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Alfred G. Gilman | |
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| Born | Alfred Goodman Gilman July 1, 1941 |
| Died | December 23, 2015(2015-12-23) (aged 74) Dallas, Texas, U.S. |
| Alma mater | Yale University (B.A., 1962) Case Western Reserve University (MD-Ph.D., 1969) |
| Known for | G proteins |
| Spouse | Kathryn Hedlund |
| Children | 3 |
| Awards | John J. Abel Award(1975) Richard Lounsbery Award(1987) Louisa Gross Horwitz Prize(1989) Nobel Prize in Physiology or Medicine(1994) |
| Scientific career | |
| Fields | Biochemistry Pharmacology |
Alfred Goodman Gilman (July 1, 1941 – December 23, 2015) was an Americanpharmacologist andbiochemist.[1] He andMartin Rodbell shared the 1994Nobel Prize in Physiology or Medicine "for their discovery ofG-proteins and the role of these proteins insignal transduction in cells."[2]
Gilman was the son ofAlfred Gilman, who co-authoredGoodman & Gilman's The Pharmacological Basis of Therapeutics withLouis S. Goodman, from whom his middle name came. He earned a BA in biology with major in biochemistry fromYale University. Immediately after graduation in 1962, he worked with Allan Conney atBurroughs Wellcome & Company, which resulted in the publication of his first two technical papers. Persuaded byEarl Wilbur Sutherland, Jr., he joinedCase Western Reserve University School of Medicine for anMD–PhD course. He obtained his degree in 1969. He then went to theNational Institutes of Health to work withMarshall Nirenberg between 1969 and 1971.
Gilman became assistant professor of pharmacology at theUniversity of Virginia School of Medicine in 1971, and full professor in 1977. He chaired the Department of Pharmacology at theUniversity of Texas Southwestern Medical Center at Dallas from 1981. Upon his retirement in 2009, he was appointed chief scientific officer of theCancer Prevention and Research Institute of Texas. He resigned in 2012. He was the founder ofRegeneron Pharmaceuticals company and the Alliance for Cellular Signaling. From 2005, he was also director ofEli Lilly and Company.
G proteins are a vital intermediary between the extracellular activation of receptors (G protein-coupled receptors) on thecell membrane and actions within the cell. Rodbell had shown in the 1960s thatGTP was involved in cell signaling. It was Gilman who actually discovered the proteins that interacted with the GTP to initiatesignalling cascades within the cell, and thus, giving the name G proteins.[3]
For his works, he received the CanadaGairdner Foundation International Award in 1984,Albert Lasker Award for Basic Medical Research and theLouisa Gross Horwitz Prize in 1989, in addition to Nobel Prize. He was elected member of theNational Academy of Sciences andAmerican Academy of Arts and Sciences, Fellow of theAmerican Association for Cancer Research Academy, and, since 2013 (or earlier), member of the advisory council of theNational Center for Science Education.[4]
Gilman was born inNew Haven, Connecticut, as he later commented, "with a scientific/academicsilver spoon" in his mouth, "or perhaps a pestle (but not the mortar)."[5] His parents were Mabel (Schmidt) andAlfred Gilman,[6] a professor at theYale School of Medicine and one of the authors of the classic pharmacology textbookGoodman & Gilman's The Pharmacological Basis of Therapeutics (nicknamed the "Blue Bible" of pharmacology).[5] His family isJewish.[7] His middle name was in honor of the co-authorLouis S. Goodman. The book was published in 1941, the year he was born. His friendMichael Stuart Brown (who was also born in 1941, and later the 1985 Nobel Prize in Physiology or Medicine laureate) joked that Gilman was "probably the only person who was ever named after a textbook."[6] (Gilman later served as one of the textbook's editors from 1980 to 2000, first collaborating with, then succeeding his father and Goodman.[8]) He had an elder sister Joanna Gilman. He grew up inWhite Plains, New York, while his father worked atColumbia University andAlbert Einstein College of Medicine.[6]
Gilman attended local elementary school in White Plains. Hoping for better education, in 1955 his parents sent him toThe Taft School inWatertown, Connecticut, where he completed grades 10 to 12. The school was known for its sports activity, and he described it as "a strict, monastic, and frankly unpleasant environment in the 1950s: academic boot camp."[5] He recalled that he was "the worst 120-pound lineman on the intramural tackle football team."[9] He studied science at Yale University. His first research project was to test theadaptor hypothesis ofFrancis Crick. He worked in the laboratory of Melvin Simpson, where he met his future wife Kathryn Hedlund.[6] (They were married in 1963.) He graduated in 1962 receiving a BA in biology with major in biochemistry.[10] During summer break in 1962, he briefly worked atBurroughs Wellcome & Company in New York, under with Allan Conney. With Conney he published his first two research papers in 1963.[11][12] He then entered a combinedMD-PhD program atCase Western Reserve University School of Medicine in Cleveland, Ohio where he wanted to study under Nobel laureate pharmacologistEarl Sutherland, who was a close friend of his father. It was Sutherland who had introduced the combined MD-PhD course, and invited Gilman to join course. But to Gilman, a seven-year program was like "an eternity in purgatory" and that he preferred not to have a degree in pharmacology, so he refused. Sutherland later persuaded him by explaining that pharmacology was "just biochemistry with a purpose."[5] However, Sutherland was departing forVanderbilt University, so Gilman studied with Sutherland's collaborator, Theodore Rall. Gilman graduated fromCase Western in 1969, then did his post-doctoral studies at theNational Institutes of Health with Nobel laureateMarshall Nirenberg from 1969 to 1971.[1] Nirenberg assigned him to work on the study of nerve endings (axons from culturedneuroblastoma cells), which he considered as "a truly boring project." Instead, against the advice of Nirenberg, he worked on a new method for studying protein binding. After six weeks of working, he showed his result to Nirenberg, who immediately communicated it and got it published in 1970.[13] The work was a simple and vital biochemical assay for studyingcyclic AMP.[14]
In 1971, Gilman was appointed assistant professor of pharmacology at theUniversity of Virginia, School of Medicine, inCharlottesville, Virginia. He became full professor in 1977. In 1981, he became chairman of the Department of Pharmacology at theUniversity of Texas Southwestern Medical Center at Dallas.[6] From 2004 he became the dean, and between 2006 and 2009 he was executive vice president for academic affairs and provost.[15] He retired from university in 2009 to hold the office the chief scientific officer of the Cancer Prevention and Research Institute of Texas. He, however, resigned after three years as he felt that the administration was under commercial and political pressures. His resignation was followed by seven senior scientists.[3]
In addition to mainstream academic position he held other key positions. He was one of the founders of Regeneron, a biotechnology company headquartered in Tarrytown, New York.[9] He was also the founder and Chair of the Alliance for Cellular Signaling, a global collaboration for the study of cell signalling.[16] He became its director from 1990. In 2005, he was appointed director of the drug company, Eli Lilly & Co.[15]
Gilman died after a long battle withpancreatic cancer inDallas,Texas, on December 23, 2015, at the age of 74. He was survived by his wife and three children, Amy Ariagno and Anne Sincovec, both of Dallas, and Edward Gilman of Austin.[3][9]
In the 1960s, Earl Sutherland and Theodore Rall discovered that cyclic AMP (thesecond messenger in signal transduction) was a responsible for activating enzymes in the cell, and that cyclic AMP is produced only when hormones (the first messengers) bind on the cell surface.[17] Cyclic AMP is formed from ATP by the enzymesadenylyl cyclase. In 1970 Martin Rodbell found that hormones did not directly influence cyclic AMP, but there existed other molecules, the third messengers. Rodbell discovered that cyclic AMP is activated when guanosine triphosphate (GTP) is released from the cell membrane. He, however, did not know how the GTP molecules were produced.[10] Gilman pursued the mystery in the signalling process. He found that inlymphoma (cancer) cells, hormones lost their activity to activate adenylyl cyclase, thereby losing their ability to produce cyclic AMP. This was due to loss of proteins in these cancer cells. When he introduced the missing protein from normal cells into the cancer cells, normal hormone action was produced. This showed that the missing membrane protein was responsible for mediating hormonal signal to cyclic AMP by producing GTP. His findings were published in a series of papers between 1977 and 1979.[18][19][20][21][22][23][24][25] In 1980, he succeeded in identifying and isolating the new protein, which he named G protein, as it specifically binds to GTP molecules.[3]
Gilman played active roles indefending science education, and opposing creationism. He opposed the Texas state board of education in 2003 when the board tried to remove evolution from science curriculum. He was the leader of scientists of theUS National Academy of Sciences, including Nobel laureates, to publicly criticize the board inThe Dallas Morning News. He eventually became member of the advisory council of theNational Centre for Science Education. He also opposed theInstitute for Creation Research on its application for certification of its graduate course. He commented: "How can Texas simultaneously launch a war on cancer and approve educational platforms that submit that the universe is 10,000 years old?" He was also one of the signatories on the petition against theLouisiana Science Education Act of 2008.[26]
Gilman was given the Canada Gairdner International Award in 1984 "For elucidating the mechanism by which peptide hormones act across cell membranes to influence cell function."[27] He received theAlbert Lasker Award for Basic Medical Research as well as theLouisa Gross Horwitz Prize fromColumbia University in 1989 together withEdwin Krebs. In 1995, Gilman received the Golden Plate Award of theAmerican Academy of Achievement.[28] In 2005, he was elected as Dean ofUniversity of Texas Southwestern Medical School, Dallas. He served on the board of advisors ofScientists and Engineers for America, an organization focused on promoting sound science in American government. He was elected as a member of the National Academy of Sciences in 1986. He was elected Fellow of theAmerican Association for Cancer Research Academy in 2013.[15] He was elected member ofAmerican Academy of Arts and Sciences. He received honorary doctorates from Case Western Reserve University, Yale University, University of Chicago, and University of Miami.[26]
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including the Nobel Lecture on 8 December 1994G Proteins and Regulation of Adenylyl Cyclase