The Gene: An Intimate History - Siddhartha Mukherjee Page 0,185

for Lamarck’s flawed theory of evolution by adaptation). Rather, giraffes arise via spontaneous variation and natural selection: a tall-necked mutant appears in an ancestral tree-grazing animal, and during a period of famine, this mutant survives and is naturally selected. August Weismann had formally tested the idea that an environmental influence could permanently alter genes by chopping off the tails of five generations of mice—and yet, mice in the sixth generation had been born with perfectly intact tails. Evolution can craft perfectly adapted organisms, but not in an intentional manner: it is not just a “blind watchmaker,” as Richard Dawkins once famously described it, but also a forgetful one. Its sole driver is survival and selection; its only memory is mutation.

Yet the grandchildren of the Hongerwinter had somehow acquired the memory of their grandparents’ famine—not through mutations and selection, but via an environmental message that had somehow transformed into a heritable one. A genetic “memory” in this form, it could act as a wormhole for evolution. A giraffe’s ancestor might be able to make a giraffe—not by trudging through the glum Malthusian logic of mutation, survival, and selection, but by simply straining its neck, and registering and imprinting a memory of that strain in its genome. A mouse with an excised tail would be able to bear mice with shortened tails by transmitting that information to its genes. Children raised in stimulating environments could produce more stimulated children. The idea was a restatement of Darwin’s gemmule formulation: the particular experience, or history, of an organism would be signaled straight to its genome. Such a system would act as a rapid-transit system between an organism’s adaptation and evolution. It would unblind the watchmaker.

Waddington, for one, had yet another stake in the answer—a personal one. An early, fervent convert to Marxism, he imagined that discovering such “memory-fixing” elements in the genome might be crucial not just to the understanding of human embryology, but also to his political project. If cells could be indoctrinated or de-indoctrinated by manipulating their gene memories, perhaps humans could be indoctrinated as well (recall Lysenko’s attempt to achieve this with wheat strains, and Stalin’s attempts to erase the ideologies of human dissidents). Such a process might undo cellular identity and allow cells to run up the Waddington landscape—turning back from an adult cell to an embryonic cell, thus reversing biological time. It might even undo the fixity of human memory, of identity—of choice.

Until the late 1950s, epigenetics was more fantasy than reality: no one had witnessed a cell layering its history or identity above its genome. In 1961, two experiments performed less than six months, and less than twenty miles, from each other would transform the understanding of genes and lend credence to Waddington’s theory.

In the summer of 1958, John Gurdon, a graduate student at Oxford University, began to study the development of frogs. Gurdon had never been a particularly promising student—he once scored 250th in a class of 250 in a science exam—but he had, as he once described it, an “aptitude for doing things on a small scale.” His most important experiment involved the smallest of scales. In the early fifties, two scientists in Philadelphia had emptied an unfertilized frog egg of all its genes, sucking out the nucleus and leaving just the cellular husk behind, then injected the genome of another frog cell into the emptied egg. This was like evacuating a nest, slinking a false bird in, and asking if the bird developed normally. Did the “nest”—i.e., the egg cell, devoid of all its own genes—have all the factors in it to create an embryo out of an injected genome from another cell? It did. The Philadelphia researchers produced an occasional tadpole from an egg injected with the genome of a frog cell. It was an extreme form of parasitism: the egg cell became merely a host, or a vessel, for the genome of a normal cell and allowed that genome to develop into a perfectly normal adult animal. The researchers called their method nuclear transfer, but the process was extremely inefficient. In the end, they largely abandoned the approach.

Gurdon, fascinated by those rare successes, pushed the boundaries of that experiment. The Philadelphia researchers had injected nuclei from young embryos into the enucleated eggs. In 1961, Gurdon began to test whether injecting the genome from the cell of an adult frog intestine could also give rise to a tadpole. The technical challenges were immense. First, Gurdon learned to use a tiny beam of ultraviolet rays