The Gene: An Intimate History - Siddhartha Mukherjee Page 0,42

1920s about the links between genes and identity, the gene itself appeared to possess little identity of its own. If a scientist had been asked what a gene was made of, how it accomplished its function, or where it resided within the cell, there would be few satisfactory answers. Even as genetics was being used to justify sweeping changes in law and society, the gene itself had remained a doggedly abstract entity, a ghost lurking in the biological machine.

This black box of genetics was pried open, almost accidentally, by an unlikely scientist working on an unlikely organism. In 1907, when William Bateson visited the United States to give talks on Mendel’s discovery, he stopped in New York to meet Thomas Hunt Morgan, the cell biologist. Bateson was not particularly impressed. “Morgan is a blockhead,” he wrote to his wife. “He is in a continuous whirl—very active and inclined to be noisy.”

Noisy, active, obsessive, eccentric—with a dervishlike mind that spiraled from one scientific question to the next—Thomas Morgan was a professor of zoology at Columbia University. His main interest was embryology. At first, Morgan was not even interested in whether units of heredity existed or how or where they were stored. The principal question he cared about concerned development: How does an organism emerge from a single cell?

Morgan had resisted Mendel’s theory of heredity at first—arguing that it was unlikely that complex embryological information could be stored in discrete units in the cell (hence Bateson’s “blockhead” comment). Eventually, however, Morgan had become convinced by Bateson’s evidence; it was hard to argue against “Mendel’s bulldog,” who came armed with charts of data. Yet, even as he had come to accept the existence of genes, Morgan had remained perplexed about their material form. “Cell biologists look; geneticists count; biochemists clean,” the scientist Arthur Kornberg once said. Indeed, armed with microscopes, cell biologists had become accustomed to a cellular world in which visible structures performed identifiable functions within cells. But thus far, the gene had been “visible” only in a statistical sense. Morgan wanted to uncover the physical basis of heredity. “We are interested in heredity not primarily as a mathematical formulation,” he wrote, “but rather as a problem concerning the cell, the egg and the sperm.”

But where might genes be found within cells? Intuitively, biologists had long guessed that the best place to visualize a gene was the embryo. In the 1890s, a German embryologist working with sea urchins in Naples, Theodor Boveri, had proposed that genes resided in chromosomes, threadlike filaments that stained blue with aniline, and lived, coiled like springs, in the nucleus of cells (the word chromosome was coined by Boveri’s colleague Wilhelm von Waldeyer-Hartz).

Boveri’s hypothesis was corroborated by work performed by two other scientists. Walter Sutton, a grasshopper-collecting farm boy from the prairies of Kansas, had grown into a grasshopper-collecting scientist in New York. In the summer of 1902, working on grasshopper sperm and egg cells—which have particularly gigantic chromosomes—Sutton also postulated that genes were physically carried on chromosomes. And Boveri’s own student, a biologist named Nettie Stevens, had become interested in the determination of sex. In 1905, using cells from the common mealworm, Stevens demonstrated that “maleness” in worms was determined by a unique factor—the Y chromosome—that was only present in male embryos, but never in female ones (under a microscope, the Y chromosome looks like any other chromosome—a squiggle of DNA that stains brightly blue—except that it is shorter and stubbier compared to the X chromosome). Having pinpointed the location of gender-carrying genes to a single chromosome, Stevens proposed that all genes might be carried on chromosomes.

Thomas Morgan admired the work of Boveri, Sutton, and Stevens. But he still yearned for a more tangible description of the gene. Boveri had identified the chromosome as the physical residence for genes, but the deeper architecture of genes and chromosomes still remained unclear. How were genes organized on chromosomes? Were they strung along chromosomal filaments—like pearls on a string? Did every gene have a unique chromosomal “address”? Did genes overlap? Was one gene physically or chemically linked to another?

Morgan approached these questions by studying yet another model organism—fruit flies. He began to breed flies sometime around 1905 (some of Morgan’s colleagues would later claim that his first stock came from a flock of flies above a pile of overripe fruit in a grocery store in Woods Hole, Massachusetts. Others suggested that he got his first flies from a colleague in New York). A year later, he was breeding maggots by