The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place. —Susan Sontag

Cancer cells can grow faster, adapt better. They are more perfect versions of ourselves.

Malignant growth and normal growth are so genetically intertwined that unbraiding the two might be one of the most significant scientific challenges faced by our species.

An illness, at the moment of its discovery, is a fragile idea, a hothouse flower—deeply, disproportionately influenced by names and classifications.

When the heart muscle is forced to push against a blocked aortic outlet, it often adapts by making every muscle cell bigger to generate more force, eventually resulting in a heart so overgrown that it may be unable to function normally—pathological hypertrophy.

the quintessential disease of pathological hyperplasia—cancer.

neoplasia—novel, inexplicable, distorted growth, a word that would ring through the history of cancer.*

In acute lymphoblastic leukemia, as in some other cancers, the overproduction of cancer cells is combined with a mysterious arrest in the normal maturation of cells.

Although superficially amorphous, bone marrow is a highly organized tissue—an organ, in truth—that generates blood in adults. Typically, bone marrow biopsies contain spicules of bone and, within these spicules, islands of growing blood cells—nurseries for the genesis of new blood. In Carla’s marrow, this organization had been fully destroyed. Sheet upon sheet of malignant blasts packed the marrow space, obliterating all anatomy and architecture, leaving no space for any production of blood.

Science begins with counting. To understand a phenomenon, a scientist must first describe it; to describe it objectively, he must first measure it. If cancer medicine was to be transformed into a rigorous science, then cancer would need to be counted somehow—measured in some reliable, reproducible way.

Penicillin, that precious chemical that had to be milked to its last droplet during World War II (in 1939, the drug was reextracted from the urine of patients who had been treated with it to conserve every last molecule), was by the early fifties being produced in thousand-gallon vats.

To cure cancer (if it could be cured at all), doctors had only two strategies: excising the tumor surgically or incinerating it with radiation—a choice between the hot ray and the cold knife.

Eight thousand miles away, in the cloth mills of Bombay (owned by English traders and managed by their cutthroat local middlemen), wages had been driven to such low levels that the mill workers lived in abject poverty, malnourished and without medical care. When English physicians tested these mill workers in the 1920s to study the effects of this chronic malnutrition, they discovered that many of them, particularly women after childbirth, were severely anemic. (This was yet another colonial fascination: to create the conditions of misery in a population, then subject it to social or medical experimentation.)

When cells divide, they need to make copies of DNA—the chemical that carries all the genetic information in a cell. Folic acid is a crucial building block for DNA and is thus vital for cell division. Since blood cells are produced by arguably the most fearsome rate of cell division in the human body—more than 300 billion cells a day—the genesis of blood is particularly dependent on folic acid. In its absence (in men and women starved of vegetables, as in Bombay) the production of new blood cells in the bone marrow halts.

We reveal ourselves in the metaphors we choose for depicting the cosmos in miniature. —Stephen Jay Gould

Both drain vitality; both stretch out the encounter with death; in both cases, dying, even more than death, defines the illness.

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.

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.

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.

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.

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.

(Bone tumors, because they form hardened and calcified tissue, are vastly more likely to survive over centuries and are best preserved.)

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.

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.

civilization did not cause cancer, but by extending human life spans—civilization unveiled it.

To name an illness is to describe a certain condition of suffering—a literary act before it becomes a medical one. A patient, long before he becomes the subject of medical scrutiny, is, at first, simply a storyteller, a narrator of suffering—a traveler who has visited the kingdom of the ill. To relieve an illness, one must begin, then, by unburdening its story.

Typhus, a stormy disease, with erratic, vaporous fevers, arose from the Greek tuphon, the father of winds—a word that also gives rise to the modern typhoon.

Influenza emerged from the Latin influentia because medieval doctors imagined that the cyclical epidemics of flu were influenced by stars and planets...

Tuberculosis coagulated out of the Latin tuber, referring to the swollen lumps of glands that l...

Lymphatic tuberculosis, TB of the lymph glands, was called scrofula, from the Latin word for “piglet,” evoking the rather morbid image of a chain of swollen glands arr...

It was in the time of Hippocrates, around 400 BC, that a word for cancer first appeared in the medical literature: karkinos, from the Greek word for “crab.” The tumor, with its clutch of swollen blood vessels around it, reminded Hippocra...

Another Greek word would intersect with the history of cancer—onkos, a word used occasionally to describe tumors, from which the discipline of oncology would take its modern name. Onkos was the Greek term for a mass or a load, or more commonly a burden; cancer was imagined as a burden carried by the body. In Greek theater, the same word, onkos, would be used to denote a tragic mask that was often “burdened” with an unwieldy conical weight on its head to denote the psychic load carried by its wearer.

Indeed, melancholia, the medieval name for “depression,” would draw its name from the Greek melas, “black,” and khole, “bile.” Depression and cancer, the psychic and physical diseases of black bile, were thus intrinsically intertwined.)

The gibbet and the graveyard—the convenience stores for the medieval anatomist—yielded

The word autopsy comes from the Greek “to see for oneself”;

Those who survived the terrifying crucible of the operating table often died even more miserable deaths in their own beds soon afterward.

Antisepsis and anesthesia were twin technological breakthroughs that released surgery from its constraining medieval chrysalis.

Billroth studied music and surgery with almost equal verve. (The professions still often go hand in hand. Both push manual skill to its limit; both mature with practice and age; both depend on immediacy, precision, and opposable thumbs.)

Surgery remains the mainstay in the treatment of localized tumors.

Halsted read a paper describing the use of a new surgical anesthetic called cocaine. At Halle, in Volkmann’s clinic, he had watched German surgeons perform operations using this drug; it was cheap, accessible, foolproof, and easy to dose—the fast food of surgical anesthesia.

radium was attacking DNA. DNA is an inert molecule, exquisitely resistant to most chemical reactions, for its job is to maintain the stability of genetic information. But X-rays can shatter strands of DNA or generate toxic chemicals that corrode DNA. Cells respond to this damage by dying or, more often, by ceasing to divide. X-rays thus preferentially kill the most rapidly proliferating cells in the body, cells in the skin, nails, gums, and blood.

The very effect of X-rays killing rapidly dividing cells—DNA damage—also created cancer-causing mutations in genes.

The trouble lies in finding a selective poison—a drug that will kill cancer without annihilating the patient. Systemic therapy without specificity is an indiscriminate bomb.

That a chemical produced by natural organisms could be derived so easily in a flask threatened to overturn the entire conception of living organisms: for centuries, the chemistry of living organisms was thought to be imbued with some mystical property, a vital essence that could not be duplicated in a laboratory—a theory called vitalism. Wöhler’s experiment demolished vitalism. Organic and inorganic chemicals, he proved, were interchangeable. Biology was chemistry: perhaps even a human body was no different from a bag of busily reacting chemicals—a beaker with arms, legs, eyes, brain, and soul.

Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old.

The campaign against cancer, Farber learned, was much like a political campaign: it needed icons, mascots, images, slogans—the strategies of advertising as much as the tools of science. For any illness to rise to political prominence, it needed to be marketed, just as a political campaign needed marketing. A disease needed to be transformed politically before it could be transformed scientifically.

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.”

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.

A model is a lie that helps you see the truth.