A Bipolar Theory of Living Processes

While the above description applies to all living cells, nevertheless cells may vary from each other sufficiently to con- A B c D Fie. 13.—Schematie drawing illustrating the progressive destruction of a typical cell. А. First effect of stimulation, hyperchromatism; B. Normal; C. Fatigue. Note the lessening of nuclear-plasma differentiation; D. Complete exhaustion. Note disappearance of nucleus-plasmar differentiation. stitute distinet groups, or the cells of any one group may vary from each other. In the latter case this variance is evidenced by variations in functroning power, in the former by variations in function. Whatever the differentiation of functioning power or of function, however, the fundamental characteristics of each cell are universal.

Histologic studies have shown that in non-living cells the nucleus and the cytoplasm have lost to a given degree the power to take differential stains, that is, there is no longer a difference in reaction between the nucleus and the cytoplasm (Fig. 13) ; and that coincident with the loss of differential stainability, there is an increased permeability of the membranes, with consequent dissolution and disappearance of the cell content. In addition to the characteristics already cited, the follow-

ing phenomena, most of which have been pointed out by Mathews, are of extreme significance in the consideration of the cells as bipolar units: At the onset of acidosis, except in the case of the braincells, autolytie enzymes appear in the cell, both proteolytic and carbohydrate- and carboxyl-splitting enzymes. That this has a bipolar significance is indicated by the fact that by means of the carbohydrate-splitting enzymes the cells receive the lipoid substances which are essential to the maintenance of the integrity of the lipoid cell-membranes, and, as we believe, to the oxidation whereby the electric potential of the cell is established and maintained.

By means of the carbohydrate-splitting enzymes also anaérobic oxygen is obtained by the cells of all the organs and tissues of the body, except the brain-cells, which depend for their oxidation upon the aérobic oxygen brought by the blood. As has been stated, it would appear that oxidation and the consequent acidity are parts of the most fundamental processes of the cell, and that variations in the relation between the H-ions and the OH-ions aré of fundamental importance to the function of the cell. If we are correct in the assumption that the primary function of the cell is to fabricate electric energy, then we may conclude that the acids produced by oxidation contribute to the production of electric energy, just as the acids and bases of a man-made battery are essential.

The mechanism within the brain-cell for the utilization of oxygen has been described by Mott as follows: * “The Nissl granules of basophile substance do not exist in the living cell. Nevertheless, the amount of this basophile staining substance in the form of Nissl granules may be regarded as evidence of the amount of energy substance (neuropotential) which the cells possessed during life. In the healthy cell it is continually undergoing disintegration and automatic reintegration... . If the living cell be examined by direct illumination, no Nissl bodies are seen in the cytoplasm, only fine dark granules like an emulsion. If living cells are examined microscopically with dark-ground illumination, they are seen to be filled with small granules or globules, each of which after escaping from the cell remains discrete. They are refractile and appear white and luminous; this

is due to a delicate covering film of a lipoid substance which encloses a colloidal fluid, probably consisting of a solution of salts and cell globulins. When the cell dies this colloidal fluid is coagulated and the precipitated proteid substance is massed together into little blocks—the Nissl granules; the intervening denser colloidal substance is continuous with the colloidal substance of the axon and dendron. Тһе film that covers each granule is stainable by vital methylene blue, and a living nerve cell stained by vital blue presents the appearance of an emulsion of minute faintly blue globules. If the living cell thus stained be kept in an atmosphere of nitrogen in a warm chamber the stored oxygen is used up and a leuco-base is formed, causing the globules to lose their color, and the cells appearing of a greenish tint. On admission of oxygen the cell again becomes blue. It thus appears possible that these granules represent a large oxygen surface, like spongy platinum, within the cell. When the cells die, the lipoidal film of the globulin-containing fluid is destroyed, coagulation occurs, and the Nissl granules are formed.

"The delicate granules filling the nerve-cells have been termed 'neuro-bions, as if they were independent living units, but this is theory." (Fig. 14.) The above statements suggest the theory that the electric potential of the cells is produced by the oxidation of the lipoid films surrounding the globules described by Mott. According to this conception, the constant supply of fats necessary to maintain these films would be supplied by the oxidation of the carbohydrates constantly brought to the cell by the blood, this oxidation being facilitated—catalyzed—by ап enzyme. The oxidation of the lipoid films of the globules would in turn be facilitated by adrenalin, which is constantly supplied. As the result of the oxidation of the lipoid films acids would be produced, with a resultant increase in the hydrogen ion concentration, and an increased potential at the cell membrane. The oxidation of the lipoids would also produce a reformation of carbohydrates, an essential provision for the assurance of an uninterrupted supply of carbohydrates in the cell, since the brain has no provision for the storage of carbohydrates. Such a reverse reaction is in accord with the findings of bio-chemists; it is known to occur in plants. Such a continuous reversal of phases in the carbohydrate-

әшов ло} рәлләѕдо eq иво 5[[әә Surə ц} AVM SI} ир цо SSeS е Чим loqureqo шлем é ит роовја st әЧоәволәтш ew, АТ 943 UL [138 ӘПІЦА uorjeurum]rr рипола I[99 плоц лотләзи ue јо SurA€I([ 061 'ASopors&qq [e1eueo) po so[drouraq seporjred jo soyesoisse ләблеү Jo оопвлвод у SOU 10 рту [eurdsoiqeieo шлем ur 905514 oq] Jo mo рэзвэ әле в[[әә 0U], -Tep Aq пәәв se вео uor[gu€S [eurds хотлојвод om} рив sessoooid ЧАМ ( :SSI[Áeg шолу) ‘зиэшолош UvIUMOJQ SUTMOYS [1198 seuo 1o[[eurs Aq pəpuno mns

‘SINOY 34519 лор eprpor umrpos чим ројволу uooq рец чом “ЦӘ? OA, 1e81e| о) эпр “әле i1ejqSriq oY], 'потелловдо Iopun sesuvyo Snooue?j -uods рәмоцв Аэчт “Sop [jews шоду s[[oÓó эмл (р) 'soAvo[ ouoxe 943 919qA пәәв OLB вәріпел2 juvi[[LIQ ‘обте ‘Вор пло4-мәп јо потдол ледшиј ur UOI[SUES шолу (ә) -sne[onu рпполе вәүәт}ле@й јо попоојод 'pegru eur A[USIH әлорр ‘бор илод-меш шолу [[o9 лерише (q) 'peorpou sem отоци е SB Пао 213 JO ҙиәшәлош proqo ure ON °үтлду-олпәи JO 10u ‘зэтро [SSIN jo потвотрит ON Айшә Á[reou savodde sno[onN ` `}пәшәлош UvIUMOIG Surmoys 'ure[do3Ko ur se[orj1ed [epro][oo ош "Ро sdvp әәліҙ Sop шол} 'sp[o9 [emoy (в) -wr[gueS 3001 [евлор ay} шоду s[[00 әлтәп SurarT "Vi

lipoid relation within the cells, together with the constant oxidation of the lipoid films of the globules would meet the hydrogen ion—electric potential requirements of the cell. The intricate network formed by the dendrites of the nerve cells makes possible the linking of the cells in various combinations; and it may well be that in different parts of the nervous system and in different organs of the body the type of communication between the cells is adapted to the nature of the specific response of that organ to stimulation. (Fig. 15.)

Whether the brain-cells are considered to be primarily condeusers of the Leyden jar type or two-fluid cells, the utmost capacity value would be secured if the cells were joined in parallel, whereas the greatest electro-motive force would be Тноз far we have considered cells аз the fundamental units of the multicellular organism, the multicellular organism being constructed on the pattern of the single cell. It would appear, however, that in turn the bipolar pattern on which the cells are constructed must have been derived from the pattern of dynamic units in the contents of the cell. According to the bipolar theory, as we' have stated, the essential characteristics of life as manifested in the cells, that is, assimilation, irritability, growth, reproduction, depend upon the presence of an electric potential which is created by oxidation. The creation of electric potential in turn requires a dielectric condenser. In the bipolar unit, the cell, we have conceived that the electric potential is produced by oxidation whereby charges are built up which are accumulated on the lipoid films—condensers— which bound the cells, the nuclei, the spherules.

If we are correct in this assumption, that the life of the component cells of the organism depends upon the creation and maintenance of an electric potential and that the various functions of life are due to variations in that potential, then within the contents of the cell—the protoplasm itself—there must also exist a mechanism for the creation of an electrie potential. And if that potential is to become effective, then there must exist within the protoplasm some method of communication among the dynamic units of varying potential, as otherwise the protoplasia would be as static as the atom. Іп other words, if the bipolar hypothesis is to hold, we must seek to discover the essential link between the lifeless colloids on the one hand and the complex organized cell on the other; and inherent in that link must be the potentialities of the single cells of the multicellular systems. Just as the physicist has found it necessary

to support his theories of the physical characteristics of visible and tangible masses by tracing those characteristics back successively to the molecule, the atom and the electron, until now he is even attempting to analyze the electron into component parts, so any theory of life must trace the essential characteristics of life back to the most primitive form of life. Thus any theory as to the nature of protoplasm must show how oxidation can be maintained, how the functions of assimilation, of irritability, of reproduction are performed; must prevision the mechanism of memory; must show the mechanism of its own creation by means of the energy of its environment.

Let us first attempt to trace a “line of ascent” of protoplasm in terms of progressive mechanisms for the availability of energy. The atom contains large stores of energy but it is static and therefore is not available excepting under certain extraordinary conditions. In molecules the energy of the comparatively loosely held atoms is more labile and therefore is more avallable. In solutions the energy of the electrolytes is freely available. The interfaces of colloids provide a mechanism for the creation of an electric potential. In protoplasm, we may suppose that the interfaces between the micelle of the colloids and the solutions in which they are suspended are more definitely constructed or fixed as monomolecular films, thus extending still further the possibility of the creation of electric potential and the availability of energy.

Every molecular or atomic disturbance in their environment must of necessity alter the potential of these differentiated micelle or spherules, thus establishing the essential characteristic. of irritability. We may consider these minute protoplasmic spherules or dynamic units to be the most primitive energy transforming units. In these infinitesimal units of energy transformation we postulate there must exist the elements which everywhere are found in the living, that is, physical structures that conduct electricity—electrolytes, and physi- са] structures that interfere with conduction—lipoids. As long as the conditions which accumulated the original charge on the lipoid film of one of these minute masses of colloid material remain unchanged the electro-static arrangement of the ions of the lipoids would remain unchanged; and when by some for-

tuitous circumstance the environmental conditions are changed then a new electrostatic condition would be established. With the return of the original conditions we may conceive that the original electrostatic condition would return. This would be, then, the earliest and minutest suggestion of memory. If we conceive that the lipoid films were originally formed by the electric potential created on the colloidal interfaces, this electric potential in turn promoting oxidation whereby again in turn electric potential is maintained or increased, so the infinitesimal energy transforming unit, the minute protoplasmic spherule, would in turn assemble or create new units in its own image. In accordance with this conception, this diminutive energy system, this dynamic unit of protoplasm has a bipolar structure; it has memory; it possesses the power of reproduction; it continuously creates energy; but it is in a state of dynamic equilibrium, for each of these spherules in this primitive protoplasmic mass is balanced by other spherules; it is not bipolar as a whole. It constantly creates energy but cannot utilize it effectively. As one reader of this manuscript has stated, “protoplasm is the boiler that creates the steam to be used by the engine of the cell.”

Protoplasm then consists of an infinite number of infinitesimal energy transforming systems which may be called micromicro cells and are the primitive forerunners of the multicellular organism. If this be the true nature of protoplasm, then as our methods improve, we shall be able to demonstrate the electric capacity of the protoplasmic contents of the cell just as we have demonstrated the electric capacity of the Прота membranes of the cell. These bipolar systems of energy transformation, whether large or small, have certain common characteristics, a common method for the establishment of electric potential, a common power of oxidation, a common mechanism for constructing the building material of which they are made. By the orientation of ions as conductors with hydro-earbons as non-conductors, every conceivable variation in the degree and form of energy production is possible. Orientated molecules arranged in dynamic and in static systems constitute memory and energy, that is, they constitute respectively the machine and the driving force.

Certain investigators have claimed that minute fibers are everywhere present in protoplasmie masses. These infinitely minute fibers may well be chains of carbon molecules, as suggested by Mathews, which may be associated with electrolytic ions such as potassium to form a dynamic system. If they exist, they offer a possibility for the establishment within the protoplasm itself of infinite action patterns. The labile property of protoplasm would thus be infinitely increased and ас- cording to the forces acting upon this or upon that protoplasm, a different action pattern or system of action patterns would be established, thus making possible the infinite variety of functions which are manifested in the cells where these patterns are made effective. That is, in the primitive protoplasm the action pattern would exist but would be static; in the cell it would become dynamic. Only by presupposing such a possible differentiation of functional capacity within the protoplasm itself сап the different functions of the cells of the multicellular organism be explained. Only by assuming the establishment within the primitive protoplasm of chains or systems of interrelated energy-transforming units, which register specific variations in the electric forces which produced it and which surround it, can the variations in specific response in the multicellular organism be established, or the variations in specific response be registered in the sex cells to be carried forward into new individuals, and produce “inherited characteristics.”

On this basis, then, the energy units of protoplasm are miniature animals and plants; the multicellular animals and plants are enlarged complex groups of protoplasmic units. *[n this hypothesis we approach, even though only in certain respects, the most recent theories of some botanists and physiologists who . . . regard the multicellular organism not as a mere assembly or colony of cells, but rather as a simple voluminous protoplasmie body in which the nuclei are inserted at different intervals as centers or foci of energy (synergids of Sachs), and in which the membranes and other intermediate structures have produced only incomplete divisions and serve merely as supports of the organism. For example, according to Sedgewick the body of the adult animal would be only an immense syncytium whose nuclei or centers of force are dispersed throughout a single protoplasmic net work binding together the whole organism.” 1

In accordance with this conception a cell consists of a great number of ultramieroscopie cells, and again within each of the basic dynamic units, which as we believe constitute the energy transforming mechanism of protoplasm, there are probably micro-micro units, still constituted on the bipolar pattern; just as smaller than the unicellular organisms, but constructed on the same pattern, are ihe bacteria; and smaller than the bacteria are the bacteriophages of d’Herelle and the organisms "within the so-called filtrable viruses which in the case of cancer have actually been photographed by Geye and Barnard.

It is probable that the structure of cells as revealed by the microscope represents but little of the dynamic system as it operates in the living; but the coalescences of the parts of these dynamic systems, as revealed by staining, indicate that the inner structure of the cells must be symmetrical. Almost without exception all substances which have been investigated by the Debye-Scherrer method. (X-rays) have shown a crystalline structure or at least a pattern arrangement similar to the pattern arrangement of crystals. This has been seen even in the micelle of colloids. In accordance with these findings, we may conceive that the ultimate structure of protoplasm is probably crystalline in character, that is,the dynamic units form systems of force as in crystals. The forces that produce protoplasm first produce films of water and hydrocarbons which provide the essential interfaces, where are produced the electric potentials which hold apart the ions which otherwise would coalesce into the form of crystals. Protoplasm then might be conceived to be a potential crystal, and the cell itself may be regarded as a large model of the infinitely small protoplasmic elastic crystal. The growth of a non-living erystal is along definite lines of force analogous to the lines of force along which protoplasmic growth is propagated. The components of the non-living crystal, however, are water tight, inelastic, there are no semi-permeable interfaces where electric charges сай be built up. In the non-living erystal, therefore, the lines of force are static, and the crystal grows by accretion but cannot reproduce itself; in the living crystal the lines of force are dynamic, and the crystal grows by reproduction.

In support of this hypothesis as to the nature of protoplasm, the following possible interpretations and applications of the theory may be cited :— 1. It suggests a mechanism for the assimilation of energy (food). | 9. It suggests a rôle for the potassium and other electrolytes which are universally present in protoplasm; in particular it assigns to potassium a primary rôle because of its peculiar property of being able to hold in its field other ions at a distance, though itself in chemical combination.

4. The assumed energy transforming units in protoplasm would provide a potential for the formation of lipoid films and for the construction of lines of force by a process of displacement of the potassium ions from the lipoid films, the potassium ions in turn carrying with them and arranging the lipoid molecules and other atoms in definite systems, thus forming lines of force for energy conduction. 5. The action of anesthetics on protoplasm is the same as the action of anesthetics on the higher structure of the entire animal, because the form and structure of each is identical. Anesthetics do not interfere similarly with energy systems below the level of life.

6. This conception of protoplasm shows why colloids and cells with no energy transforming power, such as the red blood cells and blood plasma, cannot reproduce themselves. They have no inner potential—hence no assimilative power. Т. Such a bipolar conception of protoplasm provides a normal step-up from colloids as it introduces no new form of energy transforming units. Protoplasm falls normally into place as the building material of the cell, just as cells are the building material of organs, and organs are building units of the whole organism. Throughout the line there is uniformity of form and an increasing looseness of bonds, giving increasing freedom of individual action, t.e., adaptation—a progressively elastic bipolarism. Whereas, on the other hand, below protoplasm there is the stratum of colloids, with a more static equilibrium, with closer bonds; below the colloid, the stratum of the solutions which are still more static, still more closely

bound; below the solution, successively the compound, the . molecule, the atom—the last a fixed, unchanging unit at the other end of the bipolar scale. Such a conception of protoplasm as made up of uniform energy transforming or dynamic units, each having the power of reproduction, each exquisitely labile yet each remaining electrostatic until disturbed by the application of external energy, gives specific properties to protoplasm. It unifies the action patterns of the infinite number of primary units in protoplasm which are so freely in communication each with the others. That is, the nervous system of protoplasm connects up every energy unit with every other energy unit; and these ultramieroscopie systems are connected up with the larger intracellular structures, and these with the whole cell, and each cell through the intercellular protoplasmie bridges with all the cells constituting organs; and finally through the nervous system every part of the organism 1s connected with all other parts. And so, also, the same force, the radiant energy of the sun, which created from inanimate matter the hydrocarbons, the colloids, the primal protoplasmic mass, in turn organizes and energizes the plant and the animal.

CERTAIN ESTABLISHED Кастав REGARDING Various ORGANS AND Tissus OF THE Bopy IN RELATION то THE Func- From the mass of data regarding the structure, arrangement, chemical constitution and function of the central nervous system, practically all of which would be pertinent to this discussion, the following facts are presented because of their peculiar significance. The infinite network of nerves—wires—in every reactive part of the organism shows that the electric control of the body processes, if such a control exists at all, is an all-inclusive control.

The facts that the nerve end-plates are spread over the surface of the muscle cells and that the neurones apparently connect with the cells by surface contact (Figs. 16 and 17); that, as Cajal! has demonstrated, in certain cells one branch of the neurone is apparently connected with the nucleus, and the other with the cell body (Figs. 18 and 19), thus making possible the linking of the cells in series; and that the intercommunications of the cells themselves and the end organs are not continuous but are broken by synapses—keys, these facts present a complete picture of an electrical mechanism with central batteries and connecting wires, in which the synapses intervene as make-and-break mechanisms. (See Figs.

As evidence which may indicate the nuclear origin of the brain and central nervous system may be cited certain facts regarding the development of the central nervous system. (1) The ectoblast and the endoblast are separated at the first segmentation division. (Van Beneden cited by Keibel.)? (2) The parts developed from the ectoblast are the epidermis and epidermie tissues, such as nails, hair and glands of skin, the nervous system, the external sense organs, and the mucous membrane of the mouth and anus. The skin and the specified mucous membranes are in effect external sense organs.

Fic. 17.—Termination of the fibres of the ascending branch of the cochlear nerve. (From Cajal: Histologie du Systéme Nerveux. Paris, 1911. Мо т.р. 187.) The parts developed from the ectoblast are therefore essential parts of the nervous system. (3) According to Hubrecht 3 both in Elasmobranchs and in mammals the cellular material which is present in those very earliest stages contributes especially—as it does in the trochophora—towards the formation of the anterior part, the head, and following upon this, a proliferation process is inaugurated.

(4) Hubrecht imagines that the nerve ring on the oral disk of the actinian represents the spinal cord. In the primitive streak “we encounter the material which also in the Actinia— (1) proliferates downwards from the ectoderm and produces the stomaderm; (2) coalesces with the entoderm; (3) is in direct continuity with those parts which are preparing to give rise to coelomic pouches, but are not yet continuous with the primitive enteron.” (5) The above facts would appear to indicate that the ectoblast, which produces the central nervous system, may be the principal source of the energy whereby is effected the further subdivision into the tissues derived from the endoblast, and into the mesoblast and its organs and tissues.