A Bipolar Theory of Living Processes

Vig. 18.—Drawing of longitudinal section of a spinal ganglion. (From Cajal: Histologie du Systéme Nerveux. Paris, 1911. Vol. 1, p. 131.) very early in development. In the earliest embryo in Mall’s list, the brain portion of the medullary canal is already marked off and shows beginning segmentation. Child 4 has shown that in the embryo the brain leads all other structures in growth and development, and like the bud of the plant has the highest metabolism. His and Keibel have indieated the significance of the order of development of the various organs and tissues.

(7) The power of the nervous system to create new cells is indicated by certain functions of the nucleus which have been demonstrated by Pfeffer In Pfeffer’s experiments the nervous system of multicellular organisms appears to have been shown in mimature, and his observations offer such convincing evidence in support of the conception of the nuclear Fie. 19.—Different forms of cells in the plexiform ganglion of the vagus nerve. Note in G the apparent association of one of the nerve fibres with the nucleus and of the other with the cytoplasm of the ganglion cell. (From Cajal: Histologie du Systéme Nerveux. Paris, 1911. Vol. 1, p. 440.)

origin and function of the central nervous system, that it has seemed well to include here the following extensive quotation: “After having detached by plasmolysis the cell membrane of the nucleated protoplasmic body of a plant cell, and dividing the cell сг Fic. 20.—Diagrammatie drawings illustrating five types of reflex ares. in halves, one containing a nucleus and one without any, Ве observed that only the nucleated half had surrounded itself with a new cell membrane. If, however, the part deprived of a nucleus remained united to the nucleated fragment even by only a very fine protoplasmic filament, it also was capable of secreting its little cellulose membrane.

“Pfeffer varied his experiment also in the following manner. He prepared cells of a moss protonema in such a way that an entirely isolated, anucleate mass of protoplasm remained united to the neighboring cell which contained a nucleus by means of thin filaments piercing the cell wall. In this case a membrane was formed round the anucleate fragment. But the membrane was not formed if the neighboring cell had been itself deprived of its nucleus. “In the formation of this cellular membrane in anucleated parts of the cytoplasm united by protoplasmic filaments with other nucleated portions, the maximum intervening distance observed by Pfeffer was 3.7 mm. ‘But the nucleus can certainly exercise the membrane forming stimulus at an even greater distance.’ If

Fig. 21.—Diagram of simplest possible spinal reflex mechanism. (From Johnstone: Mechanism of Life. London, 1921, p. 117.) the nucleus remains united with a whole chain of anucleated bits of cytoplasm ‘the production of the membrane appears to advance centrifugally and so to commence a little later in the more remote portions of cytoplasm, than in the bits nearer the nucleus.’ “From these experiments one is inclined to think, this author concludes, ‘that the production of a cellular membrane required the continuous transmission and coöperation of certain states of motion and vibration which radiate out from cell nuclei or rather owe their origin to the reciprocal action of nucleus and cytoplasm,’

“Oscar Hertwig makes in this connection the following remark: ‘This experiment proves that the stimulus necessary for membrane formation can be transmitted by thin connecting filaments which traverse the septum interposed between two cells. Nothing hinders us then from assuming that some similar transmission goes on in other functional conditions.’ i “But it is very probable that this nervous current or discharge Fig. 22.—Diagram illustrating method of reinforcement of afferent nerve impulse (after Herrick),

which is conducted from the nucleated cell along the protoplasmic filaments to the anucleated fragment of the contiguous cell, also passes across into the fragment even when it contains a nucleus and so also when it is replaced by an entire cell. This leads us to the conception that wherever intercellular protoplasmic connections are present, the various nuclear currents of discharges stream through these connections and so permit a general nervous flux throughout the whole network of these protoplasmic bridges, in

the meshes of which the nuclei themselves would constitute the nodal points. In this way one would have a continuous circulation or distribution of nervous energy throughout the entire organism. “The augmentation of the nervous system in these ways will have as its result an augmentation of the trophic stimulus which it exercises; so that the cells situated along these ways will grow and proliferate more rapidly, thus producing a zone characterized by

numerous mitoses. Тһе augmentation of the vital processes of these cells will in consequence of increased osmotic attraction, attract a greater quantity of nutritive fluid, exactly as the wick of Fie. 24.—Schematic drawing of the sensitive and motor paths in the sympathetic nervous system. (Redrawn from Cajal: Histologie du Sys- tème Nerveux. . Paris, 1911. Vol. 2, p. 941.) a lamp which is stimulated by a current of air draws up by capillarity a larger quantity of combustible fluid.”

(8) In support of this view may be cited also the findings of Kofoid and his collaborators in their studies of the neuromotor apparatus of certain intestinal parasites in which the primitive apparatus of flagella and the protoplasmic areas from which they originate appear to be of a truly nervous ЧУГА әзецәдер ejo2rjsvuif[od v ‘xing xrjseuro[qo1jq цо : Аләм pue propos шолу) 'Seje[[e2wp ie[n|[oorun итезләә јо snqeiedde лојош-олпәи оцј— 2 ‘srg character and to be dependent upon the nucleus both for origin and for function.” (Figs. 25 and 26.)

“The close physical connection between the blepharoplasts at the base of the flagella and the nucleus, the metabolic center of the cell, throughout the period of flagellar activity, is indicative of the intimate relation which the nucleus bears to these energy-expending structures: It cannot be merely the physical tug of the moving flagella which pulls the nucleus to its anterior position, for the blepharoplasts retain this anterior location when the nucleus moves posteriorly, the connection between them being retained merely by the slender nuclear rhizoplast. The rounding-up process in the cytoplasm of the encysting individual doubtless exerts some pressure leading to spatial readjustments, but the translation of the nucleus appears to be out of proportion to this single factor. In the active phase of the organism the nucleus 1s nearest to the center of metabolic actwity, and in the passive phase of encystment it tends to assume a place as near as possible to the center of the cytoplasmic mass, the cytostomal pouch appearing to hold it off from the fully central location.”

There is a striking analogy in the above description to the findings of Magini (cited by Cajal)? who in studies of the cerebro-electric lobe of the torpedo observed that in periods of rest the nucleolus occupied a central or slightly eccentric position in the nucleus, while in periods of activity it moved in the direction of the axon to the membrane of the nucleus where it came in contact with the point of origin of the cylinder axis, with the resultant development of the nervous (electrie) wave which discharged the electric organ. (Fig. 27.)

АП of these facts and the conjectures suggested thereby would indicate that throughout phylogeny nerve tissue like the nucleus has been an energy-producing tissue; and that the central nervous system may justly be considered the direct descendant of the nucleus of the original unicellular organism. Since in a bipolar mechanism, the electric current must flow from areas of higher to areas of lower potential, it is necessary to cite such facts as may tend to support the conception that the cells of the brain are the principal source of the electric energy that codrdinates the body and to show how the direction of the fabricated current is established.

Fic. 26.—The neuro-motor apparatus of Diplodinium Ecuadatum. Note the identical staining of micronucleus (mic) and of the neuromotor fibres communicating with the membranelles and cilia and of the motorium (m.m.). This organism is a striking example of a high degree of differentiation in a unicellular organism. (From Sharp: Diplodinium Ecuadatum with an account of its neuromotor apparatus. Univ. Calif. Publ. Zool. 1919, Vol. 13, рр. 43-122.) . . Since according to experimental findings the low-conducting

extremely thin lipoid films which surround the cell body .and the nucleus have a high electric capacity, it would seem that the potential within the cells must be very high as compared | with the potential within the axons which are surrounded by a thicker myelin sheath. The electric current, therefore, would pass from the highest potential within the cells through the zones of lower potential in the axons and nerves toward the points of lowest potential in the glands and muscles to be stimulated. In accordance with this conception, when the “wave” of potential in its passage from the cell through the axon reached a certain “pressure” the synapse would become sufficiently polarized to allow the current to pass across it to

the structures beyond. Thus the synapse may be in effect a projected part of the lipoid film surrounding the nucleus and the cell; and being endowed with less resistance to the passage of eleciric charges, after a certain pressure is reached, the current would break through. Clinically the control of the body by the energy fabricated in the brain, which we believe to be electric energy, is indicated by the result of high division of the spinal cord; by the result of the paralysis of the motor end-plates by curare; by the result of the suspension of the activity of the higher brain centers by inhalation anesthesia; by the result of breaking the nerve connection with any part; by the fact that when the supply of oxygen is cut off no energy is created and equilibrium or death follows. Any disabling influence whereby either the connection of the brain with a part of the body is broken or the function of the brain is disabled or lost renders the body helpless.

The brain cannot work continuously, but а reversible process is necessary at regular intervals to restore it. This process in the higher centers is called sleep. The more intense the activation, the more needed is sleep. The brain is the only organ that sleeps conspicuously. Of great significance is the fact that the entire man spends one-third of his time waiting for the brain to restore itself, or, according to the bipolar theory, to put itself again in the position of being able adaptively to transform potential into kinetie energy in the form of electricity, which in turn drives the body.

If the brain and central nervous system represent the nucleus of the original unicellular organism, that is, the part of highest metabolism, the highest degree of positivity, then some other organ or tissue must be its antithesis—must be the center of negativity. That the liver primarily represents certain essential functions of the cytoplasm is suggested by many facts, among which the following are of especial significance: 1. The cytoplasm of the unicellular organism receives and stores food; the liver receives and stores food (glycogen).

affinity for the acid by-products produced in the nucleus and in the cytoplasm itself; in the higher animals the liver plays a - similar rôle. 3. The nerve cells, like the nuclei of unicellular organisms, possess no neutral fat, no glucose, no acid-neutralizing material ; these are stored in the liver for the benefit of the brain as well as for itself and for other organs and tissues. 4. In the ameeba neither the cytoplasm nor the nucleus сап function without the other; in the higher animal the brain cannot function without the liver; the organism cannot function without the brain. The brain and the liver work simultaneously ; the brain and the liver are restored simultaneously.

5. The early evolutional appearance of the liver is signifieant. Although the function of the so-called hepatic cells of the polyps has been disputed, nevertheless the gradual concentration and development of these cells from the polyps through the echinoderms, annelids, insects, etc., to the fishes, reptiles, birds and mammals, make it appear that the peculiar functions of the cytoplasm which we have described above began to be assigned to specifically differentiated cells (liver) at a very early period in evolution.

6. In the embryo the anlage of the liver appears in the very earliest stages of development, being practically coincident with the appearance of the anlagen of the central nervous system. The embryonie development of the liver is exceedingly rapid, the organ almost filling the abdominal cavity in the third month, when its weight is approximately 10.5 per cent of the entire body weight, and throughout life its weight is usually about 2 per cent of the entire body weight. As Keibel and others have stated, the precocious appearance of the anlagen of certain organs is undoubtedly associated with the necessity for their early development, the anlagen mutually influencing each other in the development of the organism as a whole.

In addition to these facts, which would appear to suggest the cytoplasmic origin and function of the liver, many facts may be cited, which indicate not only the interdependence of the brain and the liver, but also their antithetic róles in the or- `Кшоўдәә}вйәц 1938 ureueipe jo uorjoefur oy} 0} ureiq oy} иг esuodsoi јо you, Surmoys в}лецә o1njeroduro[—gz 914 ganism. These facts indicate also that this interdependence is due to some relationship which is not explained by any current theory. How, for example, can we account for the progressive changes in the brain and the inevitable death after the liver is excised; or for the alteration in the functioning of the brain when the liver is damaged? (Fig. 28.) These changes are not due to a want of glycogen, for the administration of glycogen does not prevent death. It does not seem that death after hepatectomy can be due alone to the loss of the power of the liver to split up acid by-products for the following reasons: (1) Life is not prolonged by the administration of large doses of morphin for the purpose of minimizing metabolism and in consequence diminishing the amount of acid byproducts; (2) the repeated transfusion of blood does not prolong life; (3) the administration of acid-neutralizing alkalies is of no avail. It would seem that the dramatic fall in body temperature might be an important factor in the inevitable death which follows excision of the liver; but the maintenance of the normal temperature by artificial means does not prevent death. No therapeutic measure has been found of avail in acute yellow atrophy of the liver or after the excision of the liver.

In addition to the fact that death is the inevitable result of excision of the liver, there are certain other outstanding facts which cannot be interpreted by any conception of the method of operation of the organism which has thus far been proposed. Among these the following are of especial significance: 1. When the adrenals are removed the liver cells with the brain cells undergo a physical disintegration. Neither the brain nor the liver can survive without the adrenals. (Fig. 29, C and F.)

2. After decapitation, if the adrenals remain intact, the liver cells do not break down. 3. The injection of adrenalin increases the stainability of the brain cells and the liver cells. (Fig. 29, B and E.) 4. Тһе liver and the brain, and to a lesser degree the adrenals, are affected simultaneously by any cause of exhaustion. These organs work and are exhausted simultaneously ; they are restored simultaneously. Ета. 29.—Effect of the injection of adrenalin and of adrenalectomy on the cells of the brain and of the liver. A. Section of cerebellum of normal dog. B. Section of cerebellum of dog after injection of adrenalin. C. Section of cerebellum of dog after adrenalectomy. (From photomicrographs X 310.) D. Liver of normal dog. E. Liver of dog after injection of adrenalin. Е. Liver of dog after adrenalectomy. (From photomicrographs Х 1640.) Note the hyperchromatism of the Purkinje cells in B as compared with the chromatolysis in С; and the vacuolation and disappearance of nuclei in F as compared with E.

5. Want of oxygen causes loss of brain function and death. Want of liver function causes loss of brain function and death. These facts suggest that nerve cells require for their action the presence of oxygen, of adrenal function and of some role played by the liver. 6. In every experimental test the liver has been found to be exceedingly sensitive to change, even more so than the brain. This was shown in resuscitation experiments; in perfusion experiments; by observations of its unequalled rapidity of autolysis; and by measurements of its electric conductivity.

Fic. 30.—Opposite effects of the injection of (A) an acid and (B) an alkali on the electric conductivity of the brain and the liver. 7. In studies by Renauld-Capart he noted that “the first fact established was that the abdominal blood is essential to the function of the brain centers. This being demonstrated we directed our research to discover which of the abdominal organs could so affect the blood as to influence the cerebral activity. We have from the very first established that the blood which passes through the liver has the property of reéstablishing cerebral functions; following this, that the liver alone, of all the abdominal organs, has that property." *

8. Тһе chemical constitution of the liver is in harmony with the conception that it is the negative pole of a bipolar organism. Тһе liver is rich in mineral substances—potassium, sodium, phosphoric acid, chlorin, iron and alkaline earths. The tendency of the liver cells to accumulate mineral sub- Fig. 31.—Opposite effects of the injection of adrenalin on the temperature of the brain and of the liver. stances, especially metals, has been emphasized by Roger. (See Appendix A, p. 237.) On the other hand, the metallic content of the brain is exceedingly minute as compared with the liver.

Finally, and of prime importance, are the biophysical findings that the application of any stimulus causes opposite changes in the conductivity of the brain and the liver. Thus, in the stage of stimulation by any agent, the conductivity of the brain is increased; the conductivity of the liver is decreased. In the stage of exhaustion, the conductivity of the brain is decreased ; the conductivity of the liver is increased. (Fig. 30. See also Fig. 4.) In like manner, the temperature changes in the brain and the liver tend in opposite directions. (Fig. 31.)

This evidence shows the interdependence of the brain and the liver, and suggests that while the brain cells are purely oxidizing mechanisms, the liver, which is the only organ in the body supplied with venous blood, is in effect an earthy solution, certainly negative, and therefore a most suitable medium for "grounding" electric currents. In our conception of man and animals as bipolar mechanisms we assume that the brain is a passive mechanism, and that, like man-made machines, it can act only in response to some form of stimulation, which, in the animal mechanism, may be either internal or external stimulation such as light, or sound, or taste, or chemical or electrolytic change, or the suggestion of any of these by sounds or symbols. These stimuli are constantly applied. АП the activities of daily life demand that the brain respond constantly to them, while in periods of stress, an increased response is demanded.

It follows, therefore, that there must be one or more activating organs, the action of which can be applied as needed to the regulation of the response of the brain to stimulation. Variation in the activity of the brain itself implies variation in oxidation. Variation in the speed of the work done by the electricity fabricated in the brain implies variation in the passage of the electricity from the brain to the effector organs and tissues. Oxidation is markedly controlled by adrenalin. The electric conductivity of living tissues is increased by iodin. The adrenal glands produce adrenalin; the thyroid gland hoards and metabolizes iodin into an iodin-bearing hormone. 1% would seem, therefore, that to these two organs, the adrenals and the thyroid gland, may be assigned the réle of activators.