Siddhartha Mukherjee - The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

  The Senate was also getting the message. In June 1971, a modified version of the Kennedy/Javits bill appeared on the floor. On Wednesday afternoon, July 7, after dozens of testimonies by scientists and physicians, the motion was finally put to a vote. At five thirty that evening, the votes were counted: 79 in favor and 1 against.

  The swift and decisive victory in the Senate was precisely as the Laskerites had planned it. The cancer bill was now destined for the House, but its passage there promised to be a much tougher hurdle. The Laskerites had few allies and little influence in the lower chamber. The House wanted more testimony--and not just testimony from the Laskerites' carefully curated panel. It solicited opinions from physicians, scientists, administrators and policymakers--and those opinions, it found, diverged sharply from the ones presented to the Senate. Philip Lee, the former assistant secretary of health complained, "Cancer is not simply an island waiting in isolation for a crash program to wipe it out. It is in no way comparable to a moon shot--to a Gemini or an Apollo program--which requires mainly the mobilization of money, men, and facilities to put together in one imposing package the scientific knowledge we already possess." The Apollo mission and the Manhattan Project, the two models driving this War on Cancer were both technological achievements that stood on the shoulders of long and deep scientific discoveries (atomic physics, fluid mechanics, and thermodynamics). In contrast, even a cursory understanding of the process that made cells become malignant was missing. Seizing on the Laskerites' favorite metaphor, Sol Spiegelman, the Columbia University cancer scientist, argued, "An all-out effort at this time would be like trying to land a man on the moon without knowing Newton's laws of gravity." James Watson, who had discovered the structure of DNA, unloosed a verbal rampage against the Senate bill. "Doing 'relevant' research is not necessarily doing 'good' research," Watson would later write. "In particular we must reject the notion that we will be lucky. . . . Instead we will be witnessing a massive expansion of well-intentioned mediocrity."

  Others argued that the notion of a targeted war on a particular disease inevitably distracted from natural synergies with other arenas of research, forcing cancer researchers to think "inside the box." An NIH administrator complained, "In a nutshell, [the act] states that all NIH institutes are equal, but one [the NCI] is more equal than the others." Yet others argued that the metaphor of war would inevitably become a distraction. It would whip up a froth of hype and hope, and the letdown would be catastrophic. "I suspect there is trouble ahead for research in cancer," Irvine Page, the editor of a prominent scientific journal wrote. "People have become impatient with what they take to be lack of progress. Having seen what can be achieved by systems analysis, directed research, and great coordinated achievements such as the moon walk, they transfer the same thinking to the conquest of cancer all too readily." This bubble would inevitably burst if the cancer project stalled or failed.

  Nixon, meanwhile, had reached the edge of his patience. Elections were fast approaching in 1972. Earlier that year, commentators such as Bob Wiedrich from the Chicago Tribune had laid down the stakes: "If Richard Milhous Nixon . . . can achieve these two giant goals--an end to the war in Vietnam and defeat of the ravages of cancer--then he will have carved for himself in the history of this nation a niche of Lincolnesque proportions, for he will have done more than put a man on the moon."

  An end to the war in Vietnam was nowhere in sight, but a campaign against cancer seemed vastly more tractable, and Nixon was willing to force a cancer bill--any cancer bill--through Congress. When the ever-resourceful Schmidt went to visit him in the Oval Office that fall of 1971 (in part, to propose a compromise), Nixon reassured Schmidt that he would finagle--or strong-arm--a solution: "Don't worry about it. I'll take care of that."

  In November 1971, Paul Rogers, a Democrat in the House from Florida, crafted a compromise cancer bill. In keeping with the Laskerites' vision, Rogers's bill proposed a vast increase in the budget for cancer research. But in contrast to the Kennedy/Javits bill, it proposed to sharply restrict the autonomy of the National Cancer Institute. There would be no "NASA for cancer." But given the vast increase in money, the focused federal directive, and the staggering rise in hope and energy, the rhetoric of a "war" on cancer would still be fully justified. The Laskerites, their critics, and Nixon would all go home happy.

  In December 1971, the House finally put a modified version of Rogers's bill to a vote. The verdict was nearly unanimous: 350 votes for and 5 against. A week later, a House-Senate meeting resolved minor differences in their bills, and the final legislation was sent to the president to sign.

  On December 23, 1971, on a cold, windswept afternoon in Washington, Nixon signed the National Cancer Act at a small ceremony in the White House. The doors to the State Dining Room were thrown open, and the president seated himself at a small wooden desk. Photographers parried for positions on the floor around the desk. Nixon leaned over and signed the act with a quick flourish. He handed the pen as a gift to Benno Schmidt, the chair of the Panel of Consultants. Mary Lasker beamed forcefully from her chair. Farber chose not to attend.

  For the Laskerites, the date marked a bittersweet vindication. The flood of money authorized for cancer research and control--$400 million for 1972; $500 million for 1973; and $600 million for 1974 (a total of $1.5 billion over the next three years)--was a monumental achievement. If money was "frozen energy," as Mary Lasker often described it, then this, at last, was a pot of energy to be brought to full boil.

  But the passage of the bill had also been a reality check. The overwhelming opinion among scientists (outside those on the Panel of Consultants) was that this was a premature attack on cancer. Mary Lasker was bitingly critical of the final outcome. The new bill, she told a reporter, "contained nothing that was useful that gave any guts to the Senate bill."

  Humiliated by the defeat, Lasker and Sidney Farber withdrew soon after the House vote from the political world of cancer. Farber went back to Boston and nursed his wounds privately. Lasker retired to her museum-like apartment on Beekman Place in New York--a white box filled with white furniture--and switched the focus of her efforts from cancer to urban beautification projects. She would continue to actively campaign in Washington for health-related legislation and award the Lasker Prize, an annual award given to researchers for breakthroughs in medicine and biological sciences. But the insistent, urgent vigor that she had summoned during the two-decade campaign for a War on Cancer, the near-molten energy capable of flowing into any federal agency and annihilating resistance in its course, dissipated slowly. In April 1974, a young journalist went to Lasker to ask her about one of her many tulip-planting proposals for New York. At the end of the interview, the reporter asked Lasker about her perception of her own power: was she not one of the most powerful women in the country? Lasker cut the journalist short: "Powerful? I don't know. No. If I were really powerful, I'd have gotten more done."

  Scientists, too, withdrew from the war--in part, because they had little to contribute to it. The rhetoric of this war implied that its tools, its weapons, its army, its target, and its strategy had already been assembled. Science, the discovery of the unknown, was pushed to the peripheries of this battle. Massive, intensively funded clinical trials with combinations of cell-killing drugs would be heavily prioritized. The quest for universal causes and universal solutions--cancer viruses among them--would be highly funded. "We will in a relatively short period of time make vast inroads on the cancer problem," Farber had announced to Congress in 1970. His army was now "on the march," even if he and Mary Lasker had personally extricated themselves from its front lines.

  The act, then, was an anomaly, designed explicitly to please all of its clients, but unable to satisfy any of them. The NIH, the Laskerites, scientists, lobbyists, administrators, and politicians--each for his or her own reasons--felt that what had been crafted was either precisely too little or precisely too much. Its most ominous assessment came from the editorial pages of the Chicago Tribune: "A
crash program can produce only one result: a crash."

  On March 30, 1973, in the late afternoon, a code call, a signal denoting the highest medical emergency, rang through the floors of the Jimmy Fund Building. It sounded urgently through the open doors of the children's clinic, past the corridors with the cartoon portraits on the walls and the ward beds lined with white sheets and children with intravenous lines, all the way to the Brigham and Women's Hospital, where Farber had trained as an intern--in a sense retracing the trajectory of his life.

  A group of doctors and nurses in scrubs swung out toward the stairs. The journey took a little longer than usual because their destination was on the far end of the hospital, up on the eighth floor. In the room with tall, airy windows, they found Farber with his face resting on his desk. He had died of a cardiac arrest. His last hours had been spent discussing the future of the Jimmy Fund and the direction of the War on Cancer. His papers were neatly arranged in the shelves all around him, from his first book on the postmortem examination to the most recent article on advances in leukemia therapy, which had arrived that very week.

  Obituaries poured out from every corner of the world. Mary Lasker's was possibly the most succinct and heartfelt, for she had lost not just her friend but a part of herself. "Surely," she wrote, "the world will never be the same."

  From the fellows' office at the Dana-Farber Cancer Institute, just a few hundred feet across the street from where Farber had collapsed in his office, I called Carla Reed. It was August 2005, a warm, muggy morning in Boston. A child's voice answered the phone, then I was put on hold. In the background I could hear the white noise of a household in full tilt: crockery, doorbells, alarms, the radio blaring morning news. Carla came on the phone, her voice suddenly tightening as she recognized mine.

  "I have news," I said quickly, "good news."

  Her bone marrow results had just returned. A few nodules of normal blood cells were growing back interspersed between cobblestones of bone and fat cells--signs of a regenerating marrow reclaiming its space. But there was no trace of leukemia anywhere. Under the microscope, what had once been lost to cancer was slowly returning to normalcy. This was the first of many milestones that we would cross together, a moment of celebration.

  "Congratulations, Carla," I said. "You are in a full remission."

  *It would run in the New York Times on December 17.

  PART THREE

  "WILL YOU TURN

  ME OUT IF I CAN'T

  GET BETTER?"

  Oft expectation fails, and most oft there

  Where most it promises; and oft it hits

  Where hope is coldest, and despair most sits

  --William Shakespeare,

  All's Well That Ends Well

  I have seen the moment of my greatness flicker

  And I have seen the eternal Footman hold my coat, and snicker,

  And in short, I was afraid.

  --T. S. Eliot

  You are absolutely correct, of course, when you say that we can't go on asking for more money from the President unless we demonstrate progress.

  --Frank Rauscher, director of

  the National Cancer Program,

  to Mary Lasker, 1974

  "In God we trust.

  All others [must] have data"

  In science, ideology tends to corrupt; absolute ideology, [corrupts] absolutely.

  --Robert Nisbet

  Orthodoxy in surgery is like orthodoxy in other departments of the mind--it . . . begins to almost challenge a comparison with religion.

  --Geoffrey Keynes

  You mean I had a mastectomy for nothing?

  --Rose Kushner

  Farber was fortunate to have lived in the right time, but he was perhaps even more fortunate to have died at the right time. The year of his death, 1973, marked the beginning of a deeply fractured and contentious period in the history of cancer. Theories were shattered; drug discoveries stagnated; trials languished; and academic meetings degenerated into all-out brawls. Radiotherapists, chemotherapists, and surgeons fought viciously for power and information. The War on Cancer seemed, at times, to have devolved into a war within cancer.

  The unraveling began at the very center of oncology. Radical surgery, Halsted's cherished legacy, had undergone an astonishing boom in the 1950s and '60s. At surgical conferences around the world, Halsted's descendants--powerful and outspoken surgeons such as Cushman Haagensen and Jerome Urban--had stood up to announce that they had outdone the master himself in their radicalism. "In my own surgical attack on carcinoma of the breast," Haagensen wrote in 1956, "I have followed the fundamental principle that the disease, even in its early stage, is such a formidable enemy that it is my duty to carry out as radical an operation as the . . . anatomy permits."

  The radical mastectomy had thus edged into the "superradical" and then into the "ultraradical," an extraordinarily morbid, disfiguring procedure in which surgeons removed the breast, the pectoral muscles, the axillary nodes, the chest wall, and occasionally the ribs, parts of the sternum, the clavicle, and the lymph nodes inside the chest.

  Halsted, meanwhile, had become the patron saint of cancer surgery, a deity presiding over his comprehensive "theory" of cancer. He had called it, with his Shakespearean ear for phrasemaking, the "centrifugal theory"--the idea that cancer, like a malevolent pinwheel, tended to spread in ever-growing arcs from a single central focus in the body. Breast cancer, he claimed, spun out from the breast into the lymph nodes under the arm (poetically again, he called these nodes "sentinels"), then cartwheeled mirthlessly through the blood into the liver, lungs, and bones. A surgeon's job was to arrest that centrifugal spread by cutting every piece of it out of the body, as if to catch and break the wheel in midspin. This meant treating early breast cancer aggressively and definitively. The more a surgeon cut, the more he cured.

  Even for patients, that manic diligence had become a form of therapy. Women wrote to their surgeons in admiration and awe, begging them not to spare their surgical extirpations, as if surgery were an anagogical ritual that would simultaneously rid them of cancer and uplift them into health. Haagensen transformed from surgeon to shaman: "To some extent," he wrote about his patients, "no doubt, they transfer the burden [of their disease] to me." Another surgeon wrote--chillingly--that he sometimes "operated on cancer of the breast solely for its effect on morale." He also privately noted, "I do not despair of carcinoma being cured somewhere in the future, but this blessed achievement will, I believe, never be wrought by the knife of the surgeon."

  Halsted may have converted an entire generation of physicians in America to believe in the "blessed achievement" of his surgical knife. But the farther one got from Baltimore, the less, it seemed, was the force of his centrifugal theory; at St. Bartholomew's Hospital in London, a young doctor named Geoffrey Keynes was not so convinced.

  In August 1924, Keynes examined a patient with breast cancer, a thin, emaciated woman of forty-seven with an ulcerated malignant lump in her breast. In Baltimore or in New York, such a patient would immediately have been whisked off for radical surgery. But Keynes was concerned about his patient's constitutional frailty. Rather than reaching indiscriminately for a radical procedure (which would likely have killed her at the operating table), he opted for a much more conservative strategy. Noting that radiation therapists, such as Emil Grubbe, had demonstrated the efficacy of X-rays in treating breast cancer, Keynes buried fifty milligrams of radium in her breast to irradiate her tumor and monitored her to observe the effect, hoping, at best, to palliate her symptoms. Surprisingly, he found a marked improvement. "The ulcer rapidly heal[ed]," he wrote, "and the whole mass [became] smaller, softer and less fixed." Her mass reduced so rapidly, Keynes thought he might be able to perform a rather minimal, nonradical surgery on her to completely remove it.

  Emboldened by his success, between 1924 and 1928, Keynes attempted other variations on the same strategy. The most successful of these permutations, he found, involved a careful mixture of surgery a
nd radiation, both at relatively small doses. He removed the malignant lumps locally with a minor operation (i.e., without resorting to radical or ultraradical surgery). He followed the surgery with radiation to the breast. There was no stripping of nodes, no cracking or excavation of clavicles, no extirpations that stretched into six or eight hours. Nothing was radical, yet, in case after case, Keynes and his colleagues found that their cancer recurrence rate was at least comparable to those obtained in New York or Baltimore--achieved without grinding patients through the terrifying crucible of radical surgery.

  In 1927, in a rather technical report to his department, Keynes reviewed his experience combining local surgery with radiation. For some cases of breast cancer, he wrote, with characteristic understatement, the "extension of [the] operation beyond a local removal might sometimes be unnecessary." Everything about Keynes's sentence was carefully, strategically, almost surgically constructed. Its implication was enormous. If local surgery resulted in the same outcome as radical surgery, then the centrifugal theory had to be reconsidered. Keynes had slyly declared war on radical surgery, even if he had done so by pricking it with a pin-size lancet.

  But Halsted's followers in America laughed away Keynes's efforts. They retaliated, by giving his operation a nickname: the lumpectomy. The name was like a low-minded joke, a cartoon surgery in which a white-coated doctor pulls out a body part and calls it a "lump." Keynes's theory and operation were largely ignored by American surgeons. He gained fame briefly in Europe as a pioneer of blood transfusions during the First World War, but his challenge to radical surgery was quietly buried.