LIVE Nobel Prize in medicine 2025 winner is announced YouTube

Ladies and gentlemen, good morning and you're so welcome for the announcement of this year's Nobel Prize in Physiology, Dermatology and Health. My name is Thomas Bergman and I'm the Secretary General of the Nobel Assembly. I will first read the announcement in Swedish, followed by English. We will then, as usual, present some background to the prize and open it up for questions. The Nobel Assembly at the Karolinska Institute has today decided that the Nobel Prize in Physiology or Medicine, year 2025, will be divided equally between Mary Bromcoll, Fred Branstad and Shimon Sakaguchi for their discoveries concerning peripheral immune programs. The Nobel Assembly at the Karolinska Institute has today decided to award the 2025 Nobel Prize in Physiology or Medicine jointly to Mary Bromcoll, Fred Branstad and Shimon Sakaguchi for their discoveries concerning peripheral immune organs. Here are the three awards. Mary Bromcoll was born in 1961 and received a PhD from Princeton University in the United States. The work for which she is awarded was performed at the biotech company Celtic Chiroscience in Bothell, Washington. She is currently a Senior Program Manager at the Institute for Systems Biology in Seattle. Fred Branstad was born in 1960 and received a PhD in 1987 at the University of California in Los Angeles. The work for which he is awarded was performed at the same biotech company Celtic Chiroscience. He is currently a Scientific Advisor at the company he himself founded, Sonoma Biotherapeutics in San Francisco and in Seattle. Shimon Sakaguchi was born in 1951, earned an M.D. in 1976 and a PhD degree in 1983 from Kyoto University in Japan. The work for which he is awarded was initiated at IT Cancer Center Research Institute in Nagoya. He is currently a Distinguished Professor at the Immunology Frontier Research Center at Oslo University. I now turn to Professor Marie Waren Herrelius, member of the Nobel Committee, who will now describe this year's Nobel Prize. This year's Nobel Prize in Physiology or Medicine relates to how we keep our immune system under control so we can fight all imaginable microbes and still avoid autoimmune disease. Let me explain. We are constantly exposed to a myriad of microbes and our immune system has developed to protect us from them. To detect all different varieties of microbes, existing ones and ones that may come, specialized cells in our immune system, the T-cells, have receptors. We can form billions and billions of these receptors, all with different shapes that bind to different proteins. The T-cells help us fight infection and without them we cannot live long. Among all this diversity, some T-cell receptors will unavoidably recognize proteins and structures in our own bodies, so-called cell reactivity. These self-reactive T-cells may become harmful and cause autoimmune diseases such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. So how does our body solve this problem? From early life, our T-cells are generated in the bone marrow and then travel to the thymus where they go through a test. In this test, harmful self-reactive T-cells are eliminated in a process called central tolerance. For a long time, this was believed to be the only way self-tolerance is obtained. However, some self-reactive cells escape out into our circulation and are potentially dangerous. This year's Nobel Prize in Physiology or Medicine concerns the discovery of how those potentially harmful T-cells are kept in check. The discovery started with Shimon Sakaguchi's interest in the phenomenon that removing the thymus from mice three days after birth led to an over-reactive immune system which caused autoimmune diseases. However, if T-cells from healthy mice were injected, the development of autoimmune disease was prevented. Sakaguchi realized that among these injected cells there must be some cells that protect against the over-reactive immune system and autoimmune diseases. He started a long search for these cells. Years later, he discovered that if the T-cells to be transferred were depleted of cells for the cell surface protein CD25, this pool of cells would no longer protect against autoimmune diseases. But if the T-cells with CD25 were also injected, the mice were protected. Sakaguchi called these CD25 positive cells regulatory T-cells. Many researchers were, however, skeptical about the existence of regulatory T-cells. The critical missing piece would come from Mary Brunkle and Fred Ramstad. They studied a mouse strain called scurvy because of its scaly skin. The scaly skin was part of the severe autoimmune disease the mice developed. Brunkle and Ramstad wanted to find a mutation causing the disease. Other researchers had shown that the scurvy mutation was somewhere in the middle of the X-bronx cell. Today it's possible to map the mouse genome, the haplogenome, in a few days, but at the time it was an incredible challenge, unlike looking for a needle in a haystack. Brunkle and Ramstad still took on the enormous work of mapping the middle part of the X-chromosome in detail, and eventually established that the section of interest contained 20 potential genes. They then examined gene after gene. It was only with the 20th and last examined genes that they found the mutation. The faulted gene was previously unknown, but had many similarities with a group of genes called fork-head fox, or fox genes, and they named the new gene FOXP3. Brunkle and Ramstad suspected that the rare autoimmune disease IPEX, which is also linked to the X-bronx cell, could be the human variant of the scurvy mouse disease. To understand if that was the case, they analyzed samples from children with IPEX and found mutations in the FOXP3 gene. These findings connected the FOXP3 gene also to human autoimmune disease. These two key discoveries, Sakaguchi's identification of cells that regulate immune responses, and Brunkle's and Ramstad's identification of the FOXP3 gene as important for keeping the immune system in control, indicated that the FOXP3 gene could be important for regulatory T-cells. Shimon Sakaguchi was first to show that FOXP3 is actually essential for the development of the regulatory T-cells, so-called T-regs, and therefore critical in peripheral immune tolerance. This was soon followed by reports from other scientists, and unleashed a whole new field in immunology. Subsequent studies show that when auto-reactive T-cells get activated, the regulatory T-cells act to control them, both through cell-cell contacts and by soluble molecules. In this way, immune tolerance can be maintained without deleting too many T-cells, which could be needed for our protection against current or future microbes. The discoveries have spurred development of several potential new treatments. Clinical trials are ongoing to increase the number of regulatory T-cells for suppressing unwanted immune reactions in autoimmune disease or following organ transplantation. This is done either by injecting growth factors that stimulate regulatory T-cells, or by modifying regulatory T-cells in laboratories, which can then be given to patients. The opposite approach is used in trials for cancer. Cancer cells can make use of our regulatory T-cells to avoid immune reactions that could destroy the cancer cells. For cancer treatments, the focus is therefore on down-regulating or destroying the regulatory T-cells, so that our immune system can act against the malignant cells. To summarize, Mary Brunkle, Fred Hansen, and Shimon Sakaguchi have provided fundamental knowledge of how the immune system is regulated, and are therefore awarded this year's Nobel Prize in Physiology or Medicine for their discoveries concerning peripheral immune tolerance. With that, I would like to open up for questions. Have you managed to reach one of the laureates today? Yes, you said it exactly right. I was able to reach one of the laureates. That was Shimon Sakaguchi, who I reached. I got hold of him at his lab, and he sounded incredibly grateful and expressed that it was a fantastic honor. He was quite taken by the news. Fortunately, I had a lot of information to give him, so that worked out okay. Unfortunately, I wasn't able to reach any of the other two. We have their phone numbers, but they're probably on silent mode. I asked them if they had a chance to call me back. Could you please say something about the concrete treatments that are based on this year's findings? I will give the floor to, and I forgot to introduce also, we have two additional experts here. Gunilla Olsson-Hedestad, a member of the Nobel Committee, and also Olle Kjempe, chair of the Nobel Committee. Olle, if you could take that first question. What you have to realize is that this year's Nobel laureate gets the prize for discovering a principle, the principle where peripheral tolerance is mediated by TD regulatory cells that are Foxp3-positive. Having that said, there is quite a lot of development going on, but it's still early studies, which are both some negative studies and some studies that in an early phase has given positive results. Like, for example, stimulating of the IL-2 receptor in patients with atopic dermatitis. The IL-2 receptor is the same as the CD25, and there is a lot of CD25 on TD regulatory cells, and then you can stimulate them, you expand them, and you get more TDregs. That's one study that has worked, but there are many more alternatives using genetic methods to insert specific TD receptors. If you know what the receptor against the specific autoantigen is, you can get much more forceful TD regulatory cells. Or you can use the CAR-T principle, you add genetically an antibody to the area where you want this suppression to occur. But as I said, we are in the early days. Here we have one, yes. Hello, Bochum Ratjieski from the Polish television. I want to ask, as you mentioned, this year's prize, not unlike last year's, what you would call fundamental research that furthers our understanding of physiology and medicine, and then later finds its practical applications. Why does the Nobel Committee decide to, once again, emphasize this area of scientific research as fundamental in science? Maybe I could just briefly answer that. This is a prize in physiology or medicine. As you say, they are tightly connected, because physiology knowledge leads to medical treatments. Actually, as Ulle mentioned, there's a lot going on. There are currently over 200 clinical trials involving regulatory T cells. It starts there. But you're absolutely right. This is a prize for a fundamental new discovery and understanding. It's a mix of that. We don't deliberately take a decision that this year it's going to be this or that. We always take the most suitable proposal that we have scrutinized and reviewed sufficiently. And that is really worthy of a Nobel Prize. Any more? I know people are usually eager for their interviews. But maybe you have something you're curious about that everyone else would be as well. It doesn't seem so. Dan, we thank you very much for coming. Those of you who have planned interviews are welcome to find your location. We will help everyone as rapidly as possible. Thank you so much.