Pharmacology is a science inclusive of all exact knowledge of the action of substances and physical conditions upon the animal body. Therapeutics is an art employing, among other things, knowledge pharmacologically derived.

Experiments made upon man laid the foundations of pharmacology, but the limitations of such experimentation made progress slow. Experiments upon animals permit of fixed conditions and scientific controls. Such precise conditions lead to precise determinations of toxic and physiological actions, which are a useful guide in, first, determining if a drug possesses activity; second, ascertaining what that activity is; third, analyzing and explaining the determined action; and fourth, suggesting its possible range of therapeutical usefulness.

Pharmacology is a somewhat iconoclastic science. For instance, it proved that strychnine has no direct action on the heart, and that opium has no local action in depressing sensory nerve-endings. Thus doubt has been thrown upon many old therapeutic teachings. On the other hand, much new therapy has resulted, largely owing to pharmacology explaining many things. For instance, citric acid removes the calcium ions from the blood and is excreted in the urine as a carbonate. Hence we use oranges to alkalinize the urine. The hypnotics and narcotics have a selective affinity for the central nervous system because of their solubility in brain lipoid. We have learned that muscarine is stored in the heart muscle, but that atropine retards its absorption from the outside fluid; hence we now have an antidote for muscarine poisoning. Chloral is proven to diminish the oxidizing capacity of the tissues, and hence we learn when not to use chloral. Nicotine action is due to its disappearance from the blood and being taken up by the liver; and this is but one instance of selective action, which, once it is fully understood, will enrich therapy.

And we learn some strange things from pharmacology. For instance, the vegetable purgatives contain irritant principles whose absorption would irritate the kidneys. Hence we give these drugs in a more or less crude or impure state in order to prevent absorption, their natural gums and resins delaying absorption. We do not wish anthelmintics and emetics to be absorbed from the stomach; hence we are not concerned so much with remote as with immediate effects, and animal experimentation proves out these drugs for us faster than we could determine the points by clinical experimentation. It seems strange that senega is an expectorant only indirectly, through its increasing the flow of bronchial mucus by exciting the nerve-endings in the stomach, which, in turn, affects the bronchioles reflexly through the medulla.

Because a drug possesses a certain number of physiological actions it does not at all follow that, when a full dose is swallowed, the patient experiences all of those actions. Often it is necessary to administer the drug hypodermatically to realize even most of the effects. Even then, for instance, cocaine can be injected, with marked anesthesia about the site of injection and but little remote influence. Strychnine may be injected into the temporal region, and its eye effects are noted only on that one side. Ergot amines, when injected, raise blood pressure higher when the clavicular region is entered by the needle than when the forearm is selected.

Ammonium salts in the blood cause medullary convulsions; potassium in excess is markedly toxic to all living tissues. Yet ammonium and potassium salts, when injected, are excreted as rapidly as they are absorbed, and are not immediately toxic.

It takes about three days of digitalis administration before sufficient quantities reach the heart muscles to markedly influence that organ. Hence, when we give digitalis in pneumonia to influence a failing heart, we begin before the cardiac symptoms arise.

Pharmacology develops many practical points. For instance, alcohol is rapidly absorbed and carries with it substances in solution. Therefore the tinctures are advantageous when prompt absorption of a drug is desired.

And yet, despite the advances of pharmacology and pathology, much of treatment is empiric. We know little about gout and epilepsy, but we do know the value of colchicum and bromides as remedies. We don't know why the salicylates have so potent an influence upon acute rheumatic fever. So, then, let the pharmacologist be modest in his claims and in his criticism, for empiricism still has a place and much remains to be explained.

Pharmacology has yet many problems to solve.

Physiological action often depends upon chemical constitution, but not always. Urea, strophanthin, and cocaine all paralyze sensory nerve fibrils, yet there is no chemical relationship whatever between them. Why is it that isomeric modifications in alkaloids count so heavily? The dextro variety has little pharmacological action, while the laevo is very active. Why is this? Again: Why are the unstable chemicals, like muscarine and neurine, so exceedingly toxic? The pharmacologists claim that the hypophosphites are inert because they are excreted unchanged. Perhaps so; but they may be in the class with strychnine. The benzene derivatives are still a puzzle pharmacologically, though the theory of dissociation may explain discrepancies to a degree.

Pharmacology is a pure science rather than an applied one, and it tells us the probabilities regarding a drug and what its line of possible utility may be. On the other hand, pharmacology is weak as regards the pathology of remedies, concerning itself chiefly with their physiology. McCrudden, of Boston, has well said, "When and how to use drugs in disease is outside the province of pharmacology."

And, while animal experimentation is most valuable, yet it has an inherent weakness. Digitalis raises blood pressure in laboratory experiments upon animals; yet H. C. Wood, Jr., says it does not in therapeutic dosage in man. James Mackenzie, the eminent English authority in heart disease, says: "In all of our observations made at Mount Vernon Hospital and London Hospital, as well as those made in private practice, we have only found rare instances where the blood-pressure was noticeably raised, and a good number in which it was lowered."1

"How is pharmacology to differentiate between acute and chronic disease therapy? An organ may be functionally active and yet be the seat of organic disease. What guidance can pharmacology give us here? Suppose a dozen cardiac remedies are taken at random, pharmacology tells us which ones are in the digitalis group, which ones may be dangerously toxic, and which ones are inert so far as their cardiac actions are concerned. In other words, we no longer need to experiment empirically for years to determine if a given drug is promising or is not. Here pharmacology is a wonderful help. Most of our modern therapeutics is based upon pharmacology, just as modern floriculture is based upon botany; but the pharmacologist may not be a therapeutist, or the botanist a florist. But the therapeutist who knows his pharmacology proceeds with his eyes open and he gets results because he knows better than to try to get them where they are impossible, and the florist who knows his botany saves himself a world of useless experimenting.

"It takes a lot of experience to make a commercial florist of a botanist, and a world of it to make a therapeutist of a pharmacologist."2

But our especial interest here relates to the botanic drugs. Is pharmacology robbing us of them? Yes and no. Pharmacologic study has extended to many botanic drugs, crediting some and discrediting others; and it is robbing us of many claims formerly made, especially those making cure-alls of some of them. The day for cure-alls is over.

1 "Diseases of the Heart," third edition, by James Mackenzie. 2 From an editorial in The Medical Council, January, 1916.

Neither the botanist nor the pharmacologist goes very deeply into the intimate composition and physiology of plants, though a literature is developing;3 but the bacteriologist has done so as regards minute plants; and the students of the larger plants should emulate his example.

The greatest mystery tale ever written is that of bacteriology - the mystery of the minute plant and its influence upon man and the lower animals; but it is a mystery being solved. When the larger plants shall have been studied as deeply as have bacteria and molds, then will plant pharmacology take great prominence as a constructive science. True, we have been breaking alkaloids, oils, and resins out of the larger plants; but what do we know of the intimate relationships of these things in the structure of the plants themselves? Yes, there are unsolved mysteries in plant life, even when used as remedies. When pharmacologists cease to be so much obsessed with alkaloid hunting, and commence the study of the plant remedy as a whole, then will we learn much that we do not know now. As I said before, there is no place for mystery in therapeutics; but to remove certain more or less mysterious elements from therapeutics, the clinician needs to heed pharmacologic teaching more than he has in the past, and the pharmacologist needs to give sincere and unprejudiced study to the things asserted by the empiricist of clinical experience.

3 See "The Natural History of Plants," Kern and Oliver.