Theophrastus and Dioscorides were the first to begin the pharmacognostic standardization of medicinal plants; and Hildegard, Albertus Magnus, and the Arab writers built upon that foundation. By the nineteenth century pharmacognosy was a dead issue, until revived by Flukiger, Hamburg, and a few others; but more recently Pomet, Geoffrey, Berg, Tschirch, Kraemer, Schlotterbeck, and Rusby have advanced it wonderfully. Pharmaco-anatomy was the beginning, and pharmaco-physiology followed and is but partially developed. But it promises very much in the practical matter of so cultivating medicinal plants as to increase their standard of medicinal content.

In Java the Dutch have produced cinchona bark yielding 16 per cent of quinine, an immense increase. By cultivation, beets are made to yield 16 per cent of sugar. Tschirch developed the production of resinoids in the forests of Berne, and drug firms in the United States have produced an increased yield of alkaloid content in certain medicinal plants.4

If pharmacology had accomplished nothing else, it were well justified in its development of methods of drug standardization. Stewart has been an aggressive worker in this line, and he read a paper5 before the American Therapeutic Society at its session in Montreal, 1912. Some of the following data is from that paper.

Definition in the character of botanic drugs has never been fully realized; it is even more important than is adulteration. Active principles show marked variation quantitatively in medicinal plants. The Seventh United States Pharmacopeia began a scientific definition, since improved upon; and the Pure Food and Drugs Act of 1906 gave legal support to such definition. Opposition to standardization came from retail druggists and certain business interests; but the large drug houses and the medical profession upheld standardization, and opposition has now practically died out.

4"The Cultivation of Medicinal Plants," The Lilly Scientific Bulletin, series 1, Number 7, March, 1916.

5"Modern Methods of Drug Standardization," F. E. Stewart, Monthly Cyclopedia and Medical Bulletin, Jan., Feb., Mar., 1913.

The Eighth United States Pharmacopeia included certain assay processes, and even more appear in the Ninth Revision. The Eighth Revision included assay processes for twenty botanical drugs, showing that even then the subject was well advanced.

But assay processes are limited, such drugs as digitalis, apocynum, convallaria, geranium, squill, strophanthus, ergot, cannabis, and many others not adapting themselves thereto; but physiologic or pharmacodynamic methods apply to many drugs. It is stated 6 that variations in digitalis tinctures have a range as high as 400 per cent, and strophanthus tinctures 6000 per cent. How important, then, becomes physiologic standardization!

The steps in standardization include exact nomenclature and tests for identity and purity. The materia medica supply business needs to be limited to concerns employing capable experts who will properly standardize all products. Without standardization medicine and pharmacy will retrograde to the old basis of mystery and pretense, catering to the ignorant and credulous, exploiting the sick for gain, as does the patent medicine interests. The Council on Pharmacy and Chemistry of the American Medical Association, against tremendous but futile opposition, is routing out such practices from medicine and pharmacy.

6 Edmunds and Hale: Hygienic Laboratory Bulletin, Washington.

Clinical standardization is a further step now developing.

These processes have been applied almost wholly to official products; but the annual publication "New and Nonofficial Remedies" of the American Medical Association, and the Committee on Unofficial Standards of the American Pharmaceutical Association, are attempting to cover the whole field. Their efforts should be consistently upheld. Dr. Stewart well says: "The argument that therapeutists must experimentally determine the proper dosage of an agent to fit the needs of each particular case is no excuse for the tolerance of variation in the strength and potency of the remedy itself; every possible variable should be eliminated in an effort to reduce therapeutics as nearly to an exact science as is possible." It may be noted that the Government demands this of proprietary chemical fertilizers, insecticides and mixed poultry and cattle foods. Then why should not the physician demand it of all remedies, official, unofficial, and proprietary?

The United States Public Health Service, through its Hygienic Laboratory at Washington, is legally empowered to maintain standards in biologic remedies, and to inspect and license concerns producing them. Were the same supervision exercised over the production of botanic remedies, they would enjoy a professional confidence that would soon quadruple the use of these agents by physicians.

I am in position to state that commercialized medical journalism, lacking in advertising standards as it is, is open to severe indictment for maintaining the support of a class of proprietary remedies wholly contemptible from the scientific point of view and worthless from the clinical one. Honest proprietary remedies, however, have a proper place recognized by all.

Deterioration is one factor not met by standardization; but preparations of digitalis, strophan-thus, and ergot are the only botanic drugs of prominence liable to rapid deterioration, and these are readily put up in vacuum ampoules for use on such occasions as demand a certainty of full activity.

In the earlier employment of standardization methods it was deemed essential to assay for but one or, at most two, dominating alkaloids. But this thought is giving way. Perhaps I can do no better here than to quote Tschirch, who said:

"We know that rarely does a single substance suffice to produce the effect of the drug; it is the combined action of all the substances which brings about the peculiar effect. Nevertheless we must often recognize the preponderating influence of one substance, which I have characterized as dominant. It is at first by clinical experience that one gets to appreciate this fact, since it has thus been determined that the effect of employing the entire drug is rarely the same as the effect of the single so-called active principle. Moreover, Professor Burgi, of Berne, has shown positively that very often the effect of one substance can be augmented or diminished by another, and that similar substances are not additive in their effects. The 'adjuvantia' of the old pharmacologists were therefore not chimeras, but, on the contrary, a distinct idea corresponding to the name and to the thing itself.

"This ancient idea, under a new form, brings us to the study of the drug itself. Under the influence of the successes of the modern synthesis of medicaments, and the misunderstood theory of the so-called active principle, we have been gradually abandoning drugs, in spite of experiments carried on for hundreds of years, and even, in the case of certain drugs, for thousands of years. Many physicians have already disaccustomed themselves to the use of drugs. But they cannot be replaced, and the wish that I expressed in London, in 1909, 'let us go back to drugs,' found an echo much sooner than I expected, and in more extended circles than I had dared to hope.

"How can one replace rhubarb by a solution of emodin, ipecac by emetine, opium by morphine, digitalis by digitoxin, ergot by ergotoxine or by the interesting bases isolated by Barger and Dale, which according to the recent experiments of Kehrer, do not even act on the uterus? Emodin, emetine, quinine, digttoxin, and morphine are pharmacological individuals different from the drugs themselves, and should be numbered among remedies not to replace the drugs, but to stand beside them.

"Since we know that there is in the drug a dominant principle, but that the effect is not produced by this principle alone, we are more than ever obliged to make a profound chemical study of the drug in all its elements. The object of pharmaco-chemical research is not the discovery of a single active principle, but the complete analysis of the entire drug."

The detailed laboratory methods employed in the standardization of remedies need not occupy space here; they are described in works upon pharmacology, which should be consulted for details.

To close this subject, and to answer certain criticism directed by clinicians against standardization methods, permit me again to quote Stewart, who says:

"The purpose of the biologic assay, just as of the chemical assay, is to secure a means of measuring therapeutic activity and to make it possible to furnish uniform preparations. A satisfactory method which meets these requirements may or may not involve the production of physiologic reactions similar to those which the drug is intended to be the means of producing when used therapeutically. That the effect chosen as a means of standardization does not parallel the clinical effect sought is not sufficient to condemn the method. It is only necessary that the effect chosen as an earmark be always indicative of a good quality of the drug or preparation, and criticisms of methods on the ground that they are toxic methods or that the animal chosen is biologically much different from man are made only through a lack of conception of the real purpose of the physiological test, namely, to secure uniformity. The determination of the real value of a drug in the treatment of disease in man is another matter entirely."