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My
father, Alfred Gilman, could play almost any musical instrument and frequently
did so at neighborhood parties; his father owned a music store in Bridgeport,
Connecticut. My mother, Mabel Schmidt Gilman, was an excellent pianist
and gave lessons; her father was a professional trombonist, also in Bridgeport.
Despite this heritage, my musical career ended after a few years of mediocre
performance with the Yale University Concert Band during my days in college.
There were more substantial influences. My father had turned to science,
receiving his Ph.D. in Physiological Chemistry from Yale in 1931 for "Chemical
and Physiological Investigations on Canine Gastric Secretion". He then
joined the faculty of the Department of Pharmacology at the Yale Medical
School, where he and Louis S. Goodman, a young M.D., became colleagues
and close friends. A major new textbook of Pharmacology The Pharmacological
Basis of Therapeutics, was the fruit of the Goodman and Gilman collaboration,
first published in 1941. I too was born in 1941 (in New Haven, Connecticut)
and named Alfred Goodman Gilman. Perhaps my fate was sealed from that
day; as my friend Michael Brown once said, I am probably the only person
who was ever named after a textboook.
The bulk of my childhood was spent in a suburb of New York City, White
Plains, while my father was first on the faculty of The College of Physicians
and Surgeons of Columbia University and then the founding Chairman of
Pharmacology at the new Albert Einstein College of Medicine. I remember
exciting trips to the city with my parents and elder sister Joanna to
visit museums and, particularly, the Hayden Planetarium. In the early
1950's I made a reservation for a trip to the moon and was quite positive
that I wanted to be an astronomer. Alas, I eventually learned that astronomers
do little star gazing, and biology began to look more appealing. These
feelings were clearly nurtured by trips to my father's laboratory, where
I was able to watch experiments on canine renal function. There were also
elaborate pharmacological demonstrations prepared for the medical students.
All of these experiences were very visual. It is perhaps surprising that
I eventually turned to biochemical approaches to pharmacology; it is not
much fun to watch someone pipette.
My parents were less than enthusiastic about the local high school, and
I was "sent away" in 1955, not smiling, to The Taft School in Watertown,
Connecticut for grades 10 - 12. New England boys' "prep" schools were
not much fun in the 1950's. There was much I did not enjoy, from compulsory
rising bells to compulsory religion and compulsory athletics. I was surely
the worst 120-pound lineman on the intramural tackle football team. But
the education was superb, and I learned how to learn. Chemistry, physics,
and math were extraordinary, and I was even forced to write - an essay
every week. My final victory was from my English teacher. "Not bad, Gilman,"
he said, "it still sounds like a lab report, but not bad."
After Taft, college (at Yale University) was relatively easy and a lot
more fun. I majored in Biochemistry and was inspired by the best series
of lectures ever delivered - by Henry A. Harbury, who taught half the
course. The room was always overflowing, in part because the medical interns
and residents arrived to hear protein chemistry and thermodynamics come
to life; I swear it's the truth. I also had my first real opportunity
to work on my own in a lab - that of Melvin Simpson. My project was wildly
overambitious, to test Francis Crick's adapter hypothesis, but the experience
was an enormous treat because of Simpson's warmth and strong encouragement.
I met my eventual wife at this time, and she spent many late nights in
the lab with me as I manually fed planchettes into the radioactivity counter.
Perhaps she should have smelled the competition.
The summer after
college (1962) I worked in Allan Conney's lab at Burroughs Wellcome in
New York and, thanks to Conney's generosity, I published my first two
papers. There was no question in my mind that research was for me as I
headed to Case Western Reserve University in Cleveland in the fall of
1962, following the lure of cyclic AMP and a novel M.D.-Ph.D. program.
My initial interactions with Earl Sutherland are described in my Nobel
lecture and need not be repeated here. My experience in Cleveland was
most notable, socially, for my marriage to Kathryn Hedlund and the births
of our first two children and, scientifically, for interactions with Ted
Rall, my thesis advisor and now close friend. His commitment was epitomized
by the excuse, usually necessary, when I arrived home for dinner at nine:
"I just went into Ted's office at five o'clock for a few minutes to talk
about an experiment."
Rall was working on cyclic AMP in the brain, while I toiled with the thyroid
gland. The brain looked a bit more interesting, and I was particularly
struck by the molecular biologists who had "solved" their field and were
defecting to the nervous system en mass. Clonal cell lines and genetic
approaches seemed to be the answer, and I asked to work with Marshall
Nirenberg via the Pharmacology Research Associate Training Program of
the National Institute of General Medical Sciences. My experience with
Marshall (1969 1971) was enormously broadening, despite the fact that
I was "forced" (for a while) to work on cyclic AMP. I also met friends
who were to have a great influence later, particularly Joseph Goldstein,
who had not seen the neural light and was working in the residual protein
synthesis section of the Nirenberg laboratory. I had the fortune to develop
a simple and sensitive assay for cyclic AMP while in Bethesda. It helped
make second messengers accessible to everyone, and it surely made my name
visible as I looked for a job.
Continuing what was to become a habit - when moving, always move south
- I became an Assistant Professor of Pharmacology at the University of
Virginia in Charlottesville in 1971. The position was a particularly attractive
opportunity to join old friends from Cleveland, including Joseph Lamer
(the Chairman), Robert Haynes, Ferid Murad, and Bob Berne. The environment
was intellectually supportive and, slowly but surely, good things began
to happen. Crucial were the advent of ligand binding assays for receptors,
the development by Gordon Tomkins and associates of S49 cells (which were
killed by cyclic AMP), and the arrival in 1975 of a superb new postdoctoral
fellow, Elliott Ross. Elliott's hope was to get help from genetics while
unraveling the biochemistry of a complex piece of membrane biology. The
cyclic AMP system interested him, and he had planned to join Tomkins.
Gordon's untimely death forced Ross to a second choice, and I was the
beneficiary. Ross's contributions were enormous, as described in the Nobel
lecture, and his success inspired others to join the group, particularly
including his friend from Cornell, Paul Sternweis, and
John Northrop.
Joe Goldstein and Mike Brown approached me to move to Dallas in 1979,
but I was totally immersed in research and my other major preoccupation,
editing the sixth edition of Goodman and Gilman's the Pharmacological
Basis of Therapeutics. Amusingly, Martin Rodbell
almost took the job,
but, when he eventually declined, the Dallas crowd came calling again
- this time with a real talker in the lead, Donald Seldin. Very few say
no to Dr. Seldin, and I arrived in Dallas to chair the Department of Pharmacology
in 1981. I have been extraordinarily happy in Dallas and have benefitted
greatly from close interactions with colleagues like Brown and Goldstein
and from the opportunity to recruit those whom I knew to be superb - Ross
and Sternweis. I have derived great satisfaction from building what I
consider to be an excellent department, and I hope that our faculty feel
as encouraged as I did in Charlottesville. It is easy to be a successful
Chair in Dallas; our administration, particularly President Kern Wildenthal
and Dean William Neaves, and local philanthropists ensure it.
My wife and three
children, Amy, Anne, and Ted, have always been strongly supportive and
wonderfully understanding of the intense competition from my affair with
science. My children have not benefitted from the lavish fatherly attention
that I did. Despite me, they are well on their way to happy and productive
lives. I am very proud of them and of their super mother, who has made
up for my deficiencies.
From Les Prix Nobel
1994.
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