Nobel Laureates: Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg

 
The Nobel Prize in Physiology or Medicine 1968.

"for their interpretation of the genetic code and its function in protein synthesis"


Robert W. Holley (1922-1992), Har Gobind Khorana (1922- ), and Marshall W. Nirenberg (1922- ) received the Nobel Prize in Physiology or Medicine for their work in cracking the genetic code.

Holley identified and sequenced the first transfer RNA. Khorana developed techniques for synthesizing polynucleotides that could be used to program translation in cell free extracts and Nirenberg identified the amino acids that were incorporated when synthetic RNAs were used.

The presentation speech highlights the significance of this work. It ranks as one of the classic achievements in biology.

In this situation Nirenberg arrived at a very simple and ingenious solution: he realized that the biochemist had a decisive advantage over the archeologist since he could construct in the test tube a system which uses a nucleic acid as template for the formation of a protein. Such a system can be compared with a translation-machine which is fed by the scientist with a sentence written in the alphabet of nucleic acids; the machine then translates the sentence into the protein alphabet. 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.

Much of the final work was done by Khorana. During many years he had systematically devised methods which led to the synthesis of well defined nucleic acids, giant molecules with every building block in its exact position. Khorana's synthetic nucleic acids were a pre-requisite for the final solution of the genetic code.

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.

The interpretation of the genetic code and the elucidation of its function are the highlights of the last 20 years' explosive evolution of molecular biology which has led to an understanding of the details of the mechanism of inheritance. So far the work can be described as basic research. However, through this work we can now begin to understand the causes of many diseases in which heredity plays an important role.

Dr. Holley, Dr. Khorana, Dr. Nirenberg. At the end of his Nobel lecture, Edward Tatum in 1958 looked into his crystal ball and tried to predict some of the future developments in molecular biology. He suggested among other things that the solution of the genetic code might come during the lifetime of at least some of the members of his audience. This appeared to be a bold prophecy at that time. In reality it took less than three years before the first letters of the code were deciphered and, because of the ingenuity of you three, the nature of the code and much of its function in protein synthesis were known within less than eight years. Together you have written the most exciting chapter in modern biology.

This award is somewhat controversial since there are those who think that Heinrich Matthaei should have shared the Nobel Prize [see Cracking the Genetic Code: The polyU Experiment of Nirenberg and Matthaei]. At the time of the discovery, Matthaei was a post-doctoral fellow under Nirenberg. By the time he left to go back to Germany, Matthaei and Nirenberg were not on good terms.