The Polish-Swiss organic chemist Tadeus Reichstein (1897-1996) shared the Nobel Prize in Physiology or Medicine for his discoveries relating to the hormones of the adrenal cortex.
The son of Isidor Reichstein, an engineer, Tadeus Reichstein was born in Wloclawek, Poland, on July 20, 1897. In 1914, shortly after his family moved to Zurich, he became a naturalized Swiss citizen. He began the study of chemistry at the State Technical College at Zurich in 1916, qualified in 1920, and in 1922 graduated as a doctor of philosophy in chemistry. For some years thereafter he investigated the cause of the flavor of coffee. In 1929 he became lecturer in organic and pharmaceutical chemistry at the Zurich Technical College, where in 1934 he was appointed titular professor, and in 1937 associate professor, of organic chemistry. In 1933 he synthesized ascorbic acid, independently of (Sir) Norman Haworth and by a different process.
In 1938 Reichstein was appointed professor of pharmaceutical chemistry, and in 1946 also of organic chemistry, in the University of Basel. From 1948 to 1952 he supervised the design of the new Institute of Organic Chemistry at Basel, of which, having meanwhile relinquished the chair of pharmaceutical chemistry (1950), he was director until 1960.
Chemistry of the Adrenal Cortex
In 1929 a long-standing rheumatoid arthritic was, because of an acute attack of jaundice, referred to Philip Showalter Hench of the Mayo Clinic, Rochester, Minnesota. Within a few days most rheumatoid symptoms disappeared. During the next five years Hench saw 16 further cases, all of which were improved by the intercurrent jaundice. He concluded that the beneficial effect might be due to excess of a normal bile constituent or to an abnormal substance present in jaundice. He and his co-workers therefore administered bile and bile salts to rheumatoid arthritics, but no beneficial effects were observed. In 1931 Hench noted that female arthritics sometimes improved during pregnancy, and over several years he and his co-workers confirmed this fact. Hench now assumed that the improvement was due to the presence of a substance X, which was the same in jaundiced cases as in pregnant women. About 1938 he concluded that substance X was probably not derived from the bile but was a hormone found in both males and females.
About 1929 scientists first prepared extracts of the adrenal cortex which checked the symptoms following removal of the adrenals in animals and also those of Addison's disease in human patients. These extracts were named "cortin," and it seemed desirable to elucidate its composition and to prepare it in a pure state.
In 1934 E. C. Kendall, of the University of Minnesota, found that an extract thought to be pure cortin was really a mixture. In 1934 also Reichstein entered this field, and he and Kendall soon isolated about ten compounds from the adrenal cortex. Their detailed chemical investigation was mainly due to Reichstein. He soon proved that all such substances are steroids, and he continued to isolate new steroids from the cortex. By 1950, 29 were known.
The steroids were characterized by the presence of a complex nucleus, consisting of four rings bound together in a certain order to form a chain. This nucleus contained 17 carbon atoms, each bound to one or two hydrogen atoms. The nature of a particular steroid was determined by the nature of any substituent groups attached to carbon atoms in the nucleus. Of the 29 steroids isolated from the cortex by 1950, six were biologically active and not found in any other organ. They all contained 21 carbon atoms, that is, four additional to the 17 contained in the nucleus. The biological activity was dependent on the presence of a double bond. These cortical steroids were shown to influence the fluid balance of the body, the storage of sugar, and the metabolism of carbohydrates and proteins.
In 1934 both Reichstein and Kendall became interested in four of the active steroids, which Kendall called compounds A, B, E, and F. Compound E was isolated by Kendall in 1935 and about the same time by Reichstein. It was found to be 11-dehydro-17-hydroxycorticosterone. It was also found that it did not prolong the life of adrenalectomized animals but that it restored the power of their muscles to contract.
These substances were present in the adrenals in such minute amounts that to obtain enough for clinical purposes it was necessary to synthesize them. In 1937 Reichstein, starting with a bile acid, synthesized the simplest member of the group, deoxycorticosterone. Deoxycorticosterone acetate (DOCA) was soon available on an industrial scale and was satisfactorily used in treating Addison's disease.
For a long time other corticosteroids eluded synthesis. Manufacturers were not interested, as there were few patients with Addison's disease. In 1941 Hench and Kendall considered that Hench's substance X was probably Kendall's compound E, and they decided to administer compound E to rheumatoid patients as soon as a supply was available. In 1941 also the National Research Council of the United States, believing that the corticosteroids might be valuable in war, urged that attempts be made to synthesize compound A preparatory to the synthesis of compound E.
In 1943 Reichstein synthesized compound A from deoxycholic acid. His method could not be applied on a large scale, but in 1944 Kendall synthesized it by a more practical method. In 1947 Lewis H. Sarett, of the Merck Laboratories, synthesized a very small quantity of compound E from compound A. In August 1948 Hench, still searching for the hypothetical substance X, reaffirmed his decision to try Kendall's compound E on arthritics, and on September 4 he formally asked the firm of Merck for a supply sufficient for clinical trials. The small amount prepared was sent to Hench, and on September 21 his co-worker Charles H. Slocumb began to administer it to a rheumatoid arthritic. The excellent results led rapidly to the treatment of many other patients by Hench, Slocumb, and Howard F. Polley at the Mayo Clinic, and at the end of 1948 the name of compound E was changed to "cortisone." In February 1949 these workers obtained a small supply of the pituitary adrenocorticotropic hormone (ACTH), and this was also used successfully in treating rheumatoid arthritis, alone and in association with cortisone. Good results were also obtained in acute rheumatism, asthma, and the collagen diseases. The first report on the new treatment, by Hench, Kendall, Slocumb, and Polley, was presented on April 20, 1949. By the end of 1950 several thousand patients in many parts of the world had been successfully treated. In 1950 Reichstein shared with Kendall and Hench the Nobel Prize in Physiology or Medicine for their work in this field.
After 1950 Reichstein discovered many other cortical steroids, including aldosterone, a hormone that regulates the salt balance of the body. He also worked on plant glycosides, especially the aglycones of the digitalis and strophanthus groups. His published work was entirely in the form of scientific papers.
In 1947 Reichstein became an Honorary Doctor of the University of Paris, and in 1951 he was awarded the Cameron Prize of the University of Edinburgh. In 1952 he was elected a Foreign Member of the Royal Society, and in 1968 he was awarded its highest honor, the Copley Medal.
By the late 1960s Reichstein had been hard at work for 45 years and the time had come to slow down. He stepped down from his post at the University of Basel, but had no intention of being completely idle. He continued to work in his laboratory until 1987, when his ninetieth year began. Then, his name appeared in print just once more before he died in 1996. Along with 62 other Nobel laureates in 1992, he signed an appeal to the worlds' governments to end the fighting in Bosnia and Herzegovina.
Further Reading on Tadeus Reichstein
There was a biography of Reichstein in Nobel Lectures, Physiology or Medicine, 1942-1962 (1964), which also included his Nobel Lecture, as well as those of Kendall and Hench. For an account of the earlier work see R. D. H. Heard, The Hormones, vol. 1 (1948). For related aspects of the corticosteroids see A. White, P. Handler, and E. L. Smith, Principles of Biochemistry (3d ed. 1964). Also see New York Times August 6, 1996.