In the 1970s, scientists struggled with a big gap in their knowledge of cell behavior. They knew that hormones and drugs bind to receptors outside the cell and somehow send messages to the interior of the cell to make it do certain things.
“But we had no idea what linked the two things,” says Michael Brown, a Nobel laureate and molecular geneticist at the University of Texas Southwestern Medical Center in Dallas.
Dr. Alfred G. Gilman devoted his career to finding that link and, in a series of experiments in a lab on Grounds in 1977, he made a Nobel Prize-winning breakthrough.
Gilman died in December at the age of 74.
In those experiments, he and postdoctoral student Elliott Ross isolated a protein—the G protein—that helps relay signals received at the cell membrane into the cell interior. Once inside the cell, those signals tell the cell how to behave.
Gilman, who earned a medical degree and a doctorate in pharmacology at Case Western Reserve University, joined UVA’s pharmacology department in 1971 and stayed for 10 years before accepting a post at UT Southwestern.
Brown, Gilman’s longtime colleague at UT Southwestern, likens Gilman’s discovery of G proteins to finding the last missing piece of a puzzle. For the first time, scientists knew how receptors on the cell surface transmit information to the interior. This let scientists understand the intercellular signaling mechanism that influences many physiological reactions, says Brown.
Now, “anyone who studies anything in biology has to keep in mind Al’s proteins, because they affect so many different things,” from our understanding of physiological response to how prescription drugs work, Brown says. For example, one hormone in blood causes blood pressure to rise; blocking that hormone helps lower blood pressure. Since the hormone acts through G proteins, some drugs used to treat high blood pressure work by blocking the signaling system that Gilman discovered, Brown says.
After Gilman isolated G proteins at UVA, Brown and others at UT Southwestern persuaded him and his wife, Kathryn, to leave Charlottesville for Dallas in 1981. There, Gilman chaired the pharmacology department while continuing his own research.
He eventually identified all the proteins necessary for these reactions to occur within cells and showed at a molecular level how the signaling mechanism works, Brown says. Ross says that because of Gilman’s discovery, he’s been able to work on information-processing modules in human cancer cells, green algae, yeast, neurons and most things in between.
Gilman shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell “for their discovery of G proteins and the role of these proteins in signal transduction in cells.” Gilman’s research built upon and rounded out Rodbell’s work on receptors and hormone stimulation.
A rigorous scientist with no tolerance for “sloppy science,” Gilman was an outgoing and friendly man who loved to talk science over drinks in the UT Southwestern faculty club, Brown says. His colleagues would gather around to hear a good joke and, on a more serious note, ask for his opinions, Brown says. “We knew how brilliant he was.”