The Gene: An Intimate History - Siddhartha Mukherjee Page 0,12

“In nature there is no generation,” the Dutch scientist Jan Swammerdam wrote in 1669, “but only propagation.”

But not everyone could be convinced that miniature humans were infinitely encased inside humans. The principal challenge to preformation was the idea that something had to happen during embryogenesis that led to the formation of entirely new parts in the embryo. Humans did not come pre-shrunk and premade, awaiting only expansion. They had to be generated from scratch, using specific instructions locked inside the sperm and egg. Limbs, torsos, brains, eyes, faces—even temperaments or propensities that were inherited—had to be created anew each time an embryo unfurled into a human fetus. Genesis happened . . . well—by genesis.

By what impetus, or instruction, was the embryo, and the final organism, generated from sperm and egg? In 1768, the Berlin embryologist Caspar Wolff tried to finesse an answer by concocting a guiding principle—vis essentialis corporis, as he called it—that progressively shepherded the maturation of a fertilized egg into a human form. Like Aristotle, Wolff imagined that the embryo contained some sort of encrypted information—code—that was not merely a miniature version of a human, but instructions to make a human from scratch. But aside from inventing a Latinate name for a vague principle, Wolff could provide no further specifics. The instructions, he argued obliquely, were blended together in the fertilized egg. The vis essentialis then came along, like an invisible hand, and molded the formation of this mass into a human form.

While biologists, philosophers, Christian scholars, and embryologists fought their way through vicious debates between preformation and the “invisible hand” throughout much of the eighteenth century, a casual observer may have been forgiven for feeling rather unimpressed by it all. This was, after all, stale news. “The opposing views of today were in existence centuries ago,” a nineteenth-century biologist complained, rightfully. Indeed, preformation was largely a restatement of Pythagoras’s theory—that sperm carried all the information to make a new human. And the “invisible hand” was, in turn, merely a gilded variant of Aristotle’s idea—that heredity was carried in the form of messages to create materials (it was the “hand” that carried the instructions to mold an embryo).

In time, both the theories would be spectacularly vindicated, and spectacularly demolished. Both Aristotle and Pythagoras were partially right and partially wrong. But in the early 1800s, it seemed as if the entire field of heredity and embryogenesis had reached a conceptual impasse. The world’s greatest biological thinkers, having pored over the problem of heredity, had scarcely advanced the field beyond the cryptic musings of two men who had lived on two Greek islands two thousand years earlier.

“The Mystery of Mysteries”

. . . They mean to tell us all was rolling blind

Till accidentally it hit on mind

In an albino monkey in a jungle,

And even then it had to grope and bungle,

Till Darwin came to earth upon a year . . .

—Robert Frost, “Accidentally on Purpose”

In the winter of 1831, when Mendel was still a schoolboy in Silesia, a young clergyman, Charles Darwin, boarded a ten-gun brig-sloop, the HMS Beagle, at Plymouth Sound, on the southwestern shore of England. Darwin was then twenty-two years old, the son and grandson of prominent physicians. He had the square, handsome face of his father, the porcelain complexion of his mother, and the dense overhang of eyebrows that ran in the Darwin family over generations. He had tried, unsuccessfully, to study medicine at Edinburgh—but, horrified by the “screams of a strapped-down child amid the blood and sawdust of the . . . operating theater,” had fled medicine to study theology at Christ’s College in Cambridge. But Darwin’s interest ranged far beyond theology. Holed up in a room above a tobacconist’s shop on Sidney Street, he had occupied himself by collecting beetles, studying botany and geology, learning geometry and physics, and arguing hotly about God, divine intervention, and the creation of animals. More than theology or philosophy, Darwin was drawn to natural history—the study of the natural world using systematic scientific principles. He apprenticed with another clergyman, John Henslow, the botanist and geologist who had created and curated the Cambridge Botanic Garden, the vast outdoor museum of natural history where Darwin first learned to collect, identify, and classify plant and animal specimens.

Two books particularly ignited Darwin’s imagination during his student years. The first, Natural Theology, published in 1802 by William Paley, the former vicar of Dalston, made an argument that would resonate deeply with Darwin. Suppose, Paley wrote, a man walking across a heath happens upon a