Skip to content
Nobel Jews
Portrait of Alfred G. Gilman
Photo: NIH historic image, http://profiles.nlm.nih.gov/ps/retrieve/Series/4729 · Public domain via Wikimedia Commons

Nobel Prize in Physiology or Medicine · 1994

Alfred G. Gilman

He purified the first G-protein, the switch that carries hormone and drug signals into our cells.

The Nobel citation: “for their discovery of G-proteins and the role of these proteins in signal transduction in cells”
Born
July 1, 1941, New Haven, CT, USA
Died
December 23, 2015, Dallas, TX, USA
Shared with
Martin Rodbell
Affiliation at the time
University of Texas Southwestern Medical Center at Dallas, USA

Medicine prize

1994

Shared with 1 other laureate.

Age that year

53years

Born in 1941.

Headline credited impact

$22–26billion in economic value

Cumulative global sales of drugs that act on G-protein-coupled receptors, 1990-2025 (a proxy for economic activity). How it was built

Sources cited

21

Fact-checked September 24, 2026.

  • His middle name, Goodman, honours his father's co-author. Their pharmacology textbook came out in 1941, the year he was born, and a friend joked he was named after a textbook.
  • The key clue came from an experiment that worked for the wrong reason: a cell extract with its enzyme destroyed still restored the hormone response, exposing a hidden protein.
  • Told he had won the Nobel Prize, he joked that he had first activated his receptor, then his G-protein, and secreted all the adrenaline he had.
  • In 2012 he quit as chief scientist of Texas's $3 billion cancer institute, protesting a $20 million grant awarded without scientific review.
  • In 2003 he and 16 fellow Academy members, three of them Nobel laureates, urged Texas to judge biology textbooks on scientific accuracy alone.

The breakthrough

Purifying the G-protein, the relay that carries signals across the cell membrane

Hormones such as adrenaline dock on the outside of a cell, yet their message has to reach the inside. Earl Sutherland had shown that a docked hormone makes an enzyme in the membrane produce a 'second messenger' called cyclic AMP. Martin Rodbell then showed that the step in between needs a small energy-carrying molecule, GTP, and proposed a 'transducer' linking the receptor to the enzyme. Nobody knew what the transducer was. Gilman's lab at the University of Virginia attacked the question with mutant mouse lymphoma cells, a kind of blood-cancer cell. One strain, called cyc-, seemed to lack the enzyme altogether. His postdoc Elliott Ross tried to repair these cells by adding back the enzyme, extracted from other cells that had it. It worked, but for an unexpected reason: even when the enzyme in the added extract was destroyed, the hormone response came back. The mutant cells had the enzyme all along. What they lacked was a third protein, one that binds GTP. Paul Sternweis and John Northup spent years purifying it, and in 1980 they succeeded: the first G-protein, now called Gs. Think of a doorbell with a button outside and a bell inside. Rodbell showed there had to be a wire in between; Gilman's team pulled out the wire and showed what it was made of. His lab went on to purify other G-proteins, including Gi, which turns the same enzyme down.[1],[3],[4],[12]

“First I activated my receptor, then my G-Protein. I was obviously extremely excited. I think I secreted all the adrenaline I had.”
Alfred G. Gilman, Gilman describing to The New York Times how he reacted to the news of his 1994 Nobel Prize, as recalled in the paper's obituary.[6]

What it meant for humanity

G-proteins turned out to be everywhere. Gilman's lab and others found a whole family of them, relaying signals from hormones, brain chemicals, light in the eye, odours and tastes. In his Nobel lecture Gilman noted that they control processes from mating in yeast to thinking in humans. Knowing the parts helped explain disease. Cholera toxin locks one G-protein in its 'on' state, so the gut pours out salt and water, and Gilman's purified protein let his lab confirm directly that the toxin modifies it. Whooping cough toxin blocks other G-proteins. Overactive G-proteins turn up in some tumours and in McCune-Albright syndrome, a rare hormone disorder. The discovery also sits beneath a large part of modern medicine. About a third of approved drugs act on receptors that pass their message on through G-proteins, and a 2017 review found that these drugs made up about 27% of the world medicines market, with sales of roughly $890 billion from 2011 to 2015. Most were found before G-proteins were known, so the discovery explains how they work rather than having created them, and a 1996 profile noted that no disease had yet been cured because of it. Gilman's influence also ran through books and institutions. He helped edit Goodman & Gilman's The Pharmacological Basis of Therapeutics, the standard textbook his father co-wrote, built the pharmacology department at UT Southwestern in Dallas, and launched the Alliance for Cellular Signaling, a multi-lab project that made all its data freely available.

  • Cholera's deadly loss of salt and water happens because cholera toxin locks a G-protein in its active state, the Nobel Assembly explained in 1994.[3]
  • Specialised G-proteins carry the signals for sight, smell and taste, as well as for many hormones.[3],[4]
  • About a third of approved drugs (481 in a 2017 count, and near 700 by another estimate) act on G-protein-coupled receptors, which pass their signals on through G-proteins.[15],[16]
  • His Alliance for Cellular Signaling, launched with a Dallas planning meeting in 1998, set out to map signalling networks in immune and heart cells and shared all its data freely.[13],[14]

Impact in numbers

Gilman's legacy is mainly knowledge. By purifying the first G-protein he turned Rodbell's abstract 'transducer' into a molecule that could be studied, sequenced and compared, and the G-protein family now helps explain sight, smell, taste, hormone action, the damage done by cholera and whooping cough toxins, and how about a third of approved drugs work. We make one small, low-confidence claim on the outcome shared with Martin Rodbell and Robert Lefkowitz: cumulative world sales of drugs acting on G-protein-coupled receptors, about $4.4 to $5.2 trillion from 1990 to 2025. We credit Gilman with 0.5%, about $22 to $26 billion, because most of these drugs were found without any knowledge of G-proteins and Rodbell shares the discovery. Sales measure spending, not health gained. We make no lives-saved claim, since no study separates his part. His textbook editing, his department building in Dallas and his open-data signalling alliance also go uncounted.

HealthFundamental scienceEconomy

Each number is the laureate’s credited share of a real-world outcome, cumulative to 2025. The whole outcome, the share of credit, and the reasoning are shown so you can check the arithmetic. Outcomes shared with other laureates are counted once on the impact page.

  • Low confidenceRippleModeledEconomy

    Cumulative global sales of drugs that act on G-protein-coupled receptors, 1990-2025 (a proxy for economic activity)

    $22–26

    billion in economic value, credited share

    That is 0.5% of $4.4–5.2 trillion in economic value since 1990.

    How this number was built

    Range reused from the Rodbell and Lefkowitz profiles so totals line up. Low: 27% market share (Hauser 2017) of IMS prescription sales of $127.7B (1990) and $282.5B (2000) (WHO 2004, Table 4.2): 11 yrs x $55.4B avg = $0.61T; 2001-10 = 10 x avg($76.3B, $178B) = $1.27T; 2011-15 = $0.89T (Hauser); 2016-25 flat at $160B = $1.60T; total $4.37T. High: 35% (Sriram & Insel) gives $0.79T + $1.38T + $0.89T + ($178B growing 3%/yr) $2.10T = $5.16T. Nominal. Share: these drugs act through receptors that switch on G-proteins, the transducers Gilman's lab identified and purified, but most GPCR drug classes were found before G-proteins were known. As in the Rodbell profile, we give the G-protein discovery 1% of the outcome, split equally with Rodbell: 0.005 ($22B-$26B). Sales measure spending, not benefit.[3],[15],[16],[17]

    Sources: Nature Reviews Drug Discovery (via PubMed Central); Molecular Pharmacology (via PubMed Central); World Health Organization; NobelPrize.org (Nobel Assembly at Karolinska Institutet)

The double edge

We found no weapons, deliberate harms or personal scandals tied to Gilman's work. The controversies are of other kinds. The prize, limited to two people, simplified a team effort: in his Nobel lecture Gilman credited Elliott Ross with the key reconstitution experiments and Paul Sternweis and John Northup with the hard work of purification, and the first mutant cells came from Henry Bourne's group. The medical payoff has also been indirect. In 1996 a profile noted that no disease had yet been defeated because of the G-protein discoveries; their value lies mainly in explaining how drugs, hormones and toxins act. Finally, Gilman's last public post ended in dispute. In 2012 he resigned as chief scientific officer of the Cancer Prevention and Research Institute of Texas, saying commercial and political factors were influencing its grants, after a $20 million award to M.D. Anderson Cancer Center and Rice University went ahead without scientific review. Seven more senior scientists resigned later that year. The dispute concerned the agency, not misconduct by Gilman.

  • Minor

    A two-person prize for a team discovery

    Gilman's Nobel lecture credits postdoc Elliott Ross with the experiments that revealed the missing protein, and Paul Sternweis and John Northup with purifying it. The mutant cells that made the work possible were first isolated by Henry Bourne's group.[4]

  • Minor

    Slow route from discovery to cures

    A 1996 University of Washington profile observed that no disease had yet been defeated or cancer cured because of the discoveries of Rodbell and Gilman, though they had improved understanding of illnesses such as cholera.[20]

  • Minor

    Resignation from the Texas cancer institute

    Gilman became chief scientific officer of the Cancer Prevention and Research Institute of Texas, a $3 billion state agency, in 2009. He resigned three years later, criticising commercial and political influence on its grants, after a $20 million award was made without scientific review. Seven senior scientists followed him out.[6]

Against the odds

Gilman grew up in comfort, and we found no account of him facing antisemitism. His father was a Yale professor, he boarded at the Taft School, and he later said he was born with a scientific silver spoon in his mouth. His father's rise was less expected. The son of Russian Jewish parents and of a Bridgeport music-store owner, he was the first in his family to go to college. He studied and began teaching at Yale in the 1920s and 1930s, when American colleges and medical schools limited Jewish admissions. Milton Winternitz, dean of Yale's medical school from 1920 to 1935, had applications marked 'H' for Hebrew and told his admissions committee to admit no more than five Jewish students. National surveys found that in 1933-34 about 26% of Jewish applicants to US medical schools won a place, against 46% of other applicants; a 1939 B'nai B'rith study put the figures at about 25% and 50%. By the time Gilman entered Yale in the late 1950s and medical school in 1962, such barriers were fading. We found no record that they affected him or his father, so we do not claim that either overcame discrimination.

  • 1933

    Quota

    In the era when his father, the son of Russian Jewish parents, trained and taught at Yale, US medical schools admitted Jewish applicants at far lower rates, and Yale's medical dean capped Jewish admissions at five. We found no record that these limits affected Gilman or his father.[9],[11],[21]

Jewish background

Jewish fatherDistant from Jewish identity

In a 2000 interview with the chemist István Hargittai, Gilman said his father's parents were Russian Jewish and his mother's ancestors came from Western Europe. His father, the pharmacologist Alfred Gilman, was the son of a Bridgeport, Connecticut, music-store owner and the first in the family to go to college. Gilman said his family took little interest in organised religion and that his father had turned away from all formal Jewish practice. At his Connecticut boarding school, where religion was compulsory, he attended a Protestant church like most of the other boys. We found no statement by him about a Jewish identity of his own.[2],[10],[18],[19],[21]

Key dates

  1. July 1, 1941

    Born in New Haven, Connecticut, to pharmacologist Alfred Gilman and pianist Mabel Schmidt Gilman, in the year his father's famous textbook first appeared.[1],[2]

  2. 1955

    Sent from White Plains, New York, to the Taft School in Watertown, Connecticut, for his last three years of high school.[2]

  3. 1962

    Graduates from Yale in biochemistry and enters Earl Sutherland's new combined MD-PhD programme at Western Reserve University in Cleveland, after first turning it down.[2],[4],[5]

  4. 1969

    Earns his MD and PhD, then joins Marshall Nirenberg's lab at the National Institutes of Health, where he devises a simple, sensitive test for cyclic AMP.[2],[6]

  5. 1971

    Becomes an assistant professor of pharmacology at the University of Virginia in Charlottesville.[2]

  6. 1977

    With postdoc Elliott Ross, finds that mutant lymphoma cells lack not the enzyme but a separate GTP-binding protein needed to switch it on.[4],[8]

  7. 1980

    His lab reports the purification of that protein, the first G-protein, now called Gs.[3],[12]

  8. 1981

    Moves to Dallas to chair the Department of Pharmacology at the University of Texas Southwestern Medical Center.[2]

  9. 1989

    Receives the Albert Lasker Award for Basic Medical Research.[8],[21]

  10. 1994

    Awarded the Nobel Prize in Physiology or Medicine with Martin Rodbell for the discovery of G-proteins.[1],[3]

  11. 1998

    Convenes leading signalling researchers in Dallas to plan the Alliance for Cellular Signaling, a ten-year, data-sharing project.[13],[14]

  12. 2009

    Retires from UT Southwestern and becomes chief scientific officer of the Cancer Prevention and Research Institute of Texas.[6],[7]

  13. 2012

    Resigns from the Texas cancer institute, criticising commercial and political influence on its grant awards.[6]

  14. December 23, 2015

    Dies of pancreatic cancer in Dallas, aged 74.[1],[6]

Sources

  1. 1.Alfred G. Gilman - Facts · NobelPrize.org (Nobel Prize Outreach)
  2. 2.Alfred G. Gilman - Biographical (from Les Prix Nobel, The Nobel Prizes 1994) · NobelPrize.org (Nobel Foundation), 1995
  3. 3.Press release: The Nobel Prize in Physiology or Medicine 1994 · NobelPrize.org (Nobel Assembly at Karolinska Institutet), 1994
  4. 4.G Proteins and Regulation of Adenylyl Cyclase (Nobel Lecture, 8 December 1994) · NobelPrize.org, 1994
  5. 5.Interview with Alfred G. Gilman (Adam Smith, April 2007) · NobelPrize.org, 2007
  6. 6.Dr. Alfred G. Gilman, Whose Work on Proteins Won Nobel Prize, Dies at 74 (William Grimes), Wayback Machine copy · The New York Times, 2015
  7. 7.Alfred G. Gilman dies, Wayback Machine copy · National Center for Science Education, 2015
  8. 8.Alfred G. Gilman · Wikipedia
  9. 9.Alfred Gilman, 1908-1984: A Biographical Memoir (Murdoch Ritchie), Biographical Memoirs vol. 70 · National Academies Press, 1996
  10. 10.Jewish Nobel Prize Winners in Medicine (entry and note on Alfred G. Gilman) · Jinfo.org
  11. 11.The Jewish Problem in U.S. Medical Education, 1920-1955 (Edward C. Halperin, Journal of the History of Medicine 56) · Journal of the History of Medicine and Allied Sciences (via Jewish Historical Society of South Carolina), 2001
  12. 12.Purification of the regulatory component of adenylate cyclase (Northup JK, Sternweis PC, Smigel MD, Schleifer LS, Ross EM, Gilman AG, PNAS 77:6516-6520) · Proceedings of the National Academy of Sciences (PubMed record), 1980
  13. 13.Overview of the Alliance for Cellular Signaling (Gilman AG et al., Nature 420:703-706) · Nature (PubMed abstract), 2002
  14. 14.Cross talk: interview with Al Gilman (Mol Interv 1:14-21) · Molecular Interventions (PubMed abstract), 2001
  15. 15.Trends in GPCR drug discovery: new agents, targets and indications (Hauser AS et al., Nat Rev Drug Discov 16:829-842), author manuscript · Nature Reviews Drug Discovery (via PubMed Central), 2017
  16. 16.G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs? (Sriram K, Insel PA, Mol Pharmacol 93:251-258) · Molecular Pharmacology (via PubMed Central), 2018
  17. 17.The World Medicines Situation (WHO/EDM/PAR/2004.5), Table 4.2 · World Health Organization, 2004
  18. 18.Alfred Gilman Sr. · Wikipedia
  19. 19.List of Jewish Nobel laureates · Wikipedia
  20. 20.The 'G' Man: The Breakthrough that Led to the Prize (Tom Griffin), Columns, June 1996 · University of Washington Alumni Association, 1996
  21. 21.Candid Science II: Conversations with Famous Biomedical Scientists (István Hargittai), interview with Alfred G. Gilman recorded 11 July 2000, pp. 238-251 (family background pp. 245-246) · Imperial College Press (Internet Archive library record), 2002

Fact-checked on September 24, 2026 by a separate AI fact-checking pass that re-opened the sources, with 7 corrections made. How we check

Suggest a correction