A Bipolar Theory of Living Processes

“The work of Ivanow has shown that lipase has a reversible action, and the fact whether it hydrolyses or synthesizes fats is merely a question of conditions, mainly the presence or absence of water. The glycerol extract of a fat-containing seed, which extract contains the lipase, mixed with oleic acid will synthesize a fat: the addition of water will result in the hydrolysis of this fat into glycerol and fatty асла Бо “With regard to the origin of glycerol, the chemical relationship between this substance and glucose is so close as to suggest at once the possible inter-relation of the two; further, glycerol may have an origin in respiratory processes as is shown by the production of this substance during the alcoholic fermentation of sugar.”

Many excerpts from the monumental work of Cajal might be cited. Indeed his description and drawings of the histology of the central nervous system strongly corroborate the theory that electricity is fabricated in and transmitted by the central nervous system. In many instances, Cajal suggests an electrical interpretation of nervous function.” Thus in discussing the spinous processes on the protoplasmic appendages of the brain cells the author states that when stained by Ehrlich’s method the terminal spherule stains an intense blue like the protoplasm of the cell. In considering the function of these appendages, he says:

“What can be the rôle of these collateral processes? At present, we do not know. They might be considered as absorbent hairs, like the radicles of plants, as suckers, securing in the peri-nervous lymph the organic juices for the nourishment of the spongioplasm of the dendritic arborization. Or are they, as Berkley maintains, charging apparatus, the collectors of the nerve current, like the points of a static electric machine or the brushes of a dynamo.”

Cajal agrees with this latter opinion and calls attention to the enormous increase of surface thus established. His theory regarding interneuron communication to which we have referred in Chapter V is stated as follows: “The protoplasmic prolongations, the cylinder-axis extension and the cellular body are free, and nevertheless throughout the nervous system thus divided and infinitely interrupted, the currents circulate unceasingly. How can they pass? Only one answer is possible, by contact, like electric currents through a wire. But the nerve extensions, the protoplasmic appendages, the cellular body—all this in the gray matter for example, is mingled, entangled, in more or less intimate contact. In this labyrinth do the effector and affector currents pass indifferently, without order, from one cell body to

another cell-body, from one dendrite to another dendrite, from one nerve extension to another nerve extension, or from one of these three parts of one cell to any other of the three parts of another cell? Or is there, on the contrary, a well-established law which fixes the parts of the cell which should enter into contact with each other? “All the mechanism of the nervous system proves that this last supposition is the true one and that such a law exists. Our investigations have made it possible for us to identify this law. It is this: The articulation or useful and efficacious contact between two neurons is only effected between the collateral cylinder-axis татиф- cations or terminals of one neuron and the protoplasmic extension or body of another neuron; or otherwise expressed, the nerve wave passes by contact from the axillary ramifications of one cell to the body and dendrites of another or other cells. At the beginning of our researches we believed in the existence of contacts between the dendrite extensions springing from one or more cellular elements. That which made possible the existence of these dynamic communications was their limitation to a colony of neurons the functional activity of which thus combined offered something comparable to that of a battery of piles or of Leyden jars. But these protoplasmic juxtapositions have not withstood later and more meticulous investigations. They are in any case extremely rare and lack, we are persuaded, any important physiological signification. The interposition of multitudes of nerve fibres or of expansions of epithelial corpuscles carefully prevents contacts between appendages of the same kind. Similarly there are possible contacts between extensions of different kinds but emanating from different cells which for especial reasons have not entered into connection. The neuroglia prevents this as best it can. The measures taken by nature in these two instances explain a fact demonstrated recently by Weigert thanks to a special method.

We refer to the relative abundance of neuroglia fibrille in the region of the gray matter, molecular layers of the cerebrum and cerebellum, the superior olive, molecular layers of the retina, etc., where in large numbers are found demyelinized protoplasmie extensions and axis-cylinder arborizations. On the other hand at the level of the surface of charge, at the points of transmission of the current, that is to say, in the regions where the cell bodies and the dendrites aequire intimate relations with the ultimate ramifications of the axone—in all these regions the neuroglia is completely lacking. Thus by this ingenious artifice of the neuroglia, properly interpreted, we have again, if it is necessary, a confirmation of the law formulated above.

“Tt is then well-established, at present, that between the different parts of two or more neurons only one articulation is possible and valid—the articulation nervous-protoplasmic. «But under what aspects does this articulation present itself? In view of the extreme diversity of the contours and directions of the cellular parts, this articulation cannot be uniform. Yet in accordance with the law which governs nerve connections we can distinguish two grand divisions: the first in which the articulation is made between the arborizations of the cylinder axis and the body of the cells, called axo-somatique; the other in which the contact is between the cylinder axis arborization and the dendrite prolongations —axo-dendritique.

If we interpret this axo-somatique connection between the cells as analogous to the wiring of a battery in series, it becomes necessary to discover evidence that one or the other of the cell appendages is connected, at least at the moment of discharge, with the membrane of the nucleus, the other with the membrane of the cell body. Magini’s experiment already cited (р. 66) becomes of very great significance in this connection. It is described by Cajal as follows:

“Magini carried his researches to studies of the changes in the position of the nucleolus according to the physiologic state of the neurons. As the object of his study he chose the cerebro-electric lobe of the torpedo. He believes that he observed the following phenomena; that the nucleolus occupies in periods of rest a central or slightly eccentric position in the nucleus; in periods of activity, it quits its position, moves rapidly in the direction of the axone, and applies itself so vigorously against the membrane of the nucleus that it produces a protuberance. According to Magini, the cylinder axis springs from the cytoplasm at a point near the protuberance produced in the nuclear membrane by the nucleolus. The rapid displacement of the nucleolus would result in striking against the cylinder axis and developing in it a nervous wave which would discharge the electric organ.

“Tf this interesting phenomenon should be confirmed, if moreover its existence should be proved in the cerebrospinal axis of all the vertebrates, one could affirm that the discovery of Magini truly constitutes a great progress in our knowledge of the physiological mechanics of the cell.” Cajal states that Vas, Lambert and Mann all observed this eccentric position of the nucleus but that Valenza denied all these findings, and also those of Hodge, Mann and Lugaro regarding the changes in the nucleus in activity and fatigue.

The nuclear origin of the neuromotor apparatus of certain unicellular organisms as described by Kofoid and his associates appears to supply a link between the undifferentiated nucleus of the simplest protozoa and the highly differentiated nervous system of the multicellular organism and thus supplies further evidence in favor of the conception that the central nervous system of man is in truth the direct descendant of the nucleus of the original unicellular organism. 8

“The term neuromotor apparatus is used by us here and elsewhere to designate those organs of the protozoan body which carry on its coordinated motor and locomotor activities. They form a structurally continuous unit as shown in T'richomonas and Giardia connected by a rhizoplast with the nucleus as in T'richomonas, or with the central karyosome as in Giardia. On maceration of the cytoplasm in T'richomonas and Trichomitus this apparatus remains structurally intact for some time. It includes in Trichomonas the following structures: The anterior flagella, marginal filament of the undulating membrane, posterior flagellum, axostyle, parabasal body, blepharoplast, and rhizoplast. In Giardia there are added the anterolateral, posterolateral, and free ventral flagella and an axostyle terminating in the posterior flagella, the intracytoplasmie parts of the first two pairs of flagella just named, a rhizoplast going from the parabasal body presumably to the blepharoplast, and a cross commissure joining the right and left blepharoplasts. The integration of these parts in one coherent structural system and its intimate relation to the mobile cystostome are evident on an inspection of the figure. (See Fig. 25.) The repeated instances of the attachment of the blepharoplast to the nuclear membrane by a rhizoplast in the various flagellates which we have diseussed and the direct connection of the neuromotor apparatus with the karyosome of the nucleus in Giardia give presumptive evidence of a fundamental structural and functional relation between the nucleus and this complex of extranuclear organelles. The fact also that the blepharoplast and its outgrowths and connections are basophile and stain more or less deeply with iron haemotoxylin suggests affinities if not similarities, of a chemical nature.

* Added ground for regarding the extranuclear neuromotor apparatus as related to the nucleus and as evolved and derived from it is to be found in the results of Dr. О. У. Wilson's (1916) study of the life history of a soil amoeba, Naegleria gruberi. This amoeba enflagellates on the impact of various environmental factors such as access of oxygen, or of fresh culture medium, and exflagellates with equal facility. In the amoeboid phase there is no extranuclear blepharoplast, rhizoplast, or flagella, and no chromatic extranuclear organelles, though chromidial formations are abundant and varied at times in the life history. As enflagellation approaches a chromatic process grows out from the central karyosome of the nucleus forming an intranuclear rhizoplast extending to the nuclear membrane. A granule appears at its tip and as this process continues its growth peripherally through the cytoplasm, retains its terminal position until

it reaches the surface where it forms the blepharoplast connected on the one hand with the nucleus and on the other giving rise to the two flagella. In exflagellation the flagella shorten and fusing with the blepharoplast and rhizoplast appear to retreat again into the nucleus. In this connection we note the fact that no instances of mitosis were discovered in the flagellate phase, though they are to be expected, and in consequence we do not know the behavior of these organelles in that process. The centrosome or centriole is contained within the karyosome and appears here as in other amoebas at mitosis, at the ends of an axial chromatic thread in the center of the nuclear spindle. Thus in this amoeba the centrosome within the central karyosome of the nucleus originates the extranuclear neuromotor apparatus of the flagellate stage." (Kofoid.)*

“The first point favoring the idea that the neuromotor apparatus is of a truly nervous character comes from animals stained with Mallory’s connective-tissue stain. In animals treated with this combination of dyes, different organs take different colors. It is characteristic in metazoan tissues treated by these colors for different tissues to stain differently, as for example nerve fibers have an affinity for acid fuchsin and are thus dyed red while nuclei stain orange red, and cytoplasm in general becomes light pink. Such a differential stain may be used to give a clue to the function of organelles in some of the more complex of the so-called unicellular organisms. At least we may assume that structures having a similar staining reaction have the same or related chemical composition and in these so-called simple organisms probably the same general function.

“This is one of the reasons for basing our conclusion that the structures described as comprising a neuromotor apparatus are probably nervous in their function. All of the fibers, granules and motorium stain bright red when treated with Mallory’s stain, while the other structures take other colors. The only other organ which constantly stains with acid fuchsin is the micronucleus, but in this the color is not the same as in the fibers but has more of the orange G mixed with the red.” (Yocum.)’

The studies by Renauld-Capart cited in Chapter VI are of especial note in their relation to the essential interrelationship of the brain and the liver. By what he terms the “method of partial circulation,” the general circulation was as far as possible confined to the brain, the heart being conserved as a motor and the lungs as an apparatus for oxygenation. After a longer or shorter time function of the nervous centers ceased, and then by admitting the blood from different abdominal organs it was possible to discover which of these had any influence upon cerebral activity.

“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 function; following this, that the liver alone, of all the abdominal organs, has that property.

“This being true, a new problem arose. With what action has one | to deal under these conditions? Is it an action of ‘desintoxication’ or an internal secretion of nutritive material indispensable to the cerebral function? We have demonstrated that the action is not one of ‘desintoxication’ but of an internal secretion of the liver and that this consisted notably in the elaboration of a thermolabile compound without which cerebral activity is impossible. We suppose that this compound belongs in the category of ferments or catalyzers without being able to make any more precise statement regarding it.

“We then extended our research to determine what was the action of this function of internal secretion of the liver on the physiology of the neuron and particularly on its irritability. We have established that the arrest of the hepatic function produced in the neurons a state of chromatolysis which became more and more marked progressively with the loss of cerebral activity; and on the other hand, that its reéstablishment produced a demonstrable repair of the chromaphil substance corresponding to the re-appearance of the functions of the brain centers. We have also had the opportunity to observe the physiologic réle of this substance, which we consider to be the main support of functional nervous energy. We have found that the formation and the restoration of the chromaphil substance depends on the presence in the blood of the thermolabile principle secreted by the liver. Finally, we have secured proof that cerebral work, including the highest form of conscious ‘sensibility’ is absolutely dependent upon this new internal secretion of the liver.” Е

Granting the correctness of Renauld-Capart’s results another interpretation is possible. The author, by cutting off the circulation and oxidation of the liver, interfered with its fundamental activity sufficiently for its function as a negative pole to be suspended, and on the restoration of its circulation, the liver resumed its function as the negative pole of the bipolar organism. The tendency of the liver cells to accumulate mineral substances —especially metals, is emphasized by Roger: "

“There is no ground for believing that the liver arrests indiscriminately every substance brought to it by tbe portal vein. It exercises an elective action which is very clearly demonstrated by a study of the mineral salts. “Many of the mineral poisons are accumulated in the liver. Some are eliminated by the bile. Others freely pass through the gland. Thus the liver has no action on chlorid of potassium or on the chlorid and the lactate of sodium. On the contrary it takes up the iodids and the bromids and eliminates part of them by the bile. By the same route it throws off Roue of potassium and sodium salicylate.

“The action of the liver is SOMIT marked on the heavy metals. Lactate of iron is only one-third as toxic when it is injected through a branch of the portal vein as when it is introduced by a peripheral vein. Under the same conditions the albuminate of copper loses half of its toxicity. “On the other hand, the liver stores and holds for long periods the salts of mercury, of lead, of arsenic. It eliminates a small quantity of these salts by the bile. The salts of manganese, of antimony, of silver, of zinc also are eliminated by this secretion.

*[t is now generally aecepted that the accumulation of the heavy metals is due to their combinations with the nucleus. According to Siccardi and Roncato in dogs subjected to lead poisoning, the lead is reduced and remains in its metallie state in the cells of Kupffer. Moreover these anatomical elements seem to have the property of retaining many substances foreign to the organism. Thus Kupffer has shown that after the injection of India ink in the veins of a rabbit, these cells become engorged with black grains. Colin and Nathan made analogous observations with colloidal silver. Duhamel has made comparative studies of several metals or metallic colloids. In less than 15 minutes after the injection of 0.0125 kg. of colloidal platinum in the veins of a rabbit, the cells of Kupffer are filled with metal. With colloids of copper, of mercury, of selenium, of iron, of sulphur, the results are negative or at least a histochemical examination does not make it possible to find the introduced substances. But chemical analysis gives different results. Here, for example, are the tables given by Duhamel; the studies were made 15 minutes after the injection.

“Thus about two-thirds of the quantities introduced are very rapidly accumulated in the hepatic parenchyma.” Misk ?? has reported that tin is found in normal human organs in the following proportions: The amounts per kilogram of the fresh organs were as follows: The fact that in each of two fetuses examined by Misk only a trace of tin was found in the spleen makes it appear that the percentages given above for liver and spleen pertain primarily to the liver.

Bodansky 13 and Thudichum report studies which indicate that copper is a normal constituent of the brain. Bodansky’s experiments indicate that this is true also of zinc. Regarding the presence of the latter metal, however, there appears to be a difference of opinion among various investigators. It is interesting to note, however, that in fetal brains the proportion of copper was greater than in any of the adult brains studied and that in general there is a more rapid accumulation of ліпе and copper in the organs during intra-uterine life, as is also reported by Maquenne and Demoussy (noted by Bodansky) who “found in their studies on the injection of copper in the tissues of green pianis that copper is most abundant in young actively growing tissues.”

We have already referred to the extensive studies (Chapter V) in muscular function made by Hill and Hartree.** Of particular interest from the bipolar point of view is their analogy between the energy exchanges in muscle and in an electromagnet although we note that they state that “this is not a theory of contraction, but merely a physical analogy to what has already been proved in regard to the muscle and its energy relations. The analogy is a very close one, and a close analogy may be valuable in suggesting lines on which further progress can be made, as well as in showing that a certain type of mechanism is possible.

“Consider an electromagnet attracting a piece of soft iron. То make the magnet exert this attraction a current has to be passed and energy has to be expended in magnetizing the electromagnet; to maintain the attraction it is necessary to maintain the current and the expenditure of energy. On breaking the current in the electromagnet the attraction disappears, while the magnetic energy of the electromagnet and of the magnetic field vanishes as such and reappears as heat caused by induced currents. Suppose further that the current was obtained from an accumulator: in order to recharge this accumulator it is necessary to employ some kind of engine to turn a dynamo and in this recharging process heat is liberated in the engine and ‘free’ electric energy is stored in the accumulator.

“Store of free energy capable of being liberated without oxidative changes. The accumulator can have its energy released merely by pressing a key and making an electric contact, just as the muscle сап have its energy released by giving it a shock. The chemical changes liberating the energy of the accumulator do not involve any oxidative breakdowns, just as the initial processes of contraction in the muscle do not. The energy of the accumulator may be liberated largely as mechanical potential energy or work, or on the other hand if the accumulator be short-circuited it may be wasted as heat: the muscle’s internal energy similarly may appear as potential energy or work or it may as a result of various conditions, e.g., in rigor or as а result of treatment with ethyl-aleohol (Weizsäcker) appear entirely as heat.

“Trigger action for release of energy. The amount of energy required to make an electric contact and so to start the discharge of the accumulator is very small, as is the amount of energy required to stimulate a muscle. “Development and maintenance of mechanical response. Directly the key is pressed down the current starts in the coil of the electromagnet and the magnetic attraction develops. The current, however, does not immediately rise to its full value, owing to the self-induction of the coil nor does the soft iron of the magnet become magnetized instantaneously under the influence of the magnetic field of the coil: hence the attraction exerted by the magnet on the piece of iron increases gradually up to a certain limit and then remains соп-