Alfred G. Gilman, a Nobel Prize-winning American scientist who while working at the University of Virginia discovered a protein that is vital in conveying instructions to the individual cells of organs and tissues, a discovery with important medical implications, died Dec. 23 at his home in Dallas. He was 74.
Dr. Gilman shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell for finding the G protein, a key component of the multistage biochemical signaling process that initiates activity at the cellular level and enables cells to receive messages, transmit them and finally to act on them.
In this process, scientists refer to a “first messenger,” which arrives at the cell from outside, often as a hormone. The first messenger’s arrival at the outer wall of the cell eventually causes production within the cell of a “second messenger,” which prompts the cell to act.
Dr. Gilman’s discovery, the G protein, functions as what science calls a transducer, essentially a relayer of information. Activated by the arrival of the first messenger, it goes on to activate the production of the second.
In a key experiment, Dr. Gilman worked with cells that had undergone mutation. They had the ability to accept external signals. They also had the capacity to produce the internal signals that generate cellular action. But despite possession of these initial and final parts of the messaging process, the cells did not respond to stimuli.
In this situation, Dr. Gilman’s “great insight” according to one of his former students, Leonard Schleifer, was to recognize that an intermediary protein “had to exist.” In the 1970s, urged on by that belief, Dr. Gilman and his collaborators at Charlottesville discovered the G protein.
Dr. Gilman “didn’t believe in magic,” explained Schleifer, the founder, president and chief executive of Regeneron pharmaceuticals. “He believed in biochemistry.”
“Dr. Gilman was a giant in medical research,” said Daniel K. Podolsky, president of the University of Texas Southwestern Medical Center, where Dr. Gilman became the long-serving chairman of pharmacology after leaving Charlottesville.
In a statement, Podolsky added that Dr. Gilman’s “discovery of G proteins and their critical functions is a cornerstone of research across virtually every important domain of medicine.”
G proteins play a part in such processes as sight, hearing, smell and thinking. They help in the translation of the events of the physical world into the biochemical responses of the nervous system. Too much of the protein or too little, and cell function is disrupted, with disease a possible outcome.
In addition to lauding his discovery, colleagues expressed admiration for what they described as Dr. Gilman’s scientific integrity. In particular, he was known for resigning in 2012 as chief scientific officer of the Cancer Prevention and Research Institute of Texas.
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According to the Dallas Morning News, it followed his objection to what he saw as the award of a major grant without adequate outside review.
In an interview Friday, Schleifer said his former teacher “ran into a situation where Texas politics seemed to take hold,” bypassing the peer review system he instituted. “He just couldn’t stand for that.”
Alfred Goodman Gilman, who was born in New Haven, Conn., on July 1, 1941, was a scientist by choice, training and family tradition.
His father, much-honored pharmacologist Alfred Gilman, was on the faculty of the Yale Medical School and the co-author of a magisterial text on drugs and medical treatment, “The Pharmacological Basis of Therapeutics.” (His son eventually worked on later editions.)
As a boy, Dr. Gilman attended his father’s lectures and visited his laboratory. The stars also fascinated him, and he was among thousands who responded when the Hayden Planetarium, part of the American Museum of Natural History in New York, began in 1950 to accept reservations for space voyages.
He attended the private Taft School in Watertown Conn., where he said he was “the worst 120-pound lineman on the intramural tackle football team.” He found his later attendance at Yale “relatively easy and a lot more fun.” He graduated in 1962, as a biochemistry major, and went on to Case Western Reserve University in Cleveland, to enroll in a program enabling students to obtain both PhD and MD degrees simultaneously.
He finished in 1969, then spent two years in post-doctoral research at the National Institutes of Health.
In 1971, Dr. Gilman joined the U-Va. pharmacology faculty. In 1981, he went to Dallas as chairman of the pharmacology department at Southwestern. He was also dean of the UT Southwestern medical school and executive vice president for academic affairs.
He was a cofounder of Regeneron , a pharmaceutical company listed by Forbes magazine as the fourth most innovative firm in the world in 2015..
Dr. Gilman was elected to the National Academy of Sciences in 1985 and won the Lasker Basic Medical Research Award in 1989.
Survivors include his wife, Kathryn Hedlund Gilman of Dallas; and three children, Amy Ariagno and Anne Sincovec, both of Dallas, and Edward “Ted” Gilman of Austin.
Breaking from family tradition, none of Dr. Gilman’s children went into science. In an illustration of their hesitancy and his commitment, Dr. Gilman’s daughter Anne once told an interviewer that they avoided his help with their science homework “unless we had the next 12 hours to spare.”
