"Cracking" the genetic code was one of the most exciting discoveries of the twentieth century. Although philosophers and early scientists had long pondered the nature of inheritance, it was not until 1953 that James Watson (1928- ) and Francis Crick (1916- ) announced that they had determined that the code for life resides in the molecular structure of deoxyribonucleic acid (DNA). This announcement began a frenzy of investigation that still continues today. One of the hottest topics in science at the end of the twentieth century is molecular biology.
In 1954 George Gamow (1904-1968) published the first theoretical consideration of a genetic code, suggesting that amino acids fit into the "holes" on the DNA. Other scientists were also investigating the relationship.

In 1957 Crick and Gamov worked out the "central dogma," explaining how DNA makes a protein. The central theme of this idea is the "sequence hypothesis," which states that the order of pairs on the DNA determine a specific amino acid. They also suggested information goes only in one direction: from DNA to RNA to protein.
Examining how the genetic code controls synthesis of proteins, American biochemist Robert Holley began his research on RNA after studying with James F. Bonner at the California Institute of Technology in 1956. By 1960 Holley and colleagues had shown that tRNA provides instructions for the assembly of amino acids into proteins. This discovery was independent of Hoagland. Holley's team developed techniques to separate tRNA from the cell. By 1965 Holley had established how tRNA incorporates the amino acid alanine to form specific proteins. First, he determined the sequence of the nucleotides by digesting the molecule with enzymes, identifying the resulting pieces, and then figuring out how these pieces fit back together. All tRNA molecules have been determined to have similar structures. Marshall Nirenberg built a strand of tRNA comprised only of the base uracil. Calling the strand "poly U," he discovered that UUU is the codon for the amino acid phenylalanine. This finding was the first step in setting up the code for other amino acids. In 1966 the genetic code was cracked when Nirenberg and his team announced that a specific sequence of three nucleotide bases (a codon) determined each of twenty amino acids. Holley, along with Nirenberg and Har Gobind Khorana (1922- ), shared the Nobel Prize in physiology or medicine in 1968 for their studies of amino acids and proteins.