In the animal body many salts are found in solution, not as complete molecules, but as made up of their electrical components, or ions, one positive and another negative, and when a chemical action takes place, it is an action not between the molecules of the salt and the protoplasm, but between an ion of the salt and the protoplasm, or even ions of the protoplasm molecule. For many of the simpler inorganic compounds, NaCl, KC1, KBr, KI, K(OH), many metallic salts, etc., the action of the ions is fairly well established. Thus the effects of strong, hypertonic, weak or dilute, hypotonic, and normal, isotonic, salt solutions on blood-cells, on muscle-cells, and on nerve-cells are well known and readily explicable under the now known laws of ion dissociation. Space does not permit of a more extended discussion of this interesting phase of the subject.

Physiological Action and Chemical Composition. - If the action of drugs is fundamentally a chemical one, then, on a priori grounds, it may be inferred that chemical compounds with similar dissociable ions will bring about similar physiological reactions. This general line of thought opens up a most fascinating field, which is daily offering more and more positive deductions, especially along the line of the newer synthetic preparations.

Many years ago Blake suggested and worked out a complicated scheme of the toxicity of the metals, based on the periodic law of Mendeljeff,2 but it would seem, for the present, that the time has not yet come when such relationships will prove of any practical interest.

In the field of organic chemistry, however, the fundamental truths of the relationships of chemical structure and physiological action have given to pharmacotherapy some of its most highly prized drugs. The ingenuity of the pharmaceutical chemist is being taxed to the utmost in the search for new compounds.

1See Frankel, Arzneimittel Synthese, 1901.

2 He showed that between certain limits there existed certain relations between the molecular weights, the spectrum analysis, and the physiological action of the metals.

Along other lines equal diligence has been shown. Thus, a large number of the newer synthetic remedies have their drawbacks: their action is marred by certain unpleasant by-effects that have no relationship to the main action of the drug. Many are too readily soluble and exert a local action on the stomach, when it is desired that they reach the intestines; others are insoluble and do not act where it is desirable to have them do so - as, for instance, many of the intestinal antiseptics and astringents. Many other illustrations might be instanced.

One of the most fascinating problems connected with this subject is that of the combination of the useful activities of different synthetics. Thus it is possible to combine a hypnotic acting radicle with an analgesic, and in one compound get a combination of the two. Other desirable combinations naturally occur. It is unfortunate that this problem has been often accomplished very satisfactorily from the chemical point of view, but when the physiological test has been applied, the compound has been worthless, both actions having been lost by some modification of one or the other main action.

The possibilities of the problems are extensive, but the difficulties are many. One warning note should, however, be sounded. Notwithstanding the many excellent results that have been accomplished by pharmaceutical chemists, there seems to be a tendency on the part of many to offer to the medical profession a vast number of so-called new synthetics. These are not at all new, but are well-known old compounds or very slight modifications of popular compounds that do not differ at all in their main actions. Such, by dint of extensive advertising and ingeniously devised "clinical reports," they force on the practitioner as very valuable new synthetics. Reference is not here made to the imposition of the compounding of well-known remedies, such as acetanilid, etc., and the putting forth of the same under proprietary names as new synthetic compounds. Such are the sharks that prey upon the legitimate pharmaceutical chemist who is making honest efforts to give the profession much-desired remedies. They also prey on the community in that, under the guise of a secret name, they commit economic robbery, supplying at exorbitant rates what can be supplied anywhere at rational prices.

Relation of Physical Chemistry to Pharmacology and Therapeutics. - Perhaps no departments of medicine have been so subject to the criticism "unscientific" as those of pharmacology and therapeutics. Pharmacologists still hold the most contradictory-positions regarding the action of specific drugs; and therapeutists have at their disposal but few means which enable them to predict with definiteness the course of disease. Our modern therapeutic nihilism is undoubtedly the reaction of a thinking medical profession against an antiquated empiricism. But, as is customary with such reactions, the pendulum has swung too far backward. In order to restore it to its right position it is necessary that we reconstruct our knowledge of pharmacology and therapeutics, and, by beginning with its simplest problems, slowly rebuild it upon a basis of newer interpretations more in accord with modern science.

It is impossible, in this limited space, even to touch upon all the points at which physical chemistry offers immediate results in its application to the problems of pharmacology. In these pages, therefore, we shall consider only the applicability of the theory of electrolytic dissociation to the problems in hand.

According to the dissociation theory of Arrhenius, when strong acids, bases, or salts are dissolved in water (or certain other solvents), either all or a part of the molecules are split by the water into simpler substances - the electrically charged atoms or groups of atoms known as "ions." Since these strong acids, bases, and salts upon solution conduct the electric current, they are known as "electrolytes." According to Arrhenius' theory then, a solution of hydrochloric acid is made up not only of HCl molecules, but also of H-ions and Cl-ions. Similarly, a solution of sodium hydroxide contains not only molecules of NaOH, but also Na-ions and OH-ions. Ions are charged with positive or negative electricity. The negatively charged ions, which travel to the positive pole, are termed "anions "; those charged with positive electricity, and traveling toward the negative pole, are termed "kations." Thus the ions of a completely dissociated hydrochloric acid solution may be written H+ and C1-.