Dr. Judah Folkman: A true scientific giant has died

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Today is a very sad day around my lab.

I’ve just been informed that one of my scientific heroes, the man whose work inspired me to enter the research area that I entered, namely tumor angiogenesis, died last night. Yes, sadly, Dr. Judah Folkman reportedly died of a heart attack last night.

I had the honor of meeting Dr. Folkman on two or three separate occasions, one of which was for a laboratory meeting that involved discussion of our lab’s work. A self-effacing and humble man, he was a true scientist, always questioning, always thinking of new hypotheses to test based on answers that scientific experiments and clinical trials provided and, more importantly, the unanswered questions they left. Moreover, he was the consummate surgeon-scientist, a man equally at home in the operating room and clinic as in the laboratory, a member of a rare and unfortunately dying breed who was the true “triple threat” of being a great researcher, great clinician, and a great teacher. The last time I saw him was in October, when he gave one of the keynote addresses at the Breast Cancer Research Foundation in New York.

Few scientists can be said to have created a whole new and important area of investigation, but I can certainly say that about Dr. Folkman. Prior to his proposal in 1971 that targeting tumor angiogenesis (new blood vessel growth that tumors induce from the surrounding tissues in order to supply themselves with oxygen and nutrients) could be an effective new strategy to treat cancer, the idea that tumor blood vessels were an important component of how tumors grow and metastasize was not appreciated. Indeed, Dr. Folkman’s concept was greeted initially with skepticism and ridicule. Folkman didn’t whine or complain that he was misunderstood. Instead, he did what a real scientist should do: He went back to the lab. It was over two decades before Folkman’s patient, persistent research started to bear fruit with his discovery of angiostatin and then later endostatin. In the late 1990’s, due to some truly exciting results in mice, the media created a bit of a frenzy claiming that cancer was “cured” by this new therapy. Indeed, I was caught up in the excitement of the research at the time and ultimately ended up studying angiogenesis myself. Since then, although not unexpectedly the clinical results from angiogenesis inhibitors have been more modest that the hyperbolic claims of a decade ago, angiogenesis remains one of the more promising avenues for controlling cancer. Angiogenesis inhibitors have already been validated in clinical trials for cancer, macular degeneration, and other diseases, with many more in the pipeline. Later, when other investigators reported having difficulty replicating his results, he demonstrated once again what an exemplar of science-based medicine he was. Did he attack the scientists who questioned his results? No, he did what a real scientist would do: He offered advice, technical support, and even reagents, including the antiangiogenic agents themselves, until the reasons that replication was difficult were worked out and soon several labs were reporting similar results to his.

Characteristically, Dr. Folkman was very modest about this and very cautious about extrapolating the remarkable results in mice to humans. At the height of the angiogenesis media frenzy in 1998, he was known for saying in interviews, “If you have cancer and you are a mouse, we can take good care of you.” He’s also put it this way:

Folkman’s remarkable results in the laboratory set off worldwide speculation that he would be the man to cure cancer, but he was uneasy with the accolades because cancer is such a complex disease. “We never use the word ‘cure’ because it is far away,” Folkman said in one of his last interviews. “It may be that patients will have little tiny cancers that lie dormant for a long time.”

Dr. Folkman never lost his ability to inquire or to inspire. Without his example and his groundbreaking research, I can honestly say that I would not be the surgeon-scientist that I am today. It’s a shame Dr. Folkman never won the Nobel Prize. He definitely deserved it.

ADDENDUM: More on Dr. Folkman here and here.