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in-cites,
September 2001
Citing URL: http://www.in-cites.com/papers/dr-carl-nathan.html
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An
essay by:
Dr. Carl Nathan |
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 r.
Carl Nathan, Stanton Griffis Professor of Medicine at the
Weill Medical College of Cornell University, talks about the
teachers and experiences that have shaped his career. Dr. Nathan is the
author of 9 papers which have been cited a total of 7090
times, including the review, "Nitric-oxide as a secretory
product of mammalian-cells," which was published in FASEB
Journal, 6: (12) 3051-3064 September 1992. This particular
article has been cited 2,205 times, placing it among the 20
most-cited papers of the 1990s.
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"Assistant animal boy" was
my entry job. For five summers during high school and Harvard College,
I cleaned rabbit cages for Lester Grant, the inflammation scholar at
NYU. Lester loved theater. When he wasn’t taking the lab to
Shakespeare in the Park, he was playing to his students as audience.
He commanded guest appearances by Lewis Thomas, Baruj Benacerraf,
Jonathan  Uhr
and others. Listening to them and looking through the rabbit ear
chamber, I got hooked on the cataclysmic response of white cells to
injured tissue. At Harvard Medical School, John David introduced me to
the immune system. I saw innate immunity as the bridge between these
two experiences, and the macrophage as a major span.
A drive to seek biochemical answers
brought me to Manfred Karvnosky, and later to Richard Root while I was
an oncology fellow at Yale. From them I learned not just how to
measure the respiratory burst but how to think biochemically and
quantitatively. Then came a nine-year immersion in cell biology as a
faculty member at Rockefeller University with Zanvil Cohen and Samuel
Silverstein.
By the time I joined Cornell, I had
introduced the concepts of cytokine-mediated activation and
deactivation of macrophages, helped identify the first macrophage
activating factor (interferon- g
) and its therapeutic potential in
man, and demonstrated the role of the respiratory burst in macrophage
biology. These encounters with superoxide prepared me to embrace the
hypothesis that nitric oxide (NO) is a product of the innate immune
system involved in host defense. This was at a time when most
scientists thought mammalian cells are neither stupid enough nor smart
enough to produce toxic, inorganic radical gases: the conventional
wisdom was that cells ought not to try; and if they tried, must fail.
Our lab and collaborators went on to
characterize the high output pathway of NO production. We identified
NO as a cytotoxic product of activated macrophages; discovered the
roles of tetrahydrobiopterin, NADPH, O2, FAD, and FMN in NO synthesis;
identified specific enzymatic targets for cytotoxic actions of NO;
purified and cloned the inducible NO synthase (iNOS); identified
calmodulin as a sub-unit of iNOS; cloned and characterized the iNOS
promoter; showed the role of NF- k B
and IRF-1 in iNOS induction;
identified specific residues in iNOS necessary for its binding of
NADPH, tetrahydrobiopterin, heme and calmodulin; revealed the
mediation by NO of the antiviral action of IFNg
; produced (with John
Mudgett) iNOS-deficient mice; demonstrated the contribution of iNOS to
host defense against experimental tuberculosis; established that human
macrophages can express iNOS; and demonstrated neuronal expression of
iNOS in Alzheimer’s disease. Our goal now is to identify genes in
bacterial pathogens and human tumors that help confer resistance to NO
and its products, such as peroxynitrite.
Looking back over 30 years of
scientific authorship, three things stand out: the unity of the
questions; the diversity of approaches to answer them; and the
realization that all one’s papers, however many citations ESI says
they earn, will yellow, crumble and be forgotten —the best boiled
down to unattributed statements in textbooks. What lives and lasts is
the chain of teachers and trainees.
Dr. Carl Nathan
Weill Medical College of Cornell University
Department of Medicine
New York, NY, USA
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in-cites, September 2001
Citing URL: http://www.in-cites.com/papers/dr-carl-nathan.html
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