The Gene: An Intimate History - Siddhartha Mukherjee Page 0,46

bludgeoned, and drowned to death by his rivals on December 30, 1916. Even by the grim standards of Russian assassinations, the violence of this murder was a testimony to the visceral hatred that he had inspired in his enemies. In the early summer of 1918, the royal family was moved to Yekaterinburg and placed under house arrest. On the evening of July 17, 1918, a month shy of Alexei’s fourteenth birthday, a firing squad instigated by the Bolsheviks burst into the czar’s house and assassinated the whole family. Alexei was shot twice in the head. The bodies of the children were supposedly scattered and buried nearby, but Alexei’s body was not found.

In 2007, an archaeologist exhumed two partially burned skeletons from a bonfire site near the house where Alexei had been murdered. One of the skeletons belonged to a thirteen-year-old boy. Genetic testing of the bones confirmed that the body was Alexei’s. Had the full genetic sequence of the skeleton been analyzed, the investigators might have found the culprit gene for hemophilia B—the mutation that had crossed one continent and four generations and insinuated itself into a defining political moment of the twentieth century.

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I. Some of the work was also performed at Woods Hole, where Morgan would move his lab every summer.

Truths and Reconciliations

All changed, changed utterly:

A terrible beauty is born.

—William Butler Yeats, Easter, 1916

The gene was born “outside” biology. By this, I mean the following: if you consider the major questions raging through the biological sciences in the late nineteenth century, heredity does not rank particularly high on that list. Scientists studying living organisms were far more preoccupied with other matters: embryology, cell biology, the origin of species, and evolution. How do cells function? How does an organism arise from an embryo? How do species originate? What generates the diversity of the natural world?

Yet, attempts to answer these questions had all become mired at precisely the same juncture. The missing link, in all cases, was information. Every cell, and every organism, needs information to carry out its physiological function—but where does that information come from? An embryo needs a message to become an adult organism—but what carries this message? Or how, for that matter, does one member of a species “know” that it is a member of that species and not another?

The ingenious property of the gene was that it offered a potential solution to all these problems in a single sweep. Information for a cell to carry out a metabolic function? It came from a cell’s genes, of course. The message encrypted in an embryo? Again, it was all encoded in genes. When an organism reproduces, it transmits the instructions to build embryos, make cells function, enable metabolism, perform ritual mating dances, give wedding speeches, and produce future organisms of the same species—all in one grand, unified gesture. Heredity cannot be a peripheral question in biology; it must rank among its central questions. When we think of heredity in a colloquial sense, we think about the inheritance of unique or particular features across generations: a peculiar shape of a father’s nose or the susceptibility to an unusual illness that runs through a family. But the real conundrum that heredity solves is much more general: What is the nature of instruction that allows an organism to build a nose—any nose—in the first place?

The delayed recognition of the gene as the answer to the central problem of biology had a strange consequence: genetics had to be reconciled with other major fields of biology as an afterthought. If the gene was the central currency of biological information, then major characteristics of the living world—not just heredity—should be explicable in terms of genes. First, genes had to explain the phenomenon of variation: How could discrete units of heredity explain that human eyes, say, do not have six discrete forms but seemingly 6 billion continuous variants? Second, genes had to explain evolution: How could the inheritance of such units explain that organisms have acquired vastly different forms and features over time? And third, genes had to explain development: How could individual units of instruction prescribe the code to create a mature organism out of an embryo?

We might describe these three reconciliations as attempts to explain nature’s past, present, and future through the lens of the gene. Evolution describes nature’s past: How did living things arise? Variation describes its present: Why do they look like this now? And embryogenesis attempts to capture the future: How does a single cell create a living