Khorana, Har Gobind (1922- )

Khorana, Har Gobind (1922- )

Indian-born American biochemist

Har Gobind Khorana, an organic chemist who specialized in the study of proteins and nucleic acids, shared the Nobel Prize in Physiology of Medicine with Robert W. Holley (1922– ) and Marshall W. Nirenberg (1927– ) in 1968 for discoveries related to the genetic code and its function in protein synthesis . In addition to developing methods for investigating the structure of the nucleic acids, Khorana introduced many of the techniques that allowed scientists to decipher the genetic code and show how ribonucleic acid (RNA ) can specify the structure of proteins. Four years after winning the Nobel Prize, Khorana succeeded in synthesizing the first wholly artificial gene . In the 1980s Khorana synthesized the gene for rhodopsin, a protein involved in vision.

Har Gobind Khorana, youngest of the five children of Shri Ganput Rai Khorana and Shrimat Krishna Devi Khorana, was born in Raipur, in the Punjab region of India (now part of West Pakistan). His birth date was recorded as January 9, 1922, but the exact date of his birth is uncertain. Although his family was poor, his parents believed strongly in the importance of education. His father was a village agricultural taxation clerk in the British colonial government. Khorana attended D.A.V. High School in Multan (now West Punjab). After receiving his Bachelor of Science (1943, with honors) and Master's degree (1945, with honors) from Punjab University in Lahore, India, Khorana was awarded a Government of India Fellowship, which enabled him to study at Liverpool University, England, where he earned his Ph.D. in 1948. From 1948 to 1949, he worked as a postdoctoral fellow at the Federal Institute of Technology, Zurich, Switzerland, with Professor Vladimir Prelog, who had a major influence on his life-long approach to science.

After briefly returning to India, Khorana accepted a position in the laboratory of (Lord) Alexander Todd at Cambridge University (1950–52), where he studied proteins and nucleic acids. From 1952 to 1960, Khorana worked in the organic chemistry section of the British Columbia Research Council, Vancouver, Canada. The next year Khorana moved to the University of Wisconsin, Madison, Wisconsin, where he served as Co-director of the Institute for Enzyme Research and Professor of Biochemistry . In 1964, he became the Conrad A. Elvehjem Professor of the Life Sciences. In 1970, Khorana accepted the position of Alfred P. Sloan Professor, Departments of Biology and Chemistry, at the Massachusetts Institute of Technology, Cambridge, Massachusetts. From 1974 to 1980, he was Andrew D. White Professor-at-large, Cornell University, Ithaca, New York. During his long and distinguished career, Khorana has been the author or co-author of over 500 scientific publications.

In 1953, Khorana and Todd published their only coauthored paper; it described the use of a novel phosphorylating reagent. Khorana found that this reagent was very useful in overcoming problems in the synthesis of polynucleotides. Between 1956 and 1958, Khorana and his coworkers established the fundamental techniques of nucleotide chemistry. Their goal was to develop purely chemical methods of synthesizing oligonucleotides (long chains of nucleotides). In 1961, Khorana synthesized Coenzyme A, a factor needed for the activity of certain key metabolic enzymes .

In 1955, Khorana learned about Severo Ochoa's discovery of the enzyme polynucleotide phosphorylase and met Arthur Kornberg, who described pioneering research on the enzymatic synthesis of DNA . These discoveries revolutionized nucleic acid research and made it possible to elucidate the genetic code. Khorana and his coworkers synthesized each of the 64 possible triplets (codons) by synthesizing polynucleotides of known composition. Khorana also devised the methods that led to the synthesis of large, well-defined nucleic acids.

By combining synthetic and enzymatic methods, Khorana was able to overcome many obstacles to the chemical synthesis of polyribonucleotides. Khorana's work provided unequivocal proof of codon assignments and defined some codons that had not been determined by other methods. Some triplets, which did not seem to code for any particular amino acid, were shown to serve as "punctuation marks" for beginning and ending the synthesis of polypeptide chains (long chains of amino acids). Khorana's investigations also provided direct evidence concerning other characteristics of the genetic code. For example, Khorana's work proved that three nucleotides specify an amino acid, provided proof of the direction in which the information in messenger RNA is read, demonstrated that punctuation between codons is unnecessary, and that the codons did not overlap. Moreover, construction of specific polyribonucleotides proved that an RNA intermediary is involved in translating the sequence of nucleotides in DNA into the sequence of amino acids in a protein. Summarizing the remarkable progress that had been made up to 1968 in polynucleotide synthesis and understanding the genetic code, Khorana remarked that the nature of the genetic code was fairly well established, at least for Escherichia coli.

Once the genetic code had been elucidated, Khorana focused on gene structure-gene function relationships and studies of DNA-protein interactions. In order to understand gene expression, Khorana turned to DNA synthesis and sequencing. Recognizing the importance of the class of ribonucleotides known as transfer RNAs (tRNAs), Khorana decided to synthesize the DNA sequence that coded for alanine tRNA. The nucleotide sequence of this tRNA had been determined in Robert Holley's laboratory. In 1970, when Khorana announced the total synthesis of the first wholly artificial gene, his achievement was honored as a major landmark in molecular biology . Six years later, Khorana and his associates synthesized another gene. In the 1980s, Khorana carried out studies of the chemistry and molecular biology of the gene for rhodopsin, a protein involved in vision.

In 1966, Khorana was elected to the National Academy of Sciences. His many honors and awards include the Merck Award from the Chemical Institute of Canada, the Dannie-Heinneman Prize, the American Chemical Society Award for Creative Work in Synthetic Organic Chemistry, the Lasker Foundation Award for Basic Medical Research, the Padma Vibhushan Presidential Award, the Ellis Island Medal of Honor, the National Medal of Science, and the Paul Kayser International Award of Merit in Retina Research. He holds Honorary Degrees for numerous universities, including Simon Fraser University, Vancouver, Canada; University of Liverpool, England; University of Punjab, India; University of Delhi, India; Calcutta University, India; University of Chicago; and University of British Columbia, Vancouver, Canada.

See also Genetic regulation of eukaryotic cells; Microbial genetics