The Power of Transparency: How Sharing Research Led to a Nobel-Winning Discovery

By Crystal Kong and Chloe Cherng, High School Students

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Nobel-Winning Discovery

For years, scientists had a simple understanding of immune tolerance, where the body is able to recognize self-antigens as its own cells, thereby preventing autoimmune reactions and fighting harmful substances that enter the body. Scientists believed that immune tolerance was determined solely in the thymus. 

However, in 1995, Japanese scientist Shimon Sakaguchi challenged that idea and proposed that the immune system was much more complex than originally thought. His landmark study showed that a small subset of CD4⁺ T cells expressing the IL-2 receptor α-chain (CD25) acted as a brake on immune activation. When removing these cells from mice, they developed autoimmune diseases. Through this, he was able to identify a new class of immune cells, now known as regulatory T cells (Tregs), which actively protect the body from autoimmune diseases.

A few years later, in 2001, Mary Brunkov and Fred Ramsdell, two American scientists, sought to uncover why a specific strain of mice exhibited autoimmune diseases. They discovered that the fatal lymphoproliferative disorder in the scurfy mouse was caused by mutations in a previously unknown gene on the X chromosome, later identified as Foxp3. At the same time, patients with the severe autoimmune syndrome IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) showed mutations in the human equivalent of the Foxp3 gene.

This pivotal finding established Foxp3 as the master regulator of immune tolerance. Sakaguchi pieced together these discoveries and proved that the Foxp3 gene governs the development of the cells he identified in 1995, Tregs, thereby unifying the cellular and molecular foundations of immune tolerance. 

Importance of Transparency

In this key discovery, transparency made the research more ethical because Sakaguchi, Brunkow, and Ramsdell built directly on each other’s mouse experiments rather than repeating them. 

Building off an earlier experiment from his colleagues, where they removed the thymus from newborn mice, Sakaguchi tested which thymus-derived cells stopped autoimmunity. From this, he then defined a new class of T cells, regulatory T cells. Although many researchers were initially skeptical, Brunkow and Ramsdell (following earlier observations by Oak Ridge scientists) built off Sakaguchi’s findings. Using Sakaguchi’s discoveries, they studied male scurfy mice with overactive immune systems and early death, ultimately identifying that the Foxp3 gene causes autoimmunity. Sakaguchi later connected his own findings with theirs, showing that Foxp3 is the gene that enables Tregs to exist. 

By sharing results openly, they reduced the total number of mice needed and avoided repeating earlier work. Their cooperation exemplifies the ethical principle of reduction in animal research, as they advanced medical knowledge while minimizing animal suffering and use. 

Conclusion

This collaboration between Shimon Sakaguchi, Mary Brunkow, and Fred Ramsdell earned them the 2025 Nobel Prize in Physiology or Medicine. Their work laid a foundation for a new field of search and has significant implications for developing medical treatments for cancer, autoimmune diseases, and improving transplant success. Their discovery highlights the importance of transparency in research to ensure scientific progress while upholding the ethical principles of reducing, refining, and replacing animal use in experimentation.

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Works Cited

Nobel 2025: Immune tolerance and 3D in vitro models. InSphero. (2025, October 8). https://insphero.com/nobel2025-celebrating-discoveries-in-immune-tolerance/ 

Nobel prize in physiology or medicine 2025. NobelPrize.org. (2025, October 12). https://www.nobelprize.org/prizes/medicine/2025/popular-information/