A Bipolar Theory of Living Processes

In accordance with the bipolar theory, one would ‘expect that during increased activation, such as follows adrenalin injection, the brain would show an immediate increased conductivity, and that in fatigue from excessive adrenalin stimulation, it would show a decreased conductivity; that in the unborn and during the unconscious state of the newborn, the electric conductivity of the cerebrum would be lower than that of the cerebellum and that this relation would be reversed at the time when consciousness appears; that heavy physical trauma which would cause first struggle, then exhaustion, would show first an increase, then a diminution in the conductivity of the brain.

which is the analogue of hyperthyroidism, should be accompanied by an increase in the electric conductivity of the dominant tissues of the body. In accordance with the bipolar theory, excision of the liver and excision of the adrenals should cause a decrease in the electric conductivity of the brain. In accordance with such a theory, one would expect that the injection of acids would decrease conductivity, and that whereas loss of sleep would decrease conductivity, sleep itself would restore the normal conductivity of the brain. The application of these tests was regarded as an essential to prove or disprove the validity of the theory. Ifa single one of these should fail, the entire theory must fail.

To this end, therefore, a research was undertaken in which measurements were made of tissues from normal adult and immature rabbits, and from fetuses, and from rabbits subjected to various types of exhaustion—insomnia, exertion, fright, infection, surgical shock; to the action of various drugs—stimulant and depressive ; to short and prolonged anesthesia, by ether and by nitrous oxid; to the action of adrenalin in single and in repeated doses; to thyroid feeding and to acute iodism induced by the injection of iodoform; to the injection of acids and of alkalies; to the excision of organs—the thyroid, the liver, the adrenals.

The tissues and fluids measured included the cerebrum, the cerebellum, the spinal cord, the liver, the thyroid, voluntary muscle, the heart, the kidneys, the spleen, the lung, the spinal fluid, the blood, the bile. Our findings in these studies, which included the measurement of the electric conductivity of 4,764 sections from 455 rabbits and 219 sections of pathological human tissues, may be summarized as follows: 1 1. The specific normal conductivity of the cerebrum, cerebellum and liver can be estimated within a narrow range; while the normal conductivity of other tissues can be estimated

1It should be emphasized that in the measurements described here а 1000 cycle alternating current was employed, while in the capacity measurements to be described in a later section, currents of from 800 to 415 million cycles were used. within a sufficiently narrow range to determine the order of their relative conductivities. 2. The spinal fluid had the highest conductivity of any of the tissues studied, the lung and the liver the lowest. 3. The order of the conductivities of the following tissues was unchanged in all the animals studied, with the exception noted in (5); viz., spinal fluid, bile, blood, voluntary muscle, cerebrum, cerebellum, liver, lung. In a limited number of observations the conductivity of the heart fell between that of the cerebelium and the liver, but on account of the wide range of the individual measurements, this cannot be considered as established.

cording to the season and the general environment. . 5. In every normal adult animal studied the conductivity of the cerebrum was higher than the conductivity of the cerebellum. In fetuses and in very young rabbits this relation was reversed—the conductivity of the cerebellum being higher than the conductivity of the cerebrum until about the time when the young rabbit left the nest and began voluntary activities, . when the normal adult conductivity relation of the cerebrum and the cerebellum appeared to be established. А most significant corollary to this observation was found in the post-mortem examination of the brains of two patients, one of whom died after days of unconsciousness resulting from a brain tumor, while the other, who died from carcinoma of the stomach, was conscious to the end. In the patient who had been unconscious, the conductivity of the cerebellum was higher than that of the cerebrum. In the other patient, as in all our normal animals, the conductivity of the cerebrum was higher than that of the cerebellum.

6. The conductivity of the gray matter of the brain is higher than that of the white matter. 7. Exhaustion from any cause—surgical shock, insomnia, emotion (fright), infection, ete.—is marked by a diminished conductivity of the brain and an increased conductivity of the liver. 8. The immediate effect of activation appears to be an increased conductivity of the brain, tending later to decrease as the stage of exhaustion approaches. This has been shown to be an immediate effect of physical injury; an early effect of the injection of diphtheria toxin; an immediate effect of the injection of adrenalin.

9. Thyroid feeding in large doses over a prolonged period produces the typical symptoms of hyperthyroidism with ultimate exhaustion, accompanied by the changes in the conductivity of the brain, typieal of exhaustion from any other cause; ie. the conductivity of the cerebrum and.cerebellum is de creased. 10. Thyroid feeding in moderate doses until the symptoms of hyperthyroidism appear, but not to the stage of exhaustion, produces conductivity changes in the brain typical of the stage of stimulation produced by other agents; i.e., increased conductivity of the brain and decreased conductivity of the liver. These changes were diminished or reversed by the administration of adrenalin.

11. Iodoform increases the conductivity of the brain and the liver. These changes are reversed by adrenalin. 12. The injection of hydrochloric acid produced diminished conductivity of the cerebellum and cerebrum and increased conductivity of the liver. The injection of sodium bicarbonate produced increased conductivity of the cerebellum and cerebrum and decreased conductivity of the liver. 13. Rabbits were kept awake continuously for 96 hours. At the end of this period a number were killed and conductivity measurements made; others were allowed a brief period of rest of from four days to a week. At the end of the insomnia period the conductivity of the brain was decreased and the conductivity of the liver was increased; at the end of the short period of rest, the conductivity of the brain and of the liver was but little changed, if at all; at the end of the longer periods of rest, the brain was again approaching its normal conductivity.

14. А limited number of observations indicate that the changes produced by the injection of a toxin are minimized, provided the toxin is applied in the presence of morphin ; that is, excessive doses of a toxin alone decrease the conductivity of the brain and increase the conductivity of the liver; in this limited series of observations the conductivity of the brain remained practically unchanged when diphtheria toxin was administered in a morphinized animal, and the conductivity of the liver was but slightly altered.

15. А limited series of observations of the influence of various agents, which produce marked clinical effects, indicate that the progress of alteration in function produced by any agent is coincident with changes in electric conductivity. 16. In the pathological specimens studied, active malignant growths have a high conductivity in comparison with adjacent normal tissue and the inactive portions of the same growth, and with growths of а non-malignant type.

17. From our findings to date, it would appear that the intracellular changes in exhaustion and shock which are revealed by the microscope are paralleled by alterations in electrie conductivity, and that both the histologie and the electric changes bear a direct relation to the vitality of the organ. Іх a bipolar mechanism, variations in functional activity indicate variations in oxidation; variations in oxidation are manifested by variations in heat production. If heat is a constant product of functional activity, then if we could measure the progressive changes in the temperature of the various tissues and organs during the various phases of excitation and exhaustion under conditions identical with those formerly studied, we not only should be able to check our findings in the previous researches, but should be able finally to link those findings with the clinical evidence.

While previous studies had appeared to demonstrate a definite relationship between histologic changes and electric conductivity, this relationship constituting strong evidence in support of the bipolar theory, nevertheless, they did not demonstrate whether or not these apparently related findings were not merely coincident conditions, but corresponded to changes in function. Moreover, measurements of electric conductivity must be prosecuted after the death of the animal, although with proper precautions it is reasonable to believe that the changes noted at least parallel the progress of processes in the living animal. To determine finally whether or not the variations in the histologic picture and in the electric conductivity are parts of one and the same process as that manifested by changes in functional activity—oxidation—it was necessary to devise some method by which the rate of oxidation in the cells might be measured in the living animal. Only by such a measure could it be ascertained whether or not changes in electric conductivity indicate changes in oxidation. Clinical evidence would appear to demonstrate that this is the ease, but clinical evidence cannot be accurately measured, nor does it identify without question the organs which are princi-

pally concerned. Some accurate index that could be applied to the organ itself in the living animal was essential. As a means to this end, we decided to use the method of measurement employed by physicists for the measurement of minute variations in temperature, that is, to employ thermocouples so constructed that they could be applied to the brain, liver, muscle or other tissue of the living animal. 1. From the very beginning it was evident that variations in the temperature of the brain under varying conditions parallel variations in the histologic picture and in the electric conductivity of the brain under the same conditions. ‘Thus, the progress of exhaustion from any cause was marked by a progressive decrease in the temperature of the brain and the liver, the rapidity of which was in direct relation to the rate at which the degree of exhaustion advanced.

2. The stage of excitement of ether anesthesia was marked by an increase in the temperature of the brain; but during surgical anesthesia the temperature fell continuously until death. On the other hand, in an animal under nitrous oxid anesthesia, the temperature of the brain remained practically unchanged even during prolonged anesthesia. 3. After hepatectomy the temperature of the brain declined progressively until death, the résultant curve corresponding closely to that produced by continuous ether anesthesia.

4. Muscular activity, either voluntary or produced by direct electric stimulation of a nerve, was accompanied by rapid alterations in the temperature of the brain and the liver corresponding to the phases of the muscular activity—these alterations, however, being n opposite directions. 5. No significant alteration in the temperature of the liver was produced by the injection of strychnin, of an acid or of an alkali, although marked and characteristic changes, corresponding in each case to the clinical phenomena, were produced by each in the temperature of the brain.

6. Exposure of the viscera and abdominal trauma alike produced a rapid fall in the temperature of the brain and the liver, the change in the latter being in part but not entirely accounted for by the direct chilling of the liver substance. 7. The restorative effect of the introduction of hot water into the stomach was marked by an immediate elevation of the temperature of the brain which measurably preceded—in some instances by a minute or more—the resultant elevation in the temperature of the liver.

8. Of especial significance were the temperature changes which followed the injection of adrenalin under varying conditions. (a) In normal animals the temperature of the brain was increased by adrenalin, but returned immediately to or below the preceding level. (b) In normal animals the temperature of the liver was not significantly affected by the injection of adrenalin. (e) А limited number of observations indicated that the temperature of the spleen, the kidneys, voluntary muscles and intestinal walls was decreased by the injection of adrenalin.

(d) In the absence of the liver the injection of adrenalin produced a diminished or no change in the temperature of the brain. (e) In the absence of the thyroid the reaction of the brain to adrenalin was less than in normal animals. (f) In iodized animals the reaction to adrenalin appeared more promptly and was greater than in normal animals. (g) After adrenalectomy the reaction to adrenalin was approximately the same as in normal animals. (h) In morphinized animals adrenalin increased the temperature of the brain but this increase was less than in normal animals and was maintained for prolonged periods.

(i) After the administration of strychnin adrenalin caused an abrupt rise in the temperature of the brain and an abrupt fall in the temperature of the liver. (j) After hemorrhage the injection of Bayliss’ solution diminished the reaction of the brain to adrenalin. (k) The transfusion of blood after hemorrhage did not affect the normal reaction of the brain to adrenalin. Of particular significance were the findings, (a) that in voluntary muscular activity and as a result of the direct electric stimulation of a nerve the temperature of the brain and of the liver varied in opposite directions; (b) that upon the introduc-

tion of hot water into the stomach the reaction of the brain in increased temperature preceded that of the liver; (c) that the temperature of the liver was but little altered or was unchanged by the injection of adrenalin; of an acid; of an alkali. An attempt has been made to establish our assumption that the changes in the temperature of the brain after the injection of adrenalin may be justly ascribed to variations in oxidation. Preliminary experiments have shown that after the injection of adrenalin the temperature of the venous blood coming from the brain was increased to above that of the arterial blood to the brain. This finding if confirmed by later experiments will be a strong indication that the temperature changes within the brain cannot be entirely, if at all, due to variations in the blood supply to the brain.

The findings in these studies which accord with the histologic studies and the electric conductivity measurements support the conclusions, (a) that the brain is the tissue upon which depend the reactions of the organism to stimulation; (b) that the thyroid and the adrenals play essential parts in the production and maintenance of these reactions; (е) that in the performance of its function the brain is indissolubly linked with the liver. The lack of response of the brain to adrenalin in the absence of the liver, together with the opposite reactions of the brain and the liver, form vital links in the chain of evidence, whereby we may determine the function of each in the bipolar operation of the animal mechanism.

Tx organic cell may be compared to a condenser of the type of the Leyden jar in which the charge is accumulated at the surface of a dielectric between two conductors. In the case of the cell the two conductors are the electrolytic fluids within and without the cell; the dielectric is the comparatively nonconducting lipoid membrane. In a condenser of this type the thinner the dielectric the higher is the capacity. The capacity of such a condenser may be computed from the formula C= Sk

4ла sq. ст. of the dielectric, К is the dielectric constant and @ is the distance in em. between the surfaces of the dielectric. It follows that the greater the area of the surface, the higher the dielectric constant, and the thinner the dielectric, the greater will be the capacity of the condenser. In referring the elements of this formula to the biologic cell we find that the cell membrane is lipoid in character and has a dielectric constant of the order of 3.

By experimental methods Dr. Fricke has established for the red corpuscles a capacity of 0.8 microfarads per sq. cm. of cell surface; and, reversing the above formula, has calculated from this value the thickness of the cell membrane, finding it to be of the order of 4/10,000,000 of a centimeter in thickness—1.e., of the thickness of a single molecule of oil. In a previous section we have calculated that assuming an average diameter of 30 microns, the estimated approximate number of nerve cells—3,000,000,000—would give a total surface area of 8.48 sq. meters (91.4 sq. feet) ; for the estimated number of nerve cells of the cerebral cortex—1,200,000,000—

the total surface area would be 3.36 sq. meters (36.4 sq. feet) ; and for the estimated number of large cells in the cerebellar cortex—10,000,000—with an average diameter of 100 microns, the total surface area would be 0.32 sq. meters (3.4 sq. feet). On the basis of Dr. Fricke’s capacity value per sq. cm. the total capacity values of these areas can readily be calculated. Thus, for the cerebral cortex alone the total value would be 26,880 microfarads. The significance of this capacity value is shown by the fact that this would be the capacity value of a Leyden jar made of glass one-third of a millimeter in thickness with a total surface area of 114,000 square meters (2.8 acres).

Such a Leyden jar with a capacity equivalent to a single cell with a diameter of 80 microns would have a surface of 0.95 sq. em., while a Leyden jar with a capacity equivalent to that of the large brain cells with a diameter of 100 microns would require a surface of 10.2 sq. сш. While these comparisons are interesting, they are not so significant as those which give the amount of heat which would be required to supply such a difference in potential as is indicated by existing evidence. То establish a difference of potential of one volt across one farad requires 0.12 gram calories. To establish the potential indicated by the value of 0.8 microfarads per sq. em. of cell membrane, for the total surface of the 1,200,000,000 cells in the cerebral cortex would require 8 X 10? gram calories.

The figures given above not only express the high capacity value of the brain cells, but they show also that the energy which is fabricated in the brain is measurable іп electrochemical units. CERTAIN ESTABLISHED Facts REGARDING ELECTRIC ENERGY AND ITS RELATION то OTHER Tyres or ENERGY Tue energy of animals is derived from the sun, in small part directly, in large part from the light energy stored in plants in the form of carbohydrates. But just as the plant cells cannot transform simple elements into carbohydrates without light, and as many chemieal processes require for their initiation a radio-active, thermal, electrical or other catalytic agent, it is assumed that a catalytic agent is required to excite the activity of the cells of the body, whether that activity is to be expressed in terms of thermal, chemical, mechanical or electrical energy. What form of energy constitutes this catalyzing agency? Аз stated in Chapter IT, the existing forms of energy among which the choice must lie are heat, light, gravitation, intermolecular forces (surface tension, adsorption ), chemical energy, electric energy. It is obvious that neither heat energy nor any mechanical force can be transmitted by the nerve fibers to act as a catalyzing agent upon the various types of cells in the organism, exciting in each the type of activity demanded for the performance of its specific function. The form of energy to be identified, therefore, must be intermolecular or chemical or electric energy.

Since electricity controls chemical and intermolecular action, and since chemical action—oxidation—controls the production of electricity in an electric cell constructed after the pattern of the cells of the organism, we conceive that electricity liberated in the cells of the central nervous system by oxidation and conveyed to the cells by the nerve fibers acts as a catalyzing agent by means of which the energy in each cell of the organism is controlled by nerve action. Іп cells which are not innervated, the same structural arrangement is found; and in these cells also oxidation is the source of energy.

To enumerate the facts reported by many investigators regarding the rôle of electricity in vital processes would require a large volume in itself and would not be pertinent to the purposes of this thesis. We shall therefore confine ourselves to an enumeration of only those generally accepted facts regarding electricity which are especially pertinent to our conception of man and animals as bipolar mechanisms. Electricity is omnipresent in all forms of matter, in atoms, molecules, solutions, colloids. Electricity passes by means of conductors from a point of higher potential to one of lower potential, always along the path of least resistance. At any point in its passage the electric current is capable of transformation into heat energy, mechanical energy or chemical energy. An electric current is produced by a generator or battery whereby a difference of potential is maintained between the poles.