The Gene: An Intimate History - Siddhartha Mukherjee Page 0,52

rough strain mounted an immune response and survived.

Griffith performed an experiment that, unwittingly, launched the molecular biology revolution. First, he killed the virulent, smooth bacteria with heat, then injected the heat-killed bacteria into mice. As expected, the bacterial remnants had no effect on the mice: they were dead and unable to cause an infection. But when he mixed the dead material from the virulent strain with live bacteria of the nonvirulent strain, the mice died rapidly. Griffith autopsied the mice and found that the rough bacteria had changed: they had acquired the smooth coat—the virulence-determining factor—merely by contact with the debris from the dead bacteria. The harmless bacteria had somehow “transformed” into the virulent form.

How could heat-killed bacterial debris—no more than a lukewarm soup of microbial chemicals—have transmitted a genetic trait to a live bacterium by mere contact? Griffith was unsure. At first, he wondered whether the live bacteria had ingested the dead bacteria and thus changed their coats, like a voodoo ritual in which eating the heart of a brave man transmits courage or vitality to another. But once transformed, the bacteria maintained their new coats for several generations—long after any food source would have been exhausted.

The simplest explanation, then, was that genetic information had passed between the two strains in a chemical form. During “transformation,” the gene that governed virulence—producing the smooth coat versus the rough coat—had somehow slipped out of the bacteria into the chemical soup, then out of that soup into live bacteria and become incorporated into the genome of the live bacterium. Genes could, in other words, be transmitted between two organisms without any form of reproduction. They were autonomous units—material units—that carried information. Messages were not whispered between cells via ethereal pangenes or gemmules. Hereditary messages were transmitted through a molecule, that molecule could exist in a chemical form outside a cell, and it was capable of carrying information from cell to cell, from organism to organism, and from parents to children.

Had Griffith publicized this startling result, he would have set all of biology ablaze. In the 1920s, scientists were just beginning to understand living systems in chemical terms. Biology was becoming chemistry. The cell was a beaker of chemicals, biochemists argued, a pouch of compounds bound by a membrane that were reacting to produce a phenomenon called “life.” Griffith’s identification of a chemical capable of carrying hereditary instructions between organisms—the “gene molecule”—would have sparked a thousand speculations and restructured the chemical theory of life.

But Griffith, an unassuming, painfully shy scientist—“this tiny man who . . . barely spoke above a whisper”—could hardly be expected to broadcast the broader relevance or appeal of his results. “Englishmen do everything on principle,” George Bernard Shaw once noted—and the principle that Griffith lived by was utter modesty. He lived alone, in a nondescript apartment near his lab in London, and in a spare, white modernist cottage that he had built for himself in Brighton. Genes might have moved between organisms, but Griffith could not be forced to travel from his lab to his own lectures. To trick him into giving scientific talks, his friends would stuff him into a taxicab and pay a one-way fare to the destination.

In January 1928, after hesitating for months (“God is in no hurry, so why should I be?”), Griffith published his data in the Journal of Hygiene—a scientific journal whose sheer obscurity might have impressed even Mendel. Writing in an abjectly apologetic tone, Griffith seemed genuinely sorry that he had shaken genetics by its roots. His study discussed transformation as a curiosity of microbial biology, but never explicitly mentioned the discovery of a potential chemical basis of heredity. The most important conclusion of the most important biochemical paper of the decade was buried, like a polite cough, under a mound of dense text.

Although Frederick Griffith’s experiment was the most definitive demonstration that the gene was a chemical, other scientists were also circling the idea. In 1920, Hermann Muller, the former student of Thomas Morgan’s, moved from New York to Texas to continue studying fly genetics. Like Morgan, Muller hoped to use mutants to understand heredity. But naturally arising mutants—the bread and butter of fruit fly geneticists—were far too rare. The white-eyed or sable-bodied flies that Morgan and his students had discovered in New York had been fished out laboriously by hunting through massive flocks of insects over thirty years. Tired of mutant hunting, Muller wondered if he could accelerate the production of mutants—perhaps by exposing flies to heat or light or