A Bipolar Theory of Living Processes

This volume represents an attempt to present certain conclusions which are based upon researches which have been in progress continuously from their initiation in 1898 to the present time. The progress of these studies and the development of the theory which is based upon them are summarized in the introduction. An attempt has been made to include in the bibliography the titles of the publications which we have found especially valuable in the development of the bipolar theory. It is obviously impossible, however, to include the name of every author from whom we may have gained information or suggestion which has been of direct value in the development of the theory here presented.

The names of the many collaborators who have been associated with me in these studies have been mentioned in previous publications, or are cited in the text of this volume, but I should like in addition to express here my sense of indebtedness to all who have shared in the experimental details and in their interpretation and presentation. III PREVIOUSLY CONCEIVED THEORIES ов ESTABLISHED Facts REGARDING Certain ELECTRICAL PROCESSES IN THE VI CERTAIN ESTABLISHED Facts REGARDING VARIOUS ORGANS AND TissuEs OF THE Bopy IN RELATION TO THE FUNC- TION оғ EACH IN A BIPOLAR MECHANISM

ICAL PHENOMENA . m The Synaptie System Strychnin Poisoning . Tetanus The Bio- 0а. а of Disabled Or: gans and Tissues ; А У Inhalation Anesthesia Ether . : Nitrous Oxid- Oren Hyperthyroidism The Infections—Fever XI Tue UNIFORMITY or THE BIPOLAR PATTERN FROM THE Атом TO Man XII Назтогослсар RESEARCHES XIV OxipaATION— TEMPERATURE MEASUREMENTS . XVI CERTAIN ESTABLISHED Facts REGARDING ELECTRIC ENERGY AND Irs RELATION то OTHER TYPES or ENERGY Cox- Electric Energy 1 Light Energy Heat Energy Өлі ETS Interatomic, Intermolecular and Intramolecular Forces

XVII THe ELECTRICAL SIGNIFICANCE or OBRTAIN ESTABLISHED Facts REGARDING THE PRINCIPAL CONSTITUENTS OF THE B А CONSIDERATION OF THE ENERGY mi FORMATIONS IN THE Bopy FROM AN ELEC- Opposite effects of stimulation to the point of d uS on the electric conductivity of the brain and of the liver Opposite effects of stimulation on the temperature of the brain and of the liver . Schematie plan of afferent and vient nerve AN (from Cajal) 52 3 ЕЕ. Schematic plan of Шс ЧЕН sensory бе те

Sehematie representation of the comparative nucleusplasma relationship in normal and in cancer cells facing The effect of prolonged insomnia and of insomnia followed by a period of rest on the electric ER ad of the brain Schematic oo die MEA. ihe progressive а of a typical cell Е : Living nerve cells as seen with Ao Mite о TES Матіпевсо and Mott) . Termination of the fibres of the ascending branch of the cochlear nerve (from Cajal) . Different forms of cS in the E ЕН ч the vagus nerve (from Cajal) . "^

Diagrammatie drawings illustrating five VANS of VE ares (from Herrick) . Diagram illustrating Келесі of о of В пегуе impulse (after Herrick) Schematic drawing of complete sensory-motor circuit (from Cajal) қ Schematic drawing of Е шее ae жумы ОИ in Mille sympathetie nervous system (from Cajal) The neuro-motor apparatus of certain unicellular deb lates (from Kofoid) Temperature charts showings ie of response in ihe bs to the injection of adrenalin after hepatectomy

Effect of the injection of adrenalin and of adrenalectomy on the cells of the brain and of the liver . . . . . Opposite effects of the injection of an acid and of an alkali on the electric conductivity of the brain and of the liver Opposite effects of the injection of adrenalin on the temperature of the brain and of the liver Immediate and late effects of the injection of СЫ оп the electric conductivity of the brain and of the liver . Opposite effects of the infection of ате оп the temperature of the brain and of voluntary muscle .

Opposite effects of the injection of adrenalin on the temperature of the brain and of the intestinal mucosa The similarity of the progressive effects of the injection of adrenalin on the structure, the electric conductivity and the temperature of the brain . Effect of the absorption of iodin MEME on Ns бе conductivity of the brain . К Early and late effects of thyroid feeding on s cc Eh conductivity of the brain . d r^ Ar Comparative effects of the injection of RAE: in cM and in iodized animals . лкк. ру

Early and late effects of strychnin poisoning on К Ye cells; rA San LE we К И RUP RE, ст. : Early and late effects of stryehnin poisoning on d He trie conductivity of the brain and of the liver Effect of strychnin poisoning on the temperature of the brain Early and late effects of ether anesthesia on the electric conductivity of the brain and of the liver . . . . . Comparative effects of prolonged ether and of prolonged nitrous oxid anesthesia on the temperature of the brain The metamorphosis of the nucleus of the spermatid into the head of the spermatozoón (from Jordan and Ferguson) Schematie representation of the intracellular changes following fertilization (from Bóhm, Davidoff, Huber) .

Spider сей with multiple nuclei from rhabdomyosarcoma Grom Aine) ae Comparison of the electric conductivity of carcinoma of the breast with that of comparatively normal portions of the same gland TS Comparison of the electric оти of а of the uterus with that of comparatively normal tissues of the same organ . Comparison of the electric иес of е Apes of goiter with that of the comparatively normal or inactive portions of the same gland . Comparison of the electric capacity of normal and ae neoplastic tissues

Distribution of potassium in sensitive hair of Venus’s fly-trap : Parallel distribution of Е | of fate i in Te ог of Venus’s fly-trap . Phineas ум Protoplasmic celltoon UT AC MAN in Volvoz, somewhat schematized (from Wilson) . M Intercellular bridges (plasmodesms) in animal me (from Wilson) . ; : Connections between odcyte at folliclepall in svat ye (from Wilson) E : Karyoplasmie relation in Seem ME eggs Sef Cental after centrifuging (from Wilson) .

Two-, four-, eight-, and eleven-nucleate E of ono: mania Lafleuri—a parasite of the human intestine (from Kofoid and Swezy) қ Schematic representation of a HORE neal line on КО from the atom to man. . : . . facing Effect of the discharge of its "iconic organ on the brain cells of a torpedo WHEN I was a student in medical school I came for the first time in contact with the dramatic picture of failing bodily energies and death. The patient was young and strong; every organ of his body was sound; he had lost but little blood although both legs had been crushed by a locomotive. As I watched him slowly sink into death, the mental and physical prostration, the shrunken, pallid face, the cold sweating skin, the fading pulse, fixed the picture іп my mind. Autopsy revealed no lesion in any vital organ. Immediately I planned a research for the purpose of attempting to find what essential mechanism had failed. As I had watched the pulse fading so inevitably I thought that death was due to the want of circulation as the result of heart failure; but what had caused the heart to fail? It was not hemorrhage, but it appeared to me that failure of the circulation, to whatever it was due, must have been the primary cause of death, and this belief directed the course of my initial studies.

After futile experiments in an improvised laboratory in Cleveland I was fortunate enough to secure an opportunity in 1895 to pursue this research in the University College of London under the direction of Sir Victor Horsley. Since that time this study has proceeded without interruption in London, in Cleveland, in war hospitals in France, at the Western Ке- serve University Medical School, at Lakeside Hospital and in the Research Laboratories of the Cleveland Clinic Foundation. During this long search for the underlying causes of fatigue, exhaustion and death, data were accumulated which made it apparent that to understand the nature of exhaustion and death,

it was necessary first to understand the nature of life itself. The research therefore turned from a study of the nature of death to a study of the nature of life. In the progress of these studies there have been four principal stages: I. Studies of the Circulation and Respiration. П. Studies of the Blood Chemistry. III. Cytological Studies. IV. Biophysical Studies. Neither the heart nor the circulation nor the respiration was found to be the primary factor in the causation of exhaustion and death from surgical shock. Nevertheless, three outstanding facts of great clinical and scientific value emerged from these long negative studies of the circulation—negative in that they failed to identify the mechanism the failure of which leads to fatigue, exhaustion and death.

1. It was established that nerve blocking prevents surgical shock. 2. The technic and value of the direct transfusion of blood was established. 3. It was found that stimulants, as a class, increase fatigue and exhaustion; that morphin minimizes fatigue and exhaustion. Another finding of scientific interest but of little practical value was the resuscitation of the dead by adrenalin under certain limited conditions. It was found also that there was a wide range of variation among the various tissues and organs of the body in their resistance to death. The two organs which most promptly succumbed were the brain and the liver, the heart muscle and voluntary muscle being approximately one hundred times more resistant. It appeared, therefore, that these two master-tissues must be the key structures.

Having found that the changes in the circulation and the respiration which are present in exhaustion and death are endeffects and not primary causes, it seemed probable that the primary cause of exhaustion must be some change in the blood chemistry. In association with M. L. Menton, and W. J. Crozier, the chemistry of the blood in exhaustion was investigated. The reserve alkalinity was first studied with the thought that it might be diminished in exhaustion, but with negative results; then the hydrogen ion concentration was measured with the thought that it would be increased in exhaustion, again with negative results. From these studies, however, came a finding of great clinical importance—namely, that all inhalation anestheties cause a progressively increased hydrogen ion concentration, death occurring at the moment when a neutral point is reached and a positive acidity established. This finding showed clearly that the acid-alkali balance of the organism has a vital significance.

Having failed to discover the fundamental cause of death in the cireulation, the respiration or the blood, we turned to a new line of attack upon the problem—-a line suggested by Hodge's studies of changes in the ganglion cells of the honeybee in fatigue. In collaboration at first with D. H. Dolley, later with J. B. Austin and F. W. Hitchings, the cells of every organ and tissue of the body including the red blood cells were studied in animals in excitation, in exhaustion and after death from every conceivable cause. In this research, which lasted for nine years, we for the first time glimpsed a fundamental fact of first importance. First of all, these studies led to the eoneeption that there is in the organism a kinetic system, the several organs of which collaborate in the transformation of potential into kinetie energy in the form of adaptive responses muscular action, emotional excitation, febrile phenomena, ete.

able to formulate any hypothesis whereby to explain the vital role of the liver; and yet if our cytologic researches were of value, the rôle of the liver must be identified, for in these studies changes in the cells of the liver appeared consistently with the changes in the cells of the brain. In the hope of discovering the nature of the interrelationship of the brain and the liver we considered the structure of the cells, especially the following facts:—-(1) that differential stains were required to define the nucleus and the cytoplasm, the nucleus taking a basic stain, the cytoplasm an acidic stain; (2) that in exhaustion and death from any cause, even including the want of sleep, the differential stainability of the cells of the brain and of the liver was decreased or even disappeared; (3) that after the administration of a fatal dose of an alkali the differential stainability of the cells was lost; (4) that after the administration of a fatal dose of an acid the differential stainability of the cells was lost. When these observations were considered together with the fact that when the alkalinity of the blood disappears—that is, when the neutral point is reached—the animal dies, it became evident that death was associated with loss of the acid-alkali balance within the cells of the organism. What could be the vital relation between the relative acidity of the nucleus and the alkalinity of the cytoplasm? An acid colloid and an alkaline colloid separated by а semi-permeable film, a dielectric membrane, constitute an electric cell within which an electric potential exists between the positive and the negative poles. According to this conception the cells of the organism would be electric cells in which the comparatively acid nucleus would be the positive pole and the comparatively alkaline cytoplasm the negative pole.

At this point, therefore, we began to consider the organism as a bipolar mechanism and to direct our researches into the field of biophysies. According to our cytological findings it would seem that the maintenance of the acid-alkali balance between the nucleus and the cytoplasm of the cells—electrie potential—is essential to life and furnishes the energy of the living process itself. Its reduction to zero or equilibrium is death. It remained to discover how this vital potential is maintained, and we assumed that the potential was-due to oxidation and that in turn the electric potential within the cell was the physical catalyst that governed oxidation. This assumption led us to abandon physiological, chemical and microscopical methods of attack upon our problem and to turn to physics in the hope that by the application of physical methods we might identify the physical laws in accordance with which the organism is operated. Accordingly, in 1917, in collaboration with G. B. Obear, Amy F. Rowland, and Helen Hosmer, a series of researches was initiated which led to the establishment of a permanent biophysical laboratory in which the bipolar theory has been subjected to biophysical tests.

Our histological studies had indicated that the lipoid films surrounding the nucleus and the cytoplasm offered a definite resistance to the positive hydrogen ions and that in death this resistance was lowered. If this inference was correct, then the changes indicated by the microscope could be more accurately identified by measurements of the electric conductivity of the tissues. Conductivity measurements supported this assumption. If we were justified in our further assumption that the potential within the cells is maintained by oxidation, then variations in oxidation must accompany variations in activity and these variations in oxidation would be manifested by variations in temperature. This assumption was supported by biophysical tests.

If the organism is operated by electricity, one would expect that the cells would be adapted for the accumulation of electric charges. That this is the case has in turn been shown in our biophysical laboratory by Hugo Fricke. Following the lead suggested by these findings the organism has been studied as a whole to secure evidence as to the existence of a part, of highest and a part of lowest potential, and of electric currents adapted to the vital processes of the organism.

Finally, our findings from our initial study to the present have been scrutinized and correlated for the establishment of a premise which would bridge the gap between the living and the non-living and suggest a physical line of ascent from the atom to man. In this presentation of the theory we shall offer first the argument with a general survey of the supporting evidence. The evidence from histological and biophysical researches and from certain generally accepted biophysical facts has been summarized in Parts III and IV, thus making it convenient for the reader who may wish to escape the tedium of reading these details to pass at once to the conclusion offered in Part У. Certain extensive excerpts from the literature and де- tailed experimental data have been placed in the Appendix.

Any theory of the nature of life must account not only for the common fundamental phenomena of life in all forms of living beings from the simplest to the most complex, but it also must identify the fundamental form of energy to which the reactions of life can ultimately be traced. It must identify a uniform pattern or plan for the transformation and utilization of energy. It must account for the necessity for such everpresent characteristics as the acid-alkali balance, the lipoid films, the omnipresent electrolytes. It must show why a continuous supply of oxygen and continuous oxidation are necessary. It must show the mechanism of stimulation and of specific response to stimulation. It must account for the phenomena of memory. It must account not only for reproduction but also for the transmission of acquired characteristics. It must identify the operation of the unicellular and of the multicellular organism with the operation of protoplasm itself. It must show the mechanism of the creation of living matter— protoplasm—from the energy and matter of the environment.

It is obviously beyond the present scope of human knowledge to meet all these requirements. It is feasible, however, to present a theory which appears at least to point to a reasonable explanation of the essential characteristics of living organisms and of the phenomena of life itself. Mathews has stated that the difference between the living and the lifeless is a difference in the energy content of the molecules. “Тһе difference between the reactive molecules of protoplasm and the same unreactive molecules outside of protoplasm is a difference in energy content. The various chemical and physical powers of protoplasm which so strikingly differentiate it from the lifeless are due to the increase in the energy content

of the molecules. Living matter contains molecules having a high content of energy and capable of passing to a more stable dead form in which they contain less energy.” The central fact regarding living organisms then is that they are transformers of energy and that they must be operated by means of one or more of the following six forms of energy: (1) heat, (2) light, (3) gravitation, (4) intermolecular forces, (5) chemical energy, (6) electric energy.

It is obvious that the organism of a rabbit, for example, is not operated by heat energy; nor by light energy; nor by gravitational forces; nor by surface energy. It follows that the probable driving force of living organisms must be either electrical or chemical energy, or a combination of both. We therefore propose the theory that living organisms are bipolar electric mechanisms. If this theory is tenable it must meet the following requirements:

1. That electricity is a constant phenomenon of living processes. This has long been known, 2. That the application of electricity to the muscles ог glands, or to their nerve supply will cause them to perform their natural functions. This is a basic fact which is universally accepted by physiologists. 3. That the materials of which animals are constructed are specifically adapted to electrical processes. Certain generally known facts regarding the principal constituents of the body will be cited and new evidence submitted.

4, That in structure and function the unit cells which drive the organism not only are adapted to fabricate, to store and to discharge electricity, but that this is true also of the protoplasm itself. Certain generally accepted facts and certain new evidence which tend to establish this requirement will be cited. 5. That the organism as а whole is a bipolar electric mechanism bearing the pattern of the unit cells and that the unit cells are constructed on the pattern of the atom. Experimental data which tend to support this requirement will be offered.

6. That the normal and the pathological phenomena of man and animals can be interpreted in electrical terms. Summaries of experimental researches undertaken to establish this point will be given. Water, which forms more than three-fourths of the body content, has the highest known dielectric constant. This property of water is responsible for the ionization of the infinite number of molecules which water holds in suspension or in solution. Water is also one of the most important catalysts.

Electrolytic solutions and colloids which make up the bulk of the body are especially adapted to electro-chemical processes. Hydrogen ions permeate all living organisms. The slightest change in the hydrogen ion concentration fundamentally alters the organism; and it is known that hydrogen ions are of high electrical significance. Carbohydrates are the source of the hydrogen ions which are released by means of oxidation. Of the highest electric significance are the exquisitely thin, low-conducting lipoid films which surround each of the trillions of cells which compose the body. For it is a well-known physical fact that an oil film has a remarkable capacity for the aceumulation of electric charges and that the thinner the film the higher its electric capacity. While each of the other essential constituents of the organism might play a role in an organism operated by some other form of energy, these lipoid membranes could be significant only in an organism which is operated by electrical forces.