The Best American Science and Nature Writing 2011: The Best American Series by Mary Roach & Tim Folger

Author:Mary Roach & Tim Folger [Roach, Mary]
Language: eng
Format: mobi
Publisher: Houghton Mifflin Harcourt
Published: 2011-10-04T07:00:00+00:00

It wasn't Folkman's triumph that Bahcall kept coming back to, however. It was his struggle. Folkman's great insight at the Naval Medical Center occurred in 1960. O'Reilly's breakthrough experiment occurred in 1994. In the intervening years, Folkman's work was dismissed and attacked and confronted with every obstacle.

At times Bahcall tried to convince himself that elesclomol's path might be different. Synta had those exciting Phase 2 results and the endorsement of the Glaxo deal. "For the results not to be real, you'd have to believe that it was just a statistical fluke that the patients who got drugs are getting better," Bahcall said, in one of those dining-room-table moments. "You'd have to believe that the fact that there were more responses in the treatment group was also a statistical fluke, along with the fact that we've seen these signs of activity in Phase 1, and the fact that the underlying biology strongly says that we have an extremely active anticancer agent."

But then he would remember Folkman. Angiostatin and a companion agent also identified by Folkman's laboratory, endostatin, were licensed by a biotech company called EntreMed. And EntreMed never made a dime off either drug. The two drugs failed to show any clinical effects in both Phase 1 and Phase 2. Avastin was a completely different anti-angiogenesis agent, discovered and developed by another team entirely and brought to market a decade after O'Reilly's experiment. What's more, Avastin's colorectal-cancer trial—the one that received a standing ovation at ASCO—was the drug's second round. A previous Phase 3 trial for breast cancer had been a crushing failure. Even Folkman's beautifully elaborated theory about angiogenesis may not fully explain the way Avastin works. In addition to cutting off the flow of blood vessels to the tumor, Avastin seems also to work by repairing some of the blood vessels feeding the tumor, so that the drugs administered in combination with Avastin can get to the tumor more efficiently.

Bahcall followed the fortunes of other biotech companies the way a teenage boy follows baseball statistics, and he knew that nothing ever went smoothly. He could list, one by one, all the breakthrough drugs that had failed their first Phase 3 or had failed multiple Phase 2s or that turned out not to work the way they were supposed to work. In the world of serendipity and of trial and error, failure was a condition of discovery, because, when something was new and worked in ways that no one quite understood, every bit of knowledge had to be learned, one experiment at a time. You ended up with VAMP, which worked, but only after you compared daily 6-MP and daily methotrexate with daily 6-MP and methotrexate every four days, and so on, through a great many iterations, none of which worked very well at all. You had results that looked "boinking good," but only after a trial with a hundred compromises.

Chen had the same combination of realism and idealism that Bahcall did. He was the in-house skeptic at Synta. He was the one who worried the most about the hand shaking of the drugs in the SYMMETRY trial.

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