Alfred G. Gilman
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.
This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.
Alfred G. Gilman died on 23 December 2015.
Nobel Prizes and laureates
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