Vogelstein, Bert

▪ 1998

      When American cancer researcher Bert Vogelstein graduated from medical school in 1974, the underlying causes of cancer were not well understood. Although scientists knew that cancer cells were once-normal cells transformed into unruly mavericks, the reasons for the transformation were unclear—until Vogelstein took on the task of elucidating the life history of a tumour cell. For his groundbreaking work on the genetics of cancer, he was awarded the 1997 William Beaumont Prize.

      Vogelstein's decision to study cancer stemmed from his curiosity about the molecular basis of the disease as well as from his experiences working with young cancer patients during his residency in pediatrics at Johns Hopkins Hospital, Baltimore, Md. He then spent two years (1976-78) as a research associate at the National Cancer Institute. In 1982 Vogelstein set out to apply his laboratory expertise to the study of colon cancer. His goal was to identify the genes that, when damaged or defective, give rise to the disease. Analyzing DNA (the genetic material) from the cells of colon cancer tumours, he and colleagues found that a particular gene was present in a mutated form in more than one-half of all the tumours they studied. The gene in question, called K-ras, belongs to the class known as oncogenes (i.e., cancer-inducing genes). In their normal form, as proto-oncogenes, these genes stimulate cells to replicate when necessary. When damaged, however, they may signal the cell to divide ceaselessly. Could a single mutated gene then trigger the development of cancer? Evidence suggested that this was not the case, and Vogelstein suspected that a defect in another class of growth regulators—called tumour-suppressor genes for their role in preventing uncontrolled cell proliferation—might also be involved. Again studying DNA from colon cancer cells, Vogelstein eventually identified three tumour-suppressor genes, APC, DCC, and p53, mutated forms of which were found in the tumour cells. Further research on p53 showed that mutations in this gene were involved not only in colon cancer but in a host of other malignancies; in fact, p53 was implicated in more than 50% of all cancerous tumours. More recent data from Vogelstein's laboratory provided evidence of still another class of cancer-causing genes, called mismatch repair genes, whose normal function is to identify and repair defective DNA segments. Vogelstein's research made it clear that tumours develop as a result of the sequential accumulation of mutations in proto-oncogenes, tumour-suppressor genes, and mismatch repair genes. On a practical level, his work led to the development of diagnostic tests for colon cancer that promised to greatly reduce deaths from the disease.

      Vogelstein was born on June 2, 1949, in Baltimore, Md., and attended the University of Pennsylvania (B.S., 1970) and Johns Hopkins University School of Medicine (M.D., 1974). He was coauthor (with Kenneth Kinzler) of the book The Genetics of Cancer (1997) and had published more than 200 research papers in professional journals. Although Vogelstein was a driven scientist who spent most of his time in his laboratory, he relaxed by playing keyboards for Wild Type, a band made up of a number of scientists from Johns Hopkins University.

MARY JANE FRIEDRICH

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