H. Gobind Khorana, biochemist and Nobel Prize winner, dies

November 11, 2011

H. Gobind Khorana, who rose from poverty in rural India to become one of the world’s foremost biochemists and who shared the Nobel Prize for helping unravel how genetic information in a cell is used to make proteins vital for human life, died Nov. 9 at a rehabilitation facility in Concord, Mass. He was believed to be 89.

His daughter, Julia Khorana, confirmed the death but did not know the cause. Dr. Khorana was a resident of Cambridge, Mass., and an emeritus professor of biology and chemistry at the Massachusetts Institute of Technology, where he had been since 1970.

From his largely illiterate village in India’s Punjab region, Dr. Khorana won scholarships and fellowships that advanced his education. He developed an interest in researching proteins and nucleic acids while at the University of Cambridge in the early 1950s.

This was a period of rapid discovery in the field of genetics, especially at Cambridge, where scientists James Watson and Francis Crick discovered the double-helix structure of deoxyribonucleic acid (DNA). DNA is composed of four chemical bases called nucleotides — adenine, cytosine, guanine and thymine — in a certain order. It is this order that comprises the genetic information in DNA.

The question remained how this genetic information was used to join amino acids, in a specific order, for the manufacture of proteins, chemicals that help regulate the functions of life.

Working at universities in Canada and the United States, Dr. Khorana built his research off the foundations laid by Crick, Watson, Maurice Wilkins and Rosalind Franklin. (The three men won the Nobel in 1962; Franklin’s death in 1958 disqualified her for the award.)

Dr. Khorana, then at the University of Wisconsin, shared the 1968 Nobel in physiology or medicine with Robert W. Holley of Cornell University and Marshall W. Nirenberg of the National Institutes of Health. They worked independently and won the award “for their interpretation of the genetic code and its function in protein synthesis,” according to the Nobel citation.

They showed that the four DNA nucleotides form three-letter words that specify the amino acids to be joined to proteins. It is how those units of trinucleotides work — the “words” in their code — that Dr. Khorana, Nirenberg and Holley worked for years to unravel.

Nirenberg found the first so-called “word” in 1961 — UUU, for the amino acid phenylalanine — and Dr. Khorana and Holley amplified that research and helped to identify the meaning of all 64 trinucleotides.

Specifically, Dr. Khorana confirmed the belief that the code is transmitted by separate and distinct three-letter “words” and found the precise order of the nucleotides within each triplet.

He and Nirenberg also uncovered how the same amino acids are specified by more than one of the triplets and, along with others, how specific trinucleotides tell the cell to start or stop making a protein.

After receiving the Nobel, Dr. Khorana conducted research that led to the creation of the first entirely artificial gene starting from simple chemicals and, in 1976, showed that such a synthetic gene worked perfectly well inside a cell.

“It’s a major breakthrough in genetics and in chemical biology,” said Uttam L. RajBhandary, a molecular biology professor at MIT. “This work basically made it possible for scientists to think about synthesizing large genes, including perhaps the entire DNA of a living cell. Such work is, in fact, being done now.”

Before retiring from MIT in 2007, Dr. Khorana continued research into cellular components, notably examining the pigment on the retina that regulates how people perceive light.

Har Gobind Khorana was born, to the best of his knowledge, on Jan. 9, 1922, in the village of Raipur, now part of Pakistan. He was the youngest of five siblings born to a tax collector in the British colonial government. They were an impoverished Hindu family.

“Although poor, my father was dedicated to educating his children and we were practically the only literate family in the village inhabited by about 100 people,” he later wrote.

While Dr. Khorana’s early interests encompassed literature and science, his daughter said, he won a government scholarship to study science at Punjab University in Lahore.

He received a bachelor’s degree in chemistry in 1943, followed by a master’s degree two years later. A government fellowship allowed him to study at the University of Liverpool in England, and he earned a doctorate in organic chemistry in 1948.

With the help of post-graduate fellowships, he studied at the Federal Institute of Technology in Zurich and at Cambridge.

In 1952, he married a Swiss woman, Esther Sibler. She died in 2001, and their daughter Emily Khorana died in 1978. Survivors include two children, Julia Khorana of Stow, Mass., and Dave Khorana of Wakefield, Mass.

Starting in 1952, Dr. Khorana found work in Vancouver directing the organic chemistry section at the University of British Columbia. In 1959, he and a research associate, John G. Moffatt, were credited with the synthesis of coenzyme A — a key substance in cells that helps cellular metabolism. The chemical method they used to synthesize coenzyme A made it far cheaper for companies to produce, and that meant it was more broadly available to scientists.

In 1960, he moved to the University of Wisconsin and served as co-director of its Institute for Enzyme Research. While there, his Nobel work was done. He became a U.S. citizen in 1966.

In addition to the Nobel, Dr. Khorana’s honors included the prestigious Albert Lasker award for medical research in 1968 and the National Medal of Science in 1987 for “innovative contributions that significantly contributed to our understanding of gene structure, membrane function and vision.’’

In contrast with some of the more-flamboyant early figures in genetic research, notably Watson, Dr. Khorana was known for a modest, ingratiating manner. He tended to shun publicity, making many of his most important scientific announcements at departmental seminars and in scientific publications.

When he spoke out, it was against declines in scientific funding by the government and against the Vietnam War and the U.S. invasion of Iraq in 2003. He also was a signatory to a petition denouncing efforts to teach public school children “creation science” alongside evolution.

Adam Bernstein has spent his career putting the "post" in Washington Post, first as an obituary writer and then as editor. The American Society of Newspaper Editors recognized Bernstein’s ability to exhume “the small details and anecdotes that get at the essence of the person” and to write stories that are “complex yet stylish.”
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