Dr. Folkman's War: Angiogenesis and the Struggle to Defeat Cancer

Book by Robert Cooke

IT WAS A TANTALIZING idea that Judah Folkman had nurtured for nearly four decades—he had hatched it, worked it, published it, defended it, romanced it. He had withstood the ridicule of his peers. He had fought battles of medical and scientific politics. And he had endured, seemingly obsessed, never straying from the ideas in his head, the conviction in his heart, and the truth he saw in his laboratory. That was where the real battles were waged, where Folkman had been trying for nearly forty years to read and understand Nature's book, page by page. Now the time had come to see what it all amounted to. The answers were starting to trickle in from medical wards around the country, and there was little more for Folkman to do than wait, and hope.

At the core was a simple notion that had gradually matured in Folkman's mind ever since that day in 1961 when he was noodling in a navy lab in Bethesda, Maryland, a twenty-eight-year-old draftee trying to make cells grow under artificial conditions. That was when he'd first noticed a strange thing about tumors: They wouldn't grow unless they first recruited their own blood vessels. Over time he convinced himself that there had to be some way to block the growth of those blood vessels. To starve the tumor to death-and save the patient.

So Folkman had been trying to conquer cancer for nearly four decades when, in the waning days of the twentieth century, the first patients began to be infused with the natural drugs that had come from his long campaign. The new compounds had worked marvelously in mice-"We've never lost a Mouse yet," Folkman liked to say-and now they were being given the first crucial tests in men and women. Three clinical trials were under way to test one of the potent substances, endostatin, that had been discovered in Folkman's laboratory. And as many as two hundred biotechnology companies, some large and others tiny, were exploring the once-ridiculed field that Folkman had years before named "angiogenesis," meaning the growth of the blood vessels de novo needed to support tumor growth.

In Boston, where Folkman had lived, studied, and worked since leaving Ohio behind in 1953, the volunteers trooped to the Dana-Farber Cancer Institute for their daily infusions of the possible wonder drug. The infusion center was on the ground floor, equipped with a collection of beds, some of which were fashioned after chairs, designed for patients who could take their medicine sitting up. Each would take his or her place, and the dose would then be thawed. Endostatin was a precious commodity that couldn't be wasted-the first one-kilogram batch was said to be worth seven million dollars-so it was never thawed before the patient actually arrived, in case the patient didn't show up. But they always did. These were people facing terminal cancer, desperate for the cure and very relieved to find that this drug, unlike the standard chemotherapy they had received, did not make them awfully sick. Of course, they hoped the treatments would also be different in a much more important way: Chemotherapy had not worked. That's why they were here. The infusion process, during which the drug was given through an IV line, lasted twenty minutes. Then the patients would leave, returning the same time the next day, Saturdays and Sundays included.

Would the new treatment live up to its billing, actually erase tumors without dangerous side effects? Would patients who had been given little or no chance of survival emerge unscathed, as if touched by magic? No one could tell-but everyone was watching. Although the first phase of the trials was only meant to test for signs of toxicity, those involved could not resist the natural impulse to peek beyond the government-enforced protocols, hoping for signs, even the barest hint, of efficacy. The doctors running the trials, gagged by their institutions, refused to utter a public word. But the rumors were flying. The doctors talked sub rosa, and so did the nurses and interns who were close to the trials. Word got around the biomedical grapevine that at DanaFarber and both of the other experiment centers conducting the trials in Texas and Wisconsin some patients' tumors had stopped growing. One man, it was said, had experienced remarkable progress. As one insider put it, the mystery man's cancer, both the primary tumor and its dangerous metastases, had been "galloping." But since he began getting endostatin-in only small doses during the toxicity phase of the trial-his tumors had shrunk by half One patient was just one patient, but it was an encouraging