By KOSTYA MANENKOV, LAURAN NEERGAARD and LINDSEY WASSON Associated Press
STOCKHOLM (AP) — Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi won the Nobel Prize in medicine Monday for their discoveries concerning peripheral immune tolerance.
Brunkow, 64, is a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, 64, is a scientific adviser for Sonoma Biotherapeutics in San Francisco. Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan.
“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” Olle Kämpe, chair of the Nobel Committee, said.
The award, officially known as the Nobel Prize in Physiology or Medicine, is the first of the 2025 Nobel Prize announcements and was announced by a panel at the Karolinska Institute in Stockholm.
The physics prize will be announced on Tuesday, chemistry on Wednesday and literature on Thursday. The Nobel Peace Prize will be announced Friday and the Nobel Memorial Prize in economics Oct. 13.
The award ceremony will be Dec. 10, the anniversary of the death of Alfred Nobel, who founded the prizes. Nobel was a wealthy Swedish industrialist and the inventor of dynamite. He died in 1896.
The trio will share prize money of 11 million Swedish kronor (nearly $1.2 million).
The work that won the 2025 Nobel Prize in medicine
The immune system has many overlapping systems to detect and fight bacteria, viruses and other intruders. Key immune warriors such as T cells get trained on how to spot bad actors. If some instead go awry in a way that might trigger autoimmune diseases, they’re supposed to be eliminated in the thymus — a process called central tolerance.
The Nobel winners unraveled an additional way the body keeps the system in check.
The Nobel Committee said it started with Sakaguchi’s discovery in 1995 of a previously unknown T cell subtype now known as regulatory T cells or T-regs. Then in 2001, Brunkow and Ramsdell discovered a culprit mutation in a gene named Foxp3, a gene that also plays a role in a rare human autoimmune disease.
Brunkow said she and Ramsdell were working together at a biotech company, investigating why a particular strain of mice had an over-active immune system. They had to work with brand-new techniques to find the mouse gene behind the problem — but quickly realized it could be a major player in human health, too.
“From a DNA level, it was a really small alteration that caused this massive change to how the immune system works,” she told AP.
Two years later, Sakaguchi linked the discoveries to show that the Foxp3 gene controls the development of those T-regs — which in turn act as a security guard to find and curb other forms of T cells that overreact.
Why this work matters
The work opened a new field of immunology, said Karolinska Institute rheumatology professor Marie Wahren-Herlenius. Researchers around the world now are working to use regulatory T cells to develop treatments for autoimmune diseases and cancer.
Dr. Jonathan Schneck, a pathology professor at Johns Hopkins University, is among those who study T cells. He said that until the trio’s research published, immunologists didn’t understand the complexity of how the body differentiates foreign cells from its own and how it can tamp down an overreaction.
The discoveries haven’t yet led to new therapies, Schneck cautioned. But “it’s incredibly important to emphasize, this work started back in 1995 and we’re reaping the benefits but yet have many more benefits we can reap” as scientists build on their work.
How Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi reacted
Thomas Perlmann, secretary-general of the Nobel Committee, said he was only able to reach Sakaguchi by phone Monday morning.
“I got hold of him at his lab and he sounded incredibly grateful, expressed that it was a fantastic honor. He was quite taken by the news,” Perlmann said. He added that he left voicemails for Brunkow and Ramsdell.
At a news conference hours later, Sakaguchi called his win “a happy surprise.” He said he expected he’d have to wait a bit longer until the research makes more contributions in clinical science.
In the beginning, he said the area of his research was not very popular and he had to struggle at times to earn research funding. But there were other scientists who were also interested in the same area of research and their cooperation led to the achievement, he said, thanking his fellow researchers.
“There are many illnesses that need further research and treatment, and I hope there will be further progress in those areas so that findings will lead to prevention of diseases. That’s what our research is for,” he said.
Sakaguchi’s news conference was interrupted by a call from Japanese Prime Minister Shigeru Ishiba, who congratulated the scientist and asked him about the time frame for the research to be clinically applied to, for example, cancer treatment.
“Hopefully we can reach that stage in about 20 years, though I’m not sure if will still be around,” Sakaguchi told the prime minister. “But science will advance and by that time cancer will no longer be scary but treatable.”
Brunkow, meanwhile, got the news of her prize from an AP photographer who came to her Seattle home in the early hours of the morning.
She said she had ignored the earlier call from the Nobel Committee. “My phone rang and I saw a number from Sweden and thought: ‘That’s just, that’s spam of some sort.'”
“When I told Mary she won, she said, ‘Don’t be ridiculous,'” said her husband, Ross Colquhoun.
The AP could not immediately reach Ramsdell.
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Wasson reported from Seattle and Neergaard from Washington. Mari Yamaguchi in Tokyo and Stefanie Dazio and David Keyton in Berlin contributed.
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AP Nobel Prizes: https://apnews.com/hub/nobel-prizes