Crile, G. W., 1926  ·  passages 30 to 59 of 855

A Bipolar Theory of Living Processes

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The animal organism as a whole is enmeshed in a network of highly specialized electric conductors—namely, the nervous system. Та its physical composition, therefore, the body is not only highly adapted to electrical processes but its constituents in their interrelations within the organism could not be of any conceivable value in a mechanism operated by other forms of energy. The unit of structure and of function of the animal organism is the cell. An animal may in fact be regarded as a disperse

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system of cell suspensions. It is primarily essential therefore to consider the operation of the cell as a bipolar unit. The nucleus of the cell is comparatively acid, the cytoplasm is comparatively alkaline; the nucleus and the cytoplasm are separated by a semi-permeable film of very low conductivity. These characteristics of the cell indicate a difference in electric potential between the nucleus and the cytoplasm. We may therefore consider the cell as a bipolar mechanism, the nucleus being the positive element, the cytoplasm the negative element. The oxidation in the nucleus appears to be on a higher scale than the oxidation in the cytoplasm; and therefore as the electric tension increases in the nucleus, the current breaks through; the potential in the nucleus falls and in consequence the current is interrupted. Since the potential is again immediately restored by oxidation, we conceive that an interrupted current passes continually from the positive nucleus to the negative cytoplasm and in consequence a charge is accumulated on the surface films. These films of infinite thinness and of high dielectric capacity are peculiarly adapted to the storage and adaptive discharge of electric energy.

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Why is the extreme thinness of these films of advantage ? The work of the cell depends on its capacity for oxidation; oxidation, as we believe, in turn depends on the electric energy seated between the nucleus and cytoplasm; this energy depends on the voltage in the cell and on the electric charge the lipoid films will hold; the electric charge the lipoid film will hold is dependent on the thinness of the film—the thinner the film the greater the charge. Dr. Fricke has found that the film which surrounds the cells is on the order of 4/10,000,000 of a centimeter thick; and that this lipoid film has electric capacity of a high order, viz., 0.8 microfarads per square centimeter.

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We may consider then that electricity keeps the “flame of life” burning in the cell; and that the flame (oxidation) supplies the electricity which is the “vital force” of the animal. In accordance with this conception, therefore, the cell is an automatic mechanism; life as we view it is the expression of the activity of this automatic mechanism. In accordance with this conception, it is of infinite advantage to have the organism made up of trillions of units called cells

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instead of an equal mass in a single unit. The advantage of the greater surface area of the lipoid films surrounding the microscopic cells as compared with that of a single cell of equal mass is the corresponding increase in the amount of the electric charge; a corresponding increase in the amount of oxidation; a corresponding increase in working capacity. Sir Arthur Thomson has estimated that there are 28 trillion cells in the human body. On the basis of even as small an average diameter as 20 mierons the total surface area of the cells in the whole body would be equivalent to 9 acres. Meynert estimated that there are 1,200 million cells in the cerebral cortex ; thus with an assumed average diameter of 30 microns the total surface area of the cortical cells of the brain would be 3.36 square meters. On the basis of Dr. Fricke’s calculation that the electric capacity of the cell membrane per square centimeter is 0.8 microfarads—this total surface area would have a capacity equivalent to that of a Leyden jar made of glass 0.3 millimeters in thickness with a surface area of 114;000 square meters, the area of a city block.

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A homely analogy would be a comparison of four surfaces secured for writing by squaring a huge log, as compared with the amount of writing surface secured by converting the log into paper. The crude pattern of nucleus and cytoplasm could be carried out in a large animal with a range of activity comparable to that of a glacier—a log instead of a library. Furthermore, a consideration of the cell as a bipolar electrochemical unit indicates the dividing line between the living and the non-living. In accordance with this conception, the term “living” applies to the state in which there is an accumulation of electric energy on the membranes with a resultant polarization, together with a mechanism for the release of that energy to perform work. There is no more energy per mass in the living than in the non-living. In the living, energy is captured and stored and made to run the organism—in the non-living the same amount of energy exists, but is balanced; equalized ; inert; non-living.

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Two streams of water flow swiftly, each seeking the lowest level—equilibrium. One is caught and retarded, thereby building up a potential energy of position as in a mill race; in its further course this retardation is suddenly released and in the discharge of this acquired potential energy of position a water wheel is turned, and as a consequence of the turning of the wheel, heat or light or electricity is generated. The stream which has thus acquired a difference of potential may be said to live, as compared with the undisturbed river, which takes its course unchecked toward complete equilibrium.

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Two different metal plates and a suitable solution as separate units are inert—non-living; immerse the plates in the solution and connect. them with wires so that a circuit is formed and a eurrent of electricity capable of doing work is created. This corresponds to the energy function of the living. According to this conception, the physical energy in the Пу- ing and the non-living is essentially the same. In one case the energy is static—in the other it is dynamic. In the one the difference of potential is produced outside of the mechanism ; in the other the difference is constantly maintained by automatic action within the mechanism itself.

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The single cell, whether it exists independently as a unicellular organism or as one of the cells of the multicellular organism, is a bipolar mechanism, the nucleus being the positive element, the cytoplasm the negative element. As the nucleus and cytoplasm of the unicellular organisms are evolved respectively into an association of trillions of cells, thus forming the higher animals, this primary relation between the nucleus and cytoplasm is presumably still maintained among these trillions of cells, some groups of whieh may be considered as “nuclear” cells, because in them is found the highest oxidative capacity, while others, because of their comparatively low oxidative capacity, may be considered as “cytoplasmic” cells. If our conception be true, then among the positive or “nuclear” tissues there must be a tissue of the highest potential of all, and since oxidation determines potential, we are justified, on the basis of experimental studies, in considering that the brain is the positive pole in the organism. It remains to give the evi-

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dence on which we base our assumption that among the “cytoplasmic” or negative tissues, the liver has the lowest potential If the brain and the liver are the positive and the negative poles of the organism, then certain conditions would follow from this interrelationship : Fic. 3.—Effect of hepatectomy on brain cells. A. Section of cerebellum of normal dog (from photomicrograph X 310); B. Section of cerebellum of a dog after complete excision of the liver (from photomicrograph

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gether show specific changes as the result of work, would together be restored by sleep. This condition has been supported by histological and by physical researches. 2. If the negative pole—the liver—were removed, then the unit cells of the positive pole—the brain—would lose their own potential and the brain would cease to function. This is supported by experimental and clinical evidence. (Fig. 3.) 3. Since in their positive-negative relationship the functions of the brain and the liver are antithetic we would expect that their electric conductivity would vary in opposite direc-

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en lalea n n | пшн н [шин п ши п шш п шш л ши ишти а са н re tions and that the temperature changes due to stimulation would vary in opposite directions. Both of these expectations have been realized by the findings of experimental researches. (Figs. 4 and 5.) 4. It is the negative pole that accumulates waste products and keeps the circuit clear. This is a specifie function of the liver. From these premises we assume that when the great circuit between the liver and the brain is broken, the lipoid membranes, the interfacial surfaces between the colloids, interfaces in the proteins, ete., no longer receive the electrical charges on which their structure and function depend, and coagulation and death follow. Coagulation follows because the infinitesimal particles making up the colloids are no longer held apart by electrical charges. Although, as we believe, the specific activities of muscles, glands, etc., are carried on by minor circuits, nevertheless, unless the grand circuit between the brain and liver be kept intact and active, life cannot continue. According to this conception the organisms of multicellular animals as a whole are wired up in innumerable circuits—the unit of which is the nerve cell and its projected nerve fiber.

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As we have already stated, according to the bipolar theory the unit cells are so constructed that the processes of charging and of discharging follow each other in rapid succession, so that an interrupted current passes between the nucleus and the cytoplasm. Thus, in each of the unit cells of the brain, each cell would fire its charge in a rapid volley through the semipermeable membranes, the sequence being first an increase in voltage; then a break through the film; a fall in voltage; an instantaneous rise in voltage; these successive events occurring at infinitesimal intervals, just as is the case in similar apparatus made by man. Since the structure of certain cells of the brain is prolonged into highly conductive intercommunicating axons the sum of the charges of many cells may be conducted through their axons past the synapses to the muscles or glands to be

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Syoaye ejrsoddo оцу ejoN ‘лэли oq) рив ure1q oq) Jo олпдело ој ey} uo uorje[nurjs or1joo[8 Jo 309go9 ayT—"¢ ‘OT stimulated. (Fig. 6.) А part of the current, however, may presumably leak through the semi-permeable membranes and may not be consumed in the adaptive response of the muscles or glands. This portion of the current, obeying the universal law Fie. 6.—Schematic plan of afferent and efferent nerve paths. (From Cajal: Histologie du Systéme Nerveux. Paris, 1911. Vol. 2, p. 144.)

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which governs the flow of electricity from the point of highest to that of lowest potential would finally reach the point of lowest potential—the liver—and from thence be conducted back to the brain through the electrolytic fluids permeating the organism. (Fig. 7.) Тһе path from the muscles, glands, etc., to the liver, possibly may be over the sympathetic nerves everywhere present in the walls of the blood vessels. (Fig. 8.) The initiation of the energy transforming impulse in the brain and other nerve cells is due to physical forces in the internal and the external environment; that is, chemical impulses in the internal environment, and in.the external environment, the physical impulses of light, heat, contact, and sound waves. According to the bipolar hypothesis, therefore, these impulses from within or from without initiate the current which passes over one or another portion of a circuit which in-

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Fic. 7.—Schematic plan of theoretic complete sensory motor circuit. cludes about twenty-eight trillion electro-chemical units, most of which are self-charging condensers, charged up ready to be discharged by a trigger action, on the arrival of the electric impulse initiated in the circuit by the environmental stimuli. For example, a pattern of white light altered by an object falls on the rods and cones of the eye, which is continuously and in even balance responding to white light. (Fig. 9.) This disturbed balance becomes the adequate stimulus which by a trigger action discharges millions of charged condensers. We may suppose that from condenser to condenser a vast accumulating electric charge passes down through the interrupting synapses, driving muscles and glands to action, with consequences which

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]eadsopg surydoy suyor eup 'лелиј оца Jo АВојојет OY} ur serpnjg LAJ шолу) 'лолт әц JO бӘліәй 21801130]—8 ‘DIG may be commonplace or dramatic. The audion of the wireless, the stepping-up mechanism of the long distance telephone, are but weak imitations of the marvelous augmentation and step-up mechanism which probably exists in the human brain. Electricity, it would appear, is the thread which binds together in form and function the compound, the solution, the colloid, the protoplasm, the cell, the animal.

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If the bipolar theory. is correct, then it must interpret the abnormal as well as the normal phenomena of animals and man. Thus, it must interpret in electro-chemical terms such major phenomena as the emotions, physical exertion, ete. It must interpret the effect of physical and chemical injury; the effect of want of oxygen; of want of water; the effect of too much, no less than of too little heat; the defense against bacteria ; the process of healing of wounds; the effects of anestheties, and of the various drugs; the phenomena of hyperthyroidism and of thyroid defieiency ; the phenomena of ехсез- sive adrenal activity and of adrenal insufficiency.

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It must interpret the difference in physical mechanism between a fertilized and a non-fertilized cell; between a cancer and a normal cell; it must show the mechanism of stimulation and of depression; it must interpret shock, exhaustion and death; it must interpret sleep and restoration. While all of these interpretations have not been made as yet, the data thus . far aecumulated present such uniformly supporting evidence that we believe the basie evidence whereby to interpret most if not all of the phenomena of life will ultimately be secured.

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Since electric conductivity and the production of heat are basie phenomena in the operation of а bipolar mechanism, we have tested the theory by measurements of changes in electric conductivity and of heat production in various organs and parts of the body. 1. That the electric conductivity of cells would vary with stimulation and depression. 2. That the conductivity of the part of highest potential (the brain) and the conductivity of the part of lowest potential (the liver) would vary in opposite directions.

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duced by the intravenous injection of adrenalin, by physiologie doses of iodin or of thyroid extract, or by the injection of strychnin would show in the brain an increased conductivity in the stage of excitation and a diminished conductivity in the stage of fatigue, and antithetic effects in the liver. 4. That ether anesthesia in its early or excitant stage would show an increased conductivity, and in the depressant or anesthetic stage a diminished conductivity of the brain.

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5. That morphin would minimize or prevent changes in electric conductivity due to the action of adrenalin; of infection; of physical injury; of emotional excitation. 6. That the excision of the liver or of the adrenals would decrease the conductivity of the brain. 7. That prolonged consciousness carried to the state of fatigue would decrease the conductivity of the brain and that sleep would restore the normal conductivity. 8. That the actively multiplying cancer cells would show a higher conductivity than the normal cells of the tissue in which they arose; that the central autolyzing, non-growing part of a cancer would have a lower conductivity than the aggressively growing margin of the cancer; that such precancerous tissue as X-ray scars, adenomata or fibroid tumors would have a conductivity higher than that of normal tissue.

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9. That such mediating fluids as blood, cerebrospinal fluid and bile would have a high conductivity. All of these expectations have been realized by the test of electric conductivity measurements. Having found that the changes in electric conductivity were consistent with the bipolar theory, we then by means of sensitive thermocouples made simultaneous observations of the temperature changes in the various organs and tissues that might be concerned in energy transformation under the same normal and pathologic conditions as those studied in the foregoing conductivity experiments.

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Since according to our theory oxidation is the source of the difference in potential, and since heat is a constant by-product of oxidation, we would expect to find that the temperature of the brain would be increased by stimulants and decreased by depressants. We would expect to find that stimulation would produce opposite effects upon the temperature of the brain and of the liver and other relatively negative organs. Upon testing these assumptions we found that the temperature of the brain was increased and that of the liver and other negative organs was decreased or unchanged in the acute stage of stimulation by emotion, by physical injury, by strychnin injection, by the injection of adrenalin, when the output of adrenalin was artificially increased by asphyxia, in the excitant stage of ether anesthesia.

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On the other hand, if we were correct in our assumption that the liver is the center of negativity and is essential to keeping the circuit in the bipolar mechanism free from chemical by-products, then if the liver were removed, we would expect that the circuit in the bipolar mechanism would become progressively interfered with, and would finally be completely blocked with the resultant establishment of equilibrium or death. We found by experiment that when the great circuit which energizes the organism was broken by the removal of the negative pole—the liver—the temperature of the brain steadily fell until death occurred; also that when stimulants such as adrenalin were given, heat production (oxidation) within the brain bereft of its negative pole was almost or entirely prevented.

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Again, in accordance with the bipolar theory, we would expect to find a steady fall in the temperature of the brain, when the semi-permeable films around the cells, the charges upon which govern the oxidation, were rendered less permeable. We found that in the state of deep ether anesthesia, which lessens the permeability of these films and hence interferes with oxidation, the temperature of the brain and of the liver fell steadily until death occurred. |

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On the other hand, we found that in nitrous oxid anesthesia, which interferes with oxidation itself, but does not interfere with the permeability of the lipoid films surrounding the cells, the temperature of the brain decreased much more slowly. We found also that sodium, which increases permeability, and caleium, which decreases permeability, having opposite physical effects, had opposite effects on the temperature of the brain, which was increased by sodium, and decreased by calcium.

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We expected to find that in strychnin convulsions we would see violent changes in the temperature of the brain and of the liver; and our expectation was realized. ‚ Since morphin stabilizes the organism, since one of the clinical effects of morphin is the elimination of emotion, and since the emotions probably excite the adrenals to increased activity (Cannon), we expected to find that if an animal were first deeply narcotized with morphin, then given adrenalin, the morphin would lessen the change in the temperature of the brain which is produced by adrenalin in normal animals; and our expectation was realized.

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Since the intravenous injection of adrenalin causes an increased oxidation, and since asphyxia causes an increased output of adrenalin, then if an animal were asphyxiated, we expected that the consequent increase in the output of adrenalin would increase the temperature of the brain; and our expectation was realized. On the other hand, if both adrenal glands were first removed, then asphyxia could produce no increase in adrenalin, and in consequence we expected that in an adrenalectomized animal asphyxia would not cause any increase in the temperature of the brain; and our expectation was realized.

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