Monday, December 14, 2015 How to Cure Cancer

December 14. 2015 by Malcolm Gladwell

In the fall of 1963, not long after Vincent T. DeVita, Jr., joined the National Cancer Institute as a clinical associate, he and his wife were invited to a co-worker’s party. At the door, one of the institute’s most brilliant researchers, Emil Freireich, presented them with overflowing Martinis. The head of the medical branch, Tom Frei, strode across the room with a lab technician flung over his shoulder, legs kicking and her skirt over her head. DeVita, shocked, tried to hide in a corner. But some time later the N.C.I.’s clinical director, Nathaniel Berlin, frantically waved him over. Freireich, six feet four and built like a lineman, had passed out in the bathtub. Berlin needed help moving him. “Together, we pulled him up, threw his arms over our shoulders, and dragged him out through the party,” DeVita writes, in his memoir, “The Death of Cancer” (Sarah Crichton Books). “Out front, Freireich’s wife, Deanie, sat behind the wheel of their car. We tossed Freireich in the backseat and slammed the door.”

Half a century ago, the N.C.I. was a very different place. It was dingy and underfunded—a fraction of its current size—and home to a raw and unruly medical staff. The orthodoxy of the time was that cancer was a death sentence: the tumor could be treated with surgery or radiation, in order to buy some time, and the patient’s inevitable decline could be eased through medicine, and that was it. At the N.C.I., however, an insurgent group led by Frei and Freireich believed that if cancer drugs were used in extremely large doses, and in multiple combinations and repeated cycles, the cancer could be beaten. “I wasn’t sure if these scientists were maniacs or geniuses,” DeVita writes. But, as he worked with Freireich on the N.C.I.’s childhood-leukemia ward—and saw the fruits of the first experiments using combination chemotherapy—he became a convert.

DeVita decided to try the same strategy on another seemingly hopeless cause, Hodgkin’s lymphoma, a cancer that begins as a solid tumor in the lymph nodes and steadily spreads throughout the body. He teamed up with a fellow-associate named Jack Moxley. Over a few beers one night, at Au Pied de Cochon in Georgetown, the two sketched out a protocol, based loosely on what Frei and Freireich were doing with leukemia. Given the ability of cancer cells to adapt and mutate in the face of threats, they figured they needed four drugs, each effective against Hodgkin’s in its own way, so that whatever cells survived one wave had a chance of being killed by the next. They also had to be careful how frequently they gave the drugs: doses needed to be high enough to wipe out the cancer cells but not so high that they killed the patient. After several months, they settled on a regimen called MOMP: three eleven-day rounds of nitrogen mustard, Oncovin (a brand of vincristine), methotrexate, and prednisone, interspersed with ten-day recovery cycles.

“The side effects were almost immediate,” DeVita writes:

The sound of vomiting could be heard along the hallway. Night after night, Moxley and I paced outside the rooms of our patients, fearful of what might happen. Over the weeks that followed, they lost weight and grew listless, and their platelet counts sank lower and lower to dangerous levels.

Then came the surprise. Twelve of the fourteen patients in the initial trial went into remission—and nine stayed there as the months passed. In most cases, the tumors disappeared entirely, something that had never before been seen in the treatment of solid tumors. In the spring of 1965, DeVita went to Philadelphia to present the results to the annual meeting of the American Association for Cancer Research. He stood up before the crowd and ran triumphantly through the data: “ ‘Our patients were, therefore,’ I said, savoring the dramatic conclusion, ‘in complete remission.’ ”

What happened? An illustrious cancer expert named David Karnofsky made a narrow point about the appropriateness of the term “complete remission.” After that, nothing: “There were a few perfunctory questions about the severity of the side effects. But that was it.” History had been made in the world of cancer treatment, and no one seemed to care.

Vince DeVita served as the head of the National Cancer Institute from 1980 to 1988. He went on to serve as the physician-in-chief of the Memorial Sloan Kettering Cancer Center, in New York, and then ran the Yale Cancer Center, in New Haven. For the past half century, he has been at the forefront of the fight against one of the world’s most feared diseases, and in “The Death of Cancer” he has written an extraordinary chronicle. DeVita’s book is nothing like Siddhartha Mukherjee’s magisterial “The Emperor of All Maladies.” Mukherjee wrote a social and scientific biography of the disease. DeVita, as befits someone who spent a career at the helm of various medical bureaucracies, has written an institutional history of the war on cancer. His interest is in how the various factions and constituencies involved in that effort work together—and his conclusions are deeply unsettling.

When his first go-round as a clinical associate at the N.C.I. was up, DeVita took a post as a resident at Yale. At what was supposed to be a world-class hospital, he discovered that the standard of care for many cancers was woefully backward. Freireich had taught DeVita to treat Pseudomonas meningitis in leukemia patients by injecting an antibiotic directly into the spinal column—even though the drug’s label warned against that method of administration. That was the only way, Freireich believed, to get the drug past the blood-brain barrier. At Yale, DeVita writes, “you just didn’t do that kind of thing. As a result, I watched leukemic patients die.” Leukemia patients also sometimes came down with lobar pneumonia. Conventional wisdom held that that ought to be treated with antibiotics. But N.C.I. researchers had figured out that the disease was actually a fungal infection, and had to be treated with a different class of drug. “When I saw this condition in patients with leukemia and pointed it out to the chief of infectious diseases at Yale, he didn’t believe me—even when the lab tests proved my point,” DeVita continues. More patients died. Leukemia patients on chemotherapy needed platelets for blood transfusions. But DeVita’s superiors at Yale insisted there was no evidence that transfusions made a difference, despite the fact that Freireich had already proved that they did. “Ergo, at Yale,” DeVita says, “I watched patients bleed to death.”

Later, when DeVita and his fellow N.C.I. researcher George Canellos wanted to test a promising combination-chemotherapy treatment for advanced breast cancer, they had to do their trial overseas, because they couldn’t win the coöperation of surgeons at either of the major American cancer centers, Memorial Sloan Kettering or M. D. Anderson. When the cancer researcher Bernard Fisher did a study showing that there was no difference in outcome between radical mastectomies and the far less invasive lumpectomies, he called DeVita in distress. He couldn’t get the study published. “Breast surgeons made their living doing radical or total mastectomies, and they did not want to hear that that was no longer necessary,” DeVita writes. “Fisher had found it difficult to get patients referred to his study, in fact, because of this resistance.” The surgeons at Memorial Sloan Kettering Cancer Center were so stubborn that they went on disfiguring their patients with radical mastectomies for years after Fisher’s data had shown the procedure to be unnecessary. “The Death of Cancer” is an angry book, in which one of the critical figures in twentieth-century oncology unloads a lifetime of frustration with the obduracy and closed-mindedness of his profession. DeVita concludes, “There are incredibly promising therapies out there. If used to their fullest potential for all patients,