Overview
The Nobel Assembly kicked off October 2025 by awarding the Medicine Prize to three scientists who discovered the immune system's off-switch—regulatory T cells controlled by the Foxp3 gene. Mary Brunkow and Fred Ramsdell identified the gene in 2001 while studying scurfy mice that died from autoimmune storms. Shimon Sakaguchi had already discovered the cells themselves in 1995. Together, their work explains why our immune systems don't destroy us, and opened the door to treatments for everything from diabetes to lupus.
Over the following week, Stockholm announced prizes in physics for quantum circuits you can hold in your hand, chemistry for molecular frameworks with spaces big enough for gases to flow through, literature for Hungarian László Krasznahorkai's apocalyptic visions, peace for Venezuelan democracy activist Maria Corina Machado, and economics for theories explaining how creative destruction drives sustained growth. The 2025 laureates walked away with 11 million Swedish kronor each—about $1.21 million—and a place in the pantheon of scientists and thinkers who changed how we understand the world.
Key Indicators
People Involved
Organizations Involved
The body of 50 professors at Karolinska Institutet that selects Nobel laureates in Physiology or Medicine.
Independent organization awarding Nobel Prizes in Physics, Chemistry, and Economic Sciences.
Seattle-based nonprofit biomedical research organization pioneering systems approaches to studying biology and disease.
Timeline
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Stockholm Awards Ceremony
Prize CeremonyOver 1,000 guests including Swedish royalty attend Stockholm Concert Hall as laureates receive 11 million SEK prizes.
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Economics Nobel: Innovation-Driven Growth
Prize AnnouncementJoel Mokyr, Philippe Aghion, and Peter Howitt win for theories explaining sustained economic growth through creative destruction and technological progress.
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Peace Nobel: Maria Corina Machado
Prize AnnouncementVenezuelan opposition leader honored for promoting democratic rights and peaceful transition from dictatorship.
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Literature Nobel: László Krasznahorkai
Prize AnnouncementHungarian author wins for compelling, apocalyptic visions that reaffirm art's power amid terror.
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Chemistry Nobel: Molecular Frameworks
Prize AnnouncementRichard Robson, Susumu Kitagawa, and Omar Yaghi win for developing metal-organic frameworks—molecular constructions with spaces for gas flow.
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Physics Nobel: Quantum Circuits
Prize AnnouncementJohn Clarke, Michel Devoret, and John Martinis win for demonstrating macroscopic quantum mechanical tunneling in circuits you can hold.
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Medicine Nobel: Regulatory T Cells
Prize AnnouncementBrunkow, Ramsdell, and Sakaguchi win Nobel Prize in Physiology or Medicine for discoveries enabling autoimmune disease treatments.
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Cancer Immunotherapy Wins Nobel
Scientific RecognitionJames Allison and Tasuku Honjo awarded Nobel for checkpoint blockade therapy—parallel breakthrough using immune system to fight cancer.
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Crafoord Prize Previews Nobel
Scientific RecognitionRamsdell and Sakaguchi share Crafoord Prize for regulatory T cell discoveries—major award often preceding Nobel recognition.
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Foxp3 Controls Regulatory T Cells—The Connection
Scientific DiscoverySakaguchi and other researchers prove Foxp3 gene governs regulatory T cell development, linking earlier discoveries.
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Brunkow and Ramsdell Identify Foxp3 Gene
Scientific DiscoveryWorking at Darwin Molecular Corporation, they discover Foxp3 mutation causes fatal autoimmune disease in scurfy mice and IPEX syndrome in humans.
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Sakaguchi Discovers Regulatory T Cells
Scientific DiscoveryShimon Sakaguchi identifies previously unknown immune cells expressing CD4 and CD25 that prevent autoimmune attacks.
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MHC Structure Wins Nobel Prize
Scientific RecognitionBenacerraf, Dausset, and Snell awarded Nobel for describing major histocompatibility complexes—how bodies distinguish self from non-self.
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Nobel Prize Recognizes Immune Tolerance Discovery
Scientific RecognitionMacFarlane Burnet and Peter Medawar win Nobel for discovering acquired immune tolerance—the foundation for later regulatory T cell research.
Scenarios
Regulatory T Cell Therapies Become Standard Autoimmune Treatment
Discussed by: Nature, Science, frontiers in Immunology journals analyzing clinical trial progress
Building on the laureates' discoveries, engineered regulatory T cell therapies move from trials to standard treatment for multiple sclerosis, type 1 diabetes, lupus, and rheumatoid arthritis within 5-10 years. Sakaguchi's recent work improving induced Treg stability—keeping Foxp3 expression high for six weeks instead of days—makes adoptive cell therapy practical. CAR-Treg cells targeting specific antigens show particular promise: a single infusion restricts autoantibody generation in lupus models. The challenge: manufacturing costs and ensuring long-term Treg survival in hostile inflammatory environments. Success would transform 50 million American lives currently managing autoimmune conditions with immune suppressants that leave patients vulnerable to infections.
Foxp3 Gene Therapy Cures IPEX Syndrome
Discussed by: BMC Public Health, OMIM, Children's Hospital of Philadelphia clinical researchers
IPEX syndrome—caused by Foxp3 mutations—kills most affected boys by age two without bone marrow transplants. Gene therapy directly correcting Foxp3 defects could cure the disease without finding matched donors. Early CRISPR-based approaches show promise in preclinical models: restoring functional Foxp3 rescues regulatory T cell development and prevents autoimmune catastrophe. Clinical trials for IPEX gene therapy could begin within three years. Success would prove the principle for other monogenic autoimmune diseases and validate the laureates' work in the most direct way possible: fixing the exact gene they discovered prevents fatal immune dysregulation.
Treg Modulation Enhances Cancer Immunotherapy
Discussed by: Fred Hutchinson Cancer Center, PMC oncology research analyzing CAR-T and checkpoint inhibitor combinations
The flip side of preventing autoimmunity: regulatory T cells suppress anti-tumor immunity. Researchers are exploring carefully timed Treg depletion or checkpoint inhibitors combined with CAR-T cells. Pembrolizumab (anti-PD-1) after mesothelin-targeting CAR-T cells kept CAR-T cells active longer and less exhausted in mesothelioma trials. The challenge is threading the needle—suppress Tregs enough to let cancer-fighting T cells work without triggering autoimmune side effects. Success requires precision timing and dosing. Sakaguchi's improved Treg generation methods might also help restore tolerance after aggressive immunotherapy, preventing long-term autoimmune complications. This approach could make solid tumor CAR-T therapy finally work.
Historical Context
1960 Nobel Prize: Acquired Immune Tolerance
1945-1960What Happened
MacFarlane Burnet and Peter Medawar discovered that the immune system learns to tolerate 'self' tissues—you can train an immune system during development to accept foreign tissue. Medawar showed that mice exposed to cells from another strain as fetuses would later accept skin grafts from that strain. Burnet provided the theoretical framework: the immune system develops tolerance by eliminating self-reactive cells during development.
Outcome
Short term: Explained why organ transplants fail and pointed toward how to prevent rejection.
Long term: Laid foundation for transplant medicine and the entire field of immune tolerance research that produced the 2025 laureates' discoveries.
Why It's Relevant
Burnet and Medawar explained central tolerance—deleting self-reactive immune cells during development. Sakaguchi, Brunkow, and Ramsdell discovered peripheral tolerance—regulatory T cells that patrol the body and suppress autoimmune attacks that escaped central tolerance. Together, they explain how we don't destroy ourselves.
2018 Nobel Prize: Cancer Immunotherapy via Checkpoint Blockade
1992-2018What Happened
James Allison and Tasuku Honjo discovered immune checkpoints—CTLA-4 and PD-1—that act as brakes on T cells. They realized blocking these brakes unleashes immune cells to attack tumors. Allison's 1996 work on anti-CTLA-4 antibodies cured cancer in mice. Honjo cloned PD-1 in 1992 and showed it's another checkpoint. Their discoveries led to drugs like ipilimumab and pembrolizumab that have saved hundreds of thousands of cancer patients.
Outcome
Short term: Checkpoint inhibitors became standard treatment for melanoma, lung cancer, and other malignancies.
Long term: Revolutionized cancer treatment and created a $50+ billion immunotherapy industry. Side effect: autoimmune complications in 10-20% of patients.
Why It's Relevant
Allison and Honjo took the brakes off immunity to fight cancer. Sakaguchi, Brunkow, and Ramsdell discovered the brake system itself—regulatory T cells controlled by Foxp3. Both Nobel-winning discoveries manipulate the same fundamental immune tolerance machinery, just in opposite directions: one to attack tumors, one to prevent autoimmunity.
1980 Nobel Prize: Major Histocompatibility Complex
1960-1980What Happened
Baruj Benacerraf, Jean Dausset, and George Snell described the major histocompatibility complex (MHC)—the genetic system that lets immune cells distinguish 'self' from 'non-self.' Snell discovered MHC genes control tissue rejection in mice. Dausset found the human equivalent (HLA system). Benacerraf showed MHC determines which antigens trigger immune responses. This explained why transplants between unrelated individuals fail and why some people develop autoimmune diseases.
Outcome
Short term: Enabled tissue typing for transplants and explained genetic susceptibility to autoimmune diseases.
Long term: Created the foundation for understanding T cell recognition and immune system specificity, which regulatory T cells regulate.
Why It's Relevant
MHC explains how T cells recognize targets. Regulatory T cells—the 2025 laureates' discovery—use that same MHC system to police other T cells and prevent autoimmune attacks. Without MHC, you can't have adaptive immunity. Without regulatory T cells, that adaptive immunity destroys you.