We postulate that it is an adequate stimulus because the kinetic system has been evolved to defend the body against the accumulation GROWTH AND CHEMICAL PURITY 267 of useless materials of all kinds. Just as the kinetic system utilizes carbohydrates, in responding to bacterial foreign proteins, or in muscular work, so additional carbohydrate energy is used in the work of reducing and eliminating excessive food proteins ; and as a con- A. B. Section of normal adrenal of cat. Section of adrenal of cat after injections of leucin. FIG. 63. — EFFECT OF LEUCIN ON THE ADRENALS OF A CAT. Note the vacuolated space and the disappearance of the nuclei of the cells of B. (From photomicrographs, X 1640.) sequence, the calories produced by protein digestion are greater than the calories derived from the protein itself. (2) Kinetic Activation: If protein, in excess of the body's needs, acts as an adequate stimulus to the kinetic system, the resultant activation would produce 268 MAN --AN ADAPTIVE MECHANISM histologic changes in the brain, adrenals and liver; and functional changes in the thyroid and adrenals identical to the changes produced by muscular work, emotion, infection, etc. B. Section of normal liver of cat. Section of liver of cat after injections of leucin. FIG. 64. — EFFECT OF LEUCIN ON THE LIVER OF A CAT. Note the general disappearance of cytoplasm and of nuclei in B. (From photomicrographs, X 1640.) In order to test these points experimentally, we gave to animals intravenous injections of amino acids GROWTH AND CHEMICAL PURITY 269 (leucin, creatin) and of alcohol, representing the results of protein and carbohydrate digestion. These agents caused an increased output of adrenin and histologic changes in the brain, adrenals and liver, identical with those produced by other kinetic activations, such Section of cerebellum of dog after injection of peptone. A. B. Section of normal cerebellum of dog. FIG. 65. — EFFECT OF PEPTONE (PROTEIN) ON THE BRAIN-CELLS OF A DOG. Note the presence of disorganized and fatigued cells in B in contrast to the uniform appearance of cells in A. (From photomicrographs, X 310.) as exertion, emotion, infection ; clinically it is known that an excessive protein diet aggravates cases of Graves' disease, for which a restricted protein diet is routinely prescribed. (3) Diminished Kinetic Efficiency: If it is the 270 MAN --AN ADAPTIVE MECHANISM function of the kinetic system to regulate the amount of food products stored in the body, then, when an excessive amount of food is ingested, the kinetic A. Section of normal adrenal of Section of adrenal of dog after dog. injection of peptone. FIG. 66. — EFFECT OF PEPTONE (PROTEIN) ON THE ADRENALS OF A DOG. Note the vacuolated spaces, disappearance of cytoplasm and the irregu- larly placed nuclei of the cells of B, as compared with A. (From photomicrographs, X 1640.) system, occupied with breaking down and eliminat- ing this excess, will be rendered unable to respond normally to other stimuli, such as stimuli to mental and muscular work, emotion, etc. The general inef- GROWTH AND CHEMICAL PURITY 271 ficiency of the overfed is patent to every one. It is an interesting fact also, as shown by Du Bois, that protein injection does not produce increased calories B. Section of normal liver of dog. Section of liver of dog after injection of peptone. FIG. 67. — EFFECT OF PEPTONE (PROTEIN) ON THE LIVER OF A DOG. Note the disappearance of cytoplasm, the disappearance of some nuclei and the irregular shapes of others in B. (From photomicrographs, X 1640.) in the presence of fever, as would be expected. The reverse would be as improbable as it would be for an engine to blow off steam while it is struggling with a heavy overload. 272 MAN --AN ADAPTIVE MECHANISM Since excessive protein diet causes the same kinetic activation as overwork, worry or infection, we can understand why it can also precipitate the same kinetic diseases; why, also, though it may not be the real cause of any given disease, it nevertheless may be an injurious aggravating factor; and why limiting the protein diet of one suffering from a disease of the kinetic system may be as beneficial as rest, freedom from worry or getting rid of an infection. We can understand how cardiovascular and cardiorenal disease may be produced by excessive food ; and how they may be aggravated by excessive muscular work, and improved by muscular repose ; how nephritis may be augmented by excessive protein diet or improved by a rigidly limited diet. By this conception we link "metabolism" with other adaptive reactions which involve the kinetic system and are governed by the internal and external environ- ment. In other words, metabolism is not the cause but the result of internal or external environmental stimulation of the kinetic system. When the kinetic system is activated, metabolism results ; when the kinetic system is quiescent, metabolism is quiescent; when a link of the kinetic system is impaired, metabolism is impeded. When one link of the kinetic system is completely broken, metabolism — the trans- formation of energy — ceases. Metabolism depends upon the unity and integrity of the kinetic system as much as the complete action of an automobile de- pends upon the integrity of the essential parts of its motor. In fact the kinetic system is the motor of the body, the driving power — and no less the driven GROWTH AND CHEMICAL PURITY 273 power — as a result of whose action metabolism is produced. Pregnancy and Eclampsia Although, through the action of the kinetic system, the species preserves a relative purity of its chemical composition, observation shows that this standard is not always identical. The development of serologic knowledge has disclosed certain variations among normal individuals. Hektoen showed that the serum of particular groups of individuals contained isoglutinins for certain other groups, and no isoglutinins for still other groups. The source of this difference has not yet been determined. Not only is the lack of absolute chemical homogeneity among individuals shown by serologic tests, but it is also shown by the more rigid test of the transference of living parts of one animal or man to another. These observations have been made on a large scale in the direct transfusion of blood, in skin grafting and in the transplantation of organs. In blood transfusion hemolysis of the transferred blood might be easily understood when the recipient is abnormal, as, for instance, where there is pernicious anemia; but there is. also a slight hemolysis of trans- ferred blood in some apparently normal individuals. This would indicate a difference in the chemical nature of normal individuals. As to skin grafting, I have observed that, in cancer, skin grafts from the patient himself are far more successful than skin grafts from another individual. Even in the absence of disease, skin grafts from another part of the same individual grow better than grafts from another individual. Carrel 274 MAN --AN ADAPTIVE MECHANISM has shown conclusively that, in some instances, organs transplanted from the body of one animal to the body of another of the same species may undergo histologic changes. Most transplanted kidneys are broken down in time. Lexer's brilliant surgical feat of transplanting entire knee joints from one human being to another showed later that the transplant gradually disappeared and was replaced by a new structure identical in form and bulk with the transplant, but actually the result of cell multiplication by the host organism. Thus we have experimental and clinical evidence that normal individuals of the same species may possess slight chemical differences. The beginning of the process of procreation is the transplantation of a unit of tissue from one individual of a species to another individual of the same species. Species are probably only exaggerated varieties ; and varieties are exaggerations of individual differences. The reason why different species do not cross is doubt- less because the chemical reaction of the female kills the spermatozoon, which is a foreign protein. The same reason doubtless explains why varieties cross less well than individuals of the same species. And one may assume that two normal individuals who produce no offspring, but who, when they separate and remate, are fertile, are infertile in the first instance because of chemical incompatability. The spermatozoon presumably brings with it the chemical characteristic of the male. Hence, in the growth and development of the placenta and fetus there should be a slight chemical difference between the mother and the fetus, which would increase dur- GROWTH AND CHEMICAL PURITY 275 ing the period of fetal growth. The female therefore would have an increasing chemical difference to over- come. We have seen that the standard of chemical purity of the body is maintained through the action of the kinetic system. When there is a chemical difference between the growing fetus and placenta, therefore, the kinetic system of the mother would be activated exactly as when any other foreign protein is present in her body. An added increase in the work of the kinetic system would be imposed. Also, the increase in metab- olism required for the growth and activity of the fetus would give an increased production of acid by- products as a result of the increased energy transfor- mation. That the needs of the fetus are considerable is shown by the fact that during pregnancy the total food intake of the mother is greatly increased. As a result of this increased intake of food, the elaboration of material for the growth of the fetus, and the added burden of overcoming the difference in chemical standards, the kinetic system of the pregnant mother should and does exhibit greatly increased activity, as is shown by the following evidence : Brain: In the pregnant state there is progressive loss of muscular power, mental efficiency and resistance to infection. Memory, reason and endurance suffer just as they do in infection or in auto-intoxication. More direct evidence of the effect of pregnancy on the brain was found by examining the brain-cells of pregnant rabbits and cats. In our histologic studies of normal pregnancy we found evidence of brain over- work and brain deterioration. The percentage of hypo- chromatic brain-cells was above normal. In addition 276 MAN --AN ADAPTIVE MECHANISM we found that the intravenous injection into the mother (rabbit) of extract of her own placenta produced typi- cal work changes in the organs of the kinetic system. (Fig. 68.) Thus, we have direct physical evidence to A. Section of normal cerebellum of cat. B. Section of cerebellum of pregnant cat. FIG. 68. — EFFECT OF PREGNANCY ON THE BRAIN-CELLS OF A CAT. The effect of the long activation of pregnancy is well illustrated by the generally disorganized appearance of the Purkinje cells in B. (From photomicrographs, X 310.) confirm and support the experiences of everyday life. The reason why there are changes in the brain-cells and why there is evidence of fatigue is because the GROWTH AND CHEMICAL PURITY 277 brain has been driven to overwork by the requirements of pregnancy. Adrenals: It is known that the adrenals enlarge in animals in advance of their mating season and that the enlargement persists during pregnancy. Such FIG. 69. — TRACING SHOWING EFFECT OF PREGNANCY ON THE ADRENAL OUTPUT OF A CAT. (Cannon Test.) That the adrenal glands are activated during pregnancy is demonstrated by the sharp inhibition of the contractions of intestinal muscle when the blood of a pregnant cat is substituted for normal blood. seasonal enlargement and its persistence during preg- nancy indicate an adaptation to the work of pregnancy — a preparation on the part of the adrenals for a useful participation in pregnancy. In addition to this ana- tomical evidence, we found an increase of adrenin in the blood of a pregnant rabbit. (Fig. 69.) Further- 278 MAN --AN ADAPTIVE MECHANISM more, we found that intravenous injection of placental extract caused an increased output of adrenin in the mother rabbit. In addition, we have shown in our laboratory that histologic changes in the adrenals are produced during normal pregnancy in cats and rabbits. This evidence would seem to indicate that during preg- nancy the adrenal link in the kinetic system performs more than its normal amount of work. Thyroid: The thyroid enlarges during the mating season. It enlarges during courting and mating ; in most women, the thyroid undergoes some enlargement during pregnancy. This enlargement may disappear at the termination of pregnancy, and the gland return to its normal condition. But in many instances a part of the enlargement persists, and is increased with each succeeding pregnancy, resulting finally in a large goiter. That this enlargement is a work phenomenon is evidenced by the facts that in pregnancy the thyroid not only is enlarged but becomes more vascular and that two goiters excised during pregnancy from patients hav- ing no symptoms of Graves' disease and no infection, showed typical glandular hyperplasia. No other cases of such typical glandular hyperplasia have been found, excepting in patients whose kinetic systems were known to be activated, as, for instance, in Graves' disease, chronic pyogenic infection or tuberculosis. There is additional evidence, moreover, that the thyroid is hyperactivated in pregnancy. The pregnant woman has the symptoms of mild Graves' disease, excessive thyroid feeding or excessive administration of iodin, namely : excitability, tremors, exhaustion, sleepless- ness, increased metabolism, increased heart beat, GROWTH AND CHEMICAL PURITY 279 increased respiration, sweating. She is easily fatigued. Finally, negative proof is found in the fact that if iodin or thyroid extract in small doses be given during preg- nancy, the thyroid will enlarge little if at all. The func- tion of the thyroid is to metabolize iodin, that is, to make iodin available for use in the body economy. Hence, when there is hyperplasia of the thyroid, we assume that the gland is responding to an- increased call for iodin. This evidence shows that the thyroid, like the brain and adrenals, is activated during pregnancy. Muscles: Clinical evidence of the participation of the muscles in the activation of pregnancy is found in a distinct loss of muscular power, which may be due to the increased activity of the muscles in maintaining the standard of chemical purity through heat produc- tion. The muscles participate largely in heat produc- tion, and during pregnancy the body temperature is slightly above normal and further increase of tempera- ture is made with abnormal facility. Liver: That the work of the liver is increased in pregnancy is shown by urinary findings. If toxemia be present, the decrease in the urea and the increase of ammonia show that the liver is no longer able to perform the entire task of reducing the end products of protein metabolism. In the toxemia of pregnancy the appearance of a high blood-pressure, as in cardiorenal disease, and the increased H-ion concentration of the blood in the stages nearing eclampsia (Michaelis) offer clinical evidence that excessive work is performed by the liver in pregnancy. Further evidence of this fact is seen in the histologic studies of Ewing, which show that massive degeneration of the liver takes place in the 280 MAN --AN ADAPTIVE MECHANISM toxemia of pregnancy, and in our own laboratory findings of histologic changes in the livers of cats and rabbits in normal pregnancy. Moreover, Lusk and his co-workers have demonstrated by exact calori- metric methods that there is an increased energy transformation (metabolism) during pregnancy. According to this reasoning, eclampsia may be re- garded as the end result of a failure of the mechanism whose special function is the neutralization of the acid by-products resulting from the increased energy trans- formation of pregnancy. Ultimately, the liver gives way under the strain and becomes so incapacitated that the acid by-products of metabolism are not com- pletely neutralized and in consequence there occur acidosis, headache, drowsiness, stupor and convulsions. The phenomena of puerperal eclampsia have many points in common with those attending the breakdown of the acid-neutralizing mechanism in Bright's disease, in diabetes and in cirrhosis of the liver. The patho- logic phenomena of pregnancy may thus be explained as the result of excessive activation of the kinetic system. (Fig. 70.) The kinetic system takes much of the burden of producing offspring, just as it takes the burden of securing food, of combating enemies, of avoiding danger, of expressing the emotions, of overcoming in- fections and of maintaining the chemical standard of the body. In the amount of excessive energy trans- formation it entails, pregnancy may thus be compared to infection, emotion, etc. As a corollary, we may understand why pregnancy does not occur if there be deficiency of the two great activators of the kinetic system — the thyroid and the GROWTH AND CHEMICAL PURITY 281 A. B. Section of normal human cerebellum. Section of human cerebellum after (After accidental death.) death from eclampsia. FIG. 70. — EFFECT OF ECLAMPSIA ON THE BRAIN-CELLS OF A HUMAN BEING. Note the general disintegration and loss of chromatic material in the cells indicated by arrows, as compared with the deeply stained, intact cells of A. (From photomicrographs, X 310.) adrenals; and conversely why pregnancy in anemic, chlorotic, adynamic women sometimes transforms them and gives them added weight and added energy. 282 MAN --AN ADAPTIVE MECHANISM Though this explanation is wholly theoretical, it is conceivable that the vomiting of pregnancy may be due to the same cause as vomiting in acute infections or during the absorption of foreign proteins. When the body needs to split up and eliminate a foreign protein, the kinetic system will more readily accomplish this work if no more added food be taken, thus avoiding the additional work of breaking down and eliminating the amino acids derived from normal food. Thus, the foreign proteins of the chemical invasion incident to procreation (the fetus and placenta) may exert the same influence as that exerted by the chemical in- vasion in the form of bacteria. If the foreign pro- teins in bacteria can cause active vomiting, why may not the growing massive "foreign proteins" of preg- nancy? We have some evidence to support such a view in the fact that the moment the uterus is emptied, the vomiting ceases ; or if the fetus dies, the vomiting ceases. It has been offered as an explanation that the vomiting is reflex and is due to a false position of the uterus or to the mechanical expansion of the uterus by the fetus. Against this, it may be pointed out that mechanical pressure, false position, tension or surgical dilatation of the normal uterus cause no nausea ; and also that, as already stated, whatever the false position of the uterus, death or expulsion of the fetus at once ends vomiting. Since man is a transformer of energy, his unborn offspring are also transformers of energy. If after his birth man's further growth and maturity can occur only through the activity of his kinetic system, we have no reason to doubt that the growth in the uterus GROWTH AND CHEMICAL PURITY 283 is made possible only through the work of the kinetic system of the mother, aided, as the fetus develops, by the kinetic system of the child. This much is certain, that the growth of the fetus in the uterus is at a more rapid rate than its growth after birth. A prematurely born infant, — one delivered at six months, — which is kept at as even a temperature in an incubator as in the uterus, does not show a rate of growth equal to that of the fetus within the uterus. The infant is now depending upon its own kinetic system alone. That the kinetic systems of mother and offspring work together is shown by the fact that if the mother has a deficient thyroid gland, the new- born babe may have a goiter, showing that the thyroid of the fetus was called upon to supply the lack of thyroid secretion, although whether this call was made by the organism of the mother or of the fetus, or of both, is not known. A possible evidence of the exces- sive demand upon or of the deficiency of the adrenal secretion is seen in the characteristic brownish discol- oration of the skin of pregnant women. These discol- orations are analogous to those of Addison's disease and appear with pregnancy and disappear after de- livery. At term, the phenomena of labor present interest- ing examples of adaptive reactions. The preliminary pain compels attention — rest. The entire process, from the warning pain to the muscular contractions and muscular relaxations of delivery, is all an adaptation to facilitate the birth. Birth opens an enormous bleeding area. Vast blood vessels are rent asunder. Large raw areas of uterine tissue are exposed to infec- 284 MAN --AN ADAPTIVE MECHANISM tion. Yet, in the school of natural selection there have been evolved mechanisms of protection against all these menaces — mechanisms for the arrest of hem- orrhage through uterine contractions and through facilitated clotting, and mechanisms in the tissues of the genital tract and genital organs for protection against infection. In its excellent endowment with mechanisms of protection against the hazards incident to its function the genital tract is analogous to the gall bladder and the urinary bladder which are protected against communication with infected territories. Thus, in the fundamental processes of courtship, conception, pregnancy, birth and the rearing of the young do we find a series of wonderful adaptations by means of which the species effects survival. CHAPTER XI A MECHANISTIC INTERPRETATION OF THE ACTION OF CERTAIN DRUGS No more striking evidence that the organism is a physico-chemical mechanism governed by the laws of physics and of chemistry can be adduced than the reaction of the organism to certain drugs. We shall select therefore from a large amount of data facts concerning certain drugs which offer striking confirma- tory evidence in support of our major theme. In general, according to their effect upon the kinetic system, drugs may be divided into two classes : first, those that stimulate the kinetic system to increased activity, and as a consequence produce histologic changes in the brain, the adrenals and the liver; and second, those that suspend or depress the activity of the kinetic system, and as a consequence conserve the kinetic organs, as is evidenced after their adminis- tration by the lack of histologic changes in the brain, the adrenals and the liver, and in some instances by increased hyperchromatism, indicating that during the quiescent period the stores of energy in the brain, at least, have actually been increased. Strychnin Our experiments have shown that the changes in the kinetic organs produced by drugs of the first class 285 286 MAN --AN ADAPTIVE MECHANISM are precisely the same as the cycle of changes produced by the emotions, physical exertion or other forms of kinetic stimulation. For example, according to the dosage, strychnin causes intense excitement — con- vulsions — ending in exhaustion and death ; a lesser degree of excitation followed by lassitude ; slight stimulation without notable after-results ; while tho histologic changes in the brain, adrenals and liver - especially marked in the brain — display these physio- logic alterations in proportional hyperchromaiism in the active stages and %pochromatism in the stages of reaction. Opium Abundant clinical and experimental evidence exists to show that opium blocks or depresses the cerebral link of the kinetic system. Every one knows that deep opium narcotization prevents anger, fear, shock, mus- cular and mental work, and in addition the clinician knows that opium diminishes fever and controls anaphylactic phenomena. Of most vital significance to our theme, however, is the fact, established by laboratory experimentation, that deep opium narcoti- zation prevents the output of adrenin. (See Fig. 48.) Even in large doses, however, opium does not prevent the action of adrenin injected intravenously. We have shown in previous chapters that adrenin is a powerful activator of the kinetic system, but it may be well in this instance to refer again to the fact that adrenin causes all the phenomena of kinetic activity -with one exception, an increase in adrenal out- put. Adrenin causes all the phenomena of fever, of emotion and of physical exertion and even prepares the way for gross muscular activity in that it increases the capacity of the muscles to use glycogen (Cannon) ; and most significant of all, adrenin facilitates the elimi- nation of the acid by-products of muscular action. Any agent, therefore, that controls the output of ad- renin controls proportionally the conversion of energy into heat and motion. If opium acts directly on the central battery — the brain — so that its energy cannot be mobilized to drive the various organs of the body, one would infer that through its action on the brain, opium must pre- vent the histologic changes produced by kinetic stimuli. The truth of this inference is strikingly evidenced by experiments in which rabbits were given large doses of morphin either before or immediately after receiving doses of diphtheria toxin. Histologic examination of the brain, the adrenals and the liver of each of these animals showed that the morphin had almost wholly prevented the histologic changes which previous ex- periments had shown to be caused by diphtheria toxin alone. In studying the effect of morphin on the H-ion con- centration of the blood, we found that deep narcoti- zation does not change the normal alkalinity of the blood — at least not until the stage of asphyxia in fatal cases ; that in a morphinized animal psychic and traumatic stimuli cause neither the clinical nor his- tologic changes nor the degree of acidosis normally associated with a comparable degree of kinetic stimu- lation of like type ; but that the administration of morphin after the H-ion concentration of the blood 288 MAN --AN ADAPTIVE MECHANISM had been increased by exertion, by. fear, or by inhala- tion anesthesia delayed the return of the blood to its normal alkalinity. From these observations we infer that morphin interferes with the activity of the mech- anism by means of which acidity is overcome and by which the normal alkaline state is maintained. In this fact we find further evidence that oxygen metabolism is as important in acid elimination as in acid pro- 1 duction. These facts from the laboratory and the clinic lead to the conclusion that through its specific action on the brain, opium controls the kinetic system and there- fore governs the rate and extent of energy transforma- tion in response to kinetic stimuli whether from the internal or the external environment. If this be so, then opium may be made to serve a beneficial purpose in protecting the kinetic system from exhaustion and death from excessive acute activation. It is known that opium improves certain chronic diseases, in the etiology of which kinetic activation plays an important role, such diseases, for example, as cardiovascular disease, Bright's disease, neurasthenia, Graves' dis- ease, etc. What is accomplished by rest for these cases may be temporarily accomplished by opium. Opium is almost a specific in the prevention of shock and in urgent cases, therefore, the preoperative admin- istration of morphin is an essential part of the com- plete technique of anociation. Since, as we have stated, opium interferes with the neutralization of acidity, it is especially indicated as a preventive of shock, and is contraindicated during inhalation an- esthesia. ACTION OF CERTAIN DRUGS 289 Not only the shock which results from physical trauma but psychic shock as well may be mitigated by the administration of opium. Before the days of anesthesia heavy doses of laudanum diminished not only the pain but the dread and struggles of the pa- tient to whom the solace of unconsciousness during an operation was denied. During the French Revo- lution the public executioner gave opium to his victims to diminish their struggles and protests. When under the influence of opium, a cat will not spit at a dog ; a rabbit has no fear. Under opium no one is either brave or a coward, but is in a negative state into which psychic stimuli cannot penetrate. In cases of exophthalmic goiter the administration of opium will minimize or prevent the hyperthyroidism due to psychic or physical trauma. In extreme cases of Graves' disease, however, when the acid-neutralizing organs — the liver and adrenals — are nearly exhausted and a state of acidosis exists, morphin is unsafe, since it will further retard the already failing acid-neutrali- zation. It is probable that most deaths from acute infection are the result of an activation of the kinetic system to the breaking point. This fatal exhaustion in acute overwhelming cases may therefore be prevented by deep opium narcotization. In the last generation the value of opium in these cases was more generally recognized than at present. By the so-called "Alonzo Clark" method, opium was given in sufficient dosage to over- come abdominal distension and reduce the respiratory rate to eight or ten per minute. In this trancelike state the kinetic system was held almost at a stand- 290 MAN --AN ADAPTIVE MECHANISM still, the energy in the body thus being conserved until phagocytosis overcame the infection. Acids and Alkalies Laboratory experiments in which an acute acidosis was produced by the injection of various acids - A. B. C. Section of normal cere- Section of cerebellum Section of cerebellum bellum of cat. of cat after injection of of cat after injection of acid sodium phosphate, sodium bicarbonate. FIG. 71 . — THE COMPARATIVE EFFECTS OF 'AN ACID AND OF AN ALKALI ON THE BRAIN-CELLS OF CATS. Compare the Purkinje cells in the three sections, noting in C the con- serving effect of the alkali as compared with the disorganizing effect of the acid in B. (From photomicrographs, X 310.) hydrochloric acid, acid sodium phosphate, etc. - directly into the circulation gave ample evidence in gross phenomena and in histologic changes of the ACTION OF CERTAIN DRUGS 291 fact that acids interfere with the activity of the kinetic system. In every case extensive histologic changes were seen in the brain, the adrenals and the liver; and iodin determinations gave evidence of the fact that there was increased thyroid activity also. A. B. c. Section of normal Section of adrenal of Section of adrenal of adrenal of cat. cat after injection of cat after injection of acid sodium phosphate, sodium bicarbonate. FIG. 72. — THK COMPARATIVE EFFECTS OF AN ACID AND OF AN ALKALI ON THE ADRENALS OF CATS. Note the disappearance of cytoplasm in C, and the eccentric and crenated nuclei as compared with the nearly normal appearance of C. (From photomicrographs, X 1640.) On the other hand after the administration of an alkali — sodium bicarbonate — histologic studies of the brain, the adrenals and the liver showed a hyper chro- matic condition corresponding to the hyperchromatic condition produced by the administration of morphin MAN --AN ADAPTIVE MECHANISM alone, thus showing that alkalies tend to conserve while acids destroy the mechanism of energy transformation. (Figs. 71, 72, 73.) Clinical evidence of the protective value of alkalis is shown by the value of the administration of sodium A. B. c. Section of normal live.r Section of liver of cat Section of liver of cat of cat. after injection of acid after injection of sodium sodium phosphate. bicarbonate. FIG. 73. — THE COMPARATIVE EFFECTS OF AN ACID AND OF AN ALKALI ON THE LIVERS OF CATS. Note the disappearance of cytoplasm and of nuclei and the vacuolated spaces in B as compared with the conservation of cell substance in C. (From photomicrographs, X 1640.) bicarbonate in cases in which acidosis is present or is impending, and by the widespread medical use of the conserving alkalis and the restricted use of the destroy- ing acids. No one recommends acid mineral springs. ACTION OF CERTAIN DRUGS 293 lodin — Adrenin The effects of these substances, which are the es- sential constituents of thyroid secretion and of adrenal secretion respectively, and the adaptive reaction of the organic mechanism to each have already been fully discussed. It is sufficient here to repeat that both iodin and adrenin cause increased energy trans- formation, the one almost instantaneously, the other after a latent period. The effect of adrenin is evanes- cent ; the effect of iodin is sustained ; each in excessive doses causes acidosis : each in excessive doses causes histologic changes in the brain, the adrenals and the liver ; and each causes many of the phenomena of emo- tion, exertion, injury, infection and Graves' disease. Inhalation Anesthetics — Ether — Nitrous Oxid Although nitrous oxid and ether alike produce unconsciousness, the effects of their administration differ in certain respects. While we are not pre- pared to assign the cause of this difference, we can apply the test of histologic examination of the brain, the adrenals and the liver after the administration of each. Prolonged administration of ether produces histo- logic changes in these organs, corresponding in kind, if not in degree, to the histologic changes produced by strychnin, alcohol, acids, etc. After the prolonged ad- ministration of nitrous oxid, on the other hand, the cells of the brain, the adrenals and the liver are found to be hyperchromatic, as after the administration of morphia or sodium bicarbonate. Further evidence of the conser- vative power of nitrous oxid as compared with the de- A. Section of normal cerebellum of a dog. B. Section of cerebellum of a dog after injection of diphtheria toxin. C. Section of cerebellum of a dog after injection of diphtheria toxin plus morphin. D. Section of cerebellum of a dog after injection of diphtheria toxin and the continuous administration of nitrous oxid for four hours. FIG. 74. — PROTECTIVE EFFECT OF MOBPHIN AND OF NITHOUS OXID ox THE BRAIN- CELLS OF DOGS WHICH HAD RECEIVED INJECTION OF DIPHTHERIA TOXIN. Compare the Purkinje cells in C and D with the disintegrated hypochromatic cells in B. (From photomicrographs, X 310.) A. Section of normal adrenal of a dog. B. Section of adrenal of a dog after injection of diphtheria toxin. C. Section of adrenal of a dog after injection of diphtheria toxin plus morphin. D. Section of adrenal of a dog after injection of diphtheria toxin and the continuous administration of nitrous oxid for four hours. FIG. 75. — PROTECTIVE EFFECT OF MORPHIN AND OF NITROUS OXID ON THE ADRENALS OF DOGS WHICH HAD RECEIVED INJECTION OF DIPHTHERIA TOXIN. Note the general disappearance of cytoplasm and nuclei in B and compare with the normal appearance of C and the conserved nuclei in D. (From photomicrographs, X 1640.) 296 MAN --AN ADAPTIVE MECHANISM structive effect of ether was found in laboratory studies on the effect on animals of the simultaneous adminis- tration of an infection — diphtheria toxin — with ether or with nitrous oxid. In animals which received a dose of diphtheria toxin and were kept under ether anesthesia for four hours, greater histologic changes were produced in the brain, adrenals and liver than were found in other animals given a like dose of diphtheria toxin but not anesthetized at all. On the other hand, in animals given diphtheria toxin and kept for four hours under continuous nitrous oxid anesthesia, the cells of the brain, adrenals and liver not only were unchanged, but in some instances were hyperchromatic, corresponding closely to the cells of these three organs in animals which had been subjected to diphtheria toxin and morphia, or to sodium acid phosphate and sodium bicarbonate. (Figs. 74, 75, 76.) This evidence shows that by the simultaneous use of morphia and nitrous oxid, as in the operation under anociation, the greatest possible protection has been given to the kinetic system. Summary Thus, at will, by the administration of certain drugs, the kinetic organism of man and animals may be acceler- ated, retarded or its action suspended. Thus, at will, by the use of drugs we may produce in the organism phenomena which resemble those produced by fever, infection, emotion, etc., and in like manner the phenomena of sleep or death may be produced. A. Section of normal liver of a dog. B. Section of liver of a dog after injection of diphtheria toxin. C. Section of liver of a dog after injection of diphtheria toxin plus morphin. D. Section of liver of a dog after injection of diphtheria toxin and the con- tinuous administration of nitrous oxid for four hours. FIG. 76. — THE PROTECTIVE EFFECT OF MORPHIN AND OF NITROUS OXID ON THE LIVERS OF DOGS WHICH HAD RECEIVED INJECTION OF DIPHTHERIA TOXIN. Note the vacuolation of B and compare with the conservation of nuclei and cytoplasm in C. (From photomicrographs, X 1640.) CHAPTER XII ACTION PATTERNS ; CONSCIOUSNESS AND SLEEP Action Patterns WE know that the brain contains the mechanism that drives the body ; we know that environment drives the brain and that environmental forces reach the brain through the mediation of the sense organs. But what is the mechanism within the brain by means of which a given stimulus causes different effects in different brains? Why will one man run away and another attack on receipt of identical stimuli ? We postulate that the adaptive reactions of the organism are executed by mechanisms, each of which, like a wireless station, awaits the arrival of the specific impulse which is to awaken it to specific response. Between the ceptor organs of the eye, the ear, the nose, the sensory nerve endings in the skin and the nerves governing muscles and glands there intervenes an intricate network of action patterns. As over the same copper wire may be transmitted the voice, a telegraph message, a dynamic charge of electricity for firing a mine, lighting a concert hall or driving an engine, — so over the same nerve or group of nerves may be transmitted impulses destined for the pro- duction of terror, of sudden flight or of the reactions of eating or drinking. Thus during consciousness the 298 ACTION PATTERNS 299 brain is the seat of a continual flow of opposing, assist- ing, crossing and interfering impulses, the amount of fatigue produced being proportional to the number and strength of stimuli that evoke responses, whether these responses be those of gross activity or of mere perception. It is not as difficult as it seems at first to conceive how the most complex reactions have been built out FIG. 77. — CROSS-SECTION OF LEAF AND HAIR OF VENUS' FLY-TRAP. Drawing showing the cellular mechanism which corresponds to the nerve path in animals. The expansion or compression of these cells, resulting from the touch of an insect, causes the leaf to close upon the insect in a few seconds, like a trap. of the less complex by the simple process of multiply- ing the number and sources of stimuli. In the motor response of Venus' fly-trap we have a simple action 300 MAN --AN ADAPTIVE MECHANISM pattern. In my laboratory, Miss Menten identified the conducting path over which the stimulus apparently travels to the effector mechanism of Venus' fly-trap. (Fig. 77.) Here a response takes place by means of one continuous path of conduction without any break in its entire length. Without a brain or a nervous system, but with the equivalent of nerve fiber in the form of a tissue which contains lecithin-like compounds and salts similar to those in nerve tissue, the plant organism makes a response to an adequate stimulus as specific as are any of the responses made by man. When a fly alights upon the skin of man, it causes a tickling sensation and is immediately brushed off; when it lights upon the hairlike appendages of Venus' fly-trap, it is caught by the motor mechanism of the plant, bathed with digestive fluid and consumed. By an analogous process the same stimulus has caused two similar reactions in vastly dissimilar beings — one without a brain, the other with a brain. In one case the stimulus traveled to a central organ where energy was released which in turn activated a specific set of muscles to perform a specific act. In the second case the stimulus traveled directly to the effector mechanism, probably releasing energy along the way. In Venus' fly-trap but one receptor and one effector mechanism has been evolved for but one adaptive re- action. In man many receptor and effector mechanisms have been evolved for numerous reactions in response to numberless stimuli. If it were necessary for Venus' fly-trap to catch its food by running instead of by passive attraction, the plant would doubtless have evolved a mecha- ACTION PATTERNS 301 nism coordinating the organism for running — in other words, a brain. The difference between Venus' fly- trap and man is the difference between the number of mechanisms possessed by each. A multiplication of the single action pattern of Venus' fly-trap equals the mechanism of man. Pawlow has shown , in a recent work, that new re- flexes may be created in an animal by superimposing new stimuli upon older ones, simultaneously with the occurrence of old reflexes. Thus, when a dog is being fed, if he be frequently subjected to a painful electri- cal stimulus applied to a given area of skin, a reflex to this electrical stimulus will soon develop which is precisely like that shown in response to the exhibition of food. This reflex, which corresponds to an action pattern, is termed a "conditioned" reflex, in contrast to the normal or "unconditioned" reflex. As an explanation of the creation of the new reflex, Pawlow1 states that the "nervous impulse resulting from the stimulus, which formerly went to a particular region of the nervous system, is now directed to a dif- ferent one." He says: "In this way we have been able to direct the impulse from one path to another, according to the conditions ; and we cannot avoid the conclusion that this represents one of the most impor- tant functions of the highest parts of the central nerv- ous system." In some such manner, doubtless by a slow and con- tinuous process, the changing conditions of environ- ment have superimposed new stimuli upon the old until by the infinitely varying stimuli which simul- 1 Pawlow : The Investigation of the Higher Nervous Function. 302 MAN --AN ADAPTIVE MECHANISM taneously compete for entrance, the brain patterns of man have been modified and the complex reactions of social adaptations have succeeded the simple processes of food-getting and injury-avoidance which were suffi- cient for the primitive organism. Theoretical Structure of Action Patterns — Effector Ceptors The manner in which this vast multiplicity of adaptive responses is achieved and their specificity established may be inferred from the facts that the nerve paths over which impulses pass from the periph- ery to the brain are insulated ; that the nerve paths over which pass the motor impulses from the brain to the periphery are insulated ; and that the innumer- able conducting paths in the brain are not insulated. From this arrangement we infer that it is necessary that impulses from the sense organs to the brain, and impulses from the brain to the muscles, be carried in- tact and undisturbed ; whereas within the brain it is necessary — or immaterial — that impulses be dis- seminated freely. Reflection upon these two opposite types of struc- ture within the brain and without the brain suggests the following hypothesis regarding the manner in which action patterns are constructed. Let us suppose that the brain is composed of mechanisms of three general types, one for supplying motor power — the brain-cells ; another for conduct- ing this motor power as action currents; and the third, specific receptor mechanisms within the brain ACTION PATTERNS 303 whose function is that of receiving specific action currents — effector ceptors. Furthermore, we may assume that these receptor mechanisms are endowed with the quality of being permanently modified by each impulse that passes over them, as a result of which the subsequent passage of an identical impulse is facilitated. Our assumption is that the number and architecture of action patterns have been determined by natural selection ; that no pattern exists but has selection value ; and that all these patterns freely communicate with each other, and thus, indirectly, with all the cells of the brain. We suppose that in the brain there are millions of naked microscopic "wires," communicating with millions of microscopic "batteries" -the brain- cells. Thus among the brain-cells there is the freest possible intercommunication, and thus they communi- cate on the one hand with the sense organs through the peripheral nerve paths, and on the other hand through the specific receptors — effector ceptors - with the muscles of the body. At first sight this hypothesis would seem to indicate chaos within the brain and confusion without. But how such an apparently chaotic arrangement could fabricate with precision the functions of the brain becomes evident when we recall that one of the first suggestions in our hypothesis was that all the multi- tude of action patterns were not fabricated at once, but that first one and then another action pattern was developed to meet the needs of the evolving organism, each new adaptation establishing its own path of least resistance so that now, although each *u J «• 5« 5?5 M P Pi <- «• m T3 a ||| III o -^> a A IS 3 ""1 S "S-5 S o s o S3 'w ° 5 S^ -p'S r. M 2 _r .S^U a

«« to g !§K 3 ^ « rg il-"5 I*H 1 >> .S • » . 5 oo 2 o a *• gB£ c5 • c ACTION PATTERNS 305 nerve impulse on reaching the brain may have access to any one of the innumerable patterns, entrance is secured to only that pattern by which the least re- sistance is offered. That is to say, whether an im- pulse shall pass over this or that or any action pattern depends upon the degree of resistance which has been established by the past experience of the organism ; while the degree of vigor of the response depends upon the physical state of the brain-cells. The assumption that by the lack of insulation each pattern is connected with every part of the brain — with all the brain-cells — suggests an explanation of the fact that all the energy of the brain may be drawn upon by any one or by a group of action patterns ; thus, for example, the vigorous continuous use of the muscles of a hand or a foot may ultimately exhaust the entire brain. The postulation of receptor mechanisms — effector ceptors — within the brain receives some support from the following arguments : (a) In some fish receptor mechanisms are known to exist in the brain ; (6) the eye and other sense organs may be considered as re- ceptor mechanisms projected outside of the brain ; (c) the known receptor mechanism of the eye bears a resemblance to certain structures within the brain whose function may equally well be receptive (Fig. 78) ; (d) if the nerve receptor mechanisms of the eye, the ear and other sense organs are adapted to specific energies, why may not similar nerve structures within the brain likewise act as specific energy receptors? (e) if the sense receptor organs mediate between the external environment and the brain, why is it not 306 MAN — AN ADAPTIVE MECHANISM logical to assume the existence of receptor organs within the brain mediating between the inflowing impulses and the outgoing action currents? The innumerable receptor mechanisms — effector cep- tors — in the brain may be likened to hundreds of thousands of wireless receiving stations each of which registers only those messages received from the specific transmitter to which it is adjusted ; or they may be compared to a vast number of tone receptors in a great chamber, each of which will deliver its specific note only in response to sound waves of a specific length and velocity. In such manner one may suppose that each of the innumerable stimuli that reaches the brain activates only the action pattern which by that master-artificer - Environment — has been attuned to that stimulus. Application of Theory of Action Patterns If the predication of such a method of evolving character and individuality seems strange, it may be well to contemplate the steps by which man from the moment of his birth acquires the "experience" by means of which he is able to cope with environment. There are first the simple reactions of sucking, cry- ing, winking, sneezing. Gradually, more contacts, some beneficial, some harmful, are made. Objects and persons stand out from the chaos of sur- roundings, judged and catalogued by the one stand- ard of their effect on him — the infant. We may suppose that each new contact writes a new rec- ord on the delicate matrix — a record of the sev- ACTION PATTERNS 307 eral stimuli which participate in the activation — especially the coincident stimuli of the distance and of the contact ceptors. Thus the sight of the mother and the sound of her voice are coincident stimuli with those of the acquisition of food — and, as in Pawlow's dog, the action pattern of acquiring food is in physical connection with the sight stimuli and voice stimuli of the mother. Thus is associative memory devel- oped. Each new adequate stimulus writes a new record —begins a new action pattern — and when two or more stimuli act simultaneously the resultant pattern will ever after be activated in like manner by each stimulus. Thus in time, as one after another the contact stimuli of environment become associated with simultaneous distance ceptor stimuli, the action patterns are more and more activated by the associated distance ceptor stimuli alone. Thus step by step, action patterns made by the simultaneous stimulation of contact and distance ceptors become connected until in time ac- tivation is effected almost completely through distance ceptor stimuli alone. After a contact with a given object has once been associated with a sight, a sound or a smell, the taste, smell or sight of that object will excite activity toward contact or away from contact according as the object is beneficial or harmful. For example, the contact ceptor stimulus of fire would be simultaneous with the distance ceptor stimulus of light and the action pattern of withdrawal would be stimulated. Subse- quent to this association, the accompanying sight stimulus alone activates the moving-away action pattern — and the child therefore never again makes 308 MAN --AN ADAPTIVE MECHANISM contact with fire. The distance ceptor stimuli of light and heat take the place of contact ceptor stimuli. On the other hand, let the infant be given a bottle of milk ; it feels the bottle (contact stimulus) ; it sees the bottle, smells the milk (distance stimulus) ; the nipple is placed between its lips and the action pattern of sucking is excited. Thus the child obtains its first experience with a nursing bottle. The simulta- neous repetition of the same contact and distance cep- tor stimuli repeats the excitation of the same action patterns until in time the sight of the bottle alone stimulates the food-getting action pattern. Thus from contact with each new factor in the en- vironment, distance ceptor stimuli come to be inter- preted in terms of contact ceptor stimuli. In like manner sign language, spoken language and written language at first were parts of action patterns which first were stimulated by contact ceptors. The be- ginning of mathematics is the action pattern of laying one block upon another. So the natural sciences have been evolved from the simple action patterns created by such stimuli as heat, cold, movement, weight, sound and light, by an ever increasing addition of associated action patterns. Thus too has been evolved the language of emotions. Education and training are probably the sum total of secondary action pat- terns introduced into the brain, and engrafted upon the original contact ceptor action patterns. Thus the action of the individual becomes inevitable ; and by this conception we may interpret the life phenomena and actions of man and animals. The action patterns of the child, which are wrought ACTION PATTERNS 309 upon its brain by contact with its immediate family environment, are permanent. Thus language, cus- tom, religion, conduct and the conventions of races and peoples are transmitted through the generations. On the other hand, if a newborn Puritan babe, whose plastic brain has received no action pat- terns, were to be placed in the arms of a Pata- gonian Indian, its brain would receive and record the Patagonian language, customs and religion — and no other; and if that transplanted child re- mained until middle life exclusively in the new environ- ment, no influence could take from that brain all the action patterns derived from that environment, though other action patterns might be superimposed. The Hindoo, Chinaman, Brahmin, Teuton, Briton, Bushman, Christian or Pagan has acquired brain patterns which are ready-made by the environment into which he has been born and in the midst of which he has been reared ; and not until the stronger stimulus of the necessity of race preservation intervenes will the old conventions, customs and languages give way to the new. The plasticity of the brain may be observed on a large scale in the results obtained in the schools of a cosmopolitan city like New York, where the children of immigrants, drawn from all quarters of the globe from Iceland to Australia, are subjected to similar educational influences. The mass in the "melting pot," as it has aptly been termed, rapidly approaches a semblance of homogeneity, not alone in mental and moral characteristics but even in facial characteristics, as has been shown by students of physiognomy. 310 MAN --AN ADAPTIVE MECHANISM Polish, Russian, Jewish, Irish, English, German, Scandinavian, African, Spanish and Hindoo children rapidly lose their definite lines of demarcation under the steady drill of new teachings and new sur- roundings. When intermarriage shall have added its influence to that of education, the structural lineaments of race, as well as the customs and manners of these descendants of the first products of the melting pot, will in many essentials be indistinguishable from those of the descendants of the Mayflower pilgrims. The greatest single influence in bringing about this leavening of the mass and the production of a common type of humanity is the spread of commercial interests and scientific knowledge. The new ideas, new customs, new languages, new reli- gions and new inventions of invading strangers are accepted or rejected in the proportion in which they are indispensable to life. In proportion as the Mexican, the Hindoo, the Chinaman and the African need recreation, food, clothing and improved dwellings do they accept the American missionary or German hardware. One may interpret the habits, thoughts, customs and reactions of individuals, classes and races by the conception that they are produced by an activat- ing environment playing on a plastic nerve mechanism, and producing action patterns whose responses to recurring stimuli are inevitable. As with Pawlow's dog, any set of action patterns may be modified by superadded associations. ACTION PATTERNS 311 Consciousness and Sleep On the basis that the reactions of man and animals may be interpreted in terms of action patterns we may interpret the phenomena of consciousness and lack of consciousness or sleep. With the first cry of the newborn babe in response to the adequate stimulation of its contact ceptors, begins the development of consciousness. Bright lights, certain sounds, the primary colors, the sun, the green fields, sky and water, animals, people ; the experience of sitting erect, of creeping, walking and talking, of playing games, of the kindergarten ; ju- nior-grade sports ; senior-grade duties ; graduation ; human relations; marriage, — all the experiences of life from moment to moment, from day to day, from year to year, add new action patterns. Thus as the human organism progresses from infancy to manhood new action patterns are constantly added to environ- mental contacts. The activation of these patterns constitutes man's conscious life. By this conception consciousness is the response to environmental stimuli: sleep is the absence of response to environmental stimuli. For at least two months before birth, the fetus is ready to be conscious, but lacks the adequate environ- mental stimuli which cause the reactions of conscious- ness. The only difference between the unconscious fetus and the awake newborn babe is found in the few simple responses made by the latter to the stimuli of light, sound and physical contact. As consciousness increases, motor reactions increase likewise, and the time consumed in sleep lessens. 312 MAN --AN ADAPTIVE MECHANISM In certain species of animals, the maximum of con- sciousness and minimum of sleep is established promptly at birth, owing to the requirements for nutrition and the necessity for an immediate motor adaptation against constantly menacing enemies. Only in those species in which the parents are able to defend their young against enemies and to supply them with food is there a period of prolonged unconsciousness after birth. Birds which nest in the branches of trees and are hidden from their enemies sleep much of the time during the first days after they are hatched; but birds which nest on the ground, and depend for safety upon their ability to run and hide from prowling ene- mies, are conscious and able to run almost as soon as they are hatched. For example, young quail are sometimes seen running about with pieces of shell still on their backs. Aquatic birds are awake and active as soon as they are hatched. The eaglet, on the con- trary, which spends its early days on the inaccessible peaks of rocky promontories, develops slowly. The offspring of the herbivora are wide awake and able to walk, even to run, on the first day after birth. The herbivora are dependent upon flight for their safety ; while the young of the carnivora, which are able to defend their offspring, sleep for days after their birth. This, and the quality of food, may explain why the hunted herbivora eat more, and oftener, and sleep less than do the pursuing carnivora. The herbivora, need- ing to be constantly on guard, use more fuel and hence need to replenish their resources more constantly and abundantly; while the carnivora, secure from attack, divide their time between hunting and sleep- ACTION PATTERNS 313 ing, thus requiring a minimum of food — an advantage to the herbivora as well. Of all animals, the bird, perhaps, is the most intensely conscious : it transforms relatively the most energy and eats proportionally most of all. In certain physiological states in which conscious- ness is at a low ebb because of age or disease, there may be noted a similar coincidence between diminished consciousness and diminished motor adaptation. In the senile, in the anemic and in patients with cerebral softening, or in whom the brain is compressed as the re- sult of a hemorrhage or a tumor, there exists a state of diminished consciousness and a correspondingly limited capacity for muscular action which is analo- gous to these conditions in the newborn babe. It is of further interest to note, in this connection, that in these states of reduced consciousness, it requires but a small amount of an anesthetic or narcotic to produce unconsciousness or even death. In the aged, the anemic or the newborn, a small dose of morphia may be fatal. Conversely, the more intense the con- sciousness, whether from emotion or injury, the greater the amount of ether, nitrous oxid or morphia required to produce unconsciousness. It would appear from these facts, that the mecha- nism which is specifically influenced by anesthetics and narcotics is the mechanism by means of which, in a manner as yet unknown, normal sleep is produced. It is obvious that consciousness is depressed in sleep ; and that the phenomena of sleep — muscular re- laxation, incoordination, diminished consumption of oxygen, diminished output of carbon dioxid, lowered 314 MAN --AN ADAPTIVE MECHANISM metabolism, diminished rate of pulse and respiration and lowered temperature and blood-pressure — are all phenomena of diminished consciousness. (Fig. 79.) That sleep only partially suspends the brain function is indicated by the fact that during sleep there may be a partial response to stimuli, such as is indicated by the shifting of posture and by moving in response to a call. It is particularly the function of the special senses which is suspended ; and it is in response to stimulation of the special senses, as we have shown, that most of the energy of the body is expended. Nevertheless, even while the function of the special senses is suspended, there may continue in the brain a symbolic train of action in the form of word pictures or dreams which, if sleep be light, are recorded on the feeble consciousness of the sleeper and may be recalled on awakening. The subconscious memory of some dominating experience of the day may break through light sleep and cause a muscular response. That the maintenance of consciousness requires a transformation of energy by the kinetic system is evidenced by the histologic changes produced by pro- longed continuous loss of sleep in the organs of the kinetic system of rabbits, and in the fact that these lesions can be restored only during sleep ; during un- consciousness produced by nitrous oxid anesthesia ; or to some extent, when consciousness is depressed by morphia. Our experiments indicate that the lesions of the kinetic system produced by emotion, by exertion, by infection, like the lesions due to prolonged con- sciousness, are repaired only during sleep. During sleep, activating stimuli are apparently grounded. ACTION PATTERNS 315 Photo by Wm. J. Brownlow. FIG. 79. — SLEEPING CHILD. The energy expended in waking activities is being restored in sleep. Compare the relaxed position of the whole body as shown here with the muscular action in Fig. 82. 316 MAN --AN ADAPTIVE MECHANISM As daylight and darkness blend into one another by infinitesimal intervals, so that none may say where daylight ends and darkness begins, so consciousness and sleep blend into one another. The brain is the arena in which countless stimuli pass and repass, cross, combine, oppose and interfere, wax and wane in intensity, appear and disappear; now one gains the final common path, now another, thus creating an infinity of kaleidoscopic patterns, in which hopes and fears, desires, sentiments, actions, go to make up the manifold life — the consciousness of the individual. Life and adaptation to environment begin and end in unconsciousness. Unconsciousness is the basic state ; consciousness is the evoked state. The sum total of consciousness is the sum total of the adaptive responses made by the kinetic system throughout the span of life. And as these adaptive reactions vary widely from species to species, and from individual to individual, so consciousness varies. The newborn individual, like the individual weakened by some hereditary defect or disease, — the cretin, the victim of hypothy- roidism or hypopituitarism, — cannot reach a useful height of consciousness, cannot attain a large sum total of consciousness. Likewise, the individual whose thresholds are low to only a limited number of stimuli reaches but a limited degree of consciousness within the limited environment which is open to him. The man whose mind is closed to the beauties of nature, music and art has a consciousness limited to an envi- ronment devoid of a number of activating stimuli. The musician, or any specialized worker who responds intensely, and for the most part only, to the stimuli ACTION PATTERNS 317 which are connected with his work attains to but a limited degree of consciousness, and is, so to speak, unconscious to most of his environment. That indi- vidual has lived most, has experienced the highest degree and the largest sum total of consciousness, who has responded most to the widest variety of stimuli ; who has acquired and made use of the greatest number of action patterns. CHAPTER XIII PAIN, LAUGHTER AND WEEPING Pain THE specific response of pain to stimulation of the contact ceptors has been discussed in Chapter III. There we considered the distribution of pain areas; the types of contact ceptor stimuli that elicit pain ; the specificity of the pain response to the exciting stimulus ; and the fact that pain is always associated with a pro- tective muscular action. It remains to consider the biologic utility and the mechanism of the pain which is elicited by pathologic conditions. Here too the law of phylogenetic association is easily applied, for as response to contact ceptor stimulation is most intense in the parts most commonly subjected to attack and to physical injury, such as the tips of the fingers, the palms of the hands, the soles of the feet, the chest and the abdomen, while the deeply protected portions of the body, such as the liver, spleen, kidneys, brain and lungs are pain-negative, so a type of infection which is associated with pain when it involves one portion of the body may be painless when it involves another portion. Tuberculosis of the lungs, for example, is painless, while intense pain is associated with tuberculosis of the hip. I believe it will be found, on careful analysis, that the infections which are associated with pain are those 318 PAIN, LAUGHTER AND WEEPING 319 in which there is danger that the disease may be extended by muscular action, or in which fixation of the parts by continued muscular rigidity is of distinct advantage in overcoming the disease. In such diseases as scarlet fever, typhoid fever, measles, malaria, whooping cough, typhus, syphilis in the early stages, and in fact in most of the exanthe- mata in which the organism as a whole is quickly in- volved by the dissemination of infection, and in which muscular action can render no assistance, there is, as a rule, no pain. On the contrary, the infections gen- erally associated with pain are the pyogenic infections, of which local inflammation, boils, carbuncles, felons and abscesses are common instances — infections the main characteristic of which is a local point of involve- ment or focus. A fundamental and striking difference between the painless exanthemata and the painful pyogenic infec- tions is found in the fact that, in the case of the former, the protective response of the body is wholly chemical — the formation in the blood of anti-bodies which usually produce a permanent immunity, while in the latter the defense is largely phagocytic. In the pyogenic infections, in order to protect the remainder of the body, which enjoys no immunity, every possible barrier against the spread of the infection is thrown about the local point of infection. Lymph is poured out and the part is fixed by the continuous contraction of the neighboring muscles and by the inhibition of those muscles which by the ordinary exercise of their func- tions would spread the disease. As would be expected, this continuous contraction is associated with pain. 320 MAN --AN ADAPTIVE MECHANISM Wherever a continued inhibition of muscular ac- tion in the vicinity of a local infection would be of no assistance in localizing the disease, or in those parts of the body in which muscular activity is a fundamental requirement of life — as, for instance, in the lungs - there pyogenic infection is unattended by pain. Thus, no muscular rigidity and consequently no pain is as- sociated with pyogenic infections in the substance of the liver, in the substance of the kidney, within the brain, in the retroperitoneal space, in the lobes of the lungs, in the chambers of the heart or in the blood vessels of the chest or the abdomen. Another type of pain, headache, more indirectly but none the less positively, modifies muscular action in the body. Headache is one of the most common initiatory symptoms of various infections, especially of those which are accompanied by no local pain and no local muscular action. On the other hand, headache is rarely associated with peritonitis, cholecystitis, pleurisy, arthritis, appendicitis, salpingitis, childbirth, obstructions of the intestinal and the genito-urinary tract — with any condition, in short, the local symptoms of which are overwhelming enough to govern the indi- vidual, as a whole, to make him lie down and keep quiet, refuse food and possibly reject what is already in the stomach. But in diseases in which the protecting local pain is absent, such as the exanthemata, typhoid fever, auto-intoxication, in which no dominating dis- turbance acts as a policeman to put the patient to bed and to force him to refuse food that he may be in a more favorable condition to combat the oncom- ing disease — in these conditions, headache serves a PAIN, LAUGHTER AND WEEPING 321 beneficent and important purpose. The body, stricken by acute infection or poisoned by auto-intoxication, needs to rest and to fast ; hence the entire muscular system obeys the command of this single pain, located in the controlling organ of the body, and muscular relaxation follows. Strange and yet intelligible, in view of this concep- tion, is the fact that, although a headache may be induced by even a slight auto-intoxication, an abscess may exist in the brain itself without causing pain. Inhibition of muscular action is a protection in one case ; in the other it is useless. In like manner this principle may explain the acute pain that is present when an obliterative endarteritis is threatening a leg with anemic gangrene, or when one lies too long in the same position on a hard bed so that injury from local anemia threatens. But when the obliterative endarteritis threatens anemia of the brain, or when an embolism or thrombosis has produced anemia of the brain, there may be no pain, for muscular action, which in the former instance would be a protective response, in the latter would be of no use. A most striking instance of the protective nature of pain is found in the phenomena of peritonitis. Through the law of natural selection, the peritoneum, in its relation to vast fields of possible infection, has become wonderfully endowed with mechanisms for resisting and overcoming infection. If the focus can be localized, almost any infection in the peritoneum can be overcome. This localization is accomplished by holding the muscular intestinal walls still and rigid against a large volume of gas, and by quickly throwing 322 MAN --AN ADAPTIVE MECHANISM out a fixative fluid or exudation. As a secondary adap- tation, the stomach contents are ejected by vomiting, so that a protective anorexia against useless food also stands guard. If our conclusions are correct, why are certain cases, familiar to every surgeon, of widespread general peri- tonitis, cholecystitis or of other abdominal lesions unaccompanied by pain, often without muscular rigidity or tenderness even, so that the surgeon may be misled in his diagnosis, and the result may be fatal ? In seeking an explanation for these cases, which are almost invariably found either among the aged or the very young, we are led to formulate a postulate re- garding the source or the site of pain. The Site of Pain If pain is a part of a muscular response and occurs only as a result of stimulation to muscular activity by physical injury, infection, anemia or obstruction, in what part of the nervous arc may the mechanism for the production of pain be found ? Are the pain phe- nomena associated with the physical contact of the stimulus with the nerve ending ; with the process by which the impulse is transmitted along the nerve trunk ; or with the process by which the energy in the brain-cells is released and the impulse to the muscles is transmitted ? It seems most probable that pain is associated with the discharge of energy by which the motor act is made possible. If this be true, then, if every contact ceptor in the body were equally stimulated in such a manner that all stimuli reached the brain-cells simultaneously, then the brain-cells would be in equilibrium and no muscular act — hence, no pain — would result. In the nearest approach to this hypothetical condition that we know — instances of sudden and widespread burn- ing by fire — there is said to be no pain. But if all the contact ceptors of the body but one were equally stimulated and this one stimulated more strongly than the rest, then the stimulus of the latter would gain possession of the final common path and would cause a given muscular contraction and a sensa- tion of pain. It is well known that when a greater pain stimulus is thrown into competition with a lesser pain stimulus, the lesser is submerged. The schoolboy takes advantage of this fact when he initiates the novice into the mystery of the painless plucking of a hair. The simultaneous but severe application of the boot to the blindfolded victim solves the problem, and the hair is plucked painlessly through the triumph of the boot stimulus over the hair stimulus in the struggle for the possession of the final common path. This hypothesis is supported also by the fact that strong contact ceptor stimuli are often dispossessed by distance ceptor stimuli in such a way that an injury which under ordinary conditions would cause great muscular contraction and consequent pain, is endured in apathy because of the victim's complete obsession by some emotional stimulus. Instances of this kind are seen in cases of self-inflicted torture among savage tribes; in fanatics while under the stimulus of religious zeal ; in cases of physical injury received by persons obsessed by anger or fear; and, to a lesser degree, in sexual emotion. Soldiers in the 324 MAN --AN ADAPTIVE MECHANISM midst of a battle often experience no pain from a wound and may not know they are wounded until after the emotional excitation has worn off, when the sensation of warm blood on the skin may be their first warning of injury. Dr. Livingstone, the African explorer, has testified to his complete unconsciousness to pain during his struggle with a lion. Although he was torn by teeth and claws his fear overcame all other impressions. Possibly the phenomena of hysteria may also be explained on this basis, as may the unconsciousness of passing events in a person in the midst of great and overwhelming grief. By constant practice the student may secure the final common path for such impressions as are derived from the stimuli offered by the subject of his study, and so be oblivious to his surroundings. Con- centration is but another name for the exclusion of ir- relevant stimuli from the final common path. Since both psychic and mechanical stimuli cause motor phenomena by the excitation of precisely the same mechanism in the brain, and since the more rapid transformation of energy by psychic stimuli in these cases submerges the transformation of energy by physical stimuli and prevents pain, it would seem as if the phenomenon of pain must be associated with the process of releasing energy in the brain-cells and with the passage of energy to the effector mechanism -the muscles. Were a physical injury inflicted in a quiescent state equal to that inflicted without pain during a highly emotional state, there would result great pain and intense muscular activity. Another viewpoint which throws further light upon PAIN, LAUGHTER AND WEEPING 325 this hypothesis is well illustrated by the following case histories : Several years ago, a man, 78 years old, whose chief complaint was obstinate constipation was admitted to the medical ward. The abdomen was but slightly distended ; there was no fever ; no pain; no increased leucocytosis ; no muscular rigidity ; and but slight general tenderness. The patient said he had lost in weight and in strength during several previous months. A tentative diagnosis of malignant tumor of the large intestine was made, but free movements were secured rather easily and we abandoned the idea of an explora- tory operation. The patient gradually failed and died without a definite diagnosis having been made by either the medical or the surgical service. At autopsy, there was found a widespread peritonitis arising from a perforated appendix. An infant was taken ill with some indefinite disease. Several of the ablest medical and surgical consultants of a leading medical center thoroughly investigated the case. Although they could make no definite diagnosis, they all agreed that surely it could not be appendicitis, because there was no muscular rigidity and no tenderness. The autopsy showed a gangrenous appendix and general peritonitis. These two cases are illustrations of the principle that underlies the freedom from pain which results from the use of narcotics and anesthetics. It is the same principle that explains the fact that cholecys- titis may occur in the aged without other symptoms than the presence of a mass and, perhaps, very slight tenderness. It accounts, in general, for the lack of 326 MAN — AN ADAPTIVE MECHANISM well-expressed disease phenomena in the senile and in infancy. The aged, the infant and the victim of general paresis show but few symptoms of disease because of the fact that in senility the brain is so de- teriorated, and in infancy so undeveloped, that the cerebral mechanism of associative memory is inactive, hence pain and tenderness, which are among the oldest associations, are lacking. Senility and infancy are by nature normally narcotized. The senile is passing through the twilight into the night, while the infant is emerging from the shadows of dawn into the day. Hence it is, that in the extremes of life the diagnosis of injury and disease is subject to special difficulties. At such times, as regards symptoms, the entire body is as silent as the brain, the pericardium, the medias- tinum and other normally symptomless areas. For the same reason, when a patient, seriously ill with a pain- ful disease, turns upon the physician a glowing eye and an eager face, and remarks how comfortable he feels, then the end is near. The mechanism by which the transformation of energy is accomplished has run down. Energy is no longer available to register the results of stimulation in pain any more than in motion. The most convincing evidence of this hypothesis, however, is found in the prevention of postoperative pain by the use of anociation. According to our hy- pothesis (explained at length in Chapter IX), post- operative pain is due to the state of low threshold established in the brain as a result of intense or repeated injurious impulses. The site of postoperative pain is not in the traumatized field, but in the brain. If the traumatic impulses are prevented from reaching PAIN, LAUGHTER AND WEEPING 327 the brain by blocking the field of operation with local anesthesia, the brain threshold is not lowered, and there is consequently little or no postoperative pain. There is a close resemblance between the phenomena of pain habit, of education, of physical training and of love and hate. In education, in pain habit, in all emotional relations, a low brain threshold is established which facilitates the reception of specific stimuli. All these processes are motor acts or are symbolic of motor acts. We may be trained to perceive mis- fortune and pain as readily as we are trained to per- ceive mathematical formulae and moral precepts. Laughter and Weeping Much of the real nature of laughter and weeping, as of pain, is revealed by an examination of their dis- tribution ; that is, of the character of individuals among whom they are common, and of the situations to which they are incident. Laughter is an involuntary rhythmic contraction of certain respiratory muscles, accompanied usually by certain sounds. The motor act involves the respiratory apparatus primarily, but if the act is intense, it may involve not only the muscles of respiration, but also most of the other muscles of the body. There are many degrees of laughter, varying from a mere brightening of the eyes and a fleeting smile to intense hysterical and convulsive outbursts. From intense or prolonged laughter, even exhaustion may result. Laughter is sometimes accompanied by the forma- tion of tears and in many instances, in children espe- cially, laughing and weeping are readily interchanged. 328 MAN — AN ADAPTIVE MECHANISM When strongly integrated to laughter, the nervous system can perform no other function. According to Darwin, the only animals which laugh are men and monkeys. Other animals exhibit play- ful phenomena, and some exhibit certain types of facial expression which are associated with delight. But laughter, in the common sense of the word, is an attribute of the primates only; and even among men, proneness to laughter has a more or less limited distribution. It is more common, for instance, among healthy and happy, well-fed and comfortable individ- uals, than among the diseased, the oppressed and the poorly nourished. Laughter is more common among civilized than among savage races, and among highly intellectual individuals than among the stolid and crude inhabitants of the waste places of the earth. It is more frequent among individuals whose lives lie in the easy ways of luxury and leisure than among those whose waking moments are filled with an abun- dance of muscular activity. The Indian, the Eski- mau, the Hottentot, laughs seldom, according to our standards. The Canadian woodsman, the mountain guide, the lonely cowboy, the range rider of the western plains, the heavy burden bearers of the Orient, the field workers among the poorer peasantry of the Euro- pean countries, the women miners of Belgium, are all less prone to laughter — and also to weeping — than the excitable mental workers of American cities, or the lazy, well-fed and happy-go-lucky negro plantation 'hands.' The energy of the savage and of the "man with the hoe" like that of animals is preempted for a physical contest with nature. In the individual whose PAIN, LAUGHTER AND WEEPING 329 life lies in softer places there is always an excess of energy above purely muscular needs. Proneness to laughter and to weeping is modified by other conditions : by age, by sex, by training, by Photo by Brown Brothers, N.Y. FIG. 80. — LAUGHTER IN A HEALTHY CHILD. An admirable illustration of the activation of facial muscles which is associated with hearty laughter. mental states and, preeminently, by the state of health of the individual. Healthy, happy children are especially prone to laughter. (Fig. 80.) The aged 330 MAN --AN ADAPTIVE MECHANISM laugh less. Women laugh more than men. The healthy happy young woman on the verge of maturity laughs perhaps most of all, especially when slightly embarrassed. What causes laughter? Good news, high spirits, tickling, hearing and seeing others laugh ; droll stories ; flashes of wit and passages of humor ; averted injury ; threatened breaches of the conventions; and numer- ous other causes. At first glance it would seem im- probable that a single principle underlies all these diverse causes. Let us examine them, however, in the light of the fact that man is fundamentally a motor being, and that, in common with other responses to environmental stimulation, laughter is a muscular re- action. We have postulated (Chapter III) that the laughter excited by adequate stimulation of ticklish areas of the body is a recapitulation of ancestral struggles against the physical attack of biting and clawing foes on these parts. In other words, the laughter excited by tickling is a substitute for the motor act of defense against injury, and is a reaction imposed by the need for giving vent to the energy mobilized in the kinetic organs at the command of the phylogenetic stimulus. The resultartt action is purposeless, instead of purpose- ful ; but the result in the expenditure of energy is the same. If the laughter excited be sufficiently intense or prolonged, the individual is as exhausted as if he had actually struggled with an enemy. In like manner, the laughter excited by a psychic image is accompanied by a psychic conception, either clearly recognized or vaguely glimpsed, but none the PAIN, LAUGHTER AND WEEPING 331 less an action pattern. We have shown (Chapter V) that emotions and psychic concepts, being responses to distance ceptor stimulation, are as truly representa- tive of motor acts as are the responses to contact ceptor stimulation. Fear, anger and sexual love are representations of definite phylogenetic acts, which, if they do not follow directly upon the activating stimulus, leave the body in a physiological state of preparation for the act, which means that a certain amount of activating substances, which must be consumed or eliminated are thrown into the blood stream. If a motor act takes place in the midst of the emotion, the intensity of the emotion itself is lessened. A man in anger who fights, finds his anger dissipated as a result of his activity. A man in fear who flees, experiences less fear than he who waits motionless for the outcome of a situation. The activating substances thrown into the blood by any emotion may be consumed as completely by any other muscular action, as by the particular muscular action for which these chemical substances were in- tended. On this principle, the purpose and cause of laughter and of weeping may be explained. If an individual be intensely provoked to anger, one of three things might happen : he might perform no physical act, but give expression to the emotion of anger; he might engage in a physical struggle and satisfy his anger ; or he might immediately engage in violent gymnastic exercise which would consume the motor- producing elements mobilized in his body, and thus clarify the organism. Laughter and weeping are the gymnastic exercises which clarify the body under many 332 MAN --AN ADAPTIVE MECHANISM conditions of adequate stimulation to motor activity. Every one of the causes of laughter, when analyzed, resolves itself into a stimulation to motor activity of some kind. Quite by accident this point was tested in our laboratory during the course of some experiments on fear, A keen, snappy fox terrier was completely muzzled by winding a strip of adhesive plaster around his jaws, so as to include all but the nostrils. He was then turned loose upon a rabbit. When the aggressive terrier and the rabbit found themselves in close quarters, the instinct of each animal asserted itself. The rabbit crouched in fear, while the terrier, with all the assurance of its kind when confronted by its natural prey, rushed upon the rabbit as if to seize it, his muzzle glancing off at each attempt and the attack ending in awkward failure. These actions were witnessed, at various times, by various scientific visitors, and in every instance the sight provoked laughter. This laughter was undoubtedly due to the fact that in the mind of each onlooker the spectacle of the savage terrier rushing upon the helpless rabbit as if to mangle it aroused a strong desire to exert a muscular act to prevent cruelty. This integration caused a conversion of potential into kinetic energy in the brain-cells, and a discharge of activating secre- tions into the blood stream, for the purpose of pro- ducing the muscular action. When the danger was unexpectedly averted, the preparation for muscular activity was appropriated by the neutral muscular reaction of laughter. In children, almost any unexpected phenomenon, 333 such as a sudden "booing" from behind a door, will provoke laughter. In like manner, in an adult, a suddenly averted threat of danger, a breach of the conventions, sudden relief from acute nervous tension, a surprise, — indeed, any excitant, for which there is no predetermined method of physical response, — may give rise to laughter. In the same way the laugh- ter evoked by jokes may be explained. An analysis of a joke shows it to be composed of two parts, — a first part, in which is presented a stimulus to action ; and a second part, in which the story suddenly turns so that the stimulus to action is unexpectedly withdrawn ; and so there are jokes of the classes — bankers' jokes, politicians' jokes, professional men's jokes, etc. The stimulus which excites one to action, by reason of his permanent brain patterns, fails to elicit response from another collection of brain patterns, as the foe of one animal fails to inspire fear or resentment in another whose path it seldom crosses. It is interesting to note that the respiratory system, principally, is utilized for the muscular clarifying pur- pose of laughter. Why are not other muscular por- tions of the body utilized? Why do we not laugh with our feet and hands as well ? As a matter of fact, the by-products of excitation are often consumed in other motor acts than those accompanying laughter, as is shown often in public gatherings by the stamping of feet and clapping of hands of an audience excited or amused by the impassioned or humorous words of a speaker ; or by the activations of enthusiastic spec- tators at a championship ball game as pictured in Fig. 81. To be a truly adaptive phenomenon, however, 334 MAN — AN ADAPTIVE MECHANISM PAIN, LAUGHTER AND WEEPING 335 laughter must not seriously interfere with any other function. Were laughter expressed with the hands only, arboreal man might have fallen from the tree ; and if expressed by the feet, our equilibrium might be lost. Laughter, therefore, is expressed by means of a group of powerful muscles which can be spared easily without seriously interfering with the maintenance of posture or any other function. In order that the products of excitation may be quickly and completely consumed, the powerful group of expiratory muscles must have some resistance against which they can exert themselves strongly and at the same time pro- vide for adequate respiratory exchange. The inter- mittent closure of the epiglottis serves this purpose admirably, just as a horizontal bar affords the resist- ance against which the muscles of the athlete may be exercised. Weeping, like laughter, is a part of the reaction to a stimulation to some form of motor activity, which may or may not be performed. (Fig. 82.) Take the case of a mother anxiously watching the . course of a serious illness in her child. If, in caring for it, she is stimu- lated to the utmost to perform motor acts, she will continue in a state of motor tenseness until one of two events occurs — recovery or death. If relief be sudden, as, in the crisis of pneumonia, and the mother is not exhausted, she will easily laugh. If tired, she may cry. If death occur, however, the stimulus to motor activity is suddenly withdrawn and she cries aloud and may perform many motor acts as a result of the stimulation to motor activity which is no longer needed for the physical care of her child. 336 MAN — AN ADAPTIVE MECHANISM PAIN, LAUGHTER AND WEEPING 337 It is the common experience of every one to find that during a period of intense activity or intense integra- tion to activity, as in a great catastrophe or misfortune, that the power to laugh or weep has disappeared. As soon as the issue that causes the integration is deter- mined — the terror past or the doubt removed - the whole being seems to dissolve in one tremendous outburst of tears or laughter, with the result that the organism is in part immediately relieved. With this key, we can understand why laughter and crying are so closely associated, and so frequently interchangeable under the same conditions ; why either gives a sense of relief after stress ; and why neither can come until the issue which has precipitated the activation has been settled. We can understand why an averted breach of the conventions, which would have caused embarrassment, may excite laughter; and why the recital of heroic deeds of a certain type causes tears. Nowhere could this fact be more strikingly mani- fested than in the scenes of desolation and wretched- ness described by eyewitnesses of the physical and psychic results wrought by the present War of Nations in Europe. The characteristic of the people that most impresses all chroniclers is the calm, the apathy of those who have undergone physical injury or psychic stress. In the midst of battle, no one weeps ; no one laughs ; every one is integrated for muscular action, for killing or escaping. The crushing of Belgium caused no weeping until the refugees had reached a safe haven. Then they wept abnormally. I saw striking instances of this. 338 MAN --AN ADAPTIVE MECHANISM These are illustrations of the principle which we have sought to make clear in the foregoing chapters - the fact that the nervous system acts as a whole ; that it can respond to but one stimulus at a time ; and that when the nervous system is preempted by one stimulus to the point of exhaustion, it can respond to no other until an approximately normal condition of the kinetic system has been regained through rest. The lack of the power to laugh or weep, and the absence of pain among the exhausted, the senile and those weakened by disease demonstrate the fact that the kinetic system is exhausted ; that it has been integrated for response to a stimulus stronger than that to a motor activity for which laughter or weep- ing is a relieving substitute ; and that consequently the energy required for laughter or weeping is no more forthcoming than it is forthcoming for any other form of motor activity under the same conditions. A striking contrast to the absence of laughter or weeping when the brain thresholds have been raised by extreme exhaustion is found in the hypersusceptibility to both laughter and weeping, shown in cases of Graves' disease and in neurasthenia, both of which are inevitably marked by weak inhibition and a low threshold to all stimuli. In Graves' disease the motor mechanism is in an exalted state of activity. These patients, therefore, as would be expected, exhibit an extreme susceptibility to laughter and weeping because of the fact that the motor mechanism is constantly integrated by the most trivial stimuli. In Graves' disease the flood gates of tears are open. The susceptibility to pain is also PAIN, LAUGHTER AND WEEPING 339 intensified; and in these patients surgical shock is produced with abnormal facility. In the neurasthenic whose threshold also is low to stimuli, the discharge of energy in pain or laughter is equally facilitated. Since pain, like laughter and weeping, is a motor phenomenon, it is not surprising that where pain does not give rise to muscular activity, it frequently leads to weeping. CHAPTER XIV TRANSFORMATION OF ENERGY AND ACIDOSIS THE blood of man, under normal conditions, is slightly alkaline with a hydrogen-ion concentration of about 7.56 in terms of Sorenson's logarithmic notation. But although in circulating blood the H-ion concen- tration upon which the amount of acidity depends is little more than that of distilled water, the blood is potentially much more alkaline than water, being able to neutralize a considerable amount of acid. At the time of death, from whatever cause, the con- centration of H-ions in the blood is increased, the potential or actual alkalinity is decreased, and the blood becomes, in fact, neutral or acid. In order to discover what conditions tend to diminish the normal alkalinity of the blood, observations were made for me in my laboratory by Dr. M. L. Menten, Dr. W. J. Crozier, Dr. W. B. Rogers and Dr. B. I. Harrison, using electrical and chemical methods for determining the H-ion concentration of the blood under certain pathologic and physiologic conditions. As a result of these researches we are able to state that the H-ion concentration of the blood is increased by excessive muscular activity; by excessive emotional activation; by surgical shock; by asphyxia; in strychnin convulsions; by inhalation anesthetics; in the late states of li/e after excision of the pancreas, of the liver and 340 ACIDOSIS 341 of the adrenals; and by the continuous infusion of adrenin solution. On the other hand, the administration of morphia causes no change in the H-ion concentration of the blood nor does decapitation, provided artificial respira- tion is maintained. Many observations were made on animals near death from various causes. In each instance the blood became increasingly acid as death approached. This fact suggests the following question : Is the termination of life in many diseases, such as infections, Graves' disease, shock, etc., due to the failure of the body to maintain its alkalinity? Certain facts seem to support an affirmative answer to this question, namely : (1) the intravenous injection of certain acids causes death quickly ; and (2) the intravenous injec- tion of acids causes extensive histologic changes in the brain, the adrenals and the liver, which resemble the changes invariably caused by excessive activation of the kinetic system. Certainly it would seem as if anesthesia and many instances of unconsciousness are associated with in- creased H-ion concentration of the blood. As pre- viously stated, we found that the H-ion concentration of the blood is increased by alcohol, by ether and by nitrous oxid. In addition, we found that the increase in H-ion concentration was more gradual under ether administration than under nitrous oxid, an observa- tion which accords with the fact that nitrous oxid induces anesthesia more quickly than does ether. Williams has found that in animals under ether anesthesia no nerve currents are detected by the 342 MAN --AN ADAPTIVE MECHANISM Einthoven string galvanometer. If we postulate that a nerve current can pass from the brain to the muscles and glands only if there be a certain difference in potential between these parts, the absence of a nerve current in anesthetized animals may be explained on the basis that any change in the normal alkalinity of the body would diminish the difference in potential ; and hence the acidity produced by inhalation anes- thetics would so far decrease the difference in potential as to inhibit the passage of the nerve impulse. According to this hypothesis, as long as life exists, a string galvanometer of sufficient delicacy should detect a nerve current between the brain and the muscles and glands, that is, until the acidity is sufficiently increased to reduce the difference in potential to zero or the death point. During sleep one would expect a dimin- ished flow of action currents. Blood taken from a sleeping man showed normal H-ion concentration. The histologic changes in the brain, the adrenals and the liver, produced by acid sodium phosphate appar- ently, are not repaired during rest without sleep, but are repaired during sleep. Acidosis, therefore, may be caused by an intake of a smaller amount of alkalies and bases than are re- quired to maintain an alkaline or neutral state ; by an excessive rate of acid production; or by interference with one or more of the organs of acid elimination. This conception of the relation of acidity to anes- thesia and unconsciousness harmonizes many facts. It explains, for instance, how asphyxia, overwhelming emotion or excessive muscular activity, by causing acidity, may produce unconsciousness. It explains ACIDOSIS 343 the acidosis resulting from starvation, from uremia, from diabetes or from Bright 's disease ; and supplies a reason why the use of intravenous infusions of sodium bicarbonate sometimes overcomes the coma of diabetes and uremia. It may explain the quick death from chloroform, ether and nitrous oxid, and may, perhaps, suggest why unconsciousness is so commonly the immediate precursor of death. One of the most noticeable immediate effects of the administration of an inhalation anesthetic is a marked increase in the rapidity and amplitude of the respi- ration. The respiratory center has evidently been evolved to act with increased vigor proportional - within certain limits — to the increase in the H-ion concentration, whereas the centers governing the voluntary muscles are depressed with the increase in H-ion concentration. In these antithetic reactions of the higher cortical centers and the lower centers in the medulla to acidity we find a remarkable instance of adaptation, by which the animal is prevented from killing itself through the further increase in acidity which would result from continued excessive muscular activity. In other words, as the acidity produced by muscular activity increases and threatens life, the respira- tory action, by which carbon dioxid is eliminated and oxygen supplied, thus diminishing the acidity, is in- creased, while the driving power of the brain, by which acidity is produced, is lessened or inhibited, producing unconsciousness. Without this life-saving regulation, animals under stress would inevitably commit suicide. Direct chemical evidence supports the postulate that the cortical centers and the centers in the medulla 344 MAN --AN ADAPTIVE MECHANISM have been evolved to react to acidity in opposite ways ; namely, the histologic changes in the several parts of the brain, produced by the intravenous injection of hydrochloric acid, acid sodium phosphate, etc., and by such acid-producing work as muscular exertion, emotion, physical injury, etc., are uniformly unequal. These changes are striking in the cerebral cortex and slight in the medulla. It is probable that the remarkable phenomenon of anesthesia — the coexistence of unconsciousness and life — is made possible by this antithetic relation be- tween the cortex and the medulla. Within a few seconds after the beginning of nitrous oxid anesthesia the acidity of the blood is increased. This rapid acidulation is synchronous with almost instantaneous unconsciousness and increased respiration. If the amount of oxygen in the inhaled mixture be increased, a decrease in acidity occurs, together with lighter anesthesia and a decreased respiratory rate. If our premises are sound, we are justified in con- cluding that the state of anesthesia is in part, at least, the result of an induced acidity of the blood. If the reduction of alkalinity be slight, then the anesthesia is light, and the force of the nerve impulses is lessened, but the patient is still conscious of them. As the alka- linity of the blood continues to decrease, associative memory is lost, and the patient is said to be uncon- scious ; the centers governing the voluntary muscles are not wholly inhibited, however, since cutting the skin causes movements. If the alkalinity be further de- creased, there is loss of muscular tone and even the strong contact ceptor stimuli of a surgical operation do ACIDOSIS 345 not cause any muscular response. And, finally, the acidity may be increased to the point at which the re- spiratory and circulatory centers can no longer respond, and anesthetic death — that is, acid ( ?) death — fol- lows. It should be admitted, however, that increased acidity and its phenomena may be end-effects and not causes of anesthesia. Opposed to this postulate is the fact that the in- jection of sodium bicarbonate does not overcome in- halation anesthesia. Possibly there may be intra- cellular acidosis which is not easily overcome by alkalies. How valuable this fact may be, I do not know. Certain clinical phenomena are clarified, how- ever, by this postulate, and support it. For example, it is well known that inhalation anesthesia precipitates the impending acidosis which results from starvation, from extreme Graves' disease, from great exhaustion, from surgical shock and from hemorrhage, or when an animal is near death from any cause. In striking contrast to the action of inhalation anes- thetics, deep narcotization with morphin and scopolamin is induced slowly and the respiratory and pulse rates are progressively lessened. In addition, our experiments have shown that no increase in the H-ion concentration of the blood is produced by morphin or by scopolamin, no matter how deep the narcotization. In animals al- ready narcotized by morphin, the production of acid by any of the acid-producing stimuli was delayed or prevented. On the other hand, in animals in which an acidity had already been produced by ether, shock, anger or fear, the administration of morphin delayed or prevented entirely the neutralization of the acidity. In 346 MAN — AN ADAPTIVE MECHANISM other words, morphin interferes with the normal mechanism by which acidity is neutralized, possibly because its depressing action on the respiratory center is sufficient to overcome the stimulating action of acidity on that center, for, as we have stated, the neutralization of acidity is in large measure accom- plished by the increased respiration induced by the acidity itself ; possibly also because morphin prevents the output of adrenin, and adrenin measurably governs the great acid-reducing organ — the liver. Acidosis in Relation to Normal and Pathologic Phenomena If, as is now believed by physiologists, the respira- tory center is governed by the H-ion concentration of the blood, rather than by the want of oxygen merely, then the elimination of the by-products of metabolism is of paramount importance in the maintenance of the health of the organism ; and its clinical significance, as pointed out by many observers, notably Fisher, Hen- derson and Michaelis, is obvious at once. In my laboratory many observations have been made to determine the effect of the excision or functional de- pression of certain organs on the normal reaction of the blood and of the urine. When the liver is excised, the alkalinity of the blood is rapidly diminished and death follows. When the adrenals are excised, the blood maintains its normal reaction for a longer time — perhaps twice as long — but then its acidity increases rapidly and death follows. (Figs. 83, 84.) When con- nection between the brain and the remainder of the body is broken at the medulla, the blood remains normal ACIDOSIS 347 for as long as eight hours and shows no tendency to in- creased acidity. When the thyroid, spleen, testicles, kidneys, uterus, stomach or intestines, in short when any other organ than the adrenals, the liver or the A. Section of normal cere- bellum of a dog. B. Section of cerebellum of a dog after double adrenalectomy. C. Section of cerebellum of a dog after double adrenalectomy followed by injections of sodium bicarbonate. FIG. 83. — THE PROTECTIVE EFFECT ON THE BRAIN-CELLS OF A DOG OF INJECTIONS OF AN ALKALI AFTER DOUBLE ADRENALECTOMY. Note the disintegration and disappearance of Purkinje cells in B and the normal intact condition of the Purkinje cells in C. This and the following figure demonstrate the neutralizing function of the adrenals. (From photomicrographs, X 310.) pancreas is removed, there is no tendency to immedi- ate acidosis. Apparently, therefore, only the liver, the adrenals and the pancreas are principally engaged in the preservation of the normal alkaline reaction of the body fluids. The respiratory system eliminates the 348 MAN --AN ADAPTIVE MECHANISM gaseous by-products of energy transformation; the kidneys eliminate the acid salts in solution ; the liver reduces the acid by-products to render them suitable for elimination by the kidneys ; the adrenals measur- ably govern the liver and perhaps the oxidation process required for the reduction of acid by-products. Oxygen A. B. c. Section of normal liver Section of liver of a Section of liver of a of a dog. dog after double adre- dog after double adre- nalectomy. nalectomy followed by injections of sodium bicarbonate. FIG. 84. — THE PROTECTIVE EFFECT ON THE LIVER OF A DOG OF INJEC- TIONS OF AN ALKALI AFTER DOUBLE ADRENALECTOMY. Note the disappearance of cytoplasm and of nuclei from B as compared with the normal and numerous nuclei and the conserved cytoplasm in C. (From photomicrographs, X 1640.) is apparently necessary in some way to acid elimina- tion, just as oxygen is necessary to energy transforma- tion. Adrenin also is necessary to both. Let us examine some of the phenomena of normal and pathologic activation in the light of this hypothesis that acidity is the cause, rather than the result, of death ; ACIDOSIS 349 that acidity blocks, as it were, the electrical discharge from the brain, which constitutes the principal attri- bute of life itself. The respiratory rate is governed by the changes in the H-ion concentration of the blood, which result from energy transformation in the body; the pulse rate — provided local organs are normal — and also the temperature vary with the respiratory rate. We know that certain diseases are caused by failure of the organ- ism to eliminate acid by-products. Bearing these facts in mind, let us examine the phenomena of several forms of activation. In great exertion the characteristic phe- nomena are rapid respiration, rapid pulse, sweating, redness of the skin, thirst and a progressive exhaus- tion. In the great emotions, emotions sufficiently in- tense to overwhelm the individual, the characteristic phenomena are the same — rapid pulse, sweating, flushing, thirst and exhaustion. These two normal states closely resemble each other. Do they in turn resemble the phenomena of certain pathological states ? Note the phenomena of fever. In the infections the leading symptoms are increased respiration, increased pulse rate, sweating, flushed face, thirst and exhaus- tion. In Graves' disease the leading symptoms are the same. Thus four comprehensive and typical conditions — exertion, emotion, infection and Graves' disease — have certain phenomena in common, a fact which strongly suggests that these phenomena result in a large measure, at least, from the physical and chemical work involved in the elimination of acid by-products. (Fig. 85.) 350 MAN --AN ADAPTIVE MECHANISM Granting this, we can understand clearly why acidosis is so frequently seen in severe cases of Graves' disease and why acidosis results from violent fever. We can understand the occurrence of albumin and casts in the A. B. Section of normal human cerebellum. Section of human cerebellum after (After accidental death.) death from acute acidosis. FIG. 85. — EFFECT OF ACUTE ACIDOSIS ON THE BRAIN-CELLS OF A HU- MAN BEING. In B note the complete disintegration of the Purkinje cells of which but faintest traces remain. (See arrows.) (From photomicrographs, X 310.) urine as a result of exertion or emotion and in Graves' disease. The H-ion Factor in Graves' Disease Having noted that the symptoms of Graves' disease resemble closely those of extreme exertion, of intense ACIDOSIS 351 emotion and of violent infection, we now offer the follow- ing interpretation of these phenomena. Whenever there is an increased transformation of energy, the H-ion concentration of the blood is in- creased. As shown by Du Bois, in Graves' disease there is a continuous increased transformation of energy, hence an increased production of acid, and, conse- quently, an increased demand upon the acid neutraliz- ing power of the body. Let us now consider the symptoms in Graves' disease that may be due to acidosis in contradistinction to the symptoms that may be due to the activation of the kinetic system. As we have stated, H-ion concentration is controlled by three agencies : first, the elimination of carbon dioxid by means of the respiratory organs ; second, the breaking down of the acid by-products of energy transformation by the liver; and third, the elimination of the acid by-products by means of the kidneys and skin. In Graves' disease the continu- ous excessive transformation of energy steadily reduces the neutralizing bases stored in the body until acidosis automatically results from the loss of neutralizing ma- terial. In addition, in Graves' disease the most im- portant neutralizing organ — the liver — is greatly impaired — brown atrophy. The symptoms of so- called hyperthyroidism differ very little if at all from the symptoms of straight acidosis. This being so, does it not follow that postoperative hyperthyroidism is in fact an acidosis? The symptoms of acidosis are increased respiration, increased sweating, loss of mental and muscular power, restlessness and, in extreme cases, delirium and uncon- 352 MAN — AN ADAPTIVE MECHANISM Section of normal human Section of cerebellum of a soldier cerebellum. who had suffered from hunger, thirst and loss of sleep ; had made the ex- traordinary forced march of 180 miles from Mons to the Marne ; in the midst of the greatest battle in history was wounded by the explosion of a shell ; lay for hours waiting for help, and died from exhaustion soon after reaching the ambulance. Compare the faded-out exhausted Purkinje cells with the Purkinje cells in A. FIG. 86. — EFFECTS OF EXTREME ACTIVATION ON THE BRAIN-CELLS OF A SOLDIER. (From photomicrographs, X 310.) ACIDOSIS 353 A. Section of normal adrenal. B. Section of adrenal of soldier de- scribed in Fig. 86. The general disintegration of the cells, loss of cytoplasm, misshapen and eccentric nuclei illustrate the effect of emotion, exhaustion, lack of sleep, pain and trauma. FIG. 87. — EFFECTS OF EXTREME ACTIVATION ON THE ADRENALS OF A SOLDIER. (From photomicrographs, X 1640.) 354 MAN --AN ADAPTIVE MECHANISM sciousness. The increased temperature, increased pulse rate, flushed face and flushed extremities are identi- cal with the symptoms of so-called hyperthyroidism. Section of normal liver. Section of liver of soldier described in Fig. 86. The general disintegra- tion of the cells, the loss of cyto- plasm, and the vacuolated spaces within the cells illustrate the effect of emotion, exhaustion, lack of sleep, pain and surgical trauma. FIG. 88. — EFFECTS OF EXTREME ACTIVATION ON THE LIVER OF A SOLDIER. (From photomicrographs, X 1640.) Furthermore, as postoperative hyperthyroidism devel- ops and continues, practically always a stage super- ACIDOSIS 355 venes in which there is acetone in the breath, and diacetic acid in the urine — a true acidosis. The assumption that postoperative hyperthyroidism is a true acidosis explains also why it is that just be- fore death in fatal cases of Graves' disease the tempera- ture may rise as high as 107, 108 and even 109 degrees. It is because the long period of relative acidosis before the operation together with the increased acidity result- ing from the operation, has taken away from the body the safe margin of neutralizing bases and alkalies and therefore the neutralizing bases in the living protein molecules are seized by the acids. This chemical process of breaking down the living protein molecules liberates heat. This heat is the chief cause of the rise in tem- perature before death. We know that when the tem- perature rapidly rises after a period of acidosis the living molecules are breaking down — and the end is near. Summary The establishment in the body of so powerful a group of organs and mechanisms for the elimination of the acid by-products of energy transformation shows how vitally necessary is the maintenance of the normal slightly alkaline reaction of the body. This indicates that acidosis is a factor in many diseases — acute and chronic — and that the centers in the medulla are stimulated by acidosis while the higher centers are de- pressed ; it suggests an explanation of the phenomena of anesthesia, and that the ultimate cause of death is usually acidosis. (Figs. 86, 87, 88.) CHAPTER XV ELECTRO-CHEMICAL PHENOMENA PHYSICISTS tell us that, in the last analysis, the pri- mal stuff alike of matter and of energy is electricity. Whatever may be the superficial aspects of man's form 'and functions, ultimately they are phenomena of elec- tricity. We may well ask, therefore : Is the trans- formation of energy by which men and animals are enabled to adapt themselves to their environment effected through an electro-chemical mechanism? If this be true, there should be evidence to show : (1) that electricity is produced in the body ; (2) that a current of nerve action, an electrical phenomenon, always accompanies the passage of the nerve impulse ; (3) that in motor organs the electro-motive force of this current varies with the rate and extent of energy trans- formation ; (4) that when there is no transformation of energy, there is no action current ; (5) that electric- ity alone, either directly or indirectly, can excite vari- ous organs and tissues to perform their function ; (6) that in the body are structures well suited to be parts of an electro-chemical mechanism which is capa- ble of performing the work of the body ; and finally (7) that no other form of mechanism is capable of performing this work. One of the oldest established facts in the physiology of plants and animals is the fact that there is an electro- 356 ELECTRO-CHEMICAL PHENOMENA 357 negative variation during action. This was long ago studied in the sensitive plant. Bose has shown that electric currents are present in all plant activities. He has plotted curves of electric variation corresponding to periods of activity and of rest, and has shown that life and electric phenomena end simultaneously. Osterhaut has shown that the normal electric phenom- ena in kelp are changed by anesthetics, by iodin, by acidity and by varying the concentration of sodium, potassium and magnesium salts in the solution in which the kelp is immersed. He showed that the permeability of the plant cells varies with the activity of the plant, and that at death this electric phenomenon disappears. He also showed that the amount of energy in plants corresponds with the degree of permeability to electric currents at the surfaces of plant cells. R. S. Lillie established similar facts regarding the perme- ability of the larvae of the marine worm, Arenicola. Lillie and Osterhaut believe that the electric phenomena of life in animals and plants are dependent upon changes in the permeability of the semi-permeable membranes which surround vegetable and animal cells. Lillie applied Nernst's laws to the life phenomena of the Arenicola. He produced strong evidence that these are electric phenomena and are dependent, primarily, upon the permeability of the cells. The work of Lillie strongly suggests that the essential phenomena of life are identical with the phenomena of electricity, that is, with variations in ionic concentration and changes in permeability of the semi-permeable membranes — in short, with the reactions of an electro-chemical mecha- nism. Robertson showed, moreover, that by using oils, 358 MAN --AN ADAPTIVE MECHANISM alkalies and acids, most of the cellular phenomena of animals could be reproduced. After exhaustive studies of nerve currents, Williams and Crehore, making observations with an Einthoven string galvanometer, constructed an artificial nerve which gave convincing evidence that the nerve action current is identical with electricity. An extract from the report of these experiments of Williams and Crehore to the Society for Experimental Biology and Medicine, reads as follows : " Nearly two centuries ago it was surmised that the nervous impulse might be of the nature of an electric current, but in the absence of definite proof the hypoth- esis was rejected, especially as objections were raised to it which seemed insuperable. It is difficult, if not altogether impossible, to reconcile all experimental results with the consequences of the molecular theory. If, however, we regard the nerve as an electrical con- ductor with distributed capacity, we are able to ac- count for many of the fundamental experimental phenomena and also to predict the results of new ex- perimental conditions. It has long been known that the speed of electricity on wires is less than the speed in free space and the formulae for calculating these velocities are well understood. The rate of propaga- tion of electricity in a conductor similar in form, size and material to a nerve fiber should be, according to these formulae, of approximately the same order of magnitude as has been measured for the rate of the nervous impulse. " The enormous reduction of velocity (about ten million times) is chiefly attributable to the great ohmic ELECTRO-CHEMICAL PHENOMENA 359 resistance of the conductor coupled with the elec- trostatic capacity. As a result of measurements on the phrenic nerves of cats and calculations based on data of microscopic sections of nerves, we have been able to construct an artificial 'nerve' of glass, paper, tinfoil and graphite, whose total resistance and capac- ity are of the same order of magnitude as those of the cat's nerve. On applying the break E. M. F. of an induction coil to this artificial nerve and leading off to a string galvanometer in the usual manner we have obtained typical diphasic curves almost identical with those obtained from cat nerves stimulated with the same current. Of greater significance is the fact that we have been able to predict a change in the form of the curves with change in the nature of the applied E. M. F. and to predetermine the character of the change. As an example we may mention that the action current of nerves stimulated by the make or break of a constant current is of totally different form, when registered as a curve, from the diphasic curves obtained by applying a momentary E. M. F. "It seems at present altogether probable that the phenomena of electrotonus, the effects of lowering of temperature, anesthetics and other well-known phenomena of nerve will be found on investigation to be compatible with the theory that nervous phenom- ena are essentially electrical in nature." One of the oldest established facts in physiology is the electric variation in muscle and nerve action. The question has always been : Is this electric phenomenon a result or a cause of action? The work of Crehore and Williams, however, apparently proves that it is 360 MAN — AN ADAPTIVE MECHANISM neither cause nor effect, but identical with the action. Numerous observations made by means of the Ein- thoven string galvanometer show that there is a quanti- tative variation in the flow of electricity in muscular activity. There is a rhythmic variation with each heart beat ; and there is an intermittent variation in the flow of electricity over the phrenic nerves during respiration. During inhalation anesthesia no electric current can be detected except that identical with respiration and circulation. After death no electric current can be detected. During muscular action the flow of electricity along the efferent nerves is always from the brain toward the periphery. It is evident, therefore, that animals produce electricity ; and that in muscular action there is a quantitative flow of elec- tric current along the nerve fibers supplying the in- volved muscles. Can electricity alone cause the various organs and tissues to perform their functions? Answer to this query is found in the accepted physiologic fact that adequate electric stimulation of any gland or muscle in the bod}7 results in the performance of its normal function. If the body be operated by means of electric power, then the electricity must be fabricated within the body, which must of necessity then contain mechanisms for the production and storage of electricity, as well as an electro-motive apparatus and provision for maintaining a difference in potential. In short, there should be found in the body a complete electro-motive apparatus, supplying its elements and disposing of its waste matter. ELECTRO-CHEMICAL PHENOMENA 361 The motor mechanism is readily apparent : the nerve ceptors, contact, distance and chemical ; the nerve fibers leading from these to the brain ; the nerves leading from the brain to all muscles of the body; the bones and joints; the muscles — these make up the motor mechanism. With properly ad- justed electric stimulation of the various muscles by means of a faradic battery, there is no doubt that, for instance, the motor mechanism of a dog recently killed could be made to run, to fight, to bark, indeed, to perform every adaptive movement of the body. But these movements would come to an end quickly. The fuel stored in the muscles would soon be used up. The waste products of energy transformation would speedily choke the motor. An automatic mechanism, such as man, must have an automatic arrangement for pre- venting polarization of the brain battery, for renewing the elements of the battery, for bringing to the muscles new stores of energy and for taking from the muscles the hampering waste matter. To serve certain of these ends blood has been evolved. Blood floods every cell of the battery and every element of the motor ; it carries replenishing stores of energy to the brain and the muscles and brings back the waste products. The mechanisms which prevent polarization of the battery by maintaining the difference in poten- tial, and change the rate of electric discharge and the rate of fabrication of electricity remain to be pointed out. Granting that in the normal state the battery is not polarized, and that the necessary difference in poten- tial exists, we may assume that the battery in the 362 MAN --AN ADAPTIVE MECHANISM human body is, in some respects, like the battery in common use — that is, its loss of difference in poten- tial is due to the action of the battery itself. This being the case, the organs which eliminate waste matter and those which contribute additional energy may be justly regarded as the organs which preserve the difference in potential. As for the organs of elimi- nation, one would expect that for such a large energy transformer as man, the most important organ of the eliminating mechanism would be large in proportion to man's size ; that it would have a protected location in the center of the body ; that it would have a wide margin of safety to cover the emergencies of life. Furthermore, when this neutralizing organ is excised, the electro-motor would be quickly impaired ; fabri- cation of electricity would quickly be arrested ; and the animal, together with the battery, would be "dead." The organ which complies with this descrip- tion, and is the chief of those organs serving to maintain the difference of potential between the brain and the muscles, apparently is the liver. The ultimate and final ejection of the waste products, thus prepared for elimination by the liver, is accomplished by the kidneys and the lungs. In addition to this fundamental work of elimination, the liver also stores fuel — glycogen. Thus we see that there is in the body an automatic non-polarizable battery, a mechanism for keeping the muscles (the motor) cleared of waste, nerve ceptors specifically adapted to internal and external environ- mental stimuli, and nerve conductors for transmit- ting stimuli to the adaptive action patterns in the brain. ELECTRO-CHEMICAL PHENOMENA 363 In the brain is created not only the electric force that drives the muscles to fabricate heat and motion, but also the electric force that activates certain muscles to assist in the elimination of the acid by- products of energy transformation. To this end, a nerve runs to every muscle which takes part in this elimination, just as to every muscle which takes part in the act of transforming energy. The number of muscles actually engaged in the gross adaptive act are comparatively few; but the muscles engaged in the simultaneously increased actions of circulation, respira- tion and the elimination of waste matter are many. If a separate impulse were required to go from the brain to every one of the tiny muscles in the walls of the blood vessels and to every cell of the glandular tissues cooperating in the adaptive response, a vast nervous system would be needed. To obviate this need, there has apparently been evolved an organ, itself under the control of the brain, the secretion of which is capable of mobilizing all the organs and tissues in accordance with the part each is to play in the response. The secretion of this organ increases the action of the brain, raises the blood pres- sure and accelerates the circulation. It increases the efficiency of the eye by causing the eye to protrude and the pupil to dilate. It probably increases still more the difference in potential at the myoneural junction, and facilitates the neutralization of the acids resulting from energy transformation. The action of this secretion, in accordance with what would be most useful in the changeful environment, is quick — almost instantane- ous ; powerful, but fleeting. This secretion is adrenin. 364 MAN --AN ADAPTIVE MECHANISM The electric mechanism we have thus far described is wonderfully adapted to the transformation of energy and the elimination of the waste matter resulting from that activity ; it responds quickly to every adequate stimulus ; but still is a mechanism which responds at the same rate for all seasons of the year, for all phases of lifet for all moments of those phases; but such a mechanism is not yet a complete adaptive mechanism. Many periods in the life of the organism require the expenditure of energy at a much higher speed than is required at other periods. In certain seasons of the year, for example, an increased expenditure of energy is needed for adjustment to food supply and climate. In like manner, there are periods of physi- ological adjustment, such as adolescence, the period of reproduction, courting and mating, and pregnancy; periods requiring sustained physical efficiency, such as the long chase ; periods of intense metabolic activity for maintaining the chemical purity of the body, as in infection and auto-intoxication. At such times of " forced draft " on the bodily energies, there is re- quired an organ -that will speed up the activity of the whole electro-chemical mechanism for the transforma- tion of energy ; an organ the secretion of which will act primarily upon the brain, so modifying it that the threshold to all stimuli will be lowered, in order that the brain may drive the body with increased force, and the total output of energy may be constantly augmented. In distinction from the fleeting action of the secretion of the adrenals, the action of the secretion of such an accelerating organ should be slower, steadier and more persistent in its effect. ELECTRO-CHEMICAL PHENOMENA 365 The one secretion which answers these requisites is the secretion of the thyroid gland. The specific chemical constituent of the thyroid is known. It is iodin. Thyroid extract alone, or iodin alone, causes a steady rise in the rate of energy transformation, a sustained maximum and a gradual fall. With the brain, the muscles, the liver, the adrenals and the thyroid, we have the essential parts of an automaton, which stores energy in sleep and automati- cally discharges energy during consciousness ; maintains the difference in potential between brain and muscles ; mobilizes and demobilizes organs by means of the adrenals ; and adaptively varies the speed to accord with seasonal and physiologic vicissitudes by means of the thyroid. CHAPTER XVI THE INDIVIDUAL AS AN ADAPTIVE MECHANISM HAVING now presented some evidence which sug- gests the mechanistic character of certain organic proc- esses in man, let us roughly sketch his career as an individual, upon the assumption that he is an adap- tive mechanism, dependent for life, as for death, upon the physical conditions of his internal and external environment. The life of the individual begins with the union of the spermatozoon and ovum. As far as the initiation of development is concerned, this, as Loeb has shown, is essentially a physico-chemical phenomenon. The fertilized ovum may be ejected from the end of the fallopian tube ; or, after reaching the uterus, it may be cast off in a hemorrhage caused by a submucous fibroid ; in either case, it is a mechanistic end. The fetus may fail to thrive or develop in the uterus of a syphilitic mother the chemical change in whose tissues is produced by a parasite — a spirochete, the activity of which may be checked by a chemical agent — mer- cury. Again, the life of a fetus in a normal uterus may be terminated if the mother be physically injured or be the subject of strong emotion. In either case, the end is mechanistic. The life of the individual may be terminated at birth 366 SUMMARY 367 by any one of many mechanistic accidents. He may be too large to be born naturally, in that event, if no help is at hand, he dies with his mother ; or his body may be removed in pieces, that his mother may live. In the violence of birth, a blood vessel in the brain of the child may be ruptured and a clot form ; and, in con- sequence of the continued pressure on the brain by this clot, the growth of the brain may be hindered. The brain being defective, the child — the man — will be permanently defective, and, as such, will be forced to leave the main road of usefulness and happiness and take the byways as a paralytic ; — a mechanistic fate. Then again, the blood of a syphilitic mother may im- pair, but not kill, the offspring, which may be born with the disease, perchance to die early, perchance to share the mechanistic fate of his fellow with the brain clot. Again the mother of an individual may live in a goiterous region, and in consequence be wanting in thyroid efficiency. The individual, in that event, may be born a cretin. On the other hand, had the mother been given sufficient sheep's thyroid or iodin during pregnancy, she might have borne a normal child in- stead of a cretin ; or the child, if born a cretin, might be made to develop in a normal way by the adminis- tration of thyroid extract. All that stands between the stunted, stupid, dwarfed, defective cretin and the normal child is iodin; between the syphilitic defective and the normal, mercury; between the clot-palsied child and the normal, a surgical operation. If, by chance, the mother of an unborn individual be starved to emaciation, the offspring struggles with the mother against starvation ; or if the food of the 368 MAN — AN ADAPTIVE MECHANISM mother lacks salt or certain vegetables and scurvy appears, the offspring suffers also. Thus, the simplest mechanistic causes may terminate the life of the fetus or produce a weak or defective child. The first respiratory movements of the newborn babe are excited by the very delicately adjusted center in the medulla which responds to external stimuli or to slight variations in the alkalinity (H-ion concentra- tion) of the blood, this variation being produced by the asphyxia resulting from the withdrawal of the maternal circulation when the placental structures are separated. With the pressure of the lips of the newborn child against the nipple, the act of sucking is excited. The presence of milk in his mouth excites swallowing ; and the entire digestive mechanism is activated by the swallowed milk. Thus the child becomes a breathing, sucking, digesting mechanism. Light and shadow and sound soon activate his brain. Each activation of the mechanism for the execution of a given action through contact or distance stimuli facilitates the passage of repetitions of these stimuli, and thus are the first of the vast numbers of action patterns formed. In the plastic brain of the newborn babe new action patterns are made during each wakeful moment. Contact stimuli become associated with distance stimuli and associative memory is established. That the standard of chemical purity in the body may be maintained, the organs of the kinetic system are stimulated to increased activity by the presence of foreign proteins. In like manner, hunger, thirst and cold stimulate the kinetic system to activities by which food, drink and shelter may be secured. Threatened SUMMARY 369 attack activates the kinetic system for fight or flight. Dust in the nose causes the reaction of sneezing ; in the larynx, of coughing; in the eye, of winking. Obstructions of the intestine, of the bile and urinary passages cause expulsion contractions (colic). In- juries of the outer parts of the body cause pain and muscular action. Implanted in the body are unequally distributed contact ceptors — numerous in areas presented to environment; sparse or absent in protected regions. We find a correspondingly uneven distribution of defense mechanisms against phylogenetic infections and against bleeding ; most numerous in the regions phylogenetically exposed to infection and hemorrhage, and sparse or absent from shielded areas. Thus the distribution of the defense mechanisms recapitulates the selective struggle of the organism against its hostile internal and external environment. The respiratory system, the adrenals and the liver are the principal mechanisms evolved for overcoming the acid by-products of energy transformation. The respiration eliminates carbon dioxid. The liver breaks down the acid by-products thus preparing them for elimination, and the adrenals facilitate the needed oxi- dation by which this is accomplished. When acid formation is rapid therefore, as in emotion, in fighting, in running, in fever and in Graves' disease, or when acid elimination is defective, as in hemorrhage, as- phyxia, failure in circulation, the late stages of dia- betes, of cardiovascular disease or of Bright's disease, and in cases of liver insufficiency ; or when acidity is in- duced by ether, chloroform or nitrous oxid, the respira- 2n 370 MAN --AN ADAPTIVE MECHANISM tory rate is increased through the specific stimulation of the respiratory center by the increased H-ion con- centration. The kinetic system is driven only by the higher centers of the brain. They alone control the adaptive transformation of energy. Increased H-ion concentration diminishes and even arrests the driving power of the brain ; that is, it inhibits the higher centers and stimulates the respiratory and other acid- neutralizing mechanisms. This antithetic reaction of the acid-producing part of the brain and the acid- eliminating part of the brain prevents death by acidosis during muscular exertion, emotion and fever. If, however, we give an individual deep narcotiza- tion with morphia before he is given the adequate stimulus to emotion, exertion or fever, we find there is little or no transformation of energy, and his brain- cells, adrenals and liver remain histologically normal. Morphia performs a physiologic decapitation, com- pletely neutralizing the effect of the crushing injury, the overwhelming danger, or the powerful infection. As a corollary, we find that, if decreased alkalinity be present either as a result of energy transformation, of inhalation anesthesia or of some other cause, then large doses of morphia hinder or prevent the return of the blood to its normal alkalinity. Strychnin and iodin are antithetic to morphia, the first causing convulsions and the second causing the kinetic drive of fever, emo- tion or exertion. Whatever causes excessive energy transformation diminishes the alkalinity of the blood and causes an increased output of adrenin, mobilizes thyreoidin and glycogen and by increasing the electric output of the brain leads to physical exhaustion and SUMMARY 371 identical histologic lesions in the brain, adrenals and liver. If, instead of an increased transformation of energy through a short period, an individual be subjected to a prolonged period of increased transformation of energy from the diverse causes already mentioned, then we find changes of great significance in the organs of his kinetic system. The thyroid may become hyperplas- tic, as in the case of prolonged infection, pregnancy, auto-intoxication and sexual excitation. In animals and in man, likewise, we frequently find the adrenals enlarged in the breeding season, in pregnancy, in car- diovascular disease, after or during chronic infection; while injections of indol, skatol, leucin, tyrosin or peptone, intense fear and excessive muscular exertion cause an increased output of adrenin. In these states, also, the adrenals contain less adrenin, and the liver less glycogen than in the normal state. During pregnancy many organs undergo structural changes. The mammary glands enlarge ; the thyroid, adrenals, brain and liver show increased activity in the transformation of energy and in the neutralization and excretion of acid by-products. In some instances, the organs of neutralization and excretion prove inade- quate ; and in consequence, there result nephritis, high blood-pressure and rapid respiration, and finally eclampsia and death. If, however, the fetus be re- moved, the symptoms at once disappear ; a phenome- non as clearly mechanistic as the cure of auto-intoxi- cation by freeing the intestines of their poisonous contents ; as mechanistic as the amelioration of Graves'* disease by the excision of the hyperplastic lobe of the 372 MAN --AN ADAPTIVE MECHANISM thyroid ; as the relief secured for an overworked man by rest, or for the harassed individual by substituting hope for fear. All these are mechanistic phenomena in the life career of man as an individual. We have pointed out incompletely and imperfectly the mechanistic role played by the organs and tissues of the body in transforming the energy needed for the daily routine of life, and in maintaining the chemical purity of the body, especially when excessive metabol- ism results from intense emotion, infection or muscular exertion. Let us now briefly consider how the indi- vidual, like other mechanisms, is modified by the im- pairment or the deprivation of certain parts. Excision of Organs Brain: When the brain is progressively destroyed by cerebral softening, the conversion of energy in muscular action and fever is correspondingly dimin- ished. When a certain percentage of brain-cells has been lost, then the brain can no longer adequately drive the body and a state of equilibrium is reached - the • individual is dead. If the cerebral hemispheres and the cerebellum are removed from an animal, it may live for months or years, but it cannot respond to stimuli affecting the distance or contact ceptors. That is, it possesses no associative memory. A decerebrate infant is short-lived. An individual with a defective brain — an idiot — may live for many years, but his activities are limited. The function of the brain may be depressed or even temporarily suspended by mor- phia, acidosis, fever, emotion, exertion or physical SUMMARY 373 injury. In each case, the reactions of the individual as a whole are correspondingly limited. The Muscles: If the function of the muscles is lost or hindered, the reactions of the individual may be as greatly affected as by depression of the function of the brain. If the muscles are disconnected from the brain by severing the connecting nerves, or if the func- tion of the muscles is suspended by curare, the in- dividual will be as helpless as if his brain had been removed. For a time, his life may be prolonged by artificial respiration ; but he can move no muscles ; he can produce only a negligible amount of heat ; he is powerless, dumb and cold — little better than dead. We see, therefore, that the muscles bear just as mechanistic a relation to the work of the individual as a whole, as the motor of an automobile bears to the reactions of the whole machine. The Adrenals: Excision of the adrenals causes a progressive decline in muscular power and in the pro- duction of heat until death, which inevitably occurs within a few hours. The H-ion concentration of the blood increases progressively with the approach of death. The Thyroid: The excision of the thyroid in carniv- ora and in man causes a rapid diminution of muscular power and a diminution in the production of heat. Sexual desire and procreation are depressed or lost ; the mind is weak ; the individual becomes large, flabby and stupid — a repulsive human caricature. Feeding thy- roid extract to such an individual transforms him into a comparatively normal physical and mental being — a markedly mechanistic phenomenon. 374 MAN --AN ADAPTIVE MECHANISM The Liver : Excision of the liver causes within a few hours a rapid decline in muscular power and in heat production until death. Before death the H-ion con- centration of the blood increases rapidly. Testicles and Ovaries: Excision of the testicles and ovaries, before adolescence, prevents the development of the secondary sexual characteristics and prevents sex reactions and procreation. Pancreas: Excision of the pancreas interferes with sugar metabolism. Thymus: Excision of the thymus interferes with the growth of the skeleton. Hypophysis: Excision of the hypophysis interferes with growth and with sugar metabolism, while exces- sive hypophyseal secretion causes excessive growth (gigantism) . Parathyroids: Excision of these two tiny bodies interferes with calcium metabolism and may cause death by convulsion (Calcium tetanus). All these defects support a mechanistic conception. Want of Certain Chemical Elements The human mechanism may be modified not only by the loss of some of its component parts but also by depriving the body of certain food constituents. For example, the exclusion of sodium chloride from the diet soon causes death, and the removal by milling of vita- min, a tiny element in the husks of rice, has caused the death of multitudes of rice-eating people and is the cause of the disease known as beri-beri. The adminis- tration of this minute constituent of rice prevents and cures beri-beri (Craemer). SUMMARY 375 While this list is by no means complete, we have mentioned some organs and some chemical substances the removal of which handicaps or destroys the individ- ual. These organs and chemicals are purely material things, purely mechanistic in their action. We thus see that, at will, by depressing or removing this or that organ, by administering this or that external agent, muscular power and the production of heat are dimin- ished or lost ; the action of the brain may be gradually depressed until unconsciousness and death is reached. It would seem that while a man-made machine is ap- parently, it is not really, more dependent on chemistry and physics than is that complex animal mechanism, man. We have now followed, though imperfectly, the career of the individual from his beginning in fertiliza- tion, through the unconscious fetal days and the hazards of birth to his conscious adult life. We have seen him struggling to adapt himself to his environment in in- fancy and in childhood and during adolescence. We have seen his kinetic system driven by injury, by emotion, by infection ; and have seen many diseases result from his struggle with his internal and his ex- ternal environment. We have seen him complete the cycle of life through procreation. We have seen that his death results from a vital break in his mechanism, and that his ashes are returned to the elements whence they came. From conception and birth to death, we have seen that virtually every phenomenon of life is mechanistic. We have studied the imperfect record of the ascent of man's species from the time when, having been driven by powerful enemies to the trees, 376 MAN — AN ADAPTIVE MECHANISM he evolved his strategy and acquired hands, which later enabled him to fashion weapons; to the period in which he returned cautiously to the hostile ground of his ancient enemies and with better strategy resumed the battle by using the forces of nature ; to the period in which he discovered fire, fashioned simple tools and weapons, made dugouts, tamed animals and planted seeds, thus making nature herself aid him to obtain food and shelter and protection against his foes. We have seen increased power accrue to man coincidently with the development of spoken and written language from mere symbols of communication. We have seen that as man became more and more completely adapted to environment, his numbers increased, until, in his desire to possess the earth, he found his most formi- dable enemies to be his fellow men ; and hence, with the blood of man shed by man the earth has been deluged. We see that this human animal is exceedingly prone to kill, because his evolution has depended upon his ability to conquer brute animals and his fellow man. We see that his two most complete adaptations are those of killing and procreating — the inevitable sequel of the primal needs for self-preservation and for the preservation of his species. The most powerful activator of the kinetic system of man to-day is his fellow man. This is the enemy he most fears. In the midst of plenty he strives for more. He is at war with his fellows in business, in education, in the arts, in the professions, in philan- thropy and in winning mates. There is no game nor sport that is not a battle. Even the toddling child, when pursued, turns at bay when captured; an ob- SUMMARY 377 vious recall of the bloody abyss of phylogeny, since all animals turn for the final death struggle. In all his waking moments, and even in his dreams, man exerts himself against his fellows. He fears ; he hopes ; he triumphs ; he is vanquished ; he is jealous and sus- picious. Yet with all his fears and struggles, he is forever bound to his fellows by the chains of necessity, for he cannot succeed alone. Man is, of necessity, a gregarious animal. He hates and fears, while at the same time, he is grateful and dependent. The rivalry and jealousy of his life turn to grief at the death of his rival. And in these emotions and strivings are laid the foundations of many diseases. These antithetic relations between individuals are exhibited on a vast scale by nations in mutual dependence, mutual help, mutual jealousy, mutual hate, mutual efforts to kill. The effect of fear, grief, worry and jealousy on the physical body is seen in the changes in the cells of the brain, the adrenals and the liver, and in the numerous resultant diseases and disabilities. Against man's in- humanity to man, religions and philosophies have been evolved, each of which aids in proportion to its power to substitute altruism for selfishness, to substitute faith for fear. Thus in understanding the physical basis of the action of faith and hope, as opposed to fear, despair, anger and grief, we have at our command a concrete force which can be efficiently used to protect the individual. As the knowledge of disgrace and punish- ment prevents dishonesty; as the knowledge of con- tagion prevents exposure to contagion, so the mere knowledge — the conviction — that excessive anger, work, jealousy, envy, worry or grief cause physical 378 MAN --AN ADAPTIVE MECHANISM damage as serious as that produced by infections or crushing blows will constitute a powerful protection to man. The knowledge that these activations not only decrease the power of the individual to do his work, but ultimately cause numerous diseases as well, will result automatically in arousing the instinct of self- preservation, which will surround the individual with a protecting circle, through which anger, jealousy, grief, and worry cannot penetrate, just as the zone of local anesthesia in the anociated surgical operation is an impenetrable barrier between the brain and the knife, making the surgical operation shockless. In the texture and form of his bones and joints ; in the structure and distribution of his muscles; in the covering skin and the padding fat ; in the nature and distribution of his nails and hair ; in the structure and equipment of the mouth, the stomach and the intes- tines, of the kidneys, ureter and bladder and of the organs for procreation and respiration ; in the composi- tion and circulation of the blood ; in the distribution of pain ceptors, and of the defense mechanisms against dust, debris and insects, against cold and heat, and against infection and bleeding ; in the mechanisms for appreciating sound and light, color and form ; in the mechanisms for taste and for smell, for maintaining an even body temperature, for producing muscular action and for expressing the emotions ; in the nature and incidence of laughter and weeping ; in the chemical defense against bacterial invasion and against the poisons of pregnancy and auto-intoxication ; in the mechanisms of conception, of pregnancy and of birth ; in the fabrication of thought ; in the mechanisms of SUMMARY 379 communication by natural, spoken and written lan- guage ; in health and in disease — in the complete life cycle of the individual from conception to death we see clearly here and dimly there the mechanisms by means of which a sensitive being immersed in a hostile environment effects survival, — we see man — an adaptive mechanism. INDEX Abdomen, a shock-producing area of body, 88. Acid sodium phosphate, effect of, on kinetic system, 290. Aciditi^!and respiration, 116. effect of exercise of various organs on, 347. of blood. See H-ion Concentra- tion. relation of, to anesthesia, 344. Acidosis, etiology of, 7. lesions due to, repaired by sleep, 342. neutralization of, 9. relation of, to normal and patho- logic phenomena, 346. symptoms of, 35.1. ultimate cause of death, 355. See also H-ion Concentration. Acids, effect of intravenous injection of, 341. on kinetic system, 290. Action patterns, application of theory of, 303. definition of, 120. establishment of, 58. of man and animals compared, 65. theoretic structure of, 298. Adaptation, law of, 20. man's, by nervous reaction, 38. mechanism of, 22. Adaptive reaction, typical, 51. Adrenals, control of, by morphin, 205, 289. effect of pregnancy on, 277. on energy conversion, 190. function of, 9. functional changes of, in relation to energy transformation, 180. histologic changes in, 6, 164. mobilizing function of, 363. relation of, to brain, liver, thyroid, and muscles, 198. distance ceptor stimulation, 144. result of excision of, 200, 373. Adrenin, and iodin, comparison of effects of, 148. effect and function of, 144, 198. of, on brain-cells, 203. coagulation, 115. kinetic system, 293. output, effect of opium on, 286. increased by foreign proteins, fear and rage, 115, 147. physiologic response to, 145. Alkalies, effect of, on kinetic system, 290. Alonzo Clark. See Clark, Alonzo. Amphioxus, spinal tube of, 49. Anesthesia, effect of, on electric fish, 185. inhalation, effect of, on kinetic system, 293. failure of, to prevent shock, 6. relation of, to acidity, 341. Anociassociation. See Anociation. Anociation, as a conserver of life, 224. definition of, 242. effect of, on postoperative pneu- monia, 259. method of securing, 242. origin of principle of, 5. relation of, to conservation of energy, 11. results of, 252. use of opium in, 286. to prevent postoperative pain, 326. Anti-thrombin, inhibitory action of, on intravascular coagula- tion, 112. Arterio-sclerosis, etiology of, 236. Aschoffe, 183. Ascidians, anatomy of, 71. excision of nervous system of, 48. nervous system of, 49. Aseptic wound fever, etiology and prevention of, 258. Auto-intoxication, defense against, by chemical ceptors, 97. 381 382 INDEX Bacteria, beneficial to man, 100. gaso-genetic, 100. Balance, law of, 24. Beebe, 183. Benedict, 265. Beri-beri, etiology of, 374. Blood coagulation, as a chemical re- action, 111. distribution of protective me- chanisms of, 115. mechanism of, 112. Blood-pressure, effect of injuries on, 84. low, result of, 113. Bose, 55, 357. Brachiopod, 70, 71. Brain, as a creative agent of electric force, 363. cells, affinity of, for adrenin, 200. effect of excision of adrenals on, 200. development of, 49. effect of opium on, 287. pregnancy on, 275. function of, 9, 116, 190, 197. histologic changes in, 6, 168. relation of, to adrenals, liver, thyroid, and muscles, 198. result of excision of, 372. Bright's disease, etiology of, 10, 240. Cannon, 115, 144, 147, 287. Cardiovascular disease, etiology of, ' 10, 213, 234. treatment of, 234, 235. Carrel, 273. Ceptor mechanisms, location of, 73. Ceptors, absence of, 73. chemical, defensive action of, against infection, 97. definition of, 69. distribution of, 71, 108. physiological action of, 71. specific adaptation of, 105. classification of, 68. contact, function of, 106. distance, distribution of, 118. result of stimulation of, 69. effector, function of, 303. influence of impulses on, 303. effects of stimulation of, 60. Changes in iodin content, 140. Chemical differences of individuals, 274. purity, effect of kinetic system on, 275. maintenance of, 265. Chemicals, effect of lack of, 374. Circulatory system, function of, 157. Clark, Alonzo, treatment, 12, 255, 289. Clotting. See Coagulation. Coagulation, effect of adrenin on, 115. intra vascular, 112. mechanism of, 112. protective function of, 112. Cold and heat, adaptation to, 80. Colon bacillus, 101. Color obliteration, of animals, 28. Compromise, law of, 20. Consciousness, definition of, 311, 316. Conservation of energy, applied in anociation, 11. effect of, 13. law of, 44. relation of, to adaptation, 12. Contact ceptors. See Ceptors, con- tact. Conversion of energy, for reproduc- tion, 263. Cortex and medulla, antithetic rela- tion between, 344. Craemer, 374. Crehore and Williams, 121, 359. Crozier, 340. Curare, effect of, 187. Darwin, 1, 4, 21, 38, 51, 99, 122, 136, 328. Death, acidosis the ultimate cause of, 355. Degree of shock, determined by type of trauma, 84. Diabetes, cause of, 10, 218. effect of emotion on, 147. suggested treatment of, 215. Digestive system, function of, 157. tract, lack of protective mechanism in, 79. Disease, definition of, 1. origin and control of, 3. relation of, to life, 4. result of disturbed symbiosis, 101. Diseases of modern environment 11. Distance ceptors. See Ceptors, dis- tance. Disturbed symbiosis and disease, 101. Drosera, 37. Drugs, classified according to effect on kinetic system, 285. DuBois, 265, 271, 351. INDEX 383 Eclampsia, etiology of, 279. Effector ceptors. See Ceptors, ef- fector. Ehrlich, 102, 105, 107. Einthoven string galvanometer, 358, 360. Electric fish, effect of anesthesia on, 185. stimulation of glands or muscles, effect of, 360. Electro-chemical mechanism, 356. Elliott, 144. Emotion, a form of muscular activa- tion, 122, 138. adequate stimulus of, 216. effect of, on temperature, 188. physiological characteristics of, 136. purpose of, 217. without action, result of, 153. Emotional activation, a cause of acidosis, 12. Emotions, gross phenomena of, 152. Endarteritis obliterans. See Throm- bo-angiitis obliterans. Energy, adaptive variation in amount of, 159. transformation of, for reproduction, 263. periods of greatest, 161. relation of, to certain diseases, 219. variation in rate of, 160. Equilibrium, law of, 20. Ether, disadvantages of, 249. effect of, on brain, adrenals and liver, 251, 293. Ewing, 279. Exanthemata, painless, chemical re- sponse to, 319. Excision of central nervous system, effect of, 48. various organs of body, effect of, 206. Exciting stimulus, response specific to, 121. Exophthalmic goitre. See Graves' disease. Eye, protective mechanism of, 78. Fainting, biologic origin of, 113. Faith cures, mechanism of, 221. Fear and rage, likeness of, to muscular activity, 125. terror, Darwin's description of, 122. preoperative, elimination of, 6, 243. Fear, result of, on sugar output of liver, 147. Spencer on, 125. versus faith, 220. Fertilization, adaptive reaction in, 46. Fever, as a protective adaptive re- sponse, 163. cause of, 231. symptoms of, 349. Fighting, as a reflex process, 77. Final common path, principle of, 60. the path of action, 60. Fisher, 346. Fly-trap, Venus'. See Venus' Fly-trap. Form and color, obliteration of, 28. Galton, 43. Gaso-genetic bacteria of man, 100. Genital system, function of, 157. Goitre, exophthalmic. See Graves' disease. Graves' disease, physiologic changes in, 183, 193. etiology of, 10, 141, 213, 225, 234. H-ion factor in, 350. likeness of, to tuberculosis, 232. symptoms of, 141, 232, 349. treatment of, 12, 234, 235. use of opium in, 289. Haeckel, 50. Harrison, 340. Head and neck, defensive mechan- isms of, 86. Headache, etiology of, 320. Heat, adaptive reaction of, 163. production, purpose and mechan- ism of, 162. Hektoen, 273. Heliotropism in plants and animals, 47. Hemorrhage, biologic origin of, 113. treatment of, 113. Henderson, 346. Heraclitus, 23. H-ion concentration of blood, control of, 233, 340, 351. effect of emotion on, 138. morphine on, 287. on respiratory center, 233. in insomnia, 165. pregnancy, 280. measurements of, 340. result of increase of, 117. See also Acidity and Acidosis. tests, results of, 180. 384 INDEX Horsley, Sir Victor, 115. Howell, 115. Hydrochloric acid, effect of, on kinetic system, 290. Hyperactivity of brain, effect of, 197. "Hyperthyroidism," etiology and prevention of, 258. Hypophysis, result of excision of, 374. Infection, an illustration of adapta- tion to environment, 97. cause of death from, 289. effect of, on exhaustion, 8. mechanism of protection against, 254. painful pyogenic, compared with painless exanthemata, 319. Inhalation anesthesia, effect of, on kinetic system, 293. Insomnia, effect of, on exhaustion, 8. histologic changes in, 165. Integration of animal, achievement of, 119. Internal hemorrhage, remedy for, 113. lodin, changes in content, 140. effect of, on kinetic system, 293. influence of, in Graves' disease, 143. metabolism and storage of, 140. Iodized protein, effect of, 143. relation of thyroid to, 143. Kinetic activation, modification or prevention of, 214. result of jexcessive glucose, etc., on, 265. chain, interdependence of organs in, 11. diseases, definition of, 215. efficiency, effect of glucose, etc., on, 265. system, effect on, of acids, 290. adrenalin, 293. alkalies, 290. ether, 293. iodin, 293. inhalation anesthesia, 293. nitrous oxid, 293. opium, 286. strychnin, 285. chief activator of, 376. components of, 9, 158. conservation of energy in, 12. decrease of activity of, 189, 193. effect of seasons on organs of, 161. Kinetic system (continued). function of, 157. maintenance of chemical purity by, 266, 275. theory of shock, definition of, 6. Lability, result of, on evolution, 23. survival by, 31. Labor, an adaptive reaction, 283. Larval ascidians, nervous system of, 49. Larynx, protective mechanism of, 79. Laughter, etiology of, 327. in Graves' disease, 338. Law of phylogenetic association, 93. photochemical action, 47. Lexor, 274. Lillie, 357. Liver, as a neutralizing organ, 362. control of, by morphin, 205. effect of adrenin on, 144. function of, in energy conversion, 9, 190. histologic changes in, 6, 164. relation of, to distance ceptor stimulation, 148. adrenals, brain, thyroid and muscles, 198. energy transformation, 204. result of excision of, 374. rage and fear on sugar output of, 147. Livingston, 324. Loeb, 48, 219, 366. Lungs, protective mechanism of, 78. Lusk, 265, 266, 280. Lymphatic hyperplasia, indicative of overwork, 233. Lymphocytosis, common to Graves' disease and tuberculosis, 233. Man, a transformer of energy, 44. rise of, 32. Man's response to environment, 120. Marine, 183. Mechanisms of adaptation, 22. sleep and anesthesia, 313. protective, 77. Medulla and cortex, antithetic rela- tion between, 344. mechanism of, to maintain alkales- cence, 117. Mental and physical exhaustion, similarity of, 129. Menten, 340. INDEX 385 Metabolism, an example of chemical adaptation, 96. effect of excessive glucose, etc., on, 265. Metchnikoff, 103. Michaelis, 279, 346. Modern environment, diseases pro- duced by, 11. Morphin, control of adrenals and liver by, 205. effect of, 9, 186, 345, 370. See also Opium. Multicellular animals, adaptive re- actions of, 46. Muscles, function of, in energy con- version, 10, 184, 191. relation of, to adrenals, liver, brain, and thyroid, 198. result of excision of, 373. Muscular exertion, purpose of, 121. Nephritis, etiology of, 218. Nernst's law, 357. Nervous reactions, man's mode of adaptation, 38. of protoplasm, 46. system, effect of excision of, 48. first rudiment of, 49. man's mechanism of adaptation, 45. specific qualities of, 51. Nervousness, postoperative or post- traumatic, 257. Neurasthenia, etiology of, 10. Nitrous oxid, advantages of, over ether, 249. dangers in use of, 251. effect of administration of, 9, 293. histologic changes due to, 172. Novocaine, use of, 251. Obliteration of color and form, 28. Omentum, protective function of, 111. Opium, action of, 286. effect of, on adrenals, 205. kinetic system, 286. use of, in exophthalmic goitre, 289. shock, 289. technic of anociation, 288. value of, 11. See also Morphin. Osterhaut, 141, 357. Ovaries, result of excision of, 374. Pain areas, distribution of, 82, 91. biologic utility of, 318. 2c Pain, freedom from, 323. mechanism of, 318. postoperative, prevented by anocia- tion, 326. site of, 322. specific response of, 81. Painful scar, etiology of, 256. Pancreas, result of excision of, 374. Parathyroids, result of excision of, 374. Paths, receptor, conductor and ef- fector, 120. Patterns of action. See Action pat- terns. Pawlow, 301, 307. Peritoneum, protective mechanism of, 109, 110. Peritonitis, kinetic theory of, 253. protective nature of, 321. use of opium in, 12. Phagocytes, action of, 102. Phagocytic defense against infection, 319. Phagocytosis, definition of, 103. response to local infection, 97. Philogenetic association, law of, 6. memory, 7. origin of emotions, 125. specific reflexes, 77. tendencies, 218. Philogeny, definition of, 63. interpretation of, 93. Photochemical action, law of, 47. Phototropism in animals, 47. Physical and mental exhaustion, similarity of, 129. Physiologic expression of emotion, 217. Physiological phenomena of emotion, 136. Plasticity, basis of man's adaptation, 31. Pneumonia, postoperative, etiology of, 259. Postoperative gas pain, kinetic theory of, 253. morbidity records, results shown in, 251. or posttraumatic nervousness, 257. Pregnancy, effect of, on adrenals, 277. brain, 275. liver, 279. muscles, 279. thyroid, 278. vomiting, etiology of, 282. 386 INDEX Protoplasm, power of adaptive re- sponse in, 46. Protozoa, adaptive reactions of, 46. Quinin and urea hydrochlorid, use of, 255. Rage and fear, effect of, on liver and adrenin, 144. effect of, on coagulation, 115. Receptor mechanisms in brain, 304. organs, 67. Reflex arcs, definition of, 57. Reproduction, energy conversion for, 263. Respiration, rapid, cause of, in shock, 7. Respiratory rate, indicative of me- chanical injury, 83. system, function of, 157. Response to trauma, determination of, 91. Rest, therapeutic value of, 12. Restlessness in shock, cause of, 7. Robertson, 357. Rogers, 340. Romanes, 99. Rubner, 265. Sedatives, use of, 242, 246. Self-defensive mechanisms in head and neck, 86. Sherrington, 60, 70, 77, 119. Shock, chronic, 213. continued, result of, 213. etiology of, 6, 8. kinds of, 212. kinetic theory of, 6. prevention of, 5, 288. Shock-producing areas of body, 88. Skin, sensitive areas of, 84. Sleep, definition of, 311. effect of, 9. Smell, protective function of, 79. Sodium bicarbonate, effect of, on in- halation anesthesia, 345. kinetic system, 291. chloride, result of exclusion of, from diet, 374. Specialized pathway for stimuli, 45. Specific response of pain, 81. Spencer, Herbert, 4, 125. Spermatozoa, action of, 46. Splanchnic nerves, effect of division of, 147. Stability, effect of, on evolution, 23. Starling, 187. Stimulants, effect of, in exhaustion, 8. Stimuli, order of succession of, 61. specialized pathway for, 45. Stimulus, adequate, function of, 56. first stage of reaction to, 55. Strychnin, effect of, on kinetic system, 285. Summation, definition of, 62. Sweating in shock, cause of, 7. Symbiosis and parasitism, 98. Taste, protective function of, 79. Testicles, result of excision of, 374. Thirst in shock, cause of, 7. Threshold, definition of, 61. Thrombo-angiitis obliterans, etiology of, 237. Thromboplastin, distribution of, 115. function of, in coagulation, 115. neutralizing power of, 112. Thymus, result of excision of, 374. Thyroid deficiency, result of, 189, 192. excess, result of, 189, 193. function of, 10, 183, 197. pacemaker of kinetic system, 195, 232. reaction of, to distance ceptor stimulation, 140. relation of, to brain, adrenals, thyroid and muscles, 198. result of excision of, 373. seasonal effect on, 162. Tickle, reflex origin of, 74. Tickling, prolonged, effect of, 75. relation to laughter, 77. Ticklish areas, 75. Toxins, cause of exhaustion, 8. of pregnancy, defense against, 97. Transformer of energy, man a, 44. Unicellular organism, response of, 45. Urea and quinin hydrochlorid, use of, 255. Urinary system, function of, 157. Vaughn, 163. Venus' Fly-trap, action pattern of, 58. adaptive reaction of, 71. compared with man, 301. mechanism of, 51. nervous system of, 300. Vitamin, result of removal from rice, 374. INDEX 387 Vomiting, mechanism of, 80. in Graves' disease, 233. of pregnancy, etiology of, 282. Weeping, etiology of, 335. in Graves' disease, 338. Williams, 341. Williams and Crehore, 121, 359. "Work" changes, effect of emotion on, 140, 184. X-ray, lack of response to, 73. Printed in the United States of America. 'T'HE following pages contain advertisements of books by the same author or on kindred subje&s. A Mechanistic View of War and Peace BY GEORGE W. CRILE, M.D. Cloth, 8vo, $1.25 " Dynamic, driven by unforgettable pictures of the appalling destruction he has seen, Dr. Crile protests his conviction that those primitive forces which produce the disastrous phenomena of war may be utilized for the evolution of longer and more secure cycles of peace. Haunted by unfor- gettable memories, stirred so profoundly that he has come out from the university rostrum and the amphitheatre to speak in the terms of common humanity, Dr. Crile challenges his countrymen with the burden which the European war has laid upon the new world. 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