Free The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee Page B

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.
    Galvanized by his discovery, Ehrlich unleashed volleys of chemical experiments. A universe of biological chemistry opened up before him:molecules with peculiar properties, a cosmos governed by idiosyncratic rules. Some compounds switched from precursors into active drugs in the bloodstream; others transformed backward from active drugs to inactive molecules. Some were excreted in the urine; others condensed in the bile or fell apart immediately in the blood. One molecule might survive for days in an animal, but its chemical cousin—a variant by just a few critical atoms—might vanish from the body in minutes.
    On April 19, 1910, at the densely packed Congress for Internal Medicine in Wiesbaden, Ehrlich announced that he had discovered yet another molecule with “specific affinity”—this one a blockbuster. The new drug, cryptically called compound 606, was active against a notorious microbe,
Treponema pallidum
, which caused syphilis. In Ehrlich’s era, syphilis—the “secret malady ” of eighteenth-century Europe—was a sensational illness, a tabloid pestilence. Ehrlich knew that an antisyphilitic drug would be an instant sensation and he was prepared. Compound 606 had secretly been tested in patients in the hospital wards of St. Petersburg, then retested in patients with neurosyphilis at the Magdeburg Hospital—each time with remarkable success. A gigantic factory, funded by Hoechst Chemical Works, was already being built to manufacture it for commercial use.
    Ehrlich’s successes with Trypan Red and compound 606 (which he named Salvarsan, from the word
salvation
) proved that diseases were just pathological locks waiting to be picked by the right molecules. The line of potentially curable illnesses now stretched endlessly before him. Ehrlich called his drugs “magic bullets”—
bullets
for their capacity to kill and
magic
for their specificity. It was a phrase with an ancient, alchemic ring that would sound insistently through the future of oncology.

    Ehrlich’s magic bullets had one last target to fell: cancer. Syphilis and trypanosomiasis are microbial diseases. Ehrlich was slowly inching toward