Judah Folkman (actually Moses Judah Folkman) was one of the more remarkable and innovative individuals to play a role in cancer research over the last 50 years. His colleagues at Harvard Medical School stated that he was the smartest man they ever knew. When he was appointed as a full professor at age 34, he was the youngest person in the history of Harvard to achieve this distinction.
Folkman came from a long line of rabbis and was earmarked by his father and his family for that calling as well when he was born in Cleveland, Ohio, in 1933. When Folkman was 7, his father, a Reform rabbi, started taking him on his bikur cholim rounds in the hospital as a prelude to this profession, but instead the rabbi’s son developed an interest in medicine, which he pursued. His father supported him but famously said that he should be a rabbi-like doctor (you tell me what that means). He graduated Ohio State University at age 19 and went on to Harvard Medical School, and then to a surgical residency. Ultimately, he was appointed chief of pediatric surgery at Children’s Hospital in Boston at age 34.
Along the way, he started doing research early. Folkman developed the first implantable cardiac pacemaker but, despite his urging, Harvard did not apply for a patent and lost out on a fortune. He also later had a hand in the development of Norplant, a highly effective implantable form of birth control which slowly releases the effective active agent. This time Harvard did obtain the patent.
Apparently as a young Navy doctor in 1960, he was assigned to do research on blood substitutes, and he noticed that all tumors grew to the same size. He hypothesized that the tumors could not grow beyond a certain size, generally about 1 to 2 millimeters, without a blood supply—i.e., tumors needed blood vessels in order to grow and proliferate. He gave this further thought and did some lab research on it. This ultimately led to his publication in the New England Journal of Medicine 10 years later (in 1971) the hypothesis that tumor growth is angiogenesis dependent. In that paper he observed that tumors would not grow beyond millimeter size unless new capillaries developed to provide blood supply to them. He and his collaborators posited that there was some angiogenic factor that stimulated the development for such vascular growth.
At first there was widespread skepticism about his work, and the cancer research community continued to focus on the development of chemotherapy drugs that were toxic to cancer cells. He was called a charlatan. But then other laboratories discovered angiogenic factors that promoted such vascular growth. Folkman and his lab at Harvard had contracts with a variety of pharmaceutical companies to try to discover drugs that would inhibit such angiogenesis. Between 1980 and 2004, his laboratory investigated and tested 12 different agents as potential inhibitors of angiogenesis. Some of them had some degree of activity as angiogenesis inhibitors, but for one reason or another, none proved suitable to become clinically useful as an oncology drug.
In 2004, the first angiogenesis inhibitor that did prove suitable for clinical utilization, bevacizumab (or Avastin), was approved by the Food and Drug Administration for use in advanced colon cancer. It was also later approved for use against a variety of other cancers, including breast cancer, lung cancer, brain tumors and ovarian cancer. It was also very effective for macular degeneration, which resulted from a proliferation of vascular growth in the retina.
Avastin was actually a recombinant monoclonal antibody originally produced by Napoleone Ferrara, an Italian-American scientist, while he was working in the laboratories of Genentech, which continues to hold the patents for the drug. This antibody inhibited tumor growth in mice and confirmed the hypotheses that were postulated by Folkman, i.e., that inhibiting angiogenesis would help to control tumor growth.
Folkman died of a heart attack in 2008 at the age of 74 while sitting in an airport on his way to a conference.
Folkman used to say, “If your work proves successful, you are called persistent. If it proves unsuccessful, you are called stubborn.”
It was said that Folkman carried around in his pocket the names and phone numbers of his 200 active patients and, as he traveled, he would call 10 of them each night to inquire as to how they were doing. Perhaps we can rightly say he had not forgotten the bikur cholim lessons of his father, the rabbi, and was indeed a rabbi-like doctor.
May all of us have a sweet, happy and healthy New Year and may the issues of this column only be theoretical and intellectual for all of us, and may the struggles and problems of our brothers and sisters in Israel come to a rapid, successful and peaceful conclusion.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
