Pictures of Judah Folkman: http://www.usc.edu/hsc/info/pr/1vol3/320/folkman.html

http://www1.od.nih.gov/wals/folkman.html

This article appeared in the June 13, 2003 Jewish Advocate.

Yom Kippur epiphany leads to medical breakthrough

By Susie Davidson

Advocate Correspondent

30 years ago, in the rear of a Boston synagogue on Yom Kippur, Dr. Judah Folkman, a newly-appointed Professor of Surgery at Harvard Medical School and Surgeon-in-Chief at Children’s Hospital Medical Center, had a revelation.

From the beginning of his long medical career, Folkman, currently the Director of Surgical Research at Children’s Hospital and a Harvard Medical School Professor of Pediatric Surgery and Cell Biology, had been pondering the complexities of metastases, the spreading of cancer cells to other sites in the body. He knew it came down to a basic scenario where cellular inhibitors of blood vessels, which are part of the body’s natural defense system, were being overcome by a new tumor’s stimulators. However, he hadn’t been able to discern the cause of the imbalance. Suddenly in the shul, it dawned on him. It was the removal of the primary tumor which was the cause.

“It was exactly ten o'clock in the morning...we were in the corner,” recalled Folkman. “I can remember the seat we were in, because suddenly it explained everything.”

Folkman realized that the inhibitor generated in the original tumor, though small in amount, was nonetheless stable, and thus able to curtail the blood vessel growth required by the new metastases. This preventive action, however, was halted when the primary site was excised. The key was to isolate the inhibitor, with the objective of utilizing it to stem angiogenesis. Folkman’s life mission was launched.

Gains and setbacks have since plagued this most specialized, indeed revolutionary approach to fighting a disease often characterized by both inexplicability and virulence. Trials have been mixed, with Folkman at times an object of derision in the scientific community. But last week, the tides appeared to turn when Avastin, a drug based on Folkman’s theory, dramatically extended the lives of colon cancer patients, with minimal side effects to boot. “The fact that this extended life is a very major medical breakthrough,” said Folkman. “You can’t do any better than that.”

The inherent potential reverberated through the medical community as well as Wall Street, as San Francisco-based Genentech Inc., the drug’s maker, saw its stock, as well as its morale, skyrocket.

“The magnitude of the benefit far exceeded what the study was designed to demonstrate,” read a company statement, with Executive Vice President Susan Hellman observing “the potential to change the practice of treating cancer.” With this clearing of clinical trials, Avastin will soon be available in the US for patients with colon and other cancers.

Avastin, one of 60 drugs based on Folkman’s research, is not viewed as a possible cure, but rather an approach to be combined with standard chemotherapy, in an effort to hopefully render the disease as a chronic, manageable condition. To date, over 16,000 papers have been published on the approach. Folkman himself has been the subject of myriad articles and studies, including a PBS Nova documentary.

"The importance of angiogenesis is so obvious when you think about it," commented Isaiah Fidler of the M. D. Anderson Cancer Center in Houston. "The world owes Judah Folkman a debt of gratitude."

Is it time to kvell? Perhaps not yet, but for the first time, with the long-hoped-for validation of Folkman’s theory and work, hope is in the air.

Folkman, born Moses Judah Folkman in 1933 in Cleveland, often accompanied his rabbi father on hospital visitations. At the age of about seven, he told him he wanted to become a doctor. “So you can be a rabbi-like doctor,” his father responded. Clearly, the ministering instinct ran in the family; his father also obtained a Ph.D. in sociology at Ohio State so that he could perform marriage and family counseling as well. If he was out of town, Folkman’s mother would make family shiva and other visits in his stead.

“Both my parents said it was the highest thing you could do,” said Folkman. “This was their service, one by one, personal service to people. They were always on call. When you couple that with my interest in science, the two made a very good match.”

Folkman, who holds honorary degrees from five universities, received a Bachelor’s of Arts from Ohio State and an M.D. from Harvard Medical School. As an HMS student, he received several medical awards for developing the first atrio-ventricular pacemaker. He began surgical training at MGH in 1957 and became, following service as a US Navy lieutenant in Bethesda, he became Chief Resident in Surgery. After then serving 14 years as Surgeon-in-Chief at Children’s Hospital, he decided to pursue research full-time. Finally, his effort may be beginning to bear fruit for countless patients and their families.