Four Receive Gairdners For 'Tangible Achievement'

Four prolific researchers, all working at institutions in the United States, will receive or share Gairdner Foundation International Awards at a ceremony next month. The Ontario, Canada-based foundation annually presents no-strings-attached awards of $30,000 Canadian (about $22,500 U.S.) and a sculpture to honor "individuals whose work or contribution constitutes tangible achievement in the field of medical science." This year the foundation is citing: Corey S. Goodman, a professor of neurobiology in the department of molecular and cell biology at the University of California, Berkeley, an adjunct professor in the department of physiology at UC-San Francisco, and a Howard Hughes Medical Institute investigator; Richard O. Hynes, a professor of biology at the Massachusetts Institute of Technology (MIT), director of MIT's Center for Cancer Research, and a Howard Hughes Medical Institute investigator, who is sharing an award with Erkki Ruoslahti, president and CEO of the La Jolla, Calif.-based Burnham Institute and an adjunct professor of pathology at UC-San Diego; and Alfred G. Knudson, Jr., a senior member of the scientific research staff at Fox Chase Cancer Center in Philadelphia. The awards will be given October 24 at the University of Toronto. The Gairdner Foundation was established in 1957 by Toronto stockbroker and industrialist James Arthur Gairdner, who had an interest in medical research. Three to six winners are chosen each year by a medical advisory board composed of researchers from Canada, the United States, and the United Kingdom. The advisory board selects candidates from lists complied by a smaller medical review panel. First given in 1959, the awards have been presented to 247 scientific luminaries, 48 of whom subsequently received the Nobel Prize. "When you sense that the people who have gotten the award are people who you respect enormously, then the value of the award goes up," says Knudson. He was especially touched that previous winners had written him soon after his award was announced to congratulate him. NEUROLOGICAL INSIGHTS: UC-Berkeley's Corey Goodman is being honored for his work on growth cones, the growing tips of neurons. Goodman, 46, is being honored for contributions in developmental neurobiology. His work has focused on growth cones, the growing tips of neurons. Using molecular genetic approaches to study the fruit fly Drosophila, he has elucidated the mechanisms underlying how growth cones find and recognize their targets. Among his team's projects has been a genetic analysis of fasciclin II (Fas II), which acts to control the sorting out of axons, or selective fasciculation. His group also has identified connectin, a surface protein that has a repulsive function during growth cone guidance and formation of synapses. In addition, they have studied the semaphorins, a family of proteins that can serve as signals to guide growth cones. They have done genetic analysis of growth cone guidance at the midline of the developing central nervous system and have investigated the molecular mechanisms behind the ability of motoneuron growth cones to recognize specific muscle fibers. These findings may provide clinical insights into neurological disease and repair of nervous system injury. His most noted work, "Expression of engrailed proteins in arthropods, annelids, and chordates" (N.H. Patel et al., Cell, 58:955-69, 1989), has been cited more than 400 times. Goodman began his pioneering studies on the mechanisms of growth cone guidance as a postdoctoral fellow at UC-San Diego in 1977-79. Prior to joining UC-Berkeley, he was a faculty member at Stanford University's biology department, where he began his analysis of axon guidance. He received the prestigious Alan T. Waterman Award from the National Science Board in 1983. He is a member of the National Academy of Sciences (NAS). Goodman says being honored by the Gairdner Foundation was a total surprise. "You just want to go about your life, have fun, and do science because you like solving puzzles," he remarks. "And if something like this comes along, it's a total kick." Photo: Donna Coveney BIOLOGICAL REALIZATION: The "limited set of molecules" that affects all of biology interests MIT biologist Richard Hynes. Hynes and Ruoslahti are being honored jointly in recognition of their independent investigations of the interaction among cells and with the extracellular matrix that surrounds them. Interactions of cells with the extracellular matrix are altered in malignant cells; this may play a role in metastasis. According to the award citation, "this research is advancing our understanding of such processes as cell differentiation and proliferation, as well of cell adhesion and mobility." The foundation also notes the work's relevance in cancer, blood coagulation, and wound healing. Hynes, 52, has done genetic analyses of fibronectin and integrin, proteins responsible for cell-substrate adhesion. "One of the exciting things about the field is the realization that all of the different bits of biology rely on a limited set of molecules which we hope to understand," he says. He believes the awards are important because they recognize the whole area of cell adhesion. "Science and research is exciting in its own right, but the fact that it has a lot of application is what counts," he comments. His seminal paper, entitled "Integrins-A family of cell-surface receptors" (R.O. Hynes, Cell, 48:549-54, 1987), has been cited more than 2,800 times. Hynes, a native of the U.K., has been at MIT since 1975. He was the head of the biology department there from 1989 to 1991. He is a member of NAS. PROLIFIC CEO: Erkki Ruoslahti, president and chief officer of the Burnham Institute, is being honored for his work on cell-substrate adhesion. Ruoslahti, 57, studies integrin signaling and extracellular matrices. He is investigating the mechanisms of fibronectin matrix formation and its effects on tumorigenicity and metastasis. He also has focused on peptide mimics of adhesion proteins. His team has hypothesized that an epithelial cell detaching on the underlying matrix remains floating and is susceptible to apoptosis. A cell that attaches to the wrong extracellular matrix may receive a signal to undergo apoptosis, or cell death. Attachment through a "wrong" integrin can generate such a signal, whereas a cell that reattaches to the original matrix would survive. "The first hurdle for cancer cells to become metastatic," Ruoslahti says, is to be able not to commit suicide when they leave their appropriate place. His cell adhesion article entitled "New perspectives in cell adhesion-RGD and integrins" (E. Ruoslahti, M.D. Pierschbacher, Science, 238:491-7, 1987), has been cited more than 2,100 times. In addition to leading the Burnham Institute-a 350-employee, independent, nonprofit organization founded in 1976 as the La Jolla Cancer Research Foundation-Ruoslahti holds its William H. Fishman Chair in Cancer Biology. A native of Finland, he joined the institute in 1979. In 1995 he was a Nobel Fellow at the Karolinska Institute in Stockholm. ONE, TWO: The "two-hit" theory of cancer causation earned Fox Chase's Alfred Knudson, Jr. his Gairdner. Knudson, 75, notes that "I was always interested in cancer in children." He is being honored for developing the "two-hit" theory of cancer causation, which related hereditary and nonhereditary forms of retinoblastoma and other tumors. According to Knudson, 60 percent of the cases occur by chance, and 40 percent occur in children who inherited a gene. Both cases involve two events (or "hits"), the first occurring before conception and the second occurring after. Knudson investigated other hereditary cancers and found that they had similar relationships to the nonhereditary form of the same cancer. According to the Gairdner Foundation, "this hypothesis has become a paradigm for mutational theories on the origins of cancer and led directly to the concept of suppressor oncogenes." His research on antioncogenes, genes that can suppress the growth of cancer cells, has aided understanding of genetic program errors that turn normal cells into cancer cells. Knudson's paper "Mutation and cancer-a statistical study of retinoblastoma" (A.G. Knudson, Proceedings of the National Academy of Sciences, 68:820, 1971), has been cited more than 1,400 times. A member of NAS, Knudson has been at Fox Chase since 1976. In 1992, he was named a Fox Chase Distinguished Scientist and senior adviser to the president. He was center president in 1980-92 and scientific director in 1982-83. In 1995, he was appointed as special adviser to National Cancer Institute director Richard Klausner. Knudson has collaborated on research on the genetics of childhood cancer with his wife, Anna T. Meadows, director of the pediatric oncology division at Children's Hospital of Philadelphia. David C. Lyons is a writer based in Southampton, Pa.

Four Receive Gairdners For 'Tangible Achievement'

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