Judah Folkman, "the father of antiangiogenesis," a way to starve tumors of their blood supplies, died yesterday from an apparent heart attack. He was 74 years old.
Folkman, director of the Vascular Biology Program at Children's Hospital Boston, served as the hospital's surgeon in chief from 1967 to 1981. During his tenure, he published a groundbreaking article in The New England Journal of Medicine, suggesting that tumors require angiogenesis, the formation of new blood vessels (from established ones) to provide the nutrients their cells need to grow beyond a certain size. He had first had this insight in the 1960s when he was serving as a Navy surgeon and was tasked with developing a blood substitute that could be a lifesaver during combat. (At the time, it was cancer research dogma that tumors did not need new vessels to thrive.)
For much of the next two decades Folkman was treated as a pariah by his peers, who dismissed his theory outright. He was criticized whenever he announced a finding. To continue his unpopular research after all other funding sources dried up, he was forced to take a hefty sum—$23 million—from chemical company Monsanto.
Convinced he was on the right track, he persevered in the face of adversity. By the mid-1990s the tide turned in his favor when researchers in his lab discovered that two natural proteins, angiostatin and endostatin, could effectively block angiogenesis. In 1997 Folkman's group published a paper in which they described experiments showing that endostatin had dramatically reduced the sizes of aggressive malignant tumors by choking off their blood supplies. But that wasn't all: he also inadvertently discovered that the therapy not only slowed tumor growth but actually stopped it in its tracks by targeting more genetically stable blood-vessel manufacturing endothelial cells rather than the highly mutable tumor cells; this prevented the tumor from becoming immune to or developing a resistance to the proteins
In 1998 Folkman became a media sensation when Nobel scientist James Watson, co-discoverer of the DNA double helix, declared on the front page of The New York Times that he was "going to cure cancer in two years." At the time, Folkman's antiangiogenic therapies had successfully shrunk enormous mouse tumors comparable two-pound (0.9-kilogram) masses in humans. And, almost overnight, angiogenesis inhibitors became the cancer therapy du jour.
"At the beginning I felt enormous pressure," Folkman said in a 2002 interview with Scientific American. "[The news] raised expectations and demand for angiogenesis inhibitors before these drugs had completed testing in clinical trials. … For any new type of therapy there is always a dilemma about when to inform the public. If it's too early, then physicians are besieged by calls from patients for drugs that cannot be obtained. If too late, then critics say that hope was destroyed for patients with advanced disease."
Antiangiogenic drugs have had mixed results in human clinical trials over the past decade, including one in which only four of 42 patients suffering from cancers affecting hormone-producing nerve cells who were given endostatin experienced long-term relief. Today, however, many successful therapies involve angiogenesis. In early 2004 the Food and Drug Administration (FDA) approved Avastin, a drug manufactured by Genentech, for use, along with chemotherapy, for colorectal cancer; another antiangiogenic drug, thalidomide, was okayed by the FDA in 2006 for the treatment of multiple myeloma (cancer of the body's plasma cells, white blood cells that make antibodies); a few antiangiogenics have also been approved to treat macular degeneration (a progressive vision-impairing disease that destroys the macular, or central portion, of the retina).
"I'm extremely satisfied," Folkman told BusinessWeek during a 2005 interview. "In the past, we always assumed that unless you were making the patient really sick, flooding the body with these really toxic chemotherapies, the treatment wasn't working. … With these angiogenic drugs, you have none of that. All my patients comment on how much strength they have; they're all back at work."
Rakesh Jain, a professor of tumor biology at Harvard Medical School— where Folkman held appointments as both a professor of pediatric surgery and cell biology—remembers inviting Folkman to give a lecture to a class he was teaching on tumor pathophysiology at the Massachusetts of Technology in 1983. "He is one of the most mesmerizing speakers I have known in my life," Jain says of the man who would become his colleague and co-lecturer at Harvard nearly a decade later. "He humanizes science. … that's a quality I try to emulate."