Five Americans Receive 1993 Gairdner Awards

For the first time since 1983 and only the second time in the 36- year history of the prestigious Gairdner Foundation International Awards, all recipients of this year's prizes are United States- based researchers. Traditionally, the awards have had a decidedly international flavor; over the years, winners have included scientists from 12 different nations, spanning four continents. This year, the Willowdale, Ontario-based organization will honor five American researchers in the fields of gene targeting, clinical epidemiology, brain functioning, and cerebral scanning with $30,000 cash prizes. The awards will be presented in Toronto on October 22 by Rose Wolfe, chancellor of the University of Toronto. The ceremony, including brief lectures from the winners describing their research, is held at the University of Toronto each year. Since its inception in 1957, the Gairdner Foundation has honored 230 scientists. Forty of these have subsequently won the Nobel Prize. The most recent Gairdner/Nobel winners are German biologist Bert Sakmann, who won the Gairdner in 1989 and the Nobel in 1991; University of Washington biochemist Edwin G. Krebs, who won the Gairdner in 1978 and the Nobel in 1992; and University of California, San Francisco virologist Michael Bishop, who won the Gairdner in 1984 and the Nobel in 1989. Among this year's Gairdner recipients is Stanley B. Prusiner, a professor of virology and neurology at UC-San Francisco. Prusiner is being honored for "his contributions to our understanding of brain degeneration caused by novel infectious agents called prions," according to a Gairdner Foundation statement. Prions are infectious proteins that cause transmissible neurodegenerative diseases, often resulting in mental retardation and death. Prusiner's most cited paper, with 385 citations, is entitled "Novel proteinaceous infectious particles cause scrapie" (Science, 216:136, 1982), according to the Institute for Scientific Information (ISI) in Philadelphia. Prusiner, 51, received his medical degree from the University of Pennsylvania in 1968. He joined the faculty of UC-San Francisco in 1974. Another of the 1993 awardees Alvan R. Feinstein medicine and epidemiology at Yale University, "led the intellectual movement that established modern clinical epidemiology as a scientific discipline," according to the Gairdner Foundation. The foundation notes that Feinstein's "methods have led to improved classification of disease and the quantitative use of clinical signs and symptoms in the study of disease and, for example, have contributed to the prevention of rheumatic fever and to improving assessment of prognosis in cancer." "Science," Feinstein says, "is usually regarded as attempts to explicate nature: How does nature work? What are the mechanisms of disease and biology? "One can also, however, ask basic questions of how to change what nature has done or how to prevent what nature might do. Those are questions of intervention rather than explication. "In the world of medicine, those interventions occur as acts of patient care, and there hasn't been very much science devoted to that. It's usually thought of as art. What I've been saying is that if you can look at those things in a hardheaded, scientific way, you can find out what is happening to a patient at a human level as well as their white blood count." Feinstein, whose work has been cited in thousands of publications over the years, is perhaps most widely known for two books: Clinical Judgment (Huntington, N.Y., Robert E. Krieger Publishing Co. Inc., 1967) and Clinical Epidemiology (Philadelphia, W.B. Saunders Co., 1985). Feinstein, 67, is a graduate of the University of Chicago, where he received his bachelor's degree in 1947 and his medical degree in 1952. He has been at Yale since 1969. Another winner, Washington University radiation scientist Michel M. Ter-Pogossian, is being recognized by the Gairdner Foundation for his contributions to the development of the positron emission tomographic (PET) scanner. The device utilizes radioactive isotopes and gamma rays to produce a pattern of brain function helpful in the diagnosis and treatment of epilepsy, cerebrovascular disease, and other mental disorders, such as depression and schizophrenia. Ter-Pogossian says his work at Washington University in St. Louis has focused on increasing the number of practical clinical applications of cerebral scanning. "I think in the long run, the strength of PET will be helping us to understand pathophysiology," he says. "Any form of illness results from and is accompanied by local biochemical changes. And this is very true of mental diseases. Therefore, if you can study--in vivo and noninvasively--biochemical changes in various organs, you have a tool of great importance in understanding what disease is." According to ISI, Ter-Pogossian's most cited paper on PET, with about 130 citations, is entitled, "A positron emission tomograph utilizing cesium fluoride scintillation detectors" (Science, 6:125, 1982). Born in Berlin, Ter-Pogossian, 68, received his bachelor's degree from the University of Paris in 1942. He received his Ph.D. in nuclear physics from Washington in 1950 and then joined the faculty there. Mario B. Capecchi, of the University of Utah School of Medicine in Salt Lake City, and Oliver Smithies, of the University of North Carolina, Chapel Hill, will each receive the Gairdner award for their independent but similar research into the technique of gene targeting, also called gene knockout. "To me it's very appropriate that we both be recognized because we both made different contributions towards the total procedure," says Smithies, who, before joining the department of pathology at North Carolina in 1988, spent the previous 37 years as a professor at the University of Wisconsin in Madison. Smithies's early research into altering specific genes was aimed at globin genes in mammalian cells, specifically mice. "Both Mario and I, more or less at the same time, tried to apply this technique to embryonic stem cells and showed it effective," says Smithies. "I was the first person to demonstrate that it was possible to modify a natural gene in a mammalian cell in tissue culture," he says. "What Mario did was develop a very simple vector for doing these experiments, making them more practically accessible to others." Smithies's most cited paper on the subject, according to ISI, has acquired more than 260 citations, and is called "Insertion of DNA--sequences into the human chromosomal beta-globin locus by homologous recombination" (Nature, 317:230, 1985). Smithies, 67, received his Ph.D. in biochemistry from Oxford University, England in 1951. Capecchi notes that this technique allows the researcher to replicate large numbers of mice with specific genetic diseases built in, such as cystic fibrosis. "In the long run, this technique will have a much wider application and allow you to systematically modify any of those genes and change its expression pattern," he says. "We will be able to perform a detailed analysis of what the gene is doing in the intact animal." Capecchi is now working on unraveling the functioning of the complex hox genes, which are involved in specifying body structure, such as limb size and finger width. Capecchi's most cited paper, with more than 290 citations, is called "Site-directed mutagenesis by gene targeting in mouse embryo-derived stem-cells" (Cell, 51:503, 1987). Born in Verona, Italy, Capecchi, 55, received his bachelor's degree in chemistry and physics from Antioch College, Yellow Springs, Ohio, in 1961 and his Ph.D. in biophysics from Harvard University in 1967. He has been at the University of Utah since 1973.

Five Americans Receive 1993 Gairdner Awards

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