Popular Science Monthly/Volume 61/May 1902/The Physiological Effects of Electrically Charged Molecules


By Professor JACQUES LOEB,


FIVE years ago I published a series of papers on the physiological effects of the electric current which impressed upon me the long-known fact that the galvanic current is the most universal and effective stimulus for life phenomena. This fact suggested to me the idea that it should be possible to influence life phenomena just as universally and effectively by the electrically charged molecules—the ions—as we can influence them by the electric current. From that time on the whole working force of my laboratory was devoted to the investigation of the physiological effects of ions.

My first aim was to find out whether or not it is possible to alter the physiological properties of tissues by artificially changing the proportion of ions contained in these tissues. In this way originated the investigations on the effect of ions upon the absorption of water by muscles, the effects of ions upon the rhythmical contractions of muscles, and medusæ, the heart of the turtle, and the lymph hearts of the frogs, the rôle of ions in chemotropic phenomena and the influence of ions upon embryonic development, and the development of unfertilized eggs (artificial parthenogenesis). Those who have followed my work on artificial parthenogenesis may have noticed that from the start I aimed at bringing about artificial parthenogenesis through ions. It seemed to me that I could not find any better test for my idea that the electrically charged ions influence life phenomena most effectively than by causing unfertilized eggs to develop by slightly altering the proportion of ions contained in them. I believe that all these experiments proved what I expected they would prove, namely, that by slightly changing the proportion of ions in a tissue we can alter its physiological properties.

The next step taken consisted in proving that it was indeed the electrical character of the ion that determined its specific efficiency.

'Studies on the physiological effects of the valency and possibly the electrical charges of ions': Introduction and conclusion on theoretical considerations (the footnotes being omitted) of Part I. 'The toxic and antitoxic effects of ions as a function of their valency and possibly their electrical charge,' originally printed in the American Journal of Physiology. From the Hull Physiological Laboratory of the University of Chicago. I succeeded in doing this three years ago. It was known that a frog's muscle gives rise to twitchings or rhythmical contractions when immersed in certain solutions. I showed that such contractions, occurred only in solutions of electrolytes, and not in solutions of non-conductors (distilled water, various sugars, glycerine, urea). Soon after I showed the same to be true also for the rhythmical contractions of the medusæ. From observations made in my laboratory, the same fact was shown to hold for the turtle's heart by Mr. Lingle, and for the lymph hearts of the frog by Miss Moore. I am confident that this fact will be proved universally.

In the physiology of the heart one frequently encounters the statement that calcium is the stimulus for the contraction of the heart. I had found that a muscle is able to twitch rhythmically when immersed in the solution of salts with a monovalent kation,—I obtained contractions in Na-, Li-, Kb-, and Cs-salts,—but that the addition of a small quantity of a bivalent kation—Ca, Mg, Sr, Ba, Be, Mn, Co—inhibits these rhythmical contractions. This seemed to be a direct contradiction to the statement that calcium salts are the 'cause' of the heart-beat. The significance of the calcium had to be looked for, then, in another direction. It was soon found that the muscle, the apex of the heart, and a medusa contract rhythmically in a pure sodium chloride solution, but that they soon come to a standstill. If, however, a trace of a soluble calcium salt is added to the sodium chloride solution, the contractions continue much longer. I concluded from this that the pure sodium chloride solution acts, in the long run, as a poison—that is to say, brings about definite but at present unknown physical changes in the protoplasm—but that a trace of a calcium salt annihilates this toxic action. The amount of calcium necessary for this antitoxic effect is of course much smaller than the amount necessary to inhibit the rhythmical contractions. Soon after I succeeded in demonstrating conclusively the poisonous effect of a pure sodium chloride solution, and the annihilation of this effect by calcium. The eggs of a marine fish (Fundulus) develop normally in sea-water, but they can develop just as well, as I had previously found, in distilled water. The addition of ions from the outside is consequently not necessary to the development of this animal. I found, now, that, if the freshly fertilized eggs of this fish are put into a pure sodium chloride solution having a concentration equal to the concentration of the sodium chloride in the sea-water (about 5/8 m), not a single egg can develop into an embryo. If, however, a trace of a calcium salt is added to the sodium chloride solution, as many eggs develop and in just as normal a manner as in ordinary sea-water. The calcium ions in this case undoubtedly serve the purpose of annihilating the poisonous effects of a pure sodium chloride solution.

In the meantime I had become familiar with the brilliant experiments of Hardy upon the influence of ions and the galvanic current upon colloidal solutions. They indicated to me that the next step I had to take was to see whether or not the valency and the sign of the electrical charge of an ion determine its physiological effects. I suspected that the antitoxic effect of the calcium ion in the above-mentioned experiment was due to its electrical charge and decided to investigate in a more systematic way whether or not the sign and quantity of the electrical charge influence life phenomena. My experiments carried on at Woods Hole this summer showed conclusively that this is the case for the antitoxic effects of ions and probably for the production of rhythmical contractions through ions. It seems at least possible that it is true also for artificial parthenogenesis.

Theoretical Considerations.

1. We have to attempt to answer the question, How can the electrical charges of ions produce a toxic or antitoxic effect? The answer to this question must be preceded by the answer to the more general question, How can the electrical charges of ions as well as of an electric current influence life phenomena? The basis for the answer to this question will undoubtedly be found in the work of Hardy, as well as that of Bredig, on the rôle of the electrical charges of the particles in a colloidal solution. Hardy has shown that living protoplasm is to be considered as a colloidal solution, a hydrosol. Such hydrosols are suspensions of solid particles in a fluid (water). These particles are at the highest about 1,000 to 10,000 times as large as the dimension which the kinetic theory of gases assumes for the molecules. The forces which keep these particles in solution are of an electrical nature. There exists, according to Helmholtz and Quincke, a double electrical layer at the limit between particle and surrounding water.

When the colloidal particles have a positive charge, the surrounding particles of the water have an equal negative charge. It agrees with this assumption that the colloidal particles move under the influence of an electrical current in the same way as ions. They move to the anode when they carry a negative charge, and to the kathode when they carry a positive charge. Hardy has made it probable that these charges keep the particles in solution, inasmuch as through these charges they must repel each other. Hardy has shown that as soon as these charges are taken away from them the colloidal particles will no longer be held in suspension, but either fall down or rise to the surface. In this case the hydrosol is transformed into a hydrogel. These charges can either be taken away from them through the oppositely charged electrode of a battery, or through oppositely charged ions which easily give off their charge. Solutions whose colloidal particles have a negative charge can be caused to coagulate (go into the gel stage) by one of two means: either by positively charged ions, or by the positive electrode of a battery. The coagulating effect of ions increases with their valency, and much more rapidly than the valency. The most valuable among Hardy's discoveries is the fact that in a solution of white of egg the colloidal particles can be rendered either positively or negatively electric by the addition of hydrogen or hydroxyl ions. When the neutral or isoelectric point is reached, the slightest change—one feels almost inclined to use the word 'stimulus'—is sufficient to transform the solution into a gel.

But long before the critical point of a colloidal solution is reached the variation in the charge of the colloidal particles alters their physical properties. An increase in their charge has the same effect as if the viscosity of the liquid were increased.

The bulk of our protoplasm consists of colloidal material, and the physical manifestations of life, such as muscular contractions and protoplasmic motions, and the innervations, are due to changes of the condition of these colloidal solutions. We now may be able to understand why the electrical current is the universal form of stimulation. The reason may be that the particles in colloidal solutions are electrically charged, and that every alteration of the charge of the particles will result in a process of innervation or a contraction or protoplasmic motion, etc. We likewise understand why the ions, on account of their electrical charges, are equally well capable of altering the physiological properties of the tissues, as the galvanic current.

But how can the ions cause toxic and antitoxic effects through their electrical charges? In my preliminary notice on these experiments which appeared in Pflüger's Archiv in November, 1901, I pointed out the possible relation of the electrical charges to the viscosity of the protoplasm. Phenomena of cell division are, as I believe with Bütschli and Quincke, phenomena of protoplasmic streaming. Such phenomena require, as Quincke has shown, a definite degree of viscosity. If the viscosity is too great, no protoplasmic motion is possible, and the same is true if the viscosity is too small. It may be possible that the toxic charges—presumably the negative one in the case of sodium salts—alter the viscosity of the protoplasm by either making it too liquid or too viscous, thus preventing the protoplasmic motions necessary for cell division or the muscular contraction. Small quantities of oppositely charged ions with a higher valency, which give off their charge sufficiently readily, will act as antitoxic substances.

2. The thermodynamical theory of life phenomena has utterly failed to show how the thermal energy produced through the splitting up and oxidation of foodstuffs can lead to muscular contraction. Engelmann's well-known attempt at an explanation is based on a physical impossibility, in view of the fact that some muscles, especially those of the wings of insects, are capable of relaxing and contracting a large number of times in a second. The facts mentioned at the beginning of this paper point distinctly towards the possibility that part of the chemical energy in our body is transformed into electrical energy, or, in other terms, the ions formed in metabolism seem to play a role in the dynamics of life phenomena. From the facts mentioned in this paper we can see that these ions, or rather, their electrical charges, may be responsible for such physical manifestations of life as the muscular contractions and others. It remains to be explained how the electrical energy of the ions may be transformed into the mechanical energy produced by the contracting muscle. This will be discussed in the second paper, but I will point out here that I believe that the electrical energy of the ions is transformed into surface energy. It will now become necessary to pay more attention to the production of ions in metabolism than has been done before. The CO3 and PO4 ions, as well as the H ions, can no longer be considered as mere waste products of metabolism.

3. The fact that ions may act toxically through their electrical charges, and that ions with the opposite charge may act antitoxically, may open a new and very fertile field for pathology and therapeutics. As I have stated in previous papers, especially certain neuroses, and perhaps certain mental diseases, may now find their explanation. Two years ago I pointed out that we must realize the existence of physiologically balanced salt solutions, that means salt solutions in which the ions are so combined that the toxic effects of the one are counteracted by the antitoxic effects of some other ion. Any disturbance in the right proportion of monovalent ions and ions of higher valency must lead to more or less pronounced modifications of the life phenomena.