Nobel Prize in Physiology or Medicine Is Awarded for Work on Immune Systems

 

 

“Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi were awarded the prize for research showing how the body regulates its immune responses.

 

Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi were awarded the Nobel Prize in Physiology or Medicine on Monday for their discoveries of peripheral immune tolerance — the system that explains how the immune system prevents rogue cells from attacking tissues and organs.

 

Their research, the prize committee said, has contributed to medical advances in cancer and autoimmune treatments, and may help with organ transplants.

 

“This is a prize I’ve been waiting to see,” said Dr. Alexander Marson, director of the Gladstone-UCSF Institute of Genomic Immunology in San Francisco. Finding “a population of T cells that had been missed and that keeps the immune system in balance,” was central, he said, to understanding autoimmune diseases and cancers.

 

The three researchers will split a prize of 11 million Swedish kroner, or around $1.17 million.

 

Why did they receive the prize?

 

Central to the scientists’ research were their discoveries about T cells, the white blood cells that fight infection in the body. They identified a class of cells, regulatory T cells, and the genes that control them.

 

In doing so, they answered puzzling biological questions: How does the immune system know to avoid attacking the body’s own healthy cells? And if by mistake some immune system cells fail to get the message, how are those cells stopped from wreaking havoc?

 

The committee called their work “fundamental” to understanding how the body’s immune system functions.

 

In an interview after the prize announcement, Rickard Sandberg, a professor in the department of cell and molecular biology at the Karolinska Institute in Sweden and a member of the prize committee, said that the research had provided a “new handle” on how to approach autoimmune disorders, or treatments and organ transplants.

 

There are more than 200 clinical trials underway that build on their research, he said.

 

How did they make their discovery?

 

Dr. Sakaguchi, now a distinguished professor at the University of Osaka in Japan, worked out a medical mystery involving the thymus, a small organ behind the breastbone. It sorts out immune cells that might attack the body’s own tissues and organs and prevents them from getting into the bloodstream.

 

He first studied the organ as a student in the 1970s, then performed research in the United States in the 1980s. His colleagues had done an experiment that made no sense. In the first few days after a mouse is born, the thymus is supposed to train the immune system, preventing T cells that could attack the body from ever entering the bloodstream.

 

In this experiment, researchers removed the thymus from mice three days after the animals were born.

 

In theory, the organ should have done its job during those three days. Harmful T cells should never have had a chance to get to the body’s tissues and organs. Instead, the opposite happened — the immune system went wild, attacking organs.

 

But why?

 

After more than a decade of work, Dr. Sakaguchi discovered that the thymus did not stop every harmful cell from escaping into the circulation. So even though most of those cells were blocked in the mice, enough got out to go on attack against the body’s own tissues.

 

But, he learned, the thymus would have fixed that problem if it had not been removed so soon. The immune system, he discovered, has a backup system, a set of immune cells that stop mistaken attacks. It involved a new class of T cells, which he called regulatory T cells. Those mice whose thymuses were removed after three days had not had a chance to develop the regulatory T cells.

 

But what genes control this system?

 

The answer came from Dr. Brunkow and Dr. Ramsdell, working at what was then a British-owned biotechnology company outside Seattle, Celltech Chiroscience. They decided to study a strain of mice that developed a horrible autoimmune disease. Their immune systems’ attack on their own cells was so severe that the mice lived for only a few weeks.

 

The mice were missing a set of genetic instructions. In a healthy individual, these tell the immune system T cells to hold off their attack when they enter the general circulatory system.

 

After years of arduous work, the two researchers found the gene, called FOXP3. It resembled others that control other genes. And, in 2001, they reported that a rare autoimmune disease in humans called IPEX was the same as the disease in mice.

 

Without FOXP3, regulatory T cells do not form. The body does not make T cells that tell other T cells that can attack the body’s cells not to respond.

 

“This is a great recognition of the fundamental importance of distinguishing self from non-self,” said John Wherry, director of the Colton Center for Autoimmunity at the University of Pennsylvania.

 

Cancers block attacks from the immune system by attracting a thicket of regulatory T cells. With the FOXP3 gene identified, and its role understood, researchers can develop drugs to turn the immune system against these cancer cells.

 

With autoimmune diseases, there is the opposite problem. Regulatory T cells are missing or defective. Using FOXP3 as a starting point, researchers are developing drugs to teach the immune system to stop its attack.

 

Dr. Marcela Maus, director of the cellular immunotherapy program at Massachusetts General Hospital, said the work “holds tremendous potential for unlocking new therapeutic avenues in medicine.”

 

“The holy grail has been to be able to manipulate and control immunity versus tolerance," Dr. Maus said. “The work of these laureates unlocked the tolerance side of this equation.”

 

With the discoveries, Dr. Wherry said, “major sets of drugs are going into the clinic,” for preliminary testing in cancer and autoimmunity.

 

Who are the laureates?

 

Dr. Sakaguchi is an expert in immunology at the University of Osaka.

 

He was born in the city of Nagahama, about 60 miles northeast of Kyoto. As a child, he was interested in art and philosophy, but his father, a high school teacher, encouraged him to pursue science. He enrolled at Kyoto University, where he became interested in immunology. In the 1980s, he worked as a researcher at Johns Hopkins University and Stanford University, among other institutions, before returning to Japan.

 

Dr. Brunkow joined the Institute for Systems Biology in Seattle in 2009, where she studies genomics and autoimmune diseases.. She received Ph.D. in molecular biology from Princeton University.

 

Dr. Ramsdell is a scientific adviser at Sonoma Biotherapeutics, a company based in San Francisco that he co-founded. He has a Ph.D. in immunology from the University of California, Los Angeles Before joining SonomaBio, he was a senior executive at several other biotech companies.

 

What did the laureates say about winning the prize?

 

Dr. Sakaguchi called the award “a surprise and an honor” at a news conference on Monday on the campus of the University of Osaka. He got the call just after returning from a conference. “I really was elated,” he said in an interview posted on NobelPrize.org.

 

When Dr. Sakaguchi began his work, it was difficult to obtain funding. Shigeru Ishiba, Japan’s prime minister, called into the news conference and asked him why he had persisted in his research despite initial doubts about his theories.

 

“I think my stubbornness led to these results,” Dr. Sakaguchi replied.

 

Dr. Brunkow said she did not expect to win a Nobel Prize.

 

“My phone rang, and I saw a number from Sweden and thought, well that’s just spam of some sort, so I disabled the phone and went back to sleep,” she said in an interview also posted on NobelPrize.org.

 

Who won the Nobel Prize in Physiology or Medicine in 2024?

 

Victor Ambros and Gary Ruvkun were recognized for the discovery of microRNA, a tiny class of RNA molecules that play a crucial role in determining how organisms mature and function — and how they sometimes malfunction.

 

When will the other Nobel Prizes be announced?

 

The prize for physiology or medicine is the first of six Nobel Prizes that will be awarded this year. Each award recognizes groundbreaking contributions by an individual or organization in a specific field.

 

    The Nobel Prize in Physics will be awarded on Tuesday by the Royal Swedish Academy of Sciences in Stockholm. Last year, John J. Hopfield and Geoffrey E. Hinton shared the prize for work on discoveries that helped computers learn more in the way the human brain does, providing the building blocks for developments in artificial intelligence.

 

    The Nobel Prize in Chemistry will be awarded on Wednesday by the Royal Swedish Academy of Sciences in Stockholm. Last year, the prize went to Demis Hassabis, John Jumper and David Baker for work that showed the potential of artificial intelligence and other technology to predict the shape of proteins and to invent new ones.

 

    The Nobel Prize in Literature will be awarded on Thursday by the Swedish Academy in Stockholm. Last year, Han Kang, known best for her novel “The Vegetarian,” became the first writer from South Korea to receive the award.

 

    The Nobel Peace Prize will be awarded on Friday by the Norwegian Nobel Institute in Oslo. Last year, the Japanese organization Nihon Hidankyo, a grass-roots movement of atomic bomb survivors, received the award “for its efforts to achieve a world free of nuclear weapons.”

 

    Next week, the Nobel Memorial Prize in Economic Sciences will be awarded on Monday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Daron Acemoglu, Simon Johnson and James Robinson were honored for research into how institutions shape which countries become wealthy and prosperous — and how those structures came to exist in the first place.

 

All of the prize announcements are streamed live by the Nobel Prize organization.” [1]

 

1. Nobel Prize in Physiology or Medicine Is Awarded for Work on Immune Systems. Kolata, Gina; Watkins, Ali.  New York Times (Online) New York Times Company. Oct 6, 2025.