Nobel Award Reaffirms Kinship Of Chemistry and Medicine - C&EN

Nov 5, 2010 - THE key position of chemistry in present-day medicine has been amply demonstrated by the recent award of Nobel Prizes in Medicine. Three...
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General Education in Colleges and Universities That means that one cannot be concerned about elementary a n d secondary school science teaching without also being interested in what is going on at the college level. Naturally, there are a great many aspects of science teaching at the college level that might be of interest to any committee affiliated with the AAAS. The cooperative committee was particularly interested in the sprea_d of the college courses in general education, and by vote of a large majority of its members, undertook the sponsorship, in late 1948, of a study by R. A. Bullington of Northwestern Universitv of "The EPresent Status of Science Teaching in General Education in the Colleges and Universities. On the basis of information gathered from 720 different colleges and uni. versitiei Dr. Bullington concludes that ( ^ ) : General education science is rapidly occupying a position of importance in college curricula. It is growing in prevalence, popularity, and respectability. Ambitious young science teache-zrs can expect to look to this field for a carreer that will offer the same rewards a s a teaching career in one of the separate sciences. In this relatively new area of science teaching there is a tremendous challenge to teachers to perfect their -lechniques in presenting science to the nonscientist. On all sides the challenge is "being met by teachers who are improving old procedures and experimenting wi-ih new ones. From their efforts are coming methods that will be of value in all tyjpes of science courses. General education science is firmly established and widely accepted. W e can confidently expect that in the near future there will be an even greater- extension of the courses in American institutions of higher education. In this s-cientific age, we can look forward to an* increase of literacy in science that will benefit both the individual and societv and smooth the path for the progress of science. At the suggestion of the Cooperative Committee the American Comncil o n Education is now collaborating -with 18 colleges and universities in a n effort to evaluate the role of science in, and the contribution of science to, the general education course. Plans for the Future As has already been indicated t h e committee, in cooperation with the U. S. Office of Education, is starting work on the following projects. 1. Science in general education at all levels. 2. The early identification of talented youth and its proper encouiragement at precollege levels. 3. A reappraisal of earlier recommendations pertaining to the training of science and mathematics teachers. 4. Adult education in science and mathematics. Literature Cited 1. School Science and hJathematics, October 1942. p p . 6 3 6 - 5 0 . 2. Ibid., February 1943. p^>. 127-57. 3. Ibid., February 1946, prp. 107-18. 4. Bullington, R. A., Ph-D. Thesis, Northwestern University, 194£>.

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Nobel A w a r d Reaffirms Kinship Of Chemistry a n d Medicine Chemical researchers and medical men are joining forces and are making outstanding contributions to medicine . . .

X HE key position of chemistry in present-day medicine has been amply demonstrated by the recent award of Nobel Prizes in Medicine. Three times during the past four years, top medical honors have gone to members of the chemical profession. It was 1947 when American biochemists Gerty and Carl Cori received the Nobel Prize in Medicine for their study of the catalytic metabolism of glycogen. The following year, Paul Mueller, Swiss research chemist, was awarded the same distinction for his discovery of the insectkilling powers of D D T , vital weapon in the control of malaria and typhoid fever. Now in 1950, chemists have once again received international science's highest accolade. To Swiss chemist Tadeus Reichstein and to the Mayo Clinic team of biochemist Edward C. Kendall and physician Philip S. Hench goes the 1950 Nobel Prize in Medicine. The citation reads: "For their discoveries regarding the hormones of the adrenal cortex, their structure, and biological effect." As they receive their full-dress honors in Stockholm on Dec. 10, Drs. Reichstein, Kendall, and Hench may well look back across the years of scientific accomplishment that have earned for them this latest burst of world acclaim.

Reichstei:i spent many years in teaching organic and plnsiological chemistry in Zurich. In 1938 he was called to the University of Basel, where he assumed the chairmanship of the department of pharmacy and the pharmaceutical institute. Eight years later, he was appointed head of the organic division, a position which he maintains today. Even if Reichstein had never touched his hand to a test tube, he could still claim spectacular achievements. An avid mountain climber, he has scaled some of Switzerland's most treacherous peaks. In fact, several Alpine paths have already been named in his honor. Moreover, Reichstein is an accomplished skier, a devoted gardener (exotic African plants are a specialty), and a swimmer of no mean repute. Said one friend: "On a sultry summer's day, you're quite apt to find him, face upward, floating serenely dowD the Rhine." His stand-out biochemical achievements have extended across two decades. During those years, hundreds of technical papers have poured from his laboratory. Sugar chemistry alone has been the subject of over a hundred papers. Multitudes of bright young men, both foreign and Swiss, have flocked to his work bench to learn their science from a master. Commented Fragrant Research one observer: "Reichstein possesses that Like many another distinguished foreign rare, quasi-magic touch whose intervenscientist, Tadeus Reichstein is little known tion makes stubborn reactions g o and unto the general public in America. Born in willing liquids crystallize." In 1933, Reichstein developed a process Poland on July 20, 1897, Reichstein, together with his family, moved to Switzer- for synthesizing vitamin C from sorbitol, a procedure which today has wide commerland in 1906. Educated in Zurich, he received a bachelor degree in chemical engi- cial application. Later, during four whirlneering from the Eidgenossische Tech- wind years of intensive research, he and associates isolated and identified no less nische Hochschule, Swiss counterpart of MIT. In 1922, this degree was followed than 28 crystalline hormones from the by a doctorate in organic chemistry. adrenal cortex—among them cortisone. Reichstein's investigation of the adrenal Among his firsx. explorations was a study of the aromatic ingredients of roasted hormones fired his interest in cardiac glyeoEeey SL savory project which he completed cosides and aglycones, about which he has under Ruzicka in 1931. Many efforts had already written over 6 0 papers. previously been made by others to perLast year Reichstein organized a Swiss fect a soluble coffee extract. However, no mission to Africa in search of plants which great strides were noted until Reichstein might supply starting materials for horbrought out his process which today is the mone synthesis. For instance, it had prebasis for the manufacture of Nescafe. viously been found that the seeds of a

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unique species of Strophanihus contained sarmentocymarin, which would conveniently permit the bypassing of numerous steps in the manufacture of cortisone. It had originally been thought that the seeds of Strophanihus sarmcntosus (one of the more common species) had been those which yielded significant quantities of the potential cortisone raw material. This deduction has since been proved false. A team of scientists organized b y Reichstein is still in Africa hunting for the right species of Stroplianthus. Today Reichstein is focusing much of his attention on cortisone, in continuation of his studies which over the past 16 years have cut a wide swath across hormone chemistry. Independent Discoveries Paralleling the investigations of Swiss chemist Reichstein have been the closely related hormone studies of American biochemist Edward C. KendalL (For biographical sketch of Dr. Kendall, see C&EN, June 19, page 2 0 7 8 ) . This similarity of interests was never more evident than in 1936, when both Reichstein and Kendall, quite independendy, announced the isolation of 17-hydroxy-ll-dehydrocorticosterone—also variously known as Kendall's compound E, Reichstein** substance F „ and cortisone. Among Kendall's earliest pioneer efforts was his search for the active principle of the thyroid gland. Months o f research at the Mayo Clinic had gone by without success. Then one day Kendall was finally able to isolate pure, crystalline thyroxin. The date: Christmas 1914! The administering of thyroxin has since restored to well being thousands of patients suffering from faulty metabolismSeveral years later, Kendall trained his sights o n the hormones of the adrenal cortex. Between 1934 and 1936. he succeeded in isolating eight adrenal hormones—compounds A through H—all of which were identified by 1938. KendalL to his everlasting credit, foresaw the potential therapeutic value of these hormones and made them available for clinical test. Of the numerous adrenal hormones isolated in the laboratories of Reichstein and Kendall, only four—referred t o by Kendall as compounds A, B. E, and F—showed significant physiological activity. In the early days of the investigation, the available amounts of these four hormones was so pitifully small that analysis of theneffects upon two-legged creatures was out of the question. From a half ton of beef adrenal glands could be obtained ju>t enough compound A equivalent t o one tiny tablet. Kendall and coworkers were obliged to process 150 tons of beef adrenals over a period of months before they could recover a meager total of 5 0 to 6 0 grams of crystalline compound E. Obviously, all thi< was no great shakes as a streamlined production technique. For many years, there seemed only the slimmest chance that adrenal hormone therapy would have anything more than the most limited medical usefulness. Little enthusiasm could b e whipped u p for pro4170

ducing commercially enough adrenal hormones for clinical study. Then came World War II and with it the electrifying, though utterly unfounded, rumor that Luftwaffe pilots, drugged with adrenal extracts, were flying at staggering altitudes with little or no discomfort. Suddenly, U. S. research on adrenal hormones got the booster shot it needed. Perhaps these hormones might be effective in aviation medicine and in the treatment of shock and battle fatigue- In 1941, the National Research Council gave highest priority on its war agenda to adrenal cortical hormones. followed in order of importance by penicillin and antimalarials. The Big Gamble By agreement, American chemical and industrial forces concentrated their efforts on devising a synthesis of compound A. Nut only did the process have to yield compound A but it had t o lend itself to large scale production. That synthesis was accomplished in Kendall's laboratory in 1944, and a sizable sample was prepared by Merck & Co., Inc., in 1945. Compound A might work wonders, the researchers thought, in the treatment of Addison's disease, a rare affliction associated with the degeneration of the adrenal cortex. Tested on patients, the hormone, despite the best expectations, proved almost a complete failure. The fortunes of adrenal hormone therapy sank to an all-time low. In the face of discouragement, the investigators switched their campaign to the synthesis of compound E. It was a n immense gamble—in funds, in time, in technical manpower. No one really knew whether compound E in clinical trials might flop with the same resounding thud as compound A. In 1946, after more than two years of research, Lewis H. Sarett of Merck & Co., Inc., succeeded in synthesizing a few milligrams of compound E. Yields w e r e scanty, at best. About one ten-thousandth of the starting material ended up as cortisone. However, within the next 18 months, radical technical improvements, devised with the aid of Merck's Jacob van d e Kamp, permitted nearly a hundredfold increase in yield. Encouragingly, cortisone made a satisfactory showing in the treatment of Addison's disease. Strange Bodily Agent One day back in 1941. Edward Kendall and Philip Hench. who for many years had been a specialist in rheumatic diseases, conceived the idea that possibly cortisone might be effective in the treatment of rheumatoid arthritis. Hench got his first inkling of the transforming power of some unknown bodily agent and the potential reversibility of arthritis when in the early 1930*s he noted that, in 30 cases out of 34, women were relieved of the pain and symptoms of arthritis during pregnancy. A similar fading of arthritis resulted from postoperative shock and particularly if a patient developed Jaundice. Hench deduced that the abnormal output of a hormone was responsible for the temporary alleviation of arthritis's crippling agony. C H E M I C A L

Finally in 1948 there was enough cortisone on hand to put the Hypothesis to test. O n Sept. 2 1 , 1948, C. H . Slocamb of the Mayo Clinic, under the direction o f Kendall and Hench, injected a 100-mg. intramuscular dose of cortisone into a patient suffering pathetically from rheumatoid arthritis. Daily treatment was continued. In this the first real test of cortisone's potency, the beneficial effects were phenomenal. Within a week, the patient not o n l y was u p and around but gamely ventured a shopping trip to downtown Rochester . In the following months, cortisone ( a word, incidentally, coined b y Kendall and Hench) also aided in t h e treatment of rheumatic fever, leukemia, asthma, severe burns, and various eye inflammations. In the meantime, another hormone w a s likewise making a medical splash for t h e very same reasons. It w a s A C T H , which originates in the pituitary a n d is capable of rousing the adrenal cortex t o secrete cortisone or a similar steroid. However, neither doses of cortisone nor doses of ACTH permanently cured rheumatic diseases. Once the use of these hormones was terminated, back came the same old symptoms. As one medical m a n commented: "After all, no one expects t o b e cured forever of diabetes merely because h e takes one shot of insulin." Quest for Simplicity Chief problems facing cortisone researchers are the hormone's limited availability and high cost. T h e complexity of cortisone manufacture is another formidable stumbling block. N o less than 37 separate chemical reactions were required to produce the first cortisone used in the treatment of rheumatoid arthritis- Moreover, the synthesis—which was pieced together from the various reactions cleverly concocted both in the U n i t e d States and in Europe—suffered from t h e inherent weakness that it depended u p o n rare, expensive osmium tetroxide. In M a y this year, h o w ever, Kendall announced a major forward step in the simplification of the cortisone process. The n e w synthesis requires no osmium tetroxide (C&EN", June 19, page 2074). Over the years many other American scientists have contributed to t h e simplification of the cortisone process, among them T. F. Gallagher of t h e SloanKettering Institute, Percy L. Julian of the Glidden Co., and the research teams at Merck & Co., Inc. As a result of innumerable discoveries, Merck is now able to turn out thousands of grams of cortisone a month, whereas two years ago t h e supply was less than a fistful. Besides illuminating vast areas of hormone chemistry, Reichstein, Kendall, and Hench have taught a lesson. T h e y have taught that where interests overlap maxim u m progress i o chemistry and medicine demands maximum teamwork. More than that, their researches, b y placing new weapons of healing i n the hands of t h e medical profession, have illustrated the essential role of chemistry in t h e unrelenting fight against disease. AND

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