Alfred G. Gilman

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For his father, a pharmacologist and textbook author, see
Alfred Gilman (bishop)
.
Alfred G. Gilman
Dallas, Texas, U.S.
NationalityAmerican
Alma materYale University (B.A., 1962)
Case Western Reserve University (MD-Ph.D., 1969)
Known forG proteins
SpouseKathryn Hedlund
Children3
AwardsJohn J. Abel Award (1975)
Richard Lounsbery Award (1987)
Louisa Gross Horwitz Prize (1989)
Nobel Prize in Physiology or Medicine (1994)
Scientific career
FieldsBiochemistry
Pharmacology

Alfred Goodman Gilman (July 1, 1941 – December 23, 2015) was an American pharmacologist and biochemist.[1] He and Martin Rodbell shared the 1994 Nobel Prize in Physiology or Medicine "for their discovery of G-proteins and the role of these proteins in signal transduction in cells."[2]

Gilman was the son of

Earl Wilbur Sutherland, Jr., he joined Case Western Reserve University School of Medicine for an MD-PhD course. He obtained his degree in 1969. He then went to the National Institutes of Health to work with Marshall Nirenberg
between 1969 and 1971.

Gilman became assistant professor of pharmacology at the

University of Texas Southwestern Medical Center at Dallas from 1981. Upon his retirement in 2009, he was appointed chief scientific officer of the Cancer Prevention and Research Institute of Texas. He resigned in 2012. He was the founder of Regeneron Pharmaceuticals company and the Alliance for Cellular Signaling. From 2005, he was also director of Eli Lilly and Company
.

G proteins are a vital intermediary between the extracellular activation of receptors (

G protein-coupled receptors) on the cell membrane and actions within the cell. Rodbell had shown in the 1960s that GTP was involved in cell signaling. It was Gilman who actually discovered the proteins that interacted with the GTP to initiate signalling cascades within the cell, and thus, giving the name G proteins.[3]

For his works, he received the Canada

Gairdner Foundation International Award in 1984, Albert Lasker Award for Basic Medical Research and the Louisa Gross Horwitz Prize in 1989, in addition to Nobel Prize. He was elected member of the National Academy of Sciences and American Academy of Arts and Sciences, Fellow of the American Association for Cancer Research Academy, and, since 2013 (or earlier), member of the advisory council of the National Center for Science Education.[4]

Early life

Gilman was born in

Alfred Gilman,[6] a professor at the Yale School of Medicine and one of the authors of the classic pharmacology textbook Goodman & Gilman's The Pharmacological Basis of Therapeutics (nicknamed the "Blue Bible" of pharmacology).[5] His family is Jewish.[7] His middle name was in honor of the co-author Louis S. Goodman. The book was published in 1941, the year he was born. His friend Michael 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 in White Plains, New York, while his father worked at Columbia University and Albert Einstein College of Medicine.[6]

Education

Gilman attended local elementary school in White Plains. Hoping for better education, in 1955 his parents sent him to

Marshall Nirenberg from 1969 to 1971.[1] Nirenberg assigned him to work on the study of nerve endings (axons from cultured neuroblastoma 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 studying cyclic AMP.[14]

Career

In 1971, Gilman was appointed assistant professor of pharmacology at the

University 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]

Death

Gilman died after a long battle with pancreatic cancer in Dallas, 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]

Contributions

Discovery of G protein

In the 1960s, Earl Sutherland and Theodore Rall discovered that cyclic AMP (the second 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 enzymes adenylyl 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 in lymphoma (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]

Defending science education

Gilman played active roles in

defending 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 the US National Academy of Sciences, including Nobel laureates, to publicly criticize the board in The Dallas Morning News. He eventually became member of the advisory council of the National Centre for Science Education. He also opposed the Institute 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 the Louisiana Science Education Act of 2008.[26]

Awards and honours

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."

University of Texas Southwestern Medical School, Dallas. He served on the board of advisors of Scientists 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 the American Association for Cancer Research Academy in 2013.[15] He was elected member of American Academy of Arts and Sciences. He received honorary doctorates from Case Western Reserve University, Yale University, University of Chicago, and University of Miami.[26]

Key papers

Further reading

See also

References

  1. ^
    PMID 26791713
    .
  2. ^ "The Nobel Prize in Physiology or Medicine 1994". Nobel Media AB. Retrieved 22 January 2016.
  3. ^ a b c d Grimes, William (24 December 2015). "Dr. Alfred G. Gilman, Whose Work on Proteins Won Nobel Prize, Dies at 74". The New York Times. Retrieved 22 January 2016.
  4. ^ "Advisory Council". ncse.com. National Center for Science Education. Archived from the original on 2013-08-10. Retrieved 2018-10-30.
  5. ^
    PMID 21819235
    .
  6. ^ a b c d e Gilman, Alfred G. (1994). "Alfred G. Gilman - Biographical". Nobelprize.org. Retrieved March 25, 2015.
  7. ^ "Jewish Nobel Prize Winners in Medicine". www.jinfo.org. Retrieved 2023-03-30.
  8. ^ Dr. Alfred Gilman dies at 75, nytimes.com, January 14, 1985.
  9. ^ a b c Weil, Martin (26 December 2015). "Alfred G. Gilman, Nobel Prize-winning scientist, dies at 74". The Washington Post. Retrieved 22 January 2016.
  10. ^
    ISBN 978-1-4381080-70
    .
  11. PMID 13947967
    .
  12. PMID 14109205
    .
  13. PMID 4318781
    .
  14. S2CID 13119712
    .
  15. ^ a b c "Alfred G. Gilman, MD, PhD : Class of 2013". American Association for Cancer Research. Retrieved 22 January 2016.
  16. S2CID 4367083
    .
  17. PMID 13549487
    .
  18. PMID 17119
    .
  19. PMID 190227
    .
  20. PMID 195960
    .
  21. PMID 562358
    .
  22. PMID 195961
    .
  23. PMID 214461
    .
  24. PMID 429354
    .
  25. PMID 231786
    .
  26. ^ a b "Alfred G. Gilman dies". National Centre for Science Education. 28 December 2015. Retrieved 22 January 2016.
  27. ^ "Alfred G. Gilman MD, PhD". Gairdner. Retrieved 22 January 2016.
  28. American Academy of Achievement
    .

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