A Bipolar Theory of Living Processes

The adrenal glands are activators and that their aid is promptly elicited when increased metabolism—increased ‚ work—is required, is suggested by the fact that adrenalin alone produces nearly all the symptoms produced by the various causes of increased energy-transformation, such as emotion, | Ree T Fra. 32.—Immediate and late effects of the injection of adrenalin on the electrie conductivity of the brain and the liver. exertion, injury, infection. That is, adrenalin causes imcreased metabolism, increased thyroid activity, increased blood pressure, increased pulse, increased respiration, leucocytosis, increased sweating, dilation of the pupils, diversion of the blood to the surface, lowering of the threshold at the myoneural junction.

Of no less significance are the facts that adrenalin causes hyperchromatism and later chromatolysis of the brain cells just as do emotion, injury, exertion, infection; that it causes an immediate increase in the eleetrie conductivity of the brain (Fig. 32); that it increases the temperature of the. brain (Fig. 33); and that when the adrenals are removed, the brain cells rapidly degenerate, the animal rapidly loses the power to fabricate heat, and muscular and mental action; and death usually follows. We conclude, therefore, that the

Fic. 33.—Effect of the injection of adrenalin on the temperature of the brain. brain is dependent on the adrenals, both for function and for survival. Our studies of electric conductivity showed that adrenalin first increases the conductivity of the brain, as in the inceptive stage of shock, and that the conductivity is then decreased, as in other forms of stimulation. If conductivity is related to stimulation, then an increase or decrease in conductivity would be associated with an increase or decrease in function, ie, with activity or exhaustion. Our electric conductivity observations have indicated that in the inceptive stage of shock or exhaustion the conductivity of the brain is increased, while in every type of exhaustion studied, the conductivity of the brain was decreased when the state of exhaustion was

established. If the activation of the brain is a phenomenon of electric Fie. 34.—Opposite effects of the injection of adrenalin on the temperature of the brain and of voluntary muscle. energy, then since electric energy depends upon oxidation, and oxidation in part at least is controlled by adrenalin, it follows that excessive adrenalin would ultimately cause fatigue and decreased permeability. If oxidation is in part controlled by adrenalin, then the injection of adrenalin would increase oxidation and it should be possible to measure that increased oxidation by temperature variations. Our temperature studies have shown an increased temperature in the brain after the injection of адтепаћи ; but—and this is of prime significance— after the injection of adrenalin the temperature of most of the other organs and tissues was unchanged or diminished. (Figs. 31, 34 and 35.)

The experimental and clinical phenomena thus far placed in evidenee when harmonized by the bipolar theory, seem to indicate that living organisms are driven by electricity, which is fabrieated in the brain cells with the aid of adrenalin. But we have seen no evidence that the effects of adrenalin cover more than the emergencies of moments and hours, or at the most, of days. Тһе action of adrenalin is too evanescent to maintain evenly an increased receptivity, increased sensitiveness, for weeks and months. We assume that the brain has no power within itself to do this, and that, therefore, prolonged activation of the organism must be accomplished through the aid of some other organ.

The need of the organism for iodin is marked by the development of the thyroid gland as a single compact body coincidently with the emergence of animal life from the sea. ` Doubtless the lower marine animals in which the specialized gland is lacking secured sufficient iodin directly from the iodized sea-water. In the fishes and cyclostomes the thyroid is represented only by small groups of cells hardly as large as pinheads scattered along the larger blood vessels near the heart and along the gills. The gland begins to become more compact in the amphibians, and develops progressively through the various stages of land animals until it reaches its highest development in man. Тһе speeding of the metamorphosis of the tadpole by thyroid feeding has been repeatedly demonstrated. Тһе need of iodin in the marine animals, also, has

`пүепәлр® jo uorjoefur әп) 198 s[eAlojUI OAISSOISOId 3€ эреш әләм Os[e sjuouroInstoul елпувлофте) рив Хұлцоприоә әді, 'urpeuerpe jo uorjoefur oY} ләҙге s[eA1ojur ZurÁKi1€A је pep speurrue шолу тппцәдәләә әй; Јо 81014295 jo sqdeiSoiopujouq ^y 'ureiq eq) jo әлпүеләйшәҙ әц рив ÁAj1ATjonpuoo 2113299 eq? feinjonijs әй; uo штеполре jo попооГи oY} Jo 8099 олтаволбола оцу Jo Áres оцј—92 ‘DIG been strikingly demonstrated by the development of enlarged thyroid bodies in fishes kept in inland tanks, the water in which contained no trace of iodin. Marine? and his collaborators conclusively linked up the function of the thyroid with the demand of the organism for iodin when they wiped out the occurrence of goiter in the trout of the Pennsylvania State Hatcheries by adding iodin to the water.

Clinically, it is well known that iodoform poisoning causes symptoms identical with those of an, acute infection. In our laboratory we found that iodoform produced brain cell changes identical with those produced by exertion, emotion, infection, physical trauma, etc. When the secretion of the thyroid is abnormally increased as in hyperthyroidism, the whole organism becomes exquisitely sensitized, and the body functions are dramatically displayed, projecting as it were a magnified physiologic picture. Jodism alone duplicates the symptoms of hyperthyroidism.

In those chronic diseases or conditions in which an increased metabolism has continued for a considerable period of time, as, for example, in tuberculosis, in chronic infection, in the rutting season, in pregnancy, in hyperthyroidism, there is frequently a hyperplasia of the thyroid gland. Each of these states is characterized by inereased metabolism, inereased pulse, unstable heart action—excitation with consequent fatigue. The relation of the function of the thyroid to periods of prolonged stress is strikingly illustrated by the faet that in the lowest vertebrates and in certain of the lower vertebrates the groups of thyroid cells are connected with the ducts of the sexual organs. In the lower forms of life practically the only oceasion for protracted activation beyond the needs of the moment is in connection with procreation. This direct connection persists as far as the cyclostomes. The relation, however, continues to be evidenced in the higher mammals by the enlargement of the gland in periods of sexual stress—sexual excitement, menstruation, adolescence, pregnancy.

In our biophysical laboratory we found that the electric conductivity of the tissues was increased alike by the administration of iodin and of thyroid extract. (Figs. 87 and 88.) Of particular significance was our finding that the injection of adrenalin into an iodized animal produced an abrupt rise in the temperature of the brain, the amount of which far exceeded that observed in normal animals. (Fig. 39.) Тһе manner in which iodin aets as ап activating agent by controlling the phe-

Fic. 37.—Effect of the absorption of iodin (iodoform) on the electric conductivity of the brain. nomena of oxidation is suggested by the conclusions of Moureu and Dufraisse from their studies of the “catalytic properties of iodin and its compounds.” ® From previous studies they had concluded that “iodin and its compounds play catalytic rôles in the phenomena of autoxidation and that in particular under certain conditions they should possess an anti-oxidizing property.” They found that at certain concentrations compounds

of iodin had an autoxidizing action, at other concentrations an anti-oxidizing action; and that with free iodin also a retardation of oxidation preceded the acceleration of oxidation, the protraction of the former depending upon the concentration of the iodin in the solution used. “In the presence of the findings which we have presented it is in order to ask what may be the тб1е of iodin in nature. Fic. 38,—Early and late effects of thyroid feeding on the electric conductivity of the brain.

“Let us state at first that it is largely distributed throughout the mineral kingdom. It is present in notable proportions in the fundamental sphere of iodin, where live innumerable beings which often assimulate the metalloid in their organs. One finds it, moreover, in all living beings, vegetable or animal, and it is ordinarily ranked among those essential to life. (A. Gauthier, Baumann, Grey.) “According to our researches, might we not suppose that in most cases, iodin acts as an agent for the regulation of the phenomena

Fic. 39.— Comparative effects of the injection of adrenalin in normal and in iodized animals. Note the extreme and abrupt changes in the temperature of the brain in B and C as compared with the normal response to the injection of adrenalin in А. of oxidation? But feeble quantities of energy suffice to make iodin pass from the state of a positive catalyzer to that of a negative catalyzer, or inversely, according to the needs of the organism. “Following this line of thought, one cannot but be struck by the fact that the superior animals, especially those that live in a medium very poor in iodin, concentrate this element in an organ to which is attributed definitely the rôle of a regulator of oxidation —the thyroid gland.”

One further distinction should be drawn between the function of the adrenals and of the thyroid in their róle аз activating glands. It has been shown that without the adrenals the nerve cells rapidly degenerate, and death follows. Without the thyroid life may persist, but as a vegetative process only. The power of response to stimulation is lacking; the power of the organism to do work is negligible. Only sufficient electricity is generated for the essential life processes. If, however, as Kendall has dramatically demonstrated, the specific iodized product of the thyroid gland be administered to such an individual, the sensitization of the organism is inaugurated at once, response to stimulation is made possible and power to do work is established.

The one essential rôle of the blood in a bipolar mechanism would seem at first thought to be only that of an oxygen carrier, of a medium of exchange between the nerve cells and the organs and tissues which supply the elements essential to their activity. In a bipolar mechanism, however, such as we conceive the animal organism to be, not only must the principal circuit between the points of highest and of lowest potential be maintained, but a complete electric communication between all the constituent cells of each organ and tissue throughout the cireuit must be no less surely established. Such an assured intercommunication would be established by means of a fluid of high conductivity, and of neutral reaction. These essential characteristics are supplied by the blood and by the lymph, derived from the blood, by which every cell is surrounded—a medium more negative than the cytoplasm of the cells of the various organs.

In this sense, we might conceive of the blood as cytoplasm in solution, by means of which there is established a common cytoplasmic fluid connection between the liver and the brain and central nervous system, assuring the complete reciprocal functioning of these two “poles” of the bipolar mechanism. Thus we would conceive of an animal as a syncytial structure, Thus the blood would accomplish for the nervous system what the fluids of the cytoplasm of the ameba do for the nucleus—serve as the means of electric communication. In higher animals an elaborate system of nerves has been evolved to meet this need in part, but it would appear that the cytoplasmic fluid has persisted also.

This is but an extension, or adaptation to the bipolar theory of the suggestion by Wooldridge. (Mathews.)?° “The blood as a whole, including the endothelial cells of the blood vessels, may be considered to be living matter, distinguished from most other living matter by its greater fluidity. There are, however, other kinds of living matter of a liquid kind. The protoplasm of the amceba and many plant cells is so liquid that it flows readily and is in reality a circulating liquid. The blood plasma may be regarded as a very liquid protoplasm formed essentially by the cells of the vascular endothelium, by the blood cells and the hematoblasts. The blood platelets and the red blood corpuscles may be regarded, from this point of view, as homologous with the granular inclusions of many cells. Blood separated from the endothelial cells dies and clots; in just the same way a peripheral nerve dies if severed from its nutritive center. We shall in this chapter adopt this point of view of Wooldridge and consider the whole blood, the more liquid portions together with the corpuscles both white and red, the platelets, and the cells lining the blood vessels, as consisting of a great mass of living protoplasm. The processes which occur in the blood are then in many important particulars probably identical with those occurring in living matter generally. ... The alkalinity of the blood is about the same as that of the tissues generally and the methods of maintaining its alkalinity are those employed by all forms of living matter. А study of the alkalinity of the blood, its variation both physiological and pathological and the means employed to hold it constant, throws light on the alkalinity of every cell."

Many established facts regarding the phenomena of muscular activity are in accord with the bipolar theory. Electric stimulation of the controlling nerve supply of the various voluntary muscles and of the various glands of the body makes these muscles and these glands do what the brain makes them do. Stimulation of the motor area of the cortex of the brain causes muscular activity resembling everyday voluntary activities, such as closing the hand, bending the wrist, the elbow, the ankle, the knee, chewing, turning the head, turning the eyes, puckering the lips, increasing the respiration, etc. We have already cited (p. 38) the observations of Gotch and Horsley.

The severing of the nerve connection between the brain and a muscle leads not only to paralysis, but to atrophy of the muscle; but if the muscle be made to contract at certain intervals by electric stimulation, no atrophy of the muscle follows. Electricity does for the muscle, as far as its function and nutrition are concerned, what the brain does for it. Therefore, electricity is adapted to the muscle and the muscle is adapted to electricity. That muscles belong to the “cytoplasmic” division of the animal mechanism is suggested by their comparative alkalinity ; by the fact that unlike the nerve cells but in common with the other hypothetical cytoplasmic organs and tissues they store glycogen, proteins and fats, which may be utilized by the nerve cells as well; “Тп times of fasting or starvation the muscle protein is torn to pieces and converted into amino-acids, which, passing from the muscle to the blood, are carried by that internal medium to those organs of which the metabolism is keener, to the brain and nervous tissues and the heart, and serve to nourish these organs at the expense of the muscles.” (Ма- thews. ) 1!

Like the liver, so the muscles are to some degree dependent upon the adrenals. “Impulses impinging on the suprarenal glands cause these to set free substances which profoundly effect the metabolism of the muscle.” (Mathews.)?? Not only has the stimulating nerve current to the muscle been demonstrated to be an electric current, but in the response itself electricity or heat or both are generated. The activity of muscle depends upon oxidation and is related to variations in the H-ion concentration.

According to A. V. Hill “considerable electro-motive forces are produced by the activity of excited muscles or nerves—up to three or four hundredths of a volt.” 13 Hill has shown further that in a muscle the heating effect produced by the electric change accompanying a nervous impulse is not more than one hundred thousandth part of the energy liberated in a twitch. On the other hand, as he states, the electric change is sufficient to stimulate other tissues. The possibility that the nuclei of the muscle cells play an essential rôle in the phenomena of muscular action is suggested by Mathews: “А very interesting but entirely unsolved problem is the possible involvement of the nucleus in the processes of contraction and energy metabolism.” !* That the muscle cells possess an electric potential is suggested by their acid-alkali variations in periods of activity and rest, and by the elaborate mechanisms for the neutralization of the acids which are formed during work. It would appear then that the nervous impulse to a muscle is the catalyzing agent which “fires” the energy stored in the muscle cell itself and thus initiates the complex chemical changes—in themselves electrical phenomena, which produce the phenomena—motion or heat—of muscular activity.

In accordance with our general conception we may suppose that in the original unicellular mechanism, each reaction, each response to environment was an electrical response between the nucleus and the entire cell body, the essential potential being accumulated on the nuclear membrane. At a very early stage in the life of this first protozoan, however, variations in the chemical constitution of different portions of the cytoplasm must have established varying potentials within these portions and thus determined the direction of the electric current. For example, one may readily suppose that at the point at which

ingested food was received the immediate resultant changes in electrolytic concentration at that point would determine the direction of at least a portion of the electric current. It is not our purpose, even if it were possible, to consider the various steps by which from the primary differentiation of the parts of the early unicellular organism the highly differentiated multicellular organism was developed. Nor does space permit a discussion of the possible specific function of other parts and tissues than those most immediately concerned with the fabrication and release of the electrical energy which operates the bipolar mechanism.

We believe that many generally accepted facts could be marshalled whereby we might interpret in bipolar terms not only the function of the effector organs—muscles; of the essential activating organs—the thyroid and the adrenals; but also of the heart and circulatory system, which are essential for the conveyance of the secretions of the essential activating organs to the nerve cells; of the pituitary gland with its possible function of conserving the essential alkaline balance—the formula of the sea—within the organism by its regulation of the salt content of the cells and its further function of regulating skeletal growth; of the digestive system with its selective power of supplying the essential constituents of the cells.

It is sufficient to our purpose here to emphasize the fact that it would seem that each organ and tissue of the body but fulfills a role previsioned in the functions of the cytoplasm and nucleoplasm of the original simple unicellular bipolar mechanism. 3. CHILD. The Origin and Development of the Central Nervous System, Chicago, 1921. As has been emphasized in a previous chapter the neurones are nowhere in direct physical contact with each other and the lines of communication between the neurones and the muscles, glands, etc., are broken by synapses.

The synapse, as suggested by Sherrington, may be endowed with special properties: “It might restrain diffusion, bank up. osmotic pressure, restrict the movement of ions, accumulate electric charges, support a double electric layer, alter in shape and surface tension with changes in difference in potential, alter in difference of potential with changes in surface tension or in shape, or intervene as a membrane between dilute solutions of electrolytes of different concentration or colloidal suspensions with different sign of charge.” 1

The synapse then may be regarded as a highly adapted switch which now closes the circuit, now opens it; now diminishes the current, now accelerates it. An electric current flows from an area of a higher to an area of lower potential, hence the electric battery—the nerve cell— would be in constant action, excepting for the intervention of the synaptic switch. If the nerve cell and the end-organ were constantly connected, then the nerve cell would be in the position of the battery of a door-bell whose button is pegged. With the living electric circuit closed at the synapse, the nerve cell would work continually and would be exhausted just as certainly as the electric battery in a closed circuit becomes exhausted. And to the same extent the stimulated organ—the gland cell, or the muscle cell—would be worn by continuous stimulation.

The presence of a synapse as a mechanism of adaptive electric connection and disconnection is as important as the spring whieh breaks the eleetrie eurrent of the door-bell when the pressure is released. Conversely, the presence of the synapse supports the conception that there is an electrie potential in Fie. 40.—Early (B) and late (C) effects of strychnin poisoning on the brain cells. Compare the hyperchromatism. in B and the chromatolysis in C with the appearance of the normal brain cells in A. (From photomicrographs X 310.)

the living neurones; that the nerve cells act in some such manner as do accumulators. In view of this conception, the phenomena of strychnin poisoning suggest that strychnin may act on the synapses in such a way that the electric circuits of many cells are closed at once, so that there results the universal and violent stimulation of muscles which constitutes a convulsion. Moreover, not only the muscles, but other mechanisms are stimulated also, as