Alfred Goodman Gilman
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Alfred Goodman Gilman (July 1, 1941 – December 23, 2015) was an American
pharmacologist Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...
and
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
. He and
Martin Rodbell Martin Rodbell (December 1, 1925 – December 7, 1998) was an American biochemist and molecular endocrinologist who is best known for his discovery of G-proteins. He shared the 1994 Nobel Prize in Physiology or Medicine with Alfred G. Gilman for ...
shared the 1994
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
"for their discovery of G-proteins and the role of these proteins in
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
in cells." Gilman was the son of Alfred Gilman, who co-authored ''
Goodman & Gilman's The Pharmacological Basis of Therapeutics ''Goodman & Gilman's The Pharmacological Basis of Therapeutics'', commonly referred to as the Blue Bible or Goodman & Gilman, is a textbook of pharmacology originally authored by Louis S. Goodman and Alfred Gilman. First published in 1941, t ...
'' with Louis S. Goodman, from whom his middle name came. He earned a BA in biology with major in biochemistry from
Yale University Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
. Immediately after graduation in 1962, he worked with Allan Conney at Burroughs Wellcome & Company, which resulted in the publication of his first two technical papers. Persuaded by
Earl Wilbur Sutherland, Jr. Earl Wilbur Sutherland Jr. (November 19, 1915 – March 9, 1974) was an American pharmacologist and biochemist born in Burlingame, Kansas. Sutherland won a Nobel Prize in Physiology or Medicine in 1971 "for his discoveries concerning the mecha ...
, he joined
Case Western Reserve University School of Medicine Case Western Reserve University School of Medicine (CWRU SOM, CaseMed) is the medical school of Case Western Reserve University, a private research university in Cleveland, Ohio. It is the largest biomedical research center in Ohio, and is primar ...
for an
MD–PhD The Doctor of Medicine–Doctor of Philosophy (MD–PhD) is a dual doctoral program for physician–scientists, combining the professional training of the Doctor of Medicine (M.D.) degree with the research program of the Doctor of Philosophy (Ph ...
course. He obtained his degree in 1969. He then went to the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
to work with
Marshall Nirenberg Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" a ...
between 1969 and 1971. Gilman became assistant professor of pharmacology at the
University of Virginia School of Medicine The University of Virginia School of Medicine (UVA SOM or more commonly known as UVA Medicine) is the graduate medical school of the University of Virginia. The school's facilities are on the University of Virginia grounds adjacent to The Lawn, ...
in 1971, and full professor in 1977. He chaired the Department of Pharmacology at the
University of Texas Southwestern Medical Center at Dallas The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 23,000 employees, more than 3,000 full-time faculty, and nearly 4 million outpatient ...
from 1981. Upon his retirement in 2009, he was appointed chief scientific officer of the
Cancer Prevention and Research Institute of Texas The Cancer Prevention and Research Institute of Texas (CPRIT) is a state agency that funds cancer research in Texas. It is funded by bonds issued by the state of Texas. Researchers and organizations in Texas are invited to apply for grants that ...
. He resigned in 2012. He was the founder of
Regeneron Pharmaceuticals Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to ...
company and the Alliance for Cellular Signaling. From 2005, he was also director of
Eli Lilly and Company Eli Lilly and Company, Trade name, doing business as Lilly, is an American multinational Medication, pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 count ...
. G proteins are a vital intermediary between the extracellular activation of receptors (
G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...
) on the
cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
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. For his works, he received the Canada
Gairdner Foundation International Award The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a ...
in 1984,
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...
and the
Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...
in 1989, in addition to Nobel Prize. He was elected member of the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
and
American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
, 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 The National Center for Science Education (NCSE) is a Nonprofit organization, not-for-profit membership organization in the United States whose stated mission is to educate the press and the public on the scientific and educational aspects of con ...
.


Early life

Gilman was born in
New Haven, Connecticut New Haven is a city of the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound. With a population of 135,081 as determined by the 2020 United States census, 2020 U.S. census, New Haven is List ...
, as he later commented, "with a scientific/academic
silver spoon The English language expression silver spoon is synonymous with wealth, especially inherited wealth; someone born into a wealthy family is said to have "been born with a silver spoon in their mouth". As an adjective, "silver spoon" describes som ...
" in his mouth, "or perhaps a pestle (but not the mortar)." His parents were Mabel (Schmidt) and Alfred Gilman, a professor at the
Yale School of Medicine The Yale School of Medicine is the medical school of Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813. It is the sixth-oldest m ...
and one of the authors of the classic pharmacology textbook ''
Goodman & Gilman's The Pharmacological Basis of Therapeutics ''Goodman & Gilman's The Pharmacological Basis of Therapeutics'', commonly referred to as the Blue Bible or Goodman & Gilman, is a textbook of pharmacology originally authored by Louis S. Goodman and Alfred Gilman. First published in 1941, t ...
'' (nicknamed the "Blue Bible" of pharmacology). His family is
Jewish Jews (, , ), or the Jewish people, are an ethnoreligious group and nation, originating from the Israelites of History of ancient Israel and Judah, ancient Israel and Judah. They also traditionally adhere to Judaism. Jewish ethnicity, rel ...
. 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 Michael Stuart Brown ForMemRS NAS AAA&S APS (born April 13, 1941) is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of choles ...
(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." (Gilman later served as one of the textbook's editors from 1980 to 2000, first collaborating with, then succeeding his father and Goodman.) He had an elder sister Joanna Gilman. He grew up in
White Plains, New York White Plains is a city in and the county seat of Westchester County, New York, United States. It is an inner suburb of New York City, and a commercial hub of Westchester County, a densely populated suburban county that is home to about one milli ...
, while his father worked at
Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...
and
Albert Einstein College of Medicine The Albert Einstein College of Medicine is a Private university, private medical school in New York City. Founded in 1953, Einstein is an independent degree-granting institution within the Montefiore Einstein Health System. Einstein hosts Doc ...
.


Education

Gilman attended local elementary school in White Plains. Hoping for better education, in 1955 his parents sent him to
The Taft School The Taft School is a private coeducational school located in Watertown, Connecticut, United States. It enrolls approximately 600 students in grades 9–12. Overview History The school was founded in 1890 as Mr. Taft's School (renamed to ...
in
Watertown, Connecticut Watertown is a town in Litchfield County, Connecticut, United States. The town is part of the Naugatuck Valley Planning Region. The population was 22,105 at the 2020 census. It is a suburb of Waterbury. The urban center of the town is the Wat ...
, 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." He recalled that he was "the worst 120-pound lineman on the intramural tackle football team." He studied science at Yale University. His first research project was to test the
adaptor hypothesis The adaptor hypothesis is a theoretical scheme in molecular biology to explain how information encoded in the nucleic acid sequences of messenger RNA (mRNA) is used to specify the amino acids that make up proteins during the process of Translation ...
of
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the Nucleic acid doub ...
. He worked in the laboratory of Melvin Simpson, where he met his future wife Kathryn Hedlund. (They were married in 1963.) He graduated in 1962 receiving a BA in biology with major in biochemistry. During summer break in 1962, he briefly worked at Burroughs Wellcome & Company in New York, under with Allan Conney. With Conney he published his first two research papers in 1963. He then entered a combined MD-PhD program at
Case Western Reserve University School of Medicine Case Western Reserve University School of Medicine (CWRU SOM, CaseMed) is the medical school of Case Western Reserve University, a private research university in Cleveland, Ohio. It is the largest biomedical research center in Ohio, and is primar ...
in Cleveland, Ohio where he wanted to study under Nobel laureate pharmacologist Earl 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." However, Sutherland was departing for
Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private university, private research university in Nashville, Tennessee, United States. Founded in 1873, it was named in honor of shipping and railroad magnate Cornelius Vanderbilt, who provide ...
, so Gilman studied with Sutherland's collaborator, Theodore Rall. Gilman graduated from Case Western in 1969, then did his post-doctoral studies at the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
with Nobel laureate
Marshall Nirenberg Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" a ...
from 1969 to 1971. Nirenberg assigned him to work on the study of nerve endings (
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
s 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. The work was a simple and vital biochemical assay for studying
cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triph ...
.


Career

In 1971, Gilman was appointed assistant professor of pharmacology at the
University of Virginia The University of Virginia (UVA) is a Public university#United States, public research university in Charlottesville, Virginia, United States. It was founded in 1819 by Thomas Jefferson and contains his The Lawn, Academical Village, a World H ...
, School of Medicine, in
Charlottesville, Virginia Charlottesville, colloquially known as C'ville, is an independent city (United States), independent city in Virginia, United States. It is the county seat, seat of government of Albemarle County, Virginia, Albemarle County, which surrounds the ...
. He became full professor in 1977. In 1981, he became chairman of the Department of Pharmacology at the
University of Texas Southwestern Medical Center at Dallas The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 23,000 employees, more than 3,000 full-time faculty, and nearly 4 million outpatient ...
. From 2004 he became the dean, and between 2006 and 2009 he was executive vice president for academic affairs and provost. 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. 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. He was also the founder and Chair of the Alliance for Cellular Signaling, a global collaboration for the study of cell signalling. He became its director from 1990. In 2005, he was appointed director of the drug company, Eli Lilly & Co.


Death

Gilman died after a long battle with
pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...
in
Dallas Dallas () is a city in the U.S. state of Texas and the most populous city in the Dallas–Fort Worth metroplex, the List of Texas metropolitan areas, most populous metropolitan area in Texas and the Metropolitan statistical area, fourth-most ...
,
Texas Texas ( , ; or ) is the most populous U.S. state, state in the South Central United States, South Central region of the United States. It borders Louisiana to the east, Arkansas to the northeast, Oklahoma to the north, New Mexico to the we ...
, 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.


Contributions


Discovery of G protein

In the 1960s, Earl Sutherland and Theodore Rall discovered that cyclic AMP (the
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...
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. Cyclic AMP is formed from ATP by the enzymes
adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...
. 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. Gilman pursued the mystery in the signalling process. He found that in
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
(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. In 1980, he succeeded in identifying and isolating the new protein, which he named G protein, as it specifically binds to GTP molecules.


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 The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Natio ...
, including Nobel laureates, to publicly criticize the board in ''
The Dallas Morning News ''The Dallas Morning News'' is a daily newspaper serving the Dallas–Fort Worth area of Texas, with an average print circulation in 2022 of 65,369. It was founded on October 1, 1885, by Alfred Horatio Belo as a satellite publication of the ' ...
''. He eventually became member of the advisory council of the National Centre for Science Education. He also opposed the
Institute for Creation Research The Institute for Creation Research (ICR) is a creationist apologetics institute in Dallas, Texas, that specializes in media promotion of pseudoscientific creation science and interpretation of the Genesis creation narrative as a historical e ...
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.


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." He received the
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...
as well as the
Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...
from
Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...
in 1989 together with
Edwin Krebs Edwin Gerhard Krebs (June 6, 1918 – December 21, 2009) was an American biochemist. He received the Albert Lasker Award for Basic Medical Research and the Louisa Gross Horwitz Prize of Columbia University in 1989 together with Alfred Gilman ...
. In 1995, Gilman received the Golden Plate Award of the
American Academy of Achievement The American Academy of Achievement, colloquially known as the Academy of Achievement, is a nonprofit educational organization that recognizes some of the highest-achieving people in diverse fields and gives them the opportunity to meet one ano ...
. In 2005, he was elected as Dean of 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. He was elected member of
American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
. He received honorary doctorates from Case Western Reserve University, Yale University, University of Chicago, and University of Miami.


Key papers

* * * * * * * * * * * * * * * * * * * * * * * * * *


Further reading

* *


See also

*
List of Jewish Nobel laureates Of the 965 individual recipients of the Nobel Prize and the Nobel Memorial Prize in Economic Sciences between 1901 and 2023, at least 216 have been Jews or people with at least one Jewish parent, representing 22% of all recipients. Jews constitut ...


References


External links


The Official Site of Louisa Gross Horwitz PrizeProfile at Superstars of ScienceBiography at Encyclopædia BritannicaFinding Aid for the Alfred Goodman Gilman Collection, UT Southwestern Archives, UT Southwestern Medical Center
* including the Nobel Lecture on 8 December 1994 ''G Proteins and Regulation of Adenylyl Cyclase'' {{DEFAULTSORT:Gilman, Alfred G. 1941 births 2015 deaths Nobel laureates in Physiology or Medicine American Nobel laureates Richard-Lounsbery Award laureates Case Western Reserve University alumni American critics of creationism Deaths from pancreatic cancer in Texas Eli Lilly and Company people American pharmacologists Jewish American scientists Jewish chemists Taft School alumni Yale University alumni Members of the United States National Academy of Sciences Scientists from New Haven, Connecticut University of Virginia School of Medicine faculty University of Texas Southwestern Medical Center faculty Recipients of the Albert Lasker Award for Basic Medical Research Members of the National Academy of Medicine