The Gene: An Intimate History - Siddhartha Mukherjee Page 0,43

the thousands, in milk bottles filled with rotting fruit in a third-floor laboratory at Columbia University.I Bunches of overripe bananas hung from sticks. The smell of fermented fruit was overpowering, and a haze of escaped flies lifted off the tables like a buzzing veil every time Morgan moved. The students called his laboratory the Fly Room. It was about the same size and shape as Mendel’s garden—and in time it would become an equally iconic site in the history of genetics.

Like Mendel, Morgan began by identifying heritable traits—visible variants that he could track over generations. He had visited Hugo de Vries’s garden in Amsterdam in the early 1900s and become particularly interested in de Vries’s plant mutants. Did fruit flies have mutations as well? By scoring thousands of flies under the microscope, he began to catalog dozens of mutant flies. A rare white-eyed fly appeared spontaneously among the typically red-eyed flies. Other mutant flies had forked bristles; sable-colored bodies; curved legs; bent, batlike wings; disjointed abdomens; deformed eyes—a Halloween’s parade of oddballs.

A flock of students joined him in New York, each one odd in his own right: a tightly wound, precise Midwesterner named Alfred Sturtevant; Calvin Bridges, a brilliant, grandiose young man given to fantasies about free love and promiscuity; and paranoid, obsessive Hermann Muller, who jostled daily for Morgan’s attention. Morgan openly favored Bridges; it was Bridges, as an undergraduate student assigned to wash bottles, who had spotted, among hundreds of vermilion-eyed flies, the white-eyed mutant that would become the basis for many of Morgan’s crucial experiments. Morgan admired Sturtevant for his discipline and his work ethic. Muller was favored the least: Morgan found him shifty, laconic, and disengaged from the other members of the lab. Eventually, all three students would quarrel fiercely, unleashing a cycle of envy and destructiveness that would blaze through the discipline of genetics. But for now, in a fragile peace dominated by the buzz of flies, they immersed themselves in experiments on genes and chromosomes. By breeding normal flies with mutants—mating white-eyed males with red-eyed females, say—Morgan and his students could track the inheritance of traits across multiple generations. The mutants, again, would prove crucial to these experiments: only the outliers could illuminate the nature of normal heredity.

To understand the significance of Morgan’s discovery, we need to return to Mendel. In Mendel’s experiments, every gene had behaved like an independent entity—a free agent. Flower color, for instance, had no link with seed texture or stem height. Each characteristic was inherited independently, and all combinations of traits were possible. The result of each cross was thus a perfect genetic roulette: if you crossed a tall plant with purple flowers with a short plant with white flowers, you would eventually produce all sorts of mixes—tall plants with white flowers and short plants with purple flowers and so forth.

But Morgan’s fruit fly genes did not always behave independently. Between 1905 and 1908, Morgan and his students crossed thousands of fruit fly mutants with each other to create tens of thousands of flies. The result of each cross was meticulously recorded: white-eyed, sable-colored, bristled, short-winged. When Morgan examined these crosses, tabulated across dozens of notebooks, he found a surprising pattern: some genes acted as if they were “linked” to each other. The gene responsible for creating white eyes (called white eyed), for instance, was inescapably linked to maleness: no matter how Morgan crossed his flies, only males were born with white eyes. Similarly, the gene for sable color was linked with the gene that specified the shape of a wing.

For Morgan, this genetic linkage could only mean one thing: genes had to be physically linked to each other. In flies, the gene for sable color was never (or rarely) inherited independently from the gene for miniature wings because they were both carried on the same chromosome. If two beads are on the same string, then they are always tied together, no matter how one attempts to mix and match strings. For two genes on the same chromosome, the same principle applied: there was no simple way to separate the forked-bristle gene from the coat-color gene. The inseparability of features had a material basis: the chromosome was a “string” along which certain genes were permanently strung.

Morgan had discovered an important modification to Mendel’s laws. Genes did not travel separately; instead, they moved in packs. Packets of information were themselves packaged—into chromosomes, and ultimately in cells. But the discovery had a more important consequence: conceptually, Morgan had not just linked