The 1968 Nobel Prize in Medicine was awarded jointly to Marshall W. Nirenberg, Har Gobind Khorana, and Robert W. Holley. These scientists were recognized "for their interpretation of the genetic code and its function in protein synthesis."
Robert W. Holley was born in Illinois, USA. When he received the Nobel Prize, he was affiliated with Cornell University, NY, USA. Marshall W. Nirenberg was born in NY, USA. He was affiliated with the National Institutes of Health, Bethesda, MD, USA, at the time of the award.
Har Gobind Khorana was born in Raipur, India, and was affiliated with the University of Wisconsin, Madison, WI, USA when he received the award. All three scientists were recognized for their work on the genetic code and its significance in transfer of information from DNA to protein.
The deciphering of the genetic code
- Nirenberg and Khorana Discover the “Codon”
By around 1960, the basic chemical pathways through which DNA instructs protein synthesis had been established. However, the genetic code had not yet been cracked.
Marshall Nirenberg, Har Gobind Khorana, and their colleagues, were the first to determine the genetic code and show how the nucleic acid bases, with their alphabet made up of A, U, G, and C, determine the sequence of the 20 different amino acids during protein synthesis.
In 1961, Nirenberg, a biochemist from the National Institute of Arthritic and Metabolic Diseases, described the first base "triplet," a set of three nucleotides that make up a codon. The triplet coded for one of the twenty amino acids used to build proteins. This groundbreaking discovery led to the deciphering of the entire genetic code over the next five years.
A series of test-tube experiments were conducted by Nirenberg and German scientist Johann Matthaei. They added RNA chains containing only one of the 4 bases of RNA - A, G, U, and C – to a "cell free system." Radioactively tagged amino acids were also added to this system.
When a "poly-U"—RNA having only uracil bases was added to the system, radioactive measurements indicated the production of protein-like molecules made up entirely of one single amino acid - phenylalanine. This led the researchers to conclude that the base triplet UUU drives the addition of phenylalanine to growing polypeptide chains.
Continuing this technique, Nirenberg proceeded to decipher 35 base triplets by 1963 and more than 60 triplets by 1966, all of which contained three specifically ordered bases. As there were a total of 4 bases in RNA, there were 64 possible codons or triplets in the genetic code.
This meant that more than one codon could code for one amino acid, thus making the code redundant. For instance, the codons AAG and AAA code for lysine. Eventually, three of the codons - UAG, UAA, and UGA - were found to be STOP codons that signal the end of amino acid chains.
Har Gobind Khorana, a researcher from the University of Wisconsin, extended and adapted Nirenberg's work. He devised biochemical methods for producing synthetic RNA with specifically located nucleotides. The first of these nucleic acids was made up of a repeating sequence of the two nucelotides U and C, which, after translation, gave an amino acid chain made up of serine and leucine. Synthetic RNA was used later to ascertain the remainder of the genetic code.
Robert holley and nucleic acid structure
Robert Holley from Cornell University discovered a particular type of nucleic acid, transfer RNA (tRNA) and in 1965, deciphered its structure. It was the first time the structure of a biologically active nucleic acid had been established. It emerged that tRNA was the mystery molecule that Crick had proposed ten years previously in his “Adapter Hypothesis.”
Seven years after the first codon of the genetic code was described, Nirenberg, Khorana, and Holley received the Nobel Prize in Physiology or Medicine in 1968.