The Gene: An Intimate History - Siddhartha Mukherjee Page 0,26

and ratios. This method, albeit unconventional, was not unusual for his time, but it also reflected Mendel’s scientific naïveté.

“A Certain Mendel”

The origin of species is a natural phenomenon.

—Jean-Baptiste Lamarck

The origin of species is an object of inquiry.

—Charles Darwin

The origin of species is an object of experimental investigation.

—Hugo de Vries

In the summer of 1878, a thirty-year-old Dutch botanist named Hugo de Vries traveled to England to see Darwin. It was more of a pilgrimage than a scientific visit. Darwin was vacationing at his sister’s estate in Dorking, but de Vries tracked him down and traveled out to meet him. Gaunt, intense, and excitable, with Rasputin’s piercing eyes and a beard that rivaled Darwin’s, de Vries already looked like a younger version of his idol. He also had Darwin’s persistence. The meeting must have been exhausting, for it lasted only two hours, and Darwin had to excuse himself to take a break. But de Vries left England transformed. With no more than a brief conversation, Darwin had inserted a sluice into de Vries’s darting mind, diverting it forever. Back in Amsterdam, de Vries abruptly terminated his prior work on the movement of tendrils in plants and threw himself into solving the mystery of heredity.

By the late 1800s, the problem of heredity had acquired a near-mystical aura of glamour, like a Fermat’s Last Theorem for biologists. Like Fermat—the odd French mathematician who had tantalizingly scribbled that he’d found a “remarkable proof” of his theorem, but failed to write it down because the paper’s “margin was too small”—Darwin had desultorily announced that he had found a solution to heredity, but had never published it. “In another work I shall discuss, if time and health permit, the variability of organic beings in a state of nature,” Darwin had written in 1868.

Darwin understood the stakes implicit in that claim. A theory of heredity was crucial to the theory of evolution: without any means to generate variation, and fix it across generations, he knew, there would be no mechanism for an organism to evolve new characteristics. But a decade had passed, and Darwin had never published the promised book on the genesis of “variability in organic beings.” Darwin died in 1882, just four years after de Vries’s visit. A generation of young biologists was now rifling through Darwin’s works to find clues to the theory that had gone missing.

De Vries also pored through Darwin’s books, and he latched onto the theory of pangenesis—the idea that “particles of information” from the body were somehow collected and collated in sperm and eggs. But the notion of messages emanating from cells and assembling in sperm as a manual for building an organism seemed particularly far-fetched; it was as if the sperm were trying to write the Book of Man by collecting telegrams.

And experimental proof against pangenes and gemmules was mounting. In 1883, with rather grim determination, the German embryologist August Weismann had performed an experiment that directly attacked Darwin’s gemmule theory of heredity. Weismann had surgically excised the tails of five generations of mice, then bred the mice to determine if the offspring would be born tailless. But the mice—with equal and obdurate consistency—had been born with tails perfectly intact, generation upon generation. If gemmules existed, then a mouse with a surgically excised tail should produce a mouse without a tail. In total, Weismann had serially removed the tails of 901 animals. And mice with absolutely normal tails—not even marginally shorter than the tail of the original mouse—had kept arising; it was impossible to wash “the hereditary taint” (or, at least, the “hereditary tail”) away. Grisly as it was, the experiment nonetheless announced that Darwin and Lamarck could not be right.

Weismann had proposed a radical alternative: perhaps hereditary information was contained exclusively in sperm and egg cells, with no direct mechanism for an acquired characteristic to be transmitted into sperm or eggs. No matter how ardently the giraffe’s ancestor stretched its neck, it could not convey that information into its genetic material. Weismann called this hereditary material germplasm and argued that it was the only method by which an organism could generate another organism. Indeed, all of evolution could be perceived as the vertical transfer of germplasm from one generation to the next: an egg was the only way for a chicken to transfer information to another chicken.

But what was the material nature of germplasm? de Vries wondered. Was it like paint: Could it be mixed and diluted? Or was the information in germplasm discrete and carried in packets—like an