New York:
Har Gobind Khorana, who rose from a childhood of poverty in India to become a biochemist and share in a Nobel Prize for his role in deciphering the genetic code, died on Wednesday in Concord, Massachusetts. He was 89.
His death was announced by the Massachusetts Institute of Technology, where Dr Khorana was a professor emeritus.
Dr Khorana, who received his early schooling from his village teacher under a tree, advanced his education through scholarships and fellowships to become an authority on the chemical synthesis of proteins and nucleic acids, the large molecules in cells that carry genetic information.
He received the 1968 Nobel Prize in Physiology or Medicine with Robert W Holley of Cornell University and Marshall W. Nirenberg of the National Institutes of Health. They worked independently of one another and received the award for showing how genetic information is translated into proteins, which carry out the functions of a living cell.
Their experiments looked at the nucleic acids found in RNA, a chemical in cells that translates the genetic information contained in DNA. RNA is composed of four chemical bases, adenine, cytosine, uracil and guanine, which are represented by the letters A, C, U and G. The three scientists showed that these chemical bases combine to form three-letter "words" that represent amino acids, the components from which proteins are constructed. Dr Nirenberg discovered the first word, UUU, the code for phenylalanine.
Dr Khorana used chemical synthesis to combine the letters into specific defined patterns, like UCUCUCUCU, from which he deduced that UCU encoded for serine and CUC encoded for leucine. His work unambiguously confirmed that the genetic code consisted of 64 distinct three-letter words. He and Dr Nirenberg discovered that some of the words told a cell where to begin reading the code, and where to stop.
In 1972, Dr Khorana reported a second breakthrough: the construction of the first artificial gene, using off-the-shelf chemicals. Four years later, he announced that he had gotten an artificial gene to function in a bacterial cell. The ability to synthesize DNA was central to advances in genetic engineering and the development of the biotechnology industry. "He left an amazing trail of technical achievement," said Dr Thomas P Sakmar, a professor at Rockefeller University and a former student.
Dr Khorana's lab also turned out leaders in academia and industry. One former student was involved in the creation of Applied Biosystems, which developed equipment used to decode the human genome. Another student, Michael Smith, was a recipient of the 1993 Nobel Prize in Chemistry for devising a method of manipulating DNA.
Har Gobind Khorana was born in the village of Raipur in the Punjab region, which is now part of Pakistan. Not certain of the date, he said he was probably born on January 9, 1922. He was the youngest of five children of a Hindu tax clerk for the British colonial government, who was dedicated to educating his children. His family was "practically the only literate family in the village inhabited by 100 people," Dr Khorana wrote.
His aptitude for science was evident from the start. He received a scholarship to study chemistry at Punjab University, although he had been too shy to attend the required admissions interview. He received his bachelor's degree from Punjab University in 1943 and his master's from there in 1945.
After earning a doctorate in organic chemistry from Liverpool University in England in 1948, he spent a year doing postdoctoral research at the Federal Institute of Technology in Switzerland, where he secretly took up residence in a laboratory until some financing came through.
He received a research fellowship at Cambridge University, a center for the study of proteins and nucleic acids, where James D. Watson and Francis H. C. Crick would discover the double-helix structure of DNA in 1953. Dr Khorana was drawn to the field.
In 1952, he was recruited to the British Columbia Research Council in Vancouver to join a group working on nucleic acids. He developed a new method of synthesizing nucleotides, and achieved international recognition for synthesizing coenzyme A, which is involved in converting fats to energy.
His move to Canada coincided with his marriage to Esther Elizabeth Sibler, whom he had met in Switzerland. "Esther brought a consistent sense of purpose into my life at a time when, after six years' absence from the country of my birth, I felt out of place everywhere and at home nowhere," he wrote.
His wife died in 2001. Their daughter Emily Anne died in 1979. His survivors include another daughter, Julia Elizabeth, and a son, Dave Roy.
In 1960, Dr Khorana moved to the Institute for Enzyme Research at the University of Wisconsin, where he did the work that led to his Nobel Prize. His lab included researchers from 27 countries with expertise in basic chemistry, molecular biology, enzymology and biochemistry, a multidisciplinary effort unusual for its time.
Dr Khorana became an American citizen in 1966. He joined the M.I.T. faculty in 1970 and retired in 2007.
Among the honors Dr Khorana received were the Lasker Award for basic medical research in 1968 and the National Medal of Science in 1987.
Dr Khorana, an unassuming man, shied from the spotlight and did not like talking on the phone. In the weeks before he received the National Medal of Science, a stack of message slips piled up on his desk with increasingly urgent messages that the White House had called and that he should call back, Dr Sakmar said. With the ceremony date fast approaching, a representative of the White House tracked down Dr Khorana at a scientific meeting and told him he would be receiving the award. Dr Khorana assured him he would attend.