Holley

Nirenberg

Har Khorana

Robert W. Holley (b. 1922, d 1993), Cornell University, Ithaca, NY, USA; Har Gobind Khorana (b. 1922, in Raipur, India), University of Wisconsin, Madison, WI, USA; Marshall W. Nirenberg (b. 1927, d. 2010), National Institutes of Health, Bethesda, MD, USA. The Nobel Prize in Physiology or Medicine 1968.
From the presentation by P. Reichard, Member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute

During the fall of 1868, exactly 100 years ago, a young Swiss physician by the name of Friedrich Miescher isolated a new type of compound from cell nuclei. He called this compound nuclein; today we call it nucleic acid. Two years earlier, unbeknownst to Miescher, a Czech monk, Gregor Mendel, in the town of Brno finished a series of experiments which eventually turned out to be closely connected with Miescher's discovery. From very simple experiments with peas Mendel discovered that our inheritance is packaged into many independent genes. Mendel's work marked the beginning of genetics as a science.
Nucleic acids and genes - originally two widely separated concepts - together form the basis for this year's Nobel Prize for medicine, for Holley's, Khorana's and Nirenberg's investigations on the genetic code, also called the code of life.
During the 19th century the Nobel Prize had not been established. Had the prize existed it is unlikely that it would have been awarded for the discoveries of nucleic acids and genes. Miescher's results were published in extenso only after his death in 1890. Mendel reported his observations in a first publication in 1866, which received little attention and was soon forgotten.
Nucleic acid research came of age in 1944. In this year the American scientist Avery succeeded in transferring a hereditable property from one bacterium to another with the aid of pure nucleic acid, and in so doing demonstrated that genes are made up of nucleic acids.
Avery's discovery marked the beginning of a new branch of science which has come to be called molecular biology and which, up to the present time, has been concerned mainly with the biochemistry of genetics. The vitality of molecular biology is attested by the fact that today's prize is the fifth Nobel Prize in medicine since 1958 awarded to research in this area.

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Nirenberg synthesized a very simple nucleic acid, composed of a chain of only a single repeating letter. Using this nucleic acid the system produced a protein which also contained a single letter, now written in the protein alphabet. In this way Nirenberg had both deciphered the first hieroglyph and shown how the machinery of the cell can be used for the translation of the genetic code in general. After that, the field moved extremely rapidly. Nirenberg reported his first results in August 1961. Less than five years later all the details of the genetic code were established, mainly from the work of Nirenberg and Khorana.

What is the mechanism for the translation of the code within the cell? This question was successfully attacked by Holley. He is one of the discoverers of a special type of nucleic acid which has been called transfer-RNA. This nucleic acid has the capacity to read off the genetic code and to transform it to the protein alphabet. After many years' work Holley succeeded in preparing a transfer-RNA in pure form and, finally, in 1965, established its exact chemical structure. Holley's work represents the first determination of the complete chemical structure of a biologically active nucleic acid.