The Emperor of All Maladies

(#litres_trial_promo) toward death in a small room overlooking the Spanish Steps in Rome, or Byron, an obsessive romantic, who fantasized about dying of the disease to impress his mistresses. “Death and disease are often beautiful,

(#litres_trial_promo) like . . . the hectic glow of consumption,” Thoreau wrote in 1852. In Thomas Mann’s The Magic Mountain, this “hectic glow” releases a feverish creative force in its victims—a clarifying, edifying, cathartic force that, too, appears to be charged with the essence of its era.

Cancer, in contrast, is riddled with more contemporary images. The cancer cell is a desperate individualist, “in every possible sense, a nonconformist,”

(#litres_trial_promo) as the surgeon-writer Sherwin Nuland wrote. The word metastasis, used to describe the migration of cancer from one site to another, is a curious mix of meta and stasis—“beyond stillness” in Latin—an unmoored, partially unstable state that captures the peculiar instability of modernity. If consumption once killed its victims by pathological evisceration (the tuberculosis bacillus gradually hollows out the lung), then cancer asphyxiates us by filling bodies with too many cells; it is consumption in its alternate meaning—the pathology of excess. Cancer is an expansionist disease; it invades through tissues, sets up colonies in hostile landscapes, seeking “sanctuary” in one organ and then immigrating to another. It lives desperately, inventively, fiercely, territorially, cannily, and defensively—at times, as if teaching us how to survive. To confront cancer is to encounter a parallel species, one perhaps more adapted to survival than even we are.

This image—of cancer as our desperate, malevolent, contemporary doppelgänger—is so haunting because it is at least partly true. A cancer cell is an astonishing perversion of the normal cell. Cancer is a phenomenally successful invader and colonizer in part because it exploits the very features that make us successful as a species or as an organism.

Like the normal cell, the cancer cell relies on growth in the most basic, elemental sense: the division of one cell to form two. In normal tissues, this process is exquisitely regulated, such that growth is stimulated by specific signals and arrested by other signals. In cancer, unbridled growth gives rise to generation upon generation of cells. Biologists use the term clone to describe cells that share a common genetic ancestor. Cancer, we now know, is a clonal disease. Nearly every known cancer originates from one ancestral cell that, having acquired the capacity of limitless cell division and survival, gives rise to limitless numbers of descendants—Virchow’s omnis cellula e cellula e cellula repeated ad infinitum.

But cancer is not simply a clonal disease; it is a clonally evolving disease. If growth occurred without evolution, cancer cells would not be imbued with their potent capacity to invade, survive, and metastasize. Every generation of cancer cells creates a small number of cells that is genetically different from its parents. When a chemotherapeutic drug or the immune system attacks cancer, mutant clones that can resist the attack grow out. The fittest cancer cell survives. This mirthless, relentless cycle of mutation, selection, and overgrowth generates cells that are more and more adapted to survival and growth. In some cases, the mutations speed up the acquisition of other mutations. The genetic instability, like a perfect madness, only provides more impetus to generate mutant clones. Cancer thus exploits the fundamental logic of evolution unlike any other illness. If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us.

Such metaphorical seductions can carry us away, but they are unavoidable with a subject like cancer. In writing this book, I started off by imagining my project as a “history” of cancer. But it felt, inescapably, as if I were writing not about something but about someone. My subject daily morphed into something that resembled an individual—an enigmatic, if somewhat deranged, image in a mirror. This was not so much a medical history of an illness, but something more personal, more visceral: its biography.

So to begin again, for every biographer must confront the birth of his subject: Where was cancer “born”? How old is cancer? Who was the first to record it as an illness?

In 1862, Edwin Smith—an unusual character

(#litres_trial_promo): part scholar and part huckster, an antique forger and self-made Egyptologist—bought (or, some say, stole) a fifteen-foot-long papyrus from an antiques seller in Luxor in Egypt. The papyrus was in dreadful condition, with crumbling, yellow pages filled with cursive Egyptian script. It is now thought to have been written in the seventeenth century BC, a transcription of a manuscript dating back to 2500 BC. The copier—a plagiarist in a terrible hurry—had made errors as he had scribbled, often noting corrections in red ink in the margins.

Translated in 1930, the papyrus is now thought to contain the collected teachings of Imhotep, a great Egyptian physician who lived around 2625 BC. Imhotep, among the few nonroyal Egyptians known to us from the Old Kingdom, was a Renaissance man at the center of a sweeping Egyptian renaissance. As a vizier in the court of King Djozer, he dabbled in neurosurgery, tried his hand at architecture, and made early forays into astrology and astronomy. Even the Greeks, encountering the fierce, hot blast of his intellect as they marched through Egypt centuries later, cast him as an ancient magician and fused him to their own medical god, Asclepius.

But the surprising feature of the Smith papyrus is not magic and religion but the absence of magic and religion. In a world immersed in spells, incantations, and charms, Imhotep wrote about broken bones and dislocated vertebrae with a detached, sterile scientific vocabulary, as if he were writing a modern surgical textbook. The forty-eight cases in the papyrus—fractures of the hand, gaping abscesses of the skin, or shattered skull bones—are treated as medical conditions rather than occult phenomena, each with its own anatomical glossary, diagnosis, summary, and prognosis.

And it is under these clarifying headlamps of an ancient surgeon that cancer first emerges as a distinct disease. Describing case forty-five

(#litres_trial_promo), Imhotep advises, “If you examine [a case] having bulging masses on [the] breast and you find that they have spread over his breast; if you place your hand upon [the] breast [and] find them to be cool, there being no fever at all therein when your hand feels him; they have no granulations, contain no fluid, give rise to no liquid discharge, yet they feel protuberant to your touch, you should say concerning him: ‘This is a case of bulging masses I have to contend with. . . . Bulging tumors of the breast mean the existence of swellings on the breast, large, spreading, and hard; touching them is like touching a ball of wrappings, or they may be compared to the unripe hemat fruit, which is hard and cool to the touch.’ ”

A “bulging mass in the breast”—cool, hard, dense as a hemat fruit, and spreading insidiously under the skin—could hardly be a more vivid description of breast cancer. Every case in the papyrus was followed by a concise discussion of treatments, even if only palliative: milk poured through the ears of neurosurgical patients, poultices for wounds, balms for burns. But with case forty-five, Imhotep fell atypically silent. Under the section titled “Therapy,” he offered only a single sentence: “There is none.”

With that admission of impotence, cancer virtually disappeared from ancient medical history. Other diseases cycled violently through the globe, leaving behind their cryptic footprints in legends and documents. A furious febrile plague

(#litres_trial_promo)—typhus, perhaps—blazed through the port city of Avaris in 1715 BC, decimating its population. Smallpox erupted volcanically in pockets, leaving its telltale pockmarks

(#litres_trial_promo) on the face of Ramses V in the twelfth century BC. Tuberculosis rose and ebbed

(#litres_trial_promo) through the Indus valley like its seasonal floods. But if cancer existed in the interstices of these massive epidemics, it existed in silence, leaving no easily identifiable trace in the medical literature—or in any other literature.

More than two millennia pass after Imhotep’s description until we once more hear of cancer. And again, it is an illness cloaked in silence, a private shame. In his sprawling Histories,

(#litres_trial_promo) written around 440 BC, the Greek historian Herodotus records the story of Atossa, the queen of Persia, who was suddenly struck by an unusual illness. Atossa was the daughter of Cyrus, and the wife of Darius, successive Achaemenid emperors of legendary brutality who ruled over a vast stretch of land from Lydia on the Mediterranean Sea to Babylonia on the Persian Gulf. In the middle of her reign, Atossa noticed a bleeding lump in her breast that may have arisen from a particularly malevolent form of breast cancer labeled inflammatory (in inflammatory breast cancer, malignant cells invade the lymph glands of the breast, causing a red, swollen mass).

If Atossa had desired it, an entire retinue of physicians from Babylonia to Greece would have flocked to her bedside to treat her. Instead, she descended into a fierce and impenetrable loneliness. She wrapped herself in sheets, in a self-imposed quarantine. Darius’ doctors may have tried to treat her, but to no avail. Ultimately, a Greek slave named Democedes persuaded her to allow him to excise the tumor.

Soon after that operation, Atossa mysteriously vanishes from Herodotus’ text. For him, she is merely a minor plot twist. We don’t know whether the tumor recurred, or how or when she died, but the procedure was at least a temporary success. Atossa lived, and she had Democedes to thank for it. And that reprieve from pain and illness whipped her into a frenzy of gratitude and territorial ambition. Darius had been planning a campaign against Scythia, on the eastern border of his empire. Goaded by Democedes, who wanted to return to his native Greece, Atossa pleaded with her husband to turn his campaign westward—to invade Greece. That turn of the Persian empire from east to west, and the series of Greco-Persian wars that followed, would mark one of the definitive moments in the early history of the West. It was Atossa’s tumor, then, that quietly launched a thousand ships. Cancer, even as a clandestine illness, left its fingerprints on the ancient world.

But Herodotus and Imhotep are storytellers, and like all stories, theirs have gaps and inconsistencies. The “cancers” described by them may have been true neoplasms, or perhaps they were hazily describing abscesses, ulcers, warts, or moles. The only incontrovertible cases of cancer in history are those in which the malignant tissue has somehow been preserved. And to encounter one such cancer face-to-face—to actually stare the ancient illness in its eye—one needs to journey to a thousand-year-old gravesite in a remote, sand-swept plain in the southern tip of Peru.

The plain lies at the northern edge of the Atacama Desert, a parched, desolate six-hundred-mile strip caught in the leeward shadow of the giant furl of the Andes that stretches from southern Peru into Chile. Brushed continuously by a warm, desiccating wind, the terrain hasn’t seen rain in recorded history. It is hard to imagine that human life once flourished here, but it did. The plain is strewn with hundreds of graves—small, shallow pits dug out of the clay, then lined carefully with rock. Over the centuries, dogs, storms, and grave robbers have dug out these shallow graves, exhuming history.

The graves contain the mummified remains of members of the Chiribaya tribe. The Chiribaya made no effort to preserve their dead, but the climate is almost providentially perfect for mummification. The clay leaches water and fluids out of the body from below, and the wind dries the tissues from above. The bodies, often placed seated, are thus swiftly frozen in time and space.

In 1990, one such large desiccated gravesite containing about 140 bodies caught the attention of Arthur Aufderheide, a professor at the University of Minnesota in Duluth. Aufderheide is a pathologist by training but his specialty is paleopathology, a study of ancient specimens. His autopsies, unlike Farber’s, are not performed on recently living patients, but on the mummified remains found on archaeological sites. He stores these human specimens in small, sterile milk containers in a vaultlike chamber in Minnesota. There are nearly five thousand pieces of tissue, scores of biopsies, and hundreds of broken skeletons in his closet.

At the Chiribaya site

(#litres_trial_promo), Aufderheide rigged up a makeshift dissecting table and performed 140 autopsies over several weeks. One body revealed an extraordinary finding. The mummy was of a young woman in her midthirties, found sitting, with her feet curled up, in a shallow clay grave. When Aufderheide examined her, his fingers found a hard “bulbous mass” in her left upper arm. The papery folds of skin, remarkably preserved, gave way to that mass, which was intact and studded with spicules of bone. This, without question, was a malignant bone tumor, an osteosarcoma, a thousand-year-old cancer preserved inside of a mummy. Aufderheide suspects that the tumor had broken through the skin while she was still alive. Even small osteosarcomas can be unimaginably painful. The woman’s pain, he suggests, must have been blindingly intense.

Aufderheide isn’t the only paleopathologist to have found cancers in mummified specimens. (Bone tumors, because they form hardened and calcified tissue, are vastly more likely to survive over centuries and are best preserved.) “There are other cancers found in mummies where the malignant tissue has been preserved. The oldest of these is an abdominal cancer from Dakhleh in Egypt from about four hundred AD,” he said. In other cases, paleopathologists have not found the actual tumors, but rather signs left by the tumors in the body. Some skeletons were riddled with tiny holes created by cancer in the skull or the shoulder bones, all arising from metastatic skin or breast cancer. In 1914, a team

(#litres_trial_promo) of archaeologists found a two-thousand-year old Egyptian mummy in the Alexandrian catacombs with a tumor invading the pelvic bone. Louis Leakey,

(#litres_trial_promo) the anthropologist who dug up some of the earliest known human skeletons, also discovered a jawbone dating from two million years ago from a nearby site that carried the signs of a peculiar form of lymphoma found endemically in southeastern Africa (although the origin of that tumor was never confirmed pathologically). If that finding does represent an ancient mark of malignancy, then cancer, far from being a “modern” disease, is one of the oldest diseases ever seen in a human specimen—quite possibly the oldest.

The most striking finding, though, is not that cancer existed in the distant past, but that it was fleetingly rare. When I asked Aufderheide about this, he laughed. “The early history of cancer,”

(#litres_trial_promo) he said, “is that there is very little early history of cancer.” The Mesopotamians knew their migraines; the Egyptians had a word for seizures. A leprosy-like illness

(#litres_trial_promo), tsara’at, is mentioned in the book of Leviticus. The Hindu Vedas have a medical term for dropsy and a goddess specifically dedicated to smallpox. Tuberculosis was so omnipresent and familiar to the ancients that—as with ice and the Eskimos—distinct words exist for each incarnation of it. But even common cancers, such as breast, lung, and prostate, are conspicuously absent. With a few notable exceptions, in the vast stretch of medical history there is no book or god for cancer.

There are several reasons behind this absence. Cancer is an age-related disease—sometimes exponentially so. The risk of breast cancer

(#litres_trial_promo), for instance, is about 1 in 400 for a thirty-year-old woman and increases to 1 in 9 for a seventy-year-old. In most ancient societies, people didn’t live long enough to get cancer. Men and women were long consumed by tuberculosis, dropsy, cholera, smallpox, leprosy, plague, or pneumonia. If cancer existed, it remained submerged under the sea of other illnesses. Indeed, cancer’s emergence in the world is the product of a double negative: it becomes common only when all other killers themselves have been killed. Nineteenth-century doctors often linked cancer to civilization: cancer, they imagined, was caused by the rush and whirl of modern life, which somehow incited pathological growth in the body. The link was correct, but the causality was not: civilization did not cause cancer, but by extending human life spans—civilization unveiled it.

Longevity, although certainly the most important contributor to the prevalence of cancer in the early twentieth century, is probably not the only contributor. Our capacity to detect cancer earlier and earlier, and to attribute deaths accurately to it, has also dramatically increased in the last century. The death of a child with leukemia in the 1850s would have been attributed to an abscess or infection (or, as Bennett would have it, to a “suppuration of blood”). And surgery, biopsy, and autopsy techniques have further sharpened our ability to diagnose cancer. The introduction of mammography to detect breast cancer early in its course sharply increased its incidence—a seemingly paradoxical result that makes perfect sense when we realize that the X-rays allow earlier tumors to be diagnosed.

Finally, changes in the structure of modern life have radically shifted the spectrum of cancers—increasing the incidence of some, decreasing the incidence of others. Stomach cancer, for instance, was highly prevalent in certain populations until the late nineteenth century, likely the result of several carcinogens found in pickling reagents and preservatives and exacerbated by endemic and contagious infection with a bacterium that causes stomach cancer. With the introduction of modern refrigeration (and possibly changes in public hygiene that have diminished the rate of endemic infection), the stomach cancer epidemic seems to have abated. In contrast, lung cancer incidence in men increased dramatically in the 1950s as a result of an increase in cigarette smoking during the early twentieth century. In women, a cohort that began to smoke in the 1950s, lung cancer incidence has yet to reach its peak.

The consequence of these demographic and epidemiological shifts was, and is, enormous. In 1900, as Roswell Park noted, tuberculosis was by far the most common cause of death in America. Behind tuberculosis came pneumonia (William Osler, the famous physician from Johns Hopkins University, called it “captain of the men of death”

(#litres_trial_promo)), diarrhea, and gastroenteritis. Cancer still lagged

(#litres_trial_promo) at a distant seventh. By the early 1940s, cancer

(#litres_trial_promo) had ratcheted its way to second on the list, immediately behind heart disease. In that same span, life expectancy among Americans

(#litres_trial_promo) had increased by about twenty-six years. The proportion of persons above sixty years—the age when most cancers begin to strike—nearly doubled.

But the rarity of ancient cancers notwithstanding, it is impossible to forget the tumor growing in the bone of Aufderheide’s mummy of a thirty-five-year-old. The woman must have wondered about the insolent gnaw of pain in her bone, and the bulge slowly emerging from her arm. It is hard to look at the tumor and not come away with the feeling that one has encountered a powerful monster in its infancy.

Onkos (#ulink_c0ce9fa0-a28f-5a53-a184-bbd9167aac4a)

Black bile without boiling

(#litres_trial_promo) causes cancers.

—Galen, AD 130