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

, et al.Marvin Caruthers2011)−Har Gobind Khorana (1922

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www.sciencemag.org SCIENCE VOL 334 16 DECEMBER 2011 1511

PERSPECTIVES

Har Gobind Khorana, the Massa-

chusetts 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 sci-

ence and to enjoy the path it

created for each of us. His

lab worked on projects barely

accessible by the technolo-

gies available at the time. He

always had his thoughts on the

horizon, fi rmly focused on the

next challenge—irrespective

of whether it was synthesiz-

ing coenzyme A, solving the

genetic code, chemically syn-

thesizing genes, or deducing

the mechanism of light trans-

duction by bacteriorhodopsin.

Gobind was a dedicated,

driven, focused, and humble

scientist. He was fi ercely loyal to all whom

he mentored and worked with, and unyield-

ing in his drive toward the highest scientifi c

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 Rai-

pur, India, where he was born and began his

formal education. He often spoke with enor-

mous respect and pride about his father, a

local taxation clerk who insisted that he be

educated and encouraged him, despite a

great shyness and no money, to attend Punjab

University. There, on scholarships, he stud-

ied 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 Khor-

ana 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 carbodi-

imides. 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 rel-

evant pyrophosphates. He then accepted an

invitation to join a new research program

at the University of British Columbia, Van-

couver. There, Gobind used carbodiimides

to initially synthesize the deoxy- and ribo-

triphosphates and coenzyme A for which he

received considerable international recog-

nition. These syntheses provided Gobind an

entré into the use of chemistry to solve bio-

logical problems.

In 1960, Gobind moved to the Institute

for Enzyme Research in Madison, Wiscon-

sin, 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 bril-

liance that “cracked” the problem.

In 1970, only 2 years after receiving

the Nobel Prize, Gobind reported the fi rst

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 bio-

logical activity of a suppressor tRNA-encod-

ing 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 syn-

thetic molecules for site-specifi c mutagen-

esis, sequencing DNA, exponentially ampli-

fying DNA (by polymerase chain reaction),

and many other applications.

Following a Nobel Prize, many scientists

refl ect in the warm glow of their accom-

plishments, but not Gobind. Instead, he

turned his focus toward biological mem-

branes 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 postdoc-

toral fellows and several graduate students.

He was a prodigious contributor to the lit-

erature 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 tight-

knit 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. Start-

ing 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 scientifi c roots—

Vancouver, Boston, Japan, and Wisconsin,

where the University of Wisconsin intro-

duced a fellowship program focused on

giving young students from India the same

opportunities once provided to Gobind.

Many of the Khorana group have been try-

ing to decide how to best honor Gobind fol-

lowing 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 memo-

rializing him. Perhaps during the coming

year, this is exactly what we will do. The

world has lost a scientifi c giant.

Har Gobind Khorana (1922–2011)

RETROSPECTIVE

Marvin Caruthers 1 and Robert Wells 2

The remarkable work of a Nobel laureate saw

breakthroughs in chemistry, biochemistry,

and genetics.

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10.1126/science.1217138

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

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