A Bipolar Theory of Living Processes

Again let us consider one of the most common sites of cancer origin—the breast. Here is an organ whose structure contains epithelial cells, the capacity of which is low. It follows that when some cireumstanees bring into contact with these low capacity epithelial cells, cells with a relatively high potential, the latter multiply at the expense of the other breast tissue. The capacity of cancer of the breast is from two to ten times higher than the capacity of normal breast tissue. The capacity of the tissue near the cancer mass is somewhat higher than that of normal tissue. Та general, benign tumors have a higher capacity than that of the organ in which they grow, e.g., the capacity of a fibroid is higher than that of the normal uterus.

There is a general analogy to this conception of the law governing incidence of cancer in the various tissues, in the tables of Voit, which show that in starvation the weight of the brain and of the heart muscle does not change, the reason being that these tissues, the metabolism of which is at a higher rate than that of other tissues, consume the nutrition at the expense of the others. For the same reason a fetus thrives up to the point of starvation of the mother.

This conception might explain the higher incidence of cancer in old age when the generally falling metabolism would diminish the already low defense of the tissues of low capacity and lead to an inequality in an already wavering balance between the capacities of neighboring cells. Moreover, the older and the feebler the subject, the slower the growth of cancer and the better the prognosis; and per contra the younger and more vigorous the subject, the shorter the course, the more fatal the cancer. But youth has fewer cancers than old age. Our theory interprets this antithesis as follows: In the general activity of all tissues in youth it would be unusual to find the potential of any one cell raised above that of its equally vigorous neighbors, but once so phenomenal a cell has been produced, its growth energy would be enormous, rapid and fatal. In old age, on the other hand, with its universal decline in activity, although a cell may more readily become endowed with the equivalent of fertilization so that its potential and its capacity may become higher than those of its feeble neighbors, yet it would have a very moderate growth energy. In fact, cancer in the aged and feeble inevitably would appear just above the low level of low vitality, in youth just above the high level of youthful vitality. In youth the cancer must be virile; in age it must be feebler. Thus, in experimental studies cancers are not transplanted to the muscles, nor to the liver, nor to the heart, nor to the brain, but to the more negative tissues; it 1s the subeutaneous quiescent breast tissue that 1s generally selected as the site for the graft.

If one could plant a self-limited bacterium in the nucleus of a cell, its added oxidation might augment the nucleus in a manner analogous to the augmentation of the nucleus of the ovum by the spermatozoón so that in consequence cell division would be foreed. Or if one could draw the nueleus out of one cell and insert it into a sister cell, thus reinforeing its nucleus, the energy potential of the latter cell would be increased, its nutrition intake increased and cell division would follow, 1.е., a cancer would be produced.

The interpretation of another fact is made possible by the bipolar theory, namely, the like action of X-ray and radium on cancer and on fertilization. The effect of radiation is to interfere with the mechanism in the cell for the creation and storage of electric charges, an interference which as effectively prevents growth and function as does the permanent discharge of any battery. An interpretation of still another group of facts is suggested by the bipolar theory, namely, that sarcomata appear early in life and are disseminated, while epithelial growths appear later in life. A possible though admittedly not a clear interpretation of this differentiation would be that cells distributed by the blood lodge in the more vigorous oxidizing organs such as the muscles, glands, etc., while the cells spread by the lymphatics reach the lymph glands, whose metabolism is relatively low. Therefore, the older and the feebler the patient the more probable it is that the cancer cells which are most likely to metastasize will be those that reach the lymphatic glands, whose flame is burning low. Again, when the potential of a cell in the high tension thyroid rises above that of its fellows and in consequence multiplies at their expense in a fetal adenoma one would expect a wide extension of these cells and such is the case.

Certain everyday faets about treatment are also open to a biophysical interpretation. Thus, if a cancer is entirely re moved early, no return is seen; whereas if a cancer is stimulated by injury, by partial operation, by inflammation, by chemical agents, by X-ray, by radium, by heat, by electricity, the resultant struggle and survival kill off the weaker cells, leaving the stronger. When a massive treatment is given, any cells which survive will be the fittest, hence the return growth will be at the pace of the strongest, the fittest cancer cells, not of the less strong cells that did not survive. The combination of diminishing vigor on the one hand and a stepping up on the other, theoretically would bring about the unbalance required for cancer.

Руодетіс Infection.—We have already mentioned certain analogies between cancer and pyogenic infections. Certain further biologic principles governing infection which appear to be the same as those governing cancer may be cited. The resemblance between cancer and infection has been noted by many observers. Руосепіс bacteria may be regarded as free nuclei, like the fragmented nuclei seen in many unicellular organisms. If we regard the law of universal bipolarism as a necessary condition by means of which a difference in potential is created and oxidation controlled with resultant electric

charges and maintenance of potential, we interpret bacteria as free nuclei depending for their common negative pole on the common colloids such аз mud, soil, sea-water, etc., and the colloids in the tissues and fluids of animals. Bacteria then would multiply as free nuclei. According to our conception a cancer cell is a bipolar mechanism within which the nucleus is the positive, the cytoplasm the negative pole; bacteria are positive poles with lymph and tissue juices as a common negative pole. According to this conception the cancer cell and the bacterium are in a common class of high potential invaders. Now the bacterium, like the cancer cell, must depend on its ability to compete with the cells of the organism for nutrition. It is probably a consequence of this fact that bacteria, like cancer, cannot primarily compete with the cells of the organs which have a high metabolism. Bacteria, like cancer, attack best the negative tissues, the subeutaneous tissues, the fascia, the bone, surfaces that have been irritated. Bacteria stain like nuclei; bacteria almost never attack nuclei of cells, almost never muscles, most seldom of all the heart muscle. Bacteria tend to spread by the adynamie lymphatic system rather than by the dynamic blood-stream. However, as in cancer, if bacteria are potent enough, 1.е., have the required potential to multiply in the blood stream those bacteria are more apt to kill and to kill early. Both bacteria and cancer provoke white cell invasion in their advancing line; both bacteria and cancer cells multiply at the expense of their host; both may form tumors; both cause reactions; both interfere with function; both are selective as to the attacked organs, as to invasion.

As to the problems suggested by this diseussion it would seem that in polarization-capacity estimations we may have one more criterion for the diagnosis of cancer, for the microscope reveals the films which hold the charges. Тһе microscopic picture. represents the statie, the eapacity measurement, the dynamie state of the cell. Even if this should not become a method of operating room diagnosis, it may at least supplement the microscope. We may ME find in this new biophysical method not only a means of diagnosis but one of prognosis as well—low capacity relation of ds growth to the adjacent tissues would

udied further it may ie ону ‘of a tumor may at last furnish the key to the ; of radiation required as a lethal dose; or indeed may - mine whether any dose that the TT of the iism could endure would cure, so that futile efforts could Ir our conception that living processes are due to the operation of electrical forces acting in a bipolar mechanism is correct, then mental processes such as ideation and memory cannot be exceptions to what we conceive to be an all-embracing law. The intangible nature of these processes and the fact that we are dealing with infinitesimal forces and infinitesimal particles of matter make a demonstrable explanation impossible. Nevertheless, on the basis of what is demonstrable, both by the gross and mieroscopie structure of the brain, by the demonstrated laws which govern electric forces and by certain experimental evidence, we conceive that mental processes are subject to the bipolar law.

The white matter of the brain and cord like the film around the cell, around the nucleus and around the spherules within the brain cells is а Проза substance and hence, like the lipoid films of the cells, it is dielectric—it has electric capacity, as has been shown experimentally by George H. Crile Like the film around the cells, the white matter contains also certain electrolytes, principal among which are potassium, ealeium, phosphorus and sulphur.

It is well known that the passage of electricity through a substance tends to orientate the moleeules of that substance along the direction of the electrie eurrent. One can easily соп- ceive therefore that the first effect of an eleetrieal impaet upon the lipoid material of the white matter of the brain from the cells-—batteries—in the gray matter would be to orientate the fatty molecules into a chain-like arrangement. Аз this orientation would progress, as progress it must under successive electrical impacts, these chains of fatty molecules would be extended.

Thus, for example, a ray of light impinging upon the retina would set free successively the electrical charges of the surface cells and of the amplifying cells of the retina, these charges being conveyed by the optic nerve to cells in the eray matter of the brain, which in turn would be discharged with the resultant establishment of a chain of ionized lipoid molecules within the white matter. By a second similar impact, that fatty chain would be extended and rendered more stable. This orientation of the molecules in the lipoid substance of the white matter we may imagine to be accomplished by a sort of replacement process.

According to our hypothesis, as this “excitation wave" progresses, ions of potassium are progressively displaced from molecule to molecule along the path of orientated lipoid moleeules so that a progressive chain of potassium remains to constitute the essential conducting characteristics of the nerve paths. This would be in accord, as suggested by Professor Millikan in à personal communication, with certain experiments going on in his laboratory in which sodium atoms are driven through the walls of а sodium glass electric light bulb. By forcing a high voltage current through the vacuum the electronic bone bardment forced the sodium atom out of the first molecule with which it came in contact. This displaced sodium atom collided with and replaced the sodium atom in the next molecule and so on until the last sodium atom lying next to the vacuum in the electric hght bulb was displaced to the free surface on the inside of the bulb.

We may imagine that if instead of the vacuum, the bulb were filled with lipins having a certain resistance, the electronic bombardment might well have carried these sodium atoms along the line of strain and so have made a track of orientated lipoid chains holding within them the sodium ions. Within the white matter of the brain then, we would conceive that the potassium or sodium or chlorin atoms could be pushed through the membrane of a cell of the gray matter upon the receipt of an electric impulse, and so on from cell to cell by the continuance of this replacement process, electrolytic chains associated with the molecules would be established, along the line of which the passage of the electric currents generated by the cells of the

gray matter would be facilitated. These lines of force would extend progressively, forming lines of communication from cell to cell within the brain and from the brain to the muscles and glands. iw While such a facilitated pathway might be produeed by the symmetrical arrangement of any electrolyte along the track of orientated chains of lipoid molecules it would appear that this may be one at least of the specific functions of potassium for the following reasons :— (1) Potassium is the only radio-active element in the body; (2) potassium even in chemical combination has the power of orientating and of maintaining the orientation of other ions, as in a crystal; (3) the potassium and lipoids in the body have a parallel distribution; (4) pursuant to the above considerations, it would appear that potassium is the element in the organism which has the most essential properties for organizing a system.

Zwaardemaker has made the following signifieant observation which if confirmed would relate the diffusibility of the potassium atoms to the radio-active property of potassium ; and since, as we have stated, potassium is the only radio-active element normally present in living tissues, it would explain why we may consider that potassium rather than any other element is the one by means of which the nerve paths are generated. Zwaardemaker makés the statement that

“Where normal potassium, which is everywhere present, is concentrated in fixed combinations, as in the muscle tissues, it will permeate the whole surrounding tissue in all directions with its penetrating rays. In the immediate surrounding tissue only a few of the swift rays but many of the slow rays are absorbed. I feel that this continuous radiation working night and day, however weak it may be, provides a certain amount of energy which among other effects frees a small part of the atoms of potassium from their fixed combinations and releases them as diffusible potassium in solution. 16 is this free potassium which, when the permeability of the membrane is maintained, leaves the muscle cell and goes into the circulating fluid where we have found it in small amounts.” !

In accordance with the generally recognized facts regarding potassium it would follow that each potassium ion projected through the monomolecular lipoid membrane of a brain cell, would have the power of carrying with it and of orientating the ions of sodium, phosphorus and other electrolytes as well as the lipin molecules. In this way the nerve cells themselves could create from themselves a series of projections with a highly еоп- ductive property and it would follow that each of the infinite pathways in the white matter, having been thus constructed by the electric charges of the cells as the result of certain specific impulse® conveyed to the cells, would remain a specific conductor for the same type of electric discharge as that which created it.

The white matter with its organization would then be the creature of the electric battery—the nerve cell. According to this conception, the white matter was not made first and the brain cells organized afterwards, but the brain cells themselves constructed the white matter by means of the creation of specific arrangements of potassium, sodium, phosphorus, the lipins and fatty acids in specifie conducting paths, thus making the white matter a specific dynamic system. It is well known that the severed nerve fiber is recreated by the nerve cells. Thus the nerve cell may be said to secrete the nerve fiber, and in the same way the nerve cells may be said to secrete the white matter of the brain.

This conception is in accord with the observations of certain investigators regarding the distribution of potassium in living matter. Macallum, although he states that “it may also be regarded as certain that potassium does not subserve either the generation or conduction of nerve impulses” does draw the conclusion that “there is thus in living protoplasm a directing force controlling the distribution of potassium salts, a force apparently opposed to, or to express it with a due degree of caution, more refined than the ordinary physical force comprehended by the term osmosis.”

By applying Macallum’s method to the examination of nerve fibres for the presence of potassium, Macdonald found that ‘precipitates of potassium salts can be obtained at any point arbitrarily selected as the site of an injury” and contrary to the conclusions of Macallum, Macdonald believes on the basis of his own researches that potassium salts are “really present at every point in the course of the nerve fiber, and that too in “Let us then suppose that in all these events we have a modified representation of the process of excitation and its consequences upon neighboring segments of the fibre; a reversible change during which electrolytes are set free into a state of simple solution, and are then recovered from this state back into their original condition. Here truly there is the appearance and the withdrawal of a source of energy, a relay placed at every point of the nerve to ensure the continuous propagation of the excited state. Inorganic salts are set free to move; they move ever so little; the next segment of the fibre is charged as a consequence (let us say negatively) ; the colloidal state of the fibre is thus changed from its condition of equilibrium; as a result a setting free of electrolytes at this new point and the propagation of the process; in the meantime the communication of the negative charge to the onward segment has left the original segment positively charged, the state of colloidal equilibrium is thereby reproduced, and the last involved segment is brought to a condition of rest.”

“Accepting all that is taken as known of the minute microscopical structure of nerve, there is no inherent improbability in the supposition that the inorganic salts of the nerve might be there held enchained in a highly concentrated solution free to move parallel, but not at right angles to and away from the fibrillae.” ? | and again in describing the potassium deposits in the granules which appear at the cut ends of the fibers and also in portions of the fibers remote from the site of injury, Macdonald makes the following statement:

“Such granules I have observed forming at the cut ends of the fibres, but also in portions of the fibres remote from positions of injury. Such granules may, even in portions of intact fibres, be observed to increase and again to diminish in size. They may be seen at any one time to be of different sizes and in different number in neighbouring portions of the axis-cylinder. There is, therefore, no temptation to consider them as permanent units of structure, and yet, after the admission of ‘fixatives, these very granules are joined together in lines to form neuro-fibrils. The granules not being permanent units of structure, it is therefore logical to con-

clude that the fibrils thus formed by their agglutination also are not permanent units of structure. The fibrils then may be said to be observed under conditions suggestive of artificial formation. This fact also has to be taken with the complementary fact, that artefacts of just this kind might be expected to appear within the nerve-fibre. “Let us in illustration of this statement consider the possibility mainly dealt with in this paper, that the process of coagulation is attended with a sudden liberation of inorganic molecules, and therefore with a new condition of activity—molecular motion— around every centre of coagulation. It seems not unlikely that, in the extremely minute tubule of the nerve-fibre, this new activity, and the conditions of pressure occasioned by it, might systematise the spatial arrangement of these centres of activity along lines parallel to the long axis of the fibre. This being the case, there seems an ample basis for the opinion, that we should expect a symmetrical arrangement of lines of coagulated material. In fact given a sudden appearance of a uniformly distributed agency determining coagulation, we should expect the formation of ‘neurofibrils’ as a consequence of the energy changes accompanying this process.”

“T have frequently watched the granular conditions I have described pass uninterruptedly through the nodes and have thus become convinced of the uninterrupted continuity of the axiscylinder, and, therefore, of the absence of transverse membranes from these nodal points. This newly-described condition of ‘pseudo-polarisation,’ however, provides a complete explanation of the phenomenon of true longitudinal polarisation, just as it at the same time provides an explanation of the manner in which the electrolytes of the nerve may be set in motion in measurements of electrical conductivity, although usually locked up in its normal state of colloid solution.” ?

Pertinent to our conception that the actual generations of the nerve paths of action may be by the progressive deposition within orientated lipoid chains of potassium ions are the following observations of Macallum: 1. “In the spores of Equisetum arvense the cell which gives rise to the primary root hair is, from the first, very rich in potassium salts which, as the root hair begins to develop, collect at that point where the hair is to arise, and while the growth continues the inner surface of the hair membrane remains in association with the

salts. This appears to obtain also in the formation of the pollen tubes in Lilium, the potassium observed in the active cell of the grain appearing, when the tube develops, to accompany its extension downwards through the tissues of the capitate stigma. As the tube becomes very long the quantity of potassium that may be at any one point within its wall is very minute, or in traces only, but when the tube first begins to grow the amount at the point of growth is sufficient to make a clear demonstration of the fact."

Fia. 53.—Germinating spores of Hquisetwm arvense, (a) earlier, (b) later, stage. “In both the potassium seems to diffuse in advance of the cytoplasm which forms the primary root-hair. (X 250.) (From Macallum: On the distribution of potassium in animal and vegetable cells. J. Physiol, 1905, xxxii, 127.) 2. “In several preparations of Spirogyra which illustrated the process of conjugation there was found, within the tips of the outgrowing processes, and almost immediately adjacent to their terminal walls, a marked potassium reaction, quite distinct from, and much more marked than, that of the adjacent cytoplasm.” 3 (Fig. 53.)

3. Macallum found also that potassium accumulates at the lumen border of cells during secretory activity, that is at the border of the cell through which secretion takes place and that in the epithelium of the small intestine where the current goes in the opposite direction to that in the gland cells, the accumulation of potassium occurs at the portion of the cell next the basement membrane.‘ Macdonald found that not only are potassium salts present at the site of an injury to a nerve but that they are “also discoverable in regions of the fibre distant from points of injury, provided that time is given for their appearance.”