CURRENT BIOGRAPHY

NIRENBERG, MARSHALL W(ARREN)
Apr. 10, 1927- Biochemist

Address: b. National Institutes
Bethesda, Md. 20014

Man’s scientific understanding of the funda-
mental nature of life took a giant stride forward
in 1961 when Dr. Marshall W. Nirenberg dis-
covered a procedure for deciphering the “genetic
code” in living cells. His findings then and
his continuing research have opened the gates
for other scientists to vast areas of knowledge
about the processes of all life on earth, its origin,
evolution, and future. Almost equally vast is
the speculation over the eventual rewards and
dangers to man when his mastery of the genetic
code gives him the power to influence heredity.
Since 1957 Nirenberg has been associated with
the National Institutes of Health of the Depart-
ment of Health, Education, and Welfare, and
since 1962 he has been chief of the section of
biochemical genetics of the National Heart
Institute.

Marshall Warren Nirenberg was bom on
April 10, 1927 in New York City. His family
moved to Orlando, Florida when he was ten
years old, and he has always thought of Florida
as home. As a student at the University of
Florida in Gainesville, he was attracted to bio-
chemistry while working with Dr. R. L. Shirley
and Dr. George K. Davis of the Nutrition Lab-
oratory. Biochemistry was then almost unknown
to the undergraduate courses, and Nirenberg re-
calls getting a good introduction at the labora-
tory to radioisotope techniques that proved
important to him in investigating the structures
of organic compounds. He was an_assistant in
the department of biology from 1945 to 1947
and a teaching assistant there the fnllowing
year. He obtained his B.S. degree in 1948. His
fraternity at the university was Pi Lambda Phi.

While taking graduate courses at the Univer-
sity of Florida, Nirenberg worked as a resear
associate at the Nutrition Laboratory in 1951-52.
For his M.Sc. degree in biology, which he re-
ceived in 1952, he made a study of certain in-
sects in Alachua County. Dr. Lewis Berner, who
was directing Nirenberg’s research, recognized
his deeper inclination and helped him decide
to seek his Ph.D. degree in biochemistry. From
1952 to 1956 he held a teaching fellowship in
the department of biological chemistry at the
University of Michigan. Then as a_resear
fellow in 1956-57, he completed his dissertation

of Health,

1965

   

Ea

MARSHALL W. NIRENBERG

on the subject of hexose uptake in ascites tumor
cells. The University of Michigan awarded him
the Ph.D. degree in biochemistry in 1957.

A postdoctoral fellowship of the American
Cancer Society for further work in biochemistry,
under the sponsorship of Dr, DeWitt Stetten,
Jr., brought Nirenberg to the National Institutes
of Health in Bethesda, Maryland in 1957. Dur-
ing the next few years at the National Institute
of Arthritis and Metabolic Diseases, Nirenberg
doggedly pursued his research into the yet ille-
gible hieroglyphics of life’s code, When his
American Cancer Society fellowship expired in
1959, he continued at the institute under a_fel-
lowship of the Public Health Service, and in
1960 he became a research biochemist in the
institute’s section of metabolic enzymes.

The fruits of his research were summed up in
a paper on the genetic code that Nirenberg de-
livered at the International Congress of Bio-
chemistry in August 1961 in Moscow. The paper
had an electrifying impact on his fellow-scien-
tists and was followed up by two reports pub-
lished in the October issue of the Proceedings
of the National Academy of Sciences. In these
Nirenberg described how he and Dr. J. Heinrich
Matthaei, a visiting scientist from West Ger-
many, performed the milestone experiment that
cracked the genetic code. But although he had
stirred the world of biochemistry, Nirenberg re-
mained unknown to the general public until
December 1961, when news of his discoveries
appeared in the press.

The chemical “language” used to describe
Nirenberg’s findings is a metaphorical means of
expressing the way that every living cell passes
along its genetic message. The storehouse of
genetic information, which he has helped to un-
lock, is a chemical called DNA (deoxyribonucleic
acid). Another chemical, RNA (ribonucleic
acid), serves as a kind of messenger and trans-
mits the information out of the original cell.
Through the co-operation of the two acids,

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specific proteins are manufactured that are basic
to the development of new cells. Genetic in-
formation is transmitted in the form of a code
made up of precise quantities of four nucleic
acids: A (adenine), T (thymine), G (guanine),
and C (cytosine). From this genetic “alphabet”
words and sentences are formed, and their se-
quence determines each genetic trait.

Dr. Nirenberg looked for clues to the code in
the making of protein. He mixed a batch of
chemicals containing all the amino acids, ex-
cluding from them the DNA, RNA, and other
components. Then he added an artificial RNA
made up only of uracil, coded as UUU. “By
adding radioactive carbon 14 to one amino acid
at a time in each mixture,” as George Eagle
explained in the Washington Post (January 3.
1965), “Nirenberg found that the amino acid
directed into protein by UUU is phenylalanine.”
This was the first word translated from the
genetic code. A similar experiment was _per-
formed later in the year by a New York Univer-
sity group led by the Nobel Prize winner Dr.
Severo Ochoa. In January 1962 Ochoa an-
nounced that he and his colleagues had deter-
mined the coding for nineteen of the twenty
known amino acids and had predicted the base
code for the last one. Nirenberg immediately
announced substantial agreement with those find-
ings for the fifteen amino acids his team had
deciphered.

Scientists everywhere hailed Nirenberg’s feat
as the most important development in molecular
biology since the two Nobel Prize winners, James
Dewey Watson and Francis H. C. Crick, dem-
onstrated the double-spiral structure of DNA
back in 1953. Crick declared that the entire
coding problem would be solved within a year
—a prediction that proved to be too optimistic.
Nirenberg pointed out that many other scientists
in all parts of the world were adding fragments
of knowledge that would help to unravel the
life process. Later, when singled out for awards,
he insisted to the press that at least thirteen
biochemists at the National Institutes of Health
share the credit with him, including Philip
Leder and Merton Bernfield, who were most
closely associated with him in the work on the
genetic code.

At a symposium on the chemistry of heredity
in April 1962, in Atlantic City, a record-break-
ing audience of 3,000 biologists and chemists
heard Nirenberg report how he made his system
turn out tobacco virus proteins. In co-operation
with Dr. Heinz Fraenkel-Conrat and Dr. Akira
Tsugita of the University of California, he fed
tobacco virus RNA into a mixture of amino
acids derived from wrung-out sewage bacteria
whose code of life had been destroyed. Soon
the “brainless” bacteria turned out tobacco virus
proteins—something that only a tobacco leaf
could do before. In a similar way, biochemists
at the Rockefeller Institute have made Dr.
Nirenberg’s system turn out hemoglobin, the pro-
tein pigment of red blood cells of vertebrates.

In 1962 Dr. Nirenberg was appointed chief
of the section of biochemical genetics of the
National Heart Institute. Addressing a sympo-
sium at the Institute of Microbiology, Rutgers
University, in September 1962, he disclosed that
earlier in the year he and his associates had

1965

worked out three-letter combinations for each
of the twenty amino acids. Many scientists at
the symposium shared the belief that the genetic
code of life is more complicated than it was
thought the year before. Nirenberg supported this
view by presenting evidence that in addition
to the twenty three-letter words for the amino
acids, there are some twenty-five other designa-
tions for them in the code. In his opinion, the
newly discovered complexity in the genetic code
represented a step forward, since it meant that
the understanding of the code was nearer reality
and less of a laboratory ideal. He expressed his
belief that the code would be broken in the
near future.

The next step in the deciphering of the cade
was made public at a gathering of the world’s
leading biochemists in New York on July 30,
1964. Nirenberg described how he and his col-
leagues combined the chemical code symbols
into a three-letter “word” and then put all the
“words” into the test tubes with ribosomes,
amino acids, and the proper enzymes. Each
of the GUU “words,” it turned out, called for
the amino acid named valine. Thus Nirenberg
found out a code word that carried a specific
order. George Eagle of the Washington Post
reported that Nirenberg has revealed that codes
can be read and written in sequence by adding
radioactive material to see which component
comes up first, second, and third. According to
Nirenberg, his group was “just zooming”
through the translation in sequence. But he
said that biochemists in the molecular field still

could not read long genetic messages—only
fragments.
The discoveries resulting from Nirenberg’s

pure research are bound to have startling im-
plications for the world outside his laboratory,
and hardly any area of life will remain un-
affected by them. His research might eventually
tell doctors enough about the construction of
diseased cells to help wipe out diabetes, cancer,
and other illnesses. The pattern of RNA has al-
ready been further clarified by Robert W. Holley
and others, and its function, particularly in the
process of memory, is already being investigated.
Mastery of the genetic code would permit not
only the improvement of the lot of individuals
but also the slowing down of the aging process,
the correction of genetic defects, and the chang-
ing of heredity. Although most scientists look
at these prospects with exhilaration, some have
sounded sober warnings. Thus the Nobel Prize
winner Ame Tiselius has cautioned against tam-
pering with life, mind control, and heredity
abuse.

Against this background of awesome oppor-
tunities and dangers, Nirenberg takes a cautious
and realistic position. He calls his group’s work
“enlightened trial and error” and prefers to
speak of his immediate task in the laboratory.
In his view, a long and tedious building of the
foundations of basic biological knowledge is
necessary before any of the medical and other
implications can begin to be understood. “Ulti-
mately one hopes,” he wrote in an article for
Scientific American (March 1963), “that cell-
free systems will shed light on genetic control
mechanisms. Such mechanisms, still undis-
covered, permit the selective retrieval of genetic

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information.” He believes that the genetic code
is essentially universal on this planet and is
used even by species on opposite ends of the
evolutionary scale.

The National Academy of Sciences gave Dr.
Nirenberg its award for distinguished research
in molecular biology in 1962, including a $5,000
grant to continue his work. Other honors fol-
lowed; the Paul Lewis Award in Enzyme Chem-
istry of the American Chemical Society in 1963
and the Modern Medicine Award in 1964. On
February 8, 1965 President Lyndon B. Johnson
presented Nirenberg with one of eleven Nation-
al Medals of Science. He is a member of the
American Society of Biological Chemists, Amer-
ican Chemical Society, Biophysical Society,
Washington Academy of Sciences, and Sigma Xi,
the science honor society. His articles have ap-
peared in Science, Scientific American, the Pro-
ceedings of the National Academy of Sciences,
and other professional periodicals.

Modest about his scientific achievements,
Nirenberg prefers anonymity. According to one
interviewer, “He shies away from talk about
cancer cures, controlled heredity, and the pos-
sibility of international honors.” He is six feet
three inches tall, slender, and dark-haired. The
scientist is said to look ten years younger than
his age. His wife, the former Perola Zaltzman,
met him when she was a graduate exchange
student from Brazil on a fellowship at the Na-
tional Institutes of Health. Mrs. Nirenberg
now works in the clinical endocrinology branch
of the National Heart Institute. They live in
Bethesda near the institute. Dr. Nirenberg likes
to return to his laboratory in the evening to
pursue an interesting idea far into the night.
His sense of urgency about his work has made
him appreciate the way the United States has
supported scientific research. He has visited
laboratories in many other countries, but
“nowhere else in the world,” he has said, “do
the researchers get the support of anything like
the National Health Institutes. Without this
kind of help we would be many, many years
behind where we are now.”

References

Sci Am 208:33 Mr 63
Washington (D.C.) Post E p2 Ja 3 °65

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