Children's mourns the death of Dr. Judah Folkman
January 15, 2008
On January 14, Dr. Judah Folkman, founder of the field of angiogenesis, died unexpectedly in Denver, Colo., while en route to Vancouver for one of the thousands of lectures that he gave to scientists around the world. A visionary and scientific pioneer, Dr. Folkman was founder and director of the Vascular Biology Program at Children's Hospital Boston, and a professor of Pediatric Surgery and Cell Biology at Harvard Medical School.
Dr. Judah Folkman, 1933-2008When Dr. Folkman first proposed, in the 1970s, that a cancer could be kept in check by cutting off its blood supply, he faced skepticism from a scientific community that simply wasn't ready for his ideas. But he persevered, even when there were setbacks, and today, more than 1,000 laboratories worldwide are engaged in the study of angiogenesis, the field he founded. As a result of Dr. Folkman's vision and resilience, more than 10 new cancer drugs are currently on the market, and more than 1.2 million patients worldwide are now receiving anti-angiogenic therapy.
Folkman's work has also spawned intensive research into stimulators of angiogenesis, to treat conditions such as heart attacks where a new network of blood vessels is needed, as well as research to control abnormal angiogenesis in non-cancerous diseases such as macular degeneration and diabetic retinopathy. The FDA-approved angiogenesis inhibitors Macugen and Lucentis have slowed vision loss and even restored vision in some patients with macular degeneration.
"The world has lost a bright light, but his contributions live on in the thousands of researchers he mentored, new treatments that his work spawned, and patients for whom he always deeply cared and to whom he gave so generously of his time and knowledge," said James Mandell, MD, President and Chief Executive Officer, at Children's Hospital Boston, who began his urologic training at Children's when Folkman was surgeon-in-chief. "For 30 years, I and countless other clinicians and scientists have relied on his clinical insight, expertise wonderful advice and wise counsel. We will miss him dearly."
Dr. Folkman first speculated in the 1960s that angiogenesis is also integral to the complex biology that enables and encourages the growth of tumors and other forms of cancer. He spent the last four decades validating this hypothesis, beginning with a seminal paper published in The New England Journal of Medicine in 1971. In this paper, he proposed the revolutionary concept that tumors are unable to grow beyond a certain size unless they have a dedicated blood supply, and that "successful" tumors secrete an unknown substance (which he then called tumor angiogenesis factor, or TAF) that encourages new blood vessel growth. The process of angiogenesis, Folkman argued, helps transform a tumor from a small cluster of mutated cells to a large, malignant growth. Rather than waging a toxic chemical and radiation battle with a tumor, one could starve it into submission by shutting down its blood supply.
More than thirty years later, angiogenesis inhibitors and stimulators present powerful new weapons in the armamentarium against cancer and a host of other illnesses, including heart and eye disease. At least 50 angiogenesis inhibitors are in clinical trials around the world, and more than 1,000 laboratories in universities and industry are conducting angiogenesis research.
"Dr Folkman's contributions profoundly influenced both science and medicine," said Bruce Zetter, PhD, Chief Scientific Officer at Children's. "He was a superb physician, a brilliant and creative, scientist and an extraordinary mentor. His work has given rise to new treatments for cancer, for many forms of eye disease and for a variety of other diseases characterized by the abnormal growth of new blood vessels. "
At least 50 angiogenesis inhibitors - including endostatin, angiostatin, 2ME2 (Panzem), and a thrombospondin analog -- are in clinical trials today for cancer, and 10, including Avastin and Thalomid are FDA-approved. A variety of other drugs have been discovered to have unexpected anti-angiogenic effects, including the anti-inflammatory drug celecoxib (Celebrex); rosiglitazone (Avandia), a drug commonly used to treat Type 2 diabetes; doxycycline, a common antibiotic; and some cancer drugs that also have other mechanisms of action, including Erbitux, Herceptin, Velcade and Tarceva. Even some conventional chemotherapy drugs have demonstrated anti-angiogenic effects when given in frequent, smaller doses. Folkman envisions that someday angiogenesis inhibitors will be used together or in combination with conventional anticancer therapies such as chemotherapy, radiotherapy, immunotherapy, gene therapy, or vaccine therapy.
Earlier in his career, Folkman also made important contributions to medical technology and surgery. While a student at Harvard Medical School, for example, he developed one of the first implantable pacemakers. While at the National Naval Medical Center in Bethesda in the early 1960s, he 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.
"Judah's research combined fundamental understanding of tumorigenesis and angiogenesis with major practical applications of these insights," said Jeffrey Flier, Dean of Harvard Medical School. "In addition, he had a profound influence on generations of Harvard medical students. While directing an unusually large laboratory with many lines of inquiry, he always made time for students and teaching. He was an extraordinary role model for faculty and students at Harvard Medical School."
Folkman is the author of some 400 peer-reviewed papers and more than 100 book chapters and monographs. He also holds multiple honorary degrees and is the recipient of numerous national and international awards. He has been 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. In 2006, Folkman was one of seven people appointed by President Bush to the National Cancer Advisory Board of the National Institutes of Health.
Born in Cleveland in 1933, Folkman graduated cum laude from The Ohio State University, Columbus, Ohio, in 1953. He continued his education at Harvard Medical School, where he graduated magna cum laude in 1957. Folkman began his surgical residency at the Massachusetts General Hospital and served as chief resident in surgery from 1964-1965.
Folkman began his career as an instructor in surgery for Harvard's Surgical Service at Boston City Hospital Boston, was recruited to Harvard Medical School as the youngest person ever appointed full professor, and became the Julia Dyckman Andrus Professor of Pediatric Surgery in 1968. From 1967 he served as Surgeon-in-Chief at the 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, Hannah.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 377-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.
Judah Folkman, MD