
Nobel Prize in Physiology or Medicine · 2000
Paul Greengard
Showed how dopamine and other brain chemicals change nerve cells from the inside, guiding research on mental illness and drugs.
The Nobel citation: “for their discoveries concerning signal transduction in the nervous system”
- Born
- December 11, 1925, New York, NY, USA
- Died
- April 13, 2019, New York, NY, USA
- Shared with
- Arvid Carlsson, Eric Kandel
- Affiliation at the time
- Rockefeller University, USA
Medicine prize
2000
Shared with 2 other laureates.
Age that year
75years
Born in 1925.
Headline credited impact
$109.8–119.8million in economic value
Cumulative net sales of Caplyta (lumateperone), 2020-2025 (a proxy for economic activity). How it was built
Sources cited
21
Fact-checked September 24, 2026.
- His mother died giving birth to him. He gave all of his $400,000 Nobel money to found a prize for women scientists named after her.
- In 1948 he decided against graduate study in physics: the only fellowships came from the Atomic Energy Commission, and he would not help build deadlier weapons.
- In World War II he worked as a Navy electronics technician at MIT on an early-warning system against kamikaze planes.
- His idea that brain signals run through slow chemical chains inside nerve cells was at first met with skepticism and even hostility.
- A company he co-founded developed Caplyta, a drug for schizophrenia and bipolar depression approved eight months after his death.
The breakthrough
How brain chemicals send slow, lasting messages inside nerve cells
Nerve cells talk across tiny gaps called synapses. Some messages are fast, taking less than a thousandth of a second, like flipping a light switch. Greengard studied the slow ones, which take from tens of milliseconds to seconds. He found that when dopamine, a chemical messenger, lands on its receptor, the cell makes a second, inside messenger called cyclic AMP. That turns on enzymes called protein kinases, which stick small phosphate tags onto other proteins. A tagged protein changes shape and behaves differently. Think of it like a thermostat rather than a light switch: it does not send the signal itself, but it changes how strongly the cell reacts to the next one. The tags can alter ion channels, receptors and even which genes are switched on. In 1983 his lab reported a protein now called DARPP-32. It sits where dopamine and other signals meet, like a conductor directing many other molecules. His lab showed that antipsychotic drugs and many drugs of abuse change the tagging of DARPP-32. This helped explain how those drugs act, and gave a map for designing new ones.[2],[3],[6],[7]
“it was greeted initially with enormous skepticism, and at times down-right hostility, by the scientific community.”
What it meant for humanity
Before Greengard, many scientists thought brain signaling was almost entirely electrical. He helped show that most chemical messengers in the brain work through slow chains of reactions inside the receiving cell. That idea became standard textbook science, and it changed how researchers think about the diseases linked to dopamine, including Parkinson's disease, schizophrenia, ADHD and addiction. The Nobel committee said these discoveries were crucial for understanding how disturbed signaling causes neurological and psychiatric illness. His DARPP-32 work gave drug researchers a way to see where antipsychotics, stimulants and drugs of abuse act inside nerve cells. It also underpins the memory research of his co-laureate Eric Kandel, whose short-term memory mechanism uses the same protein tagging. Later, his lab found a protein, p11, that is reduced in brain tissue from depressed patients, and a protein, GSAP, that helps make the amyloid found in Alzheimer's plaques. Both became research targets. Soon after his Nobel Prize he co-founded Intra-Cellular Therapies to turn signaling research into medicines. Its drug lumateperone, sold as Caplyta, was approved in the United States for schizophrenia in December 2019 and later for bipolar depression and, with antidepressants, major depression. He also tried to change who gets recognized in science. He and his wife, the sculptor Ursula von Rydingsvard, used his whole Nobel award to start the Pearl Meister Greengard Prize for women in biomedical research. Its winners have included Elizabeth Blackburn and Jennifer Doudna.
- Showed that dopamine works by raising cyclic AMP and switching on protein kinases that tag other proteins, the basic model of slow signaling in the brain.[2],[6]
- Found DARPP-32, a central switch protein whose state is changed by antipsychotic drugs and by drugs of abuse.[3],[7]
- His lab linked the protein p11 to depression (2006) and the protein GSAP to Alzheimer's amyloid (2010), opening new research targets.[8],[9]
- Co-founded Intra-Cellular Therapies, whose drug Caplyta is approved for schizophrenia, bipolar depression and, with antidepressants, major depression.[10],[11],[13],[17]
- Used his full $400,000 Nobel award to create a prize for women in biomedical science, awarded since 2004.[4],[5]
Impact in numbers
Greengard's main gift is knowledge. He showed that most chemical messages in the brain work by setting off slow chains of reactions that tag proteins inside nerve cells. This model now frames research on Parkinson's disease, schizophrenia, depression, ADHD, addiction and Alzheimer's disease, and it helped explain how many existing psychiatric drugs work. No study measures lives saved or health gained from that understanding, so we do not invent a number for it. We make one small, low-confidence claim: sales of Caplyta, the drug from the company he co-founded, about $2.2 to $2.4 billion from 2020 to 2025. We credit him with 5 percent, because the company licensed the compound from Bristol Myers Squibb in 2005 and company scientists did the drug's development and testing. Sales measure spending, not benefit. His prize for women scientists and the many researchers he trained 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 net sales of Caplyta (lumateperone), 2020-2025 (a proxy for economic activity)
$109.8–119.8
million in economic value, credited share
That is 5% of $2.2–2.4 billion in economic value since 2020.
How this number was built
Yearly net product sales from company filings: 2020 $22.5M, 2021 $81.7M, 2022 $249.1M, 2023 $462.2M, 2024 $680.5M (Intra-Cellular); J&J reported $700M from 2 April to 28 December 2025. Low: sum = $2,196M, leaving out Jan-Mar 2025 sales that no opened source reports. High: adds Q1 2025 assumed equal to Q4 2024's $199.2M = $2,395M. Nominal dollars, not inflation-adjusted; because most sales fell in 2023-2025, converting to 2024 dollars would change the total by only about 1-2 percent. Share 0.05: Greengard co-founded Intra-Cellular and its approach of targeting signaling inside nerve cells grew from his work, but the compound was licensed from Bristol Myers Squibb in 2005 (s10) and then developed, tested and sold by company teams (s11); he is not an author on the lumateperone papers. Credit: about $110M-$120M. Sales measure spending, not health gained.[10],[11],[12],[13],[14],[15],[16],[17]
Sources: US Securities and Exchange Commission (EDGAR); US Securities and Exchange Commission (EDGAR); US Securities and Exchange Commission (EDGAR); US Securities and Exchange Commission (EDGAR); US Securities and Exchange Commission (EDGAR); US Securities and Exchange Commission (EDGAR); BioPharma Dive; Advances in Pharmacology (PubMed)
The double edge
Greengard's discoveries were basic science and are not known to have been misused. One serious controversy touched his lab. In 2018 a federal jury found Rockefeller University liable for race and national-origin discrimination against an Iranian-born scientist who worked in his lab, under his supervision, until 2007. He was not a defendant, and the jury rejected her retaliation claim, but the verdict was upheld on appeal. The drug developed by the company he co-founded also carries the standard risks of its class, including boxed warnings.
- Moderate
Discrimination verdict over treatment of a scientist in his lab
In 2018 a federal jury found Rockefeller University liable under New York City law for race and national-origin discrimination against Dr. Effat Emamian, an Iranian-born scientist in Greengard's lab who was not reappointed in 2007. The case centered on her treatment in his lab; he was not a defendant. The jury rejected her retaliation claim. The court cut her $2 million emotional-distress award to $200,000, plus $250,000 back pay; an appeals court affirmed in 2020.[18],[19]
- Minor
Caplyta carries boxed warnings like others in its class
Like other antipsychotics, Caplyta carries a boxed warning of higher death rates in elderly patients with dementia-related psychosis, and, like antidepressants, a warning about suicidal thoughts in young people. These are class-wide risks, not problems specific to Greengard's science.[16]
Against the odds
Greengard was born in New York City in 1925, when many American universities limited how many Jewish students they admitted. Columbia, Harvard and Yale began restricting Jewish admissions in the early 1920s, and most US medical schools had quotas on Jewish students by the 1920s that lasted until after World War II. No source we found says Greengard himself was held back by these barriers, and he was raised Christian. His hardest early loss was personal: his mother died the day he was born, and he grew up cut off from her Jewish family. At 17 he joined the Navy and spent three years as an electronics technician during World War II. After the war he made a principled choice to leave physics rather than work on weapons, and moved into a field that barely existed yet. His central idea was at first met with skepticism and even hostility, because physiologists thought brain signals were purely electrical and biochemists rarely studied the brain. He kept at it for decades until the idea became standard science.
1925
Other
His Jewish mother, Pearl Meister, died giving birth to him. He was raised by an Episcopalian stepmother and kept apart from his mother's family until late in life.[1]
—
Quota
He grew up when Ivy League colleges and most US medical schools limited Jewish admissions. This was the wider climate; no source says he personally faced a quota.[20],[21]
1942
War
Joined the US Navy at 17 and served three years in World War II as an electronics technician, working at MIT on an early-warning system against kamikaze aircraft.[1],[4]
—
Other
His model of slow chemical signaling in nerve cells was at first met with enormous skepticism and at times hostility from other scientists.[3]
Jewish background
Greengard's mother, Pearl Meister, was Jewish, and Nature's obituary says he was born into a Jewish family. His father's side traced back to a great-great-grandfather who moved from Koenigsberg to St. Louis in the 1850s. His mother died giving birth to him, and his father remarried an Episcopalian woman when he was 13 months old. She raised him in the Christian tradition, and he was kept apart from his mother's family until late in life. In his Nobel autobiography he wrote that he had come to know them only recently and was delighted to find so many of them working in science, government and other fields. He named his prize for women scientists after his mother.[1],[4]
Key dates
December 11, 1925
Born in New York City. His mother, Pearl Meister, dies giving birth to him.[1]
1942
Joins the US Navy at 17; works at MIT on an early-warning system against kamikaze planes.[1],[4]
1948
Graduates from Hamilton College in mathematics and physics; turns down physics funding tied to the Atomic Energy Commission.[1]
1953
Earns his PhD at Johns Hopkins University, then does postdoctoral work in London, Cambridge and Amsterdam.[1]
1959
After a year of research at the US National Institutes of Health, becomes director of biochemistry at Geigy Research Laboratories.[1],[4]
1968
Becomes professor of pharmacology at Yale University, where his signaling work begins.[1],[4]
1972
His lab reports a dopamine-sensitive enzyme that makes cyclic AMP in the brain.[6]
1983
Reports the protein later named DARPP-32 and moves to Rockefeller University in New York.[1],[7]
October 9, 2000
Awarded the Nobel Prize in Physiology or Medicine with Arvid Carlsson and Eric Kandel.[2]
2004
The Pearl Meister Greengard Prize for women scientists, funded by his Nobel award, is first given.[4]
2006
His lab links the protein p11 to depression.[8]
2010
His lab identifies GSAP, a protein that helps produce Alzheimer's amyloid.[9]
April 13, 2019
December 2019
Caplyta, from the company he co-founded, is approved in the US for schizophrenia.[11]
Sources
- 1.Paul Greengard - Biographical · NobelPrize.org (Nobel Prize Outreach), 2000
- 2.Press release: The Nobel Prize in Physiology or Medicine 2000 · The Nobel Assembly at Karolinska Institutet, 2000
- 3.The Neurobiology of Dopamine Signaling (Nobel Lecture, 8 December 2000) · NobelPrize.org, 2000
- 4.Paul Greengard (1925-2019): Nobel laureate who traced signals through the brain (Georgina Ferry), Nature 569:488 · Nature, 2019
- 5.Pioneering neuroscientist and Nobel laureate Paul Greengard dies at 93 · The Rockefeller University, 2019
- 6.Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the 'dopamine receptor' (Kebabian, Petzold, Greengard), PNAS 69:2145-9 · Proceedings of the National Academy of Sciences (PubMed), 1972
- 7.A dopamine- and cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions (Walaas, Aswad, Greengard), Nature 301:69-71 · Nature (PubMed), 1983
- 8.Alterations in 5-HT1B receptor function by p11 in depression-like states (Svenningsson et al.), Science 311:77-80 · Science (PubMed), 2006
- 9.Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease (He et al.), Nature 467:95-8 · Nature (PubMed), 2010
- 10.How Intra-Cellular surprised Wall Street by breaking character (interview with founder Sharon Mates) · BioPharma Dive, 2024
- 11.A review of the pharmacology and clinical profile of lumateperone for the treatment of schizophrenia (Snyder et al.), Adv Pharmacol 90:253-276 · Advances in Pharmacology (PubMed), 2021
- 12.Intra-Cellular Therapies reports fourth quarter and full-year 2020 financial results (Form 8-K, Exhibit 99.1) · US Securities and Exchange Commission (EDGAR), 2021
- 13.Intra-Cellular Therapies reports fourth quarter and full-year 2021 financial results (Form 8-K, Exhibit 99.1) · US Securities and Exchange Commission (EDGAR), 2022
- 14.Intra-Cellular Therapies reports fourth quarter and full-year 2022 financial results (Form 8-K, Exhibit 99.1) · US Securities and Exchange Commission (EDGAR), 2023
- 15.Intra-Cellular Therapies reports fourth quarter and full-year 2023 financial results (Form 8-K, Exhibit 99.1) · US Securities and Exchange Commission (EDGAR), 2024
- 16.Intra-Cellular Therapies reports fourth quarter and full-year 2024 financial results (Form 8-K, Exhibit 99.1) · US Securities and Exchange Commission (EDGAR), 2025
- 17.Johnson & Johnson Annual Report on Form 10-K for fiscal year 2025 · US Securities and Exchange Commission (EDGAR), 2026
- 18.Emamian v. Rockefeller University (2d Cir. 2020) · FindLaw Caselaw, 2020
- 19.$2.25 Million Verdict in Race/National Origin Discrimination Case Against Rockefeller University · Beldock Levine & Hoffman LLP (plaintiff's counsel), 2018
- 20.Why Did the United States Medical School Admissions Quota for Jews End? (Halperin EC), Am J Med Sci 358(5):317-325 · American Journal of the Medical Sciences (PubMed), 2019
- 21.How the Ivy League's Jewish quotas shaped higher education (interview with Mark Oppenheimer) · Inside Higher Ed, 2022
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
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