The Emperor of All Maladies. Siddhartha Mukherjee
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Название: The Emperor of All Maladies
Автор: Siddhartha Mukherjee
Издательство: HarperCollins
Жанр: Прочая образовательная литература
isbn: 9780007435814
isbn:
Li did not have to wait long. A few weeks after the first case, another patient, a young woman called Ethel Longoria327, was just as terrifyingly ill as the first patient. Her tumors, growing in grapelike clusters in her lungs, had begun to bleed into the linings of her lungs—so fast that it had become nearly impossible to keep up with the blood loss. “She was bleeding so rapidly,”328 a hematologist recalled, “that we thought we might transfuse her back with her own blood. So [the doctors] scrambled around and set up tubes to collect the blood that she had bled and put it right back into her, like an internal pump.” (The solution bore the quintessential mark of the NCI. Transfusing a person with blood leaking out from her own tumor would have been considered extraordinary, even repulsive, elsewhere, but at the NCI, this strategy—any strategy—was par for the course.) “They stabilized her and then started antifolates. After the first dose, when the doctors left for the night, they didn’t expect that they’d find her in rounds the next morning. At the NCI, you didn’t expect. You just waited and watched and took surprises as they came.”
Ethel Longoria hung on. At rounds the next morning, she was still alive, breathing slowly but deeply. The bleeding had now abated to the point that a few more doses could be tried. At the end of four rounds of chemotherapy330, Li and Hertz expected to see minor changes in the size of the tumors. What they found, instead, left them flabbergasted: “The tumor masses disappeared, the chest X-ray improved, and the patient looked normal,” Freireich wrote. The level of choriogonadotropin, the hormone secreted by the cancer cells, rapidly plummeted toward zero. The tumors had actually vanished. No one had ever seen such a response. The X-rays, thought to have been mixed up, were sent down for reexamination. The response was real: a metastatic, solid cancer had vanished with chemotherapy. Jubilant, Li and Hertz rushed to publish329 their findings.
But there was a glitch in all this—an observation so minor that it could easily have been brushed away. Choriocarcinoma cells secrete a marker, a hormone called choriogonadotropin, a protein that can be measured with an extremely sensitive test in the blood (a variant of this test is used to detect pregnancies). Early in his experiments, Li had decided that he would use that hormone level to track the course of the cancer as it responded to methotrexate. The hcg level, as it was called, would be a surrogate for the cancer, its fingerprint in the blood.
The trouble was, at the end of the scheduled chemotherapy, the hcg level had fallen to an almost negligible value, but to Li’s annoyance, it hadn’t gone all the way to normal. He measured and remeasured it in his laboratory weekly, but it persisted, a pip-squeak of a number that wouldn’t go away.
Li became progressively obsessed with the number. The hormone in the blood, he reasoned, was the fingerprint of cancer, and if it was still present, then the cancer had to be present, too, hiding in the body somewhere even if the visible tumors had disappeared. So, despite every other indication that the tumors had vanished, Li reasoned that his patients had not been fully cured. In the end, he seemed almost to be treating a number rather than a patient; ignoring the added toxicity of additional rounds of the drug, Li doggedly administered dose upon dose until, at last, the hcg level sank to zero.
When the Institutional Board at the NCI got wind of Li’s decision, it responded with fury. These patients were women who had supposedly been “cured” of cancer. Their tumors were invisible, and giving them additional chemotherapy was tantamount to poisoning them with unpredictable doses of highly toxic drugs. Li was already known to be a renegade, an iconoclast. This time, the NCI felt, he had gone too far. In mid-July, the board summoned331 him to a meeting and promptly fired him.
“Li was accused of experimenting on people,”332 Freireich said. “But of course, all of us were experimenting. Tom [Frei] and Zubrod and the rest of them—we were all experimenters. To not experiment would mean to follow the old rules—to do absolutely nothing. Li wasn’t prepared to sit back and watch and do nothing. So he was fired for acting on his convictions, for doing something.”
Freireich and Li had been medical residents together in Chicago. At the NCI, they had developed a kinship as two outcasts. When Freireich heard about Li’s dismissal333, he immediately went over to Li’s house to console him, but Li was inconsolable. In a few months, he huffed off to New York, bound back for Memorial Sloan-Kettering. He never returned to the NCI.
But the story had a final plot twist. As Li had predicted, with several additional doses of methotrexate, the hormone level that he had so compulsively trailed did finally vanish to zero. His patients finished their additional cycles of chemotherapy. Then, slowly, a pattern began to emerge. While the patients who had stopped the drug early inevitably relapsed with cancer, the patients treated on Li’s protocol remained free of disease—even months after the methotrexate had been stopped.
Li had stumbled on a deep and fundamental principle of oncology: cancer needed to be systemically treated long after every visible sign of it had vanished. The hcg level—the hormone secreted by choriocarcinoma—had turned out to be its real fingerprint, its marker. In the decades that followed, trial after trial would prove this principle. But in 1960, oncology was not yet ready for this proposal. Not until several years later did it strike the board that had fired Li so hastily that the patients he had treated with the prolonged maintenance strategy would never relapse. This strategy—which cost Min Chiu Li his job—resulted in the first chemotherapeutic cure of cancer in adults.
A model is a lie that helps334 you see the truth.
—Howard Skipper
Min Chiu Li’s experience with choriocarcinoma was a philosophical nudge for Frei and Freireich. “Clinical research is a matter of urgency,”335 Freireich argued. For a child with leukemia, even a week’s delay meant the difference between life and death. The academic stodginess of the leukemia consortium—its insistence on progressively and systematically testing one drug combination after another—was now driving Freireich progressively and systematically mad. To test three drugs, the group insisted336 on testing “all of the three possible combinations and then you’ve got to do all of the four combinations and with different doses and schedules for each.” At the rate that the leukemia consortium was moving, he argued, it would take dozens of years before any significant advance in leukemia was made. “The wards were filling up with these terribly sick children.337 A boy or girl might be brought in with a white cell count of three hundred and be dead overnight. I was the one sent the next morning to speak with the parents. Try explaining Zubrod’s strategy of sequential, systematic, and objective trials to a woman whose daughter has just slumped into a coma and died,” Freireich recalled.
The permutations of possible drugs and doses were further increased when yet another new anticancer agent was introduced at the Clinical Center in 1960. The СКАЧАТЬ