Alfred G. Gilman, a Nobel laureate who concluded his academic career in the role of chief scientific officer of the Cancer Prevention and Research Institute of Texas, died Dec. 23, 2015. Gilman, 74, had pancreatic cancer.
Gilman shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell of the National Institute of Environmental Health Sciences for their discovery of G proteins—guanine nucleotide-binding regulatory proteins. G proteins are central to signaling transduction, the process of receiving signals from outside the cell and activating a range of cellular responses.
G proteins are found in nearly all cells, and are central to body processes that include vision, smell, hormone secretion, and thinking in humans. Problems in G-protein signaling contribute to a range of diseases, including cholera, whooping cough, and cancer.
At UT Southwestern, Gilman served as chairman of pharmacology and dean of the medical school. He was also a former executive vice president for academic affairs and provost at UT Southwestern Medical Center.
In addition to being an academic luminary, Gilman was an exceptional teacher. Once, in 1973, while teaching a pharmacology class at the University of Virginia, Gilman threw out a question: “How do drugs work?”
One student, Leonard Schleifer, had the answer: They work through receptors on the surface of cells.
“Al then reached behind the auditorium lectern, took out a six-pack of Budweiser, and threw it at me,” Schleifer recalled in a conversation recently. “That started a 40-year friendship.”
Later, Gilman encouraged Schleifer to change his academic focus from MD to MD and PhD, and later still he mentored the younger man as he founded Regeneron Pharmaceuticals Inc.—where Gilman served as a co-founder and a board member.
Speaking with this reporter, Schleifer was having difficulty switching to past tense when talking about Gilman. “He has an extreme, if not exaggerated, sense of right and wrong, good and evil, fair and unfair, and when he sees the wrong side of these equations, he cannot sit idly by,” said Schleifer. “Al says what he believes is right and fervently follows that path.”
At CPRIT, a Texas taxpayer-funded institution that spends $300 million a year on cancer research and other cancer-related endeavors, Gilman developed what scientists describe as one of the finest peer review system in existence.
When politicians tried to interfere with the manner in which CPRIT funds were allocated, Gilman resigned. In a spectacular display of solidarity, scientists who were involved in CPRIT’s peer review walked out as well.
A year before his death, Gilman provided a detailed account of his battle to protect public money from what he described as an arrogantly conceived, sloppily executed incursion.
In the upcoming weeks, starting with next week’s issue, The Cancer Letter will run a series of stories that re-examine the CPRIT controversy based on Gilman’s account of his decision to become a whistleblower. The stories of the ungluing of CPRIT and controversies at MD Anderson Cancer Center developed concurrently, and while some of these events have been described in The Cancer Letter before, the series will present this material systematically, with the benefit of historical perspective—and Gilman’s insight.
Gilman took the CPRIT job in 2009. He resigned three years later, bringing attention to the scandal that would otherwise have gone unnoticed.
An argument can be made that Gilman’s very public departure in 2012 created an obligation for his successor at CPRIT to recreate the premier peer review system Gilman put together.
“Whatever CPRIT has managed to accomplish is directly attributable to Al’s vision for the program,” said Margaret Kripke, his successor as the scientific director. “Basically, the program is the one Al set up initially, and I don’t see that changing in the near future.”
Named After a Medical Text
“Dr. Gilman was a giant in medical research. His discovery of G proteins and their critical functions is a cornerstone of research across virtually every important domain of medicine,” said Daniel Podolsky, president of UT Southwestern Medical Center, said in a statement. “As a scientist, teacher, and leader, Dr. Gilman’s contributions are legion. He mentored many scientists who have gone on to become leaders in their fields, and his dedication to serving UT Southwestern was unwavering.”
Gilman served as chairman of pharmacology at UT Southwestern for more than two decades. He retired from the Medical Center in 2009 as a regental professor emeritus to assume the position of chief scientific officer of CPRIT, a position he held until 2012.
On Dec. 4, 2014, the UT System Board of Regents approved the creation of the Alfred G. Gilman Distinguished Chair in Pharmacology, which supports the chairman of the Department of Pharmacology and efforts in pharmacology. The endowment, totaling $1 million, was made possible by a variety of donors, and the inaugural holder of the chair is David Mangelsdorf, chairman of pharmacology at UT Southwestern, who was Gilman’s successor in the department.
In 2012, Gilman became the first UT Southwestern Nobel laureate to donate his medal to the Perot Museum of Nature and Science, saying it gave him enormous pleasure to think that it might inspire a new generation of scientists.
Gilman was born July 1, 1941, in New Haven, Conn., the son of the renowned pharmacologist Alfred Gilman, who was on the faculty at Yale University and who, along with Louis Goodman, authored the preeminent textbook The Pharmacological Basis of Therapeutics.
The elder Gilman chose his son’s middle name, Goodman, in honor of Dr. Goodman. Gilman often said that he was named after a textbook. He became the editor of multiple editions of that textbook from 1980 to 1990.
The younger Dr. Gilman received his bachelor of science summa cum laude in biochemistry from Yale in 1962, followed by his M.D. and doctorate degree in pharmacology in 1969 from Case Western Reserve University. He completed his postdoctoral training in the Laboratory of Biochemical Genetics at NIH (1969 to 1971). From there, he went to the University of Virginia, where he discovered G proteins in 1977.
In 1981, he became chairman of pharmacology at UT Southwestern, where he continued to characterize G proteins. His observations provided the first firm molecular basis for understanding certain signal transduction processes present throughout nature.
“In 1981, Al Gilman became our neighbor in a nearby lab on the fifth floor. We immediately became friends because of several shared passions, particularly for hard core science. Of all the scientists I have known, Al had the most unrelenting commitment to scientific integrity. He could not abide sloppy or phony science, and he said so openly, even when it would have been much safer to stay silent. We may never see the like of him again,” Nobel Laureate Michael Brown, regental professor of the UT System, director of the Erik Jonsson Center for Research in Molecular Genetics and Human Disease, said in a statement.
The UT System Board of Regents named Gilman a Regental Professor in 1995.
In 2004, Gilman became director of a new research center at UT Southwestern—the Cecil H. and Ida Green Comprehensive Center for Molecular, Computational and Systems Biology—devoted to a new field he described as working “to begin to understand how all the ‘parts’ of cells—genes, proteins, and many other molecules—work together to create complex living organisms.” That same year, he was named dean of UT Southwestern Medical School. In 2006, he added the title of executive vice president for academic affairs and provost of UT Southwestern.
Along with the Nobel Prize, his many honors included election to the National Academy of Sciences (1985), winning the Lasker Basic Medical Research Award (1989), and an honorary doctor of medicine from Yale University (1997).
Immediate survivors include wife Kathryn; daughters, Amy Ariagno and Anne Sincovec; and son, Edward Gilman.
