The Gene: An Intimate History - Siddhartha Mukherjee Page 0,74

1950s. Veer southwest again, and the journey brings you to the Science Museum on Exhibition Road to encounter the “gene molecule” in person. The original Watson and Crick model of DNA, with its hammered metal plates and rickety rods twisting precariously around a steel laboratory stand, is housed behind a glass case. The model looks like a latticework corkscrew invented by a madman, or an impossibly fragile spiral staircase that might connect the human past to its future. Crick’s handwritten scribbles—A, C, T, and G—still adorn the plates.

The revelation of the structure of DNA by Watson, Crick, Wilkins, and Franklin brought one journey of genes to its close, even as it threw open new directions of inquiry and discovery. “Once it had been known that DNA had a highly regular structure,” Watson wrote in 1954, “the enigma of how the vast amount of genetic information needed to specify all the characteristics of a living organism could be stored in such a regular structure had to be solved.” Old questions were replaced by new ones. What features of the double helix enabled it to bear the code of life? How did that code become transcribed and translated into actual form and function of an organism? Why, for that matter, were there two helices, and not one, or three or four? Why were the two strands complementary to each other—A matched with T, and G matched with C—like a molecular yin and yang? Why was this structure, of all structures, chosen as the central repository of all biological information? “It isn’t that [DNA] looks so beautiful,” Crick later remarked. “It is the idea of what it does.”

Images crystallize ideas—and the image of a double-helical molecule that carried the instructions to build, run, repair, and reproduce humans crystallized the optimism and wonder of the 1950s. Encoded in that molecule were the loci of human perfectibility and vulnerability: once we learned to manipulate this chemical, we would rewrite our nature. Diseases would be cured, fates changed, futures reconfigured.

The Watson and Crick model of DNA marked the end of one conception of the gene—as a mysterious carrier of messages across generations—to another: as a chemical, or a molecule, capable of encoding, storing, and transferring information between organisms. If the keyword of early-twentieth-century genetics was message, then the keyword of late-twentieth-century genetics might be code. That genes carried messages had been abundantly clear for half a century. The question was, could humans decipher their code?

* * *

I. Experiments carried out by Alfred Hershey and Martha Chase in 1952 and 1953 also confirmed that DNA was the carrier of genetic information.

II. Hemoglobin has multiple variants, including some that are specific to the fetus. This discussion applies to the most common, and best-studied, variant, which exists abundantly in blood.

III. In 1951, long before James Watson would become a household name around the world, the novelist Doris Lessing took a three-hour walk with the young Watson, whom she knew through a friend of a friend. During the entire walk, across the heaths and fens near Cambridge, Lessing did all the talking; Watson said not one word. At the end of the walk, “exhausted, wanting only to escape,” Lessing at last heard the sound of human speech from her companion: “The trouble is, you see, that there is only one other person in the world that I can talk to.”

IV. In her initial studies on DNA, Franklin was not convinced that the X-ray patterns suggested a helix, most likely because she was working on the dry form of DNA. Indeed, at one point Franklin and her student had sent around a cheeky note announcing the “death of the helix.” However, as her X-ray images improved, she gradually began to envision the helix with the phosphates on the outside, as indicated by her notes. Watson once told a journalist that Franklin’s fault lay in her dispassionate approach to her own data: “She did not live DNA.”

V. But was it her photograph? Wilkins later maintained that the photograph had been given to him by Gosling, Franklin’s student—and therefore it was his to do with what he desired. Franklin was leaving King’s College to take up a new job at Birkbeck College, and Wilkins thought that she was abandoning the DNA project.

“That Damned, Elusive Pimpernel”

In the protein molecule, Nature has devised an instrument in which an underlying simplicity is used to express great subtlety and versatility; it is impossible to see molecular biology in proper perspective until this peculiar combination of virtues has