April 23, 2002
Brookhaven Lab Scientist Wins Environmental Mutagen Society Award
Upton, NY - Richard Setlow, a senior biophysicist at the U.S. Department of Energy's Brookhaven National Laboratory, has been named the recipient of the 2002 Environmental Mutagen Society (EMS) Award. He is being recognized for his research contributions to the field of environmental mutagenesis, which involves the study of how various agents in the environment, such as chemicals and radiation, lead to DNA damage and how that damage is repaired. DNA is the material that forms the molecular basis for heredity.
The award will be formally announced at the annual EMS meeting in Anchorage, Alaska, on April 30. Setlow will receive a plaque and monetary award.
"I am pleased to be chosen for this award," said Setlow. "I am gratified that discoveries I've made have had wide application in many fields and have advanced scientific understanding of how genetics, the environment, and human health are interconnected."
Specifically, Setlow is being honored for his discovery of nucleotide excision repair and the development of a method called bromouracil photolysis to study excision repair. He also was cited for his discovery of a crucial link between unrepaired DNA damage and cancer.
Almost forty years ago, Setlow and his colleagues at Oak Ridge National Laboratory discovered that certain DNA defects caused by ultraviolet light lead to biological damage. He also showed that, in normal bacterial cells, these defects could be removed by cellular enzymes, a process known as nucleotide excision repair. This repair cuts out the damaged regions and patches the resulting holes. This groundbreaking research led to great interest in repair, since certain genetic diseases stem from inherited deficiencies in DNA repair.
In the early 1970s, Setlow and James Regan, a colleague at Oak Ridge National Laboratory, developed bromouracil photolysis, a method to measure DNA repair that became a standard technique. They incorporated bromouracil, an analog of thymine, into the repaired patches of DNA. Exposure of the repair patches to long-wavelength ultraviolet light resulted in DNA breaks in the bromouracil. From the ultraviolet dose and the numbers of breaks, they were able to calculate the numbers and sizes of the repaired regions arising from chemical or physical agents in the environment.
At Brookhaven in the early 1990s, Setlow and his colleagues began investigating the role of melanoma-susceptibility genes and tumor-suppressor genes in causing melanomas. They found that the most serious form of skin cancer, known as malignant melanoma, is induced by all wavelengths of the sun's ultraviolet rays. Based on experiments using tropical fish, which, like humans, develop melanoma from exposure to sunlight, this surprising discovery contradicted the long-held belief that only short ultraviolet light wavelengths were potentially harmful.
Currently, Setlow is working with Japanese collaborators on NASA-funded research to estimate the magnitude of mutations in sperm of astronauts resulting from exposure to high-energy cosmic rays in outer space. As a model, they are using fish native to Japan, called medaka. Male fish are exposed to energetic nuclei from Brookhaven’s particle accelerator, the Alternating Gradient Synchrotron, and mated with unexposed females. Mutations in the sperm result in color changes in fertilized embryos that are easily observed because the embryos are transparent.
In a study funded by the Environmental Protection Agency planned for the near future, Setlow and Brookhaven’s Lynn Mendelman will work with Marine Sciences at Stony Brook University to investigate potential mutagens in sediments around Long Island Sound. For this study, they will use transgenic medaka fish in which genes can be isolated to measure mutations.
Setlow received his A.B. from Swarthmore College in 1941 and his Ph.D. in physics from Yale University in 1947. He taught physics and biophysics at Yale University before he joined the Biology Division at Oak Ridge National Laboratory in 1961. He came to Brookhaven in 1974, and in 1979 was named Chair of the Laboratory's Biology Department. In 1986, he became Brookhaven's Associate Director for Life Sciences. He returned to full-time research in 1998.
Among his many honors, Setlow won the 1988 Enrico Fermi Award, the most prestigious scientific award given by the U.S. Department of Energy, for his contributions to the fields of radiation biophysics and molecular biology. He has served on various advisory boards, including the Office of Technology Assessment and the Food and Drug Administration. Setlow has also served as president of the Biophysical Society and president of the Comite International de Photobiologie. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and numerous other professional organizations.