January 2012

Retrospective: Har Gobind Khorana (1922 – 2011)

 

Retrospective_Khorana 
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.

MIT
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.

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