The Emperor of All Maladies: A Biography of Cancer (16 page)

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 extracted
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 prints
, 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 room
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 alizarin
, the brilliant red chemical that imitated natural carmine, reached twelve thousand tons, dwarfing the amount being produced by Perkin’s factory in London. German chemists rushed to produce brighter, stronger, cheaper chemicals and muscled their way into textile factories all around Europe. By the mid-1880s, Germany had emerged as the champion of the chemical arms race (which presaged a much uglier military one) to become the “dye basket” of Europe.

Initially, the German textile chemists lived entirely in the shadow of the dye industry. But emboldened by their successes, the chemists began to synthesize not just dyes and solvents, but an entire universe of new molecules: phenols, alcohols, bromides, alkaloids, alizarins, and amides, chemicals never encountered in nature. By the late 1870s, synthetic chemists in Germany had created more molecules than they knew what to do with. “Practical chemistry” had become almost a caricature of itself: an indus
try seeking a practical purpose for the products that it had so frantically raced to invent.

Early interactions between synthetic chemistry and medicine had largely been disappointing. Gideon Harvey, a seventeenth-century physician, had once called chemists the “
most impudent, ignorant, flatulent, fleshy
, and vainly boasting sort of mankind.” The mutual scorn and animosity between the two disciplines had persisted. In 1849, August Hofmann, William Perkin’s teacher at the Royal College, gloomily acknowledged the chasm between medicine and chemistry: “
None of these compounds have, as yet
, found their way into any of the appliances of life. We have not been able to use them . . . for curing disease.”

But even Hofmann knew that the boundary between the synthetic world and the natural world was inevitably collapsing.
In 1828, a Berlin scientist named Friedrich Wöhler
had sparked a metaphysical storm in science by boiling ammonium cyanate, a plain, inorganic salt, and creating urea, a chemical typically produced by the kidneys. The Wöhler experiment—seemingly trivial—had enormous implications. Urea was a “natural” chemical, while its precursor was an inorganic salt. 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.

With vitalism dead, the extension of this logic to medicine was inevitable. If the chemicals of life could be synthesized in a laboratory, could they work on living systems? If biology and chemistry were so interchangeable, could a molecule concocted in a flask affect the inner workings of a biological organism?

Wöhler was a physician himself, and with his students and collaborators he tried to backpedal from the chemical world into the medical one. But his synthetic molecules were still much too simple—mere stick figures of chemistry where vastly more complex molecules were needed to intervene on living cells.

But such multifaceted chemicals already existed: the laboratories of the dye factories of Frankfurt were full of them. To build his interdisciplinary bridge between biology and chemistry, Wöhler only needed to take a short day-trip from his laboratory in Göttingen to the labs of Frankfurt. But neither Wöhler nor his students could make that last connection. The vast panel of molecules sitting idly on the shelves of the German textile chemists, the precursors of a revolution in medicine, may as well have been a continent away.

It took a full fifty years after Wöhler’s urea experiment for the products of the dye industry to finally make physical contact with living cells.
In 1878, in Leipzig, a twenty-four-year-old
medical student, Paul Ehrlich, hunting for a thesis project, proposed using cloth dyes—aniline and its colored derivatives—to stain animal tissues. At best, Ehrlich hoped that the dyes might stain the tissues to make microscopy easier. But to his astonishment, the dyes were far from indiscriminate darkening agents. Aniline derivatives stained only parts of the cell, silhouetting certain structures and leaving others untouched. The dyes seemed able to discriminate among chemicals hidden inside cells—binding some and sparing others.

This molecular specificity, encapsulated so vividly in that reaction between a dye and a cell, began to haunt Ehrlich.
In 1882, working with Robert Koch
, he discovered yet another novel chemical stain, this time for mycobacteria, the organisms that Koch had discovered as the cause of tuberculosis. A few years later, Ehrlich found that certain toxins, injected into animals, could generate “antitoxins,” which bound and inactivated poisons with extraordinary specificity (these antitoxins would later be identified as antibodies). He purified a potent serum against diphtheria toxin from the blood of horses, then moved to the Institute for Sera Research and Serum Testing in Steglitz to prepare this serum in gallon buckets, and then to Frankfurt to set up his own laboratory.

But the more widely Ehrlich explored the biological world, the more he spiraled back to his original idea. The biological universe was full of molecules picking out their partners like clever locks designed to fit a key: toxins clinging inseparably to antitoxins, dyes that highlighted only particular parts of cells, chemical stains that could nimbly pick out one class of germs from a mixture of microbes. If biology was an elaborate mix-and-match game of chemicals, Ehrlich reasoned, what if some chemical
could discriminate bacterial cells from animal cells—and kill the former without touching the host?

Returning from a conference late one evening, in the cramped compartment of a night train from Berlin to Frankfurt, Ehrlich animatedly described his idea to two fellow scientists, “
It has occurred to me
that . . . it should be possible to find artificial substances which are really and specifically curative for certain diseases, not merely palliatives acting favorably on one or another symptom. . . . Such curative substances—
a priori
—must directly destroy the microbes responsible for the disease; not by ‘action from a distance,’ but only when the chemical compound is fixed by the parasites. The parasites can only be killed if the chemical compound has a particular relation, a specific affinity for them.”

By then, the other inhabitants of Ehrlich’s train compartment had dozed off to sleep. But this rant in a train compartment was one of medicine’s most important ideas in its distilled, primordial form. “Chemotherapy,” the use of specific chemicals to heal the diseased body, was conceptually born in the middle of the night.

Ehrlich began looking for his “curative substances” in a familiar place: the treasure trove of dye-industry chemicals that had proved so crucial to his earlier biological experiments.
His laboratory was now physically situated
near the booming dye factories of Frankfurt—the Frankfurter Anilinfarben-Fabrik and the Leopold Cassella Company—and he could easily procure dye chemicals and derivatives via a short walk across the valley. With thousands of compounds available to him, Ehrlich embarked on a series of experiments to test their biological effects in animals.

He began with a hunt for antimicrobial chemicals, in part because he already knew that chemical dyes could specifically bind microbial cells. He infected mice and rabbits with
Trypanosoma gondii
, the parasite responsible for the dreaded sleeping sickness, then injected the animals with chemical derivatives to determine if any of them could halt the infection. After several hundred chemicals, Ehrlich and his collaborators had their first antibiotic hit: a brilliant ruby-colored dye derivative that Ehrlich called Trypan Red. It was a name—a disease juxtaposed with a dye color—that captured nearly a century of medical history.