THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 282, No. 39, Issue of September 28, p.

e31, 2007
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A.

Classics
A PAPER IN A SERIES REPRINTED TO CELEBRATE THE CENTENARY OF THE JBC IN 2005

JBC Centennial
1905–2005
100 Years of Biochemistry and Molecular Biology

Novel Metabolic Pathways in Virus Infection: the Work of

Seymour Cohen
Virus-induced Acquisition of Metabolic Function. I. Enzymatic Formation of
5-Hydroxymethyldeoxycytidylate
(Flaks, J. G., and Cohen, S. S. (1959) J. Biol. Chem. 234, 1501–1506)
Virus-induced Acquisition of Metabolic Function. IV. Thymidylate Synthetase in
Thymine-requiring Escherichia coli Infected by T2 and T5 Bacteriophages

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(Barner, H. D., and Cohen, S. S. (1959) J. Biol. Chem. 234, 2987–2991)
Seymour Stanley Cohen was born
in Brooklyn, New York in 1917. He
received a B.S. from the City College
of New York in 1936 and then began
his graduate studies at Columbia
University’s College of Physicians
and Surgeons with Journal of Bio-
logical Chemistry (JBC) Classics au-
thor Erwin Chargaff (1). Cohen’s
first paper on lysophosphatides was
published in the JBC in 1939 (2), and
subsequent studies, including com-
ponents of his doctoral dissertation
titled “The Thromboplastic Protein
from Lungs,” also appeared in the
JBC.
Cohen received his Ph.D in 1941
and then did a postdoctoral fellow-
ship at the Rockefeller Institute,
where he worked with Wendell M.
Stanley on plant viruses. He re-
turned to Columbia University in
1942 and worked for a year as a re-
search associate in biochemistry. In
1943, Cohen left New York for the
University of Pennsylvania and be-
came Instructor in Pediatrics at the
University of Pennsylvania’s Chil-
dren’s Hospital in 1945. He was sub-
sequently named Assistant Professor
of Biochemistry in Pediatrics in
Seymour Cohen 1947, then Associate Professor in
1950, and finally Professor in 1954.
Cohen was also the American Cancer Society Charles Hayden Professor of Biochemistry
(1957–1971) and the Hartzell Professor of Therapeutic Research (1963–1971). In addition, he
was Chairman of the Department of Therapeutic Research from 1963 to 1971.
This paper is available on line at http://www.jbc.org e31
e32 Classics
Cohen began working on bacterial viruses in 1945. His was the first systematic exploration
of the biochemistry of virus-infected cells and of how viruses multiply. In 1953, he and Gerard
R. Wyatt discovered that T-even phage DNA contains a unique pyrimidine base, 5-hydroxym-
ethylcytosine, instead of the normal cytosine (3). In the first JBC Classic reprinted here, Cohen
and Joel G. Flaks describe the novel enzyme, deoxycytidylate hydroxymethylase, that con-
verted dCMP to 5-hydroxymethyl-dCMP, which was ultimately converted to the triphosphate
and incorporated into DNA. The enzyme was only found in E. coli cells infected with a T
bacteriophage that contained 5-hydroxymethylcytosine in its DNA.
In the second JBC Classic, Cohen and Hazel D. Barner present evidence that phage infection
also stimulates the formation of a new form of thymidylate synthase, even though this enzyme
was already known to exist in uninfected bacteria. Because Cohen had shown in his earlier
work that T-even phage infection leads to a severalfold increase in the rate of DNA synthesis,
this work suggested that the virus needed not only novel enzymes to produce the unique base
but also needed to augment the activities of pre-existing enzymes to promote the big metabolic
shift toward DNA synthesis.
The discovery that virus infection creates new metabolic pathways and affects flux through
existing pathways was of importance because it suggested that virus-specified enzymes could
be used as biochemical targets for antiviral agents.
In 1971, Cohen left the University of Pennsylvania for the University of Colorado in Denver.

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He then went to the State University of New York at Stony Brook in 1976, where he was
named Distinguished Professor of Pharmacological Sciences and American Cancer Society
Professor. In 1985, Cohen became Emeritus Professor of Pharmacological Sciences at the State
University of New York at Stony Brook. He currently lives in Woods Hole, Massachusetts,
where he is working on a text on polyamines and on a biography of the chemist, Thomas
Cooper.
Cohen received many awards and honors during his career including the Eli Lilly Award in
bacteriology and immunology in 1951, the Mead Johnson Award given by the American
Academy of Pediatrics in 1952, the Newcomb Cleveland Award of the American Association for
the Advancement of Science in 1955, the French Society of Biological Chemists Medal in 1964,
the Borden Award of the American Association of Medical Colleges in 1967, the Passano
Award in 1974, and a medal from the Alumni Foundation of the City College of New York in
1978. He was also one of two scientists in the United States in 1957 to receive a lifetime grant
from the American Cancer Society. Cohen served on the editorial boards of Virology, the
Journal of Biological Chemistry, Bacteriological Reviews, and the Journal of Bacteriology. He
is a member of the American Academy of Arts and Sciences (1963) and the National Academy
of Sciences (1967) and served as president of the Society of General Physiologists in 1968.
Nicole Kresge, Robert D. Simoni, and Robert L. Hill

REFERENCES
1. JBC Classics: Vischer, E., and Chargaff, E. (1948) J. Biol. Chem. 176, 703–714 (http://www.jbc.org/cgi/content/
full/280/24/e21)
2. Chargaff, E., and Cohen, S. S. (1939) On lysophosphatides. J. Biol. Chem. 129, 619 – 628
3. Wyatt, G. R. and Cohen, S. S. (1953) The bases of the nucleic acids of some bacterial and animal viruses: the
occurrence of 5-hydroxymethylcytosine. Biochem J. 55, 774 –782
 Novel Metabolic Pathways in Virus Infection: the Work of Seymour Cohen
Nicole Kresge, Robert D. Simoni and Robert L. Hill
J. Biol. Chem. 2007, 282:e31.

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