HG Khorana

Har Gobind Khorana (1922−2011) Marvin Caruthers, et al.

Science 334, 1511 (2011); DOI: 10.1126/science.1217138

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PERSPECTIVES RETROSPECTIVE

Har Gobind Khorana (1922–2011)

The remarkable work of a Nobel laureate saw breakthroughs in chemistry, biochemistry, and genetics.

Marvin Caruthers1 and Robert Wells2

CREDIT: MIT NEWS OFFICE

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA. 2Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA. E-mail: marvin.caruthers@ colorado.edu; bodow1938@comcast.net 1

educated and encouraged him, despite a great shyness and no money, to attend Punjab University. There, on scholarships, he studied chemistry and received his bachelor’s and master’s degrees. Upon graduating, he obtained a government fellowship to study at the University of Liverpool, where he earned a Ph.D. in organic chemistry in 1948.

Gobind did his postdoctoral work at the Federal Institute of Technology (ETH) in Switzerland with Vladimir Prelog. There he met Esther, who became his wife. Esther, who died in 2001, was the bedrock foundation upon which Gobind was able to forge his life’s work. Often we were invited to the Khorana home to share a meal with Esther, Gobind, and their children, Julia, Emily (who died in 1979), and David. Many of his close friends and colleagues believe that Gobind’s slow, steady deterioration in health and spirit dates from his loss of Esther.

At the ETH, Gobind rediscovered an obscure class of reagents—the carbodiimides. Upon his return to England in 1950, he worked in the laboratory of Sir Alexander Todd, where he found that the carbodiimides could be used to synthesize biologically relevant pyrophosphates. He then accepted an invitation to join a new research program at the University of British Columbia, Vancouver. There, Gobind used carbodiimides to initially synthesize the deoxy- and ribotriphosphates and coenzyme A for which he received considerable international recognition. These syntheses provided Gobind an entré into the use of chemistry to solve biological problems.

In 1960, Gobind moved to the Institute for Enzyme Research in Madison, Wisconsin, where he did his Nobel Prize winning work on elucidating the genetic code. He was a brilliant strategist and organizer for blending the research of many postdoctoral fellows. I (R.W.) and others worked hard during this time, but it was Gobind’s brilliance that “cracked” the problem.

In 1970, only 2 years after receiving

the Nobel Prize, Gobind reported the first chemical synthesis of a gene [coding for yeast alanine transfer RNA (tRNA)]. That year, he moved to MIT, where his laboratory reported the synthesis, expression, and biological activity of a suppressor tRNA-encoding gene His work with the genetic code and gene synthesis demonstrated what could be done with synthetic DNA and RNA. Today, biologists and biochemists use these synthetic molecules for site-specific mutagenesis, sequencing DNA, exponentially amplifying DNA (by polymerase chain reaction), and many other applications.

Following a Nobel Prize, many scientists reflect in the warm glow of their accomplishments, but not Gobind. Instead, he turned his focus toward biological membranes and elucidated the mechanism of proton transport in light transduction by bacteriorhodopsin. His most recent work was with the mammalian visual sensory system and G protein–coupled receptors.

Gobind trained more than 150 postdoctoral fellows and several graduate students.

He was a prodigious contributor to the literature with more than 450 publications, and has received numerous honors and awards, including the Lasker Foundation Award and the National Medal of Science.

The Khorana group has always been a tightknit association of colleagues who interact easily and enjoy one another’s company. All of us know the entire group stretching from those in Vancouver to the present. Starting in Cambridge in 1985, we periodically have had large group meetings. In addition to Cambridge, these meetings have been in places close to Gobind’s scientific roots— Vancouver, Boston, Japan, and Wisconsin, where the University of Wisconsin introduced a fellowship program focused on giving young students from India the same opportunities once provided to Gobind.

Many of the Khorana group have been trying to decide how to best honor Gobind following his death. If we could ask him, we are sure his answer would be to have another Khorana Symposium to discuss excellent science and not waste the moment memorializing him. Perhaps during the coming year, this is exactly what we will do. The world has lost a scientific giant.

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H

ar Gobind Khorana, the Massachusetts Institute of Technology’s (MIT) Alfred P. Sloan Professor of Biology and Chemistry emeritus, died on 9 November 2011. One of us (M.C.), on the first day as a young postdoctoral fellow, greeted him as “Dr. Khorana.” He responded, “Everyone calls me Gobind and so should you.” And so it was for all those fortunate enough to have worked with him.

As our lifelong friend and mentor, Gobind taught us how to do good science and to enjoy the path it created for each of us. His lab worked on projects barely accessible by the technologies available at the time. He always had his thoughts on the horizon, firmly focused on the next challenge—irrespective of whether it was synthesizing coenzyme A, solving the genetic code, chemically synthesizing genes, or deducing the mechanism of light transduction by bacteriorhodopsin.

Gobind was a dedicated, driven, focused, and humble scientist. He was fiercely loyal to all whom he mentored and worked with, and unyielding in his drive toward the highest scientific ideals and goals. He repeatedly attacked immense and challenging problems, likely with little idea of how he would eventually solve them—but solve them he did. Gobind sent the following from Stockholm during the Nobel Prize ceremonies, for which he received the honor in 1968 for Physiology or Medicine: “Group III: You too can win Nobel Prizes. Never cease to discover your potential. Waste no time on your presumed shortcomings. Do not forget Federation Abstracts. Merry Christmas.” This sums up part of Gobind’s philosophy.

Gobind’s trek to Stockholm began in Raipur, India, where he was born and began his formal education. He often spoke with enormous respect and pride about his father, a local taxation clerk who insisted that he be

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