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Dr. Judah Folkman (1933-2008): The epitome of what a science-based physician should be

The name of this blog is Science-Based Medicine. The reason it is so called is because we, the bloggers who will be contributing, believe that “the best method for determining which interventions and health products are safe and effective is, without question, good science.” Sadly, one of the people who best represented this very sort of philosophy, Dr. Judah Folkman (1933-2008), has died. Dr. Folkman was the epitome of everything that a science-based surgeon or physician should be, and he was first among my scientific and surgical heroes.

Few scientists can be said to have created a whole new and important area of investigation. Dr. Folkman certainly did that. Prior to his initial proposal, originally published 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) might be an effective new strategy to treat cancer, the concept that tumor blood vessels were an important contributor to the growth and metastasis of tumors was generally poorly appreciated, if at all. Indeed, Dr. Folkman’s initial article was greeted with skepticism and, in some cases, outright ridicule. This is where Dr. Folkman distinguished himself. Did he whine or complain that he was misunderstood? No, at least not in public. Instead, he did what a real scientist should do: He went back to the lab to test his hypothesis. It was over two decades of grueling work, during which Dr. Folkman had to develop methodology to culture vascular endothelial cells and measure tumor angiogenesis in in vitro and in vivo models before he could even think about testing angiogenesis inhibitors, until Folkman’s patient, persistent research started to produce results, first with his discovery of angiostatin and then later endostatin, to be followed by a flood of other antiangiogenic compounds. 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.

In the late 1990′s, due to some truly exciting results in mice, Dr. Folkman became famous, as the media created a bit of a frenzy claiming that cancer would soon be “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. Alas, it was not to be. 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. Lives are being saved, and the lives of cancer patients have been extended using drugs developed from Dr. Folkman’s initial, seemingly heretical idea.

I had the honor of meeting Dr. Folkman in person 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 and how the results could be used to improve the care of cancer patients. 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, every bit as vital the last time I saw him give a talk in October as he was the first time I saw him a decade earlier. That’s one reason why I considered it such a shock to learn of his death today.

Characteristically, Dr. Folkman was modest and cautious about his accomplishments. He was especially cautious about extrapolating the remarkable results he had achieved in mice to how angiogenesis inhibition would work in humans. At the height of the angiogenesis media frenzy in 1998, Dr. Folkman 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.

Posted in: Basic Science, Medical Academia, Pharmaceuticals, Surgical Procedures

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4 thoughts on “Dr. Judah Folkman (1933-2008): The epitome of what a science-based physician should be

  1. Harriet Hall says:

    Modesty and caution seem to be characteristics of many good scientists and few if any pseudoscientists or charlatans.

    William Withering’s classic book on his discovery of foxglove, published in 1785, described all the failures as well as the successes among his cases. He said, “Time will fix the real value upon this discovery, and determine whether I have imposed upon myself and others, or contributed to the benefit of science and mankind.”

  2. Blake Stacey says:

    I second Harriet Hall‘s observation with regard to modesty and caution. (The latest example I heard about for Doing It Wrong is HPV denialism, on the part of Newstarget.) It’s regrettable that those of us in other fields may hear about exciting results, like discoveries in tumor angiogenesis, but we don’t learn about the people who make those discoveries and the ways they can serve as role models.

  3. Pingback: Judah Folkman

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