The Emperor of All Maladies. Siddhartha Mukherjee
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with cancer—cancer-curing at times, cancer-causing at others—dampened the initial enthusiasm of cancer scientists. Radiation was a powerful invisible knife—but still a knife. And a knife, no matter how deft or penetrating, could only reach so far in the battle against cancer. A more discriminating therapy was needed, especially for cancers that were nonlocalized.
In 1932, Willy Meyer200, the New York surgeon who had invented the radical mastectomy contemporaneously with Halsted, was asked to address the annual meeting of the American Surgical Association. Gravely ill and bedridden, Meyer knew he would be unable to attend the meeting, but he forwarded a brief, six-paragraph speech to be presented. On May 31, six weeks after Meyer’s death, his letter was read aloud to the roomful of surgeons. There is, in that letter, an unfailing recognition that cancer medicine had reached some terminus, that a new direction was needed. “If a biological systemic after-treatment were added in every instance,” Meyer wrote, “we believe the majority of such patients would remain cured after a properly conducted radical operation.”
Meyer had grasped a deep principle about cancer. Cancer, even when it begins locally, is inevitably waiting to explode out of its confinement. By the time many patients come to their doctor, the illness has often spread beyond surgical control and spilled into the body exactly like the black bile that Galen had envisioned so vividly nearly two thousand years ago.
In fact, Galen seemed to have been right after all—in the accidental, aphoristic way that Democritus had been right about the atom or Erasmus had made a conjecture about the Big Bang centuries before the discovery of galaxies. Galen had, of course, missed the actual cause of cancer. There was no black bile clogging up the body and bubbling out into tumors in frustration. But he had uncannily captured something essential about cancer in his dreamy and visceral metaphor. Cancer was often a humoral disease. Crablike and constantly mobile, it could burrow through invisible channels from one organ to another. It was a “systemic” illness, just as Galen had once made it out to be.
Those who have not been trained in chemistry201 or medicine may not realize how difficult the problem of cancer treatment really is. It is almost—not quite, but almost—as hard as finding some agent that will dissolve away the left ear, say, and leave the right ear unharmed. So slight is the difference between the cancer cell and its normal ancestor.
—William Woglom
Life is . . . a chemical incident202.
—Paul Ehrlich
—as a schoolboy, 1870
A systemic disease demands a systemic cure—but what kind of systemic therapy could possibly cure cancer? Could a drug, like a microscopic surgeon, perform an ultimate pharmacological mastectomy—sparing normal tissue while excising cancer cells? Willy Meyer wasn’t alone in fantasizing about such a magical therapy—generations of doctors before him had also fantasized about such a medicine. But how might a drug coursing through the whole body specifically attack a diseased organ?
Specificity refers to the ability of any medicine to discriminate between its intended target and its host. Killing a cancer cell in a test tube is not a particularly difficult task: the chemical world is packed with malevolent poisons that, even in infinitesimal quantities, can dispatch a cancer cell within minutes. 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. For an anticancer poison to become a useful drug, Meyer knew, it needed to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient.
The hunt for such specific, systemic poisons for cancer was precipitated by the search for a very different sort of chemical. The story begins with colonialism and its chief loot: cotton. In the mid-1850s, as ships from India and Egypt laden with bales of cotton unloaded their goods in English ports, cloth milling boomed into a spectacularly successful business in England, an industry large enough to sustain an entire gamut of subsidiary industries. A vast network of mills sprouted up in the industrial basin of the Midlands, stretching through Glasgow, Lancashire, and Manchester. Textile exports dominated the British economy. Between 1851 and 1857203, the export of printed goods from England more than quadrupled—from 6 million to 27 million pieces per year. In 1784, cotton products had represented a mere 6 percent of total British exports. By the 1850s, that proportion had peaked204 at 50 percent.
The cloth-milling boom set off a boom in cloth dyeing, but the two industries—cloth and color—were oddly out of technological step. Dyeing, unlike milling, was still a preindustrial occupation. Cloth dyes had to be extracted205 from perishable vegetable sources—rusty carmines from Turkish madder root, or deep blues from the indigo plant—using antiquated processes that required patience, expertise, and constant supervision. Printing on textiles with colored dyes (to produce the ever-popular calico prints206, for instance) was even more challenging—requiring thickeners, mordants, and solvents in multiple steps—and often took the dyers weeks to complete. The textile industry thus needed professional chemists to dissolve its bleaches and cleansers, to supervise the extraction of dyes, and to find ways to fasten the dyes on cloth. A new discipline called practical chemistry, focused on synthesizing products for textile dyeing, was soon flourishing in polytechnics and institutes all over London.
In 1856, William Perkin, an eighteen-year-old student at one of these institutes, stumbled on what would soon become a Holy Grail of this industry: an inexpensive chemical dye that could be made entirely from scratch. In a makeshift one-room laboratory in his apartment in the East End of London (“half of a small but long-shaped room207 with a few shelves for bottles and a table”) Perkin was boiling nitric acid and benzene in smuggled glass flasks and precipitated an unexpected reaction. A chemical had formed inside the tubes with the color of pale, crushed violets. In an era obsessed with dye-making, any colored chemical was considered a potential dye—and a quick dip of a piece of cotton into the flask revealed the new chemical could color cotton. Moreover, this new chemical did not bleach or bleed. Perkin called it aniline mauve.
Perkin’s discovery was a godsend for the textile industry. Aniline mauve was cheap and imperishable—vastly easier to produce and store than vegetable dyes. As Perkin soon discovered, its parent compound could act as a molecular building block for other dyes, a chemical skeleton on which a variety of side chains could be hung to produce a vast spectrum of vivid colors. By the mid-1860s, a glut of new synthetic dyes, in shades of lilac, blue, magenta, aquamarine, red, and purple flooded the cloth factories of Europe. In 1857, Perkin, barely nineteen years old, was inducted into the Chemical Society of London as a full fellow, one of the youngest in its history to be thus honored.
Aniline mauve was discovered in England, but dye making reached its chemical zenith in Germany. In the late 1850s, Germany, a rapidly industrializing nation, had been itching to compete in the cloth markets of Europe and America. But unlike England, Germany had scarcely any access to natural dyes: by the time it had entered the scramble to capture colonies, the world had already been sliced up into so many parts, with little left to divide. German cloth millers thus threw themselves into the development of artificial dyes, hoping to rejoin an industry that they had once almost given up as a lost cause.
Dye making in England had rapidly become an intricate chemical business. In Germany—goaded by the textile industry, cosseted by national subsidies, and driven by expansive economic growth—synthetic chemistry underwent an even more colossal boom. In 1883, the German output of alizarin208, the brilliant red chemical that imitated natural carmine, reached twelve thousand tons, dwarfing the amount being produced by Perkin’s