The Gene: An Intimate History - Siddhartha Mukherjee Page 0,61

the secret code of life.

Similarity and difference; order and diversity; message and matter. Schrödinger was trying to conjure up a chemical that would capture the divergent, contradictory qualities of heredity—a molecule to satisfy Aristotle. In his mind’s eye, it was almost as if he had seen DNA.

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I. The quote has also been attributed to Rudolf Hess, Hitler’s deputy.

II. Ploetz would join the Nazis in the 1930s.

III. Curtis Merriman, an American psychologist, and Walter Jablonski, a German ophthalmologist, also performed similar twin studies in the 1920s.

IV. The exact number is hard to place. See Gerald L. Posner and John Ware, Mengele: The Complete Story, for the breadth of Mengele’s twin experiments.

“That Stupid Molecule”

Never underestimate the power of . . . stupidity.

—Robert Heinlein

Oswald Avery was fifty-five in 1933 when he heard of Frederick Griffith’s transformation experiment. His appearance made him seem even older than his years. Frail, small, bespectacled, balding, with a birdlike voice and limbs that hung like twigs in winter, Avery was a professor at the Rockefeller University in New York, where he had spent a lifetime studying bacteria—particularly pneumococcus. He was sure that Griffith had made some terrible mistake in his experiment. How could chemical debris carry genetic information from one cell to another?

Like musicians, like mathematicians—like elite athletes—scientists peak early and dwindle fast. It isn’t creativity that fades, but stamina: science is an endurance sport. To produce that single illuminating experiment, a thousand nonilluminating experiments have to be sent into the trash; it is battle between nature and nerve. Avery had established himself as a competent microbiologist, but had never imagined venturing into the new world of genes and chromosomes. “The Fess”—as his students affectionately called him (short for “professor”)—was a good scientist but unlikely to become a revolutionary one. Griffith’s experiment may have stuffed genetics into a one-way taxicab and sent it scuttling toward a strange future—but Avery was reluctant to climb on that bandwagon.

If the Fess was a reluctant geneticist, then DNA was a reluctant “gene molecule.” Griffith’s experiment had generated widespread speculations about the molecular identity of the gene. By the early 1940s, biochemists had broken cells apart to reveal their chemical constituents and identified various molecules in living systems—but the molecule that carried the code of heredity was still unknown.

Chromatin—the biological structure where genes resided—was known to be made of two types of chemicals: proteins and nucleic acids. No one knew or understood the chemical structure of chromatin, but of the two “intimately mixed” components, proteins were vastly more familiar to biologists, vastly more versatile, and vastly more likely to be gene carriers. Proteins were known to carry out the bulk of functions in the cell. Cells depend on chemical reactions to live: during respiration, for instance, sugar combines chemically with oxygen to make carbon dioxide and energy. None of these reactions occurs spontaneously (if they did, our bodies would be constantly ablaze with the smell of flambéed sugar). Proteins coax and control these fundamental chemical reactions in the cell—speeding some and slowing others, pacing the reactions just enough to be compatible with living. Life may be chemistry, but it’s a special circumstance of chemistry. Organisms exist not because of reactions that are possible, but because of reactions that are barely possible. Too much reactivity and we would spontaneously combust. Too little, and we would turn cold and die. Proteins enable these barely possible reactions, allowing us to live on the edges of chemical entropy—skating perilously, but never falling in.

Proteins also form the structural components of the cell: filaments of hair, nails, cartilage, or the matrices that trap and tether cells. Twisted into yet other shapes, they also form receptors, hormones, and signaling molecules, allowing cells to communicate with one another. Nearly every cellular function—metabolism, respiration, cell division, self-defense, waste disposal, secretion, signaling, growth, even cellular death—requires proteins. They are the workhorses of the biochemical world.

Nucleic acids, in contrast, were the dark horses of the biochemical world. In 1869—four years after Mendel had read his paper to the Brno Society—a Swiss biochemist, Friedrich Miescher, had discovered this new class of molecules in cells. Like most of his biochemist colleagues, Miescher was also trying to classify the molecular components of cells by breaking cells apart and separating the chemicals that were released. Of the various components, he was particularly intrigued by one kind of chemical. He had precipitated it in dense, swirling strands out of white blood cells that he had wrung out of human pus in surgical dressings. He had found the