Biography of Har Gobind Khorana

Har Gobind Khorana (born 1922) was an Indian organic chemist and cowinner of the 1968 Nobel Prize for physiology or medicine. His research in chemical genetics vastly extended our understanding of how the chemicals of a cell nucleus transmit information to succeeding generations of cells.

Har Gobind Khorana was born in Raipur on January 9, 1922. After obtaining a doctorate in chemistry from the University of Liverpool, he worked with V. Prelog at the Federal Institute of Technology in Zurich and with Sir Alexander Todd at Cambridge University. From 1952 to 1960 he was head of the Organic Chemistry Group of the British Commonwealth Research Council in Vancouver, and for part of this period he was visiting research professor at the Rockefeller University in New York City. He moved to the University of Wisconsin in 1960 and in 1964 was named to the Conrad A. Elvehjem chair in life sciences at the Institute of Enzyme Research.

Khorana's research embraced many fields: peptides and proteins; chemistry of phosphate esters, nucleic acids, and viruses; and chemical genetics. It was his work in chemical genetics that secured for him three coveted prizes: the Merck Award of the Chemical Institute of Canada in 1958, the Louisa Gross Horwitz Prize of Columbia University in 1968, and the Nobel Prize in the same year.

Khorana's work supplements the research of Marshall Nirenberg and Robert Holley. In 1961, while experimenting with the intestinal bacterium Escherichia coli, Nirenberg had deciphered the coded messages that DNA (deoxyribonucleic acid) sends to RNA (ribonucleic acid), which in turn prescribes the synthesis of new proteins. Further experiments revealed codes for most of the known amino acids normally present in proteins. But, although the nucleotide composition became known, gaps in the knowledge about the order of the nucleotide remained.

With his coworkers Khorana resolved this gap by synthesizing all of the 64 possible trinucleotides. He used synthetic polydeoxyribonucleotides of known sequence to direct the synthesis of long, complementary, polyribonucleotides in reactions catalyzed by the enzyme RNA polymerase. By preparing RNA-like polymers with alternating sequence, he demonstrated that such a polymer directs the synthesis of a polypeptide with alternating amino acids--leucine and serine.

After testing a large number of such polymers, Khorana afforded a clear proof of codon assignments and confirmed that the genetic language is linear and consecutive and that three nucleotides specify an amino acid. In addition, he proved the direction in which the information of the messenger RNA is read and that the code words cannot overlap. The manner in which polyribonucleotides are manufactured afforded the clearest proof that the sequence of nucleotides in DNA specifies the sequence of amino acids in proteins through the intermediary of an RNA.

In 1970 Khorna left the University of Wisconsin for the Massachusetts Institute of Technology, becoming the Alfred P. Sloan Professor. He was associated with Cornell University from 1974 to 1980 as well. Also in 1970, Khorana made a major breakthrough when he announced the synthesis of the first artificial gene. Six years later, Khorana and his team created a second artificial gene, this one capable of functioning in a living cell. This valuable work laid the foundation for a future in which scientists could use artificial genes to synthesize important proteins or to cure hereditary diseases in humans. In recent years, Khorana has synthesized the gene for bovine rhodopsin, the retinal pigment that converts light energy into electrical energy.

Khorana, who became an American citizen in 1966, has developed a reputation as a tireless worker who once went 12 years without a vacation. He enjoys hiking, listening to music, and often takes his scientific inspiration from long daily walks. With his wife, Esther Elizabeth Sibler, he raised two daughters, Julia Elizabeth and Emily Anne, and one son, Dave Roy.

Further Reading

• An autobiographical sketch by Khorana, his Nobel lecture, and the presentation speech of the Nobel Committee (all in English) appear in the annual Les Prix Nobel en 1968 (1969). A good source for understanding genetical research and Khorana's work is Robert H. Haynes and Philip C. Hanawalt, eds., The Molecular Basis of Life: An Introduction to Molecular Biology (1968). His work is also discussed in Carl R. Woese, The Genetic Code: The Molecular Basis for Genetic Expression (1967).