knowledge became specialized, medical men more and more devoted their activity exclusively to medical practice. Because of its inefficiency at that time medicine lost its prestige. In recent times, however, medicine is becoming an effective science; one marvelous discovery has followed another, and the efficiency of medical practice has been rapidly increasing. Medicine makes habitable to man hitherto uninhabitable parts of the world. It prevents disease; and, with increasing theoretical and practical efficiency, medicine is learning to alleviate and cure disease and prevent injuries. Medical sciences and medical men have steadily risen in the esteem of civilized mankind. May not the medical sciences and medical men become again the standard bearers of morality, especially of international morals?

To accomplish these objects, it is proposed to organize as large and effective an Association as may be possible, of men and women engaged in the medical sciences or in medical practice, under the name of

THE MEDICAL BROTHERHOOD

FOR THE FURTHERANCE OF INTERNATIONAL MORALITY

It is obvious that such a Brotherhood could not exercise an important influence at once. But our modest expectation for prompt results should not prevent us from attempting now to take the first step in the right direction. Many important results have often had small beginnings.

A committee of physicians and medical investigators request you herewith to enroll as a member, and to declare your willingness to endorse and support the moral standard which the medical profession generally upholds when called upon to perform its patriotic duties in international strife.

It should be expressly understood that it is not the object of the proposed Brotherhood to influence the feelings and views of anyone regarding the problems involved in the present war. It is desired merely to bring to the full consciousness of the members of the medical profession the exceptional moral position which all civilized nations, even while at war, permit and expect medical men to occupy, at least so long as they remain in the medical profession and act in this capacity. This consciousness cannot fail to elevate the moral standards of physicians. Furthermore, after the close of the present war, the Brotherhood could without doubt facilitate the reunion of the members of the medical profession of all the nations which are now at war and increase good feeling among them. A humanitarian body such as this proposed Brotherhood, if already in existence and ready for service, might and could be of the greatest usefulness in many ways.

The foregoing Appeal, signed by the members of the Executive and Advisory Committees, as listed above, has been widely circulated among physicians and others engaged in the advancement of medical sciences.

Any reader of this statement of the objects and proceedings of the Medical Brotherhood, who may be eligible for election to membership and who, not having enrolled as a member, desires to join the Brotherhood, is hereby invited to communicate with the President, or the Secretary, or any other officer.

Biochemical Laboratory of Columbia University,
College of Physicians and Surgeons, New York.

RESULTS OF STUDIES ON VITAMINES AND DEFICIENCY DISEASES, DURING THE YEARS

In my book on vitamines and deficiency diseases, which appeared early in 1914, and in several other articles published about the same time, these subjects were reviewed very extensively. The present article is written with the purpose of reviewing the progress of the work in this field since the publication of my book. For the benefit of any who may not be familiar with this particular branch of science, however, the chief data obtained prior to 1914 will also be briefly summarized.

The subject of vitamines owes its existence to results of the study of beriberi, a disease occurring in oriental countries where rice is used as staple food. This disease was first regarded either as an

* An abstract of this review constituted an address by the author, at the 22nd meeting of the Columbia University Biochemical Association, at the Columbia Medical School, April 9, 1915 (BIOCHEM. BULL., 1915, iv, p. 266). A review of further developments in the study of vitamines, since April, 1915, will be published by the author in a late issue of Volume V of the BIOCHEMICAL BULLETIN.

intoxication or an infection. The remarkable increase in the frequency of its incidence during the past twenty-five years suggested to several excellent workers in tropical medicine that the greater number of recent cases has been due to the introduction of modern machinery for the decortication of rice. It was shown that in certain parts of the Malay States and India, where either hand-milled rice or parboiled rice (rice steamed previous to decortication) is used, the incidence of beriberi is much less frequent than in parts where machine-milled rice is used as food. A suspicion arose that with the removal of the superficial layers of the rice grain, an ingredient is lost which is essential for the maintenance of life on a rice diet. This lost constituent was regarded, at first, as a kind of antidote, or antitoxin, against hypothetical intestinal poisons produced during the digestion of rice.

Uncertainty continued until 1897, when Eijkman observed that fowls, which had been fed on residues of food supplied in a hospital with beriberi patients, developed a disease that closely resembled human beriberi. This condition in fowls was called Polyneuritis gallinarum. This very important discovery paved the way for the experimental investigation of beriberi.

Eijkman found, also, that alcoholic extracts of rice-polishings cured experimental polyneuritis in chickens. He believed the effects of such extracts were due to the presence of an antidote. Schaumann, in 1910, advanced another theory, which was based on the alleged fact that foodstuffs able to cure polyneuritis contain high percentages of organic phosphorus. He concluded, therefore, that beriberi is due to lack of organo-phosphorus compounds in the food. In accord with this view, he found that yeast is an excellent curative agent. The phosphorus-deficiency theory was advanced at a time when there was a widespread belief that lipoids had important physiological and pharmacological properties. Recently it has been shown that the animal organism is able to synthesize lipoids and other organo-phosphorus compounds from phosphoric acid, provided the remaining constituents (radicals) are available. We now know, also, that the importance hitherto attributed to lipoids was dependent very largely upon substances of basic nature which occurred incidentally in lipoid fractions. The phosphorus-deficiency theory of Schaumann had to be abandoned when it was shown, in my early experiments with yeast, that, after hydrolysis for 24 hr., with 20 percent sulfuric acid sol., yeast retained its curative properties. The experimental data indicated that the active substance was comparatively simple in chemical nature, more or less basic in character and, to some extent, thermostable in acid solution.

On the assumption that the active substance contains nitrogen, the alcoholic extracts of different foodstuffs were fractioned by means of the usual methods for the separation of organic bases. Chemical attention, however, was chiefly devoted to extracts from yeast and rice-polishings. It was found that vitamine was precipitated with phosphotungstic acid, partially with mercuric chlorid in alcoholic sol., and with silver nitrate and baryta, the latter precipitation proving to be the best for the isolation of vitamine. The curative fraction obtained in this way was very small-between 3-5 gm. from 100 k. of dry yeast, or 1000 k. of rice polishings.

This fraction, administered orally or subcutaneously to beriberi pigeons, exhibited the following effects: The animals recovered very speedily, often in 2-3 hr., but it was found impossible to keep them permanently on polished rice even when injections were repeated every few days. By further fractioning the curative material from yeast, three substances were obtained. One was definitely identified as nicotinic acid. The second substance, when completely purified, proved to be inactive but represents without doubt a new chemical substance; this is now undergoing a complete investigation. The third substance was obtained only in traces. None of these three products, given either separately or together, showed anything like the action of the original fraction. Thus far rice-polishings, as we shall see later in this résumé, have yielded nothing in this connection but nicotinic acid. It does not seem improbable that this substance is a decomposition product of an unstable vitamine.

It is not surprising that little has been achieved in the elucidation of the chemical structure of these puzzling substances. In their study unusual experimental difficulties are encountered which will be discussed below. Even a relatively simple problem like the chemical structure of adrenalin required a series of years for solution.