Gobind Khorana (1922 - 2011)

 

Har Gobind (Hargobind) Khorana was a biochemist specializing in polynucleotide synthesis. He was awarded the Nobel Prize in Physiology or Medicine in 1968 along with Robert Holley and Marshall Nirenberg "for their interpretation of the genetic code and its function in protein synthesis."

Khorana was born in Raipur, Pujab, British India (now Pakistan) in 1922. After graduating from Punjab University in Lahore (British India) he went to the University of Liverpool (United Kingdom) to complete a Ph.D. Following several post-docs in Zurich (Switzerland) and Cambridge (UK) he accepted a job at the British Columbia Research Council, in Vancouver, Canada in 1952.

According to his colleague, Uttam Rajbhandary,

Gobind was so excited that he was going to start a lab of his own. He looked at the map of Canada, saw where Vancouver was for the first time, and off he went ...

In 1960 he moved to the University of Wisconsin, Madison (United States) and in 1970 he moved again, this time to the Massachusetts Institute of Technology in Boston (United States). Gobind Khorana died in Concord, Massachusetts on Wednesday, November 9, 2011.

Canadians like to think of Gobind Khorana as an honorary Canadian because of his stay in Vancouver from 1952-1960. His three children were born there.

Khorana worked on polynucleotide synthesis using both chemical synthesis and combinations of chemical synthesis plus enzyme synthesis. His contribution to cracking the genetic code was to make synthetic polynucleotides that could be used to prime in vitro translation. For example, his lab made all of the synthetic, double-stranded, DNA molecules shown below (from the Khorana Nobel Lecture).

These short pieces of double-stranded DNA were copied by DNA polymerase to produce very long stretches of DNA with tandem repeats of the sequence in the synthetic polynucleotides. This was a fortuitous property of DNA polymerase due to slippage during replication. Those DNA molecules then served as templates for the synthesis of RNA by RNA polymerase, which also makes long molecules of repeated sequences due to slippage.

These RNAs are then added to a mixture of ribosomes and aminoacyl-tRNAs to see which ones can stimulate protein synthesis when supplied with the appropriate amino acid. The results for poly-UC are shown below.

Polypeptides are only made when the in vitro translation mixture is supplied with serine or leucine. There are only two possible triplet codons in poly-UC, UCU or CUC, so these must correspond to the codons for serine and leucine although you don't know which is which. The results with poly-CCU revealed that the codon CUC specifies leucine.

Khorana had a big influence on my decision to become a biochemist although I never met him until 1980 when he came to Toronto to receive the Gairdner Foundation Annual Award. In the autumn of 1967 I was in my final year of a biology degree at Carleton University in Ottawa (Canada). Saran A. Narang, a former post-doc in Khorana's lab who had worked on the synthesis of di- and tri- nucleotides, had just joined the National Research Council of Canada in Ottawa and he was giving a series of lectures at NRC on the chemistry of nucleotides and polynucleotides on two successive Fridays (Oct. 20 and Oct. 27, 1967). The most interesting part of the lectures was the description of chemical synthesis. Remember, these were exciting times—the genetic code had just been cracked and here was an opportunity to hear from a participant how Gobind Khorana's lab had contributed to this effort. It was the year before he won the Nobel Prize,

I still have my notes from those lectures. Here's a copy of the reading list (right). Note that there are 15 papers from Khorana's lab!

I was so impressed by the biochemistry that I decided to apply to biochemistry departments for graduate school. It was the first time that I really appreciated how a fundamental knowledge of biochemistry related to genetics and molecular biology and all of biology.

“Even while doing all this research, he was always really interested in education, in students and young people,” his daughter Julia Khorana said. “After he retired, students would come to visit and he loved to talk to them about the work they were doing. He was very loyal to them, and they were very loyal to him, too.”

Prof. Rajbhandary says he will remember Khorana for his drive and focus, but also his humility. “As good as he was, he was one of the most modest people I have known,” he says. “What he accomplished in his life, coming from where he did, is truly incredible.” [Punjab's Nobel Laureate]

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[Hat Tip: Douglas Theobald on Panda's Thumb]