Perhaps there is only one cardinal sin: impatience. Because of impatience we were driven out of Paradise, because of impatience we cannot return.
The 325,000 patients with cancer who are going to die this year cannot wait; nor is it necessary, in order to make great progress in the cure of cancer, for us to have the full solution of all the problems of basic research . . . the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures.
Why don’t we try to conquer cancer by America’s 200th birthday? What a holiday that would be!
—Advertisement published in
the New York Times by the Laskerites,
“They form a society”
All of this demonstrates why few research scientists are in policy-making positions of public trust. Their training for detail produces tunnel vision, and men of broader perspective are required for useful application of scientific progress.
I am aware of some alarm in the scientific community that singling out cancer for . . . a direct presidential initiative will somehow lead to the eventual dismantling of the National Institutes of Health. I do not share these feelings. . . . We are at war with an insidious, relentless foe. [We] rightly demand clear decisive action—not endless committee meetings, interminable reviews and tired justifications of the status quo.
In 1831, Alexis de Tocqueville, the French aristocrat, toured the United States and was astonished by the obsessive organizational energy of its citizens. “Americans of all ages, all conditions, and all dispositions constantly form associations . . . of a thousand other kinds—religious, moral, serious, futile, general or restricted, enormous or diminutive,” Tocqueville wrote. “Americans make associations to give entertainments, to found seminaries, to build inns, to construct churches, to diffuse books, to send missionaries to the antipodes. . . . If it is proposed to inculcate some truth or to foster some feeling by the encouragement of a great example, they form a society.”
More than a century after Tocqueville toured the States, as Farber sought to transform the landscape of cancer, he instinctively grasped the truth behind Tocqueville’s observation. If visionary changes were best forged by groups of private citizens forming societies, then Farber needed such a coalition to launch a national attack on cancer. This was a journey that he could not begin or finish alone. He needed a colossal force behind him—a force that would far exceed the Jimmy Fund in influence, organization, and money. Real money, and the real power to transform, still lay under congressional control. But prying open vast federal coffers meant deploying the enormous force of a society of private citizens. And Farber knew that this scale of lobbying was beyond him.
There was, he knew, one person who possessed the energy, resources, and passion for this project: a pugnacious New Yorker who had declared it her personal mission to transform the geography of American health through group-building, lobbying, and political action. Wealthy, politically savvy, and well connected, she lunched with the Rockefellers, danced with the Trumans, dined with the Kennedys, and called Lady Bird Johnson by her first name. Farber had heard of her from his friends and donors in Boston. He had run into her during his early political forays in Washington. Her disarming smile and frozen bouffant were as recognizable in the political circles in Washington as in the salons of New York. Just as recognizable was her name: Mary Woodard Lasker.
Mary Woodard was born in Watertown, Wisconsin, in 1900. Her father, Frank Woodard, was a successful small-town banker. Her mother, Sara Johnson, had emigrated from Ireland in the 1880s, worked as a saleswoman at the Carson’s department store in Chicago, and ascended briskly through professional ranks to become one of the highest-paid saleswomen at the store. Salesmanship, as Lasker would later write, was “a natural talent” for Johnson. Johnson had later turned from her work at the department store to lobbying for philanthropic ventures and public projects—selling ideas instead of clothes. She was, as Lasker once put it, a woman who “could sell . . . anything that she wanted to.”
Mary Lasker’s own instruction in sales began in the early 1920s, when, having graduated from Radcliffe College, she found her first job selling European paintings on commission for a gallery in New York—a cutthroat profession that involved as much social maneuvering as canny business sense. In the mid-1930s, Lasker left the gallery to start an entrepreneurial venture called Hollywood Patterns, which sold simple prefab dress designs to chain stores. Once again, good instincts crisscrossed with good timing. As women joined the workforce in increasing numbers in the 1940s, Lasker’s mass-produced professional clothes found a wide market. Lasker emerged from the Depression and the war financially rejuvenated. By the late 1940s, she had grown into an extraordinarily powerful businesswoman, a permanent fixture in the firmament of New York society, a rising social star.
In 1939, Mary Woodard met Albert Lasker, the sixty-year-old president of Lord and Thomas, an advertising firm based in Chicago. Albert Lasker, like Mary Woodard, was considered an intuitive genius in his profession. At Lord and Thomas, he had invented and perfected a new strategy of advertising that he called “salesmanship in print.” A successful advertisement, Lasker contended, was not merely a conglomeration of jingles and images designed to seduce consumers into buying an object; rather, it was a masterwork of copywriting that would tell a consumer why to buy a product. Advertising was merely a carrier for information and reason, and for the public to grasp its impact, information had to be distilled into its essential elemental form. Each of Lasker’s widely successful ad campaigns—for Sunkist oranges, Pepsodent toothpaste, and Lucky Strike cigarettes among many others—highlighted this strategy. In time, a variant of this idea, of advertising as a lubricant of information and of the need to distill information into elemental iconography would leave a deep and lasting impact on the cancer campaign.
Mary and Albert had a brisk romance and a whirlwind courtship, and they were married just fifteen months after they met—Mary for the second time, Albert for the third. Mary Lasker was now forty years old. Wealthy, gracious, and enterprising, she now launched a search for her own philanthropic cause—retracing her mother’s conversion from a businesswoman into a public activist.
For Mary Lasker, this search soon turned inward, into her personal life. Three memories from her childhood and adolescence haunted her. In one, she awakes from a terrifying illness—likely a near-fatal bout of bacterial dysentery or pneumonia—febrile and confused, and overhears a family friend say to her mother that she will likely not survive: “Sara, I don’t think that you will ever raise her.”
In another, she has accompanied her mother to visit her family’s laundress in Watertown, Wisconsin. The woman is recovering from surgery for breast cancer—radical mastectomies performed on both breasts. Lasker enters a dark shack with a low, small cot with seven children running around and she is struck by the desolation and misery of the scene. The notion of breasts being excised to stave cancer—“Cut off?” Lasker asks her mother searchingly—puzzles and grips her. The laundress survives; “cancer,” Lasker realizes, “can be cruel but it does not need to be fatal.”
In the third, she is a teenager in college, and is confined to an influenza ward during the epidemic of 1918. The lethal Spanish flu rages outside, decimating towns and cities. Lasker survives—but the flu will kill six hundred thousand Americans that year, and take nearly fifty million lives worldwide, becoming the deadliest pandemic in history.
A common thread ran through these memories: the devastation of illness—so proximal and threatening at all times—and the occasional capacity, still unrealized, of medicine to transform lives. Lasker imagined unleashing the power of medical research to combat diseases—a power that, she felt, was still largely untapped. In 1939, the year that she met Albert, her life collided with illness again: in Wisconsin, her mother suffered a heart attack and then a stroke, leaving her paralyzed and incapacitated. Lasker wrote to the head of the American Medical Association to inquire about treatment. She was amazed—and infuriated, again—at the lack of knowledge and the unrealized potential of medicine: “I thought that was ridiculous. Other diseases could be treated . . . the sulfa drugs had come into existence. Vitamin deficiencies could be corrected, such as scurvy and pellagra. And I thought there was no good reason why you couldn’t do something about stroke, because people didn’t universally die of stroke . . . there must be some element that was influential.”
In 1940, after a prolonged and unsuccessful convalescence, Lasker’s mother died in Watertown. For Lasker, her mother’s death brought to a boil the fury and indignation that had been building within her for decades. She had found her mission. “I am opposed to heart attacks and cancer,” she would later tell a reporter, “the way one is opposed to sin.” Mary Lasker chose to eradicate diseases as some might eradicate sin—through evangelism. If people did not believe in the importance of a national strategy against diseases, she would convert them, using every means at her disposal.
Her first convert was her husband. Grasping Mary’s commitment to the idea, Albert Lasker became her partner, her adviser, her strategist, her coconspirator. “There are unlimited funds,” he told her. “I will show you how to get them.” This idea—of transforming the landscape of American medical research using political lobbying and fund-raising at an unprecedented scale—electrified her. The Laskers were professional socialites, in the same way that one can be a professional scientist or a professional athlete; they were extraordinary networkers, lobbyists, minglers, conversers, persuaders, letter writers, cocktail party–throwers, negotiators, name-droppers, deal makers. Fund-raising—and, more important, friend-raising—was instilled in their blood, and the depth and breadth of their social connections allowed them to reach deeply into the minds—and pockets—of private donors and of the government.
“If a toothpaste . . . deserved advertising at the rate of two or three or four million dollars a year,” Mary Lasker reasoned, “then research against diseases maiming and crippling people in the United States and in the rest of the world deserved hundreds of millions of dollars.” Within just a few years, she transformed, as BusinessWeek magazine once put it, into “the fairy godmother of medical research.”
The “fairy godmother” blew into the world of cancer research one morning with the force of an unexpected typhoon. In April 1943, Mary Lasker visited the office of Dr. Clarence Cook Little, the director of the American Society for the Control of Cancer in New York. Lasker was interested in finding out what exactly his society was doing to advance cancer research, and how her foundation could help.
The visit left her cold. The society, a professional organization of doctors and a few scientists, was self-contained and moribund, an ossifying Manhattan social club. Of its small annual budget of about $250,000, it spent an even smaller smattering on research programs. Fund-raising was outsourced to an organization called the Women’s Field Army, whose volunteers were not represented on the ASCC board. To the Laskers, who were accustomed to massive advertising blitzes and saturated media attention—to “salesmanship in print”—the whole effort seemed haphazard, ineffectual, stodgy, and unprofessional. Lasker was bitingly critical: “Doctors,” she wrote, “are not administrators of large amounts of money. They’re usually really small businessmen . . . small professional men”—men who clearly lacked a systematic vision for cancer. She made a $5,000 donation to the ASCC and promised to be back.
Lasker quickly got to work on her own. Her first priority was to make a vast public issue out of cancer. Sidestepping major newspapers and prominent magazines, she began with the one outlet of the media that she knew would reach furthest into the trenches of the American psyche: Reader’s Digest. In October 1943, Lasker persuaded a friend at the Digest to run a series of articles on the screening and detection of cancer. Within weeks, the articles set off a deluge of postcards, telegrams, and handwritten notes to the magazine’s office, often accompanied by small amounts of pocket money, personal stories, and photographs. A soldier grieving the death of his mother sent in a small contribution: “My mother died from cancer a few years ago. . . . We are living in foxholes in the Pacific theater of war, but would like to help out.” A schoolgirl whose grandfather had died of cancer enclosed a dollar bill. Over the next months, the Digest received thousands of letters and $300,000 in donations, exceeding the ASCC’s entire annual budget.
Energized by the response, Lasker now set about thoroughly overhauling the flailing ASCC in the larger hopes of reviving the flailing effort against cancer. In 1949, a friend wrote to her, “A two-pronged attack on the nation’s ignorance of the facts of its health could well be undertaken: a long-range program of joint professional-lay cooperation . . . and a shorter-range pressure group.” The ASCC, then, had to be refashioned into this “shorter-range pressure group.” Albert Lasker, who joined the ASCC board, recruited Emerson Foote, an advertising executive, to join the society to streamline its organization. Foote, just as horrified by the mildewy workings of the agency as the Laskers, drafted an immediate action plan: he would transform the moribund social club into a highly organized lobbying group. The mandate demanded men of action: businessmen, movie producers, admen, pharmaceutical executives, lawyers—friends and contacts culled from the Laskers’ extensive network—rather than biologists, epidemiologists, medical researchers, and doctors. By 1945, the nonmedical representation in the ASCC governing board had vastly increased, edging out its former members. The “Lay Group,” as it was called, rechristened the organization the American Cancer Society, or the ACS.
Subtly, although discernibly, the tone of the society changed as well. Under Little, the ASCC had spent its energies drafting insufferably detailed memorandums on standards of cancer care for medical practitioners. (Since there was little treatment to offer, these memoranda were not particularly useful.) Under the Laskers, predictably, advertising and fund-raising efforts began to dominate its agenda. In a single year, it printed 9 million “educational” pieces, 50,000 posters, 1.5 million window stickers, 165,000 coin boxes, 12,000 car cards, and 3,000 window exhibits. The Women’s Field Army—the “Ladies’ Garden Club,” as one Lasker associate scathingly described it—was slowly edged out and replaced by an intense, well-oiled fund-raising machine. Donations shot through the roof: $832,000 in 1944, $4,292,000 in 1945, $12,045,000 in 1947.
Money, and the shift in public visibility, brought inevitable conflicts between the former members and the new ones. Clarence Little, the ASCC president who had once welcomed Lasker into the group, found himself increasingly marginalized by the Lay Group. He complained that the lobbyists and fund-raisers were “unjustified, troublesome and aggressive”—but it was too late. At the society’s annual meeting in 1945, after a bitter showdown with the “laymen,” he was forced to resign.
With Little deposed and the board replaced, Foote and Lasker were unstoppable. The society’s bylaws and constitution were rewritten with nearly vengeful swiftness to accommodate the takeover, once again emphasizing its lobbying and fund-raising activities. In a telegram to Mary Lasker, Jim Adams, the president of the Standard Corporation (and one of the chief instigators of the Lay Group), laid out the new rules, arguably among the more unusual set of stipulations to be adopted by a scientific organization: “The Committee should not include more than four professional and scientific members. The Chief Executive should be a layman.”
In those two sentences, Adams epitomized the extraordinary change that had swept through the ACS. The society was now a high-stakes juggernaut spearheaded by a band of fiery “laymen” activists to raise money and publicity for a medical campaign. Lasker was the center of this collective, its nucleating force, its queen bee. Collectively, the activists began to be known as the “Laskerites” in the media. It was a name that they embraced with pride.
In five years, Mary Lasker had raised the cancer society from the dead. Her “shorter-range pressure group” was working in full force. The Laskerites now had their long-range target: Congress. If they could obtain federal backing for a War on Cancer, then the scale and scope of their campaign would be astronomically multiplied.
“You were probably the first person to realize that the War against Cancer has to be fought first on the floor of Congress—in order to continue the fight in laboratories and hospitals,” the breast cancer patient and activist Rose Kushner once wrote admiringly to Mary Lasker. But cannily, Lasker grasped an even more essential truth: that the fight had to begin in the lab before being brought to Congress. She needed yet another ally—someone from the world of science to initiate a fight for science funding. The War on Cancer needed a bona fide scientific sponsor among all the advertisers and lobbyists—a real doctor to legitimize the spin doctors. The person in question would need to understand the Laskerites’ political priorities almost instinctually, then back them up with unquestionable and unimpeachable scientific authority. Ideally, he or she would be immersed in cancer research, yet willing to emerge out of that immersion to occupy a much larger national arena. The one man—and perhaps the only man—who could possibly fit the role was Sidney Farber.
In fact, their needs were perfectly congruent: Farber needed a political lobbyist as urgently as the Laskerites needed a scientific strategist. It was like the meeting of two stranded travelers, each carrying one-half of a map.
Farber and Mary Lasker met in Washington in late 1940s, not long after Farber had shot to national fame with his antifolates. In the winter of 1948, barely a few months after Farber’s paper on antifolates had been published, John Heller, the director of the NCI, wrote to Lasker introducing her to the idea of chemotherapy and to the doctor who had dreamed up the notion in Boston. The idea of chemotherapy—a chemical that could cure cancer outright (“a penicillin for cancer,” as the oncologist Dusty Rhoads at Memorial Hospital liked to describe it)—fascinated Lasker. By the early 1950s, she was regularly corresponding with Farber about such drugs. Farber wrote back long, detailed, meandering letters—“scientific treatises,” he called them—educating her on his progress in Boston.
For Farber, the burgeoning relationship with Lasker had a cleansing, clarifying quality—“a catharsis,” as he called it. He unloaded his scientific knowledge on her, but more important, he also unloaded his scientific and political ambition, an ambition he found easily reflected, even magnified, in her eyes. By the mid-1950s, the scope of their letters had considerably broadened: Farber and Lasker openly broached the possibility of launching an all-out, coordinated attack on cancer. “An organizational pattern is developing at a much more rapid rate than I could have hoped,” Farber wrote. He spoke about his visits to Washington to try to reorganize the National Cancer Institute into a more potent and directed force against cancer.
Lasker was already a “regular on the Hill,” as one doctor described her—her face, with its shellacked frieze of hair, and her hallmark gray suit and pearls omnipresent on every committee and focus group related to health care. Farber, too, was now becoming a “regular.” Dressed perfectly for his part in a crisp, dark suit, his egghead reading-glasses often perched at the edge of his nose, he was a congressman’s spitting image of a physician-scientist. He possessed an “evangelistic pizzazz” for medical science, an observer recalled. “Put a tambourine in [his] hands” and he would immediately “go to work.”
To Farber’s evangelistic tambourine, Lasker added her own drumbeats of enthusiasm. She spoke and wrote passionately and confidently about her cause, emphasizing her points with quotes and questions. Back in New York, she employed a retinue of assistants to scour newspapers and magazines and clip out articles containing even a passing reference to cancer—all of which she read, annotated on the margins with questions in small, precise script, and distributed to the other Laskerites every week.
“I have written to you so many times in what is becoming a favorite technique—mental telepathy,” Farber wrote affectionately to Lasker, “but such letters are never mailed.” As acquaintance bloomed into familiarity, and familiarity into friendship, Farber and Lasker struck up a synergistic partnership that would stretch over decades. In a letter written in 1954, Farber used the word crusade to describe their campaign against cancer. The word was deeply symbolic. For Sidney Farber, as for Mary Lasker, the cancer campaign was indeed turning into a “crusade,” a scientific battle imbued with such fanatical intensity that only a religious metaphor could capture its essence. It was as if they had stumbled upon an unshakable, fixed vision of a cure—and they would stop at nothing to drag even a reluctant nation toward it.
“These new friends of chemotherapy”
The death of a man is like the fall of a mighty nation
That had valiant armies, captains, and prophets,
And wealthy ports and ships all over the seas
But now it will not relieve any besieged city
It will not enter into an alliance
—Czeslaw Milosz, “The Fall”
I had recently begun to notice that events outside science, such as Mary Lasker’s cocktail parties or Sidney Farber’s Jimmy Fund, had something to do with the setting of science policy.
In 1951, as Farber and Lasker were communicating with “telepathic” intensity about a campaign against cancer, a seminal event drastically altered the tone and urgency of their efforts. Albert Lasker was diagnosed with colon cancer. Surgeons in New York heroically tried to remove the tumor, but the lymph nodes around the intestines were widely involved, and there was little that could be done surgically. By February 1952, Albert was confined to the hospital, numb with the shock of diagnosis and awaiting death.
The sardonic twist of this event could not have escaped the Laskerites. In their advertisements in the late 1940s to raise awareness of cancer, the Laskerites had often pointed out that one in four Americans would succumb to cancer. Albert was now the “one in four”—struck by the very disease that he had once sought to conquer. “It seems a little unfair,” one of his close friends from Chicago wrote (with vast understatement), “for someone who has done as much as you have to forward the work in this field to have to suffer personally.”
In her voluminous collection of papers—in nearly eight hundred boxes filled with memoirs, letters, notes, and interviews—Mary Lasker left few signs of her response to this terrifying tragedy. Although obsessed with illness, she was peculiarly silent about its corporality, about the vulgarity of dying. There are occasional glimpses of interiority and grief: her visits to the Harkness Pavilion in New York to watch Albert deteriorate into a coma, or letters to various oncologists—including Farber—inquiring about yet another last-ditch drug. In the months before Albert’s death, these letters acquired a manic, insistent tone. He had seeded metastasis into the liver, and she searched discreetly, but insistently, for any possible therapy, however far-fetched, that might stay his illness. But for the vast part, there was silence—impenetrable, dense, and impossibly lonely. Mary Lasker chose to descend into melancholy alone.
Albert Lasker died at eight o’clock on the morning of May 30, 1952. A small private funeral was held in the Lasker residence in New York. In his obituary, the Times noted, “He was more than a philanthropist, for he gave not only of his substance, but of his experience, ability and strength.”
Mary Lasker gradually forged her way back to public life after her husband’s death. She returned to her routine of fund-raisers, balls, and benefits. Her social calendar filled up: dances for various medical foundations, a farewell party for Harry Truman, a fund-raiser for arthritis. She seemed self-composed, fiery, and energetic—blazing meteorically into the rarefied atmosphere of New York.
But the person who charged her way back into New York’s society in 1953 was fundamentally different from the woman who had left it a year before. Something had broken and annealed within her. In the shadow of Albert’s death, Mary Lasker’s cancer campaign took on a more urgent and insistent tone. She no longer sought a strategy to publicize a crusade against cancer; she sought a strategy to run it. “We are at war with an insidious, relentless foe,” as her friend Senator Lister Hill would later put it—and a war of this magnitude demanded a relentless, total, unflinching commitment. Expediency must not merely inspire science; it must invade science. To fight cancer, the Laskerites wanted a radically restructured cancer agency, an NCI rebuilt from the ground up, stripped of its bureaucratic excesses, intensely funded, closely supervised—a goal-driven institute that would decisively move toward finding a cancer cure. The national effort against cancer, Mary Lasker believed, had become ad hoc, diffuse, and abstract. To rejuvenate it, it needed the disembodied legacy of Albert Lasker: a targeted, directed strategy borrowed from the world of business and advertising.
Farber’s life also collided with cancer—a collision that he had perhaps presaged for a decade. In the late 1940s, he had developed a mysterious and chronic inflammatory disease of the intestines—likely ulcerative colitis, a debilitating precancerous illness that predisposes the colon and bile duct to cancer. In the mid-1950s (we do not know the precise date), Farber underwent surgery to remove his inflamed colon at Mount Auburn Hospital in Boston, likely choosing the small and private Cambridge hospital across the Charles River to keep his diagnosis and surgery hidden from his colleagues and friends on the Longwood campus. It is also likely that more than just “precancer” was discovered upon surgery—for in later years, Mary Lasker would refer to Farber as a “cancer survivor,” without ever divulging the nature of his cancer. Proud, guarded, and secretive—reluctant to conflate his battle against cancer with the battle—Farber also pointedly refused to discuss his personal case publicly. (Thomas Farber, his son, would also not discuss it. “I will neither confirm nor deny it,” he said, although he admitted that his father lived “in the shadow of illness in his last years”—an ambiguity that I choose to respect.) The only remnant of the colon surgery was a colostomy bag; Farber hid it expertly under his white cuffed shirt and his four-button suit during his hospital rounds.
Although cloaked in secrecy and discretion, Farber’s personal confrontation with cancer also fundamentally altered the tone and urgency of his campaign. As with Lasker, cancer was no longer an abstraction for him; he had sensed its shadow flitting darkly over himself. “[It is not] necessary,” he wrote, “in order to make great progress in the cure of cancer, for us to have the full solution of all the problems of basic research . . . the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures.”
“Patients with cancer who are going to die this year cannot wait,” Farber insisted. Neither could he or Mary Lasker.
Mary Lasker knew that the stakes of this effort were enormous: the Laskerites’ proposed strategy for cancer ran directly against the grain of the dominant model for biomedical research in the 1950s. The chief architect of the prevailing model was a tall, gaunt, MIT-trained engineer named Vannevar Bush, who had served as the director of the Office of Scientific Research and Development (OSRD). Created in 1941, the OSRD had played a crucial role during the war years, in large part by channeling American scientific ingenuity toward the invention of novel military technologies for the war. To achieve this, the agency had recruited scientists performing basic research into projects that emphasized “programmatic research.” Basic research—diffuse and open-ended inquiry on fundamental questions—was a luxury of peacetime. The war demanded something more urgent and goal-directed. New weapons needed to be manufactured, and new technologies invented to aid soldiers in the battlefield. This was a battle progressively suffused with military technology—a “wizard’s war,” as newspapers called it—and a cadre of scientific wizards was needed to help America win it.
The “wizards” had wrought astonishing technological magic. Physicists had created sonar, radar, radio-sensing bombs, and amphibious tanks. Chemists had produced intensely efficient and lethal chemical weapons, including the infamous war gases. Biologists had studied the effects of high-altitude survival and seawater ingestion. Even mathematicians, the archbishops of the arcane, had been packed off to crack secret codes for the military.
The undisputed crown jewel of this targeted effort, of course, was the atomic bomb, the product of the OSRD-led Manhattan Project. On August 7, 1945, the morning after the Hiroshima bombing, the New York Times gushed about the extraordinary success of the project: “University professors who are opposed to organizing, planning and directing research after the manner of industrial laboratories . . . have something to think about now. A most important piece of research was conducted on behalf of the Army in precisely the means adopted in industrial laboratories. End result: an invention was given to the world in three years, which it would have taken perhaps half-a-century to develop if we had to rely on prima-donna research scientists who work alone. . . . A problem was stated, it was solved by teamwork, by planning, by competent direction, and not by the mere desire to satisfy curiosity.”
The congratulatory tone of that editorial captured a general sentiment about science that had swept through the nation. The Manhattan Project had overturned the prevailing model of scientific discovery. The bomb had been designed, as the Times scoffingly put it, not by tweedy “prima-donna” university professors wandering about in search of obscure truths (driven by the “mere desire to satisfy curiosity”), but by a focused SWAT team of researchers sent off to accomplish a concrete mission. A new model of scientific governance emerged from the project—research driven by specific mandates, timelines, and goals (“frontal attack” science, to use one scientist’s description)—which had produced the remarkable technological boom during the war.
But Vannevar Bush was not convinced. In a deeply influential report to President Truman entitled Science the Endless Frontier, first published in 1945, Bush had laid out a view of postwar research that had turned his own model of wartime research on its head: “Basic research,” Bush wrote, “is performed without thought of practical ends. It results in general knowledge and an understanding of nature and its laws. This general knowledge provides the means of answering a large number of important practical problems, though it may not give a complete specific answer to any one of them. . . .
“Basic research leads to new knowledge. It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn. . . . Basic research is the pacemaker of technological progress. In the nineteenth century, Yankee mechanical ingenuity, building largely upon the basic discoveries of European scientists, could greatly advance the technical arts. Now the situation is different. A nation which depends upon others for its new basic scientific knowledge will be slow in its industrial progress and weak in its competitive position in world trade, regardless of its mechanical skill.”
Directed, targeted research—“programmatic” science—the cause célèbre during the war years, Bush argued, was not a sustainable model for the future of American science. As Bush perceived it, even the widely lauded Manhattan Project epitomized the virtues of basic inquiry. True, the bomb was the product of Yankee “mechanical ingenuity.” But that mechanical ingenuity stood on the shoulders of scientific discoveries about the fundamental nature of the atom and the energy locked inside it—research performed, notably, with no driving mandate to produce anything resembling the atomic bomb. While the bomb might have come to life physically in Los Alamos, intellectually speaking it was the product of prewar physics and chemistry rooted deeply in Europe. The iconic homegrown product of wartime American science was, at least philosophically speaking, an import.
A lesson Bush had learned from all of this was that goal-directed strategies, so useful in wartime, would be of limited use during periods of peace. “Frontal attacks” were useful on the war front, but postwar science could not be produced by fiat. So Bush had pushed for a radically inverted model of scientific development, in which researchers were allowed full autonomy over their explorations and open-ended inquiry was prioritized.
The plan had a deep and lasting influence in Washington. The National Science Foundation (NSF), founded in 1950, was explicitly created to encourage scientific autonomy, turning in time, as one historian put it, into a veritable “embodiment [of Bush’s] grand design for reconciling government money and scientific independence.” A new culture of research—“long-term, basic scientific research rather than sharply focused quests for treatment and disease prevention”—rapidly proliferated at the NSF and subsequently at the NIH.
For the Laskerites, this augured a profound conflict. A War on Cancer, they felt, demanded precisely the sort of focus and undiluted commitment that had been achieved so effectively at Los Alamos. World War II had clearly surcharged medical research with new problems and new solutions; it had prompted the development of novel resuscitation techniques, research on blood and frozen plasma, on the role of adrenal steroids in shock and on cerebral and cardiac blood flow. Never in the history of medicine, as A. N. Richards, the chairman of the Committee on Medical Research, put it, had there been “so great a coordination of medical scientific labor.”
This sense of common purpose and coordination galvanized the Laskerites: they wanted a Manhattan Project for cancer. Increasingly, they felt that it was no longer necessary to wait for fundamental questions about cancer to be solved before launching an all-out attack on the problem. Farber had, after all, forged his way through the early leukemia trials with scarcely any foreknowledge of how aminopterin worked even in normal cells, let alone cancer cells. Oliver Heaviside, an English mathematician from the 1920s, once wrote jokingly about a scientist musing at a dinner table, “Should I refuse my dinner because I don’t understand the digestive system?” To Heaviside’s question, Farber might have added his own: should I refuse to attack cancer because I have not solved its basic cellular mechanisms?
Other scientists echoed this frustration. The outspoken Philadelphia pathologist Stanley Reimann wrote, “Workers in cancer must make every effort to organize their work with goals in view not just because they are ‘interesting’ but because they will help in the solution of the cancer problem.” Bush’s cult of open-ended, curiosity-driven inquiry—“interesting” science—had ossified into dogma. To battle cancer, that dogma needed to be overturned.
The first, and most seminal, step in this direction was the creation of a focused drug-discovery unit for anticancer drugs. In 1954, after a furious bout of political lobbying by Laskerites, the Senate authorized the NCI to build a program to find chemotherapeutic drugs in a more directed, targeted manner. By 1955, this effort, called the Cancer Chemotherapy National Service Center (CCNSC), was in full swing. Between 1954 and 1964, this unit would test 82,700 synthetic chemicals, 115,000 fermentation products, and 17,200 plant derivatives and treat nearly 1 million mice every year with various chemicals to find an ideal drug.
Farber was ecstatic, but impatient. “The enthusiasm . . . of these new friends of chemotherapy is refreshing and seems to be on a genuine foundation,” he wrote to Lasker in 1955. “It nevertheless seems frightfully slow. It sometimes becomes monotonous to see more and more men brought into the program go through the joys of discovering America.”
Farber had, meanwhile, stepped up his own drug-discovery efforts in Boston. In the 1940s, the soil microbiologist Selman Waksman had systematically scoured the world of soil bacteria and purified a diverse series of antibiotics. (Like the Penicillium mold, which produces penicillin, bacteria also produce antibiotics to wage chemical warfare on other microbes.) One such antibiotic came from a rod-shaped microbe called Actinomyces. Waksman called it actinomycin D. An enormous molecule shaped like an ancient Greek statue, with a small, headless torso and two extended wings, actinomycin D was later found to work by binding and damaging DNA. It potently killed bacterial cells—but unfortunately it also killed human cells, limiting its use as an antibacterial agent.
But a cellular poison could always excite an oncologist. In the summer of 1954, Farber persuaded Waksman to send him a number of antibiotics, including actinomycin D, to repurpose them as antitumor agents by testing the drugs on a series of mouse tumors. Actinomycin D, Farber found, was remarkably effective in mice. Just a few doses melted away many mouse cancers, including leukemias, lymphomas, and breast cancers. “One hesitates to call them ‘cures,’” Farber wrote expectantly, “but it is hard to classify them otherwise.”
Energized by the animal “cures,” in 1955 he launched a series of trials to evaluate the efficacy of the drug in humans. Actinomycin D had no effect on leukemias in children. Undeterred, Farber unleashed the drug on 275 children with a diverse range of cancers: lymphomas, kidney sarcomas, muscle sarcomas, and neuroblastic tumors. The trial was a pharmacist’s nightmare. Actinomycin D was so toxic that it had to be heavily diluted in saline; if even minute amounts leaked out of the veins, then the skin around the leak would necrose and turn black. In children with small veins, the drug was often given through an intravenous line inserted into the scalp.
The one form of cancer that responded in these early trials was Wilms’ tumor, a rare variant of kidney cancer. Often detected in very young children, Wilms’ tumor was typically treated by surgical removal of the affected kidney. Surgical removal was followed by X-ray radiation to the affected kidney bed. But not all Wilms’ cases could be treated using local therapy. In a fraction of cases, by the time the tumor was detected, it had already metastasized, usually to the lungs. Recalcitrant to treatment there, Wilms’ tumors were usually bombarded with X-rays and assorted drugs but with little hopes of a sustained response.
Farber found that actinomycin D, administered intravenously, potently inhibited the growth of these lung metastases, often producing remissions that lasted months. Intrigued, he pressed further. If X-rays and actinomycin D could both attack Wilms’ metastases independently, what if the agents could be combined? In 1958, he set a young radiologist couple named Giulio D’Angio and Audrey Evans and an oncologist named Donald Pinkel to work on the project. Within months, the team had confirmed that X-rays and actinomycin D were remarkably synergistic, each multiplying the toxic effect of the other. Children with metastatic cancer treated with the combined regimen often responded briskly. “In about three weeks lungs previously riddled with Wilms’ tumor metastasis cleared completely,” D’Angio recalled. “Imagine the excitement of those days when one could say for the first time with justifiable confidence, ‘We can fix that.’”
The enthusiasm generated by these findings was infectious. Although combination X-ray and chemotherapy did not always produce long-term cures, Wilms’ tumor was the first metastatic solid tumor to respond to chemotherapy. Farber had achieved his long-sought leap from the world of liquid cancers to solid tumors.
By the late 1950s, Farber was bristling with a fiery brand of optimism. Yet visitors to the Jimmy Fund clinic in the mid-1950s might have witnessed a more nuanced and complex reality. For Sonja Goldstein, whose two-year-old son, David, was treated with chemotherapy for Wilms’ tumor in 1956, the clinic seemed perpetually suspended between two poles—both “wonderful and tragic . . . unspeakably depressing and indescribably hopeful.” On entering the cancer ward, Goldstein would write later, “I sense an undercurrent of excitement, a feeling (persistent despite repeated frustrations) of being on the verge of discovery, which makes me almost hopeful.
“We enter a large hall decorated with a cardboard train along one wall. Half way down the ward is an authentic-looking stop sign, which can flash green, red, and amber lights. The train’s engine can be climbed into and the bell pulled. At the other end of the ward is a life-size gasoline pump, registering amount sold and price. . . . My first impression is one of overweening activity, almost snake pit-like in its intensity.”
It was a snake-pit—only of cancer, a seething, immersed box coiled with illness, hope, and desperation. A girl named Jenny, about four years old, played with a new set of crayons in the corner. Her mother, an attractive, easily excitable woman, kept Jenny in constant sight, holding her child with the clawlike intensity of her gaze as Jenny stooped to pick up the colors. No activity was innocent here; anything might be a sign, a symptom, a portent. Jenny, Goldstein realized, “has leukemia and is currently in the hospital because she developed jaundice. Her eyeballs are still yellow”—presaging fulminant liver failure. She, like many of the ward’s inhabitants, was relatively oblivious to the meaning of her illness. Jenny’s only concern was an aluminum teakettle to which she was deeply attached.
“Sitting in a go-cart in the hall is a little girl, who, I think at first, has been given a black eye. . . . Lucy, a 2-year old, suffers from a form of cancer that spreads to the area behind the eye and causes hemorrhaging there. She is not a very attractive child, and wails almost incessantly that first day. So does Debbie, an angelic-looking 4-year old whose face is white and frowning with suffering. She has the same type of tumor as Lucy—a neuroblastoma. Alone in a room lies Teddy. It takes many days before I venture inside it, for, skeleton-thin and blinded, Teddy has a monstrosity for a face. His tumor, starting behind the ear, has engulfed one side of his head and obliterated his normal features. He is fed through a tube in the nostril, and is fully conscious.”
Throughout the ward were little inventions and improvisations, often devised by Farber himself. Since the children were usually too exhausted to walk, tiny wooden go-carts were scattered about the room so that the patients could move around with relative freedom. IV poles for chemotherapy were strung up on the carts to allow chemo to be given at all times during the day. “To me,” Goldstein wrote, “one of the most pathetic sights of all that I have seen is the little go-cart, with the little child, leg or arm tightly bandaged to hold needle in vein, and a tall IV pole with its burette. The combined effect is that of a boat with mast but no sail, helplessly drifting alone in a rough, uncharted sea.”
Every evening, Farber came to the wards, forcefully driving his own sail-less boat through this rough and uncharted sea. He paused at each bed, taking notes and discussing the case, often barking out characteristically brusque instructions. A retinue followed him: medical residents, nurses, social workers, psychiatrists, nutritionists, and pharmacists. Cancer, he insisted, was a total disease—an illness that gripped patients not just physically, but psychically, socially, and emotionally. Only a multipronged, multidisciplinary attack would stand any chance of battling this disease. He called the concept “total care.”
But despite all efforts at providing “total care,” death stalked the wards relentlessly. In the winter of 1956, a few weeks after David’s visit, a volley of deaths hit Farber’s clinic. Betty, a child with leukemia, was the first to die. Then it was Jenny, the four-year-old with the aluminum teakettle. Teddy, with retinoblastoma, was next. A week later, Axel, another child with leukemia, bled to death, with hemorrhages in his mouth. Goldstein observed, “Death assumes shape, form, and routine. Parents emerge from their child’s room, as they have perhaps done periodically for days for short rests. A nurse takes them to the doctor’s small office; the doctor comes in and shuts the door behind him. Later, a nurse brings coffee. Still later, she hands the parents a large brown paper bag, containing odds and ends of belongings. A few minutes later, back at our promenade, we note another empty bed. Finish.”
In the winter of 1956, after a prolonged and bruising battle, Sonja’s son, three-year-old David Goldstein, died of metastatic Wilms’ tumor at the Jimmy Fund clinic, having spent the last few hours of his life delirious and whimpering under an oxygen mask. Sonja Goldstein left the hospital carrying her own brown paper bag containing the remains of her child.
But Farber was unfazed. The arsenal of cancer chemotherapy, having been empty for centuries, had filled up with new drugs. The possibilities thrown open by these discoveries were enormous: permutations and combinations of medicines, variations in doses and schedules, trials containing two-, three-, and four-drug regimens. There was, at least in principle, the capacity to re-treat cancer with one drug if another had failed, or to try one combination followed by another. This, Farber kept telling himself with hypnotic conviction, was not the “finish.” This was just the beginning of an all-out attack.
In her hospital bed on the fourteenth floor, Carla Reed was still in “isolation”—trapped in a cool, sterile room where even the molecules of air arrived filtered through dozens of sieves. The smell of antiseptic soap pervaded her clothes. A television occasionally flickered on and off. Food came on a tray labeled with brave, optimistic names—Chunky Potato Salad or Chicken Kiev—but everything tasted as if it had been boiled and seared almost to obliteration. (It had been; the food had to be sterilized before it could enter the room.) Carla’s husband, a computer engineer, came in every afternoon to sit by her bed. Ginny, her mother, spent the days rocking mechanically in a chair, exactly as I had found her the first morning. When Carla’s children stopped by, in masks and gloves, she wept quietly, turning her face toward the window.
For Carla, the physical isolation of those days became a barely concealed metaphor for a much deeper, fiercer loneliness, a psychological quarantine even more achingly painful than her actual confinement. “In those first two weeks, I withdrew into a different person,” she said. “What went into the room and what came out were two different people.
“I thought over and over again about my chances of surviving through all this. Thirty percent. I would repeat that number to myself at night. Not even a third. I would stay up at night looking up at the ceiling and think: What is thirty percent? What happens thirty percent of the time? I am thirty years old—about thirty percent of ninety. If someone gave me thirty percent odds in a game, would I take the odds?”
The morning after Carla had arrived at the hospital, I walked into her room with sheaves of paper. They were consent forms for chemotherapy that would allow us to instantly start pumping poisons into her body to kill cancer cells.
Chemotherapy would come in three phases. The first phase would last about a month. The drugs—given in rapid-fire succession—would hopefully send the leukemia into a sustained remission. They would certainly kill her normal white blood cells as well. Her white cell count would drop in free fall, all the way to zero. For a few critical days, she would inhabit one of the most vulnerable states that modern medicine can produce: a body with no immune system, defenseless against the environment around it.
If the leukemia did go into remission, then we would “consolidate” and intensify that remission over several months. That would mean more chemotherapy, but at lower doses, given over longer intervals. She would be able to leave the hospital and return home, coming back every week for more chemotherapy. Consolidation and intensification would last for eight additional weeks, perhaps longer.
The worst part, perhaps, I kept for last. Acute lymphoblastic leukemia has an ugly propensity for hiding in the brain. The intravenous chemotherapy that we would give Carla, no matter how potent, simply couldn’t break into the cisterns and ventricles that bathed her brain. The blood-brain barrier essentially made the brain into a “sanctuary” (an unfortunate word, implying that your own body could be abetting the cancer) for the leukemia cells. To send drugs directly into that sanctuary, the medicines would need to be injected directly into Carla’s spinal fluid, through a series of spinal taps. Whole-brain radiation treatment—highly penetrant X-rays dosed directly through her skull—would also be used prophylactically against leukemia growth in her brain. And there would be even more chemotherapy to follow, spanning over two years, to “maintain” the remission if we achieved it.
Induction. Intensification. Maintenance. Cure. An arrow in pencil connecting the four points on a blank piece of paper. Carla nodded.
When I went through the avalanche of chemotherapy drugs that would be used over the next two years to treat her, she repeated the names softly after me under her breath, like a child discovering a new tongue twister: “Cyclophosphamide, cytarabine, prednisone, asparaginase, Adriamycin, thioguanine, vincristine, 6-mercaptopurine, methotrexate.”
“The butcher shop”
Randomised screening trials are bothersome. It takes ages to come to an answer, and these need to be large-scale projects to be able to answer the questions. [But . . .] there is no second-best option.
—H. J. de Koning,
Annals of Oncology, 2003
The best [doctors] seem to have a sixth sense about disease. They feel its presence, know it to be there, perceive its gravity before any intellectual process can define, catalog, and put it into words. Patients sense this about such a physician as well: that he is attentive, alert, ready; that he cares. No student of medicine should miss observing such an encounter. Of all the moments in medicine, this one is most filled with drama, with feeling, with history.
Annals of Internal Medicine, 1993
It was in Bethesda, at the very institute that had been likened to a suburban golfing club in the 1940s, that the new arsenal of oncology was deployed on living patients.
In April 1955, in the midst of a humid spring in Maryland, a freshly recruited researcher at the National Cancer Institute named Emil Freireich walked up to his new office in the redbrick Clinical Center Building and found, to his exasperation, that his name had been misspelled on the door, with the last five letters lopped off. The plate on the door read EMIL FREI, MD. “My first thought, of course, was: Isn’t it typical of the government?”
It wasn’t a misspelling. When Freireich entered the office, he confronted a tall, thin young man who identified himself as Emil Frei. Freireich’s office, with the name correctly spelled, was next door.
Their names notwithstanding, the two Emils were vastly different characters. Freireich—just thirty-five years old and fresh out of a hematology fellowship at Boston University—was flamboyant, hot-tempered, and adventurous. He spoke quickly, often explosively, with a booming voice followed often by an even more expressive boom of laughter. He had been a medical intern at the fast-paced “Ward 55” of the Cook County Hospital in Chicago—and such a nuisance to the authorities that he had been released from his contract earlier than usual. In Boston, Freireich had worked with Chester Keefer, one of Minot’s colleagues who had subsequently spearheaded the production of penicillin during World War II. Antibiotics, folic acid, vitamins, and antifolates were stitched into Freireich’s soul. He admired Farber intensely—not just the meticulous, academic scientist, but the irreverent, impulsive, larger-than-life Farber who could antagonize his enemies as quickly as he could seduce his benefactors. “I have never seen Freireich in a moderate mood,” Frei would later say.
If Freireich had been a character in a film, he would have needed a cinematic foil, a Laurel to his Hardy or a Felix to his Oscar. The tall, thin man who confronted him at the door at the NCI that afternoon was that foil. Where Freireich was brusque and flamboyant, impulsive to a fault, and passionate about every detail, Frei was cool, composed, and cautious, a poised negotiator who preferred to work backstage. Emil Frei—known to most of his colleagues by his nickname, Tom—had been an art student in St. Louis in the thirties. He had attended medical school almost as an afterthought in the late 1940s, served in the navy in the Korean War, and returned to St. Louis as a resident in medicine. He was charming, soft-spoken, and careful—a man of few, chosen words. To watch him manage critically ill children and their testy, nervous parents was to watch a champion swimmer glide through water—so adept in the art that he made artistry vanish.
The person responsible for bringing the two Emils to Bethesda was Gordon Zubrod, the new director of the NCI’s Clinical Center. Intellectual, deliberate, and imposing, a clinician and scientist known for his regal composure, Zubrod had arrived at the NIH having spent nearly a decade developing antimalaria drugs during World War II, an experience that would deeply influence his early interests in clinical trials for cancer.
Zubrod’s particular interest was children’s leukemia—the cancer that Farber had plunged into the very forefront of clinical investigation. But to contend with leukemia, Zubrod knew, was to contend with its fieriness and brittleness, its moody, volcanic unpredictability. Drugs could be tested, but first, the children needed to be kept alive. A quintessential delegator—an “Eisenhower” of cancer research, as Freireich once called him—Zubrod quickly conscripted two young doctors to maintain the front lines of the wards: Freireich and Frei, fresh from their respective fellowships in Boston and St. Louis. Frei drove cross-country in a beat-up old Studebaker to join Zubrod. Freireich came just a few weeks later, in a ramshackle Oldsmobile containing all his belongings, his pregnant wife, and his nine-month-old daughter.
It could easily have been a formula for disaster—but it worked. Right from the start, the two Emils found that they shared a unique synergy. Their collaboration was symbolic of a deep intellectual divide that ran through the front lines of oncology: the rift between overmoderated caution and bold experimentation. Each time Freireich pushed too hard on one end of the experimental fulcrum—often bringing himself and his patients to the brink of disaster—Frei pushed back to ensure that the novel, quixotic, and often deeply toxic therapies were mitigated by caution. Frei and Freireich’s battles soon became emblematic of the tussles within the NCI. “Frei’s job,” one researcher recalled, “in those days was to keep Freireich from getting in trouble.”
Zubrod had his own schemes to keep leukemia research out of trouble. As new drugs, combinations, and trials proliferated, Zubrod worried that institutions would be caught at cross-purposes, squabbling over patients and protocols when they should really be battling cancer. Burchenal in New York, Farber in Boston, James Holland at Roswell Park, and the two Emils at the NCI were all chomping at the bit to launch clinical trials. And since ALL was a rare disease, every patient was a precious resource for a leukemia trial. To avert conflicts, Zubrod proposed that a “consortium” of researchers be created to share patients, trials, data, and knowledge.
The proposal changed the field. “Zubrod’s cooperative group model galvanized cancer medicine,” Robert Mayer (who would later become the chair of one of these groups) recalls. “For the first time, an academic oncologist felt as if he had a community. The cancer doctor was not the outcast anymore, not the man who prescribed poisons from some underground chamber in the hospital.” The first group meeting, chaired by Farber, was a resounding success. The researchers agreed to proceed with a series of common trials, called protocols, as soon as possible.
Zubrod next set about organizing the process by which trials could be run. Cancer trials, he argued, had thus far been embarrassingly chaotic and disorganized. Oncologists needed to emulate the best trials in medicine. And to learn how to run objective, unbiased, state-of-the-art clinical trials, they would need to study the history of the development of antibiotics.
In the 1940s, as new antibiotics had begun to appear on the horizon, physicians had encountered an important quandary: how might one objectively test the efficacy of any novel drug? At the Medical Research Council in Britain, the question had taken on a particularly urgent and rancorous note. The discovery of streptomycin, a new antimicrobial drug in the early forties, had set off a flurry of optimism that tuberculosis could be cured. Streptomycin killed tuberculosis-causing mycobacteria in petri dishes, but its efficacy in humans was unknown. The drug was in critically short supply, with doctors parrying to use even a few milligrams of it to treat a variety of other infections. To ration streptomycin, an objective experiment to determine its efficacy in human tuberculosis was needed.
But what sort of experiment? An English statistician named Bradford Hill (a former victim of TB himself) proposed an extraordinary solution. Hill began by recognizing that doctors, of all people, could not be entrusted to perform such an experiment without inherent biases. Every biological experiment requires a “control” arm—untreated subjects against whom the efficacy of a treatment can be judged. But left to their own devices, doctors were inevitably likely (even if unconsciously so) to select certain types of patients upfront, then judge the effects of a drug on this highly skewed population using subjective criteria, piling bias on top of bias.
Hill’s proposed solution was to remove such biases by randomly assigning patients to treatment with streptomycin versus a placebo. By “randomizing” patients to each arm, any doctors’ biases in patient assignment would be dispelled. Neutrality would be enforced—and thus a hypothesis could be strictly tested.
Hill’s randomized trial was a success. The streptomycin arm of the trial clearly showed an improved response over the placebo arm, enshrining the antibiotic as a new anti-TB drug. But perhaps more important, it was Hill’s methodological invention that was permanently enshrined. For medical scientists, the randomized trial became the most stringent means to evaluate the efficacy of any intervention in the most unbiased manner.
Zubrod was inspired by these early antimicrobial trials. He had used these principles in the late 1940s to test antimalarials, and he proposed using them to lay down the principles by which the NCI would test its new protocols. The NCI’s trials would be systematic: every trial would test a crucial piece of logic or hypothesis and produce yes and no answers. The trials would be sequential: the lessons of one trial would lead to the next and so forth—a relentless march of progress until leukemia had been cured. The trials would be objective, randomized if possible, with clear, unbiased criteria to assign patients and measure responses.
Trial methodology was not the only powerful lesson that Zubrod, Frei, and Freireich learned from the antimicrobial world. “The analogy of drug resistance to antibiotics was given deep thought,” Freireich remembered. As Farber and Burchenal had discovered to their chagrin in Boston and New York, leukemia treated with a single drug would inevitably grow resistant to the drug, resulting in the flickering, transient responses followed by the devastating relapses.
The situation was reminiscent of TB. Like cancer cells, mycobacteria—the germs that cause tuberculosis—also became resistant to antibiotics if the drugs were used singly. Bacteria that survived a single-drug regimen divided, mutated, and acquired drug resistance, thus making that original drug useless. To thwart this resistance, doctors treating TB had used a blitzkrieg of antibiotics—two or three used together like a dense pharmaceutical blanket meant to smother all cell division and stave off bacterial resistance, thus extinguishing the infection as definitively as possible.
But could two or three drugs be tested simultaneously against cancer—or would the toxicities be so forbidding that they would instantly kill patients? As Freireich, Frei, and Zubrod studied the growing list of antileukemia drugs, the notion of combining drugs emerged with growing clarity: toxicities notwithstanding, annihilating leukemia might involve using a combination of two or more drugs.
The first protocol was launched to test different doses of Farber’s methotrexate combined with Burchenal’s 6-MP, the two most active antileukemia drugs. Three hospitals agreed to join: the NCI, Roswell Park, and the Children’s Hospital in Buffalo, New York. The aims of the trial were kept intentionally simple. One group would be treated with intensive methotrexate dosing, while the other group would be treated with milder and less intensive dosing. Eighty-four patients enrolled. On arrival day, parents of the children were handed white envelopes with the randomized assignment sealed inside.
Despite the multiple centers and the many egos involved, the trial ran surprisingly smoothly. Toxicities multiplied; the two-drug regimen was barely tolerable. But the intensive group fared better, with longer and more durable responses. The regimen, though, was far from a cure: even the intensively treated children soon relapsed and died by the end of one year.
Protocol I set an important precedent. Zubrod’s and Farber’s cherished model of a cancer cooperative group was finally in action. Dozens of doctors, nurses, and patients in three independent hospitals had yoked themselves to follow a single formula to treat a group of patients—and each one, suspending its own idiosyncrasies, had followed the instructions perfectly. “This work is one of the first comparative studies in the chemotherapy of malignant neoplastic disease,” Frei noted. In a world of ad hoc, often desperate strategies, conformity had finally come to cancer.
In the winter of 1957, the leukemia group launched yet another modification to the first experiment. This time, one group received a combined regimen, while the other two groups were given one drug each. And with the question even more starkly demarcated, the pattern of responses was even clearer. Given alone, either of the drugs performed poorly, with a response rate between 15 and 20 percent. But when methotrexate and 6-MP were administered together, the remission rate jumped to 45 percent.
The next chemotherapy protocol, launched just two years later in 1959, ventured into even riskier territory. Patients were treated with two drugs to send them into complete remission. Then half the group received several months of additional drugs, while the other group was given a placebo. Once again, the pattern was consistent. The more aggressively treated group had longer and more durable responses.
Trial by trial, the group crept forward, like a spring uncoiling to its end. In just six pivotal years, the leukemia study group had slowly worked itself to giving patients not one or two, but four chemotherapy drugs, often in succession. By the winter of 1962, the compass of leukemia medicine pointed unfailingly in one direction. If two drugs were better than one, and if three better than two, then what if four antileukemia drugs could be given together—in combination, as with TB?
Both Frei and Freireich sensed that this was the inevitable culmination of the NCI’s trials. But even if they knew it subconsciously, they tiptoed around the notion for months. “The resistance would be fierce,” Freireich knew. The leukemia ward was already being called a “butcher shop” by others at the NCI. “The idea of treating children with three or four highly cytotoxic drugs was considered cruel and insane,” Freireich said. “Even Zubrod could not convince the consortium to try it. No one wanted to turn the NCI into a National Institute of Butchery.”
An Early Victory
. . . But I do subscribe to the view that words have very powerful texts and subtexts. “War” has truly a unique status, “war” has a very special meaning. It means putting young men and women in situations where they might get killed or grievously wounded. It’s inappropriate to retain that metaphor for a scholarly activity in these times of actual war. The NIH is a community of scholars focused on generating knowledge to improve the public health. That’s a great activity. That’s not a war.
—Samuel Broder, NCI director
In the midst of this nervy deliberation about the use of four-drug combination therapy, Frei and Freireich received an enormously exciting piece of news. Just a few doors down from Freireich’s office at the NCI, two researchers, Min Chiu Li and Roy Hertz, had been experimenting with choriocarcinoma, a cancer of the placenta. Even rarer than leukemia, choriocarcinoma often grows out of the placental tissue surrounding an abnormal pregnancy, then metastasizes rapidly and fatally into the lung and the brain. When it occurs, choriocarcinoma is thus a double tragedy: an abnormal pregnancy compounded by a lethal malignancy, birth tipped into death.
If cancer chemotherapists were generally considered outsiders by the medical community in the 1950s, then Min Chiu Li was an outsider even among outsiders. He had come to the United States from Mukden University in China, then spent a brief stint at the Memorial Hospital in New York. In a scramble to dodge the draft during the Korean War, he had finagled a two-year position in Hertz’s service as an assistant obstetrician. He was interested in research (or at least feigned interest), but Li was considered an intellectual fugitive, unable to commit to any one question or plan. His current plan was to lie low in Bethesda until the war blew over.
But what had started off as a decoy fellowship for Li turned, within a single evening in August 1956, into a full-time obsession. On call late one evening, he tried to medically stabilize a woman with metastatic choriocarcinoma. The tumor was in its advanced stages and bled so profusely that the patient died in front of Li’s eyes in three hours. Li had heard of Farber’s antifolates. Almost instinctually, he had made a link between the rapidly dividing leukemia cells in the bone marrow of the children in Boston and the rapidly dividing placental cells in the women in Bethesda. Antifolates had never been tried in this disease, but if the drugs could stop aggressive leukemias from growing—even if temporarily—might they not at least partially relieve the eruptions of choriocarcinoma?
Li did not have to wait long. A few weeks after the first case, another patient, a young woman called Ethel Longoria, 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,” 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 chemotherapy, 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 publish 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 summoned him to a meeting and promptly fired him.
“Li was accused of experimenting on people,” 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 dismissal, 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.
Mice and Men
A model is a lie that helps you see the truth.
Min Chiu Li’s experience with choriocarcinoma was a philosophical nudge for Frei and Freireich. “Clinical research is a matter of urgency,” 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 insisted 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. 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 newcomer, vincristine, was a poisonous plant-alkaloid that came from the Madagascar periwinkle, a small, weedlike creeper with violet flowers and an entwined, coiled stem. (The name vincristine comes from vinca, the Latin word for “bind.”) Vincristine had been discovered in 1958 at the Eli Lilly company through a drug-discovery program that involved grinding up thousands of pounds of plant material and testing the extracts in various biological assays. Although originally intended as an antidiabetic, vincristine at small doses was found to kill leukemia cells. Rapidly growing cells, such as those of leukemia, typically create a skeletal scaffold of proteins (called microtubules) that allows two daughter cells to separate from each other and thereby complete cell division. Vincristine works by binding to the end of these microtubules and then paralyzing the cellular skeleton in its grip—thus, quite literally, evoking the Latin word after which it was originally named.
With vincristine added to the pharmacopoeia, leukemia researchers found themselves facing the paradox of excess: how might one take four independently active drugs—methotrexate, prednisone, 6-MP, and vincristine—and stitch them together into an effective regimen? And since each drug was potentially severely toxic, could one ever find a combination that would kill the leukemia but not kill a child?
Two drugs had already spawned dozens of possibilities; with four drugs, the leukemia consortium would take not fifty, but a hundred and fifty years to finish its trials. David Nathan, then a new recruit at the NCI, recalled the near standstill created by the avalanche of new medicines: “Frei and Freireich were simply taking drugs that were available and adding them together in combinations. . . . The possible combinations, doses, and schedules of four or five drugs were infinite. Researchers could work for years on finding the right combination of drugs and schedules.” Zubrod’s sequential, systematic, objective trials had reached an impasse. What was needed was quite the opposite of a systematic approach—an intuitive and inspired leap of faith into the deadly abyss of deadly drugs.
A scientist from Alabama, Howard Skipper—a scholarly, soft-spoken man who liked to call himself a “mouse doctor”—provided Frei and Freireich a way out of the impasse. Skipper was an outsider to the NCI. If leukemia was a model form of cancer, then Skipper had been studying the disease by artificially inducing leukemias in animals—in effect, by building a model of a model. Skipper’s model used a mouse cell line called L-1210, a lymphoid leukemia that could be grown in a petri dish. When laboratory mice were injected with these cells, they would acquire the leukemia—a process known as engraftment because it was akin to transferring a piece of normal tissue (a graft) from one animal to another.
Skipper liked to think about cancer not as a disease but as an abstract mathematical entity. In a mouse transplanted with L-1210 cells, the cells divided with nearly obscene fecundity—often twice a day, a rate startling even for cancer cells. A single leukemia cell engrafted into the mouse could thus take off in a terrifying arc of numbers: 1, 4, 16, 64, 256, 1,024, 4,096, 16,384, 65,536, 262,144, 1,048,576 . . . and so forth, all the way to infinity. In sixteen or seventeen days, more than 2 billion daughter cells could grow out of that single cell—more than the entire number of blood cells in the mouse.
Skipper learned that he could halt this effusive cell division by administering chemotherapy to the leukemia-engrafted mouse. By charting the life and death of leukemia cells as they responded to drugs in these mice, Skipper emerged with two pivotal findings. First, he found that chemotherapy typically killed a fixed percentage of cells at any given instance no matter what the total number of cancer cells was. This percentage was a unique, cardinal number particular to every drug. In other words, if you started off with 100,000 leukemia cells in a mouse and administered a drug that killed 99 percent of those cells in a single round, then every round would kill cells in a fractional manner, resulting in fewer and fewer cells after every round of chemotherapy: 100,000 . . . 1,000 . . . 10 . . . and so forth, until the number finally fell to zero after four rounds. Killing leukemia was an iterative process, like halving a monster’s body, then halving the half, and halving the remnant half.
Second, Skipper found that by adding drugs in combination, he could often get synergistic effects on killing. Since different drugs elicited different resistance mechanisms, and produced different toxicities in cancer cells, using drugs in concert dramatically lowered the chance of resistance and increased cell killing. Two drugs were therefore typically better than one, and three drugs better than two. With several drugs and several iterative rounds of chemotherapy in rapid-fire succession, Skipper cured leukemias in his mouse model.
For Frei and Freireich, Skipper’s observations had an inevitable, if frightening, conclusion. If human leukemias were like Skipper’s mouse leukemias, then children would need to be treated with a regimen containing not one or two, but multiple drugs. Furthermore, a single treatment would not suffice. “Maximal, intermittent, intensive, up-front” chemotherapy would need to be administered with nearly ruthless, inexorable persistence, dose after dose after dose after dose, pushing the outermost limits of tolerability. There would be no stopping, not even after the leukemia cells had apparently disappeared in the blood and the children had apparently been “cured.”
Freireich and Frei were now ready to take their pivotal and intuitive leap into the abyss. The next regimen they would try would be a combination of all four drugs: vincristine, amethopterin, mercaptopurine, and prednisone. The regimen would be known by a new acronym, with each letter standing for one of the drugs: VAMP.
The name had many intended and unintended resonances. Vamp is a word that means to improvise or patch up, to cobble something together from bits and pieces that might crumble apart any second. It can mean a seductress—one who promises but does not deliver. It also refers to the front of a boot, the part that carries the full brunt of force during a kick.
Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.
If we didn’t kill the tumor, we killed the patient.
—William Moloney on the early days
VAMP—high-dose, life-threatening, four-drug combination therapy for leukemia—might have made obvious sense to Skipper, Frei, and Freireich, but to many of their colleagues, it was a terrifying notion, an abomination. Freireich finally approached Zubrod with his idea: “I wanted to treat them with full doses of vincristine and amethopterin, combined with the 6-MP and prednisone.” The ands in the sentence were italicized to catch Zubrod’s attention.
Zubrod was stunned. “It is the dose that makes a poison,” runs the old adage in medicine: all medicines were poisons in one form or another merely diluted to an appropriate dose. But chemotherapy was poison even at the correct dose.* A child with leukemia was already stretched to the brittle limits of survival, hanging on to life by a bare physiological thread. People at the NCI would often casually talk of chemotherapy as the “poison of the month.” If four poisons of the month were simultaneously pumped daily into a three- or six-year-old child, there was virtually no guarantee that he or she could survive even the first dose of this regimen, let alone survive week after week after week.
When Frei and Freireich presented their preliminary plan for VAMP at a national meeting on blood cancers, the audience balked. Farber, for one, favored giving one drug at a time and adding the second only after relapse and so forth, following the leukemia consortium’s slow but steady method of adding drugs carefully and sequentially. “Oh, boy,” Freireich recalled, “it was a terrible, catastrophic showdown. We were laughed at and then called insane, incompetent, and cruel.” With limited patients and hundreds of drugs and combinations to try, every new leukemia trial had to wind its way through a complex approval process through the leukemia group. Frei and Freireich, it was felt, were making an unauthorized quantum leap. The group refused to sponsor VAMP—at least not until the many other trials had been completed.
But Frei wrangled a last-minute compromise: VAMP would be studied independently at the NCI, outside the purview of the ALGB. “The idea was preposterous,” Freireich recalled. “To run the trial, we would need to split with the ALGB, the very group that we had been so instrumental in founding.” Zubrod wasn’t pleased with the compromise: it was a break from his cherished “cooperative” model. Worse still, if VAMP failed, it would be a political nightmare for him. “If the children had died, we’d be accused of experimenting on people at this federal installation of the National Cancer Institute,” Freireich acknowledged. Everyone knew it was chancy territory. Embroiled in controversy, even if he had resolved it as best he could, Frei resigned as the chair of the ALGB. Years later, Freireich acknowledged the risks involved: “We could have killed all of those kids.”
The VAMP trial was finally launched in 1961. Almost instantly, it seemed like an abysmal mistake—precisely the sort of nightmare that Zubrod had been trying to avoid.
The first children to be treated “were already terribly, terribly ill,” Freireich recalled. “We started VAMP, and by the end of the week, many of them were infinitely worse than before. It was a disaster.” The four-drug chemo regimen raged through the body and wiped out all the normal cells. Some children slumped into near coma and were hooked to respirators. Freireich, desperate to save them, visited his patients obsessively in their hospital beds. “You can imagine the tension,” he wrote. “I could just hear people saying, ‘I told you so, this girl or boy is going to die.’” He hovered in the wards, pestering the staff with questions and suggestions. His paternal, possessive instincts were aroused: “These were my kids. I really tried to take care of them.”
The NCI, as a whole, watched tensely—for its life, too, was on the line. “I did little things,” Freireich wrote. “Maybe I could make them more comfortable, give them a little aspirin, lower their temperatures, get them a blanket.” Thrown into the uncertain front lines of cancer medicine, juggling the most toxic and futuristic combinations of drugs, the NCI doctors fell back to their oldest principles. They provided comfort. They nurtured. They focused on caregiving and support. They fluffed pillows.
At the end of three excruciating weeks, a few of Freireich’s patients somehow pulled through. Then, unexpectedly—at a time when it was almost unbearable to look for it—there was a payoff. The normal bone marrow cells began to recover gradually, but the leukemia went into remission. The bone marrow biopsies came back one after another—all without leukemia cells. Red blood cells and white blood cells and platelets sprouted up in an otherwise scorched field of bone marrow. But the leukemia did not return. Another set of biopsies, weeks later, confirmed the finding. Not a single leukemia cell was visible under the microscope. This—after near-complete devastation—was a remission so deep that it exceeded the expectations of everyone at the NCI.
A few weeks later, the NCI team drummed up enough courage to try VAMP on yet another small cohort of patients. Once again, after the nearly catastrophic dip in counts—“like a drop from a cliff with a thread tied to your ankles,” as one researcher remembered it—the bone marrow recovered and the leukemia vanished. A few days later, the bone marrow began to regenerate, and Freireich performed a hesitant biopsy to look at the cells. The leukemia had vanished again. What it had left behind was full of promise: normal cobblestones of blood cells growing back in the marrow.
By 1962, Frei and Freireich had treated six patients with several doses of VAMP. Remissions were reliable and durable. The Clinical Center was now filled with the familiar chatter of children in wigs and scarves who had survived two or three seasons of chemotherapy—a strikingly anomalous phenomenon in the history of leukemia. Critics were slowly turning into converts. Other clinical centers around the nation joined Frei and Freireich’s experimental regimen. The patient “is amazingly recovered,” a hematologist in Boston treating an eleven-year-old wrote in 1964. Astonishment slowly gave way to buoyancy. Even William Dameshek, the opinionated Harvard-trained hematologist and one of the most prominent early opponents of VAMP, wrote, “The mood among pediatric oncologists changed virtually overnight from one of ‘compassionate fatalism’ to one of ‘aggressive optimism.’”
The optimism was potent, but short-lived. In September 1963, not long after Frei and Freireich had returned from one of those triumphant conferences celebrating the unexpected success of VAMP, a few children in remission came back to the clinic with minor complaints: a headache, a seizure, an occasional tingling of a nerve in the face.
“Some of us didn’t make much of it at first,” a hematologist recalled. “We imagined the symptoms would go away.” But Freireich, who had studied the spread of leukemia cells in the body for nearly a decade, knew that these were headaches that would not go away. By October, there were more children back at the clinic, this time with numbness, tingling, headaches, seizures, and facial paralysis. Frei and Freireich were both getting nervous.
In the 1880s, Virchow had observed that leukemia cells could occasionally colonize the brain. To investigate the possibility of a brain invasion by cancer cells, Frei and Freireich looked directly at the spinal fluid using a spinal tap, a method to withdraw a few milliliters of fluid from the spinal canal using a thin, straight needle. The fluid, a straw-colored liquid that circulates in direct connection with the brain, is a surrogate for examining the brain.
In the folklore of science, there is the often-told story of the moment of discovery: the quickening of the pulse, the spectral luminosity of ordinary facts, the overheated, standstill second when observations crystallize and fall together into patterns, like pieces of a kaleidoscope. The apple drops from the tree. The man jumps up from a bathtub; the slippery equation balances itself.
But there is another moment of discovery—its antithesis—that is rarely recorded: the discovery of failure. It is a moment that a scientist often encounters alone. A patient’s CT scan shows a relapsed lymphoma. A cell once killed by a drug begins to grow back. A child returns to the NCI with a headache.
What Frei and Freireich discovered in the spinal fluid left them cold: leukemia cells were growing explosively in the spinal fluid by the millions, colonizing the brain. The headaches and the numbness were early signs of much more profound devastations to come. In the months that followed, one by one, all the children came back to the institute with a spectrum of neurological complaints—headaches, tinglings, abstract speckles of light—then slumped into coma. Bone marrow biopsies were clean. No cancer was found in the body. But the leukemia cells had invaded the nervous system, causing a quick, unexpected demise.
It was a consequence of the body’s own defense system subverting cancer treatment. The brain and spinal cord are insulated by a tight cellular seal called the blood-brain barrier that prevents foreign chemicals from easily getting into the brain. It is an ancient biological system that has evolved to keep poisons from reaching the brain. But the same system had likely also kept VAMP out of the nervous system, creating a natural “sanctuary” for cancer within the body. The leukemia, sensing an opportunity in that sanctuary, had furtively climbed in, colonizing the one place that is fundamentally unreachable by chemotherapy. The children died one after the other—felled by virtue of the adaptation designed to protect them.
Frei and Freireich were hit hard by those relapses. For a clinical scientist, a trial is like a child, a deeply personal investment. To watch this sort of intense, intimate enterprise fold up and die is to suffer the loss of a child. One leukemia doctor wrote, “I know the patients, I know their brothers and sisters, I know their dogs and cats by name. . . . The pain is that a lot of love affairs end.”
After seven exhilarating and intensive trials, the love affair at the NCI had indeed ended. The brain relapses after VAMP seemed to push morale at the institute to the breaking point. Frei, who had so furiously tried to keep VAMP alive through its most trying stages—twelve months of manipulating, coaxing, and wheedling—now found himself drained of his last stores of energy. Even the indefatigable Freireich was beginning to lose steam. He felt a growing hostility from others at the institute. At the peak of his career, he, too, felt tired of the interminable institutional scuffles that had once invigorated him.
In the winter of 1963, Frei left for a position at the MD Anderson Cancer Center in Houston, Texas. The trials were temporarily put on hold (although they would eventually be resurrected in Texas). Freireich soon left the NCI to join Frei in Houston. The fragile ecosystem that had sustained Freireich, Frei, and Zubrod dissolved in a few months.
But the story of leukemia—the story of cancer—isn’t the story of doctors who struggle and survive, moving from one institution to another. It is the story of patients who struggle and survive, moving from one embankment of illness to another. Resilience, inventiveness, and survivorship—qualities often ascribed to great physicians—are reflected qualities, emanating first from those who struggle with illness and only then mirrored by those who treat them. If the history of medicine is told through the stories of doctors, it is because their contributions stand in place of the more substantive heroism of their patients.
I said that all the children had relapsed and died—but this is not quite true. A few, a small handful, for mysterious reasons, never relapsed with leukemia in the central nervous system. At the NCI and the few other hospitals brave enough to try VAMP, about 5 percent of the treated children finished their yearlong journey. They remained in remission not just for weeks or months, but for years. They came back, year after year, and sat nervously in waiting rooms at trial centers all around the nation. Their voices deepened. Their hair grew back. Biopsy after biopsy was performed. And there was no visible sign of cancer.
On a summer afternoon, I drove through western Maine to the small town of Waterboro. Against the foggy, overcast sky, the landscape was spectacular, with ancient pine and birch forests tipping into crystalline lakes. On the far edge of the town, I turned onto a dirt road leading away from the water. At the end of the road, surrounded by deep pine forests, was a tiny clapboard house. A fifty-six-year-old woman in a blue T-shirt answered the door. It had taken me seventeen months and innumerable phone calls, questions, interviews, and references to track her down. One afternoon, scouring the Internet, I had found a lead. I remember dialing the number, excited beyond words, and waiting for interminable rings before a woman answered. I had fixed up an appointment to meet her that week and driven rather recklessly to Maine to keep it. When I arrived, I realized that I was twenty minutes early.
I cannot remember what I said, or struggled to say, as a measure of introduction. But I felt awestruck. Standing before me against the door, smiling nervously, was one of the survivors of that original VAMP cohort cured of childhood leukemia.
The basement was flooded and the couch was growing mildew, so we sat outdoors in the shadows of the trees in a screened tent with deerflies and mosquitoes buzzing outside. The woman—Ella, I’ll call her—had collected a pile of medical records and photographs for me to look through. As she handed them over, I sensed a shiver running through her body, as if even today, forty-five years after her ordeal, the memory haunts her viscerally.
Ella was diagnosed with leukemia in June 1964, about eighteen months after VAMP was first used at the NCI. She was eleven years old. In the photographs taken before her diagnosis, she was a typical preteen with bangs and braces. In the photograph taken just six months later (after chemotherapy), she was transformed—bald, sheet-white from anemia, and severely underweight, collapsed on a wheelchair and unable to walk.
Ella was treated with VAMP. (Her oncologists in Boston, having heard of the spectacular responses at the NCI, had rather bravely chosen to treat her—off trial—with the four-drug regimen.) It had seemed like a cataclysm at first. The high doses of vincristine caused such severe collateral nerve damage that she was left with a permanent burning sensation in her legs and fingers. Prednisone made her delirious. The nurses, unable to deal with a strong-willed, deranged preteen wandering through the corridors of the hospital screaming and howling at night, restrained her by tying her arms with ropes to the bedposts. Confined to her bed, she often crouched in a fetal position, her muscles wasting away, the neuropathy worsening. At twelve years of age, she became addicted to morphine, which was prescribed for her pain. (She “detoxed” herself by sheer force of will, she said, by “lasting it out through the spasms of withdrawal.”) Her lower lip is still bruised from the time she bit herself in those awful months while waiting out the hour for the next dose of morphine.
Yet, remarkably, the main thing she remembers is the overwhelming feeling of being spared. “I feel as if I slipped through,” she told me, arranging the records back into their envelopes. She looked away, as if to swat an imaginary fly, and I could see her eyes welling up with tears. She had met several other children with leukemia in the hospital wards; none had survived. “I don’t know why I deserved the illness in the first place, but then I don’t know why I deserved to be cured. Leukemia is like that. It mystifies you. It changes your life.” My mind briefly flashed to the Chiribaya mummy, to Atossa, to Halsted’s young woman awaiting her mastectomy.
Sidney Farber never met Ella, but he encountered patients just like her—long-term survivors of VAMP. In 1964, the year that Ella began her chemotherapy, he triumphantly brought photographs of a few such patients to Washington as a sort of show-and-tell for Congress, living proof that chemotherapy could cure cancer. The path was now becoming increasingly clear to him. Cancer research needed an additional thrust: more money, more research, more publicity, and a directed trajectory toward a cure. His testimony before Congress thus acquired a nearly devotional, messianic fervor. After the photographs and his testimony, one observer recalled, any further proof was “anticlimactic and unnecessary.” Farber was now ready to leap out from the realm of leukemia into the vastly more common real cancers. “We are attempting to develop chemicals which might affect otherwise incurable tumors of the breast, the ovary, the uterus, the lung, the kidney, the intestine, and highly malignant tumors of the skin, such as the black cancer, or melanoma,” he wrote. The cure of even one such solid cancer in adults, Farber knew, would singularly revolutionize oncology. It would provide the most concrete proof that this was a winnable war.
* Since most of the early anticancer drugs were cytotoxic—cell-killing—the threshold between a therapeutic (cancer-killing) dose and a toxic dose was extremely narrow. Many of the drugs had to be very carefully dosed to avoid the unwarranted but inextricably linked toxicity.
An Anatomist’s Tumor
It took plain old courage to be a chemotherapist in the 1960s and certainly the courage of the conviction that cancer would eventually succumb to drugs.
—Vincent DeVita, National Cancer Institute
investigator (and eventually NCI director)
On a chilly February morning in 2004, a twenty-four-year-old athlete, Ben Orman, discovered a lump in his neck. He was in his apartment, reading the newspaper, when, running his hand absentmindedly past his face, his fingers brushed against a small swelling. The lump was about the size of a small dried grape. If he took a deep breath, he could swallow it back into the cavity of his chest. He dismissed it. It was a lump, he reasoned, and athletes were used to lumps: calluses, swollen knees, boils, bumps, bruises coming and going with no remembered cause. He returned to his newspaper and worry vanished from his mind. The lump in his neck, whatever it was, would doubtless vanish in time as well.
But it grew instead, imperceptibly at first, then more assertively, turning from grape-size to prune-size in about a month. He could feel it on the shallow dip of his collarbone. Worried, Orman went to the walk-in clinic of the hospital, almost apologetic about his complaints. The triage nurse scribbled in her notes: “Lump in his neck”—and added a question mark at the end of the sentence.
With that sentence, Orman entered the unfamiliar world of oncology—swallowed, like his own lump, into the bizarre, cavitary universe of cancer. The doors of the hospital opened and closed behind him. A doctor in a blue scrub suit stepped through the curtains and ran her hands up and down his neck. He had blood tests and X-rays in rapid succession, followed by CT scans and more examinations. The scans revealed that the lump in the neck was merely the tip of a much deeper iceberg of lumps. Beneath that sentinel mass, a chain of masses coiled from his neck down into his chest, culminating in a fist-size tumor just behind his sternum. Large masses located in the anterior chest, as medical students learn, come in four T’s, almost like a macabre nursery rhyme for cancer: thyroid cancer, thymoma, teratoma, and terrible lymphoma. Orman’s problem—given his age and the matted, dense appearance of the lumps—was almost certainly the last of these, a lymphoma—cancer of the lymph glands.
I saw Ben Orman nearly two months after that visit to the hospital. He was sitting in the waiting room, reading a book (he read fiercely, athletically, almost competitively, often finishing one novel a week, as if in a race). In the eight weeks since his ER visit, he had undergone a PET scan, a visit with a surgeon, and a biopsy of the neck lump. As suspected, the mass was a lymphoma, a relatively rare variant called Hodgkin’s disease.
More news followed: the scans revealed that Orman’s cancer was confined entirely to one side of his upper torso. And he had none of the ghostly B symptoms—weight loss, fever, chills, or night sweats—that occasionally accompany Hodgkin’s disease. In a staging system that ran from I to IV (with an A or B added to denote the absence or presence of the occult symptoms), he fell into stage IIA—relatively early in the progression of the disease. It was somber news, but of all the patients shuttling in and out of the waiting room that morning, Orman arguably carried the most benign prognosis. With an intensive course of chemotherapy, it was more than likely—85 percent likely—that he would be cured.
“By intensive,” I told him, “I mean several months, perhaps even stretching out to half a year. The drugs will be given in cycles, and there will have to be visits in between to check blood counts.” Every three weeks, just as his counts recovered, the whole cycle would begin all over again—Sisyphus on chemotherapy.
He would lose his hair with the first cycle. He would almost certainly become permanently infertile. There might be life-threatening infections during the times when his white counts would bottom out nearly to zero. Most ominously, the chemo might cause a second cancer in the future. He nodded. I watched the thought pick up velocity in his brain, until it had reached its full impact.
“It’s going to be a long haul. A marathon,” I stammered apologetically, groping for an analogy. “But we’ll get to the end.”
He nodded again silently, as if he already knew.
On a Wednesday morning, not long after my meeting with Orman, I took a shuttle across Boston to see my patients at the Dana-Farber Cancer Institute. Most of us called the institute simply “the Farber.” Large already in life, Sidney Farber had become even larger in death: the eponymous Farber was now a sprawling sixteen-story labyrinth of concrete crammed full of scientists and physicians, a comprehensive lab-cum-clinic-cum-pharmacy-cum-chemotherapy-unit. There were 2,934 employees, dozens of conference rooms, scores of laboratories, a laundry unit, four banks of elevators, and multiple libraries. The site of the original basement lab had long been dwarfed by the massive complex of buildings around it. Like a vast, overbuilt, and overwrought medieval temple, the Farber had long swallowed its shrine.
As you entered the new building, an oil painting of the man himself—with his characteristic half-scowling, half-smiling face—stared back at you in the foyer. Little bits and pieces of him, it seemed, were strewn everywhere. The corridor on the way to the fellows’ office was still hung with the cartoonish “portraits” that he had once commissioned for the Jimmy Fund: Snow White, Pinocchio, Jiminy Cricket, Dumbo. The bone marrow needles with which we performed our biopsies looked and felt as if they came from another age; perhaps they had been sharpened by Farber or one of his trainees fifty years ago. Wandering through these labs and clinics, you often felt as if you could stumble onto cancer history at any minute. One morning I did: bolting to catch the elevator, I ran headlong into an old man in a wheelchair whom I first took to be a patient. It was Tom Frei, a professor emeritus now, heading up to his office on the sixteenth floor.
My patient that Wednesday morning was a seventy-six-year-old woman named Beatrice Sorenson. Bea, as she liked to be called, reminded me of one of those tiny insects or animals that you read about in natural-history textbooks that can carry ten times their weight or leap five times their height. She was almost preternaturally minuscule: about eighty-five pounds and four and a half feet tall, with birdlike features and delicate bones that seemed to hang together like twigs in winter. To this diminutive frame, however, she brought a fierce force of personality, the lightness of body counterbalanced by the heftiness of soul. She had been a marine and served in two wars. Even as I towered over her on the examination table, I felt awkward and humbled, as if she were towering over me in spirit.
Sorenson had pancreatic cancer. The tumor had been discovered almost accidentally in the late summer of 2003, when she had had a bout of abdominal pain and diarrhea and a CT scan had picked up a four-centimeter solid nodule hanging off the tail of her pancreas. (In retrospect, the diarrhea may have been unrelated.) A brave surgeon had attempted to resect it, but the margins of the resection still contained some tumor cells. Even in oncology, a dismal discipline to begin with, this—unresected pancreatic cancer—was considered the epitome of the dismal.
Sorenson’s life had turned upside down. “I want to beat it to the end,” she had told me at first. We had tried. Through the early fall, we blasted her pancreas with radiation to kill the tumor cells, then followed with chemotherapy, using the drug 5-fluorouracil. The tumor had grown right through all the treatments. In the winter, we had switched to a new drug called gemcitabine, or Gemzar. The tumor cells had shrugged the new drug off—instead mockingly sending a shower of painful metastases into her liver. At times, it felt as if we would have been better off with no drugs at all.
Sorenson was at the clinic that morning to see if we could offer anything else. She wore white pants and a white shirt. Her paper-thin skin was marked with dry lines. She may have been crying, but her face was a cipher that I could not read.
“She will try anything, anything,” her husband pleaded. “She is stronger than she looks.”
But strong or not, there was nothing left to try. I stared down at my feet, unable to confront the obvious questions. The attending physician shifted uncomfortably in his chair.
Beatrice finally broke the awkward silence. “I’m sorry.” She shrugged her shoulders and looked vacantly past us. “I know we have reached an end.”
We hung our heads, ashamed. It was, I suspected, not the first time that a patient had consoled a doctor about the ineffectuality of his discipline.
Two lumps seen on two different mornings. Two vastly different incarnations of cancer: one almost certainly curable, the second, an inevitable spiral into death. It felt—nearly twenty-five hundred years after Hippocrates had naively coined the overarching term karkinos—that modern oncology was hardly any more sophisticated in its taxonomy of cancer. Orman’s lymphoma and Sorenson’s pancreatic cancer were both, of course, “cancers,” malignant proliferations of cells. But the diseases could not have been further apart in their trajectories and personalities. Even referring to them by the same name, cancer, felt like some sort of medical anachronism, like the medieval habit of using apoplexy to describe anything from a stroke to a hemorrhage to a seizure. Like Hippocrates, it was as if we, too, had naively lumped the lumps.
But naive or not, it was this lumping—this emphatic, unshakable faith in the underlying singularity of cancer more than its pluralities—that galvanized the Laskerites in the 1960s. Oncology was on a quest for cohesive truths—a “universal cure,” as Farber put it in 1962. And if the oncologists of the 1960s imagined a common cure for all forms of cancer, it was because they imagined a common disease called cancer. Curing one form, the belief ran, would inevitably lead to the cure of another, and so forth like a chain reaction, until the whole malignant edifice had crumbled like a set of dominoes.
That assumption—that a monolithic hammer would eventually demolish a monolithic disease—surcharged physicians, scientists, and cancer lobbyists with vitality and energy. For the Laskerites, it was an organizing principle, a matter of faith, the only certain beacon toward which they all gravitated. Indeed, the political consolidation of cancer that the Laskerites sought in Washington (a single institute, a single source of funds, led by a single physician or scientist) relied on a deeper notion of a medical consolidation of cancer into a single disease, a monolith, a single, central narrative. Without this grand, embracing narrative, neither Mary Lasker nor Sidney Farber could have envisioned a systematic, targeted war.
The illness that had brought Ben Orman to the clinic late that evening, Hodgkin’s lymphoma, was itself announced late to the world of cancer. Its discoverer, Thomas Hodgkin, was a thin, short, nineteenth-century English anatomist with a spadelike beard and an astonishingly curved nose—a character who might have walked out of an Edward Lear poem. Hodgkin was born in 1798 to a Quaker family in Pentonville, a small hamlet outside London. A precocious child, he grew quickly into an even more precocious young man, whose interests loped freely from geology to mathematics to chemistry. He apprenticed briefly as a geologist, then as an apothecary, and finally graduated from the University of Edinburgh with a degree in medicine.
A chance event enticed Hodgkin into the world of pathological anatomy and led him toward the disease that would bear his name. In 1825, a struggle within the faculty of St. Thomas’ and Guy’s hospital in London broke up the venerable institution into two bickering halves: Guy’s hospital and its new rival, St. Thomas’. This divorce, like many marital spats, was almost immediately followed by a vicious argument over the partition of property. The “property” here was a macabre ensemble—the precious anatomical collection of the hospital: brains, hearts, stomachs, and skeletons in pickling jars of formalin that had been hoarded for use as teaching tools for the hospital’s medical students. St. Thomas’ hospital refused to part with its precious specimens, so Guy’s scrambled to cobble together its own anatomical museum. Hodgkin had just returned from his second visit to Paris, where he had learned to prepare and dissect cadaveric specimens. He was promptly recruited to collect specimens for Guy’s new museum. The job’s most inventive academic perk, perhaps, was his new title: the Curator of the Museum and the Inspector of the Dead.
Hodgkin proved to be an extraordinary Inspector of the Dead, a compulsive anatomical curator who hoarded hundreds of samples within a few years. But collecting specimens was a rather mundane task; Hodgkin’s particular genius lay in organizing them. He became a librarian as much as a pathologist; he devised his own systematics for pathology. The original building that housed his collection has been destroyed. But the new museum, where Hodgkin’s original specimens are still on display, is a strange marvel. A four-chambered atrium located deep inside a larger building, it is an enormous walk-in casket-of-wonders constructed of wrought iron and glass. You enter a door and ascend a staircase, then find yourself on the top floor of a series of galleries that cascade downward. Along every wall are rows of formalin-filled jars: lungs in one gallery, hearts in another, brains, kidneys, bones, and so forth. This method of organizing pathological anatomy—by organ system rather than by date or disease—was a revelation. By thus “inhabiting” the body conceptually—by climbing in and out of the body at will, often noting the correlations between organs and systems—Hodgkin found that he could recognize patterns within patterns instinctually, sometimes without even consciously registering them.
In the early winter of 1832, Hodgkin announced that he had collected a series of cadavers, mostly of young men, who possessed a strange systemic disease. The illness was characterized, as he put it, by “a peculiar enlargement of lymph glands.” To the undiscerning eye, this enlargement could easily have been from tuberculosis or syphilis—the more common sources of glandular swelling at that time. But Hodgkin was convinced that he had encountered an entirely new disease, an unknown pathology unique to these young men. He wrote up the case of seven such cadavers and had his paper, “On Some Morbid Appearances of the Absorbent Glands and Spleen,” presented to the Medical and Chirurgical Society.
The story of a compulsive young doctor putting old swellings into new pathological bottles was received without much enthusiasm. Only eight members of the society reportedly attended the lecture. They filed out afterward in silence, not even bothering to record their names on the dusty attendance roster.
Hodgkin, too, was a little embarrassed by his discovery. “A pathological paper may perhaps be thought of little value if unaccompanied by suggestions designed to assist in the treatment, either curative or palliative,” he wrote. Merely describing an illness, without offering any therapeutic suggestions, seemed like an empty academic exercise to him, a form of intellectual frittering. Soon after publishing his paper, he began to drift away from medicine altogether. In 1837, after a rather vicious political spat with his superiors, he resigned his post at Guy’s. He had a brief stint at St. Thomas’ hospital as its curator—a rebound affair that was doomed to fail. In 1844, he gave up his academic practice altogether. His anatomical studies slowly came to a halt.
In 1898, some thirty years after Hodgkin’s death, an Austrian pathologist, Carl Sternberg, was looking through a microscope at a patient’s glands when he found a peculiar series of cells staring back at him: giant, disorganized cells with cleaved, bilobed nuclei—“owl’s eyes,” as he described them, glaring sullenly out from the forests of lymph. Hodgkin’s anatomy had reached its final cellular resolution. These owl’s-eye cells were malignant lymphocytes, lymph cells that had turned cancerous. Hodgkin’s disease was a cancer of the lymph glands—a lymphoma.
Hodgkin may have been disappointed by what he thought was only a descriptive study of his disease. But he had underestimated the value of careful observation—by compulsively studying anatomy alone, he had stumbled upon the most critical revelation about this form of lymphoma: Hodgkin’s disease had a peculiar propensity of infiltrating lymph nodes locally one by one. Other cancers could be more unpredictable—more “capricious,” as one oncologist put it. Lung cancer, for instance, might start as a spicular nodule in the lung, then unmoor itself and ambulate unexpectedly into the brain. Pancreatic cancer was notoriously known to send sprays of malignant cells into faraway sites such as the bones and the liver. But Hodgkin’s—an anatomist’s discovery—was anatomically deferential: it moved, as if with a measured, ordered pace, from one contiguous node to another—from gland to gland and from region to region.
It was this propensity to spread locally from one node to the next that poised Hodgkin’s uniquely in the history of cancer. Hodgkin’s disease was yet another hybrid among malignant diseases. If Farber’s leukemia had occupied the hazy border between liquid and solid tumors, then Hodgkin’s disease inhabited yet another strange borderland: a local disease on the verge of transforming into a systemic one—Halsted’s vision of cancer on its way to becoming Galen’s.
In the early 1950s, at a cocktail party in California, Henry Kaplan, a professor of radiology at Stanford, overheard a conversation about the plan to build a linear accelerator for use by physicists at Stanford. A linear accelerator is an X-ray tube taken to an extreme form. Like a conventional X-ray tube, a linear accelerator also fires electrons onto a target to generate high-intensity X-rays. Unlike a conventional tube, however, the “linac” imbues massive amounts of energy into the electrons, pushing them to dizzying velocities before smashing them against the metal surface. The X-rays that emerge from this are deeply penetrating—powerful enough not only to pass through tissue, but to scald cells to death.
Kaplan had trained at the NCI, where he had learned to use X-rays to treat leukemia in animals, but his interest had gradually shifted to solid tumors in humans—lung cancer, breast cancer, lymphomas. Solid tumors could be treated with radiation, he knew, but the outer shell of the cancer, like its eponymous crab’s carapace, needed to be penetrated deeply to kill cancer cells. A linear accelerator with its sharp, dense, knifelike beam might allow him to reach tumor cells buried deep inside tissues. In 1953, he persuaded a team of physicists and engineers at Stanford to tailor-make an accelerator exclusively for the hospital. The accelerator was installed in a vaultlike warehouse in San Francisco in 1956. Dodging traffic between Fillmore Street and Mission Hill, Kaplan personally wheeled in its colossal block of lead shielding on an automobile jack borrowed from a neighboring garage owner.
Through a minuscule pinhole in that lead block, he could now direct tiny, controlled doses of a furiously potent beam of X-rays—millions of electron volts of energy in concentrated bursts—to lancinate any cancer cell to death. But what form of cancer? If Kaplan had learned one lesson at the NCI, it was that by focusing microscopically on a single disease, one could extrapolate into the entire universe of diseases. The characteristics that Kaplan sought in his target were relatively well defined. Since the linac could only focus its killer beam on local sites, it would have to be a local, not a systemic, cancer. Leukemia was out of the question. Breast and lung cancer were important targets, but both were unpredictable, mercurial diseases, with propensities for occult and systemic spread. The powerful oculus of Kaplan’s intellect, swiveling about through the malignant world, ultimately landed on the most natural target for his investigation: Hodgkin’s disease.
“Henry Kaplan was Hodgkin’s disease,” George Canellos, a former senior clinician at the NCI told me, leaning back in his chair. We were sitting in his office while he rummaged through piles of manuscripts, monographs, articles, books, catalogs, and papers, pulling out occasional pictures of Kaplan from his files. Here was Kaplan, dressed in a bow tie, looking at sheaves of papers at the NCI. Or Kaplan in a white coat standing next to the linac at Stanford, its 5-million-volt probe just inches from his nose.
Kaplan wasn’t the first doctor to treat Hodgkin’s with X-rays, but he was certainly the most dogged, the most methodical, and the most single-minded. In the mid-1930s, a Swiss radiologist named Rene Gilbert had shown that the swollen lymph nodes of Hodgkin’s disease could effectively and dramatically be reduced with radiation. But Gilbert’s patients had typically relapsed after treatment, often in the lymph nodes immediately contiguous to the original radiated area. At the Toronto General Hospital, a Canadian surgeon named Vera Peters had furthered Gilbert’s studies by broadening the radiation field even farther—delivering X-rays not to a single swollen node, but to an entire area of lymph nodes. Peters called her strategy “extended field radiation.” In 1958, analyzing the cohort of patients that she had treated, Peters observed that broad-field radiation could significantly improve long-term survival for early-stage Hodgkin’s patients. But Peters’s data was retrospective—based on the historical analysis of prior-treated patients. What Peters needed was a more rigorous medical experiment, a randomized clinical trial. (Historical series can be biased by doctors’ highly selective choices of patients for therapy, or by their counting only the ones that do the best.)
Independently of Peters, Kaplan had also realized that extended field radiation could improve relapse-free survival, perhaps even cure early-stage Hodgkin’s disease. But he lacked formal proof. In 1962, challenged by one of his students, Henry Kaplan set out to prove the point.
The trials that Kaplan designed still rank among the classics of study design. In the first set, called the L1 trials, he assigned equal numbers of patients to either extended field radiation or to limited “involved field” radiation and plotted relapse-free survival curves. The answer was definitive. Extended field radiation—“meticulous radiotherapy” as one doctor described it—drastically diminished the relapse rate of Hodgkin’s disease.
But Kaplan knew that a diminished relapse rate was not a cure. So he delved further. Two years later, the Stanford team carved out a larger field of radiation, involving nodes around the aorta, the large arch-shaped blood vessel that leads out of the heart. Here they introduced an innovation that would prove pivotal to their success. Kaplan knew that only patients that had localized Hodgkin’s disease could possibly benefit from radiation therapy. To truly test the efficacy of radiation therapy, then, Kaplan realized that he would need a strictly limited cohort of patients whose Hodgkin’s disease involved just a few contiguous lymph nodes. To exclude patients with more disseminated forms of lymphoma, Kaplan devised an intense battery of tests to stage his patients. There were blood tests, a detailed clinical exam, a procedure called lymphangiography (a primitive ancestor of a CT scan for the lymph nodes), and a bone marrow biopsy. Even so, Kaplan was unsatisfied: doubly careful, he began to perform exploratory abdominal surgery and biopsy internal nodes to ensure that only patients with locally confined disease were entering his trials.
The doses of radiation were now daringly high. But gratifyingly, the responses soared as well. Kaplan documented even greater relapse-free intervals, now stretching out into dozens of months—then years. When the first batch of patients had survived five years without relapses, he began to speculate that some may have been cured by extended field X-rays. Kaplan’s experimental idea had finally made its way out of a San Francisco warehouse into the mainstream clinical world.
But hadn’t Halsted wagered on the same horse and lost? Hadn’t radical surgery become entangled in the same logic—carving out larger and larger areas for treatment—and then spiraled downward? Why did Kaplan succeed where others had failed?
First, because Kaplan meticulously restricted radiotherapy to patients with early-stage disease. He went to exhaustive lengths to stage patients before unleashing radiation on them. By strictly narrowing the group of patients treated, Kaplan markedly increased the likelihood of his success.
And second, he succeeded because he had picked the right disease. Hodgkin’s was, for the most part, a regional illness. “Fundamental to all attempts at curative treatment of Hodgkin’s disease,” one reviewer commented memorably in the New England Journal of Medicine in 1968, “is the assumption that in the significant fraction of cases, [the disease] is localized.” Kaplan treated the intrinsic biology of Hodgkin’s disease with utmost seriousness. If Hodgkin’s lymphoma had been more capricious in its movement through the body (and occult areas of spread more common, as in some forms of breast cancer), then Kaplan’s staging strategy, for all his excruciatingly detailed workups, would inherently have been doomed to fail. Instead of trying to tailor the disease to fit his medicine, Kaplan learned to tailor his medicine to fit the right disease.
This simple principle—the meticulous matching of a particular therapy to a particular form and stage of cancer—would eventually be given its due merit in cancer therapy. Early-stage, local cancers, Kaplan realized, were often inherently different from widely spread, metastatic cancers—even within the same form of cancer. A hundred instances of Hodgkin’s disease, even though pathologically classified as the same entity, were a hundred variants around a common theme. Cancers possessed temperaments, personalities—behaviors. And biological heterogeneity demanded therapeutic heterogeneity; the same treatment could not indiscriminately be applied to all. But even if Kaplan understood it fully in 1963 and made an example of it in treating Hodgkin’s disease, it would take decades for a generation of oncologists to come to the same realization.
An Army on the March
Now we are an army on the march.
—Sidney Farber in 1963
The next step—the complete cure—is almost sure to follow.
NCI director, 1963
The role of aggressive multiple drug therapy in the quest for long-term survival [in cancer] is far from clear.
—R. Stein, a scientist in 1969
One afternoon in the late summer of 1963, George Canellos, then a senior fellow at the NCI, walked into the Clinical Center to find Tom Frei scribbling furiously on one of the institute’s blackboards. Frei, in his long white coat, was making lists of chemicals and drawing arrows. On one side of the board was a list of cytotoxic drugs—Cytoxan, vincristine, procarbazine, methotrexate. On the other side was a list of new cancers that Zubrod and Frei wanted to target: breast, ovarian, lung cancers, lymphomas. Connecting the two halves of the blackboard were chalky lines matching combinations of cytotoxic drugs to cancers. For a moment, it almost looked as if Frei had been deriving mathematical equations: A+B kills C; E+F eliminates G.
The drugs on Frei’s list came largely from three sources. Some, such as aminopterin or methotrexate, were the products of inspired guesswork by scientists (Farber had discovered aminopterin by guessing that an antifolate might block the growth of leukemia cells). Others, such as nitrogen mustard or actinomycin D, came from serendipitous sources, such as mustard gas or soil bacteria, found accidentally to kill cancer cells. Yet others, such as 6-MP, came from drug-screening efforts in which thousands of molecules were tested to find the handful that possessed cancer-killing activity.
The notable common feature that linked all these drugs was that they were all rather indiscriminate inhibitors of cellular growth. Nitrogen mustard, for instance, damages DNA and kills nearly all dividing cells; it kills cancer cells somewhat preferentially because cancer cells divide most actively. To design an ideal anticancer drug, one would need to identify a specific molecular target in a cancer cell and create a chemical to attack that target. But the fundamental biology of cancer was so poorly understood that defining such molecular targets was virtually inconceivable in the 1960s. Yet, even lacking such targets, Frei and Freireich had cured leukemia in some children. Even generic cellular poisons, dosed with adequate brio, could thus eventually obliterate cancer.
The bravado of that logic was certainly hypnotic. Vincent DeVita, another fellow at the institute during that time, wrote, “A new breed of cancer investigators in the 1960s had been addressing the generic question of whether or not cytotoxic chemotherapy was ever capable of curing patients with any type of advanced malignancies.” For Frei and Zubrod, the only way to answer that “generic question” was to direct the growing armamentarium of combination chemotherapy against another cancer—a solid tumor this time—which would retrace their steps with leukemia. If yet another kind of cancer responded to this strategy, then there could be little doubt that oncology had stumbled upon a generic solution to the generic problem. A cure would then be within reach for all cancers.
But which cancer would be used to test the principle? Like Kaplan, Zubrod, DeVita, and Canellos also focused on Hodgkin’s disease—a cancer that lived on the ill-defined cusp between solid and liquid, a stepping-stone between leukemia and, say, lung cancer or breast cancer. At Stanford, Kaplan had already demonstrated that Hodgkin’s lymphoma could be staged with exquisite precision and that local disease could be cured with high-dose extended field radiation. Kaplan had solved half the equation: he had used local therapy with radiation to cure localized forms of Hodgkin’s disease. If metastatic Hodgkin’s disease could be cured by systemic and aggressive combination chemotherapy, then Zubrod’s “generic solution” would begin to sound plausible. The equation would be fully solved.
Outspoken, pugnacious, and bold, a child of the rough-and-tumble Yonkers area of New York who had bulldozed his way through college and medical school, Vincent DeVita had come to the NCI in 1963 and fallen into the intoxicating orbit of Zubrod, Frei, and Freireich. The unorthodoxy of their approach—the “maniacs doing cancer research,” as he called it—had instantly fascinated him. These were the daredevils of medical research, acrobats devising new drugs that nearly killed patients; these men played chicken with death. “Somebody had to show the skeptics that you could actually cure cancer with the right drugs,” he believed. In the early months of 1964, he set out to prove the skeptics wrong.
The first test of intensive combination chemotherapy for advanced-stage Hodgkin’s disease, led by DeVita, combined four drugs—methotrexate, vincristine (also called Oncovin), nitrogen mustard, and prednisone, a highly toxic cocktail called MOMP. Only fourteen patients were treated. All suffered the predictable consequences of combination chemotherapy; all were hospitalized and confined in isolation chambers to prevent infections during the life-threatening drop in blood counts. As expected, the regimen was sharply criticized at the NCI; this, again, was a quantum leap into a deadly world of mixed poisons. But Frei intervened, silencing the critics and allowing the program to continue.
In 1964, DeVita modified the regimen further. Methotrexate was substituted with a more powerful agent, procarbazine, and the duration of treatment was lengthened from two and a half months to six months. With a team of young, like-minded fellows at the NCI, DeVita began to enroll patients with advanced Hodgkin’s disease in a trial of this new cocktail, called MOPP. Like lymphoblastic leukemia, Hodgkin’s disease is a rare illness, but the researchers did not need to look hard to find patients. Advanced Hodgkin’s disease, often accompanied by the spectral B symptoms, was uniformly fatal. Young men and women (the disease typically strikes men and women in their twenties and thirties) were often referred to the NCI as hopeless cases—and therefore ideal experimental subjects. In just three years, DeVita and Canellos thus accumulated cases at a furious clip, forty-three patients in all. Nine had been blasted with increasing fields of radiation, à la Kaplan, and still progressed inexorably to disseminated, widely metastatic disease. Others had been treated with an ad hoc mix of single agents. None had shown any durable response to prior drugs.
So, like the younger band of leukemics that had gone before them, a fresh new cohort appeared at the institute every two weeks, occupying the plastic chairs of the Clinical Center, lining up for the government-issued cookies and awaiting the terrifying onslaught of the experimental drugs. The youngest was twelve, not even a teenager yet, with lymphoma cells packed in her lungs and liver. A thirteen-year-old boy had Hodgkin’s in his pleural cavity; malignant fluid had compressed itself into the lining between his chest wall and lung and made it hard to breathe. The oldest was a sixty-nine-year-old woman with Hodgkin’s disease choking off the entrance to her intestine.
If the terror of VAMP was death by infection—children slumped on ventilators with no white blood cells to speak of and bacteria streaming in their blood—then the terror of MOPP was more visceral: death by nausea. The nausea that accompanied the therapy was devastating. It appeared suddenly, then abated just as suddenly, almost capable of snapping the mind shut with its intensity. Many of the patients on the protocol were flown in from nearby cities every fortnight. The trip back home, with the drugs lurching in the blood and the plane lurching in the air, was, for many, a nightmare even worse than their disease.
The nausea was merely a harbinger. As DeVita charged ahead with combination chemotherapy, more complex and novel devastations were revealed. Chemotherapy caused permanent sterility in men and some women. The annihilation of the immune system by the cytotoxic drugs allowed peculiar infections to sprout up: the first adult case of a rare form of pneumonia, caused by an organism, Pneumocystis carinii (PCP), was observed in a patient receiving MOPP (the same pneumonia, arising spontaneously in immune-compromised gay men in 1981, would auger the arrival of the HIV epidemic in America). Perhaps the most disturbing side effect of chemotherapy would emerge nearly a decade later. Several young men and women, cured of Hodgkin’s disease, would relapse with a second cancer—typically an aggressive, drug-resistant leukemia—caused by the prior treatment with MOPP chemotherapy. As with radiation, cytotoxic chemotherapy would thus turn out to be a double-edged sword: cancer-curing on one hand, and cancer-causing on the other.
But the evidently grim litany of side effects notwithstanding, even early in the course of treatment, there was payoff. In many of the young men and women, the palpable, swollen lymph nodes dissolved in weeks. A twelve-year-old boy from Illinois had been so ravaged by Hodgkin’s that his weight had sunk to fifty pounds; within three months of treatment, he gained nearly half his body weight and shot up two feet in height. In others, the stranglehold of Hodgkin’s disease loosened on the organs. Pleural effusions gradually cleared and the nodes in the gut disappeared. As the months passed, it was clear that combination chemo had struck gold once again. At the end of half a year, thirty-five of the forty-three patients had achieved a complete remission. The MOPP trial did not have a control group, but one was not needed to discern the effect. The response and remission rate were unprecedented for advanced Hodgkin’s disease. The success would continue in the long-term: more than half the initial cohort of patients would be cured.
Even Kaplan, not an early believer in chemotherapy, was astonished. “Some of the patients with advanced disease have now survived relapse free,” he wrote. “The advent of multiple-drug chemotherapy has dramatically changed the prognosis of patients with previously untreated stage III or stage IV Hodgkin’s disease.”
In May 1968, as the MOPP trial was ascending to its unexpected crescendo, there was equally unexpected news in the world of lymphoblastic leukemia.
Frei and Freireich’s VAMP regimen had trailed off at a strange and bleak point. Combination chemo had cured most of the children of leukemia in their blood and bone marrow, but the cancer had explosively relapsed in the brain. In the months following VAMP in 1962, most of these children had hobbled back to the clinic with seemingly innocuous neurological complaints and then spiraled furiously toward their deaths just a week or two afterward. VAMP, once widely touted as the institute’s success story, had turned, instead, into its progressive nightmare. Of the fifteen patients treated on the initial protocol, only two still survived. At the NCI, the ambition and bravado that had spurred the original studies was rapidly tipping toward a colder reality. Perhaps Farber’s critics had been right. Perhaps lymphoblastic leukemia was a disease that could, at best, be sent into a flickering remission, but never cured. Perhaps palliative care was the best option after all.
But having tasted the success of high-dose chemotherapy, many oncologists could not scale back their optimism: What if even VAMP had not been intensive enough? What if a chemotherapy regimen could be muscled up further, pushed closer to the brink of tolerability?
The leader of this gladiatorial camp was a protégé of Farber’s, a thirty-six-year-old oncologist, Donald Pinkel, who had been recruited from Boston to start a leukemia program in Memphis, Tennessee.* In many ways, Memphis was the antipode of Boston. Convulsing with bitter racial tensions and rock-and-roll music—gyrating between the gold and pink of the Graceland mansion in its south and the starkly segregated black neighborhoods in its north—Memphis was turbulent, unpredictable, colorful, perennially warm, and, medically speaking, virtually a no-man’s-land. Pinkel’s new hospital, called St. Jude’s (named, aptly enough, after the patron saint of lost causes), rose like a marooned concrete starfish out of a concrete parking lot on a barren field. In 1961, when Pinkel arrived, the hospital was barely functional, with “no track record, uncertain finances, an unfinished building, no employees or faculty.”
Still, Pinkel got a chemotherapy ward up and running, with nurses, residents, and fellows trained in administering the toxic, mercurial drugs. And flung far from the epicenters of leukemia research in New York and Boston, Pinkel’s team was determined to outdo every other leukemia trial—the edge outmoding the center—to push the logic of high-dose combination chemotherapy to its extreme. Pinkel thus hammered away in trial after trial, edging his way toward the outer limit of tolerability. And Pinkel and his collaborators emerged with four crucial innovations to the prior regimens.†
First, Pinkel reasoned that while combinations of drugs were necessary to induce remissions, combinations were insufficient in themselves. Perhaps one needed combinations of combinations—six, seven, or even eight different chemical poisons mixed and matched together for maximum effect.
Second, since the nervous system relapses had likely occurred because even these highly potent chemicals could not breach the blood-brain barrier, perhaps one needed to instill chemotherapy directly into the nervous system by injecting it into the fluid that bathes the spinal cord.
Third, perhaps even that instillation was not enough. Since X-rays could penetrate the brain regardless of the blood-brain barrier, perhaps one needed to add high-dose radiation to the skull to kill residual cells in the brain.
And finally, as Min Chiu Li had seen with choriocarcinoma, perhaps one needed to continue chemotherapy not just for weeks and months as Frei and Freireich had done, but for month after month, stretching into two or even three years.
The treatment protocol that emerged from these guiding principles could only be described as, as one of Pinkel’s colleagues called it, “an all-out combat.” To start with, the standard antileukemic drugs were given in rapid-fire succession. Then, at defined intervals, methotrexate was injected into the spinal canal using a spinal tap. The brain was irradiated with high doses of X-rays. Then, chemotherapy was bolstered even further with higher doses of drugs and alternating intervals, “in maximum tolerated doses.” Antibiotics and transfusions were usually needed, often in succession, often for weeks on end. The treatment lasted up to two and a half years; it involved multiple exposures to radiation, scores of blood tests, dozens of spinal taps, and multiple intravenous drugs—a strategy so precise and demanding that one journal refused to publish it, concerned that it was impossible to even dose it and monitor it correctly without killing several patients in the trials. Even at St. Jude’s, the regimen was considered so overwhelmingly toxic that the trial was assigned to relatively junior physicians under Pinkel’s supervision because the senior researchers, knowing its risks, did not want to run it. Pinkel called it “total therapy.”
As fellows, we called it “total hell.”
Carla Reed entered this form of hell in the summer of 2004. Chemotherapy and radiation came back-to-back, one dark tide after another. Some days she got home in the evening (her children already in bed, her husband waiting with dinner) only to turn around and come back the next morning. She lost sleep, her hair, and her appetite and then something more important and ineffable—her animus, her drive, her will. She walked around the hospital like a zombie, shuffling in small steps from the blue vinyl couch in the infusion room to the water dispenser in the central corridor, then back to the couch in those evenly measured steps. “The radiation treatment was the last straw,” she recalled. “Lying on the treatment table as still as death, with the mask on my face, I often wondered whether I would even wake up.” Even her mother, who had flown in and out of Boston regularly during Carla’s first month of treatment, retreated to her own house in Florida, red-eyed and exhausted.
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,
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.
The agent responsible for carrying the cancer, Rous concluded, was not a cell or an environmental carcinogen, but some tiny particle lurking within a cell. The particle was so small that it could easily pass through most filters and keep producing cancer in animals. The only biological particle that had these properties was a virus. His virus was later called Rous sarcoma virus, or RSV for short.
The discovery of RSV, the first cancer-causing virus, felled a deep blow to the somatic mutation theory and set off a frantic search for more cancer viruses. The causal agent for cancer, it seemed, had been found. In 1935, a colleague of Rous’s named Richard Schope reported a papillomavirus that caused wartlike tumors in cottontail rabbits. Ten years later, in the mid-1940s, came news of a leukemia-causing virus in mice and then in cats—but still no sign of a bona fide cancer virus in humans.
In 1958, after nearly a three-decade effort, the hunt finally yielded an important prize. An Irish surgeon, Denis Burkitt, discovered an aggressive form of lymphoma—now called Burkitt’s lymphoma—that occurred endemically among children in the malaria-ridden belt of sub-Saharan Africa. The pattern of distribution suggested an infectious cause. When two British virologists analyzed the lymphoma cells from Africa, they discovered an infectious agent lodged inside them—not malaria parasites, but a human cancer virus. The new virus was named Epstein-Barr virus or EBV. (EBV is more familiar to us as the virus that causes infectious mononucleosis, or mono.)
The grand total of cancer-causing viruses in humans now stood at one. But the modesty of that number aside, the cancer virus theory was in full spate now—in part because viruses were the new rage in all of medicine. Viral diseases, having been considered incurable for centuries, were now becoming potentially preventable: the polio vaccine, introduced in the summer of 1952, had been a phenomenal success, and the notion that cancer and infectious diseases could eventually collapse into a single pathological entity was simply too seductive to resist.
“Cancer may be infectious,” a Life magazine cover piece asserted in 1962. Rous received hundreds of letters from anxious men and women asking about exposures to cancer-causing bacteria or viruses. Speculation soon inched toward hysteria and fear. If cancer was infectious, some wondered, why not quarantine patients to prevent its spread? Why not send cancer patients to sanitation wards or isolation facilities, where TB and smallpox victims had once been confined? One woman who believed that she had been exposed to a coughing lung cancer patient wrote, “Is there something I can do to kill the cancer germ? Can the rooms be fumigated . . .? Should I give up my lease and move out?”
If the “cancer germ” had infected one space most acutely, it was the imagination of the public—and, equally, the imagination of researchers. Farber turned into a particularly fervent believer. In the early 1960s, goaded by his insistence, the NCI inaugurated a Special Virus Cancer Program, a systematic hunt for human cancer viruses patterned explicitly after the chemotherapy discovery program. The project snowballed into public prominence, gathering enormous support. Hundreds of monkeys at the NCI-funded lab were inoculated with human tumors with the hopes of turning the monkeys into viral incubators for vaccine development. Unfortunately, the monkeys failed to produce even a single cancer virus, but nothing dimmed the optimism. Over the next decade, the cancer virus program siphoned away more than 10 percent of the NCI contract budget—nearly $500 million. (In contrast, the institute’s cancer nutrition program, meant to evaluate the role of diet in cancer—a question of at least equal import—received one-twentieth of that allocation.)
Peyton Rous was rehabilitated into the scientific mainstream and levitated into permanent scientific sainthood. In 1966, having been overlooked for a full fifty-five years, he was awarded the Nobel Prize for physiology and medicine. On the evening of December 10 at the ceremony in Stockholm, he rose to the podium like a resurrected messiah. Rous acknowledged in his talk that the virus theory of cancer still needed much more work and clarity. “Relatively few viruses have any connection with the production of neoplasms,” Rous said. But bulldogish and unwilling to capitulate, Rous lambasted the idea that cancer could be caused by something inherent to the cells, such as a genetic mutation. “A favorite explanation has been that oncogenes cause alterations in the genes of the cells of the body, somatic mutations as these are termed. But numerous facts, when taken together, decisively exclude this supposition.”
He groused elsewhere: “What have been [the fruits] of this somatic mutation hypothesis? . . . Most serious of all the results of the somatic mutation hypothesis has been its effect on research workers. It acts as a tranquilizer on those who believe it.”
Rous had his own tranquilizer to offer: a unifying hypothesis that viruses caused cancer. And many in his audience, in no mood for caveats and complexities, were desperate to swallow his medicine. The somatic mutation theory of cancer was dead. The scientists who had studied environmental carcinogenesis needed to think of other explanations why radium or soot might cause cancer. (Perhaps, the virus theorists reasoned, these insults activated endogenous viruses.)
Two superficial theories were thus stitched audaciously—and prematurely—into one comprehensive whole. One offered a cause: viruses caused cancer (although a vast majority of them were yet undiscovered). The second offered a cure: particular combinations of cytotoxic poisons would cure cancer (although specific combinations for the vast majority of cancers were yet undiscovered).
Viral carcinogenesis clearly demanded a deeper explanation: how might viruses—elemental microbes floating from cell to cell—cause so profound a change in a cell’s physiology as to create a malignant cell? The success of cytotoxic chemotherapy provoked equally fundamental questions: why had a series of rather general poisons cured some forms of cancer, while leaving other forms completely unscathed?
Obviously, a more fundamental explanation lurked beneath all of this, an explanation that would connect cause and cure. So some researchers urged patience, diligence, and time. “The program directed by the National Cancer Institute has been derided as one that puts the cart before the horse by searching for a cure before knowing the cause,” Kenneth Endicott, the NCI director, acknowledged in 1963. “We have certainly not found a cure for cancer. We have a dozen chemicals which are somewhat better than those known before the program began but none are dramatically better. They prolong the patient’s life somewhat and make him more comfortable, but that is all.”
But the Laskerites had little time for such nuanced descriptions of progress; this cart would have to drag the horse. “The iron is hot and this is the time to pound without cessation,” Farber wrote to Lasker. The groundwork for an all-out battle had already been laid. All that was necessary was to put pressure on Congress to release funds. “No large mission or goal-directed effort [against cancer], supported with adequate funds has ever been organized,” Mary Lasker announced in an open letter to Congress in 1969.
Lasker’s thoughts were echoed by Solomon Garb, a little-known professor of pharmacology at the University of Missouri who shot to prominence by publishing the book Cure for Cancer: A National Goal in 1968. “The theme of this book,” Garb began, “is that the time has come for a closer look at cancer research and for a new consolidation of effort aimed at cure or control of cancer. . . . A major hindrance to cancer effort has been a chronic, severe shortage of funds—a situation that is not generally recognized. It is not enough, however, to point this out or to repeat it; it is also necessary to explain how additional funds would be used, what projects they would pay for, why such projects deserve support, and where the skilled scientists and technicians to do the work would come from.”
Garb’s book was described as a “springboard to progress,” and the Laskerites certainly sprang. As with Farber, a doctor’s word was the ultimate prescription. That Garb had prescribed precisely the strategy advocated by the Laskerites instantly transformed him in their eyes into a messianic figure. His book became their bible.
Religious movements and cults are often founded on a tetrad of elements: a prophet, a prophecy, a book, and a revelation. By the summer of 1969, the cancer crusade had acquired three of these four essential elements. Its prophet was Mary Lasker, the woman who had guided it out of the dark wilderness of the 1950s into national prominence just two decades later. Its prophecy was the cure for childhood leukemia, inaugurated by Farber’s experiments in Boston and ending with Pinkel’s astonishing successes in Memphis. Its book was Garb’s Cure for Cancer. The final missing element was a revelation—a sign that would auger the future and capture the imagination of the public. In the spirit of all great revelations, this one would also appear unexpectedly and mystically out of the blue. It would apparition, quite literally, from the heavens.
At 4:17 p.m. EDT on July 20, 1969, a fifteen-ton spacecraft moved silently through the cold, thin atmosphere above the moon and landed on a rocky basalt crater on the lunar surface. A vast barren landscape—a “magnificent desolation”—stretched out around the spacecraft. “It suddenly struck me,” one of the two astronauts would recall, “that that tiny pea, pretty and blue, was the earth. I put up my thumb and shut one eye, and my thumb blotted out the planet.”
On that pea-size blue planet glimmering on the horizon, this was a moment of reckoning. “It was a stunning scientific and intellectual accomplishment,” Time reported in July 1969, “for a creature who, in the space of a few million years—an instant in evolutionary chronology—emerged from primeval forests to hurl himself at the stars. . . . It was, in any event, a shining reaffirmation of the optimistic premise that whatever man imagines he can bring to pass.”
The cancer crusaders could not have asked for a more exuberant vindication for their own project. Here was another “programmatic” effort—planned, targeted, goal-oriented, and intensely focused—that had delivered its results in record time. When Max Faget, the famously taciturn engineer of the Apollo program, was later asked to comment on the principal scientific challenge of the moon landing, he could only come up with a single word: “Propulsion.” The impression was that the moon walk had turned out to be a technological cakewalk—no more complicated than building a more powerful jet plane, magnifying it several dozenfold, and pointing it vertically at the moon.
The Laskerites, transfixed in front of their flickering television sets in Boston, Washington, and New York on the evening of the moon landing, were primed to pick up on all these analogies. Like Faget, they believed that the missing element in the cancer crusade was some sort of propulsion, a simple, internal vertical thrust that would transform the scale and scope of their efforts and catapult them toward the cure.
In fact, the missing propulsion, they believed, had finally been found. The success against childhood leukemia—and more recently, Hodgkin’s disease—stood out as proofs of principle, the first hesitant explorations of a vast unexplored space. Cancer, like the moon, was also a landscape of magnificent desolation—but a landscape on the verge of discovery. In her letters, Mary Lasker began to refer to a programmatic War on Cancer as the conquest of “inner space” (as opposed to “outer space”), instantly unifying the two projects.
The moon landing thus marked a turning point in the life cycle of the cancer crusade. In the past, the Laskerites had concentrated much of their efforts on political lobbying in Washington. When advertisements or posters had been pitched directly to the public, they had been mainly educational. The Laskerites had preferred to maneuver backstage, preferring political advocacy to public advocacy.
But by 1969, politics had changed. Lister Hill, the Alabama senator and one of Mary Lasker’s strongest supporters, was retiring after several decades in the Senate. Senator Edward Kennedy, Farber’s ally from Boston, was so deeply embroiled in the Chappaquiddick scandal (in July 1969, a car carrying Kennedy and a campaign worker veered off a Martha’s Vineyard bridge and sank underwater, drowning his passenger; Kennedy was tried for manslaughter, although eventually acquitted) that he had virtually disappeared into legislative oblivion. The Laskerites were now doubly orphaned. “We’re in the worst,” Lasker recalled. “We’re back to a phase that we were in the early fifties when . . . we had no friend in the Senate. We went on constantly—but no effective sympathy.”
With their voices now muted in Washington, with little sympathy in the House and no friend in the Senate, the Laskerites were forced to revamp the strategy for their crusade—from backstage political maneuvering to front-stage public mobilization. In retrospect, that turn in their trajectory was well-timed. The success of Apollo 11 may have dramatically affected the Laskerites’ own view of their project, but, more important perhaps, it created an equally seismic shift in the public perception of science. That cancer could be conquered, just as the moon had been conquered, was scarcely a matter of doubt. The Laskerites coined a phrase to describe this analogy. They called it a “moon shot” for cancer.
* The Jimmy Fund was launched in May 1948. September 1968 marked its twenty-first year. The date of Jimmy’s “birthday” was arbitrarily assigned by Farber.
“A moon shot for cancer”
The relationship of government to science in the post-war years is a case in point. Without very much visible deliberation, but with much solemnity, we have in little more than a decade elevated science to a level of extraordinary influence in national policy; and now that it is there, we are not very certain what to do with it.
—William Carey, 1963
What has Santa Nixon given us lately?
—New York Times, 1971
On December 9, 1969, on a chilly Sunday morning, a full-page advertisement appeared in the Washington Post:*
Mr. Nixon: You can cure cancer.
If prayers are heard in Heaven, this prayer is heard the most:
“Dear God, please. Not cancer.”
Still, more than 318,000 Americans died of cancer last year.
This year, Mr. President, you have it in your power to begin to end this curse.
As you agonize over the Budget, we beg you to remember the agony of those 318,000 Americans. And their families.
. . . We ask a better perspective, a better way to allocate our money to save hundreds of thousands of lives each year.
. . . Dr. Sidney Farber, Past President of the American Cancer Society, believes: “We are so close to a cure for cancer. We lack only the will and the kind of money and comprehensive planning that went into putting a man on the moon.”
. . . If you fail us, Mr. President, this will happen:
One in six Americans now alive, 34,000,000 people, will die of cancer unless new cures are found.
One in four Americans now alive, 51,000,000 people, will have cancer in the future.
We simply cannot afford this.
A powerful image accompanied the text. Across the bottom of the page, a cluster of cancer cells was loosely grouped into a mass. Some of these cells were crumbling off that mass, sending a shower of metastatic fingerlings through the text. The letters e and r in cancer had been eaten through by these cells, like holes punched out in the bone by breast cancer.
It is an unforgettable picture, a confrontation. The cells move across the page, almost tumbling over each other in their frenzy. They divide with hypnotic intensity; they metastasize in the imagination. This is cancer in its most elemental form—naked, ghoulish, and magnified.
The Times ad marked a seminal intersection in the history of cancer. With it, cancer declared its final emergence from the shadowy interiors of medicine into the full glare of public scrutiny, morphing into an illness of national and international prominence. This was a generation that no longer whispered about cancer. There was cancer in newspapers and cancer in books, cancer in theater and in films: in 450 articles in the New York Times in 1971; in Aleksandr Solzhenitsyn’s Cancer Ward, a blistering account of a cancer hospital in the Soviet Union; in Love Story, a 1970 film about a twenty-four-year-old woman who dies of leukemia; in Bang the Drum Slowly,a 1973 release about a baseball catcher diagnosed with Hodgkin’s disease; in Brian’s Song,the story of the Chicago Bears star Brian Piccolo, who died of testicular cancer. A torrent of op-ed pieces and letters appeared in newspapers and magazines. One man wrote to the Wall Street Journal describing how his family had been “plunged into numb agony” when his son was diagnosed with cancer. “Cancer changes your life,” a patient wrote after her mastectomy. “It alters your habits. . . . Everything becomes magnified.”
There is, in retrospect, something preformed in that magnification, a deeper resonance—as if cancer had struck the raw strings of anxiety already vibrating in the public psyche. When a disease insinuates itself so potently into the imagination of an era, it is often because it impinges on an anxiety latent within that imagination. AIDS loomed so large on the 1980s in part because this was a generation inherently haunted by its sexuality and freedom; SARS set off a panic about global spread and contagion at a time when globalism and social contagion were issues simmering nervously in the West. Every era casts illness in its own image. Society, like the ultimate psychosomatic patient, matches its medical afflictions to its psychological crises; when a disease touches such a visceral chord, it is often because that chord is already resonating.
So it was with cancer. As the writer and philosopher Renata Salecl described it, “A radical change happened to the perception of the object of horror” in the 1970s, a progression from the external to the internal. In the 1950s, in the throes of the Cold War, Americans were preoccupied with the fear of annihilation from the outside: from bombs and warheads, from poisoned water reservoirs, communist armies, and invaders from outer space. The threat to society was perceived as external. Horror movies—the thermometers of anxiety in popular culture—featured alien invasions, parasitic occupations of the brain, and body snatching: It Came from Outer Space or The Man from Planet X.
But by the early 1970s, the locus of anxiety—the “object of horror,” as Salecl describes it—had dramatically shifted from the outside to the inside. The rot, the horror—the biological decay and its concomitant spiritual decay—was now relocated within the corpus of society and, by extension, within the body of man. American society was still threatened, but this time, the threat came from inside. The names of horror films reflected the switch: The Exorcist; They Came from Within.
Cancer epitomized this internal horror. It was the ultimate emergence of the enemy from within—a marauding cell that crawled out of one’s own body and occupied it from the inside, an internal alien. The “Big Bomb,” a columnist wrote, was replaced by “the Big C”:
“When I was growing up in the 1950s, it was The Bomb. This thing, The Bomb, belonged to a generation of war babies. . . . But we are fickle even about fear. We seem to have dropped our bombphobia now without, in any way, reducing the reasons for it. Cancer now leads this macabre hit parade. The middle-sized children I know seem to think that death comes, not with a bang but with a tumor. . . . Cancer is the obsession of people who sense that disaster may not be a purposeful instrument of public policy but a matter of accidental, random carelessness.”
These metaphorical shifts were more powerful, more pervasive, and more influential than the Laskerites could even have imagined. The Times ad represented a strategic realignment of power. By addressing their letter to the president on behalf of “millions of Americans,” the Laskerites performed a tactically brilliant about-face. In the past, they had pleaded to the nation for funds for cancer. Now, as they pleaded for the nation for a more coordinated attack on cancer, they found themselves colossally empowered in the public imagination. The cure for cancer became incorporated into the very fabric of the American dream. “To oppose big spending against cancer,” one observer told the historian James Patterson, was to “oppose Mom, apple pie, and the flag.” In America, this was a triumvirate too powerful for even the president to ignore.
Impatient, aggressive, and goal-driven, the president, Richard Milhous Nixon, was inherently partial to impatient, aggressive, and goal-driven projects. The notion of science as an open-ended search for obscure truths bothered and befuddled him. Nixon often groused that scientists didn’t “know a goddamn thing” about the management of science. Nor was he particularly sympathetic to open-ended scientific funding. Corn-fed and fattened on increasingly generous federal grants, scientists (often called “nuts” or “bastards” by members of his administration) were thought to have become arrogant and insular. Nixon wanted them “to shape up.”
For Nixon, this “shaping up” meant wresting the control of science out of the hands of academic “nutcases” and handing it over to a new cadre of scientific bureaucrats—science managers who would bring discipline and accountability to science. The replacement of Nixon’s science adviser, Lee DuBridge, a scholarly, old-school atomic physicist from Caltech, with Ed David, an impulsive, fast-paced engineer-turned-manager from the Bell research labs, was meant as a signal to the scientific community to get into shape. David was the first presidential science adviser to emerge out of an industrial lab and to have no direct connection with a university. His mandate was to get an effective science operation that would redirect its energies toward achieving defined national goals. What scientists needed—what the public demanded—was not an “endless frontier” (à la Vannevar Bush) but a discipline with pragmatic frontiers and well-defined ends.
Lasker’s job, then, was to convert the already converted. In 1969, deploying her typical strategic genius, Mary Lasker proposed that a “neutral” committee of experts, called a Commission on the Conquest of Cancer, be created to advise the president on the most efficient strategy to mount a systematic response to cancer. The commission, she wrote, should “include space scientists, industrialists, administrators, planners, and cancer research specialists . . . entrusted to outline the possibilities for the conquest of cancer for the Congress of the United States at whatever cost.”
Of course, Lasker ensured that there was nothing neutral about the commission (eventually called the Panel of Consultants). Its members, chosen with exquisite deliberateness, were all Lasker’s friends, associates, and sympathizers—men and women already sold on the War on Cancer. Sidney Farber was selected as the cochairman, along with Senator Ralph Yarborough from Texas (Yarborough, like Lister Hill, was one of the Laskers’ oldest allies in Congress). Solomon Garb was appointed on account of his book. Joseph Burchenal was brought in from Memorial Hospital, James Holland from Roswell Park, Henry Kaplan from Stanford. Benno Schmidt, a partner in a prominent New York investment firm and a major donor to Memorial Hospital, joined the group. (An energetic organizer, Schmidt was eventually asked to replace Farber and Yarborough to head the panel; that Schmidt was a Republican and a close confidant of President Nixon’s was a marked plus.) Politics, science, medicine, and finance were thus melded together to craft a national response. To reinforce the facade of neutrality, Yarborough wrote to Mary Lasker in the summer of 1970, “asking” her to join (although he scribbled at the bottom, “Your letter should have been the first mailed. It was your genius, energy and will to help.”)
The panel’s final report, entitled the National Program for the Conquest of Cancer, was issued in the winter of 1970, and its conclusions were predictable: “In the past, when the Federal Government has desired to give top priority to a major scientific project of the magnitude of that involved in the conquest of cancer, it has, on occasion, with considerable success, given the responsibility for the project to an independent agency.” While tiptoeing around the idea, the panel was proposing the creation of an independent cancer agency—a NASA for cancer.
The agency would start with a budget of $400 million, then its allocations would increase by $100 million to $150 million per year, until, by the mid-1970s, it would stand at $1 billion. When Schmidt was asked if he thought that the country could “afford such a program,” he was unhesitant in his reply: “Not only can we afford the effort, we cannot afford not to do it.”
On March 9, 1971, acting on the panel’s recommendations, Ted Kennedy and Jacob Javits floated a Senate Bill—S 1828, the Conquest of Cancer Act—to create a National Cancer Authority, an independent, self-governing agency for cancer research. The director of the authority would be appointed by the president and confirmed by the Senate—again underscoring an extraordinary level of autonomy. (Usually, disease-specific institutes, such as the National Heart Institute, were overseen by the NIH.) An advisory board of eighteen members would report back to Congress about progress on cancer. That panel would comprise scientists, administrators, politicians, physicians—and, most controversially, “lay individuals,” such as Lasker, Foote, and Bobst, whose sole task would be to keep the public eye trained sharply on the war. The level of funding, public scrutiny, and autonomy would be unprecedented in the history of the NIH—and arguably in the history of American science.
Mary Lasker was busy maneuvering behind the scenes to whip up support for the Kennedy/Javits bill. In January 1971, she fired off a cavalcade of letters to her various friends seeking support for the independent cancer agency. In February, she hit upon another tactical gem: she persuaded her close friend Ann Landers (her real name was Eppie Lederer), the widely read advice columnist from Chicago, to publish a column about cancer and the Kennedy bill, positioning it exactly at the time that the vote was fermenting in the Senate.
Landers’s column appeared on April 20, 1971. It began solemnly, “Dear Readers: If you are looking for a laugh today, you’d better skip Ann Landers. If you want to be part of an effort that might save millions of lives—maybe your own—please stay with me. . . . How many of us have asked the question, ‘If this great country of ours can put a man on the moon why can’t we find a cure for cancer?’”
Landers’s answer to that question—echoing the Laskerites—was that cancer was missing not merely a medical cure but a political cure. “If enough citizens let their senators know they want Bill S-34 passed, it will pass. . . . Vote for S-34,” she pleaded. “And sign your name please.”
Even Landers and Lasker were shocked by the ensuing “blizzard” of mail. “I saw trucks arriving at the Senate,” the journalist Barbara Walters recalled. Letters poured in by the bagful—about a million in all—pushing the Senate mailroom to its breaking point. One senator wrote that he received sixty thousand letters. An exasperated secretary charged with sorting the mail hung up the sign IMPEACH ANN LANDERS on her desk. Stuart Symington, the senator from Missouri, wrote to Landers begging her to post another column advising people to stop writing. “Please Eppie,” he begged, “I got the message.”
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.