Har Gobind Khorana (1922–2011) Chemical Biologist Who Helped to Establish the Genetic Code

COMMENT OBITUARY Har Gobind Khorana (1922–2011) Chemical biologist who helped to establish the genetic code.

ar Gobind Khorana, who died on Columbia Research Council. The council’s manipulation before individual genes from 9 November 2011 at the age of 89, director, Gordon Shrum, had come from any organism had been characterized. And was a pioneer and a visionary. That Canada to interview him and said: “You can in 1971, he wrote about the need to amplify Hsomeone with such a humble background have all the freedom to do what you want”, the synthetic gene, using a series of steps that could rise to become an icon of molecular but we don’t have much in terms of facilities. looks eerily similar to the technique for this biology is a testament to his extraordinary Shrum said candidly that he wanted to hire now known as PCR. drive, discipline and striving for excellence. an organic chemist because they were cheap A deep thinker, Khorana put much thought His background was in chemistry, but — needing only test tubes to do research. into choosing a problem to work on. He was his interests lay in applying chemistry to Undaunted, Khorana accepted the offer, not influenced by its difficulty or the time problems in biology. By doing so, he started and established an outstanding research needed to solve it, as long as it was of funda- the field of ‘chemical biology’. For mental importance. He often said: his work on uncovering the genetic “If you want to get far, you have to code, Khorana was awarded the travel alone.” Yet he was always well Nobel Prize in Physiology or Medi- prepared, making “pilgrimages” to cine in 1968. work in laboratories — ranging from Khorana’s chemical synthesis of Stanford University in California to the first gene in 1970, followed by the National Cancer Center of Tokyo his synthesis of a related gene and — before undertaking new projects. demonstration in 1979 that it was As a mentor, Khorana set high functional in a bacterium, was a standards. He was loyal to the people landmark in genetics. This work ush- who helped him and to the institu- WISCONSIN–MADISON LIBRARIES UNIV. ered in the era of recombinant DNA tions at which he worked. He could and underlies the in vitro assembly be demanding, but he was no more of whole genomes from shorter DNA so of others than he was of himself. strands. One associate said: “He showed us Khorana was born in Raipur, a what excellence in science was and small village in the Punjab province we learnt to recognize it.” of what is now Pakistan, but was then Gobind was modest, humble and India. His father, an agricultural taxa- avoided publicity. He loved music, tion clerk, believed in education; and swimming and long walks, and had a Khorana and his siblings were the only liter- programme. curiosity that lasted until the end. Three days ate children in the village. Despite poor edu- In 1960, he moved to the University of before he passed away, I was by his hospital bed cational facilities, Khorana completed high Wisconsin–Madison, where he worked on and we talked about glucose and the brain. school and went on to receive bachelor’s and the genetic code and chemical synthesis of Gobind used the solitude of hiking to master’s degrees in chemistry from Univer- a transfer RNA gene. In 1970, he moved to think about scientific problems, and always sity of the Punjab in Lahore. In 1945, Khorana the Massachusetts Institute of Technology carried a pen and notecards to write down moved to the University of Liverpool, UK, in Cambridge, where he switched to work- his thoughts. On the day of his Nobel prize under a Government of India Fellowship. He ing on membranes and signal transduction, announcement, he was among the last at the was slated to study insecticides and fungi- problems on which he worked for more than university to hear about it. As he often did, cides, but because of lack of space was asked 30 years until his retirement in 2007. he had gone to a rented cottage by a lake out- to pursue organic chemistry. It was there that side Madison with no telephone or radio, to he obtained a PhD in 1948 working on the A DEEP THINKER write papers. His wife Esther had to drive chemistry of melanins with Roger Beer. Much of Khorana’s early work used a class over to give him the news. At the celebration, Having seen much German scientific of reagents called carbodiimides, which he I remember him enthusiastically explaining literature, Khorana wanted to do postdoc- had come across in Zurich while translating his latest work on the blackboard to two toral research in a German-speaking country. papers from German to English. In Van- professors holding glasses of champagne. So he went to the Swiss Federal Institute couver, his use of these reagents led to the Gobind was at heart an experimental of Technology (ETH) in Zurich, where he synthesis of nucleotide coenzymes and scientist. With him gone, we have lost an worked for 11 months on alkaloid chemistry oligonucleotides, and brought him into con- extraordinary man. ■ with Vladimir Prelog. His stay was short — tact with biochemists Arthur Kornberg, Paul he received no stipend and had to sustain Berg, Saul Roseman, Jerry Hurwitz, Fritz Uttam L. RajBhandary is in the himself on savings. Fortunately, in 1949, he Lipmann, Charles Dekker and Leon Heppel, Department of Biology, Massachusetts received a fellowship to work with Alexander many of whom spent summers in his lab. Institute of Technology, Cambridge, Todd at the University of Cambridge, UK, on Khorana was a pioneer. Spanning chem- Massachusetts 02139, USA. He joined peptides and nucleotides. istry, biology and physics, he was doing Khorana’s lab as a postdoc in 1962 and has In 1952, Khorana moved to Vancouver to interdisciplinary research before the cur- been a close friend and colleague since. start his own research group at the British rent trend. In 1968, he wrote about gene e-mail: [email protected]