Har Gobind Khorana
1922-
Indian-born American Organic Chemist and Biochemist
In 1968 Har Gobind Khorana shared the Nobel Prize in Medicine or Physiology with Robert W. Holley (1922-1993) and Marshall W. Nirenberg (1927- ) "for their interpretation of the genetic code and its function in protein synthesis." As a result of their independent, but interrelated nucleic acid researches, they were able to break the genetic code and prove that the universal language of nucleic acids is spelled out in three-letter words. Each codon, or triplet, codes for a specific amino acid. Specifically designed oligonucleotides, which can be thought of as artificial genes, became essential tools in research and biotechnology for sequencing, cloning, and bioengineering new plants and animals.
Khorana was the youngest of five children born to Hindu parents in Raipur, a village of about 100 people in Punjab, India, which is now part of West Pakistan. His father, who was dedicated to his children's education, was an agricultural taxation clerk in the British government. Khorana attended D.A.V. High School in Multan, and earned his B.Sc. and M.Sc. from the Punjab University in Lahore in 1943 and 1945, respectively. In 1945 a Government of India Fellowship allowed him to go to the University of Liverpool, England, where he was awarded the Ph.D. in 1948. For further training, Khorana spent a year in the laboratory of Vladimir Prelog (1906- ) at the Federal Institute of Technology in Zurich, Switzerland. After a brief stay in India, Khorana returned to England from 1950 to 1952, where he obtained a fellowship to work with G. W. Kenner and Alexander Todd (1907-1997). During this period, Khorana became interested in both proteins and nucleic acids.
In 1952 he received an offer of a research position in the organic chemistry section of the British Columbia Research Council and the University of British Columbia, Canada. Although Khorana first received international recognition during this period for the synthesis of coenzyme A, he generally focused his research group on biologically interesting phosphate esters and nucleic acids. In 1960 Khorana moved to the Institute for Enzyme Research at the University of Wisconsin, Madison, where he became Professor of Biochemistry and co-director of the Institute. In 1970 he accepted the position of Alfred P. Sloan Professor of Biology and Chemistry at Massachusetts Institute of Technology. He has also served as visiting professor at Stanford University, Harvard Medical School, Cornell University, and Rockefeller University.
While at the University of Wisconsin, Khorana devised methods for synthesizing specific oligonucleotides, that is, long chains of RNA in which the base sequences were precisely known. Khorana was able to replicate each of the 64 possible codons (triplets) and create RNA-like molecules. He could then demonstrate, for example, that an oligonucleotide containing alternating triplets of CUC and UCU directed the synthesis of a polypeptide in which leucine alternated with serine. Using this approach, Khorana proved that the code consisted of three-letter, non-overlapping words, read in a specific linear fashion. The code was also shown to have "punctuation marks," that is, certain triplets dictated the beginning and the ending of polypeptide chain synthesis. Khorana and his associates worked out methods for the chemical synthesis of both RNA and DNA polynucleotides. His announcement in 1970 of the complete synthesis of the gene for alanine transfer RNA, the first wholly artificial gene, was greeted as a major landmark in molecular biology.
In the 1980s Khorana turned to research on the chemistry and molecular biology of rhodopsin, the light transducing pigment of the retina, and bacteriorhodopsin, (a form of rhodopsin found in bacteria). Khorana's group synthesized the gene for rhodopsin and studied its mechanisms of action and expression. In the 1990s Khorana's work on vision led to the discovery that the misfolding of defective rhodopsin might be responsible for the inherited form of blindness known as retinitis pigmentosa. Studies of these mutant forms of rhodopsin may help explain certain clinical findings associated with retinitis pigmentosa.
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