The Emperor of All Maladies: A Biography of Cancer (32 page)

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Authors: Siddhartha Mukherjee

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BOOK: The Emperor of All Maladies: A Biography of Cancer
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Carla withdrew even more deeply into her own world. Her melancholy hardened into something impenetrable, a carapace, and she pulled into it instinctually, shutting everything out. She lost her friends. During her first few visits, I noticed that she often brought a cheerful young woman as a companion. One morning, I noticed that the friend was missing.

“No company today?” I asked.

Carla looked away and shrugged her shoulders. “We had a falling-out.” There was something steely, mechanical in her voice. “She needed to be needed, and I just couldn’t fulfill that demand. Not now.”

I found myself, embarrassingly enough, sympathizing with the missing friend. As Carla’s doctor, I needed to be needed as well, to be acknowledged, even as a peripheral participant in her battle. But Carla had barely any emotional energy for her own recuperation—and certainly none to spare for the needs of others. For her, the struggle with leukemia had become so deeply personalized, so interiorized, that the rest of us were ghostly onlookers in the periphery:
we
were the zombies walking outside her head. Her clinic visits began and ended with awkward pauses. Walking across the hospital in the morning to draw yet another bone marrow biopsy, with the wintry light crosshatching the rooms, I felt a certain dread descend on me, a heaviness that bordered on sympathy but never quite achieved it.

Test came after test. Seven months into her course, Carla had now visited the clinic sixty-six times, had had fifty-eight blood tests, seven spinal taps, and several bone marrow biopsies. One writer, a former nurse, described the typical course of “total therapy” in terms of the tests involved: “From
the time of his diagnosis, Eric’s illness had lasted 628 days. He had spent one quarter of these days either in a hospital bed or visiting the doctors. He had received more than eight hundred blood tests, numerous spinal and bone marrow taps, 30 X-rays, 120 biochemical tests, and more than two hundred transfusions. No fewer than twenty doctors—hematologists, pulmonologists, neurologists, surgeons, specialists and so on—were involved in his treatment, not including the psychologist and a dozen nurses.”

How Pinkel and his team convinced four- and six-year-olds in Memphis to complete that typical routine remains a mystery in its own right. But he did.
In July 1968, the St. Jude’s team published
its preliminary data on the results of the most advanced iteration of total therapy. (Pinkel’s team would run eight consecutive trials between 1968 and 1979, each adding another modification to the regimen.) This particular trial, an early variant, was nonrandomized and small, a single hospital’s experience with a single cohort of patients. But despite all the caveats, the result was electrifying. The Memphis team had treated thirty-one patients in all. Twenty-seven of them had attained a full remission. The median time to relapse (the time between diagnosis and relapse, a measure of the efficacy of treatment) had stretched out to nearly five years—more than twenty times the longest remissions achieved by most of Farber’s first patients.

But most important, thirteen patients, about a third of the original cohort, had
never
relapsed. They were still alive, off chemotherapy. The children had come back to the clinic month after month.
The longest remission was now in its sixth year
, half the lifetime of that child.

In 1979, Pinkel’s team revisited
the entire cohort of patients treated over several years with total therapy. Overall, 278 patients in eight consecutive trials had completed their courses of medicines and stopped chemotherapy. Of those, about one-fifth had relapsed. The rest, 80 percent—remained disease free after chemotherapy—“cured,” as far as anyone could tell. “ALL in children cannot be
considered an incurable disease
,” Pinkel wrote in a review article. “Palliation is no longer an acceptable approach to its initial treatment.”

He was writing to the future, of course, but in a more mystical sense he was writing back to the past, to the doctors who had been deeply nihilistic about therapy for leukemia and had once argued with Farber to let his children quietly “die in peace.”

*
Although trained in Boston under Farber, Pinkel had spent several years at the Roswell Park Cancer Institute in Buffalo, New York, before moving to Memphis in 1961.


The Roswell Park group, led by James Holland, and Joseph Burchenal at the Memorial Hospital in New York continued to collaborate with Pinkel in developing the leukemia protocols.

The Cart and the Horse

I am not opposed to optimism
, but I am fearful of the kind that comes from self-delusion.

—Marvin Davis, in the
New England Journal
of Medicine
, talking about the “cure” for cancer

The iron is hot and this is the time
to pound without cessation.

—Sidney Farber to Mary Lasker,
September 1965

One swallow is a coincidence, but two swallows make summer. By the autumn of 1968, as the trials in Bethesda and in Memphis announced their noteworthy successes, the landscape of cancer witnessed a seismic shift.
In the late fifties, as DeVita recalled
, “it took plain old courage to be a chemotherapist . . . and certainly the courage of the conviction that cancer would eventually succumb to drugs. Clearly, proof was necessary.”

Just a decade later, the burden of proof had begun to shift dramatically. The cure of lymphoblastic leukemia with high-dose chemotherapy might have been dismissed as a biological fluke, but the success of the same strategy in Hodgkin’s disease made it seem like a general principle. “A revolution [has been] set in motion,” DeVita wrote. Kenneth Endicott, the NCI director, concurred: “The next step—the complete cure—is almost sure to follow.”

In Boston, Farber greeted the news by celebrating the way he knew best—by throwing a massive public party. The symbolic date for the party was not hard to come by. In September 1968, the Jimmy Fund turned twenty-one.
*
Farber recast the occasion as the symbolic twenty-first birthday of Jimmy, a coming-of-age moment for his “child with cancer.” The Imperial Ballroom of the Statler Hotel, outside which the Variety Club had once positioned
its baseball-shaped donation box for Jimmy in the 1950s, was outfitted for a colossal celebration. The guest list included Farber’s typically glitzy retinue of physicians, scientists, philanthropists, and politicians. Mary Lasker couldn’t attend the event, but she sent Elmer Bobst from the ACS. Zubrod flew up from the NCI. Kenneth Endicott came from Bethesda.

Conspicuously missing from the list was the original Jimmy himself—Einar Gustafson. Farber knew of Jimmy’s whereabouts (he was alive and well, Farber told the press opaquely) but deliberately chose to shroud the rest in anonymity. Jimmy, Farber insisted, was an icon, an abstraction. The real Jimmy had returned to a private, cloistered life on a farm in rural Maine where he now lived with his wife and three children—his restored
normalcy
a sign of victory against cancer. He was thirty-two years old. No one had seen or photographed him for nearly two decades.

At the end of the evening, as the demitasse cups were being wheeled away, Farber rose to the stage in the full glare of the lights. Jimmy’s Clinic, he said, now stood at “the most fortunate time in the history of science and medicine.” Institutions and individuals across the nation—“the Variety Club, the motion picture industry, the Boston Braves . . . the Red Sox, the world of sports, the press, the television, the radio”—had come together around cancer. What was being celebrated in the ballroom that evening, Farber announced, was not an individual’s birthday, but the birth of a once-beleaguered community that had clustered around a disease.

That community now felt on the verge of a breakthrough. As DeVita described it, “The missing piece of the therapeutic puzzle, effective chemotherapy for systemic cancers,” had been discovered. High-dose combination chemotherapy would cure
all
cancers—once the right combinations had been found. “
The chemical arsenal,” one writer noted
, “now in the hands of prescribing physicians gives them every bit as much power . . . as the heroic surgeon wielding the knife at the turn of the century.”

The prospect of a systematic solution to a cure intoxicated oncologists. It equally intoxicated the political forces that had converged around cancer. Potent, hungry, and expansive, the word
war
captured the essence of the anticancer campaign. Wars demand combatants, weapons, soldiers, the wounded, survivors, bystanders, collaborators, strategists, sentinels, victories—and it was not hard to find a metaphorical analogue to each of these for this war as well.

Wars also demand a clear definition of an enemy. They imbue even
formless adversaries with forms. So cancer, a shape-shifting disease of colossal diversity, was recast as a single, monolithic entity. It was
one
disease. As Isaiah Fidler, the influential Houston oncologist, described it succinctly, cancer had to possess “
one cause, one mechanism and one cure
.”

If clinical oncologists had multidrug cytotoxic chemotherapy to offer as their unifying solution for cancer—“one cure”—then cancer scientists had their own theory to advance for its unifying cause: viruses. The grandfather of this theory was
Peyton Rous
, a stooping, white-haired chicken virologist who had been roosting quietly in a laboratory at the Rockefeller Institute in New York until he was dragged out of relative oblivion in the 1960s.

In 1909 (note that date: Halsted had just wrapped up his study of the mastectomy; Neely was yet to advertise his “reward” for the cure for cancer), then a thirty-year-old scientist freshly launching his lab at the Rockefeller Institute, Peyton Rous had been brought a tumor growing on the back of a hen of a black-and-white species of chicken called Plymouth Rock. A rare tumor in a chicken might have left others unimpressed, but the indefatigable Rous secured a $200 grant to study the chicken cancer. Soon, he had categorized the tumor as a sarcoma, a cancer of the connective tissues, with sheet upon sheet of rhomboid, fox-eyed cells invading the tendons and muscle.

Rous’s initial work on the chicken sarcoma was thought to have little relevance to human cancers. In the 1920s, the only known causes of human cancer were environmental carcinogens such as radium (recall Marie Curie’s leukemia) or organic chemicals, such as paraffin and dye by-products, that were known to cause solid tumors. In the late eighteenth century, an English surgeon named Percivall Pott had argued that cancer of the scrotum, endemic among chimney sweeps, was caused by chronic exposure to chimney soot and smoke. (We will meet Pott again in subsequent pages.)

These observations had led to a theory called the somatic mutation hypothesis of cancer. The somatic theory of cancer argued that environmental carcinogens such as soot or radium somehow permanently altered the structure of the cell and thus caused cancer. But the precise nature of the alteration was unknown. Clearly, soot, paraffin, and radium possessed the capacity to alter a cell in some fundamental way to generate a
malignant cell. But how could such a diverse range of insults all converge on the same pathological insult? Perhaps a more systematic explanation was missing—a deeper, more fundamental theory of carcinogenesis.

In 1910, unwittingly, Rous threw the somatic theory into grave doubt. Experimenting with the spindle-cell sarcoma, Rous injected the tumor in one chicken into another chicken and found that the cancer could be transmitted from one bird to another. “
I have propagated a spindle-cell sarcoma
of the common foul into its fourth generation,” he wrote. “The neoplasm grows rapidly, infiltrates, metastasizes, and remains true to type.”

This was curious, but nonetheless still understandable—cancer was a disease of cellular origin, and transferring cells from one organism to another might have been expected to transmit the cancer. But then Rous stumbled on an even more peculiar result. Shuttling tumors from one bird to another, he began to pass the cells through a set of filters, a series of finer and finer cellular sieves, until the cells had been eliminated from the mix and all that was left was the filtrate derived from the cells. Rous expected the tumor transmission to stop, but instead, the tumors continued propagating with a ghostly efficacy—at times even increasing in transmissibility as the cells had progressively vanished.

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