AMERICA'S NOBEL LAUREATES IN MEDICINE, PHYSIOLOGY AND CHEMISTRY In celebration of the Sesquicentennial of the National Library of Medicine — second edition AMERICA'S NOBEL LAUREATES IN MEDICINE, PHYSIOLOGY AND CHEMISTRY "A Tribute to America's Living Nobel Prize Winners' By Larry Thompson With Support From The Friends of the National Library of Medicine The National Center for Health Education Second Edition Summer 1988 INTRODUCTION In 1986, the National Library of Medicine celebrated the 150th anniversary of its founding. As part of the Sesquicentennial activities, a Tribute Dinner was held to honor America's Hving Nobel laureates in medicine, physiology, and chemistry, and a journal was published documenting their contributions. Given the strong interest the first edition of the Nobel Laureate Journal generated, the Friends of the NLM, the National Center for Health Education, and the National Library of Medicine decided to publish an updated version. Time constraints prevented the first edition from including the biographies of the Nobel laureates who were not able to attend the Tribute Dinner. This edition is intended to be a comprehensive survey of America's living Nobel laureates in medicine, physiology, and chemistry. It is hoped that this publication wUl provide a useful overview of these Americans' great scientific accompHshments. In addition, we hope the vital link between great breakthroughs in science and access to the world's best medical information is clearly documented. THE FRIENDS OF THE NATIONAL LIBRARY OF MEDICINE Edwin C. Whitehead Chairman Paul G. Rogers Vice Chairman Thomas E. Bryant, M.D., J.D. President WiUiam J. Haney Treasurer Keith R. Krueger Executive Director David Baltimore, M.D. WUliam B. Bean, M.D. Paul Berg, Ph.D. Prof. Sune Bergstrom Francis Bonner, Jr., M.D. L. Thompson Bowles, M.D. Edward N. Brandt, Jr., M.D. Thomas E. Bryant, M.D., J.D. Holly Shipp Buchanan Joseph A. Califano, Jr. John J. Creedon Martin M. Cummings, M.D. Nicholas E. Davies, M.D. Lois DeBakey, Ph.D. Michael E. DeBakey, M.D. Roger Egeberg, M.D. Alice Fordyce Donald S. Fredrickson, M.D. Hanno Fuchs Eugene Gardner George Goldstein, M.D. Gary L. Hammon William J. Haney Antoinette Hatfield Peatsy Hollings William Hubbard, M.D. Donald Kennedy, Ph.D George Kozmetsky, D.C.S. Mary Lasker LaSalle D. Leffall, Jr., M.D. Terry L. Lierman Salvador E. Luria, M.D. Florence Mahoney Margaret E. Mahoney Phillip Manning, M.D. Robert Q. Marston, M.D. Carol M. McCarthy, Ph.D., J.D. Peggy L. McFadden, CRNA, B.S John McGovern, M.D. Gerald J. Mossinghoff Emily Norton, R.N. Robert G. Petersdorf, M.D. John H. Pinto Calvin Plimpton, M.D. Frank Press, Ph.D Barbara Redman, Ph.D., FAAN, R.N. Julius B. Richmond, M.D. Frederick Robbins, M.D. Paul G. Rogers, J.D. James Sammons, M.D. Frank E. Samuel, Jr. David Satcher, M.D. Benno C. Schmidt Carl J. Schramm, Ph.D., J.D. Morris M. Sender James H. Shannon, M.D. Cecil G. Sheps, M.D. John F. Sherman, M.D. Stephen P. Strickland, Ph.D. Louis W. Sullivan, M.D. Samuel O. Thier, M.D. Bernard R. Tresnowski Monroe E. Trout, M.D., J.D. P. Roy Vagelos, M.D. Henry Wendt III Edwin C. Whitehead Rosalind C. Whitehead Patricia Woolf, Ph.D. THE NATIONAL LIBRARY OF MEDICINE: THE WORLD'S LINK TO HEALTH From a few shelves of books to the world's largest medical library — this is the amazing story of the National Library of Medicine (NLM). In 1836, when those first shelves were officially designated as the Library of the Army Surgeon General's Office, no one would have imagined that over 150 years later this tiny nucleus would have grown to more than 3.5 million books and thousands of journals, reports, and pictures — aU available to the world's dedicated physicians and scientists, who use this information to help everyone attain the birthright of good health. It was just such a dedicated physician who made the National Library of Medicine the treasure it is today. Dr. John Shaw BiUings, a CivU War surgeon, was the guiding spirit who put the library on its path to greatness by becoming its director in 1865. Its growth began almost immediately and, in 1866, he found more space for the coUection in Ford's Theatre in Washington, the site of Lincoln's assassination. Medical and scientific knowledge was burgeoning at the time, and Billings was devoted to acquiring all that was significant in the heahng arts. As a result, the collection grew with great speed. It was the dawn of a new scientific age in medicine, and researchers were making discoveries constantly. Reports of their findings were arriving daily at the Hbrary, where they were not only cataloged and shelved, but shared with anyone who was interested — a tradition that is more alive today than ever. Expanding so quickly, the Hbrary soon outgrew its cramped quarters in the theatre. With great foresight, BUlings had been active not only as a librarian, but also as a persuasive spokesman for medical information services. Through skiUful presentations, he was able to convince the Congress and the President that the library must grow to fulfill its mission as the nation's principal source of medical knowledge. As a result of his efforts, the Hbrary moved in 1887 into its own headquarters on the mall in downtown Washington. Under his guidance, its collection and influence grew dramatically, and its international reputation as the world's most comprehensive coUection of medical information began to build. Billings's thirty-year stewardship of the library has left a lasting monument, not just in bricks and mortar or books and paper, but in the ever-growing improvement in the nation's health. After BiUings, the Hbrary continued to expand its holdings and services. In 1956, an Act of Congress transferred the governance of the collection from the Department of Defense to the Department of Health, Education and Welfare (now the Department of Health and Human Services). At the same time it gave the collection (by then known as the .Armed Forces Medical Library) a new name reflecting its scope: the National Library of Medicine. Keeping pace with the enormous flow of new medical information, the library in 1962 once again moved into a new and much larger building, this time on the National Institutes of Health campus in Bethesda, Maryland. In 1968 it formally became part of NIH. FinaUy, to accommodate the latest computer equipment for information storage and retrieval, a second building, the Lister Hill Center, was opened in Bethesda in 1980. The National Library of Medicine Today Today, with materials in seventy languages and the capability to exchange information internationally, the National Library of Medicine is a worldwide link among all health professionals. In the United States, NLM is the hub of the national network of 7 regional medical Hbraries, 125 resource libraries at medical schools and 4,000 local medical Hbraries placed strategically in every area of the country. Most physicians and scientists are only minutes away from one of these network libraries, permitting ready access to the riches of the world's medical Hterature. The computer revolution is bringing that literature even closer to the nation's practicing physicians. From their own offices, doctors can use MEDLINE, NLM's computer database of over five miUion references to journal articles. Searches that used to take days are completed in minutes. MEDLINE, growing at a rate of 300,000 entries a year, allows individuals not only to caU up a Hst of pertinent articles, but also to print abstracts for many of those articles at their own terminals. Already MEDLINE is available at 5,000 institutions, including universities, medical schools, hospitals, government agencies, and businesses. Now more and more individual health professionals are discovering that using MEDLINE in their offices gives them immediate access to the vital information they need to fight their patients' iUnesses and bring them back more quickly to healthy, productive lives. Every day more health professionals are finding MEDLINE and NLM to be indispensable to their practice. In the Future at the National Library of Medicine The future of medical communication and education is taking shape now at the National Library of Medicine. Specifically, NLM's Lister HU1 National Center for Biomedical Communications is at the forefront of applications of the latest technology to the ancient art of medicine. The center played a lead role in developing MEDLINE in the late sixties, and since then it has conducted a number of valuable communications experiments using NASA satellites, microwave and cable television, and computer-assisted instruction. Currently the Lister HiU Center is investigating the exciting potential of microcomputer, optical videodisc, and voice-recognition technologies to develop truly interactive medical education programs. In addition, artificial intelligence techniques are being applied to the development of "expert systems" that will assist health practitioners in treating systems. The National Library of Medicine: Communication is the Goal From a few books on a shelf to the most sophisticated computer technology, NLM's story is one of amazing growth and development. Throughout its history, however, its goal has remained the same: to be ready to communicate as quickly as possible all the biomedical information available wherever it is needed. As the National Library of Medicine begins the next 150 years, we look forward to communication breakthroughs that are now almost impossible to imagine. And, it is a certainty that the NLM will continue in the vanguard of the information revolution. fM THE NOBEL PRIZES, 1901-1986 It may seem ironic that Alfred Bernhard Nobel, a chemist and industrialist specializing in the production of explosives and inventions of warfare, established a prize to be awarded to those who "conferred the greatest benefit on mankind." Yet to those who knew him well, this was not surprising. Even while experimenting with the most powerful explosives, his ambition was to insure their safe use. Nobel devoted years to discovering a way to use the explosive power of nitroglycerin in a safer and more stable form. Perhaps his dedication derived partly from the tragic loss of his brother in an explosion at their father's research laboratory. Whatever the reason, Alfred Nobel left an enduring legacy the world will always value. Today, the Nobel Prize is the most prestigious and coveted award in the world. The elaborate process for selecting its laureates, as described in Nobel's wiU, along with its history of outstanding recipients in all categories, has estabhshed the Nobel Prize as the highest international award. Nobel was bom in Stockholm in 1833. In 1842, his father, also a technician and inventor, moved his famUy to St. Petersburg, where he manufactured submarine mines and torpedoes, of his own design, for the Russian government. As a young man, Alfred became active in his father's business and traveled widely in Europe and America. Returning to Sweden in 1859, he experimented with the production of nitroglycerin in his father's laboratory. It was there in 1866 that he invented dynamite, an explosive made of nitroglycerin absorbed in a porous material. Thus, for the first time, the explosive power of nitroglycerin was available in a stable form. He formed a company and established plants and offices around the world, making it one of the early multinational corporations. After he died in 1896, most of his fortune, valued then at $8,311,000, went to establish a fund for the Nobel Prizes. Interest from the fund was to be distributed annually "in the form of prizes to those who have . . . conferred the greatest benefit on mankind." Further, the interest was to be divided into five equal portions to be awarded to persons who had made the most important contributions in physics, chemistry, medicine or physiology, and literature, and to the one who had done the most or the best work for fostering fraternity among nations, for the abolition of standing armies, and for the holding and promotion of peace conferences. Nobel stipulated that the prizes for physics and chemistry be awarded by the Swedish Academy of Sciences, for physiology or medicine by the Karolinska Institute in Stockholm, for literature by the Swedish Academy, and for peace by a five-member committee, elected by the Norwegian Storting (Parliament). No consideration was to be given to the nationality of the candidates. The first prizes were awarded in 1901. In 1968, the Riksbank, the central bank of Sweden, created the Nobel Prize in economics to commemorate the bank's 300th anniversary. The bank provides the same amount of money allotted for the other prizes, and the Swedish Royal Academy of Science selects the winner(s). AU the prizes are presented on December 10th, the annversary of Nobel's death, in Stockholm, except for the peace prize, which is given in Oslo. The cash prize is accompanied by a diploma and a gold medal, and each laureate gives a lecture on the work for which the prize was awarded. These lectures are published annually by the Nobel Foundation in Les Prix Nobel. AMERICA'S NOBEL LAUREATES IN MEDICINE, PHYSIOLOGY AND CHEMISTRY 1934 Physiology or Medicine A f m lthough it still E ^k kills, pernicious JtLm JELm anemia no long- er captures the public mind as does cancer or acquired immune defi- ciency syndrome (AIDS). Yet, since it was first described in 1849, per- nicious anemia was a mysterious and lethal disease. With the help of the late Dr. George R. Minot, with whom he shared the Nobel Prize, Dr. Mur- phy helped introduce "the era of liver therapy," in which liver ex- tracts were injected into the mus- cle of patients with pernicious anemia in an effort to restore nor- mal red blood cell levels. Although the treatment worked dramatically well — "We have been allowed the thrill of watching the patient through a few days of depression following the institu- tion of liver therapy until remis- sion occurs with its often sudden and almost unbelievable sense of well-being simultaneously with the maximum increase of the re- ticulocytes or new red blood cells," Dr. Murphy said in his No- bel address — there still were problems. "The problem ... has been the practical one of making treatment more bearable for the victim of pernicious anemia, who must necessarily continue treat- ment indefinitely in order to main- tain a satisfactory state of health." Even then, there were issues of efficiency and cost control. Dr. Murphy concluded his re- markably short Nobel lecture with "a motion picture which wUl illus- trate many points more clearly than I could discuss them here." In 1934, that must have been a daz- zHng display. Born in Stoughton, Wisconsin, in 1892, Dr. Murphy received his A.B. from the University of Oregon in 1914 and his M.D. from Harvard Medical School in 1920. He remained affiliated with Har- vard's Peter Bent Brigham Hospi- tal for most of his professional life, retiring as emeritus professor in 1958. Chemistry very introductory E chemistry class- .maa^HaHaH room in America has a periodic table of the elements on a wall somewhere, it is chemis- try's touchstone. The table's bot- tom row contains elements that do not occur in nature — the so- called transuranium elements. These elements are man-made, created in the blinding, high-ener- gy collisions of uranium, plu- tonium, and other heavy nuclei with accelerated particles, the ions of low atomic number elements such as carbon, nitrogen, and oxy- gen, among others. Dr. Seaborg, working with Dr. Edward O. Lawrence and others at the accelerators on the hUl behind the University of California at Berkeley campus, played a role in creating 10 and naming 9 of the 13 transuranium elements, those car- rying the atomic numbers 94 to 102 — including plutonium (94), americium (95), curium (96), berkehum (97), cahfornium (98), einsteinium (99), fermium (100), mendelevium (101), nobelium (102), and element 106. Born in Ishpeming, Michigan, in 1912, Dr. Seaborg received his A.B. in chemistry from the Uni- versity of CaUfornia at Los An- geles in 1934. He received his Ph.D. in chemistry in 1937 from the University of California at Berkeley, where he has served as a faculty member since that time. Rising through the academic ranks at Berkeley, he served as Chancel- lor from 1958 to 1961. Twice Dr. Seaborg received a leave of ab- sence from California: once during World War II when he was in charge of plutonium chemistry for the Manhattan Project at the Uni- versity of Chicago's MetaUurgical Laboratory, and again when he served as chairman of the Atomic Energy Commission (appointed by Presidents Kennedy, Johnson, and Nixon) from 1961 to 1971. He continues his work at the Univer- sity of California as university pro- fessor of chemistry, as associate director of the Lawrence Berkeley Laboratory, and as chairman of the Lawrence Hall of Science. Chemistry 1962 Peace Linus C. Pauling was born in Portland, Oregon, in 1901. He received his bachelor's degree in 1922 from Oregon State CoUege and his Ph.D. degree in chemistry in 1925 from the California In- stitute of Technology. Dr. PauHng is the only man to win two Nobel Prizes in different categories: He was awarded the Nobel Prize in Chemistry for 1954 and the Nobel Peace Prize for 1962. Dr. Pauling has always been a man of science. He spent most of his professional Hfe studying the nature of the chemical bonds that hold atoms together. His experimental work included x-ray diffraction of crystallized proteins to study their structure, insights into the molecular basis of general anesthesia, and the role of abnormal molecules in causing disease—such as the deformed he- moglobin molecule in sickle ceU anemia. His chemical studies in- cluded an extension of the valence theory of atomic bonds to include metals and intermetallic com- pounds, theoretical work on the structure of atomic nuclei and in- sights into the process of nuclear fission. Dr. Pauling has received many other awards in the fields of chem- istry, mineralogy, biology, medi- cine, and peace. He has published over 600 scientific papers, about 200 articles on social and political questions, and many books, one of which (The Nature of the Chemi- cal Bond) is one of the most cited scientific books of the twentieth century. He is the founder of and a research professor at the Linus Pauling Institute of Science and Medicine in Palo Alto, California. Frederick C. Robbins 1954 Physiology or Medicine T he collaboration between Dr. Rob- .*.t^^a bins and his co-lau- reates, Drs. John F. Enders and Thomas H. WeUer, proved to be an unusually productive one. In Janu- ary 1948, following completion of his pediatric training, Dr. Robbins joined the Research Division of infectious Diseases that had been estabHshed by Dr. Enders about a year previously at Boston's ChU- dren's Hospital. Dr. WeUer, a med- ical school classmate and former roommate, was already in the labo- ratory. A major interest of the group was the growth of viruses in tissue culture. Although poliomyelitis was originally not their principal inter- est, they did conduct experiments with poliovirus and discovered that it could be grown in cultures of nonnervous cells. They then de- veloped methods for assaying the growth of the virus in culture. These findings made it possible to develop vaccines and to use tissue culture methods as substitutes for animals. This latter finding was particularly important as up until this time the only universally sus- ceptible experimental animal had been monkeys. The techniques they developed for studying pol- iovirus proved to be useful in the study of a variety of other viral diseases (e.g., measles, German measles, and mumps), and the de- velopment of vaccines for their control. The growth of the poliovirus in nonnervous tissue helped to estab- lish, contrary to the belief of some, that poliomyelitis was primarily an infection of the intestinal tract, with only an occasional invasion of the bloodstream and secondary infection of the nervous system. Born in Auburn, Alabama, in 1916, Dr. Robbins received a B.A. in 1936 and an M.S. in 1938 from the University of Missouri, at Co- lumbia. In 1940, he received his M.D. from Harvard University. He then served four years in the U.S. Army in charge of a virus and rickettsial diseases laboratory. For two years he was stationed in Italy, where he supervised a study that established that the rickettsia of Q Fever was the cause of epidemics of febrile disease and pneumonia in American troops in Italy. This was the first time Q Fever had been recognized in this part of the world. After his military service, Dr. Robbins worked at Children's Hospital in Boston and at Harvard University before finally settling in 1952 at Case Western Reserve University School of Medicine as a professor of pediatrics and the director of the Department of Pedi- atrics and Contagious Diseases at the Cleveland City Hospital (now Metropolitan General Hospital). He also served as dean of the School of Medicine at Case West- ern Reserve from 1966 through 1980 and as president of the In- stitute of Medicine of the National Academy of Sciences from 1980 through 1985. Dr. Robbins is now university professor emeritus and dean emeritus of the School of Medicine at Case Western Reserve University. 1954 Physiology or Medicine p oho had been a terr- ible scourge. Pools wJE^m closed; parents kept their children out of crowds. Then the cause, a threesome of closely related viruses, was discovered. Dr. WeUer and his colleagues, Drs. John Enders and Frederick Rob- bins, successfully cultivated the poUo virus when they learned to "substitute the test tube for the monkey." That allowed them, for the first time, to grow large amounts of the virus in tissue cul- tures. This breakthrough helped lead to the development of a suc- cessful polio vaccine. In addition to working on polio, Dr. Weller developed ways to grow other viruses in tissue cul- tures. These techniques led to the isolation of important new viruses, including rubella, which causes German measles and the varicella- zoster virus, which causes chicken pox and shingles. As a pediatrician specializing in infectious diseases, Dr. Weller also showed that viral infections can be transmitted from a pregnant moth- er to her fetus. An important exam- ple of new agents he isolated and named are the cytomegaloviruses. He showed that these new viruses, such as the rubella virus, are im- portant causes of intrauterine fetal damage. As director of the Center for the Prevention of Infectious Diseases at the Harvard School of PubUc Health from 1966 to 1981, Dr. Weller carried out important stud- ies on Schistosoma mansoni, the cause of schistosomiasis, a serious and widespread tropical parasitic disease. Born in 1915, Dr. Weller re- ceived his B.S. in 1936 from the University of Michigan (where his father was professor of pathology) and his M.S. in 1937; he received his M.D. from Harvard in 1940. Except for his service in the Army Medical Corps from 1942 to 1945 (where he rose from first lieutenant to major), Dr. Weller has been with Harvard throughout his career. Previously Richard Pearson Strong Professor of Tropical Pub- lic Health he was named professor emeritus in 1985. George W. Beadle 1958 Physiology or Medicine TJ is tools were classic: fruit ..^L. JKLm flies, the red bread mold Neurospora crassa, and maize. With them, he helped lay the foundation for the field of chemical genetics by showing convincingly that each individual gene produces one specific pro- tein — though the theory initiaUy was described as "one gene-one enzyme." Dr. Beadle and his partner Ed- ward L. Tatum, both then at Stan- ford University, made mutants of Neurospora with radiation — which was known to change the gene's DNA — and grew the al- tered mold in a richly supple- mented growth media. They then searched for mutants that could not survive without supplemented me- dia and quickly found dozens, in- cluding mutant 299, which required vitamin B6 to grow, and mutant 1085, which required thiamine-vitamin Bl. The mutants arose because the radiation changed a single gene that pro- duced an individual enzyme that performed some essential function needed for survival, such as the synthesis or processing of vi- tamins. The work was further refined as it became clear that some proteins have more than one unique string of amino acids, or a polypeptide. Some proteins, such as hemo- globin, contain two different poly- peptide chains to make the mature protein, with two genes encoding the directions for the different polypeptides. Born in Wahoo, Nebraska, in 1903, Dr. Beadle received his B.S. in 1926 and his M.S. in 1927 from the University of Nebraska. Cor- nell University awarded him a Ph.D. in 1931. Altogether, he spent 20 years at the California Institute of Technology during two dif- ferent stays, and 9 years at Stan- ford University and several other institutions before settling at the University of Chicago in 1961, where he was president of the uni- versity until 1968. Dr. Beadle now lives in Pomona, California. Joshua Lederberg 1958 Physiology or Medicine or the past 40 years, bacteria have «A. provided the model system for study in molecular ge- netics. In 1946, Dr. Lederberg dis- covered that a form of sexual reproduction occurs in these mi- croorganisms, demonstrating that they possess a genetic mechanism similar to that of humans. Com- bine this with their simple struc- ture and rapid growth cycles, and one has a superb system on which to base a study of genetic develop- ment. Dr. Lederberg was born in Montclair, New Jersey, in 1925. He earned his Bachelor's degree at Columbia University, and attended its College of Physicians and Sur- geons for two years, but then took sabbatical leave to work at Yale with Dr. Edward J. Tatum, a pi- oneer in bacterial genetics. Never returning to medical school, he re- ceived his Ph.D. from Yale in 1947. Dr. Lederberg was professor of genetics at the University of Wisconsin from 1947 to 1959. In 1952, he and Norton Zinder dem- onstrated that bacterial genetic in- formation is also passed when bits of chromosomic material are in- corporated into viruses that infect other bacterial cells. Other studies revealed a number of other genetic particles in bacteria that have be- come instrumental in recombinant DNA research, and substantiated how to think about bacteria in ge- netic terms. He received the Nobel Prize for this work in 1958, along with Dr. Tatum and Dr. George Beadle. In 1959, Dr. Lederberg moved to Stanford University Medical School, where he became chair- man of the Department of Genet- ics. At Stanford, he collaborated with E. A. Feigenbaum in artificial intelligence, pioneering the de- velopment of "expert systems." In 1978, he was appointed to the pres- idency of the Rockefeller Univer- sity, the post he holds today. Dr. Lederberg was active in planning the Mariner and Viking missions to Mars, and has served as a consultant to the Arms Control Disarmament Agency and to the World Health Organization. In ad- dition, he has written a weekly syndicated column for The Wash- ington Post on the social impact of scientific progress. Dr. Lederberg is science's answer to the oft-re- peated criticism that scientists have narrow interests. 1959 Physiology or Medicine In 1953, the fundamental structure of deoxy- ribonucleic acid (DNA) was described for the first time, but its twisted ladder shape told little about how it directed the produc- tion of proteins or how it was faithfully reproduced to pass ge- netic instructions from one ceUular generation to the next. Dr. Romberg worked on the lat- ter problem, and discovered the synthetic pathways by which the activated subunits of DNA — the four types of nucleic acid, or nu- cleotides — are produced. His work also led to the discovery of some of the enzymes that unzip the two halves of the DNA ladder and then align activated nucleotides along each half in a complemen- tary way. This enzyme-controlled aligning produces two identical copies of the original piece of DNA. Although his main research continues to focus on biochemical questions, Dr. Romberg also has worked on reactions in the Krebs cycle that converts food into a form of stored energy that can be used in chemical reactions and phospholipid synthesis. Bom in Brooklyn, New York, in 1918, Dr. Romberg received his B.S. from the City College of New York in 1937 and his M.D. from the University of Rochester in 1941. The following year, he moved to the National Institutes of Health and began studying rat nutrition. In 1946, he studied enzymology with Dr. Severo Ochoa, with whom he shared the Nobel Prize. In 1953, Dr. Romberg moved to Washington University School of Medicine in St. Louis as chairman of the Department of Microbiol- ogy, to begin the work for which he is best known. In 1959, he became professor and chairman of the De- partment of Biochemistry at Stan- ford University. Physiology or Medicine F nzymes are the key E to all biological ac- ata^HaHmnH tions, to the chem- istry of life itself. Dr. Ochoa spent much of his research career work- ing on enzymatic mechanisms, providing insights into biological oxidation, synthesis and energy transfer, and contributing to the understanding of the basic steps in carbohydrate and fatty acid metab- olism, carbon dioxide utilization and nucleic acid biosynthesis. Dr. Ochoa received his Nobel for purifying in 1955 and working out the chemistry of poly- nucleotide phosphorlase, an en- zyme that can produce chains of RNA without the need of a DNA template. The enzyme proved crit- ical in working out, in the begin- ning of the 1960's, how DNA carried the instructions of heredity. His familiarity with this enzyme made Dr. Ochoa a key competitior in the race to decipher the genetic code, a race ultimately won by Nobel laureate Dr. Marshall Niren- berg. Other work by Dr. Ochoa in- cluded research into the function of vitamin Bl oxidative phos- phorylation, reductive carboxyla- tion of ketoglutaric and pyruvic acid, photochemical reduction of pyridine nucleotides in photo- synthesis, and condensing en- zyme, a key enzyme in the Rrebs citric acid cycle. Born in Luarca, Spain, in 1905, Dr. Ochoa received his B.S. from Malaga College in 1921. He re- ceived his M.D. from the Univer- sity of Madrid Medical School in 1929. He spent much of his for- mative years under the influence and guidance of other Nobel win- ners, including Dr. Santiago Ramon y Cajal and Dr. Otto Meyerhoff. He had an internation- al scientific career, including stops at the Raiser Wilhelm Institut fur Biologie in Berlin-Dahlem: the National Institute for Medical Re- search in Hampstead London: Ox- ford University: and the University of Madrid. He came to the United States in 1940, working first at the Washington University School of Medicine in St. Louis — with Drs. Carl and Gery Cori, who also won a Nobel prize —and then at New York University College of Medicine in 1942. He became an American citizen in 1956. Dr. Ochoa now lives in Madrid. Chemistry T he quiet green of a forest glen belies J^. the frenetic activity within every leaf as they use the energy of sunlight to drive a cas- cade of chemical reactions that — adding together the activity of all the plants in the world each year — convert an estimated 150 billion tons of carbon from carbon dioxide in the air and about 25 billion tons of hydrogen from wa- ter into 400 billion tons of oxygen and enough energy to maintain an- imal life and provide the fossil fuels that propel nearly every hu- man enterprise. This process of photosynthesis is believed to be at least 30 percent efficient and, in some circum- stances, approaching 100 percent efficient. But the chemistry in- volved is hideously complicated. From 1845, when it was first dis- covered, until the 1930s, all scien- tists knew about photosynthesis was that carbon dioxide and water went in and oxygen came out. Dr. Calvin, however, using radioactive elements to label and trace organic molecules, began to unravel the process. In the 1940s, when radi- oactive carbon became available, he finally was able to decipher the central, critical steps and show that when sunlight strikes chlorophyll, the plant's green pigment splits water into hydrogen and oxygen; hydrogen enters into synthetic re- actions with carbon that lead to energy being stored in the form of sugar; oxygen, in this case, is a waste product. The identification of the various pathways in the pho- tosynthetic carbon reduction cycle took approximately eleven years, from 1947 to 1958. Born in St. Paul, Minnesota, in 1911, Dr. Calvin received his B.S. in chemistry from Michigan Col- lege of Mining & Technology. He received his Ph.D. in chemistry from the University of Minnesota in 1935. After postdoctoral work at the University of Manchester in England, Dr. Calvin began his teaching and research career in the departments of Chemistry and Molecular Biology at the Univer- sity of California at Berkeley, where he was the director of sever- al laboratories, associate director of the Lawrence Berkeley Labora- tory and, since 1971, has been uni- versity professor of chemistry. 1962 Physiology or Medicine Like many of the great advances in science, the discov- ery of the structure of the genes depended on chance, the personal chemistry between researchers, and the work of many other col- leagues who produced supporting information. In 1951, Dr. Watson had moved to Cambridge University in En- gland to continue his postdoctoral work when he met Dr. Francis H.C. Crick and Dr. Maurice H.F. Wilkins. Watson had become con- vinced that gene replication could only be understood when the struc- ture of deoxyribonucleic acid, the chemical that makes up genes, was known. Working with x-ray diffraction data on crystals of DNA produced by Dr. Rosalind Franklin, the team HteraUy cut out cardboard models of DNA's subunits, and put them together in different ways until they came up with a model that fit the diffraction data. Their model was a double heUx with pairs of nucleotide subunits turned inward like the rungs on a twisted ladder. In a single-page paper published in Nature magazine, Drs. Watson and Crick literally changed the face of biology. The discovery of DNA's structure led to the un- ravelling of many fundamental questions in biology, such as how DNA controlled the production of proteins and how DNA itself was replicated. Bom in Chicago in 1928, Dr. Watson received a B.S. in zoology in 1947 from the University of Chi- cago. He received his Ph.D. from the University of Indiana in 1950 after working on the effects of x-rays on the multiplication of bacterial viruses. He worked at Cambridge University from 1951 to 1953, and then spent two years at the California Institute of Technol- ogy. From 1955 to 1976, he was a professor at Harvard University. Since 1968, Dr. Watson has been director of the Cold Spring Harbor Laboratory on Long Island. Physiology or Medicine Understanding how the body makes and uses fatty acids and cholesterol has had a profound impact on the treatment and prevention of major disorders, especially heart disease. Dr. Bloch and his fellow Nobel laureate, Feodor Lynen, were the first to elucidate the fundamental mecha- nisms for fat metabolism. The early work showed that one important precursor of cholesterol was acetic acid. Dr. Bloch worked through the steps in the bio- synthesis of sterols, from acetic acid to squalene to the cycHzation of squalene to lanosterol, leading to the intermediates of lanosterol and to cholesterol. He also contrib- uted to the understanding of the biosynthesis of glutathione and of fatty acids. This work laid the basis for the development of "enzyme suicide" inhibition as a rational approach to drug design. Born in Neisse, Germany, in 1912, Dr. Bloch came to the United States in 1936 after studying chem- ical engineering in Munich. In 1938, he received his Ph.D. in bio- chemistry at Columbia University. Working with the late Rudolf Schoenheimer, he pioneered meta- boHc investigations with the aid of radioactive isotopes. His work in- volved labehng compounds with "heavy hydrogen," then a new technique that he helped perfect. He joined the faculty of Colum- bia and later that of the University of Chicago. In 1954 he was named Higgins Professor of Biochemistry at Harvard University, where he carried out many of his experi- ments on fat and sterol bio- synthesis. In 1982, he was named the Newton-Abraham Visiting Professor and FeUow of Lincoln CoUege, Oxford. 1966 Physiology or Medicine After a quarter- century of studying the re- lationship between cancer and hor- mones, Dr. Huggins discovered that androgens (male hormones) stimulated the growth of prostate cancer ceUs and that castration or the use of female sex hormones could shrink prostatic cancer. This led to the first successful chemo- therapy for maHgnancy in humans. Dr. Huggins's work led to the hormone-dependent cancer theory, which has been shown to play a role in breast cancer. His other anticancer work has included the experimental production of leuk- emia and mammary cancer in ani- mals so that these diseases can be studied under controlled condi- tions. From these laboratory ex- periments, Dr. Huggins has developed hormone treatments for at least seven types of human can- cer. Trained as a surgeon, research became the passion of his life. He once said: "One pits his wits against apparently inscrutable Na- ture. She can refuse to speak, but she cannot give a wrong answer. Her vocabulary consists only of three words — yes, no, and may- be. It is the genius of research to frame the question so simply that a conditional answer is prohibited." Bom in 1901 in Halifax, Canada, he later became a U.S. citizen. Dr. Huggins received his B.S. in 1920 from Acadia University in Nova Scotia, and his M.D. in 1924 from Harvard University. From 1927 to the present, he has worked at the University of Chicago Medical School. Physiology or Medicine D H orn in New York M City in 1906, Dr. ■JaHaHHi^^ Wald received his B.S. in zoology from New York University in 1927. He received his Ph.D. in zoology from Columbia University in 1932. At Columbia he was a student and research as- sistant of Professor Selig Hecht. On receiving his Ph.D., Dr. Wald was awarded a National Re- search Council Fellowship in Biol- ogy (1932-1934), and began working in the laboratory of Otto Warburg in Berlin-Dahlem, where Dr. Wald first identified vitamin A in the retina. Vitamin A had just been isolated in the laboratory of Paul Rarrer in Zurich, where Wald completed the identification. Then he worked in the laboratory of Otto Meyerhof at the Raiser Wilhelm Institute in Heidelberg. The sec- ond year of the Fellowship was spent at the Department of Phys- iology of the University of Chi- cago. Dr. Wald came to Harvard in the fall of 1934 as a tutor in biochemi- cal sciences and has been there ever since: as instructor and tutor in biology (1935-1944); associate professor (1944-1948); and pro- fessor, receiving the Higgins Chair in Biology in 1968. Dr. Wald is now Higgins Professor of Biology Emeritus. He was awarded the Nobel Prize in Physiology or Medicine in 1967, jointly with Drs. R. A. Hartline and H.R. Granit. Along with the many awards he has won, Dr. Wald was elected to the National Academy of Sciences in 1950 and to the American Philo- sophical Society in 1958. He is a Fellow of the American Academy of Arts and Sciences in Boston and the Optical Society of America. In 1963-1964 he was a Guggenheim Fellow, spending the year at Cambridge University, England, where he was elected an Overseas Fellow of Churchill College. He is also an Honorary Member of the Cambridge Philosophical Society (1969). Robert W. Holley 1968 Physiology or Medicine T he genetic code resides deep in a •ata^L^ cell's nucleus, far from the protein-synthesizing ma- chinery that puts the genetic blue- print into action. A number of researchers sought the connection between deoxyribonucleic acid and the order of a protein's amino acids. Three forms of ribonucleic acid, a chemical cousin of the gene itself, play key roles — one car- ries the message from the DNA, messenger RNA; one is incorpo- rated into protein factories called ribosomes; and a third, transfer RNA, carries amino acids into the ribosomes according to the se- quence specified by the messenger RNA. Dr. Holley was one of the scien- tists trying to understand that rela- tionship. He spent a decade first isolating and then determining the exact structure of the transfer RNA that carries alanine. By 1964, he had worked out the exact order of the nucleotides in the alanine transfer RNA, a discovery that opened up a deeper understanding of protein synthesis. Bom in Urbana, Illinois, in 1922, Dr. Holley received his A.B. in chemistry from the University of IUinois in 1942. In 1947, he earned his Ph.D. in organic chem- istry while working with Professor Alfred T. Blomquist at Cornell University. He also worked with Professor Vincent du Vigneaud at Cornell University Medical Col- lege, where he participated in the first chemical synthesis of pen- iciUin. He spent 20 years associ- ated with Cornell University, eventuaUy becoming chairman of the biochemistry department from 1965 to 1966. The work on the alanine transfer RNA was done at a U.S. Department of Agriculture laboratory on the Cornell campus. Since 1968, Dr. Holley has worked at the Salk Institute in La Jolla, California, in recent years studying the factors that control cell division in mammals. H. Gobind Khorana 1968 Physiology or Medicine Dr. Rhorana, like other scientists in the early 1960s, including co-laureates Dr. Marshall W. Nirenberg and Dr. Severe Ochoa, turned his analyti- cal skUls to deciphering the genet- ic code, then one of the hottest races in science. Although Dr. Nirenberg generally is credited with cracking the code first — various arrangements of the four different types of DNA subunits called nucleotides that specify which amino acids are placed in a protein — Dr. Rhorana shares the honor because he was the first to succeed in synthesizing artificial polynucleotides — bits of genes. He also extended Nirenberg's nitrocellulose binding technique for testing each of the 64 possible combinations of nucleotide trip- lets. Those studies helped prove that each set of three nucleotides in the gene specifies a single amino acid in the protein. Dr. Rhorana showed that the triplets do not overlap and that in protein syn- thesis, they are read in sequence without gaps between them. In ad- dition to helping crack the genetic code, Dr. Rhorana was the first to synthesize an artificial gene. His earlier work included studies on alkaloids and the synthesis of co- enzyme A. Bom in Raipur, India, in 1922, Dr. Rhorana later became an American citizen. He received his B.Sc. in 1943 and his M.Sc. in 1945 from the Punjab University. He earned his Ph.D. from Liverpool University in 1948. Since 1970, Dr. Rhorana has been Sloan Professor of Chemistry and Biology at the Massachusetts Institute of Tech- nology. Ph.D. 1968 Physiology or Medicine T he structure of de- oxyribonucleic JEL acid (DNA), the chemical essence of the gene, was identified in 1953, but it left a key question unanswered. How did the four types of nucleotide subunits that composed the DNA helix de- termine the sequence of the 20 amino acids that make up all pro- teins? In the summer of 1957, Dr. Mar- shaU Nirenberg came to the Na- tional Institutes of Health as a postdoctoral fellow and became intrigued by the problem. As is often the case, a simple, elegant experiment provided the first crit- ical clue to cracking the code. Dr. Nirenberg's work suggested that every combination of three DNA subunits represented a different amino acid. He presented the first few codes in Moscow in the sum- mer of 1961 and a race imme- diately began for the rest of the 64 possible codes. Several laboratories, many bet- ter equipped than Dr. Nirenberg's two-man operation, began to fill in more of the 64 possible combina- tions of nucleic acids. Researchers from other NIH laboratories pitched in to help Nirenberg com- pete, often working around the clock. By December, 1961, Dr. Nirenberg's group published a large number of tentative code words. The race was won, though it took several more years to fill in aU of the details. Dr. Nirenberg shared the Nobel Prize for Physiology or Medicine with Drs. Robert Holley and H. Gobind Rhorana. Dr. Nirenberg was born in New York City in 1927. He graduated from the University of Florida in 1948 with a B.S. in zoology and chemistry and received an M.S. in 1952. He earned his Ph.D. in bio- chemistry from the University of Michigan in 1957. Dr. Nirenberg is the chief of the Laboratory of Bio- chemical Genetics in the National Heart, Lung and Blood Institute at the National Institutes of Health. He is currently studying the genes involved in the development of the brain and nervous system. Salvador E. Luria 1969 Physiology or Medicine Dr. Luria, along with Dr. Max Delbruck of the California Institute of Technology, with whom he shared the Nobel Prize, was one of the fathers of the phage group, a band of researchers who worked out the rephcation mechanism and the genetic struc- ture of viruses that infect bacteria, and the genetics of bacteria them- selves. Dr. Luria's work laid the foundation for what eventually be- came the field of molecular biolo- gy- By studying generation after generation of different viruses while developing techniques to purify them, Dr. Luria was the first to discover that genetic mutations in viruses caused the proteins on their surfaces to change, allowing them to escape attacks by the body's immune system and aUow- ing the viruses themselves to at- tack cells that they previously could not enter. These sorts of mu- tations explain how new strains of influenza arise from time to time, causing epidemics among popula- tions that are not protected against them. Years before biologists called for a moratorium on some types of genetic engineering research in the mid-1970s, Dr. Luria expressed hope about the promise of the emerging field of molecular biolo- gy, but also concern about the con- sequences of humans being able to tinker with their own genes. Dr. Luria has long been part of the social conscience of the scientific community, championing a variety of causes, including the anti-war movement during Vietnam, a posi- tion that caused his name, along with those of other scientists, to turn up on a blacklist put together by the federal government. Bom in Turin, Italy, in 1912, Dr. Luria received his M.D. from the University of Turin in 1935, and went on to become a specialist in radiology at the University of Rome. After serving in the Italian Army from 1935 to 1938, he be- came a researcher at the Institut du Radium in Paris, and then moved to the United States, where he be- came a citizen in 1947. From 1940 to 1942, he was a researcher at Columbia University, then became a professor at Indiana University from 1942 to 1950 and at the Uni- versity of IUinois from 1950 to 1959. Since 1959, he has been the Sedgwick Professor of Biology, la- ter institute professor and director of the Center for Cancer Research at the Massachusetts Institute of Technology. Physiology or Medicine Nerve cells do not touch each other. They communicate through neu- rotransmitters, chemicals squirted into the synapses, the spaces be- tween the ends of nerve cells. But little was known about how neu- rotransmitters were formed, regu- lated or inactivated. Dr. Axelrod was the first to define the mecha- nisms that regulate the formation and inactivation of noradrenalin, one of the brain's most important neurotransmitters. This discovery led to a better understanding of human behavior and has disclosed the action of psychoactive and antidepressant drugs. A person suffering from severe depression may, for example, have a shortage of available nor- adrenalin. Neurotransmitters, once secreted, are quickly broken down to prevent them from continuously stimulating a nerve, Dr. Axelrod showed. Antidepressant drugs have been designed to reduce the speed with which noradrenahn is inactivated, giving a more near- normal firing of those neurons. He also discovered the biochemical actions of the pineal gland and en- zymes that form and metabolize neurotransmitters, hormones, and that detoxify drugs. Dr. Axelrod, along with Ber- nard Brodie, contributed to the de- velopment of the widely use pain- killing drug Tylenol. Born in the ghettos of New York City in May, 1912, Dr. Ax- elrod received his B.S. from the City College of New York in 1933 and his M.A. from New York Uni- versity in 1941. Because he lacked sufficient money to continue his education, he worked in a food- testing laboratory. In 1950, he moved to the National Institute of Mental Health, and, believing he could not get a promotion without one, he went back for his Ph.D., which he received from George Washington University in 1955. Recently retired as chief of the NIMH Section on Pharmacology, he continues to perform research as a guest worker at the National Institute of Mental Health and acts as a consultant to a biotechnology company and several nonprofit or- ganizations. 1972 Chemistry G m enes carry mfor- ^L mation linearly, ^^B^.^ like a piece of audio tape. But cells and bodies are three-dimensional, and so are the proteins that make them up. How is it that this linear information in the gene could result in three-di- mensional proteins that are able to perform a biological task? Working with ribonuclease, an en- zyme that breaks up molecules of ribonucleic acid, Dr. Anfinsen was able to successfully show that the three-dimensional, globular shape of the protein, and its catalytically active cleft, were determined by the sequence of the amino acids in the protein. Eariier workers had shown that the sequence of a pro- tein's amino acids was determined by the sequence of nucleotides in the gene. Dr. Anfinsen's experi- ments helped elucidate the process of protein folding within the cell by which proteins attain their three-dimensional shapes. Born in Monessen, Pennsyl- vania, in 1916, Dr. Anfinsen re- ceived his B.A. from Swarthmore College in 1937 and an M.S. in organic chemistry from the Uni- versity of Pennsylvania in 1939. He was a visiting investigator at the Carlsberg Laboratory in Copenhagen during 1939 and 1940. He received his Ph.D. from Harvard University in 1943, and for seven years was an instructor and assistant professor of biolog- ical chemistry at the Harvard Med- ical School. During 1947 and 1948, he was a senior fellow of the American Cancer Society at the Medical No- bel Institute. In 1950, Dr. Anfinsen became chief of the Laboratory of Cellular Physiology and Metabolism in what is now the National Heart, Lung and Blood Institute of the National Institutes of Health. He later was chief of the Laboratory of Chemical Biology in what is now the National Institute of Diabetes and Digestive and Ridney Dis- eases. Since 1982, Dr. Anfinsen has been a professor of biology at the Johns Hopkins University. 1972 Physiology or Medicine M erald M. Edel- ^^ man was born in ^^^^^ New York City in 1929. He earned his B.S. degree at Ursinus College, and an M.D. at the University of Pennsylvania. He spent a year at the Johnson Foun- dation for Medical Physics, an^ after a medical house officership at the Massachusetts General Hospi- tal, he served as a captain in the Army Medical Corps. He earned his Ph.D. at the Rockefeller Institute in 1960 where he has re- mained throughout his dis- tinguished career. At present, he is Vincent Astor Professor at the Rockefeller University. Edelman has a broad range of intellectual interests both in and outside of science. He has made significant contributions in bio- physics, protein chemistry, immu- nology, cell biology, and neurobiology. His early studies on the structure and diversity of anti- bodies led to the Nobel Prize for Physiology or Medicine in 1972. He then turned his interest to mechanisms involved in the reg- ulation of primary cellular pro- cesses, particularly the control of cell growth and the development of multiceUular organisms. In the course of this work he has focused on ceU-ceU interactions in early embryonic development and in the formation and function of the nervous system. These interests led to the discovery of cell adhe- sion molecules (CAMs), the func- tion of which is of great significance for the development and morphology of brain struc- tures. In addition to the Nobel Prize, Gerald Edelman has been the re- cipient of numerous awards and honors including many honorary degrees, and memberships in the National Academy of Sciences, the American Philosophical So- ciety, and the Academy of Sci- ences, Institute of France. In addition, he is director of the Neu- rosciences Institute and scientific chairman of the Neurosciences Research Program. 1974 Physiology or Medicine Individual cells, like the human body itself, are composed of different organs, or organelles, that perform the biological activities needed for survival. Dr. de Duve, working with the ceU fractionation tech- niques developed by fellow Nobel winner, Dr. Albert Claude of Rockefeller University in New York, and combining them with biochemical analysis and electron microscopy, discovered two of the cell's organelles: lysosomes and peroxisomes. Lysosomes are the cell's stomach. They keep the cell's powerful degradative en- zymes contained in sacs within the cell's cytoplasm so materials taken up from both outside and inside the ceU can be safely di- gested. Peroxisomes play a central role in the metabolic production and breakdown of hydrogen per- oxide. In later work, Dr. de Duve sought to understand the relation- ship between lysosomes and dis- eases. Bom in England in 1917, Dr. de Duve, a citizen of Belgium, was educated at the University of Lou- vain, receiving his M.D. in 1941, the equivalent of a Ph.D. in 1945, and a Master's degree in chemis- try in 1946. He conducted re- search in Stockholm and St. Louis before becoming a professor of biochemistry at the University of Louvain in 1951. In 1961, he also became a professor at Rockefeller University, and, in 1974, he be- came the Andrew W. Mellon Pro- fessor at Rockefeller. He now divides his time be- tween New York and Brussels where, in 1975, he created the In- ternational Institute of Cellular and Molecular Pathology, in close collaboration with Rockefeller University. The institute's work concentrates on basic cellular and molecular biology, biochemistry, and immunology, and on the ap- pUcations of these disciplines to medicine. George E. Palade 1974 Physiology or Medicine Many ceUular structures are far too small to be perceived even by the most powerful Hght microscope. The discovery that a stream of electrons can be used to "see" structures opened new windows into the cell that Dr. Palade learned to exploit, thus ushering in a new era in cellular anatomy. By using centrifugation tech- niques to isolate purified cell com- ponents and by improving preparation techniques for elec- tron microscopic studies, Dr. Pal- ade and his colleagues discovered ribosomes, the protein-synthesiz- ing factories of the cell, for which he received the Nobel Prize. Continuing the work of the late Dr. Albert Claude, a co-laureate, Dr. Palade combined structural studies of cells with biochemical assays of cell fractions to discover the ribosome and identify its func- tion. He also defined the fine struc- ture of the mitochondria (the ceU's power plant) and, in collaboration with Dr. Reith Porter, studied the structure of the endoplasmic re- ticulum in different cell types. They established that the endo- plasmic reticulum is a network of membrane-bound channels ex- tending from the nucleus through most of the cytoplasm. The chan- nels are used for the transport and sorting of proteins produced by the ribosomes attached to their mem- branes. They then used the same inte- grated structural and biochemical research approach soon after to decipher the processes and define the pathways used by cells to syn- thesize secretory and membrane proteins and to direct them to their proper destinations. When Dr. Palade received an honorary degree from Columbia University, President Michael Sovem said, "Your early work es- tablished the isolation and char- acterization of subcellular components as a major research tool, which it has remained to this day. You subsequently solved the major problem of fixation of tissues for electron microscopy, enabling that technique to become a critical tool for research in bio- logy and for diagnosis in medicine. .. . Your achievements have con- tinued unabated." Bom in Ro- mania in 1912, Dr. Palade later became a U.S. citizen. He received his M.D. from the School of Medi- cine of the University of B ucharest in 1940. After serving in the Roma- nian Army Medical Corps during World War II, he came to the Rockefeller University in New York in 1946, where he met Dr. Claude. In 1973, Dr. Palade be- came a senior research scientist in the Department of Cell Biology at Yale University, where he con- tinues to explore the implications of his work for pathology and clinical medicine. David Baltimore 1975 Physiology or Medicine In 1975, at the age of 37, David Baltimore became one of the youngest re- cipients of the Nobel Prize in Physiology or Medicine, honored along with Howard Temin for their simultaneous but independent dis- covery of reverse transcriptase, a viral enzyme able to copy the in- formation in RNA into DNA. It was a discovery that elucidated the mystery of how viruses that store their information in RNA man- aged to infect cells that store their genes in DNA, thus challenging existing dogma. They shared the prize with Renato Dulbecco. Dr. Baltimore is a leader and spokesperson for science on many issues, including genetic research, priorities for national research, and on matters of international con- cern, such as biological warfare and the regulation of science. He was cochairman of a major study of AIDS, sponsored by the Nation- al Academy of Sciences and the Institute of Medicine. The result, Confronting AIDS, was pub- lished in 1986. Dr. Baltimore's current research covers three areas: cancer-induc- ing viruses, the immune system, and poliovirus. In each he seeks to define the biochemical events un- derlying changes in gene expres- sion and gene structure in the mammalian ceU. He has a special interest in the immunology of AIDS. After receiving his B.A. with honors in chemistry from Swarthmore College in 1960, he went to MIT to begin graduate studies. A year later he went to Rockefeller University, from which he received a Ph.D. in biolo- gy in 1964. He did postdoctoral research at MIT and at the Albert Einstein CoUege of Medicine, then became a research associate at the Salk Institute in 1965. In 1968, he returned to MIT as an associate professor, became professor of bi- ology in 1972, and was appointed American Cancer Society Re- search Professor in 1973. In 1974, he joined the staff of the MIT Cen- ter for Cancer Research, where he remained untU he was named di- rector of the Whitehead Institute, an independent research institu- tion affiliated with MIT, in 1982. Besides his position as director of the Whitehead Institute, Dr. Baltimore is also a professor of biology at MIT. Renato Dulbecco 1975 Physiology or Medicine i w ince the early part of V W the century, re- ^^^^r searchers knew that some animal viruses could cause cancer, but no one understood how. Dr. Dulbecco performed pi- oneering work describing the in- teraction between tumor-causing viruses and the genetic material of the infected cell. He worked out many of the techniques used by researchers to study the molecular biology of animal viruses, includ- ing techniques used by co-laure- ates Drs. David Baltimore and Howard Temin — both of whom worked under Dr. Dulbecco at one point in their careers — to dis- cover how RNA viruses infected and transformed normal cells into cancer cells. Dr. Dulbecco also made significant discoveries about the mechanisms by which DNA tumor viruses transformed normal cells into cancer cells. German Army took over following the coUapse of Mussolini's gov- ernment, Dr. Dulbecco joined the resistance. After liberation, he served on the first postwar Turin City Council, but eventually re- turned to research. In 1946, Dr. Salvador Luria, on a visit to Turin, encouraged Dr. Du- lbecco to come to the United States. In 1947, he began work with Dr. Luria at Indiana Univer- sity. He joined the California In- stitute of Technology in 1949 and stayed there until moving to the Salk Institute in La JoUa, Cafifor- nia, in 1962. In 1971, he joined the Imperial Cancer Research Fund in London, but returned to the Salk Institute as the Senior Clayton Foundation Investigator in 1977 where he continues his research today. Bom in Catanzaro, Italy, in Feb- ruary 1914, Dr. Dulbecco received his M.D. from the University of Turin in 1936. After being wounded on the Russian front dur- ing World War II, he was sent back to Turin to recuperate. When the Howard M. Temin 1975 Physiology or Medicine Initially, and for the next six years, no one beheved him. In 1964, Dr. Temin first introduced his hypothesis that the genetic information of the Rous sarcoma virus was converted from the RNA genes of the vims to a DNA form, and then the viral DNA was integrated into the in- fected cell. No one beUeved him because the hypothesis violated the Central Dogma of biology, which said that biological infor- mation flowed from DNA to RNA to protein. RNA usuaUy was thought of as a messenger carrying the informa- tion for the sequence of amino acids in proteins from the DNA to the protein-making machinery. To suggest that information flowed the other way, back to DNA, vio- lated the Central Dogma. But then Dr. Temin and, inde- pendently, Dr. David Baltimore from the Massachusetts Institute of Technology, discovered the vir- al enzyme — known as reverse transcriptase — that Hterally cop- ied the genetic information from RNA into DNA. The case was proved; the violated dogma was adjusted. Reverse transcriptase has proved invaluable in the search for disease-causing genes and in the development of the genetic engi- neering industry, which now can produce previously rare proteins in nearly unlimited quantities. Dr. Temin also developed the provirus hypothesis for RNA viruses, which correctly described how some viruses can integrate their genes into the genetic material of the host cell and be inherited along with the other genes by the subse- quent generations. The provirus can remain quiescent within the cell, produce new infectious vir- uses, or sometimes transform the cell into a cancer that grows un- controllably. Bom in Philadelphia in 1934, Dr. Temin received his B.A. from Swarthmore CoUege in 1955 and his Ph.D. from the CaUfornia In- stitute of Technology in 1959, where he stayed for another year. In 1960, he moved to the McArdle Laboratory for Cancer Research in the medical school of the Univer- sity of Wisconsin in Madison, where he has spent his entire aca- demic and research career. During his time there, he became a full professor, then Wisconsin Alumni Research Foundation Professor of Cancer Research, and, in 1974, American Cancer Society Pro- fessor of Viral Oncology and Cell Biology. 1976 Physiology or Medicine While study- ing genetic variations in human blood, Dr. Blumberg dis- covered an antigen in an Aus- tralian aborigine that reacted with an antibody in the blood of a trans- fused hemophUia patient. He and his coUeagues subsequently show- ed that the antigen was on the surface of the hepatitis B virus, which causes diseases of world- wide importance. These include primary cancer of the Hver, one of the most common cancers in the world. The discovery had practical consequences: it revolutionized blood banking by providing a way to test donated blood to prevent transfusion-caused hepatitis. These tests are now routinely used to screen blood donors and have led to the prevention of certain kinds of posttransfusion hepatitis. Blumberg and Millman intro- duced a vaccine to prevent hepati- tis B infection that is now used widely among high-risk individu- als, particularly health care work- ers and newborn children already infected with the virus. Its major use is in large national programs in the People's RepubHc of China, Taiwan, Rorea, Gambia, and elsewhere, in which all newborns are vaccinated. A major rationale for these national campaigns is to reduce the risk for primary cancer of the Hver. Bom in New York in 1925, Dr. Blumberg received his B.S. in physics from Union CoUege, in 1946 and his M.D. from the Col- lege ofPhysicians and Surgeons of Columbia University in 1951. Ox- ford University (Balhol CoUege), awarded him a Ph.D. in bio- chemistry in 1957. From 1957 to 1964, he was chief of the Geo- graphic Medicine and Genetics section of the National Institutes of Health. He then became associate director for Clinical Research, Fox Chase Cancer Center, in Phila- delphia where he now is vice presi- dent for Population Oncology. Dr. Blumberg is also a university pro- fessor of medicine and anthropol- ogy at the University of Pennsylvania. Dr. Carlton Gajdusek 1976 Physiology or Medicine Dr. Gajdusek's work achieved a breakthrough that revolutionized thinking in mi- crobiology and neurology. With his associates, he showed that a "slow" viral infection was respon- sible for kuru, an exotic chronic degenerative disease. They went on to relate their findings to a wide range of other degenerative neu- rological diseases, "with incalcul- able implications for all of medicine, especially as it apphes to the basic process of degenera- tions and aging." In his Nobel speech, he summed up some of the implications of his studies. "For neurology, specifically, we have considerable new insights into the whole range of presenile demen- tias and, in particular, the large problems of Alzheimer's disease and the senile dementias." His travels and studies of dis- ease in exotic areas started at the Institut Pasteur in Teheran in 1952. He worked on epidemic diseases in Iran, Afghanistan, Turkey, In- dia, and South America. Most im- portant was his study of kuru in New Guinea, which demonstrated the then unknown phenomenon of a "slow" viral infection, taking years to be evident and always leading to death. The viruses of kuru, senile virus dementia, and scrapie are unlike any others yet described: they are resistant to al- most everything that inactivates other viruses, and they contain no nonhost protein. Fortunately, the threat of kuru is disappearing, not because of direct medical inter- vention, but because of social change. Ritual cannibalism is no longer practiced as a rite of mourn- ing, and this has meant that the contamination from brain tissue of kuru victims heavily infected with the vims has stopped. Dr. Gajdusek was born in Yonkers, New York, in 1923, to a Slovak father and a first-genera- tion Hungarian-American mother. His interest in science was encour- aged by his aunt, Dr. Irene Dor- broczki and by Dr. William J. Youden of the Boyce Thompson Institute Laboratories in Yonkers, where, while still a teenager, he was the first to synthesize the weed killer 2,4-D. He took his B.S. in biophysics from the University of Rochester, summa cum laude, in 1943, his M.D. from Harvard in 1946, and postdoctorate training in physical chemistry at the Califor- nia Institute of Techonology. William N. Lipscomb 1976 Chemistry T he bonds between molecules and their •»^Bl*» interactions are the essence of chemistry. Dr. Lipscomb developed a model to explain the molecular structure and chemical bonding of boranes, and developed an explanation of how two electrons can bind to- gether three atoms. Long interested in the relation- ship between structure and func- tion, Dr. Lipscomb was among the first to describe the three-dimen- sional structure of enzymes and other proteins. He used nuclear magnetic resonance to study com- plex molecules, and low-tempera- ture x-ray diffraction to work out the three-dimensional structure of biochemical crystals — including enzymes. Bom in Cleveland in 1919, Dr. Lipscomb received his B.S. from the University of Kentucky in 1941. He entered the California In- stitute of Technology, where he began studying physics, but, under the influence of Dr. Linus Pauling, switched to chemistry; he received his Ph.D. in 1946. Dr. Lipscomb then joined the Chemistry Depart- ment at the University of Min- nesota, where he became a full professor and chief of the Physical Chemistry Division. In 1959, Dr. Lipscomb became professor of chemistry at Harvard University and, in 1971, he was named Abbott and James Law- rence Professor of Chemistry. Physiology or Medicine As so often is the case, an intense interest in a branch of research began with an inspiring lecture. Hans Selye had come to Paris in the late 1940s to lecture about "his alarm reaction and the endocrinology of the gen- eral adaptation syndrome," Dr. GuUlemin wrote. "I went to hear him. The magnetism of the man was extraordinary." As a consequence, Dr. Guillemin moved to Dr. Selye's newly created Institute of Experi- mental Medicine and Surgery at the University of Montreal and be- gan learning experimentation in endocrinology while completing work on his M.D. Dr. Guillemin received his M.D. from the Faculty of Medicine of Lyon, related to the University of Dijon, France, in 1949. He continued his work in Montreal and later received his Ph.D. in physiology from the Uni- versity of Montreal in 1953. After settling at Baylor Univer- sity College of Medicine, where he stayed from 1953 to 1970, Dr. GuUlemin searched for the neu- !Hi roendocrine secretions of the hy- pothalamus, a part of the brain that through the pituitary gland con- trols all endocrine glands, includ- ing the thyroid, gonads, and the adrenal cortex. His work at Baylor, in coUaboration with co-laureate Dr. Andrew V. SchaUy, resulted in the identification and synthesis of thyrotropin-releasing factor, lu- teinizing-hormone releasing factor and a factor inhibiting the secre- tion of growth hormone. Dr. GuUlemin was bom in 1924 in Dijon, France, and later became a U.S. citizen.He received a B.A. in 1941 and a B.Sc. in 1942 from the University of Dijon. After working in Montreal and Houston, he moved to the Salk Institute in La Jolla, California, in 1970, where he remains today. 1977 Physiology or Medicine Dr. Schally was in a race. He and Dr. Roger Guillemin each struggled to be die first to identify, isolate, and syn- thesize the hypothalamic hor- mones and then apply them clinically. Corticotropin-releasing factor (CRH) was discovered in 1955. Thyrotropin-releasing hor- mone (TRH) was identified in 1966, and luteinizing hormone-re- leasing hormone (LH-RH) in 1971. Dr. Schally described the 1971 announcement of LH-RH as one of the most exciting moments of his life because it established him as the victor in a race to be the first to isolate a hormone that has proved to be the critical link between re- productive functions and the brain's pituitary gland. The dis- covery had important diagnostic and therapeutic applications. His work with brain hormones continued including investigations into the use of antagonists of LH- RH, work with prolactin release- inhibiting factor, somatostatin and its analogs, and attempts to under- stand the connection between the hypothalamus and obesity. Since 1978, Dr. Schally has been work- ing on hormone-dependent can- cers, and is now the chief of the Endocrine, Polypeptide and Can- cer Institute. Some of the new ap- proaches to cancer treatment he developed are now the subject of clinical trials. Born in Wilno, Poland, in 1926, Dr. Schally initially was a Canadi- an citizen before becoming a cit- izen of the United States. He received a B.Sc. in biochemistry from McGill University in 1955 and a Ph.D. in 1957. Like his co- laureate Dr. Guillemin, Dr. Schally did research at the Baylor Univer- sity College of Medicine in Houston, Texas. Dr. Schally came to New Or- leans, Louisiana, in 1962 to orga- nize the Veterans Administration- Tulane University laboratory for hypothalamic research. He be- came a full professor of medicine at Tulane in 1967 and section head and professor of experimental medicine in 1980. Rosalyn S. Yalow, Ph.D. 1977 Physiology or Medicine A f m ntibodies — E ^L proteins pro- «JL Jk± duced by the body to fight infections — have the abUity to specifically recognize the shapes of different molecules. This makes antibodies very selec- tive. Antibodies also are so sensi- tive that they can identify and bind a molecule even if it is present in very smaU concentrations. But it took Dr. Yalow, working with Dr. Solomon A. Berson, to figure out how to combine anti- bodies with radioactive tracers to create radioimmunoassay, a tech- nique that aUows scientists to mea- sure incredibly small quantities (down to a picogram, or 10 to the minus 12 grams) of hundreds of different biological substances. Dr. Yalow initially used the tech- nique to measure insulin levels in diabetics, leading to the discovery that in adult onset diabetes the blood level of insuHn can be high but its sugar-metabohzing action is blocked. The technique has been used to detect many other com- pounds in the body, including in- fectious agents such as the hepatitis vims, concentrations of antibiotics and other drugs, and growth hormones. Dr. Yalow was bom in 1921 and raised in New York City. Com- mitted to mathematics by seventh grade and excited by chemistry in high school, she planned to be- come a chemist when she entered Hunter College, where physics also caught her interest. She gradu- ated in 1941 with a Bachelor's de- gree in both chemistry and physics. Although she wanted to study physics in graduate school, she was pressured into taking secre- tarial courses and landed a job as secretary for Dr. Rudolph Schoenheimer, a well-known bio- chemist at Columbia University's College of Physicians and Sur- geons. Her secretarial career, however, was short-lived because Dr. Yalow was offered a graduate assistantship in the Physics De- partment at the University of Illin- ois — the first woman in the program since 1917 — where she earned an M.S. in 1942 and a Ph.D. in 1945. She came back to New York City in 1945 and joined the Bronx Veterans Administration Hospital in 1947, where she has spent most of her professional life. In 1972, she became a senior medical in- vestigator at the VA, and in 1986 she was also named Solomon A. Berson Distinguished Professor at Large at Mount Sinai School of Medicine. Physiology or Medicine Dr. Nathans had been studying the regulation of protein synthesis directed by a bacterial vims when he developed an interest in viruses that cause tumors in animals. While he was on sabbatical in 1969 exploring the molecular biology of tumor vir- uses, his Johns Hopkins colleague Hamilton O. Smith wrote to tell him that he had purified an enzyme from bacteria that cut long mole- cules of DNA — the chemical that carries genetic information — at specific sites. Seeing the signifi- cance of this discovery, Dr. Nathans on his return to Johns Hopkins began to use Smith's en- zyme and other restriction endo- nucleases (identified later as "chemical scissors") to break up the DNA of a tumor vims into distinct fragments that could be separated by electrophoresis. These techniques allowed him to isolate individual genes and map them on the viral chromosome and to biochemically construct site- specific mutants of the virus. Ex- tensions of these methods have been widely used to analyze viral and cellular genomes, to recom- bine genetic elements, and to iden- tify genes related to human diseases. Dr. Nathans was born in Wilmington, Delaware, in 1928. He received his B.S. in chemistry at the University of Delaware and his M.D. from Washington Uni- versity in St. Louis, where he worked with Oliver H. Lowry. Af- ter completing a medical residen- cy, he joined Fritz Lipmann's laboratory at the Rockefeller Uni- versity. Since 1962, he has been a faculty member at Johns Hopkins. Dr. Nathans is currently university professor of molecular biology and genetics and senior investiga- tor of the Howard Hughes Medical Institute. 1978 Physiology or Medicine In the microscopic battles between bacteria and the viruses that infect them (bacteriophages), one of the bacte- ria's most potent defenses are en- zymes that selectively dice up the deoxyribonucleic acid, the chemi- cal essence of the genes — of the invading virus while leaving the bacteria's own DNA intact. These enzymes are able to recognize the specific sequence of DNA sub- units (called nucleotides) that are present in the viruses, but not in the bacterial DNA. Dr. Smith discovered the first of these enzymes, now called restric- tion endonucleases, in the bacteria Haemophilus influenzae. Today, more than a hundred restriction endonucleases of different specif- icities are known. Fellow Johns Hopkins University researcher Dr. Daniel Nathans, and subsequently other scientists, discovered ways to use the enzymes to perform pre- viously impossible studies on ge- netic material, chopping the DNA into manageable sizes and cloning it into carrier molecules (called plasmids) that can be used to re- produce the specific gene end- lessly. These techniques helped give rise to the entire biotechnology/ gene engineering industry that al- ready is producing such important pharmaceuticals as insulin for dia- betics, growth factors, clotting fac- tors, and even vaccines —such as the one against hepatitis B virus infections. Bom in New York City in 1931, Dr. Smith received his A.B. from the University of California at Berkeley in 1952 and his M.D. from Johns Hopkins University Medical School in 1956. He stud- ied human and viral genetics while serving in the U.S. Navy, and by 1962, he had focused his research on molecular genetics. In 1967, Dr. Smith joined the Department of Microbiology at the Johns Hopkins Medical School and be- gan the work that eventually led to the isolation of the restriction en- donucleases. 1979 Chemistry D ^J breakthrough Jma*^^ discovery of hydroboration enabled chemical synthesis of previously impossible purity and yields. This basic dis- covery aUows wide-scale produc- tion of many biologically active substances, including synthetic amino acids, carbohydrates, hor- mones, vitamins and steroids. Dr. Brown was bom in London in 1912 to Jewish immigrants from the Ukraine. The family moved to Chicago in 1914, where his father worked as a carpenter and later opened a hardware store. When his father died in 1926, Dr. Brown left high school to work in the store. His mother, seeing his lack of interest in business and his de- votion to reading, soon took over the shop keeping and sent him back to school. Graduating from high school in 1930 in the depths of the Depres- sion, he was only able to attend college part-time. With encour- agement from his chemistry in- structors, he was in the first graduating class of Wright Junior CoUege in 1935. He went on to the University of Chicago, where he received his B.S. in 1936 and his Ph.D. in 1938. After beginning his career at Wayne State University in Detroit, he went to Purdue in 1947 as professor of chemistry, becoming in 1978 the Wetherili Research Professor Emeritus with honors from around the world. He maintains an active research pro- gram, achieving his one-thou- sandth publication in October 1986. 1979 Physiology or Medicine F nter nearly any ra- 1 diology depart- .^h.iiM.IW ment in any good- sized hospital in America and you will find a CAT scanner, a diagnos- tic imaging system that produces slice-like images of the body's soft internal tissues that could never be seen before without surgery. The CAT, or computerized axial to- mography, scanner revolutionized diagnostic radiology and has been called one of the most important advances in medical technology since the discovery of x-rays. Dr. Cormack developed the mathematical equations necessary to reconstruct the data collected by the CAT scanner's array of x-ray beams into an image of the body's organs. Although he had been in- terested in problems related to CAT scanning in the 1950s and had published papers on it in the 1960s, few people realized the medical applications of his work. As a re- sult, he did not begin full-time work on the calculations needed to perform CAT scans until the early 1970s, by which time fellow laure- ate, Godfrey N. Hounsfield, was developing the first practical CAT scanning system for general health care. Born in Johannesburg, South Africa, in 1924, Dr. Cormack stud- ied electrical engineering and re- ceived a B.Sc. in 1944 and an M.Sc. in 1945 from the University of Cape Town, where he was a professor of physics from 1946 to 1956. He came to Harvard Univer- sity as a researcher in 1956, then moved over to Tufts University as a professor in 1957, where he re- mains today. He is now an Ameri- can citizen. 1980 Physiology or Medicine R ■ aruj Benacerraf m understood well ^^^^F the difference be- tween those who responded al- lergically to dust or mold and those who did not. He had suffered bron- chial asthma as a child, an experi- ence that instilled in him a deep curiosity about allergic phe- nomena. Although his research career led him to laboratories around the world, he eventually settled at New York University, and, for a time, at the National Institutes of Health, where inbred strains of guinea pigs and mice helped Dr. Benacerraf and his colleagues dis- cover the immune response, /r, genes that regulate proteins on the surface of white blood cells. These genes play a central role in the manner in which the immune sys- tem recognizes the foreign pro- teins — known as antigens — of infectious agents such as viruses and bacteria. From his animal experiments, Dr. Benacerraf concluded that the Ir genes were part of the body's major histocompatibility complex, a central set of genes that regulate the immune system. His key in- sights into the mechanisms of im- munity have had implications for a number of diseases and for organ transplantation. Born in Caracas, Venezuela, in 1920 to a Sephardic family orig- inally from North Africa, he was educated in Paris until 1939, when his family fled the coming war. In 1940, he moved to New York City, eventually attending Columbia University to prepare for medical school. He received his M.D. from the Medical College of Virginia in 1945. After becoming an Ameri- can citizen and serving as a physi- cian in the U.S. Army, Dr. Benacerraf returned to Columbia to begin his research career in im- munology in 1948. After spending some time in Paris, he moved to the Pathology Department of New York University in 1956, and in 1968, to the National Institutes of Health. He stayed at NIH for two years before moving for the last time to Harvard University, where he is chairman of the Pathology Department and president of the Dana Farber Cancer Institute. Paul Berg 1980 Chemistry T ■ he 1950s and 1960s had been an excit- J^ ing time of rapid insight into the genetic chemis- try — now called molecular biol- ogy — of simple prokaryotic organisms, the vimses and bacte- ria. But Dr. Berg wondered whether the genetic chemistry of higher organisms, the eukaryotes, including mammals, had the same organization. Working with the mammalian virus SV40, Dr. Berg began using the then newly discovered restric- tion endonucleases, enzymes that selectively slice DNA into smaller pieces, to create a physical map of S V40's circular chromosome. The ability of S V40 to integrate its gen- es into the chromosomes of the cell it infects made Dr. Berg wonder whether it was possible to perma- nently introduce new genes into a cell. To test that idea, he developed a procedure for joining two different DNA molecules together in the lab. Once the hybrid DNA was made, Dr. Berg's group learned how to put it into cells in ways that it would produce proteins encoded by the new DNA. This advance- ment helped lead to the develop- ment of the entire field of biotechnology, in which once scarce pharmaceutical proteins can now be made in nearly un- limited quantities. Early concerns about the safety of introducing new genes into cells led Dr. Berg and others to call for a brief moratorium on certain kinds of experiments in the mid-1970s until certain safety questions could be answered. Since then, the mor- atorium has been lifted and the research judged to be safe. Bom in New York City in 1926, Dr. Berg received his B.S. from the Pennsylvania State University in 1948 and his Ph.D. from Western Reserve University in 1952. After postdoctoral studies with Herman Kalckar in Copenhagen, Dr. Berg worked with Dr. Arthur Romberg at Washington University in St. Louis in 1953 and 1954 and then continued on his own there until 1959, when he moved to the De- partment of Biochemistry in the Stanford University School of Medicine. He is now the Willson Professor of Biochemistry at Stan- ford and director of the Beckman Center for Molecular and Genetic Medicine. Chemistry I n the early 1950s, Dr. James Watson and Dr. .^L. Francis Crick described the shape of DNA, the chemical essence of the genes: nearly a de- cade later, the genetic code was broken. The next major hurdle would be finding a chemical pro- cess for identifying the sequence of the four nucleotides (DNA sub- units, often referred to simply as A, C, G, and T) that make up the genetic alphabet. Dr. Gilbert and Allan Maxam of Harvard worked out a chemical degradation method in which each of the four nucleotides in radioac- tively labeled pieces of DNA could be selectively destroyed, creating DNA fragments of varying lengths. These fragments could then be sorted by elec- trophoresis through a gel — like forcing them through a sieve with an electric field. The radioactive labels show the location of each fragment in the gel on x-ray film, and the identity of the last base on each fragment can then be read directly. Taking the order of all the fragments together gives the order of the several thousand nu- cleotides that make up a gene. Thousands of genes have been se- quenced since the techniques of Dr. Gilbert and Dr. Frederick San- ger, a British Nobel Prize winner who developed a different tech- nique for sequencing DNA, be- came widely available. Dr. Gilbert was bom in Boston in 1932. He graduated from Har- vard College with an A.B. in chemistry and physics in 1953 and an A.M. from Harvard University in physics in 1954. In 1957, he received his Ph.D. in mathematics from Cambridge University, where he met Dr. James Watson, who eventuaUy led him into mo- lecular biology. Except for a brief period when he was chairman of Biogen N.V., a biotechnology company in Cambridge, Mas- sachusetts, and Geneva, Switzer- land, Dr. Gilbert has spent his entire career at Harvard, where he is now chairman of the Depart- ment of Cellular and Developmen- tal Biology. Physiology or Medicine Dr. Snell is best known for his studies of the major histocompatibility complex or MHC, a group of closely linked genes, present in most and perhaps all vertebrates, that plays a major role in the regulation of immune processes. The complex was dis- covered independently in studies with mice by Drs. Snell and Peter Gorer, and was named histocom- patibility^, or H-2. It took several years of work, using the two dif- ferent methodologies developed by the two investigators — and part of it in joint studies — before the great complexity of H-2 was even partly appreciated. The dem- onstration by Dr. Jean Dausset of a similar group of genes in humans, and by Dr. Baruj Benacerraf of an immunological role for H-2, first led to an appreciation of its impor- tance. Numerous special strains of mice (congenic resistant strains) developed by Dr. Snell played a major role in much subsequent work. Dr. Snell was born in Bradford, Massachusetts in 1903. He re- ceived his B.S. from Dartmouth College in 1926 and an Sc.D. from Harvard in 1930. After three years of teaching and two years as a postdoctoral fellow at the Univer- sity of Texas, he moved to the Jackson Laboratory in Bar Harbor, Maine, where he remained until his retirement in 1973. While at the University of Texas, Dr. Snell demonstrated for the first time that x-rays can pro- duce hereditary changes in mam- mals (mice), and that the changes involve chromosome rearrange- ments rather than mutations of individual genes. Since his retire- ment, Dr. Snell has written, jointly with Drs. Dausset and Nathenson, a book on the MHC and related subjects, and has recently com- pleted a book on ethics. Chemistry T he action of hemo- globin, the oxygen- .J^. carrying red pig- ment found in red blood cells, de- pends on iron. The ability of chlorophyll to capture light and split water depends on magne- sium. Other important molecules within the human body and throughout the living world de- pend on inorganic metals bound to organic chemicals. "The inorganic fragment is not merely a weakly attached innocent bystander," Dr. Hoffmann said during his Nobel lecture on the relationship between metals and the hydrocarbon molecules of Hfe. "It transforms essentially and strongly the bonding relationships in the molecule." Dr. Hoffmann has spent his re- search career trying to bring order out of the chaos of these complex chemical relationships. Using what he calls "applied theoretical chemistry," he blends computa- tions stimulated by experimenta- tion with the construction of generalized models and frame- works to understand the geometry and reactivity of molecules, from organic and inorganic molecules to infinitely extended structures. Bom in Zloczow, Poland (now in the Soviet Union), in 1937, Dr. Hoffmann became an American citizen in 1955. He received his B.S. in chemistry from Columbia University in 1958. Harvard Uni- versity awarded him an M.A. in 1960 and a Ph.D. in 1962. From 1962 to 1965, he stayed at Harvard as a Junior Fellow then moved to ComeU University, where he has remained since 1965. He is now the John A. Newman Professor of Physical Science at Cornell. A col- lection of his poetry, entitled "The Metamict State," was pubUshed in 1987. In 1989, he wUl present an Annenberg/Public Broadcasting Corporation production called "The Chemical World," an intro- duction to chemistry in 26 half- hour shows. Physiology or Medicine When the im- age of a scene falls on the retina, each of its 125 million receptors is influenced according to the amount of light falling on them. It is then up to the nerves in the retina and the brain to interpret these patterns of activity into form, color, movement, and depth. Working with cats and monkeys, Dr. Hubel and his colleague, fel- low laureate Dr. Torsten N. Wiesel, have studied the way in which the visual information is processed in the early stages in the brain, es- pecially in the primary visual cor- tex. The work has also contributed to understanding binocular vision and the importance of early visual stimulation in development. It has led to practical applications in cat- aract surgery for infants and in surgery for strabismus, such as cross-eye. Dr. Hubel was bom in 1926 in Windsor, Canada. He was brought up in Montreal and educated at McGUl University, from which he received his B.Sc. in 1947 and his M.D. in 1951. He came to the United States in 1954 and spent a year at Johns Hopkins University before entering the U.S. Army. He was assigned to work in the Neu- ropsychiatry Division of the Wal- ter Reed Army Institute of Research, where he began his re- search career. He is now John Franklin Enders University Pro- fessor of Neurobiology at the Har- vard Medical School. Physiology or Medicine Left brain, right brain. The two sides of the brain are linked through the corpus cal- losum — the brain's largest cable of nerve fibers. Reports that cut- ting the human callosum causes no detectable symptoms led Dr. Sper- ry to his "split-brain" research. He and his students showed that cal- losal cutting stops cross-integra- tion of conscious experience, leaving left and right minds work- ing in parallel. Analyses of the "split-brain" human faculties re- vealed the now-familiar left/right differences, and that the right brain is not retarded, as was previously thought, but has its own more spa- tial, less linear, form of intellect. This understanding changed theo- ries of education and the concep- tion of human consciousness. Dr. Sperry's earlier work show- ed that brain networks for behavior can be preorganized in the growth process. A vast chemical prewir- ing scheme gives each neuron a chemical identity determining its selective outgrowths and connec- tions. His findings disclosed the role in vertebrate development of specification at the cellular level and of individual cell-to-cell inter- actions. In doctoral research under Dr. Paul A. Weiss, Sperry showed by nerve/muscle transplantations that nerves are not functionaUy in- terchangeable and that the brain's wiring was not nearly as plastic as was formerly supposed. His mid-1960s mentalistic theory of consciousness has since become the dominant view in psychology. In later work he explored the wide- ranging implications of this "con- sciousness revolution" for sci- ence, philosophy, and social values. Bom in Hartford, Connecticut, in 1913, Dr. Sperry received an A.B. in English and an M.A. in psychology from Oberlin College, and a Ph.D. in zoology in 1941 from the University of Chicago. After posts at Harvard University, the Yerkes Laboratories, the Uni- versity of Chicago, and the Na- tional Institutes of Health, he moved to the California Institute of Technology in 1954, where until 1984 he was Hixon Professor of Psychobiology and then Trustee's Professor Emeritus. 1981 Physiology or Medicine F or the retina lining the back of the eye ..i^La. to capture light and turn it into images the brain can understand, the neurons making up the retina must be organized into "ocular dominance columns." Working with his then-Harvard colleague Dr. David H. Hubel, Dr. Wiesel discovered that each neu- ron responds best to a particular stimulus and that for vision to work, all of the neurons must oper- ate in concert, with each firing in a complicated arrangement. The neurons then transmit this visual information to the brain, where it can be interpreted. They had, ac- cording to the Nobel committee, discovered the essence of "infor- mation processing in the visual system." Their work provides insights into the importance of early visual stimulation in proper development and problems relating to binocular vision. Bom in Uppsala, Sweden, in 1924, Dr. Wiesel later became a U.S. citizen. He received his M.D. from the Rarolinska Institute in Stockholm in 1954. He came to 1954. He came to Johns Hopkins University in 1955, then moved to Harvard University in 1959. He remained at Harvard for 24 years, finally moving to Rockefeller Uni- versity, where he is the Vincent and Brooke Astor Professor. Barbara McCHntock 1983 Physiology or Medicine M regor Mendel's ^L principles of he- ^^^^^r redity had been rediscovered only 21 years before Dr. McCHntock took Dr. C.B. Hutchinson's course, the only one open to the undergraduates of Cor- nell University. Although genetics as a discipline was not universally accepted by biologists of the time, she found it fascinating. In Janu- ary 1922, after the course was over, Dr. Hutchinson called Dr. McCHn- tock and invited her to take the only other genetics course — this one for graduate students — of- fered at Cornell. "Obviously, this telephone call cast the die for my future," Dr. McCHntock wrote. "I remained in genetics thereaf- ter." Her early studies focused on the chromosomes of the maize plant, their components, and the relation of these to gene order and expres- sion. That the genome was essen- tially stable was taken for granted at the time. In the mid-1940s, however, Dr. McClintock dis- covered the mobility of a class of genetic elements that was present in the maize genome. Such ele- ments could transpose from one location to another, either within the same chromosome or to an- other chromosome. When inserted at a gene locus, the elements could take over control of of gene ex- pression. Such elements have sin- ce been found in a number of organisms, both plant and animal, and their nature has been explored at the molecular level. Bom in Hartford, Connecticut, in June 1902, Dr. McClintock re- ceived all of her degrees from Cor- nell University in Ithaca, N.Y.: B.S. in 1923, M.S. in 1925, and Ph.D. in 1927. This was followed by several research fellowships and five years as an assistant pro- fessor at the University of Mis- souri. In 1942, she moved to the Department of Genetics of the Carnegie Institution of Wash- ington at Cold Spring Harbor, New York (now the Cold Spring Harbor Laboratory), where she spent the rest of her career and where she resides today. Chemistry A # m 11 chemical reac- E ^k tions fall into <4L JL two categories. One is oxidation-reduction, in which electrons are transferred from one atom to the other. Such reactions are important because of the products that may be formed: for example the industrial produc- tion of sulfuric acid from sulfur, oxygen, and water or the electroly- tic refining of copper.They are also important because of the energy they release: for example, the ox- idation of sugar as it occurs in living cells. The transferring of electrons in a chemical reaction, however, is not a simple, straight- forward process. Instead, it leads to rearrangements of atoms as the electrons move about. Dr. Taube worked out the com- plicated electron interactions in metal complexes and determined that electrons move from one place to another by using a "chemical bridge." His discovery of these electron activities has had impor- tant implications for industry. and M.D. degrees from the Uni- versity of Saskatchewan in 1935 and 1937, respectively, and his Ph.D. from the University of Cal- ifornia at Berkeley in 1940. He taught at Berkeley for a year be- fore moving to Cornell University in 1941, when he also became a naturalized American citizen. In 1946, he moved to the University of Chicago, where he served a term as chairman of the Chemistry De- partment. In 1962, Dr. Taube be- came a professor of chemistry at Stanford University, where he served as chairman of the depart- ment from 1972 to 1974 and from 1978 to 1979. He is still at Stan- ford. Born in Neudorf, Canada, in 1915, Dr. Taube received his B.S. 1984 Chemistry p roteins and the smaU- er peptides are both .J^* made from amino acids. The 20 different available amino acids determine the three- dimensional shape and biological properties of every protein. Synthesizing peptides and pro- teins by hand for biological study was a laborious process. To make life easier for the protein re- searcher, Dr. Merrifield de- veloped a technique called "solid-phase peptide synthesis," a rapid, automated method for as- sembling amino acids, one by one, into larger and larger chains. The first amino acid is anchored on an insoluble matrix of polystyrene (a common plastic) and then each ad- ditional amino acid is added in the desired order to make a complete protein. The method makes poss- ible systematic studies of the bio- logical activity of enzymes, hormones, and even antibodies. It also allows researchers to make sufficient quantities of proteins and peptides to study their three- dimensional structures and to de- termine how structure affects the proteins' action in the body. This technique earned Dr. Mer- rifield the moniker "the Henry Ford of protein synthesis," since he used an assembly line approach to solve the difficult chemistry problems associated with in vitro peptide synthesis. This develop- ment is credited with aiding in the treatment and prevention of a number of diseases and genetic disorders and with stimulating progress in genetic engineering. Bom in Fort Worth, Texas, in 1921, he received his B.A. from the University of California at Los Angeles in 1943 and his Ph.D. in 1949. In 1944, Dr. Merrifield came to the then Rockefeller Institute for Medical Research; he became a professor at the RockefeUer Uni- versity in 1966, where he con- tinues his work today. Michael S. Brown 1985 Physiology or Medicine A # M s the Nobel As- E ^^ sembly of the ^Ekm mJE^ Rarolinska In- stitute in Stockholm stated, Dr. Brown, with his collaborator, Dr. Joseph L. Goldstein, "revolu- tionized our knowledge about the regulation of cholesterol metabo- lism and the treatment of diseases caused by abnormally elevated cholesterol levels in the blood." For this, the two researchers re- ceived the Nobel Prize in Physiol- ogy or Medicine. The discovery of LDL recep- tors —proteins on the surface of cells that capture cholesterol-car- rying low-density lipoproteins (LDL) and pull them into the cell where they can be used — was the first step in a series of investiga- tions by the two scientists. Their further studies, combining genet- ics and molecular biology, helped make it possible to use rationally designed drugs and diets to lower the amount of cholesterol in peo- ple whose high cholesterol levels increased their chances of heart disease. Dr. Brown received both his B.S. and M.D. at the University of Pennsylvania. He received his M.D. in 1966, then served for two years on the staff of the Mas- sachusetts General Hospital in Boston, where he met Dr. Gold- stein. They both later joined the National Institutes of Health, where Dr. Brown worked with Dr. Earl Stadtman in the Laboratory of Biochemistry. In 1971, Dr. Brown moved to the University of Texas Health Science Center in Dallas. In 1972, Dr. Goldstein joined the him and the two continued their collab- oration there. Bom in New York City in 1941, Dr. Joseph L. Goldstein 1985 Physiology or Medicine F inding the answers to two fundamental JE^m questions affecting heart disease — How does the body regulate the level of cho- lesterol in the blood? How might cholesterol metabolism be altered to lower the level of cholesterol in the blood? — earned Dr. Gold- stein and Dr. Michael S. Brown, the Nobel Prize in Medicine or Physiology. Cholesterol, a sticky molecule associated with a process that nar- rows the coronary arteries, is man- ufactured in the liver and is essential for cell membranes and the production of certain hor- mones. Because cholesterol can- not be dissolved in water, it must be carried through the blood as part of a special protein complex. Several types of protein-cho- lesterol complexes move the cho- lesterol to and from the liver. One critical form is called low-density lipoprotein (LDL), a high level of which has been shown to be asso- ciated with increased risk of heart disease. In 1973, Drs. Goldstein and Brown discovered that the sur- face membranes of certain cells carry molecules called receptors, proteins that bind LDL and re- move it from the blood, thus lowering its concentration. Their work provided a key in- sight into the natural metabolism of cholesterol in the body, and has already helped lead to new drugs that may help millions of individu- als lower their cholesterol levels and thus their chances of a heart attack. As Dr. Goldstein once said, "Once one knows one has this receptor, one can begin to study the factors that turn it on and off, whether that is drugs or diet or any number of other things." Born in Sumter, South Car- olinia, in 1940, Dr. Goldstein re- ceived a B.S. from Washington and Lee University. In 1966 he received his M.D. from the Uni- versity of Texas Health Science Center in Dallas, where the chair- man of medicine offered him a future faculty position even before his graduation from medical school. He spent two years at the Massachusetts General Hospital as a house officer, and it was there that he met Dr. Brown, who has been his collaborator since they joined the Health Science Center faculty in the early 1970s. Herbert A. Hauptman 1985 Chemistry T here had been argu- ments about how ,^B^ much information a beam of diffracted x-ray light could provide about a crystal's structure. The crystallographers of the 1950s felt the information was limited. Dr. Hauptman and his col- league, Dr. Jerome Rarle, who were both then at the Naval Re- search Laboratory in Washington, D.C., believed differently. They determined that the struc- ture of a compHcated crystal could be deduced from x-ray patterns using a fundamentally different analysis, called the "direct meth- od." It was a mathematical for- mulation and a procedural approach that led to a quicker way to determine a crystal's shape, a breakthrough both in speed and accuracy. It allowed the team to determine the structures of mole- cules previously deemed too com- plicated for analysis. Within the next 12 years, many other molecu- lar structures, such as reserpine, a drug used in the 1960s to treat high blood pressure and some nervous and mental disorders, were also solved. Today, tens of thousands of structures have been determined with increased speed using their techniques. Thirty years ago, it took two years to work out the structure of a simple antibiotic molecule with only 15 atoms. Now, the structure of a 50-atom molecule can be determined in two days, and many others in the 100-200 atom range have been solved. Although now widely hailed as a breakthrough with profound im- plications for work in many dif- ferent scientific fields, their work was initially greeted with disbelief and criticism when first presented in 1954. It took nearly 15 years for crystallographers — who then could not understand the complex mathematical calculations — to accept the approach. Today, Hauptman and Rarle are recogn- ized as founders of a new era of research on molecular structure. Dr. Hauptman, was bom in New York City in 1917. He received a B.S. from the City College of New York in 1937. While working at the Naval Research Laboratory in 1955, he completed work for his Ph.D. at the University of Mary- land. Since 1970, Dr. Hauptman has been with the Medical Foundation of Buffalo, a small research center, that early on saw the potential of his work. From 1972 to 1988, he was research director of the foun- dation and, since 1986, he has been its president. Jerome Karle 1985 Chemistry In the world of biology and medicine, shape is everything. Genes deter- mine the order of amino acid sub- units in each protein, but it is the three-dimensional shape of the en- tire protein that makes it work. Identifying a molecule's shape is essential to understanding the relationship between its structure and its physical, chemical and bio- logical properties. Scientists had learned to make crystals of important molecules, blast them with x-rays, and then, by observing how the crystals scat- tered the x-rays, calculate the crys- tal's shape. The process was laborious, requiring years to deter- mine the structure of even simple molecules with only a few atoms. In the early 1950s, Dr. Rarle, working in collaboration with his wife, Dr. Isabella Lugoski Rarle (herself a physical chemist) and Dr. Herbert A. Hauptman, de- veloped the "direct method" for determining the three-dimensional structure of crystalline materials. They created a series of mathe- matical formulas that allowed them to quickly interpret x-ray di- ffraction data to determine the structure of a number of biolog- ically important molecules, in- cluding hormones, vitamins, and antibiotics — molecules vastly more complex than previous tech- niques could analyze. There was oniy one problem. No one believed them. Fellow sci- entists failed to appreciate the im- plications of the mathematics used by Rarle and his group, so there was some acrimony. In the preface to his Nobel lecture, Karle con- cludes with a thanks for the sup- port from his wife "both technical and spiritual. . . . This was es- pecially helpful during the early 1950s when a large number of fel- low scientists did not believe a word we said." Within a decade, their techniques became the stan- dard approach to crystallography. Bom in New York City in 1918, Dr. Karle received his B.S. iri chemistry and biology in 1937 from the City College of New York and his M.S. from Harvard Uni- versity in 1938. The University of Michigan awarded him both an M.S. and a Ph.D in physical chem- istry in 1944, though the work had been completed a year earlier. Before attending Michigan, he worked for the New York State Health Department in Albany where he devised the standard method for determining the amount of fluoride in drinking wa- ter. In 1943, he joined the Univer- sity of Chicago's portion of the Manhattan Project. In 1946, Dr. Karle and his wife went to work at the Naval Research Laboratory in Washington, D.C, where he cur- rently is the chief scientist of the Laboratory for the Structure of Matter. Stanley Cohen 1986 Physiology or Medicine It was another example of chance favoring the pre- pared mind. In the early 1950s Dr. Cohen joined Dr. Rita Levi-Montalcini's laboratory at Washington University in St. Louis as a young postdoctoral re- searcher. She had discovered the existence of a biologically active protein that stimulated nerve growth. While conducting experiments in which salivary gland extracts, a source of the nerve growth factor, were injected into newborn mice, Dr. Cohen noticed that the mice opened their eyelids sooner than expected and grew teeth faster than normal. This observation, and dogged chemical analysis, led to the discovery of epidermal growth factor, a protein that stimulates the growth of epidermal cells, which make up the outer layers of the skin and other organs. Although Dr. Cohen empha- sizes the value of his work in un- derstanding the fundamental growth activities of cells, it has also had important practical con- sequences for understanding how cells grow normally and how their abnormal growth causes diseases such as cancer and muscular dys- trophy, and the delayed healing of wounds. Epidermal growth factor even has been used experimentally to produce skinlike sheets of cells used to treat burn victims. Bom in Brooklyn in 1922, Dr. Cohen received his undergraduate degree in both biology and chem- istry from Brooklyn College, where he became interested in cell biology and embryonic develop- ment. He received his M.A. in zo- ology from Oberlin College in 1945 and his Ph.D. from the Uni- versity of Michigan in 1948. He learned to use radioisotopes at Washington University in the early 1950s, where he met Dr. Arthur Romberg, himself a Nobel Prize winner. He later joined co-laureate Dr. Levi-Montalcini in the Zoolo- gy Department. In 1959, Dr. Cohen moved to Vanderbilt University to explore the chemistry and biology of epi- dermal growth factor. He remains at Vanderbilt, where, since 1976, he has been an American Cancer Society Research Professor and since 1986, distinguished pro- fessor. Dudley R. Herschbach 1986 Chemistry When two chemicals react with each other to produce some third substance, their atoms go through a series of complex reactions, for- ming and breaking chemical bonds, creating short-lived chemi- cal intermediates, and finally arriv- ing at an energetically stable configuration. Chemists had speculated about the existence and the characteris- tics of these chemical intermedi- ates, but it was difficult to perform experiments that would help shed light on the problem. Then Dr. Herschbach figured out a way to develop a new experimental ap- proach. Borrowing techniques from atomic physicists who had learned to study atoms by colliding them at extremely high speeds and then studying their subatomic frag- ments, Dr. Herschbach built a ma- chine to squirt chemically pure beams of elementary chemicals — actually whole molecules — into a vacuum chamber. In the chamber the molecules smashed into each other, and creating chemical frag- ments that flew off in different directions. The fragments could be captured and analyzed to produce a picture of the chemical interac- tions. The initial reactions pri- marily involved alkali atoms and alkyl iodides. Dr. Herschbach was bom in San Jose, California, in June 1932. Of his years at nearby Campbell High School, he wrote: "I was at least as interested in football and other sports; perhaps that presaged my later pursuit of molecular colli- sions." In 1954, Dr. Herschbach received his B.S. in mathematics from Stanford University and his M.S. in chemistry a year later. He then moved to Harvard University, which awarded him an A.M. in physics in 1956 and a Ph.D. in chemical physics in 1958. In 1959, Dr. Herschbach moved to the University of California at Berkeley to begin work on mo- lecular beam devices. He returned to Harvard in 1963, where he be- came Frank B. Baird, Jr., Professor of Science in 1976. Dr. Herschbach also served as chairman of chemi- cal physics, 1964-1977; chairman of chemistry, 1977-1980; and co- master of Currier House 1981-1986. He lives in Lincoln! Massachusetts. Chemistry T he development of new instruments to ..^L. understand how chemicals reacted with each other already was underway when Dr. Lee arrived at the University of California at Berkeley to begin his graduate studies in 1962. He quick- ly proved his instrument develop- ment skills while working on ion- molecule reactions during studies of molecular interactions. With his Ph.D. in hand, Dr. Lee joined the lab of co-laureate Dr. Dudley Herschbach at Harvard University in February 1967 and helped build the first crossed mo- lecular beam apparatus for non- alkali reactions. "At first people thought he was just a brilliant experimentalist, the kind of guy who knew how to design and make the hardware that will do the experiment," said one colleague. "But it turned out Yuan Lee was just an ultramodest person .. . he also was a brilliant theoreti- cian." Hsinchu, Taiwan, Dr. Lee started his education under the Japanese occupation of Taiwan. His ele- mentary education was disrupted when Hsinchu's populace fled into the mountains to survive the bomb- ings of World War II. He received his B.S. in chemistry from the Na- tional Taiwan University in 1959 and his M.S. from the National Tsinghua University. He received his Ph.D. from the University of California at Berkeley in 1965. After his work in Dr. Herschbach's lab, Lee moved to the University of Chicago in Octo- ber 1968 to construct a new genera- tion of crossed molecular beam apparatus. In 1974, he returned to the University of California at Berkeley as a professor of chemis- try and a principal investigator at the Lawrence Berkeley Labora- tory, where his lab now runs more than half a dozen molecular beam devices. He became an American citizen the same year. Born in November 1936 in Rita Levi-Montalcini 1986 Physiology or Medicine T he research began with a chance ex- a^fl^ periment: mouse sarcoma tissue transplanted into a three-day old chick embryo caused nearby nerve fibers to grow ex- plosively. But the tumor cells produced too little of the unknown factor to iden- tify, so Dr. Levi-Montalcini trav- eled to Rio de Janerio, where a friend had built an efficient tissue culture system. There, she devised a technique that allowed her to explore the effect of mouse sar- coma factor in virtro on sensory and sympathetic ganglia of the chick embryo, working in the De- partment of Zoology at Wash- ington University in St. Louis with biochemist and co-laureate Dr. Stanly Cohen, she explored this factor's effect on its target cells. Then luck intervened again. The team used snake venom as part of the preparation, expecting it to stop nerve growth. Instead, it proved to be a potent source of nerve growth stimulation. Their subsequent dis- covery that mouse submandicular salivary glands are an even more potent source of the molecule, known since 1964 as the nerve growth factor (NGF) marked the beginning of the extensive studies she has pursued ever since to iden- tify the chemical nature of NGF and explore its spectrum and mechanism of action. The discovery of NGF created a whole new field of research that led to the discovery of a number of growth factors including epider- mal growth factor, found by Dr. Cohen. Research in the late 1970s linked the discovery of oncogenes, genes that can convert normal cells into cancerous cells, to some growth factors. Dr. Levi-Montalcini was bom in Turin, Italy, in 1909, and later be- came a dual U.S. and Italian cit- izen. She graduated from medical school in Turin in 1936 with a de- gree in medicine and surgery. The politics of anti-Semitism during World War II blocked her from performing research or working as a physician, and she ended up in- stalling a small research lab in her bedroom. She returned to the Uni- versity of Turin in 1945 where she stayed, until moving to Wash- ington University in 1956 for what was supposed to be a brief visit as a guest researcher. She stayed in St. Louis until 1977, when she retired as a full professor. From 1969 to 1978, she commuted between St. Louis and the Institute of Cell Biol- ogy of the Italian National Council of Research in Rome, which she directed during that time. Since retiring in 1979 she has been a guest professor at the institute. We wish to acknowledge the inval- uable help of the National Center for Health Education in putting together this commemorative jour- nal.