Alfred G. Gilman was an American pharmacologist and biochemist who is best remembered for inventing the G-protein. He earned his bachelor’s degree from Yale University and his M.D. and Ph. D. from Case Western Reserve University. He then became an Assistant Professor of Pharmacology at the University of Virginia’s School of Medicine. He set out to discover the missing link in Martin Rodbell’s work on cyclic AMP and guanosine triphosphate from this point (ATP). The investigation led to the discovery of G-protein, a critical link between receptors on the cell membrane and subsequent actions within the cell; a discovery that earned him the Nobel Prize in Physiology or Medicine nearly fourteen years later. Meanwhile, he accepted a position as Chairman of the Department of Pharmacology at the University of Texas Southwestern Medical Center, where he remained until his retirement. He was then appointed Chief Scientific Officer at the Cancer Prevention and Research Institute of Texas, but resigned after three years due to commercial and political interference. He lived another three years before succumbing to pancreatic cancer.
Childhood & Adolescence
Alfred Goodman Gilman was born in New Haven, Connecticut, on July 1, 1941. Alfred Zack Gilman, his father, was a pharmacologist best known for pioneering the use of nitrogen mustard in chemotherapy. He was also a co-author of the seminal text ‘Goodman and Gilman’s The Pharmacological Basis of Therapeutics’.
Mabel Schmidt Gilman, his mother, was an accomplished pianist and piano teacher. Joanna Gilman was his elder sister. The family resided in White Plains, a wealthy suburb north of New York City.
Alfred Goodman began his education at a White Plains elementary school. He was later transferred to The Taft School in Watertown, Connecticut, in 1955. He completed his tenth and twelfth grades here.
Gilman enrolled at Yale University after graduating from high school to pursue a B. Sc degree. He was particularly moved by Henry A. Harbury’s lectures on protein chemistry and thermodynamics in this regard. Additionally, he enjoyed working at Melvin Simpson’s laboratory and benefited from the latter’s warmth and strong encouragement.
He eventually earned a B. Sc. in biology with a concentration in biochemistry from Yale in 1962. He recognized his desire to conduct research at this point and joined Allan Conney’s laboratory at Burroughs Wellcome & Company in New York. He published his first two papers here.
Earl Wilbur Sutherland, Jr., renowned for his discovery of cyclic AMP and a close friend of his father, persuaded young Gilman to enroll in a combined M.D.-Ph.D. program at Case Western Reserve University in Cleveland. Although he initially expressed reservations, he eventually enrolled in the program in the fall of 1962.
He completed his doctoral work here under the supervision of Sutherland’s collaborator, Theodore Rall, who was at the time studying cyclic AMP in the brain. Gilman began his work on the thyroid gland under his supervision. Finally, in 1969, he earned both an M.D. and a Ph.D.
Career of Alfred G. Gilman
Alfred G. Gilman began his post-doctoral work at the National Institute of General Medical Sciences shortly after earning his M.D. and PhD degrees in 1969 through the Pharmacology Research Associate Training Program. Marshall Nirenberg assigned him to work on axons from cultured neuroblastoma cells while he was here.
Gilman, on the other hand, found the work completely uninteresting. As a result, he began developing a novel technique for studying protein binding. Nirenberg lauded the work and arranged for its publication in 1970. It was quickly accepted as a straightforward but critical biochemical test for studying cyclic AMP.
His work established him as a national figure, and he was appointed Assistant Professor of Pharmacology at the University of Virginia’s School of Medicine in 1971. He then began studying the process by which chemical signals are transmitted from the outside to the inside of a cell, a process known as transduction.
Martin Rodbell had already established that when guanosine triphosphate (GTP) is released from the cell membrane, cyclic AMP is activated. However, the mechanism of GTP synthesis was unknown. Gilman began his research on signaling in mutant cells.
He later discovered that leukemia cells were unable to respond to external signals transmitted by hormones due to the loss of certain proteins. He then implanted the missing proteins from normal cells into the cancerous cells’ membranes, restoring the cell’s transduction capacity.
Gilman began publishing the results of his experiments in a series of papers beginning in 1977. He also became a full professor that year and continued working on the same project.
In 1980, he identified the specific protein that was responsible for the loss of transduction in cancerous cells. He named it G-protein after the fact that it interacts with guanosine triphosphate molecules, which are required for transduction.
Gilman moved to the University of Texas Southwestern Medical Center in 1981 as Chairman of the Department of Pharmacology, retiring in 2009. Meanwhile, he was appointed dean in 2004 and executive vice president for academic affairs and provost in 2006.
After retiring in 2009, he became Chief Scientific Officer of the Cancer Prevention and Research Institute of Texas. It was a government agency authorized to spend $3 billion over a ten-year period on cancer research and prevention programs in Texas.
Gilman resigned from the position in 2012, citing an excessive amount of commercial and political interference. He was particularly outraged by a $20 million commercial grant that was awarded without scientific review to the M.D. Anderson Cancer Center and Rice University.
Gilman was also involved in a number of other projects outside of his mainstream academic work. From 1980 to 2000, he edited several editions of his father’s and friend Goodman’s ‘Goodman and Gilman’s The Pharmacological Basis of Therapeutics’.
Additionally, he co-founded Regenere, a biotechnology company, and the Alliance for Cellular Signaling, a global collaboration for the study of cell signaling. He also participated actively in the ‘creation-evolution controversy,’ vehemently defending science education.
Significant Works of Alfred G. Gilman
Alfred G. Gilman is best known for discovering the G protein. His work in this field has aided scientists in their understanding of how the body receives signals from a variety of hormones and how it responds to various stimuli such as light and odor.
Additionally, his research established that G-proteins are involved in “everything from sexual behavior in yeast to cognition in humans” and that their absence disrupts the normal signal transduction process, resulting in a variety of diseases such as hereditary glandular disorders, cancer, cholera, diabetes, whooping cough, and alcoholism.
Awards of Alfred G. Gilman
Alfred G. Gilman was awarded the 1994 Nobel Prize in Physiology or Medicine for his “discovery of G-proteins and their role in cell signal transduction.” “‘. He shared the award with Martin Rodbell, another researcher on the same subject.
Gilman received the 1984 Canada Gairdner International Award “for elucidating the mechanism by which peptide hormones influence cell function across cell membranes.”
Apart from that, he was awarded the John J. Abel Award in 1975, the Richard Lounsbery Award in 1987, the Louisa Gross Horwitz Prize in 1989, and the Albert Lasker Award for Basic Medical Research in 1989. (1989).
Personal History and Legacies
Alfred G. Gilman met his future wife, Kathryn Hedlund, while they were both working at Yale University’s Melvin Simpson’s laboratory. They later married while he was a student at Cleveland’s Case Western Reserve University.
Amy, Anne, and Edward (Ted) were the couple’s three children, and they had five grandchildren. Mrs. Gilman was a staunch supporter of her husband’s work and almost single-handedly cared for the family.
Gilman died of pancreatic cancer near the end of his life. He passed away on 23 December 1915, following a protracted battle with the disease.
Estimated Net Worth
The Estimated Net Worth of Alfred G. Gilman is unknown.
Trivia
Alfred Goodman Gilman later stated that he was born “with a scientific/academic silver spoon” due to his father, Alfred Zack Gilman, being a well-known academic and scientist. He also mentioned at one point that he was born with a pestle but not a mortar.
Gilman received his middle name from Louis S. Goodman, who coauthored with his father the book ‘Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Many years later, his friend and Nobel Laureate Michael Stuart Brown joked that Gilman was “Almost certainly the only person ever named after a text book”.