January 2012

Har Gobind Khorana (1922—2011)


Photo courtesy of Massachusetts Institute for Technology News Office

Har Gobind Khorana, the Sloan professor emeritus of chemistry and biology at the Massachusetts Institute of Technology, died on Nov. 9 in Concord, Mass., at age 89. He was my postdoctoral mentor from 1964 to 1966 and a dear, lifelong friend. During the mid-1960s, his research team, consisting of about 16 postdoctoral fellows a large group even for that time), solved the genetic code. This achievement was remarkable, because this moniker had not even been coined when I joined his team at the Institute for Enzyme Research at the University of Wisconsin. However, when I assumed my professorship in the department of biochemistry in Madison 24 months later, all 64 codon assignments as well as the stop and start codons had been determined by two different experimental strategies and were published. In 1968, Gobind shared the Nobel Prize in physiology or medicine with Robert W. Holley of Cornell University and Marshall W. Nirenberg of the National Institutes of Health for these discoveries and, over the years, was the recipient of numerous other prizes and accolades.


Gobind pioneered the interface of biology and chemistry long before this topic became popular. His contributions spanned peptides and proteins, carbohydrates, nucleic acids and membranes.

Vancouver and Madison
In 1952, he began his academic career in Vancouver at the British Columbia Research Council, where he pioneered methodologies to synthesize nucleotides and achieved international recognition for synthesizing coenzyme A. He also developed, almost single-handedly, the steps to synthesize small ribo- and deoxyribo-oligonucleotides. He moved eight years later to the Institute for Enzyme Research in Madison, Wis., where he undertook his Nobel Prize work. Undoubtedly, his knowledge of enzymology and the biochemistry of peptides as well as oligonucleotides provided a trove of experience for the genetic code problem. He could both strategize and organize, skillfully marrying the research programs of a large number of postdoctoral fellows. I and other fellows worked hard during this time, but Gobind’s brilliance deserves the credit.

In 1970, he quickly moved on to report another breakthrough: the construction of the first synthetic gene (for yeast alanine transfer RNA) using commercially available chemicals. Then, six years later, he showed that the synthetic gene for a different tRNA with all the necessary signals for expression in vivo functioned in a bacterial cell. The current biotechnology industry and genetic engineering methodologies are dependent on chemically synthesized segments of DNA or RNA, and Gobind’s discoveries were critical to these developments.

He joined the MIT faculty in 1970 and retired in 2007. During this period, his lab focused mostly on biological membranes and bioenergetics and elucidated the mechanism of proton transport in light transduction by bacteriorhodopsin in the purple membrane. His most recent work was in the mammalian visual sensory system and involved G-protein-coupled receptors. His approach continued to be multidisciplinary, involving biochemistry, genetics, chemistry and cell biology.

He mentored more than 150 postdoctoral fellows and several graduate students. A notable number of these scientists are now leaders in academia, biotechnology industries and government service. Gobind was a prodigious contributor to the scientific literature, with more than 450 original, refereed publications. After the synthesis of the alanine tRNA gene, an entire issue (Dec. 28, 1972) of the Journal of Molecular Biology was devoted to publishing a series of 13 of his papers; I can’t recall ever observing this feat by another scientist.


The beginning
Born in the village of Raipur, which was then nestled in India’s Punjab region and now within the bounds of Pakistan, Gobind was the youngest of five children. While his father was a Hindu tax clerk for the British colonial government and the family lived in poverty, Gobind once wrote that his was “practically the only literate family in the village of 100 people.” He repeatedly told stories of his early education from his teacher under a tree. Moreover,I remember his glee in telling me of his pride when his father gave him a pencil for one of his birthdays but then broke it in half and told him only to use half at a time.

His university training began at Punjab University, where he studied chemistry on a scholarship and earned his bachelor’s degree in 1943 and his master’s degree in 1945. He was admitted although he had been too shy to attend the required admissions interview. He earned a Ph.D. in organic chemistry from Liverpool University in 1948 and then spent a year as a postdoctoral researcher at the Swiss Federal Institute of Technology, now known as ETH Zurich. There, he secretly camped out in a lab until Cambridge University came through with some funds. For this further training in England, he worked with Lord Alexander Todd on the chemistry of small molecules. Cambridge had become a stronghold of protein and nucleic acid biochemistry; Watson and Crick would discover the double-helical structure of DNA in 1953.

Always humble and hardworking, Gobind embodied dedication and drive. He treated his students and staff thoughtfully and fairly, and he demonstrated his loyalty to them time and again. Although quiet by nature, he was not timid when it came to upholding ideals and pursuing goals. In fact, I repeatedly saw him attack grand challenges that I was confident he had little idea how to solve, but I nonetheless trusted that he would succeed. He had tremendous scientific courage. This is a very rare trait in these days of limited funding, which strongly selects against such ambitious projects. He had high expectations for himself and his fellows.

His lectures were a model of organization and clarity. He always stressed the concept of informing his audience and not trying to impress them. And one of his favorite quotes, attributed to Otto Loewi, was, “We must be modest except in our aims.” I believe this sums up well a part of his philosophy.

His wonderful wife, Esther, who died in 2001, was his close love and helpmate; in fact, for some years, she was even his chauffeur, as he chose not to drive to keep his mind on his science. He is survived by his daughter Julia and son, Dave, and was predeceased in 1979 by his daughter Emily.

Gobind was famous for his long walks and talks, usually about science or nature, with friends and associates around the world. During one of my visits to his Rockport, Mass., retreat along with my wife, Dotty, we decided to walk into the hamlet for an afternoon tea; unfortunately, it was raining, but we proceeded anyway. On the entire two-hour walk, he happily recited a poem by heart with great gusto.

Our science was strengthened immeasurably by his efforts.

Robert D. Wells (bodow1938@comcast.net) is the Welch and Regents professor emeritus at the Institute of Biosciences and Technology-Houston. The editorial contributions of Uttam RajBhandary (MIT) are gratefully acknowledged.

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