Har Gobind Khorana is considered a major contributor to the science of genetics. In addition to developing a relatively inexpensive method of synthesizing acetyl coenzyme A, a complex molecule used in biochemical research, he succeeded in cracking the genetic code of yeast by synthesizing parts of a nucleic acid molecule--an achievement for which he shared the Nobel Prize for physiology or medicine. Khorana went on to do other significant work, including the synthesis of the first completely artificial gene.
Khorana was born around January 9, 1922 in the small village of Raipur, India (now a part of West Pakistan), the youngest of five children of Ganpat Rai Khorana, a tax collector for the British colonial government, and Krishna (Devi) Khorana. His family, although poor, was one of the few literate families in his village. He received his early education under a tree in outdoor classes conducted by the village teacher, and went on to attend high school in Multan, Punjab (India). He later studied chemistry on a government scholarship at the Punjab University in Lahore, graduating with honors in 1943 and receiving a Masters of Science with honors in 1945.
After obtaining his M.S., Khorana went to the University of Liverpool on a Government of India Fellowship to study organic chemistry; there he earned a Ph.D. in 1948 for his research on the structure of the bacterial pigment violacein. From England, Khorana went to Zurich, Switzerland as a postdoctoral fellow to study certain alkaloids (organic bases) under the tutelage of Vladimir Prelog, and after a brief visit to India in 1949, returned to England. From 1950 to 1952, Khorana worked at Cambridge University under Sir Alexander Todd, who later received the Nobel Prize for his work with nucleic acids (large molecules in the nucleus of the cell). While working with Todd, Khorana, too, became interested in the biochemistry of nucleic acids.
In 1952, Khorana took a position as director of the British Columbia Research Council's Organic Chemistry Section, located at the University of British Columbia in Vancouver. There he made his first contribution to the field of biochemistry when he and a colleague, John G. Moffat, announced in 1959 that they had developed a process for synthesizing acetyl coenzyme A , an essential molecule in the biochemical processing of proteins, fats and carbohydrates within the human body. A complex structure, this coenzyme had previously been available only by an astronomically expensive method of isolating the compound from yeast. Moffat and Khorana were able to synthesize acetyl coenzyme A relatively cheaply, thereby making it widely available for research. This work gave Khorana international recognition within the scientific community.
In 1960, Khorana moved to the University of Wisconsin in Madison to accept a position as co-director of the Institute for Enzyme Research. He became a professor of biochemistry in 1962, and in 1964 was named to the Conrad A. Elvelijem Professorship of the life sciences. Khorana then began focusing his research on genetics--specifically, on the biochemistry of nucleic acids, the biosynthesis of enzymes, and on deciphering the genetic code.
At the time Khorana began his research in genetics, scientists already knew much about genes and how they determine heredity. They had discovered that genes are located on chromosomes in the cell nucleus, and that genes are made of deoxyribonucleic acid (DNA) , a nucleic acid which controls the biochemical processes of the cell and governs an organism's inherited traits. DNA's double-helix shape resembles a spiral staircase with regularly spaced steps, with each step consisting of a pair of chemical compounds called nucleotides. The four different types of nucleotides are arranged on the staircase in a pattern of heredity-carrying code "words."
To decipher this code, scientists needed to learn how those words were translated into a second "alphabet" consisting of 20 types of amino acids, the building blocks of protein. Part of this translation had been accomplished prior to Khorana's work. The DNA in the nucleus of a cell causes another nucleic acid called messenger ribonucleic acid (mRNA) to be produced; the messenger RNA then attaches itself to ribosomes, where the cell's proteins are produced. Another type of RNA, called transfer RNA, transports loose amino acids to the ribosomes, where messenger RNA uses them to construct proteins.
Scientists knew that the code word on each transfer RNA molecule indicated the kind of amino acid it would deliver, and instructed it to take it only to a complimentary messenger RNA. They had also figured out that there were 64 possible combinations of nucleotides, each with its own signal. What they did not know was which nucleotide word called for which amino acid.
In 1961, Dr.Marshall Warren Nirenberg of the National Institutes of Health successfully decoded most of the messages in the nucleotides. Khorana carried Nirenberg's work even further, adding significant details. In 1964 he synthesized parts of the nucleic acid molecule, and later was able to duplicate each of the 64 possible genetic words in the DNA staircase. He was able to map out the exact order of the nucleotides, and showed that the code is always transmitted by three-letter words. He also learned that certain nucleotides order the cell to start or stop making proteins.
Khorana's research was based in part on work done separately by both Nirenberg and Robert W. Holley of Cornell University, who completed the first delineation of a complete nucleic acid molecule in 1966. For their contributions to deciphering the genetic code, these three scientists were awarded the 1968 Nobel Prize for Physiology or Medicine. At the presentation ceremony, the three were commended for having "written the most exciting chapter in modern biology."
Two years later, Khorana made another contribution to the field of genetics when he and his colleagues succeeded in synthesizing the first artificial DNA gene of yeast. Khorana announced his achievement in a characteristically modest way, by informing a small symposium of biochemists at the University of Wisconsin in June 1970. He also announced that he and most of his research team would move to the Massachusetts Institute of Technology in the fall. As he explained to a friend, "You stay intellectually alive longer if you change your environment every so often." Khorana joined MIT's faculty as the Alfred P. Sloan Professor of Biology and Chemistry.
Khorana's accomplishments in the laboratory include the artificial synthesis of another gene found in Escherichia coli, an intestinal bacteria known commonly as E. coli. Outside the laboratory, his professional activities include membership in several scientific societies, including the National Academy of Sciences and the American Academy of Arts and Sciences. He also served on the editorial board of the Journal of the American Chemical Society for many years, and published more than 200 articles on technical subjects in that journal and other professional publications.
Khorana has received numerous accolades in addition to the Nobel Prize, including the Lasker Award and the American Chemical Society award. He also was awarded an honorary doctorate by the University of Chicago, and he was named a fellow by Churchill College in Cambridge, England. Khorana also has been a visiting professor at Rockefeller University and Stanford University, and has given lectures at numerous scientific meetings.
Khorana married Esther Elizabeth Sibler in 1952. The couple has two daughters, Julia Elizabeth and Emily Anne, and one son, Dave Roy. Khorana became an American citizen in 1966. Extremely committed to his work, he seldom takes time off, and once went 12 years without taking a vacation. He takes daily long walks, carrying with him an index card to record any ideas that might come to him. He also enjoys going on hikes and listening to music.
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