Judah Folkman

In the Book of Genesis, Judah is depicted as a man of extraordinary physical ability; a legendary hero able to hurl boulders at enemies and grind lumps of iron into dust. The real-life Judah, by comparison, was a milder quantity. He spoke with an almost child-like glee to the swarm of medical students surrounding him, adjusting his glasses constantly and digressing with unerring regularity to work anecdotes about his grand-daughter into the conversation.

By no means was he any less intimidating.

History may yet end up remembering Judah Folkman, who passed away earlier this year at Denver International Airport, as the man who cured cancer. While the distinction between reality and hyperbole hinges on the success of a series of anti-cancer drug trials currently being carried out, there is an undeniable realisation amongst the medical community that it has lost one of its best and brightest in the struggle against cancer.

Judah Folkman was born in Cleveland in 1933, and graduated from Ohio State University in 1953. An MD at Harvard Medical School followed in 1957, as did a surgical residency at the Massachusetts General Hospital. During this period, Folkman developed the first implantable atrio-ventricular pacemaker and received a number of awards for his work. His greater claim to fame followed between 1960 to 1962, while doing research at the National Navy Medical Center in Bethesda. It was during this period that Folkman developed an interest in tumor growth in isolated perfused organs and developed the notion of cancer being an angiogenic disease (i.e., one that requires the formation of new blood vessels). Folkman believed that the rapid growth of cancerous cells needed a constant supply of blood, and that tumours would fail to grow larger than the head of a pin unless they secreted some mystery chemical that stimulated the formation of new capillaries. Blocking this pathway, he speculated, could offer an entirely new means of treating the disease.

The idea was met with equal quantities of indifference and ridicule. Medical journals refused to publish the work, and peer-reviewers were scathing in their criticism. It took until 1971, when the editor of the New England Journal of Medicine finally decided to bypass existing protocol, that Folkman’s seminal paper on angiogenesis appeared in print.

Only two papers cited the work in the decade following publication. One of them panned the idea altogether.

Undeterred, Folkman bet his career on his theory and continued pushing ahead with the belief that he was onto something. In 1983, his laboratory identified a substance that stimulated the growth of capillaries, and in 1985 the first compound inhibiting this effect was discovered. Soon, dozens more followed, and by 1998, the New York Times published a front-page story on how Folkman had discovered two natural compounds that dramatically shrank tumours in mice by cutting off the cancer’s blood supply. In 2004, a landmark trial of Avastin successfully prolonged the lives of patients with terminal colon cancer. Nobel laureate James Watson, who discovered the double-helix structure of DNA, was sufficiently moved to proclaim, “Judah is going to cure cancer in two years.” Watson eventually accepted the statement was exaggerated, but Folkman’s transformation from a dream merchant to a reluctant hero in the fight against cancer was complete.

Folkman’s papers have now been cited over ten thousand times.

Many promising breakthroughs to cure cancer in recent times can be traced to Folkman’s initial work. In the last year alone, Rakesh Jain at the MGH discovered that anti-angiogenic chemicals may be useful in restoring normal blood flow through tumours, allowing chemotherapeutic agents to better permeate through malignant tissue. Anti-angiogenic agents have also found use beyond cancer treatment; chemicals that prevent the formation of new blood vessels are increasingly being used to treat disorders such as “wet” macular degeneration, where the proliferation of leaky capillaries eventually damages the retina.

It will be some time before Folkman’s legacy can be assessed in its entirety, but his story is interesting from many perspectives. It has all the makings of a cheesy feel-good Hollywood flick, where the underdog triumphs deliciously at the end against all odds – the sort of sappy melodrama predisposed to legacies of bumper-stickers and fridge-magnets.

For starters there are the usual bits about staying faithful to something you believe in. Folkman relished almost as much in his achievements as he did in his ability to realise them in the face of persistent criticism. He often talked about how there was a fine line between persistence and obstinacy, one that was defined exclusively by success. At the same time, he was careful to caution that the key to confronting opposition was to choose a problem that is worth persisting with – little was gained by being pig-headed in general.

The philosophy to persist with good ideas was allayed with a belief that revolutionary changes are always slow in their acceptance. A skew case of this is provided by Robert Langer, one of Folkman’s students, and currently an institute professor at MIT; Langer has filed over five hundred patents on proposals that were rejected by funding agencies, with the underlying belief that they must necessarily correspond to ideas that were so far ahead of their time that people failed to understand them altogether.

Finally, even those who only witnessed Folkman for a few moments felt compelled to revise their beliefs that a person can be too old to be productive in society. Folkman was involved in dozens of projects right till the end, while a block down Longwood Ave, Eugene Braunwald is still going strong while closing in on the age of eighty. Neither ever became too successful to eschew trifles such as teaching first-year MD students or going out for lunch with them once in a while.

Not so long ago the opportunity presented itself to sit in on a particular Dean Kamen talk on the subject of how teenagers would much rather be basketball players these days than researchers and engineers. While the lament is hardly surprising, coming as it does from a self-proclaimed uber-geek like Kamen, there is more than a shred of truth in the comment. Science may be many things, but it is scarcely replete in glamour. Judah Folkman, or Iman Ali. Whom would you rather spend an evening with? Take your pick. Just this once, though, let us take a step back and mutter a silent prayer. Not just for Folkman, but for all those individuals – past, present and future – who soldier on behind the scenes, anonymously, driven only by the faintest of hopes that some day, the frontiers of medicine will finally yield.