Miracles of Saint Judah

One of the more amusing aspects of the recent flurry of stories about two promising new cancer treatments is the way researcher Judah Folkman, the son of a rabbi, has been hailed as a secular saint-even though all his miracles, as he’s the first to admit, have taken place in mice.

Hardly a week had passed after the now-notorious May 3 front-page story in The New York Times, which described the work of Folkman’s lab at Children’s Hospital in Boston on endostatin and angiostatin, before Folkman was canonized. As the noted molecular biologist Yogi Berra once observed, “It’s dj vu all over again.”

Anti-angiogenic factors work by blocking the formation of new blood vessels to tumors, essentially starving the cancer. Last November, Folkman’s group reported in Nature that repeated courses of one such agent, endostatin, cured three different kinds of implanted tumors in mice.

Since we live in an age when the fate of a few genetically challenged rodents can send shivers through the stock market, revisiting the scene of this crime for a moment affords an opportunity to reiterate a few obvious points about biotechnology, the press and the public. With apologies to Wallace Stevens, here are Five Ways of Looking at a Breakthrough.

The Magic Bullet Syndrome: We’ve all been spoiled by penicillin, a magic bullet the likes of which we’ll probably not see again in our lifetime. Every few years, however, a new cancer treatment heads into the clinic with the kind of buildup more suitable to Hollywood than to Harvard. Connoisseurs of this form of hopeful hype will recall the examples of interferon (heralded by a cover story in Life in 1979), interleukin-2 (cover stories in Fortune and Newsweek in 1985), monoclonal antibodies (another Fortune story in 1987), tumor necrosis factor, shark cartilage…you name it. Between IPOs and voracious news cycles, every dog of a molecule has its day in the biotech business.The Salk Complex: This is a special concoction of the press and the lay public. We like our breakthroughs to be singular, the product of soloists or divas or maestros. If they’ve struggled mightily upstream against the tide of Conventional Wisdom, all the better for the story line. Jonas Salk’s polio vaccine, the model of 20th century scientific heroism, arrived at a unique moment of American innocence, optimism and gratitude, but you saw some of the Salk treatment in the Folkman coverage, especially in the suggestion that scientists used to snicker at angiogenesis as an approach. I heard plenty of laughter when I sat in on a Folkman talk not long ago-but only because he has such a great sense of humor. In fact, any narrative that depicts the scientist as a lone wolf hero ignores the reality that science is a collaborative, synergistic, community-driven enterprise.

The Brilliant Lab Chief: As beloved as Judah Folkman is in the world of molecular biology, his lab is no different than others. He handles the High Concept scientific approach and brings in the dough, but others-usually postdocs and fellows-provide the elbow grease that turns pipe dreams into peer-reviewed papers. If endostatin ever becomes a major drug, Michael O’Reilly, a research fellow in Folkman’s lab who isolated the molecule, deserves a lot of credit. In his talks, Folkman amply and wittily acknowledges the contribution of O’Reilly and others. But these collaborative subtleties generally don’t find their way into the news stories.

There Are Always Other Ways to Skin a Cat: EntreMed Inc., the biotech company holding the rights to angiostatin and endostatin, made the usual bottle-rocket run on Wall Street on the basis of the initial press coverage without having made, much less tested, the drugs under study. Meanwhile, many other companies have anti-angiogenesis factors in clinical trials.

Among these other companies are Agouron Pharmaceuticals, Imclone Systems, Sugen and Magainin Pharmaceuticals. They all have promising agents in trials, but you wouldn’t know that from reading the stories about Folkman’s work.

The Lazarus Bullet: Many agents that begin as “magic bullets” subsequently lose much of their luster-as endostatin may do. But some of those old, discredited magic potions subsequently rise from the dead. Since the endostatin story exploded in early May, the Food and Drug Administration (FDA) has recommended several of them. At the end of May, an FDA advisory panel recommended approval of a monoclonal antibody that counteracts the effects of tumor necrosis factor in Crohn’s disease. Several days later, a form of interferon received approval for the treatment of chronic hepatitis C in combination with a second antiviral drug. Neither of those treatments represent cures; they represent incremental improvements in care.

But that, in the end, may be the real story of magic bullets. They’re hardly magic, but given enough time and experimentation, they often do work as bullets. And in the war against an enemy as tough as cancer (not to mention many other diseases), perhaps the most important thing is to have a little ammunition that works, rather than the perfect ordnance which, like magic, is illusory.