Perhaps the panel members were served an inedible lunch. Perhaps the meeting room was too hot or cold. Whatever the reason, the members reconvened in a grumpy mood. One of the seven declared that in her opinion—founded not on clinical experience, only on the morning’s 30-minute tutorial—no antibiotics were needed for infected diabetic ulcers. “Just cut the infected tissue out and throw it in the garbage can,” she declared. One after another of the members agreed. The panel’s chairman, Dr. William Craig, pointedly disagreed. Nevertheless, the vote was 7-5 not to approve the drug, a decision upheld formally by the FDA some months later. Michael Zasloff’s 13-year crusade to use peptides against drug resistant bacteria was finished.
Over the next two years, Zasloff himself came to wonder if animal peptides would ever work in people. Perhaps the way to go was to focus on human peptides—plenty of those had been found—and to try to strengthen the barrier of innate immunity to fight human infections.
In a desperate bid to keep his company alive, Zasloff pushed squalamine into clinical trials as an appetite suppressant. He was serious. It was the Hail Mary play, as he put it, that might save the day. But no one else seemed to believe he could pull it off.
In the fall of 2000, Zasloff’s own directors lost faith. The scientist whose discovery had inspired the company was made a consultant—pushed out, as Zasloff later admitted—and the corporate direction changed. The clinical tests with squalamine as an appetite suppressant were carried on: the stuff did look promising, wacky as the route to its application may have been. Early results had shown squalamine to be effective, as well, against ovarian and non-small-cell lung cancer. But in corporate press releases, no further mention was made of antibiotics—or peptides. From now on, the company would use genomics to find new targets and new natural substances like hormones as drugs. To make that perfectly clear, the name Magainin was changed to Genaera.
In his more contemplative moments, Zasloff admitted he’d made mistakes. But he had no regrets about his role in establishing a burgeoning new field: some 3,000 articles on peptides had been written since his seminal paper of 1987, some 500 peptides discovered. The innate immune system was now part of science. And for Zasloff, the most promising aspect of peptides was still their potency against resistant bacteria. They’d persisted through most, if not all, of evolutionary history. In all that time, bacteria had never become resistant to them. Was it too much to suggest that they constituted the Achilles’ heel of pathogens? That bacteria never would become resistant to peptides? “They’ve had a billion years to fend these things off,” Zasloff said, “and this is what we’ve got.”