A Bipolar Theory of Living Processes

The first effect of a lively hemorrhage is to call out an emergency increase in adrenalin (Cannon). We therefore expected that in an acute hemorrhage the temperature of the brain would show a temporary rise; and our expectation was realized. These observations on so fundamental a group of facts as the expected variations in temperature and electric conductivity run parallel with another great group of observations which are just as fundamental, but have a mueh larger chance of error. I refer to the microscopic changes in the size and in the differential stainability of the cells of the leading organs of the body in excitation and fatigue. These carefully studied changes in the eells suggested the bipolar theory. Та these experiments we found that vital function varied with the differential stainability of the cells of the brain and of the liver and to a lesser degree of the cells of the adrenal cortex. If the acid-

Fic. 11.—Schematic representation of the comparative nucleus-plasma relationship in normal and in cancer cells. alkali stain of the nucleus and of the cytoplasm respectively is a measure of the respective intensities of the acid or nuclear part of the cell and of the alkaline or cytoplasmic part of the cell, and if the energy of the organism is dependent on the difference in potential and the difference in potential is due to the relative acidity and alkalinity, then the cytologic studies by Dr. Austin, Dr. Hitchings and myself strongly support the electrochemical or bipolar theory.

If oxidation in the cells is due to the electric potential, and if oxidation and the film condenser are essential to life, then it would appear that the potential can be handed on only by a division of the cell, the division of the cell including a division of the mechanism which creates the potential in such a way as to provide in each new cell a difference of potential; i.e., the “flame of life" must necessarily be handed on from cell to cell. - Thus, we may conceive that when the spermatozoón which has the characteristics of a nuclear structure is added to the nucleus of the ovum, a greatly augmented nucleus is formed with a corresponding increase in oxidative capacity; hence a capacity for attracting and using food—increasing іп size—and in consequence multiplying by cell division.

By analogy we may conceive that the facilitation of cell division in cancer depends, in some way as yet unknown, upon an increase іп the relative size of the oxidative or nuclear part | of the cell as compared with the lack of a like change in the neighboring cells. Such an increase in oxidative capacity would add to the bulk of the cell, just as the increase in oxidative capacity in fertilization increases the size of the ovum. (Fig. 11.) By the division of both the nucleus and the cytoplasm the relatively high electric potential would be handed on to the daughter cells, in which in turn the potential would be correspondingly high and thus the process would become progressive

at the expense of the neighboring cells. ‘Thus, in the case of a group of cells which have been injured by repeated slight trauma, or by irritation of any kind so that the cells are alternately injured and repaired, we may suppose that one cell may have become fused with another and lose a part of its cytoplasm; or that by other means the oxidative capacity of the nucleus as compared with that of the cytoplasm may have been increased with a resultant increased size of the nucleus and hence increased potential. This cell would then multiply at the expense of its neighbors and a cancer would develop.

If a battery is made to work continuously by keeping its circuit closed, -polarization of the plates will take place and the battery is said to be exhausted, which means that the difference of potential has diminished or disappeared. It would appear to be more than a mere analogy that such is the mechanism whereby prolonged consciousness unbroken by sleep leads to exhaustion and death. If the period of work, 1.е., if the passage of electric current is short, as in a single heart-beat, then the degree of polarization is proportionately small. The small degree of polarization which results from a single heart-beat requires a proportionately short time for depolarization or sleep, 1.е., the pause in the heart cycle may be regarded as its period of sleep. The heart, with its nerve mechanism, takes normally from seventy to ninety naps a minute, and thus is kept depolarized or rested as it works.

We may suppose that the nerve cells which operate the respiratory mechanism become depolarized, or sleep, from sixteen to eighteen times per minute and that thus the respiratory mechanism is kept depolarized or rested as it works. The salivary glands, the intestinal nerve-muscle mechanism, the digestive glands, etc., we may suppose have alternating periods of work and polarization, and. of sleep and depolarization. Regarded superficially, the functions of respiration, of circulation, of digestion, carry on as if they never rested, never slept; but their sum total of short periods of sleep is relatively

as long as the total period of sleep of that part of the brain whose work creates consciousness, and therefore spends no more time in sleep, but sleeps more continuously. As for the portion of the brain which governs conscious activity, the periods of work, and therefore of polarization of Fic. 12.—The effect of prolonged insomnia and of insomnia followed by a period of rest on the electrie conductivity of the brain. (Percentile variations.) the cells that supply the electric power for consciousness, for emotion and for muscular action, are longer than the periods of work demanded by the heart, by the respiratory mechanism or by the digestive mechanism. Thus the option of evolution apparently has been to run the organism on long shifts or shorter ones.

If the changes in the nerve cells seen in fatigue from various kinds of work and from prolonged enforced consciousness are identical in appearance; if these physical changes are restored only during sleep; and if the degree of cell change varies with the amount of work done at a stretch without sleep—that is, with the amount of electric energy that has originated in or traversed a given cell—then it would require more time and deeper sleep to restore the electrical balance of the cell after prolonged heavy muscular exertion than after a day of restful quiet. And this is demonstrated by experience. It would appear that the degree of exhaustion equals the protraction of consciousness multiplied by its intensity.

Sleep, being a negative phase, cannot be compelled. Consciousness, being a positive phase, can be compelled, even unto death. Normal man cannot sleep unto death; he can sleep only to restoration—no more. If the bipolar theory is correct then it must stand the crucial test of the clinic not only in the interpretation of pathological processes but also in the indication of methods of conservation and restoration. If the operation of the organism can be interpreted by the laws of physics, then methods for the protection and restoration of the organism should be dictated by the same laws. For the optimum operation of the bipolar organism, the maintenance of an optimum difference of potential, the following conditions are essential:

3. Maintenance of the semi-permeability of the lipoid cell membranes. 5. Maintenance of the integrity of the poles of the organism, that is of the cells in the brain and the liver. 6. Sufficiently long and sufficiently frequent periods of sleep. NI The practical application of these principles in the treatment of the “bad risk” patient may be briefly outlined as follows: 1. Water is given in abundance by every route; 2000 to 4000 с.с. or more given by hypodermoclysis most quickly reaches the cells.

2. Oxidation is promoted by the maintenance of an ade quate circulation, by transfusion if the volume of blood is below normal, and by digitalization to strengthen the myoeardium if the minute volume is diminished by a weakened myocardium. 3. The semi-permeability of the cell membranes is conserved by the avoidance of ether anesthesia and the employment of nitrous oxid-oxygen analgesia—not anesthesta—plus local anesthesia. 4. An optimum temperature is secured by the obvious measures indicated by the needs of the individual case. Of peculiar value are large hot packs over the abdominal viscera, or the application of diathermy during the operation itself. The administration of hot fluids by mouth not only supplies local heat and water but, as experiments have shown, its effects are instantly manifested by increased oxidation in the brain.

5. The integrity of the brain and the liver is kept from further damage by environmental control; by the infliction of minimum trauma; in certain cases by performing the operation in the patient’s room; and above all by securing adequate sleep and rest. The protective effect of morphin in particular is needed and when that is contra-indicated other narcotics and sedatives should be utilized to promote the urgently needed periods of depolarization. The fundamental necessity is the maintenance of a difference in potential—this is the maintenance of life.

Тнат electro-chemical processes play an important róle in the phenomena of life has long been held by biophysicists and physiologists. The similarity of the nerve or action current to an electric current seems to have been observed by the physicists as soon as the characteristics of the production and conveyance of electric currents began to be recognized. In 1835, a French physicist, Becquerel, included a section on the action of electricity on organic bodies in an experimental treatise on electricity and magnetism * and from the evidence he presents draws the conclusion:

“These facts are sufficient to show that electricity probably plays a great role in the animal economy; and that it should also be included among the means whereby life is maintained in organized bodies. But in what way do these bodies, when they begin to develop, put into action this electric principle whose action persists throughout their life? Of this we are completely ignorant. This is, without doubt, one of the mysteries of creation, which man will never be able to fathom.”

Of special interest are Becquerel’s observations of the phenomena presented by different varieties of electric fish: “Tf one shall some day discover that the electric fluid plays a part in the phenomena of life, it will be by studying the peculiar property possessed by certain fish, whereby when they are touched by the hand they produce a reaction similar to that produced by the Leyden jar, and by meditating on the conclusions one can draw therefrom to be applied to physiology in general.”

Becquerel reports Galvani’s experiments on the electric fish which showed that when connection between the brain and the electric organ was broken, the fish could not deliver a shock; a fact also established by Spallanzani: “1. We think therefore that the electricity is fabricated in the brain under the control of the will. “2. In our opinion the difference between the electric fish and other animals is that in the former nature has placed organs designed for condensing the electricity which emanates from the brain, augmenting its tension in such a way as to make of it, as it were, an offensive arm; whereas in the latter this same electricity has only the tension necessary to produce natural contractions and to accomplish the various functions which are expected oft."

Becquerel not only believed that voluntary museular action is due to electrical action but he advanced the theory that the chemical changes within the organism are also due to electrical action: “Tt is not enough to advance the opinion that the organic functions operate under the influence of electric forces, it is necessary also to try to prove this by showing that there can exist in the body electric currents which are capable of producing chemical changes."

Of striking interest 1s the citation of researches on the acidalkali reactions of the body by Donné, who made the following conclusion : “Electric currents exist in animals at the surface of the membranes and in the various organs. ‘This theory rests on the principle that when two bodies, one acid and the other alkaline (or . each one playing that róle in their reciprocal reactions) are separated by a membrane, a multitude of electrie currents continually work through this intermediary.

“Electricity acts in two ways within the animal economy. It may produce contractions and other derangements of the equilibrium of the organic parts or it may control the chemical reactions which either promote the secretions or are prejudicial to their production." It is not until within comparatively recent years that much corroborative evidence in favor of the bipolar theory has been added to these earlier findings and observations. The following observations and conclusions indicate the present trend of thought among many investigators:

` Du Bois Reymond held that the action current is an electric current; Crehore and Williams? put forward strong evidence in favor of the identity of the action current and electricity. Burdon-Sanderson * demonstrated that motor plants such as Venus’s Fly Trap and the Sensitive Plant show electric variations during their specific response to stimulation; Waller * extended these observations and called these electric variations “blaze currents of action.” Bose® has found evidence of the identity of vegetable and animal activity, and by most ingenious experiments has shown that electrical phenomena attend the activities of plants, concluding therefrom that electricity plays an important róle in the vital phenomena.

Piper ? showed that sound waves originate an electric current in the auditory nerves of fish; Loeb * has shown by what physieal and chemical processes rays of light orientate the simpler animals; Steinach $ has identified the electric mechanism by means of which the fish maintains its equilibrium. Einthoven and Jolly ° and others have confirmed the discovery made by Holmgren in 1866, that when light falls on the retina an electric current is produced in the optic nerve. Воуіе,!° by brilliant experiments has carried this work into newer fields.

Gotch and Horsley 1! have shown that during electric stimulation of the cortex, causing muscular action of the leg, a sustained electro-motive force is present in the spinal cord during the continuance of the stimulation. Not only did they demonstrate the presence of an electric wave, but they were able also to identify the conduction paths in the spinal cord over which this wave travelled, thus showing the intricate pathway along which the current found its way from the cortex to the muscles. Gotch and Horsley also demonstrated a persistent negative variation in the cord during electric stimulation of the Rolandie area.

Nernst 1? supposed that the electrolytes in the axis cylinder lie within membranes which are impermeable to certain ions, and that when an electric current is passed through a nerve it is conveyed by the dissociated electrolytes, causing an accumulation of positive ions at one point and of negative ions at another. When the concentration reaches a certain point excitation occurs. А. V. Hill!? supports Nernst's general theory; MeClendon,'* Bayliss," Lille!9 and others take a similar view.

By microchemical methods Macallum !* showed that since it contains a greater concentration of electrolytes, the axis cylinder is a better conductor than the medullary sheath. Meyer "® found that alteration in the concentration of the electrolytes in the sea-water in which the nerve of a marine animal was suspended altered equally the rate of electric conductivity of the water and the rate of nerve conduction. Tashiro 1? has demonstrated that as the result of the passage of the normal action current down a nerve fiber, carbon dioxid is given off and oxygen is consumed. Moreover, whether in the ease of a normal or an applied electrical current, no heat is produced. А. V. Hill 29 has confirmed Tashiro’s findings as to the absence of heat.

В. S. Ше?! has developed an analogy between the local electrical effects in metals and in living tissue, as exemplified by the passive state in metals and by nervous conduction in tissue. He considers that the phenomena in each case are due to the formation of local electrical currents, resulting in the case of metals, from local changes in surface tension; and in nervous tissue, from local changes in the permeability of the surface film or membrane. In each case the phenomena are subject to rapid “spreading” depending on the rate of the reaction which initiates it. He states that in nerve tissue “a relation of direct proportion should thus exist between the electric conductivity of the medium and the rate of propagation of the excitation wave.”

Howell ?? states that when nerves of one kind are sutured to nerves of another kind, the reaction is determined by the end mechanism; and he states further that efferent nerves are like electric wires—the effect of their stimulation depends on the mechanism found at their ends. premise, whereby we extend the application of the electric phenomena observed and measured by these and other investigators to include the entire operation of the animal mechanism, and assign to electrical energy the fundamental function of a catalyzing agent by means of which energy is liberated for every activation of the organism.

LOEB. Forced Movements, Tropisms and Animal Conduct, Philadelphia, 1918. STEINACH, vide Starling. Principles of Human Physiology, Philadelphia, 1915, p. 603. MCCLENDON. The Physical Chemistry of Vital Phenomena, Princeton, 1917. Ir every animal organism is a bipolar mechanism, then the unit primary cell in which the life of every individual begins, and each of the constituent cells of the organism at each stage in its development must be a bipolar unit. It seems well to group here the facts regarding the structure and function of the unit cells which are in accord with the bipolar theory, although a general discussion was offered in Chapter IT.

The contents of the living cell are divided into two distinct parts by a semi-permeable membrane, and the cell itself is separated from the surrounding fluids by a semi-permeable membrane. These membranes, as we have noted in a preceding chapter, are exceedingly thin; according to Dr. Fricke’s finding, they are of the order of four ten-millionths of a centimeter in thickness. On account of its lipoid character such a membrane would have a high capacity for oxidation; and on account of its high dielectric constant, it would have a high capacity for the accumulation of electric charges. If we supplement the calculation on page 17 by a like calculation to include the total number of nerve cells in the central nervous system—3,000,000,000 aecording to Meynert—the total surface area would be 91.3 square feet. The 10,000,000 large cells of the cerebellar cortex, at an assumed average diameter of 100 microns, would have a surface area of 3.4 square feet. When one imagines the addition to these areas of the total area of the nuclear membranes, and of the lipoid films covering the spherules within the protoplasmic contents of the cells, the enormous capacity of the nervous system for oxidation and for the accumulation of electric charges is at once obvious.

Not only are the contents of the living cell divided into two distinct parts by a semi-permeable membrane, but these two parts are highly differentiated, as is evidenced by the fact that differential stains are required for their definition. Thus the cytoplasm of the living cells of the multicellular animals, like that of the primal сей which supposedly originated in the alkaline waters of the sea, is alkaline in reaction; the nucleus is comparatively acid. Two colloidal solutions of different reactions, 1.е., the one acid and the other alkaline or of different degrees of alkalinity, separated from each other by a selective semi-permeable membrane, constitute an electric cell.