Har Gobind Khorana 1922-, American biochemist, b. Raipur (now in Pakistan), Ph.D. Univ. of Liverpool, 1948. He became a U.S. citizen in 1966, and has been a professor at the Massachusetts Institute of Technology since 1970. Khorana, Marshall W. Nirenberg , and Robert W. Holley were awarded the 1968 Nobel Prize in physiology or medicine for their discoveries concerning the genetic code and its function in protein synthesis. Khorana confirmed Nirenberg's finding that the arrangement of the four types of nucleotides on the DNA molecule (see nucleic acid ) determines the chemical composition and function of new cells; he then built on this finding and determined the nucleotide combinations that form specific amino acids. Khorana was also the first scientist to synthesize strings of nucleotides.

Khorana, Har Gobind

AMERICAN BIOCHEMIST 1922–

Har Gobind Khorana was born in a small village in British India, in which his family was among the few literate residents. He received his M.S. from the University of Lahore, and in 1945 he was awarded a grant to study for a Ph.D. at the University of Liverpool. He then went on to complete postdoctoral work in Switzerland and at Cambridge. It was there, while working with Alexander Todd, that Khorana became interested in both nucleic acids and proteins, the study of which became his life's work.

In 1952 G. M. Shrum, head of the British Research Council on the campus of the University of British Columbia, Vancouver, Canada, offered Khorana the opportunity to form his own research group on whatever topic he wished. His group became very successful in developing methods for synthesizing phosphate ester derivatives of nucleic acids, and in 1959 he and John G. Moffatt announced the synthesis of acetyl coenzyme A (acetyl CoA), a molecule essential to the biochemical processing of proteins fats and carbohydrates. Prior to this work, the coenzyme had to be extracted from yeast by a very laborious and expensive process, so this discovery led to Khorana's international recognition within the scientific community and he received many job offers as a result. He accepted the position of codirector of the Institute for Enzyme Research at the University of Wisconsin.

In the early 1960s it had been recognized that DNA and RNA (in the form of messenger RNA [mRNA]) were somehow involved in the synthesis of proteins in living cells. Whereas the basic building blocks of DNA are the four nucleotides adenosine (A), cytosine (C), guanine (G), and thymine (T)—in RNA, uracil (U) is substituted for thiamine—the basic building blocks of all proteins are twenty amino acids strung together in different sequences to produce individual proteins. In 1961, Marshall W. Nirenberg, and Heinrich J. Matthaei announced that they had created a synthetic mRNA, which, when inserted into E. coli bacteria, always caused the addition of one amino acid phenylalanine to a growing strand of linked amino acid. They also determined that if they synthesized RNA with three units of uracil joined together, it caused an amino acid chain consisting entirely of phenylalanine to be produced.

These experiments, which proved that mRNA transmits the genetic information from DNA, thus directing the creation of specific complex proteins, stimulated Khorana to use his expertise in polynucleotide synthesis to uncover the exact mechanisms involved. The results were spectacular. Within a few short years his research group was able to establish which serial combinations of nucleotides form which specific amino acids; that nucleotide instructions (genetic code ) are always transmitted to the cell in groups of three called codons; and that some of the codons direct the cell to start or stop the manufacture of proteins. For this work Khorana, along with Nirenberg and biochemist Robert W. Holley, was awarded the Nobel Prize in physiology in 1968.

In 1970 Khorana announced the creation of the first artificial DNA gene of yeast. At the same time, he and most of his research team moved to the Massachusetts Institute of Technology (MIT) because, as he explained, "You stay intellectually alive longer if you change your environment every so often" (McMurray, p. 1089). Since going to MIT, Khorana has reported major advances concerning how rhodopsin, the photo receptor in the human eye, functions.

see also Codon; Nucleic Acids; Todd, Alexander.

John E. Bloor

Bibliography

McMurray, Emily J., ed. (1995). Notable Twentieth-Century Scientists. Detroit, MI: Gale Research.

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). □