Khorana, Har Gobind WORLD OF MICROBIOLOGY AND IMMUNOLOGY324•
holdfasts and other deeper tissues of the kelps, then the forest
can regenerate quite well from the disturbance. In California,
for example, kelp harvesters are only allowed to cut in the top
4 ft (1.4 m) of the water column, leaving the deeper parts of
the forest intact. The kelp harvesting is done using a large
barge-like apparatus, which can collect as much as 605 tons
(550 metric tons) of kelp per day.
Kelp forests also have an extremely large indirect value
to the economy, by serving as the critical habitat for many
species of fish and shellfish that are harvested in the coastal
fishery. The forests are also critical habitat for many species of
indigenous biodiversity. This has an indirect benefit to the
coastal economy, through recreational activities associated
with ecotourism.KKhorana, Har GobindHORANA, HARGOBIND(1922- )
Indian-born American biochemistHar Gobind Khorana, an organic chemist who specialized in
the study of proteins and nucleic acids, shared the Nobel Prize
in Physiology of Medicine with Robert W. Holley (1922– )
and Marshall W. Nirenberg (1927– ) in 1968 for discoveries
related to the genetic codeand its function in protein synthe-
sis. In addition to developing methods for investigating the
structure of the nucleic acids, Khorana introduced many of the
techniques that allowed scientists to decipher the genetic code
and show how ribonucleic acid(RNA) can specify the structure
of proteins. Four years after winning the Nobel Prize, Khorana
succeeded in synthesizing the first wholly artificial gene. In
the 1980s Khorana synthesized the gene for rhodopsin, a pro-
tein involved in vision.
Har Gobind Khorana, youngest of the five children of
Shri Ganput Rai Khorana and Shrimat Krishna Devi Khorana,
was born in Raipur, in the Punjab region of India (now part of
West Pakistan). His birth date was recorded as January 9,
1922, but the exact date of his birth is uncertain. Although his
family was poor, his parents believed strongly in the impor-
tance of education. His father was a village agricultural taxa-
tion clerk in the British colonial government. Khorana
attended D.A.V. High School in Multan (now West Punjab).
After receiving his Bachelor of Science (1943, with honors)
and Master’s degree (1945, with honors) from Punjab
University in Lahore, India, Khorana was awarded a
Government of India Fellowship, which enabled him to study
at Liverpool University, England, where he earned his Ph.D.
in 1948. From 1948 to 1949, he worked as a postdoctoral fel-
low at the Federal Institute of Technology, Zurich,
Switzerland, with Professor Vladimir Prelog, who had a major
influence on his life-long approach to science.
After briefly returning to India, Khorana accepted a
position in the laboratory of (Lord) Alexander Todd at
Cambridge University (1950–52), where he studied proteins
and nucleic acids. From 1952 to 1960, Khorana worked in the
organic chemistry section of the British Columbia Research
Council, Vancouver, Canada. The next year Khorana moved to
the University of Wisconsin, Madison, Wisconsin, where heserved as Co-director of the Institute for Enzyme Research
and Professor of Biochemistry. In 1964, he became the Conrad
A. Elvehjem Professor of the Life Sciences. In 1970, Khorana
accepted the position of Alfred P. Sloan Professor,
Departments of Biology and Chemistry, at the Massachusetts
Institute of Technology, Cambridge, Massachusetts. From
1974 to 1980, he was Andrew D. White Professor-at-large,
Cornell University, Ithaca, New York. During his long and dis-
tinguished career, Khorana has been the author or co-author of
over 500 scientific publications.
In 1953, Khorana and Todd published their only co-
authored paper; it described the use of a novel phosphorylat-
ing reagent. Khorana found that this reagent was very useful
in overcoming problems in the synthesis of polynucleotides.
Between 1956 and 1958, Khorana and his coworkers estab-
lished the fundamental techniques of nucleotide chemistry.
Their goal was to develop purely chemical methods of syn-
thesizing oligonucleotides (long chains of nucleotides). In
1961, Khorana synthesized Coenzyme A, a factor needed for
the activity of certain key metabolic enzymes.
In 1955, Khorana learned about Severo Ochoa’s discov-
ery of the enzyme polynucleotide phosphorylase and met Arthur
Kornberg, who described pioneering research on the enzymatic
synthesis of DNA. These discoveries revolutionized nucleic acid
research and made it possible to elucidate the genetic code.
Khorana and his coworkers synthesized each of the 64 possible
triplets (codons) by synthesizing polynucleotides of known
composition. Khorana also devised the methods that led to the
synthesis of large, well-defined nucleic acids.
By combining synthetic and enzymatic methods,
Khorana was able to overcome many obstacles to the chemi-
cal synthesis of polyribonucleotides. Khorana’s work pro-
vided unequivocal proof of codon assignments and defined
some codons that had not been determined by other methods.
Some triplets, which did not seem to code for any particular
amino acid, were shown to serve as “punctuation marks” for
beginning and ending the synthesis of polypeptide chains
(long chains of amino acids). Khorana’s investigations also
provided direct evidence concerning other characteristics of
the genetic code. For example, Khorana’s work proved that
three nucleotides specify an amino acid, provided proof of the
direction in which the information in messenger RNA is read,
demonstrated that punctuation between codons is unnecessary,
and that the codons did not overlap. Moreover, construction of
specific polyribonucleotides proved that an RNA intermediary
is involved in translating the sequence of nucleotides in DNA
into the sequence of amino acids in a protein. Summarizing
the remarkable progress that had been made up to 1968 in
polynucleotide synthesis and understanding the genetic code,
Khorana remarked that the nature of the genetic code was
fairly well established, at least for Escherichia coli.
Once the genetic code had been elucidated, Khorana
focused on gene structure-gene function relationships and
studies of DNA-protein interactions. In order to understand
gene expression, Khorana turned to DNA synthesis and
sequencing. Recognizing the importance of the class of
ribonucleotides known as transfer RNAs (tRNAs), Khorana
decided to synthesize the DNA sequence that coded for ala-womi_K 5/6/03 3:29 PM Page 324