By Scott Allen, Globe Staff
Dr. Judah Folkman, a world famous cancer researcher whose insights led to a whole new field of medicine, knew that his relentless pursuit of ideas could wear people out. For 36 years, sometimes in the face of deep skepticism, the renowned Children's Hospital Boston researcher stuck by his belief that tumors could be stopped by cutting off the blood supply they need to grow -- even when his experiments sometimes fizzled.
"If your idea succeeds, everybody says you're persistent," Dr. Folkman liked to joke. "If it doesn't succeed, you're stubborn."
Dr. Folkman, 74, collapsed and died Monday at Denver International Airport while he was awaiting a flight to Vancouver for a medical conference. The cause of death has not yet been determined.
Yesterday, friends and colleagues remembered Moses Judah Folkman as one of the world's most brilliant -- and persistent -- medical researchers, a man whose work has spawned 10 new cancer drugs and launched dozens more into various stages of human testing. Along the way, Dr. Folkman's research into the role of blood vessels in fostering disease also produced breakthrough treatments for a leading cause of blindness. He also made the pivotal discovery in the development of a form of birth control that is implanted under the woman's skin.
"He was indefatigable and unquenchable. There's no such thing in his lexicon as a defeat. It's only a learning point," said Dr. David Nathan, the former president of Dana-Farber Cancer Institute who often debated cancer ideas with Dr. Folkman when Nathan was chief of medicine at Children's. "There are very few Roman candles like him."
Dr. Folkman will also be remembered for his extraordinary work as a mentor to the next generation of scientists, training top researchers such as tissue engineering pioneer Robert Langer, now of MIT, who was drawn to Dr. Folkman's lab for the chance to work with a man who seemed to overflow with ideas and energy. In recent months, Dr. Folkman had been campaigning for more generous federal financial support of young researchers, such as the 120 working with him, complaining in one of his last interviews that the "superstars" of tomorrow are being driven from the field by federal budget cuts.
At his lab yesterday, "everyone, I think, felt they had lost a parent," said Children's Chief Scientific Officer Bruce Zetter, himself a cancer researcher trained in Dr. Folkman's lab. "You trusted him. You respected his judgment. You felt he had your best interests at heart and, at the same time, you're dealing with one of the greatest minds in the country."
Dr. Folkman deliberately shielded his wife Paula and their two daughters from the limelight that often followed him -- he was heralded, somewhat hyperbolically, as the man who would cure cancer on page one of the New York Times in 1998. But, yesterday, Dr. Folkman's widow said she had long since made peace with sharing her husband with the world and that she always knew where she stood in his eyes.
"We were married 47-and-a-half years and every single one of those years, every day, he told me he loved me," said Paula Folkman in an interview. "No one knows what a love story it was. And it was."
A self-confessed "science nerd" from the time he was small -- his mother Bessie Folkman read young Judah the biography of Isaac Newton as a bedtime story -- Dr. Folkman didn't care about fortune and fame. "He didn't know how to use an ATM, to tell you the truth," confessed his wife, who put money in her husband's wallet so that he could buy lunch.
Dr. Folkman did care passionately about ideas and pushing them as far as they could go, something he traced back to his childhood in Michigan and Ohio where his parents required the three Folkman children to talk at the dinner table about something new they had learned that day. Many years later, when Dr. Folkman became chief of surgery at Children's Hospital, he followed a similar approach, always pressing the surgeons to come up with new ideas.
"We would sit at a blackboard every week and he would say, 'Okay, what are your unsolved problems in clinical medicine right now and what can we do in the lab to figure them out?' " Dr. James Mandell recalled of the surgery department meetings Dr. Folkman ran in the late 1970s. Mandell, who considers Dr. Folkman a mentor, is now president of Children's Hospital.
Dr. Folkman's daughter Marjorie Folkman, of New York, said her father took the same brainstorming approach to raising children. "He would play games with us and point to things and say, 'What can we imagine that is? If it's not a tree, what else can it be?' " she said.
A magna cum laude graduate of Harvard Medical School in 1957, Dr. Folkman trained as a surgeon at Massachusetts General Hospital before serving as a lieutenant in the Navy from 1960 to 1962. While stationed at the National Naval Medical Center in Maryland, Dr. Folkman and a colleague discovered that silicone rubber could be used to promote the gradual release of drugs below the skin, the basis of Norplant, the implantable birth control device.
Returning to Boston, Dr. Folkman went to work as a surgeon at Boston City Hospital where the legendary cancer researcher Sidney Farber, for whom the Dana-Farber Cancer Institute was named, discovered him. Though Dr. Folkman had little experience operating on children, Dr. Nathan recalled that Farber "moved heaven and earth" to recruit Dr. Folkman to work with him at Children's Hospital, even sending him to learn pediatric surgery from future Surgeon General Dr. C. Everett Koop in Philadelphia.
But Dr. Folkman's free-thinking style went against the grain of conservative Boston medicine and his willingness to talk publicly about theories before they were proven made him a frequent target of criticism, especially after the 1971 publication of his first paper on the role of blood vessels in the growth of tumors. At the time, cancer specialists overwhelmingly focused on the use of surgery and toxic chemotherapy drugs to stop cancer's spread, and Dr. Folkman's idea of cutting off cancer's blood supply seemed peripheral to the war on cancer.
When Dr. Folkman's research made national headlines in 1972, colleagues accused him of offering people false hope about breakthroughs that had not yet occurred. In hindsight, Dr. Folkman agreed, but he never gave up trying to prove tumors would shrink if their blood supply dried up. Over time, Dr. Folkman's increasingly impressive results treating cancer in mice wore adversaries down, convincing many of them to join him in looking for compounds that could shut down the formation of blood vessels feeding tumors.
Finally, in 2004, the Food and Drug Administration approved the first drug based on Dr. Folkman's research. Although Avastin was proven only to add a few months on average to the life expectancy of patients with advanced colon cancer, the drug added years to some patients' lives -- and without the sometimes debilitating side effects of chemotherapy. Today, more than 1,000 laboratories are experimenting with drugs that target a tumor's blood supply and 1.2 million patients have prescriptions for at least one of the 10 that have been approved.
Some cancer specialists have been disappointed that Avastin and other similar drugs, called angiogenesis inhibitors, haven't had a more dramatic impact, but Dr. Folkman wasn't one of them, pointing out that cancer is one of the most complex diseases known. In an interview with the Globe in November, Dr. Folkman conceded that it's much harder to cut off cancer's blood supply than he once believed.
"The ideas are simple, but getting them figured out is very complicated," Dr. Folkman said. "We never use the word 'cure' because it is far away." Instead, Dr. Folkman said, various angiogenesis inhibitors could be combined to keep tumors in check for the long term.
Dr. Folkman had more dramatic success against age-related macular degeneration, which causes blindness by destroying the central part of the retina. Angiogenesis inhibitors have shown such success in restoring vision that one patient recently gave $100,000 to Children's Hospital in gratitude, according to Robert Cooke, author of the 2001 biography, "Dr. Folkman's War."
Paula Folkman said the family plans funeral services for Sunday at Temple Israel in Boston, but the exact time had not been set yesterday. In addition to his wife and daughter, Dr. Folkman is survived by another daughter Laura Steuer of California, and one granddaughter.
Paula Folkman said Dr. Folkman's father, a rabbi, had once hoped his son would follow in his footsteps, but, when Judah made it clear he wanted to be a doctor, Jerome Folkman urged him to be "a rabbi-like doctor." Looking back, she said, "I think Judah accomplished exactly that."
Scott Allen can be reached at firstname.lastname@example.org.
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