Judah Folkman

For most of his career, Judah Folkman, the pioneering cancer researcher who died late Monday at 74 of an apparent heart attack, was scorned by everyone but the government.

As a young naval surgeon in Bethesda, Maryland, he and a fellow researcher noticed that mice tumors stopped growing when removed from the body, but resumed their explosive growth when reattached. As his biographer Robert Cooke described that mid-1960s incident to the Associated Press, "that was the clue that set him off. He reasoned there was some barrier that stopped those tumors from growing. And after years of banging his head against the wall he realized that it was the blood supply."

Folkman hypothesized that inhibiting the regulatory protein that triggered the production of new blood vessels would slow tumor growth. It wouldn't be a cure for cancer. He was always cautious about his claims. His hope was to develop a mechanism for controlling tumors, and perhaps turning the dread disease from a death sentence into a chronic condition.

Today, there's nearly a dozen anti-angiogensis drugs either on or approaching the market and dozens more in development. Every one of them owe their existence to Folkman's discoveries, which would not have been possible without the almost uninterrupted financial support of the National Cancer Institute over four decades.

Son of a Columbus rabbi and a social worker, he saw medicine as a way to emulate his parents' dedication to community service. Yet he was no altruist. In the last decade of his life, he worked closely with numerous pharmaceutical companies as his insights moved from bench to bedside. He recently joined the board, took stock options and consulting fees from start-up Synta Pharmaceuticals, which is investigating new cancer drugs.

But for most of his career, he was on the NCI grants treadmill. Most cancer researchers never accepted his theory that blocking blood vessel growth could control cancer. Folkman ignored them as he doggedly pursued his search for the proteins that stimulated and stopped blood vessel growth. Like so many physician-researchers of his generation, he had been inspired as a young man by Sinclair Lewis' Arrowsmith and Paul DeKruif's The Microbe Hunters, whose core message was that failure was an inescapable part of scientific life.

The fact that he was brilliant as well as stubborn didn't hurt. A graduate of Ohio State, he became a full professor at Harvard Medical School by the time he was 33. They placed his lab at Children's Hospital in Boston next to John Enders, who had won the Nobel Prize for his work on polio. At one point, when NCI was about to turn him down for a grant (which didn't happen because Mary Lasker intervened with the National Institutes of Health scientific advisory board), Enders told him not to worry.

"This just proves that there are no experts of the future," he said. "There are only experts of the past, and they sit on the study section."

It took nearly three decades to isolate the proteins that turned blood vessel growth on and off -- endostat and angiostat. The crucial paper was published in 1993. After that it was only a matter of time before drug companies found inhibitors that blocked vascular endothelial growth factor (VEGF). Folkman himself is listed as an inventor on 49 patents, many of them licensed through Children's Hospital to private firms. The first to market with its own molecule was Genentech, which won approval for Avastin (bevacizumab) from the Food and Drug Administration in February 2004.

As predictable as sundown, the press turned his emergence from obscurity into a storm-filled night. In May 1998, Gina Kolata splashed a sensational story across the front page of the New York Times headlined, "Hope in the Lab: A Cautious Awe Greets Drugs That Eradicate Tumors in Mice." The story proclaimed a cure for cancer was on the horizon, and featured DNA co-discover James Watson claiming Folkman was going to cure cancer in two years. A day later Kolata had a multi-million dollar book deal and the stock of the company that Folkman was working with soared.

Within days, the inevitable caveats and cautionary statements emerged. The Times told Kolata to reject her book deal. Folkman had never wanted his work to be sensationalized in that way. "I don't think angiogenesis inhibitors will be the cure for cancer," he wrote a few months later in Scientific American. "But I do think that they will make cancer more survivable and controllable, especially in conjunction with radiation, chemotherapy, and other treatments."

Anti-angiogenesis drugs must be ranked as one of the great advances in the long-running war on cancer. They are a novel way of extending life for months and even years in some cases. They have far fewer side effects than traditional chemotherapy drugs, which are indiscriminate cell killers and therefore highly toxic.

And, they owe their existence to a government-financed system of basic medical research that sustains unpopular ideas over the arc of a long career. Folkman dedicated his life to science, not making money. The result is medical progress, and a lot of companies making a lot of money.

Posted by gooznews at January 15, 2008 10:48 PM