Cancer research pioneer Judah Folkman, the Andrus Professor of Pediatric Surgery and professor of cell biology at Harvard Medical School (HMS), died on Jan. 14 of a heart attack. Folkman, who was also the director of the Vascular Biology Program at Children’s Hospital Boston, was 74.
Folkman had a brilliant, if contentious, career. Nobody believed him when, in the 1960s, he claimed that the growth of cancers could be stopped, even reversed, by blocking the tiny vessels that feed them blood. Over the years, however, he survived peer rejection of his theory and went on to develop drugs that did what he predicted they would do.
Folkman, who was born in Cleveland in 1933, showed his promise early; there were even intimations that he would some day revolutionize medicine when, in high school, he made a crude machine to keep a rat’s heart pumping blood. During his medical training in the 1950s, Folkman and another student built an implantable pacemaker to shock weakened hearts back into a normal rhythm.
Graduating cum laude from Ohio State University, Columbus, in 1953, Folkman went on to Harvard Medical School, where, in 1957, he graduated magna cum laude. His surgical residency was spent at Massachusetts General Hospital. In 1964 and 1965, he served as chief resident in surgery there.
In the early 1960s, as a lieutenant in the Navy, Folkman co-developed silicone rubber implantable polymers for the sustained release of drugs, work that launched the field of controlled-release technology and led to the development of Norplant, a birth-control method for women.
It was also while he was serving in the Navy that Folkman made the discovery that came to dominate his life. In 1961, he and a colleague noticed that malignant mouse tumors implanted into isolated organs never grow beyond the size of a pinhead. But replant those tumors into the bodies of live animals, and they expand rapidly. From this, Folkman came up with the then-radical idea that tumors secrete proteins able to stimulate the growth of hair-thin blood vessels that bring them nutrients and carry away their wastes. He applied the name “angiogenesis,” meaning “birth of blood vessels,” to this process.
Today, no scientist or physician doubts the existence of angiogenesis or its role in cancer, but in the early 1970s Folkman’s idea was heavily criticized. “Fantasy,” some experts labeled it.
It was in a 1971 paper in the New England Journal of Medicine that Folkman put forward the hypothesis that all tumor growth is angiogenesis-dependent. The paper founded a new field of scientific inquiry: angiongenesis research. Folkman’s laboratory initiated clinical trials of antiangiogenic therapy. Angiogenesis inhibitors have since received FDA approval for the treatment of cancer and macular degeneration. Twenty-seven other countries in addition to the United States have approved these drugs. Folkman’s research has succeeded in placing antiangiogenic therapy on a firm scientific foundation.
By 1997, Folkman and his colleagues at Boston’s Children’s Hospital found a natural compound they called endostatin, which blocks the growth of blood vessels and shrinks tumors without the usual harsh side effects of chemotherapy.
Folkman wrote nearly 400 original peer-reviewed papers and more than 100 book chapters and monographs. He was elected to the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, and the Institute of Medicine of the National Academy of Sciences. He held honorary degrees from 15 universities and is the recipient of numerous national and international awards.
He had a distinguished teaching career. After his role as an instructor in surgery for Harvard’s Surgical Service at Boston City Hospital, he was promoted to Professor of Surgery at HMS, and became the Julia Dyckman Andrus Professor of Pediatric Surgery in 1968. From 1967 he served as surgeon-in-chief at Children’s Hospital Boston for 14 years.
A longtime resident of Brookline, Mass., Folkman is survived by his wife, the former Paula Prial (of Fall River, Mass.), daughters Laura and Marjorie, and one granddaughter.