Rabbits vs. scientific dogma: what you need to know about the Nobel Prize in Medicine

The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Bruncoe, Fred Ramsdell and Shimon Sakaguchi for discoveries in the workings of the immune system that pave the way for treatments for autoimmune diseases and cancer, as well as easier organ transplantation. The mechanism they discovered is called peripheral immune tolerance - sounds confusing, let's figure it out.

Human immunity is a powerful mechanism that daily fights pathogenic bacteria and viruses, suppresses the formation of cancerous tumors, and generally acts as a means of defense of the body, without which it is impossible to survive in our dangerous world. Children with congenital immunodeficiency (i.e. immunity that does not work) usually do not survive to the age of two without special treatment.

The foundations for understanding the workings of immunity were laid by Russian and French biologist Ilya Mechnikov and German immunologist and chemist Paul Ehrlich, for which they were awarded the Nobel Prize in 1908.

However, here is a paradox - having undoubtedly advanced science, Ehrlich's authority blocked the study of an entire medical field - autoimmune diseases - for decades. He was, admittedly, the first to ask the question: can the body's immune system turn against itself, starting to destroy cells and tissues instead of "invaders" - foreign cells? And, having conducted a number of experiments, he answered - no, it can not, it would be too dangerous. Therefore, there must be mechanisms preventing such a development - in his book "Selected Studies of Immunity", published in 1906, he called them "horror autotoxicus" (horror autotoxicus) of the organism.

What Ehrlich was right about was that such mechanisms do exist. However, unfortunately, they sometimes break down, but it was only discovered half a century later.

"The father of autoimmunity research," as The Washington Post called him, American scientist Noel Rose in the 1950s studied the reaction of the immune system of rabbits to thyroglobulin, a protein found in the thyroid gland. To his surprise, he found that under certain conditions the rabbit's immune system reacted even to its own thyroglobulin, and the immune system thus activated began to attack the thyroid.

Rose's supervisor, Ernest Witebsky, a student of Ehrlich's pupil, was so amazed by the result that he almost closed the study. However, he had the scientific integrity to repeat the experiments again and again, and when he was convinced that there was no error - to write together with Paul an article, which at first they did not want to publish, because it contradicted what "everyone knows": there can be no autoimmune diseases, because so said the great Ehrlich.

Unfortunately, they are.

In the popular medical series "Dr. House" someone from the team of the great diagnostician almost in every episode suggests that the patient has lupus, or rather, systemic lupus erythematosus - an autoimmune disease affecting various tissues and organs and with not always clear symptoms. It is mentioned almost 30 times in different episodes, although the diagnosis was confirmed only once, fans of the series have calculated.

The constant mention of lupus was used for comic effect, even when House lost his team and called in a random janitor to help him, the janitor also suggested that the patient had lupus ("because my grandmother had it"). But there is absolutely nothing comical about the disease itself, and the fact that it is constantly suspected, but can not prove, clearly shows the difficulties of diagnosing autoimmune diseases. According to the American Lupus Foundation, it affects 1.5 million people in the U.S. and about 5 million people worldwide, and 10-15% of them will die prematurely due to complications.

According to Oxford University, there are now more than 80 types of these diseases, including rheumatoid arthritis, type 1 diabetes and multiple sclerosis. A study of the 19 most common ones found that about 10% of the UK population has them. The Washington Post estimates that about 20 million Americans in the U.S. will suffer from these diseases in 2020.

"The exact causes of autoimmune diseases, particularly with regard to the relative contribution of genetic predisposition or environmental factors, also remain largely unclear," the Oxford University study said.

In addition, the number of patients has been rising in recent years, wrote Molly Murray, president and CEO of the Autoimmune Disease Association. There has been a 3-12% annual increase in the incidence of the disease, "reaching epidemic levels," she said.

However, there are still no cures for these diseases. There are only ways to keep symptoms under control, such as taking insulin for type 1 diabetes. This is why research that brings us closer to understanding the nature and treatment of autoimmune diseases is so important.

The 2025 Nobel Prize winners have discovered immune system defenders - regulatory T cells (T-reg) that prevent immune cells from attacking their own bodies. Once again, this required a great deal of scientific curiosity and an unconventional approach to something that "everybody knows".

In the 1980s, "everyone knew" that the main "fighters" of immunity - T-cells - mature in a special organ - the thymus gland (thymus). T-cells potentially capable of damaging the body's own tissues are selected and destroyed there, a process called central immune tolerance, the Nobel Committee said. However, Shimon Sakaguchi from the Research Institute of Aichi Cancer Center (Nagoya, Japan) noticed an oddity: in some mice with removed thymus immunity, instead of weakening, on the contrary, "went wild" and began to attack the body.

He hypothesized that the thymus produced different types of T cells, including those capable of regulating immunity and preventing autoimmune reactions. By 1995, he was able to isolate and describe this new type, regulatory T cells, which are responsible for controlling autoimmune reactions no longer in the thymus but directly in the tissues of the body. This was called peripheral immune tolerance.

Not everyone believed him at first - and then two other Nobel laureates, Mary Bruncoe and Fred Ramsdell, who worked in the 1990s at Celltech Chiroscience (USA), came on the scene. They investigated a line of mice with a scurfy (rough skin) mutation - which is also an autoimmune disease. By 2001, they had discovered the FOXP3 gene that causes this condition and proved that damage to the same human gene was responsible for a rare autoimmune disease, IPEX syndrome in humans.

Two more years later, Sakaguchi and other researchers demonstrated that it is FOXP3 that controls the development of regulatory T cells, which prevent other T cells from mistakenly attacking the body's own tissues and also ensure that the immune system "calms down" after it has repelled an attack by bacteria or viruses.

Targeting regulatory T cells has significant therapeutic potential for the treatment of autoimmune diseases and allergies, as well as for reducing the risk of transplant rejection. In addition, strategies to enhance antitumor immunity by eliminating or deactivating regulatory T cells that "protect" the tumor, making it "invisible" to the immune system, are being actively developed, as explained in the materials of the Nobel Committee.

According to the Clinicaltrials database, 187 clinical trials investigating different uses of regulatory T cells have been reported so far.

In particular, they are led by SonomaBio, where Ramsdell is a co-founder and scientific advisor. In 2023, SonomaBio entered into a partnership with Regeneron, a large biotech company(capitalization of about $60 billion), to develop new therapies using regulatory T cells.

Meanwhile, Ramsdell reportedly missed the very news that he had won the Nobel Prize because he was on a digital detox - hiking somewhere in the middle of nowhere in Idaho. Hopefully, he'll come back with fresh energy and invent a cure for autoimmune diseases. People really need that kind of medicine.

This article was AI-translated and verified by a human editor