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Robert Cooke

The revolutionary doctor

JUDAH FOLKMAN JUDAH FOLKMAN
Email|Print|Single Page| Text size + By Robert Cooke
January 17, 2008

THE HARDEST PART of holding a conversation with Judah Folkman was getting past his beeper. Every couple of minutes, he'd get beeped and would offer advice to someone, somewhere about how to deal with cancer, find a doctor, look for something that might save a life.

As a physician, Folkman, who died Monday, was patient-oriented. When he was a master surgeon at Children's Hospital, Folkman gave his home phone number to patients. "They never abused it," he once said.

Similarly, when traveling, Folkman carried patients' phone numbers so he could call at least 10 per night to answer questions and offer advice. They were not his patients - he wasn't practicing medicine anymore - but he called to help anyway.

As a teacher, he was the best. Several times Folkman won the medical school's annual award for quality teaching, and his lectures were always crowded. Countless physicians recall his mentoring ability. Many of them are now deans and department heads at medical centers around the country and abroad. He could be blunt when necessary, warning medical students "you have chosen a service profession. Get used to it." If they didn't like long hours, coping with patients, and being on call, "then do something else. You could be a banker."

As a researcher pursuing what many colleagues considered a screwy idea - angiogenesis - Folkman faced severe opposition. One rejection notice from a review committee said, "This is just dirt." Another said his results "exist only in the mind of the principal investigator." A few years ago he posted a notice from the National Institutes of Health - announcing angiogenesis would be a major research topic in several institutes - right next to a rejection note that earlier dismissed his ideas as worthless. He liked the irony.

Folkman's central idea was that a tumor, like any living thing, requires nutrients and oxygen to survive and grow. But these supplies cannot seep through tissue fast enough to support an expanding tumor, so new blood vessels must grow near to deliver a rich supply. This means a tumor has to somehow induce a new network of capillaries to grow close, and keep growing as the tumor expands in size.

Folkman suggested the tumor must release a signal - a hormone-like growth factor - that stimulates blood vessel growth, mimicking the way blood vessels react to repair a wound. And if that is true, he said, then opposing factors must also exist that the body uses to shut off blood vessel growth once wound repairs have been made. All those ideas turned out to be true - but very complicated and hard to prove.

Finding the proof was extraordinarily difficult, in part because Folkman was working long hours as head of surgery at Children's Hospital, and trying to run a laboratory chasing this idea about halting cancer growth by drying up its blood supply. Worse, his willingness to discuss the idea generated enthusiasm for treatments that didn't exist, and he was accused of raising false hopes. Much ridicule followed. He later gave up his surgery duties to work on research full time.

Dr. Harold Varmus, Nobel laureate and former head of the NIH, once recalled that Folman "was described as this guy in a hair shirt working on an island in Boston Harbor." Thus Folkman was viewed by many as an isolated, obsessed man pursuing an illusion. "Judah was thought of as a sort of renegade scientist, trained as a surgeon, pursuing a phenomenon most of us thought of as peripheral to the central issues of cancer," Varmus explained.

But Folkman persevered, despite having to find, modify, and even invent the tools and techniques needed to prove his point. His research team surmounted barrier after barrier, learning to grow blood vessel cells in culture, finding ways to stimulate and/or block their growth. In the mid-1990s they showed that natural agents - such as angiostatin and endostatin - do exist, and cause tumors to shrink as he predicted. But they haven't yet been tested well enough to win approval.

However, this work did lead directly to new drugs - the best known is Avastin - that are now being used by more than a million cancer patients worldwide, actually extending lives. Similar drugs are also, for the first time, helping restore some vision in people blinded by the "wet" kind of macular degeneration. It's a revolution in eye care.

And the bottom line? The Nobel committee at the Karolinska Institute in Stockholm moved too slowly. It doesn't give the cherished prize posthumously.

Robert Cooke is author of "Dr. Folkman's War, Angiogenesis and the Struggle to Defeat Cancer."

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