Tracking Down a Killer
If you use footnotes in scientific papers as the measure of a scientist's preeminence, then Bert Vogelstein, C'70, ranks as the world's greatest scientist. Not long ago, the Institute for Scientific Information conducted a count of citations in important scientific publications and put Vogelstein at the top of its list of authors whose work is cited most often by the scientific community. Vogelstein himself has published over 150 articles in scientific journals; his papers on colon cancer are regarded by medical researchers as classic studies.
Over the last decade, there has been a revolution in cancer research. "I can sum the revolution up in one statement," said Vogelstein. "'Cancer is, in essence, a genetic disease.'" He should know: he helped make the revolution. A professor of oncology and director of the molecular genetics laboratory at the Johns Hopkins Oncology Center, Vogelstein continues to play a leading role in researchers' understanding of the genetic mechanisms underlying colon cancer. Tracking down and implicating more than half a dozen genes that give rise to malignancies, Vogelstein has compiled one of the most detailed and unified profiles of how a cancer unfolds.
After graduating summa cum laude from Penn's undergraduate mathematics program, Vogelstein earned an MD at The Johns Hopkins School of Medicine. He chose to devote his medical career to research on the genetics of cancer after watching one of his first patients, a five year old girl, die of leukemia. "Kids get cancer too," he told an interviewer. "There was so little known about what causes their diseases and so little that we could do for them that I thought the study of genetics might provide a few answers and that this would be a worthwhile way to spend my life."
Since focusing his research on colon cancer in 1981, Vogelstein and his colleagues have done far more than show the disease is a genetic disorder. Vogelstein's accumulated findings provide scientists with a portrait of the key genetic events--the accumulation of five or six mutations within a single cell--that transform a normal cell into a tumor. A set of misguided biochemical cues in the cyclic birth and death of colon-lining cells causes oncogenes and tumor-suppresser genes to propel a cell down the road that leads to malignancy. "Cancer is like a car with the accelerator pushed to the floor and failing brakes," explained Vogelstein.
Another class of genes called mismatch-repair genes, which correct routine mistakes that occur when DNA is duplicated during cell division, are also implicated in a process of accumulated mutations. The run-away growth brought on by cells' refusal to die the programmed death known as apoptosis, combined with unrestrained mutations in the proliferating cells, eventually develop into a polyp, a mass that buds from the colon's interior wall. The polyp's cells continue to undergo genetic changes and the protuberance finally becomes a malignant tumor. Colon cancer, estimated to strike over 130,000 Americans annually, is the nation's third deadliest cancer, resulting in about 56,500 deaths each year.
"Vogelstein was really the first to subject a given type of human cancer to systematic study," said Dr. Robert Weinberg of MIT. "He plotted out a biography of colon cancer from conception to its malignant progression in terms of genes that are mutated in a cancer cell. He is the most productive cancer researcher alive today--and that's not a small compliment." In 1979, Weinberg, a cancer researcher, identified the first cancer causing gene in humans.
Graduates of Vogelstein's lab have founded laboratories at Hopkins, Columbia, and other academic institutions. Many are conducting their own genetic research programs to lay open the inner workings of cancers in other organs. "That's our legacy," Vogelstein points out. And that's not a small compliment either.