GNN - Genetics and Genomics Timeline

In a landmark address to the British Society of Experimental Biology, entitled "On Protein Synthesis," Francis Crick proposed ideas that proved of the greatest importance to DNA research. Written for a general audience as much as for biochemists and molecular biologists, the paper became a classic that, as Horace Freeland Judson wrote in a historical appraisal, "permanently altered the logic of biology."

Francis H. C. Crick
Courtesy The Salk Institute

Crick argued that the principal function of genes—which, as he and James Watson had suggested four years earlier, are contained in DNA—is the manufacture of proteins. In great numbers and variety, proteins are the basic stuff of life processes—each comprised of some combination of about twenty amino acids. Genes appeared to control the orderly assembly of amino acids, as basic building blocks, into proteins. "Once the central and unique role of proteins is admitted," argued Crick, "there seems little point in genes doing anything else."

To understand protein synthesis, Crick proposed two general principles. Both were consonant with what was known about DNA, but neither was yet definitively supported by experimental evidence.

• The Sequence Hypothesis: The order of bases in a portion of DNA represents a code for the amino acid sequence of a specific protein. Each "word" in the code would name a specific amino acid. From the two-dimensional genetic text, written in DNA, are forged the whole diversity of uniquely shaped three-dimensional proteins.

In this context, Crick discussed the "coding problem"—how the ordered sequence of the four bases in DNA might constitute genes that encode and disburse information directing the manufacture of proteins. Crick hypothesized that, with four bases to DNA and twenty amino acids, the simplest code would involve "triplets"—in which sequences of three bases coded for a single amino acid.

Crick also formulated, for the first time, a basic organizing principle for research into genetic mechanisms.

• The Central Dogma: Information is transmitted from DNA and RNA to proteins, but information cannot be transmitted from a protein to DNA.

In light of the Central Dogma, Crick examined what was known about the mechanics of protein synthesis. He discussed how information contained in DNA, from the nucleus of the cell, was transmitted to the site of protein manufacture in the cell's cytoplasm. He speculated, from available evidence, on the role of cytoplasmic RNA. Many of these issues would be resolved within a few years.

Governing the details of all these discussions was Crick's insistence on the central role of protein synthesis from the master molecule, DNA. "In the protein molecule," wrote Crick, "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 been clearly grasped."

Francis H. C. Crick winner of the
1960 Albert Lasker Award for Basic Medical Research

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