The Gene: An Intimate History - Siddhartha Mukherjee Page 0,76

or cellular function specified by a protein. “A gene,” Beadle wrote in 1945, “can be visualized as directing the final configuration of a protein molecule.” This was the “action of the gene” that a generation of biologists had been trying to comprehend: a gene “acts” by encoding information to build a protein, and the protein actualizes the form or function of the organism.

Or, in terms of information flow:

Beadle and Tatum shared a Nobel Prize in 1958 for their discovery, but the Beadle/Tatum experiment raised a crucial question that remained unanswered: How did a gene “encode” information to build a protein? A protein is created from twenty simple chemicals named amino acids—Methionine, Glycine, Leucine, and so forth—strung together in a chain. Unlike a chain of DNA, which exists primarily in the form of a double helix, a protein chain can twist and turn in space idiosyncratically, like a wire that has been sculpted into a unique shape. This shape-acquiring ability allows proteins to execute diverse functions in cells. They can exist as long, stretchable fibers in muscle (myosin). They can become globular in shape and enable chemical reactions—i.e., enzymes (DNA polymerase). They can bind colored chemicals and become pigments in the eye, or in a flower. Twisted into saddle clasps, they can act as transporters for other molecules (hemoglobin). They can specify how a nerve cell communicates with another nerve cell and thus become the arbiters of normal cognition and neural development.

But how could a sequence of DNA—ATGCCCC . . . etc.—carry instructions to build a protein? Watson had always suspected that DNA was first converted into an intermediate message. It was this “messenger molecule,” as he called it, that carried the instructions to build a protein based on a gene’s code. “For over a year,” he wrote in 1953, “I had been telling Francis [Crick] that the genetic information in DNA chains must be first copied into that of complementary RNA molecules,” and the RNA molecules must be used as “messages” to build proteins.

In 1954, the Russian-born physicist-turned-biologist George Gamow teamed with Watson to form a “club” of scientists to decipher the mechanism of protein synthesis. “Dear Pauling,” Gamow wrote to Linus Pauling in 1954, with his characteristically liberal interpretation of grammar and spelling, “I am playing with complex organic molecules (what I never did before!) and geting [sic] some amusing results and would like your opinnion [sic] about it.”

Gamow called it the RNA Tie Club. “The Club never met as a whole,” Crick recalled: “It always had a rather ethereal existence.” There were no formal conferences or rules or even basic principles of organization. Rather, the Tie Club was loosely clustered around informal conversations. Meetings happened by chance, or not at all. Letters proposing madcap, unpublished ideas, often accompanied by hand-scribbled figures, were circulated among the members; it was a blog before blogs. Watson got a tailor in Los Angeles to embroider green woolen ties with a golden strand of RNA, and Gamow sent a tie, and a pin, to each in the group of friends that he had handpicked as club members. He printed a letterhead and added his own motto: “Do or die, or don’t try.”

In the mid-1950s, a pair of bacterial geneticists working in Paris, Jacques Monod and François Jacob, had also performed experiments that had dimly suggested that an intermediate molecule—a messenger—was required for the translation of DNA into proteins. Genes, they proposed, did not specify instructions for proteins directly. Rather, genetic information in DNA was first converted into a soft copy—a draft form—and it was this copy, not the DNA original, that was translated into a protein.

In April 1960, Francis Crick and Jacob met at Sydney Brenner’s cramped apartment in Cambridge to discuss the identity of this mysterious intermediate. The son of a cobbler from South Africa, Brenner had come to England to study biology on a scholarship; like Watson and Crick, he too had become entranced by Watson’s “religion of genes” and DNA. Over a barely digested lunch, the three scientists realized that this intermediate molecule had to shuttle from the cell’s nucleus, where genes were stored, to the cytoplasm, where proteins were synthesized.

But what was the chemical identity of the “message” that was built from a gene? Was it a protein or a nucleic acid or some other kind of molecule? What was its relationship to the sequence of the gene? Although they still lacked concrete evidence, Brenner and Crick also suspected that it was RNA—DNA’s molecular cousin. In 1959, Crick wrote