The Emperor of All Maladies: A Biography of Cancer (3 page)

How, precisely, a future generation might learn to separate the entwined strands of normal growth from malignant growth remains a mystery. (
“The universe,” the twentieth-century biologist
J. B. S. Haldane liked to say, “is not only queerer than we suppose, but queerer than we
can
sup
pose”—and so is the trajectory of science.) But this much is certain: the story, however it plays out, will contain indelible kernels of the past. It will be a story of inventiveness, resilience, and perseverance against what one writer called the most “relentless and insidious enemy” among human diseases. But it will also be a story of hubris, arrogance, paternalism, misperception, false hope, and hype, all leveraged against an illness that was just three decades ago widely touted as being “curable” within a few years.

In the bare hospital room ventilated by sterilized air, Carla was fighting her own war on cancer. When I arrived, she was sitting with peculiar calm on her bed, a schoolteacher jotting notes. (“But what notes?” she would later recall. “I just wrote and rewrote the same thoughts.”) Her mother, red-eyed and tearful, just off an overnight flight, burst into the room and then sat silently in a chair by the window, rocking forcefully. The din of activity around Carla had become almost a blur: nurses shuttling fluids in and out, interns donning masks and gowns, antibiotics being hung on IV poles to be dripped into her veins.

I explained the situation as best I could. Her day ahead would be full of tests, a hurtle from one lab to another. I would draw a bone marrow sample. More tests would be run by pathologists. But the preliminary tests suggested that Carla had acute lymphoblastic leukemia. It is one of the most common forms of cancer in children, but rare in adults. And it is—I paused here for emphasis, lifting my eyes up—often curable.

Curable.
Carla nodded at that word, her eyes sharpening. Inevitable questions hung in the room: How curable? What were the chances that she would survive? How long would the treatment take? I laid out the odds. Once the diagnosis had been confirmed, chemotherapy would begin immediately and last more than one year. Her chances of being cured were about 30 percent, a little less than one in three.

We spoke for an hour, perhaps longer. It was now nine thirty in the morning. The city below us had stirred fully awake. The door shut behind me as I left, and a whoosh of air blew me outward and sealed Carla in.

PART ONE
 
“OF BLACKE CHOLOR,
WITHOUT BOYLING”

In solving a problem of this sort
, the grand thing is to be able to reason backwards. That is a very useful accomplishment, and a very easy one, but people do not practice it much.

—Sherlock Holmes, in Sir Arthur Conan Doyle’s
A Study in Scarlet

Physicians of the Utmost Fame

Were called at once; but when they came

They answered, as they took their Fees,

“There is no Cure for this Disease.”

—Hilaire Belloc

Its palliation is a daily task
, its cure a fervent hope.

—William Castle,
describing leukemia in 1950

In a damp
fourteen-by-twenty-foot laboratory in Boston on a December morning in 1947, a man named Sidney Farber waited impatiently for the arrival of a parcel from New York. The “laboratory” was little more than a chemist’s closet, a poorly ventilated room buried in a half-basement of the Children’s Hospital, almost thrust into its back alley. A few hundred feet away, the hospital’s medical wards were slowly thrumming to work. Children in white smocks moved restlessly on small wrought-iron cots. Doctors and nurses shuttled busily between the rooms, checking charts, writing orders, and dispensing medicines. But Farber’s lab was listless and empty, a bare warren of chemicals and glass jars connected to the main hospital through a series of icy corridors. The sharp stench of embalming formalin wafted through the air. There were no patients in the rooms here, just the bodies and tissues of patients brought down through the tunnels for autopsies and examinations. Farber was a pathologist. His job involved dissecting specimens, performing autopsies, identifying cells, and diagnosing diseases, but never treating patients.

Farber’s specialty was pediatric pathology
, the study of children’s dis
eases. He had spent nearly twenty years in these subterranean rooms staring obsessively down his microscope and climbing through the academic ranks to become chief of pathology at Children’s. But for Farber, pathology was becoming a disjunctive form of medicine, a discipline more preoccupied with the dead than with the living. Farber now felt impatient watching illness from its sidelines, never touching or treating a live patient. He was tired of tissues and cells. He felt trapped, embalmed in his own glassy cabinet.

And so, Farber had decided to make a drastic professional switch. Instead of squinting at inert specimens under his lens, he would try to leap into the life of the clinics upstairs—from the microscopic world that he knew so well into the magnified real world of patients and illnesses. He would try to use the knowledge he had gathered from his pathological specimens to devise new therapeutic interventions. The parcel from New York contained a few vials of a yellow crystalline chemical named aminopterin. It had been shipped to his laboratory in Boston on the slim hope that it might halt the growth of leukemia in children.

Had Farber asked any of the pediatricians circulating in the wards above him about the likelihood of developing an antileukemic drug, they would have advised him not to bother trying. Childhood leukemia had fascinated, confused, and frustrated doctors for more than a century. The disease had been analyzed, classified, subclassified, and subdivided meticulously; in the musty, leatherbound books on the library shelves at Children’s—Anderson’s
Pathology
or Boyd’s
Pathology of Internal Diseases
—page upon page was plastered with images of leukemia cells and appended with elaborate taxonomies to describe the cells. Yet all this knowledge only amplified the sense of medical helplessness. The disease had turned into an object of empty fascination—a wax-museum doll—studied and photographed in exquisite detail but without any therapeutic or practical advances. “
It gave physicians plenty to wrangle over
at medical meetings,” an oncologist recalled, “but it did not help their patients at all.” A patient with acute leukemia was brought to the hospital in a flurry of excitement, discussed on medical rounds with professorial grandiosity, and then, as a medical magazine drily noted, “
diagnosed, transfused—and sent home to die
.”

The study of leukemia had been mired in confusion and despair ever
since its discovery. On March 19, 1845, a Scottish physician, John Bennett, had described an unusual case, a twenty-eight-year-old slate-layer with a mysterious swelling in his spleen. “
He is of dark complexion
,” Bennett wrote of his patient, “usually healthy and temperate; [he] states that twenty months ago, he was affected with great listlessness on exertion, which has continued to this time. In June last he noticed a tumor in the left side of his abdomen which has gradually increased in size till four months since, when it became stationary.”

The slate-layer’s tumor might have reached its final, stationary point, but his constitutional troubles only accelerated. Over the next few weeks, Bennett’s patient spiraled from symptom to symptom—fevers, flashes of bleeding, sudden fits of abdominal pain—gradually at first, then on a tighter, faster arc, careening from one bout to another. Soon the slate-layer was on the verge of death with more swollen tumors sprouting in his armpits, his groin, and his neck. He was treated with the customary leeches and purging, but to no avail. At the autopsy a few weeks later, Bennett was convinced that he had found the reason behind the symptoms. His patient’s blood was chock-full of white blood cells. (White blood cells, the principal constituent of pus, typically signal the response to an infection, and Bennett reasoned that the slate-layer had succumbed to one.) “The following case seems to me particularly valuable,” he wrote self-assuredly, “as it will serve to demonstrate the existence of true pus, formed universally within the vascular system.”
*

It would have been a perfectly satisfactory explanation except that Bennett could not find a source for the pus. During the necropsy, he pored carefully through the body, combing the tissues and organs for signs of an abscess or wound. But no other stigmata of infection were to be found. The blood had apparently spoiled—suppurated—of its own will, combusted spontaneously into true pus. “
A suppuration of blood
,” Bennett called his case. And he left it at that.

Bennett was wrong, of course, about his spontaneous “suppuration” of blood. A little over four months after Bennett had described the slater’s illness, a twenty-four-year-old German researcher,
Rudolf
Virchow, independently published a case report with striking similarities to Bennett’s
case. Virchow’s patient was a cook in her midfifties. White cells had explosively overgrown her blood, forming dense and pulpy pools in her spleen. At her autopsy, pathologists had likely not even needed a microscope to distinguish the thick, milky layer of white cells floating above the red.

Virchow, who knew of Bennett’s case, couldn’t bring himself to believe Bennett’s theory. Blood, Virchow argued, had no reason to transform impetuously into anything. Moreover, the unusual symptoms bothered him: What of the massively enlarged spleen? Or the absence of any wound or source of pus in the body? Virchow began to wonder if the blood itself was abnormal. Unable to find a unifying explanation for it, and s
eeking a name for this condition
, Virchow ultimately settled for
weisses Blut
—white blood—no more than a literal description of the millions of white cells he had seen under his microscope. In 1847, he changed the name to the more academic-sounding “leukemia”—from
leukos
, the Greek word for “white.”

Renaming the disease—from the florid “suppuration of blood” to the flat
weisses Blut
—hardly seems like an act of scientific genius, but it had a profound impact on the understanding of leukemia. An illness, at the moment of its discovery, is a fragile idea, a hothouse flower—deeply, disproportionately influenced by names and classifications. (More than a century later,
in the early 1980s, another change in name
—from
gay related immune disease
(GRID) to
acquired immuno deficiency syndrome
(AIDS)—would signal an epic shift in the understanding of that disease.
^*
) Like Bennett, Virchow didn’t understand leukemia. But unlike Bennett, he didn’t pretend to understand it. His insight lay entirely in the negative. By wiping the slate clean of all preconceptions, he cleared the field for thought.