One Man's Quest To Cure Cancer

Over the next few years Folkman became convinced of his hunch. Tumors that he implanted in rabbits' eyes did not grow at all until blood vessels, spreading from the cornea, reached them. It was just like a pioneer town that didn't grow until the railroad tracks got there. But when the blood vessels did arrive, the tumor grew as fast as a Western boomtown: more than 100 times their original size in 10 to 15 days. Now Folkman realized something even more revolutionary: tumor cells must secrete some natural compound to induce blood vessels to sprout tiny capillaries. Without the come-hither molecule, capillaries do not connect to a tumor; without a custom-grown blood supply, the tumor stays dormant.

That observation offered several fat targets for treatment. Theoretically, you can interfere with the tumor cell so it does not secrete the molecular signal that summons blood vessels. Or you can throw a biological monkey wrench at the blood vessels so they cannot receive this signal, or cannot respond to it. Either way, the tumor should shrink. But the possibilities were even greater, because blood vessels are not one-way streets. Besides bringing oxygen and nutrients to tumors, they serve as escape routes. Cancer cells break off from the tumor, enter the bloodstream and colonize distant points to produce secondary tumors. It is these metastases, not the primary tumor, that often kill. Without blood vessels, there is no railroad out of town; without a railroad, there are no metastatic escapees.

Folkman submitted his first major paper laying out the theory of blood vessels and cancer to ""many good journals.'' All rejected it, saying his conclusion was not supported by the data he submitted. The New England Journal of Medicine finally ran it, in 1971. Throughout the 1970s, ""the reaction was mainly hostility and ridicule,'' recalls Folkman. ""People would ask me [at scientific meetings], "You really don't believe that, do you?' '' An application for a research grant from the government was denied; the reviewer deemed the subject ""just in your imagination.''

Joining Folkman's lab seemed like professional suicide. ""People warned me not to hook up with him,'' says cell biologist Bruce Zetter, who nevertheless agreed to join Folkman's search for ways to grow capillary cells in a dish and who now heads his own lab at Children's. Dr. Henry Brem, who worked with Folkman in 1973 and is now a neurological oncologist at Johns Hopkins University, recalls his first-year pathology professor's catching flak ""just for mentioning Folkman's hypothesis that angiogenesis plays a role in tumor growth. The biggest names at Harvard were saying it didn't belong in the med-school curriculum.'' Conventional wisdom held that angiogenesis was an inflammatory process having nothing to do with tumor progression. For 10 years, whenever Folkman got up to speak at a scientific meeting, he would ""hear people laughing in the corner,'' he says. Or the room would empty out. ""Everybody had to go to the bathroom at once,'' he says.

The nadir came in 1974. ""A lot of people who worked for us just left,'' Folkman says. ""They said, "We're not making any progress'.'' Biology had become so focused on genes and the proteins they made that if a theory didn't fit this paradigm, it was dismissed. ""At Harvard there was almost this rule that if you didn't come up with a molecule in five years it must not exist,'' says Dr. Steven Brem, a brother of Henry's and now a neurosurgeon at the H. Lee Moffitt Cancer Center in Tampa, Fla. Folkman's five years were almost up. Low on research money, he and a colleague accepted an unheard-of 12-year, $23 million grant from the Monsanto Co. It created a firestorm at Harvard Medical School, where Folkman had (and has) a joint appointment. No one there had ever before accepted that kind of industry money. Now, of course, corporate money flows like distilled water into America's university labs.

At national meetings, scientists would greet one of Folkman's presentations with a knowing ""Oh, I see Folkman has cured cancer--again.'' ""I would always come home very depressed,'' Folkman says. His wife, Paula, an alto who sings with the Boston Symphony at Tanglewood and is the daughter of a doctor who made house calls, was his source of strength. He often had her read his manuscripts, and, except when he was traveling, would walk home to have dinner with her and their two daughters, one now an elementary-school teacher and one a modern dancer. His students remember his lectures on how to keep a marriage intact (he wed in 1960) almost as well as they remember his seminars on angiogenesis.