We cannot here bring forward even a few of the facts that go to prove the truth of the dissociation theory of Arrhenius; but there are an abundance of the same to show that the chemical (and consequently the physiological, pathological, and pharmacological) effects of most of the electrolytes are entirely dependent upon their constituent ions, and are independent of the nature of the molecules. For example: hydrochloric acid dissociates into H-3 and Cl-ions; NaCl dissociates into Na- and Cl-ions. These solutions are the same in so far as they both contain Cl-ions, but different in that one contains H- and the other Na-ions. These differences determine the differences in the properties of the two solutions.

A single experiment may serve to fix more clearly the fact that it is, indeed, the ions, and not the molecules, that determine the activity of an electrolyte in solution. If an iron nail is put into an aqueous solution of HC1, the iron is immediately attacked and H is liberated. If, however, the nail is put into a solution of HC1 in benzene, no such chemical action takes place. The water in the first case converts the HC1 into H- and Cl-ions. Benzene has practically no such dissociating powers, and the HC1 remains in the molecular state. The molecules of HC1 are incapable of attacking the iron.

It may, then, be accepted as true in general that the chemical characteristics of an electrolyte are dependent upon the nature of the ions contained therein. Thus the chemical characteristics of an aqueous solution of HC1 are determined by the H- and Cl-ions it contains. All acids yield H-ions, and it is because of this fact that all acids have certain general properties. The differences between the solutions of two different acids that contain the same number of H-ions are determined by the differences between their anions. Since, now, the physiological effects of a substance are dependent upon its chemical nature, and since the chemical nature of an electrolyte is, in the main, dependent upon the nature of its ions, it follows that the physiological effects of an electrolyte are determined by the nature of its ions.

When an electrolyte is administered as a therapeutic agent, before it can produce any effect it must be in solution. Water is the universal solvent in the body. But when an electrolyte is dissolved in water, it is dissociated into ions. The therapeutic effects of such an electrolyte must, then, be dependent upon the ions which it yields. For example, in the administration of a dose of sodium iodide, we deal not with the effects of the Nal molecules, but with the effects of the Na- and I-ions into which the sodium iodide dissociates.

Although Dreser showed in 1894 that the relative toxicity of the mercury salts is determined by the number of Hg-ions that the salt yields upon solution in water, and although Kahlenberg and True were the first to show that the poisonous effects of various electrolytes upon the roots of the bean are determined by the nature of their ions, the credit of recognizing the widespread physiological importance of the theory of electrolytic dissociation belongs to Jacques Loeb.

A series of papers originating from the laboratory of this investigator have brought proof of the following facts. The poisonous effects of acids and alkalies2 upon muscle are determined by the number of the H- and OH-ions they yield, and is independent of the nature of the acid (in the case of the inorganic acids) or alkali. Another paper3 shows that the amount of water absorbed by a muscle from equimolecular salt solutions is influenced not only by the laws of osmotic pressure, but also by the nature of the ions in the solutions. The absorption of water from equimolecular solutions of sodium, potassium, and calcium salts by muscle is analogous to the absorption of water by the Na-, K-, and Ca-soaps, for while muscle absorbs but little water in the sodium solution, it absorbs an enormous amount in the potassium solution, while it actually loses water in the calcium solution. A most important contribution to our knowledge of life phenomena is found in the discovery that Na-ions are absolutely necessary for the production of rhythmical contractions in voluntary muscle,4 in heart muscle,5 and in the contractile swimming bell of the medusa.6 Yet a heart beating rhythmically in a pure sodium chloride solution soon comes to a standstill. If, however, a little calcium be added, the heart may continue to beat for hours.

What bearing, now, has the theory of electrolytic dissociation upon the problems of pharmacology? We have for years been accustomed to see the effects of different salts grouped under general headings. Thus we have become acquainted with the general effects of potassium and sodium salts, the salts of iron and lead, and the general properties of iodides and bromides. Never, however, has the question been asked, Why do these salts arrange themselves in such groupings? We have learned that certain salts having certain characteristics in common may at will be substituted for one another. We have known, moreover, that although certain groups of salts, such as the salts of Hg, Ag, Pb, Cu, etc., all have highly poisonous properties, yet that the fatal dose of the individual members of such groups differs greatly from one another. Then we have been impressed with the fact that many organic salts, or salts combined with organic substances, are either entirely without effect, or else behave entirely differently from the ordinary salts. These are a few of the facts which become at once intelligible in the light of the dissociation theory.

We have said before that in the process of solution an electrolyte is dissociated, and that in consequence we deal, in the main, no longer with the properties of its molecules, but of the ions that constitute the molecules. We know, for example, that we can substitute, at will, sodium iodide for potassium iodide in order to produce certain therapeutic effects. These salts are alike in that they both yield I-ions; they differ in that the former yields Na-ions, while the latter yields K-ions. Any similarity manifested in the therapeutic effects of these two salts is determined by the similarity of their anions. . But we know that the potassium iodide is much more depressant than the sodium salt. This is due to the direct poisonous effects of the K-ions upon muscle and nerves, an effect not exhibited by Na-ions. It is because all the iodides yield I-ions that they are grouped under a general heading. It is the effect of the I-ions that we seek in administering this drug in syphilis. Provided we give equal doses of I-ions, one salt may at will be substituted for the other. It is the secondary benign or deleterious action of the kations, however, which determines which salt we employ.