One Man's Quest To Cure Cancer

The Monsanto grant got Folkman's experiments back on track. In 1981 he quit his position as surgeon-in-chief at Children's (and one third of his salary) to devote himself full time to research. Someone who combines research and surgery never has it easy, he once said: ""His counterpart in basic science thinks he is a dilettante researcher, his clinical colleagues think he is unsafe and his mother-in-law says, "He's 35 years old and still working with animals. When will he be a real doctor?' ''

Folkman was determined to identify the substances that ooze out of tumors and attract capillaries. In 1983, two of his scientists, Michael Klagsbrun and Yuen Shing, isolated such a substance. It was named ""basic fibroblast growth factor.'' Finally there was an actual molecule, not just a nifty idea, and researchers who had been standing (or carping) on the sidelines climbed on the angiogenesis bandwagon. Even serendipity smiled on Folkman. A culture of blood-vessel cells that Donald Ingber had been growing in Folkman's lab got contaminated. A yeast fungus had apparently blown in. Standard procedure is to chuck a contaminated cell line. But Ingber had a hunch. In a replay of Alexander Fleming's noticing that bacteria did not grow near penicillin mold, Ingber saw that the blood vessels had retreated from the fungus. He had discovered an angiogenesis inhibitor, now called TNP-470.

Many fields of science are infamous for professors who work their students like galleon slaves and hog all the credit. Folkman is famous for the opposite. He was inspired to pursue a career in medicine by visits he made to the sick with his rabbi father. Students recall Folkman's hints that he once had not been treated well by a superior, ""and he vowed then and there that he would be different,'' says Zetter. Folkman is generous with colleagues and competitors alike, mailing samples of cell lines to anyone who asks. He won't add his name to papers reporting research that others did in his lab (many professors take full credit merely for running the place).

After Ingber and Folkman's discovery of the anti-angiogenesis agent in fungus, other researchers suggested that a tumor secretes not only a substance that stimulates angiogenesis, but one that inhibits it, too. That would explain why, when a surgeon removes a primary tumor, little satellite tumors sometimes start acting up, like kids whose teacher has stepped out. The teacher here is the tumor that secretes an anti-angiogenesis molecule that keeps smaller tumors in check; absent the tumor, the smaller tumors can grow--and kill. In 1994, Dr. Michael O'Reilly in Folkman's lab isolated such an angiogenesis inhibitor; he called it angiostatin. He discovered a second, endostatin, in 1996. Endostatin so stifles blood-vessel growth that human cancers grafted onto mice actually shrink, as O'Reilly, Folkman and colleagues reported last November. Those results were the spark that flamed into last week's hype, and hope, about a cure for cancer.

Folkman once said that treatment based on the angiogenesis model would be available within five years. That was in 1972. Now he points to dozens of books in the conference room. ""All those books, those red books,'' he says. ""Those are all experiments [of ours] that didn't pan out.'' According to a 1997 editorial in the journal Science, by the early years of the next decade cancer will overtake heart disease as the nation's No. 1 killer. Everyone--doctors, scientists and, most of all, today's patients and tomorrow's--hopes that Folkman's current lab book does not wind up on the shelf of failures.

TURNING THE TABLES ON TUMORS