Any history of the human genome project must begin with the publication of "Molecular structure of Nucleic Acids" by Watson and Crick, in the 25 April 1953 issue of Nature. Four years after that milestone, in a review in Science, Robert Sinsheimer summarized the case for linkage of DNA with heredity -- the evidence for which, even at that time, was circumstantial. "I believe this hard-won recognition of the role of DNA," he concluded, "has brought us into a new era in genetics and biochemistry."

Another key step toward thinking about a complete human genetic sequence was the investigation of the structure and function of transfer RNA -- the three-nucleotide coding units that are linked to specific amino acids and that allow the instructions embedded in the DNA code to be translated into actual proteins. Some of that work was played out in classic papers published in Science during the early 1960s by Marshall Nirenberg, Robert Holley, and their colleagues. In 1968, Maxine Singer published an eloquent tribute to Nirenberg, Holley, and Har Gobind Khorana, who shared the year's Nobel Prize in Medicine or Physiology. In light of their separate but mutually reinforing accomplishments in illuminating the three-base tRNA, "these three men," she wrote, "together constitute a triplet of great sense."

First Steps Toward a Genetic Chemistry
Robert L. Sinsheimer
Science, 7 June 1957, v. 125 (3258): 1123-1128
[PDF] (520K)

RNA Codewords and Protein Synthesis
Marshall Nirenberg, Philip Leder
Science, 25 September 1964, v. 145 (3639): 1399-1407
[PDF] (850K)

Structure of a Ribonucleic Acid
Robert W. Holley et al.
Science, 19 March 1965, v. 147 (3664): 1462-1465
[PDF] (351K)

1968 Nobel Laureate in Medicine or Physiology
Maxine F. Singer
Science, 25 October 1968, v. 162 (3852): 433-436
[PDF] (665K)