STAMP

Then did I beat them as small as the dust of the earth, I did stamp them as the mire of the street, and did spread them abroad.

—Samuel 22:43

Cancer therapy is like beating the dog with a stick to get rid of his fleas.

—Anna Deavere Smith, Let Me Down Easy

February was my cruelest month. The second month of 2004 arrived with a salvo of deaths and relapses, each marked with the astonishing, punctuated clarity of a gunshot in winter. Steve Harmon, thirty-six, had esophageal cancer growing at the inlet of his stomach. For six months, he had soldiered through chemotherapy as if caught in a mythical punishment cycle devised by the Greeks. He was debilitated by perhaps the severest forms of nausea that I had ever encountered in a patient, but he had to keep eating to avoid losing weight. As the tumor whittled him down week by week, he became fixated, absurdly, on the measurement of his weight down to a fraction of an ounce, as if gripped by the fear that he might vanish altogether by reaching zero.

Meanwhile, a growing retinue of family members accompanied him to his clinic visits: three children who came with games and books and watched, unbearably, as their father shook with chills one morning; a brother who hovered suspiciously, then accusingly, as we shuffled and reshuffled medicines to keep Steve from throwing up; a wife who bravely shepherded the entire retinue through the whole affair as if it were a family trip gone horribly wrong.

One morning, finding Steve alone on one of the reclining chairs of the infusion room, I asked him whether he would rather have the chemotherapy alone, in a private room. Was it, perhaps, too much for his family—for his children?

He looked away with a flicker of irritation. “I know what the statistics are.” His voice was strained, as if tightening against a harness. “Left to myself, I would not even try. I’m doing this because of the kids.”

“If a man die,” William Carlos Williams once wrote, “it is because death / has first possessed his imagination.” Death possessed the imagination of my patients that month, and my task was to repossess imagination from death. It is a task almost impossibly difficult to describe, an operation far more delicate and complex than the administration of a medicine or the performance of surgery. It was easy to repossess imagination with false promises; much harder to do so with nuanced truths. It demanded an act of exquisite measuring and remeasuring, filling and unfilling a psychological respirator with oxygen. Too much “repossession” and imagination might bloat into delusion. Too little and it might asphyxiate hope altogether.

In his poignant memoir of his mother’s illness, Susan Sontag’s son, David Rieff, describes a meeting between Sontag and a prominent doctor in New York. Sontag, having survived uterine and breast cancer, had been diagnosed with myelodysplasia, a precancerous disease that often sours into full-blown leukemia. (Sontag’s myelodysplasia was caused by the high-dose chemotherapy that she had received for the other cancers.) The doctor—Rieff calls him Dr. A.—was totally pessimistic. There was no hope, he told her flatly. And not just that; there was nothing to do but wait for cancer to explode out of the bone marrow. All options were closed. His word—the Word—was final, immutable, static. “Like so many doctors,” Rieff recalls, “he spoke to us as if we were children but without the care that a sensible adult takes in choosing what words to use with a child.”

The sheer inflexibility of that approach and the arrogance of its finality was a nearly fatal blow for Sontag. Hopelessness became breathlessness, especially for a woman who wanted to live twice as energetically, to breathe the world in twice as fast as anyone else—for whom stillness was mortality. It took months before Sontag found another doctor whose attitude was vastly more measured and who was willing to negotiate with her psyche. Dr. A. was right, of course, in the formal, statistical sense. A moody, saturnine leukemia eventually volcanoed out of Sontag’s marrow, and, yes, there were few medical options. But Sontag’s new physician also told her precisely the same information, without ever choking off the possibility of a miraculous remission. He moved her in succession from standard drugs to experimental drugs to palliative drugs. It was all masterfully done, a graded movement toward reconciliation with death, but a movement nonetheless—statistics without stasis.

Of all the clinicians I met during my fellowship, the master of this approach was Thomas Lynch, a lung cancer doctor, whom I often accompanied to clinic. Clinics with Lynch, a youthful-looking man with a startling shock of gray hair, were an exercise in medical nuance. One morning, for instance, a sixty-six-year-old woman, Kate Fitz, came to the clinic having just recovered from surgery for a large lung mass, which had turned out to be cancerous. Sitting alone in the room, awaiting news of her next steps, she looked nearly catatonic with fear.

I was about to enter the room when Lynch caught me by the shoulder and pulled me into the side room. He had looked through her scan and her reports. Everything about the excised tumor suggested a high risk of recurrence. But more important, he had seen Fitz folded over in fear in the waiting room. Right now, he said, she needed something else. “Resuscitation,” he called it cryptically as he strode into her room.

I watched him resuscitate. He emphasized process over outcome and transmitted astonishing amounts of information with a touch so slight that you might not even feel it. He told Fitz about the tumor, the good news about the surgery, asked about her family, then spoke about his own. He spoke about his child who was complaining about her long days at school. Did Fitz have a grandchild? he inquired. Did a daughter or a son live close by? And then, as I watched, he began to insert numbers here and there with a light-handedness that was a marvel to observe.

“You might read somewhere that for your particular form of cancer, there is a high chance of local recurrence or metastasis,” he said. “Perhaps even fifty or sixty percent.”

She nodded, tensing up.

“Well, there are ways that we will tend to it when that happens.”

I noted that he had said “when,” not “if.” The numbers told a statistical truth, but the sentence implied nuance. “We will tend to it,” he said, not “we will obliterate it.” Care, not cure. The conversation ran for nearly an hour. In his hands, information was something live and molten, ready to freeze into a hard shape at any moment, something crystalline yet negotiable; he nudged and shaped it like glass in the hands of a glassblower.

An anxious woman with stage III breast cancer needs her imagination to be repossessed before she will accept chemotherapy that will likely extend her life. A seventy-six-year-old man attempting another round of aggressive experimental chemotherapy for a fatal, drug-resistant leukemia needs his imagination to be reconciled to the reality that his disease cannot be treated. Ars longa, vita brevis. The art of medicine is long, Hippocrates tells us, “and life is short; opportunity fleeting; the experiment perilous; judgment flawed.”

For cancer therapeutics, the mid and late 1980s were extraordinarily cruel years, mixing promise with disappointment, and resilience with despair. As physician-writer Abraham Verghese wrote, “To say this was a time of unreal and unparalleled confidence, bordering on conceit, in the Western medical world is to understate things. . . . When the outcome of treatment was not good, it was because the host was aged, the protoplasm frail, or the patient had presented too late—never because medical science was impotent.

“There seemed to be little that medicine could not do. . . . Surgeons, like Tom Starzl . . . were embarking on twelve- to fourteen-hour ‘cluster operations’ where liver, pancreas, duodenum and jejunum were removed en bloc from a donor and transplanted into a patient whose belly, previously riddled with cancer, had now been eviscerated, scooped clean in preparation for this organ bouquet.

“Starzl was an icon for that period in medicine, the pre-AIDS days, the frontier days of every-other-night call.”

Yet even the patients eviscerated and reimplanted with these “organ bouquets” did not make it: they survived the operation, but not the disease.

The chemotherapeutic equivalent of that surgical assault—of eviscerating the body and replacing it with an implant—was a procedure known as autologous bone marrow transplant, or ABMT, which roared into national and international prominence in the mid-1980s. At its core, ABMT was based on an audacious conjecture. Ever since high-dose, multidrug regimens had succeeded in curing acute leukemia and Hodgkin’s disease in the 1960s, chemotherapists had wondered whether solid tumors, such as breast or lung cancer, had remained recalcitrant to chemotherapeutic obliteration simply because the bludgeon of drugs used was not powerful enough. What if, some had fantasized, one could tip the human body even closer to the brink of death with even higher doses of cytotoxic drugs? Might it be dragged back from that near-lethal brink, leaving cancer behind? What if one could double, or even quadruple, the dosage of drugs?

The dose limit of a drug is set by its toxicity to normal cells. For most chemotherapy drugs, that dose limit rested principally on a single organ—the bone marrow, whose whirring cellular mill, as Farber had found, was so exquisitely sensitive to most drugs that patients administered drugs to kill cancer were left with no normal blood-forming cells. For a while, then, it was the bone marrow’s sensitivity to cytotoxic drugs that had defined the outer horizon of chemotherapeutic dosage. The bone marrow represented the frontier of toxicity, an unbreachable barrier that limited the capacity to deliver obliterative chemotherapy—the “red ceiling” as some oncologists called it.

But by the late 1960s, even that ceiling had seemed to lift. In Seattle, one of Farber’s early protégés, E. Donnall Thomas, had shown that bone marrow, much like a kidney or liver, could be harvested from one patient and transplanted back—either into the same patient (called autologous transplantation) or into another patient (termed allogeneic transplantation).

Allogeneic transplantation (i.e., transplanting foreign marrow into a patient) was temperamental—tricky, mercurial, often deadly. But in some cancers, particularly leukemias, it was potentially curative. One could, for instance, obliterate a marrow riddled with leukemia using high-dose chemo and replace it with fresh, clean marrow from another patient. Once the new marrow had engrafted, the recipient ran the risk of that foreign marrow turning and attacking his or her own body as well as any residual leukemia left in the marrow, a deadly complication termed graft-versus-host disease or GVHD. But in some patients, that trifecta of assaults—obliterative chemotherapy, marrow replacement, and the attack on the tumor by foreign cells—could be fashioned into an exquisitely potent therapeutic weapon against cancer. The procedure carried severe risks. In Thomas’s initial trial at Seattle, only twelve out of a hundred patients had survived. But by the early 1980s, doctors were using the procedure for refractory leukemias, multiple myeloma, and myelodysplastic syndrome—diseases inherently resistant to chemotherapy. Success was limited, but at least some patients were eventually cured.

Autologous bone marrow transplantation was, if conceivable, the lighter fraternal twin of allogeneic transplantation. Here, the patient’s own marrow was harvested, frozen, and transplanted back into his or her body. No donor was needed. The principal purpose was not to replace diseased marrow (using a foreign marrow) but to maximize chemotherapeutic dosage. A patient’s own marrow, containing blood-forming cells, was harvested and frozen. Then blisteringly high levels of drugs were administered to kill cancer. The frozen marrow was thawed and implanted. Since the frozen marrow cells were spared the brunt of chemotherapy, transplantation allowed doctors, theoretically at least, to push doses of chemo to their ultimate end.

For advocates of megadose chemotherapy, ABMT breached a final and crucial roadblock. It was now possible to give five- or even tenfold the typical doses of drugs, in poisonous cocktails and combinations once considered incompatible with survival. Among the first and most fervent proponents of this strategy was Tom Frei—cautious, levelheaded Frei, who had moved from Houston to Boston as the director of Farber’s institute. By the early 1980s, Frei had convinced himself that a megadose combination regimen, bolstered by marrow transplantation, was the only conceivable solution in cancer therapy.

To test this theory, Frei hoped to launch one of the most ambitious trials in the history of chemotherapy. With his ear for catchy acronyms, Frei christened the protocol the Solid Tumor Autologous Marrow Program—or STAMP. Crystallized in that name was the storm and rage of cancer medicine; if brute force was needed, then brute force would be summoned. With searing doses of cytotoxic drugs, STAMP would trample its way over cancer. “We have a cure for breast cancer,” Frei told one of his colleagues in the summer of 1982. Uncharacteristically, he had already let his optimism fly to the far edge of brinkmanship. The first patient had not even been enrolled on trial.

VAMP had succeeded, Frei privately believed, not just because of the unique chemotherapeutic synergy among the drugs, but also because of the unique human synergy at the NCI—that cocktail of brilliant young minds and risk-taking bodies that had coalesced in Bethesda between 1955 and 1960. In Boston, two decades later, Frei assiduously set about re-creating that same potent atmosphere, tossing out deadwood faculty and replacing it with fresh new blood. “It was an intensely competitive place,” Robert Mayer, the oncologist, recalled, “a pressure cooker for junior and senior faculty.” Trial-running was the principal currency of academic advancement, and volley after volley of trials were launched at the institute with a grim, nearly athletic, determination. Metaphors of war permeated the Farber. Cancer was the ultimate enemy, and this was its ultimate crucible, its epic battleground. Laboratory space and clinical space were deliberately intermingled through the floors to create the impression of a highly sophisticated interlocking machine dedicated to a single cause. On blackboards mounted on laboratory walls, complex diagrams with zigzagging arrows and lines depicted the life line of a cancer cell. To walk through the narrow corridors of the institute was to feel immersed in a gigantic, subterranean war room, where technological prowess was on full display and every molecule of air seemed poised for a battle.

In 1982, Frei recruited William Peters, a young doctor from New York, as a fellow at the institute. Peters was an academic all-star. He had graduated from Pennsylvania State University with three majors, in biochemistry, biophysics, and philosophy, then steamrollered his way through the College of Physicians and Surgeons at Columbia, earning both an M.D. and a Ph.D. Affable, determined, enthusiastic, and ambitious, he was considered the most able corporal among the troops of junior faculty at the Farber. The relationship between Frei and Peters was almost instantly magnetic, perhaps even parental. Peters was instinctually drawn to Frei’s reputation, creativity, and unorthodox methods; Frei, to Peters’s energy and enthusiasm. Each saw in the other an earlier or later incarnation of himself.

On Thursday afternoons, fellows and faculty at the Farber gathered in a conference room on the sixteenth floor. The room was symbolically set on the highest floor of the building, its large windows, overlooking the evergreen fens of Boston, and its wood-paneled walls, blond and reflective, creating a light-immersed casket suspended midair. Lunch was catered. The doors were closed. It was a time dedicated to academic thinking, sealed away from the daily whir of labs and clinics in the floors below.

It was at these afternoon conferences that Frei began to introduce the idea of megadose combination chemotherapy with autologous marrow support to the fellows and junior faculty. In the fall of 1983, he invited Howard Skipper, the soft-spoken “mouse doctor” who had so deeply influenced Frei’s early work, to speak. Skipper was inching toward higher and higher doses of cytotoxic drugs in his mouse models and spoke enthusiastically about the possibility of curative treatment with these megadose regimens. He was soon after followed by Frank Schabel, another scientist who had demonstrated that combining agents, in doses lethal for the marrow, possessed synergistic effects on mouse tumors. Schabel’s lecture was particularly galvanizing, a “seminal event,” as Peters described it. After the talk, as Frei recalled, the room was abuzz with excitement; Schabel was surrounded by young, eager investigators mesmerized by his ideas. Among the youngest, and by far the most eager, was Bill Peters.

Yet the surer Frei became about megadose chemotherapy, the less sure some others around him seemed to get. George Canellos, for one, was wary, right from the outset. Wiry and tall, with a slight stoop and a commanding basso-profundo voice, Canellos was the closest to Frei’s equal at the institute, an original member of the NCI from its heady early days in the mid-1960s. Unlike Frei, though, Canellos had turned from advocate to adversary of megadose chemo regimens, in part because he had been among the first to notice a devastating long-term side effect: as doses escalated, some chemotherapeutic drugs damaged the marrow so severely that, in time, these regimens could precipitate a premalignant syndrome called myelodysplasia, a condition that tended to progress to leukemia. The leukemias that arose from the ashes of chemotherapy-treated marrows carried such grotesque and aberrant mutations that they were virtually resistant to any drugs, as if their initial passage through that fire had tempered them into immortality.

With Canellos arguing one side and Frei the other, the institute split into bitterly opposing camps. But Peters and Frei were unstoppably enthusiastic. By late 1982, with Frei’s guidance, Peters had written a detailed protocol for the STAMP regimen. A few weeks later, the Institutional Review Board at the Farber approved STAMP, giving Peters and Frei the green light to begin their trial. “We were going to swing and go for the ring,” Peters recalled. “That drove us. You had to believe you were going to pull off something that was going to change history.”

The first patient to “change history” with STAMP was a thirty-year-old commercial driver from Massachusetts with breast cancer. A grim, determined, hefty woman hardened by the gritty culture of truck stops and highways, she had been treated and re-treated with multiple standard and escalating regimens of chemotherapy. Her tumor, a friable, inflamed disk of tissue, was nearly six centimeters wide, hanging visibly off her chest wall. But having “failed” all the conventional treatments, she had become virtually invisible to the institute. Her case was considered so terminal that she had been written off from every other experimental protocol. When she signed on to Peters’s protocol, no one objected.

Marrow transplantation begins, of course, by “harvesting” bone marrow. On the morning of the first harvest, Peters went down to the leukemia clinic and gathered his arms full of bone marrow needles. He wheeled his first patient over to the operating room at the neighboring Beth Israel hospital (the Farber had no operating rooms) and began pulling out the marrow, plunging a steel trocar repeatedly into the hip and drawing out the cells, leaving a hip pockmarked with red bruises. Each time he pulled, a few droplets of reddish sludge gathered in the syringe.

Then disaster struck. As Peters pulled out a specimen, the marrow needle broke, leaving a piece of steel buried deeply in his patient’s hip. For a few minutes, pandemonium broke out in the operating room. Nurses made frantic phone calls to the floors, asking for surgeons to step in to help. An hour later, using a pair of orthopedic pliers to dig into the hip, Peters recovered the needle.

Later that evening, the full impact of that moment struck Peters. It had been a close shave. “The ultimate trial of chemotherapeutic intensification,” Peters said, “almost broke its back on an old needle.” For Peters and Frei, it was an all-too-obvious metaphor for the rustiness and obsolescence of the status quo. The War on Cancer was being waged by timorous doctors (unwilling to maximize chemotherapy) with blunt, outmoded weapons.

For a few weeks after that initial tumult, Peters’s life fell into a reasonably stable routine. Early mornings, dodging Canellos and other muttering skeptics, he rounded on his patients on the far corner of the twelfth floor, where a few rooms had been set aside for the trial. Evenings were spent at home with Masterpiece Theatre playing in the background as he sharpened needles physically and sharpened the trial intellectually. As the trial gathered speed, it also gained visibility. Peters’s first few patients had been last-ditch, hopeless cases, women with tumors so deeply recalcitrant to all drugs that they were readily enrolled in experimental trials as a last resort in the hope of obtaining even a minor remission. But as rumors of the trial coursed through networks of patients and friends, cancer patients began to contact Peters and Frei to try the megadose strategy up front—not after they had failed more conventional regimens, but before they had even tried anything else. In the late summer of 1983, when a previously untreated woman with metastatic breast cancer enrolled in STAMP, as Peters recalled, the institute stood up to take notice. “Suddenly, everything broke loose and things came apart.”

The woman was thirty-six years old—charming, sophisticated, intense, coiled and tightened into a spring by her yearlong battle with illness. She had watched her mother die of an aggressive breast cancer that had been fiercely resistant to conventional therapy. Instinctually, she was convinced that hers would be just as virulent and just as resistant. She wanted to live and wanted the most aggressive therapy up front, without soldiering through trials that would, she was convinced, fail anyway. When Peters offered her STAMP, she grasped at it without hesitation.

Her clinical course was among the most closely watched in the history of the institute. Fortunately for Peters, chemotherapy and transplantation went smoothly. On the seventh day after megadose chemotherapy, when Frei and Peters hurried down to the basement to look at the first chest X-ray after treatment, they found that they had been beaten to it. An entire congregation of curious doctors had gathered in the room like a jury and was huddled around the films. Against the sharp, fluorescent light, her chest X-ray showed a marked response. The metastatic deposits peppered around in her lung had shrunk visibly, and even the swollen lymph nodes around it had visibly recessed. It was, as Peters recalls, “the most beautiful remission you could have imagined.”

As the year drew on, Peters treated and transplanted more cases and obtained beautiful remissions. By the summer of 1984, the database of transplanted cases was large enough to begin to discern patterns. The medical complications of the STAMP regimen had, of course, been predictably ghastly: near-lethal infections, severe anemia, pneumonias, and hemorrhages in the heart. But under the clouds of X-rays, blood tests, and CT scans, Peters and Frei saw a silvery inkling. The remissions produced by STAMP, they were convinced, had all been more durable than those produced by conventional chemotherapy. It was only an impression—at best, a guess. To prove that point, Peters needed a randomized trial. In 1985, with Frei’s encouragement, he left Boston to set up a STAMP program at Duke University in North Carolina. He wanted to leave the Farber’s “pressure cooker” behind for a quiet and stable academic place where he could run a trial in peace.

As William Peters dreamed of a quiet and stable environment to test megadose chemotherapy, the world of medicine was overturned by an unexpected and seemingly unrelated event. In March 1981, in the journal Lancet, a team of doctors reported eight cases of a highly unusual form of cancer called Kaposi’s sarcoma in a cohort of men in New York. The disease was not new: named after a nineteenth-century Hungarian dermatologist, Kaposi’s sarcoma had long been recognized as a slow-growing, violet-colored, indolent tumor that crept along the skin of elderly Italian men that, while occasionally serious, was often considered a somewhat glorified form of a mole or carbuncle. But all the Lancet cases were virtually unrecognizable forms of the disease, violent and aggressive variants that had exploded into bleeding, metastatic, blue-black macules spread all over the bodies of these young men. All eight of the men were homosexual. The eighth case drew particular alarm and interest: this man, with lesions on his head and back, was also diagnosed with a rare pneumonia called PCP caused by the organism Pneumocystis carinii. An outbreak of one obscure illness in a cluster of young men was already outlandish. The confluence of two suggested a deeper and darker aberration—not just a disease, but a syndrome.

Far away from New York, the sudden appearance of Pneumocystis carinii was also raising eyebrows at the Centers for Disease Control in Atlanta, Georgia. The CDC is the nation’s medical radar screen, an agency that tracks emerging diseases to discern patterns and contain their spread. Pneumocystis pneumonia only occurs in humans when the immune system is severely compromised. The principal victims had been cancer patients whose white blood cells had been decimated by chemotherapy. (DeVita had encountered it in Hodgkin’s patients treated with four-drug chemo.) The new cases of PCP made little sense: these were young, previously healthy men who had suddenly succumbed to PCP with their immune systems on the verge of collapse.

By the late summer of that year, as the coastal cities sweltered in a heat wave, the CDC began to sense that an epidemiological catastrophe was forming out of thin air. Between June and August 1981, the weather vane of strange illnesses swung frantically around its pivot: additional clusters of PCP, Kaposi’s sarcoma, cryptococcal meningitis, and rare lymphomas were reported in young men in cities throughout America. The common pattern behind all these diseases, aside from their disproportionate predilection for gay men, was a massive, near-total collapse of the immune system. A letter in Lancet called the disease “gay compromise syndrome.” Others called it GRID (gay-related immune deficiency) or, more cruelly, gay cancer. In July 1982, with an understanding of the cause still missing, the disease finally stumbled upon its modern name, acquired immunodeficiency syndrome, or AIDS.

Twinned conspicuously at this birth, the trajectories of AIDS and cancer were destined to crisscross and intersect at many levels. And it was Sontag, again, writing piercingly from her New York apartment (from whose terraced windows she could observe the AIDS epidemic whirling through the streets of Chelsea below), who immediately recognized the symbolic parallels between the two diseases. In a trenchant essay written as a reply to her earlier Illness as Metaphor, Sontag argued that AIDS, like cancer, was becoming not just a biological disease but something much larger—a social and political category replete with its own punitive metaphors. Like cancer patients, AIDS patients were also paralyzed and shrouded by those metaphors—stripped bare, like the cancer patient in Solzhenitsyn’s Cancer Ward, then forced to don the ghoulish uniform of their disease. The stigmas attached to cancer—guilt, secrecy, shame—were recycled and refitted for AIDS, acquiring tenfold force and potency: sexual guilt, sexual secrecy, sexual shame. If cancer, as Sontag had once argued, was perceived as the product of spoiled germ, of biological mutability gone wild, then AIDS was the result of contaminated germ, of social mutability gone wild: men unmoored from the usual conventions of society, metastasizing from coast to coast on airplanes, carrying disease and devastation within them. A patient afflicted with AIDS thus evaporated from individual existence and morphed instantly into an imagined archetype—a young gay man, fresh out of the bathhouses, defiled and ravaged by profligacy, now lying namelessly in the hospital wards of New York or San Francisco.

Sontag concerned herself with metaphorical parallels, but down in those wards, the medical battles also paralleled the battles fought against cancer. In the early days, among the first doctors to encounter and treat AIDS patients were oncologists. One of the “sentinel” diseases of immunodeficiency was Kaposi’s sarcoma, an explosive variant of an indolent cancer that had appeared without warning on the bodies of young men. In San Francisco, at the epicenter of the epidemic, the first clinic to be organized for AIDS patients was thus a sarcoma clinic that began to meet weekly beginning in September 1981 led by a dermatologist, Marcus Conant, and an oncologist, Paul Volberding. Volberding personified the crisscrossing fates of the two diseases. Trained as an oncologist at the University of California, San Francisco, he had spent a rather disappointing stint in the laboratory studying mouse retroviruses and, frustrated, switched from the lab to clinical oncology at San Francisco General Hospital.

For Volberding, and for many of his earliest patients, AIDS was cancer. To treat his sarcoma patients, Volberding borrowed various chemotherapy regimens from the NCI’s protocols.^* But more than chemotherapy protocols, Volberding borrowed something more ineffable—an ethos. At San Francisco General, at the end of a long linoleum-floored corridor with chipped paint on the walls and naked lightbulbs dangling from wires, Volberding and his team created the world’s first AIDS ward, called Ward 5B, which was explicitly modeled after the cancer wards that he had seen as a fellow. “What we did here,” he recalls, was “exactly like an oncology unit, but with a different focus, AIDS. . . . But it really was modeled on oncology units, where you have complex medical diseases with a lot of psychosocial overlay, a lot of use of drugs that are complex and require a sophisticated nursing staff and psychosocial support staff.”

Nurses, many of them gay men, gravitated to Ward 5B to tend their friends (or returned poignantly, as the epidemic bloomed, as patients themselves). Doctors reinvented medicine here, pitting their wits against a hostile, mysterious disease that they couldn’t quite fathom that was plaguing a community that they didn’t quite understand. As the patients boiled up with bizarre, spectral fevers, rules were unshackled and reinvented, creating a ward that came to resemble the unorthodox lives of the men who inhabited it. Fixed visiting hours were eliminated. Friends, companions, lovers, and family members were allowed, even encouraged, to sleep overnight in accompanying cots to help patients through those burning, hallucinatory nights. On Sunday afternoons, a San Francisco dancer catered elaborate brunches featuring tap dancing, feather boas, and marijuana-laced brownies. Farber may not have envisioned these particular innovations, but this, too, in a community drenched with grief, was its own, inimitable interpretation of “total care.”

Politically, too, AIDS activists borrowed language and tactics from cancer lobbyists, and then imbued this language with their own urgency and potency. In January 1982, as AIDS cases boomed, a group of six men founded Gay Men’s Health Crisis in New York, a volunteer organization dedicated to fighting AIDS through advocacy, lobbying, campaigning, and protest. Early volunteers decamped outside discos, bars, and bathhouses soliciting donations and distributing posters. From its office in a crumbling Chelsea brownstone, GMHC coordinated an extraordinary national effort to bring AIDS awareness to the masses. These were the Laskerites of AIDS, albeit without the gray suits and pearls.

The seminal scientific breakthrough in the AIDS epidemic was, meanwhile, unfolding in a laboratory at the Institut Pasteur in Paris. In January 1983, Luc Montagnier’s group found the sign of a virus in a lymph node biopsy from a young gay man with Kaposi’s sarcoma and in a Zairean woman who had died of immune deficiency. Montagnier soon deduced that this was an RNA virus that could convert its genes into DNA and lodge into the human genome—a retrovirus. He called his virus IDAV, immuno-deficiency associated viruses, arguing that it was likely the cause of AIDS.

At the National Cancer Institute, a group led by Robert Gallo was also circling around the same virus, although under a different name. In the spring of 1984, the two efforts converged dramatically. Gallo also found a retrovirus in AIDS patients—Montagnier’s IDAV. A few months later, the identity of the virus was confirmed by yet another group in San Francisco. On April 23, 1984, Margaret Heckler, the Health and Human Services secretary, thus appeared before the press with a bold statement about the future of the epidemic. With a causal agent in hand, a cure seemed just a few steps away. “The arrow of funds, medical personnel, research . . . has hit the target,” she said. “We hope to have a vaccine ready for testing in about two years. . . . Today’s discovery represents the triumph of science over dread disease.”

But AIDS activists, facing the lethal upswirl of the epidemic that was decimating their community, could not afford to wait. In the spring of 1987, a group of volunteers splintered away from GMHC to form a group named the AIDS Coalition to Unleash Power, or ACT UP. Led by a sardonic and hyperarticulate writer named Larry Kramer, ACT UP promised to transform the landscape of AIDS treatment using a kind of militant activism unprecedented in the history of medicine. Kramer blamed many forces for aiding and abetting the epidemic—he called it “genocide by neglect”—but chief among the neglecters was the FDA. “Many of us who live in daily terror of the AIDS epidemic,” Kramer wrote in the Times, “cannot understand why the Food and Drug Administration has been so intransigent in the face of this monstrous tidal wave of death.”

Symptomatic of this intransigence was the process by which the FDA evaluated and approved lifesaving drugs for AIDS, a process that Kramer characterized as terminally lazy and terminally slow. And terminally gaga: the slow, contemplative “academic” mechanism of drug testing, Kramer groused, was becoming life-threatening rather than lifesaving. Randomized, placebo-controlled trials were all well and good in the cool ivory towers of medicine, but patients afflicted by a deadly illness needed drugs now. “Drugs into bodies; drugs into bodies,” ACT UP chanted. A new model for accelerated clinical trials was needed. “The FDA is fucked-up, the NIH is fucked-up . . . the boys and girls who are running this show have been unable to get whatever system they’re operating to work,” Kramer told his audience in New York. “Double-blind studies,” he argued in an editorial, “were not created with terminal illnesses in mind.” He concluded, “AIDS sufferers who have nothing to lose, are more than willing to be guinea pigs.”

Even Kramer knew that that statement was extraordinary; Halsted’s ghost had, after all, barely been laid to rest. But as ACT UP members paraded through the streets of New York and Washington, frothing with anger and burning paper effigies of FDA administrators, their argument ricocheted potently through the media and the public imagination. And the argument had a natural spillover to other, equally politicized diseases. If AIDS patients demanded direct access to drugs and treatments, should other patients with terminal illnesses not also make similar demands? Patients with AIDS wanted drugs into bodies, so why should bodies with cancer be left without drugs?

In Durham, North Carolina, a city barely touched by the AIDS epidemic in 1987, the sound and fury of these demonstrations may have seemed like a distant thunderclap. Deeply ensconced in his trial of megadose chemotherapy at Duke University, William Peters could not possibly have predicted that this very storm was about to turn south and beat its way to his door.

The STAMP regimen—mega-dose chemotherapy for breast cancer—was gathering momentum day by day. By the winter of 1984, thirty-two women had completed the Phase I “safety” study—a trial designed to document whether STAMP could safely be administered. The data looked promising: although clearly toxic, selected patients could survive the regimen. (Phase I studies are not designed to assess efficacy.) In December that year, at the fifth annual Breast Cancer Symposium in San Antonio, Texas, there was abundant optimism about efficacy as well. “There was so much excitement within the cancer community that some were already convinced,” the statistician Donald Berry recalls. Peters was his typically charming self at the conference—boyish, exuberant, cautious, but inveterately positive. He called the meeting a “small victory.”

After San Antonio, the early-phase trials gathered speed. Emboldened by the positive response, Peters pushed for evaluating STAMP not just for metastatic breast cancer, but as an adjuvant therapy for high-risk patients with locally advanced cancer (patients with more than ten cancer-afflicted lymph nodes). Following Peters’s initial observations, several groups across the nation also hotly pursued megadose chemotherapy with bone marrow transplantation. Two years later, with early-phase trials completed successfully, a randomized, blinded, Phase III trial was needed. Peters approached the Cancer and Leukemia Group B (CALGB), the centralized group that acted as a clearinghouse for clinical trials, to sponsor a definitive multicenter, randomized clinical trial.

On a winter afternoon, Peters flew up from Duke to Boston to detail a STAMP trial to the CALGB for its approval. As expected, vicious arguments broke out in the room. Some clinicians still contended that STAMP was, in fact, no different from cytotoxic chemotherapy taken to its extreme brink—stale wine being sold in a new bottle. Others contended that the chemotherapeutic battle against cancer needed to be taken to the brink. The meeting stretched hour upon hour, each side hotly debating its points. In the end, the CALGB agreed to sponsor the trial. Peters left the conference room on the sixth floor of the Massachusetts General Hospital feeling bewildered but relieved. When the hinged saloon door of the room swung closed behind him, it was as if he had just emerged out of a nasty barroom brawl.