For days, one of the world’s most prestigious scientific bodies could not reach the man it had just honored. While the scientific community celebrated the announcement of the 2025 Nobel Prize in Physiology or Medicine, one of its three new laureates, American immunologist Fred Ramsdell, was completely unaware, enjoying a digital detox while backpacking in the remote backcountry of the American West. His colleagues and the Nobel committee itself were left trying to penetrate a silent wilderness to deliver news that would change his life.
The prize, announced early Monday in Stockholm, recognizes Ramsdell, his American colleague Mary Brunkow, and Japanese researcher Shimon Sakaguchi for their foundational discoveries of regulatory T-cells, a critical component of the immune system that prevents it from attacking the body’s own tissues. Their collective work has unlocked a new field of immunology and paved the way for novel therapeutic strategies against autoimmune diseases like multiple sclerosis and type 1 diabetes. Yet, as the world learned of their achievement, Dr. Ramsdell was “living his best life,” as a spokesperson from his lab put it, far from the reach of cell service or email.
An Unreachable Laureate
The annual tradition of the pre-dawn phone call from Stockholm to a new Nobel winner hit a snag on Monday. While the committee successfully, though not without some difficulty, reached Dr. Brunkow in Seattle, all attempts to contact Dr. Ramsdell at his San Francisco-based lab, Sonoma Biotherapeutics, failed. The reason soon became clear: the 64-year-old senior adviser was on a long-planned, multi-week hiking trip with his wife, deliberately off the grid.
Jeffrey Bluestone, a friend of Ramsdell’s and a co-founder of the lab, confirmed the situation to reporters. “I have been trying to get a hold of him myself. I think he may be backpacking in the backcountry in Idaho,” Bluestone said, highlighting the difficulty of the task. The trip reportedly spanned the mountain ranges of Idaho, Wyoming, and Montana. At the press conference in Stockholm, Thomas Perlmann, secretary-general of the Nobel committee, made a public appeal after their own efforts proved fruitless. “I asked them to, if they have a chance, call me back,” Perlmann stated, a rare and public admission of their inability to connect with a new laureate.
The news blackout for Ramsdell finally broke by chance. As he and his wife, Laura O’Neill, were returning from their trek, they stopped to fix an issue with their car. It was during this unplanned pause that O’Neill switched on her mobile phone. It was immediately flooded with dozens of messages of congratulations. Speaking later to the media, Ramsdell expressed his shock, stating that he “certainly didn’t expect to win the Nobel Prize.” He added, “It never crossed my mind.”
The Science Behind the Prize
The work that earned the trio the Nobel Prize fundamentally altered the understanding of how the immune system maintains balance, a concept known as peripheral immune tolerance. For decades, scientists sought to understand why the immune system, armed with cells capable of destroying any target, does not normally cause widespread damage to the body’s own healthy tissues. The laureates’ research provided a definitive answer by identifying and characterizing a master regulator of the immune response.
Guardians of the System
The core of their discovery is a special population of immune cells called regulatory T-lymphocytes, or Tregs. These cells act as the immune system’s dedicated “security guards.” Their primary function is to suppress aggressive immune reactions, preventing other immune cells from launching attacks against the body’s own cells and organs. This protective brake is essential for preventing devastating autoimmune diseases. When the Treg system malfunctions or is insufficient, the immune system can mistake friend for foe, leading to conditions such as rheumatoid arthritis, inflammatory bowel disease, and lupus.
A Landmark Timeline
The path to this discovery was built on decades of incremental and collaborative work. The first major breakthrough came in 1995 from Dr. Sakaguchi, 74, at Osaka University. He was the first to identify a specific molecular marker on T-cells that signaled their regulatory function, providing the first concrete evidence of this previously unknown class of immune cells. His work established the foundation for the entire field. Six years later, in 2001, Ramsdell and Brunkow, now a senior project manager at the Institute for Systems Biology, made another pivotal discovery. They identified a key gene that governs the development and function of these regulatory T-cells, solidifying the scientific understanding of how these crucial guardians operate at a molecular level.
Three Scientists Share the Honor
The prize celebrates three distinct but complementary careers that together solved a central puzzle in immunology. Dr. Shimon Sakaguchi of Osaka University is widely regarded as the pioneer who first brought regulatory T-cells to light. His persistence in studying a small subset of immune cells laid the groundwork for all subsequent research.
In the United States, Dr. Mary Brunkow and Dr. Fred Ramsdell provided the critical genetic and functional insights that followed. Their 2001 paper became a landmark publication that propelled the field forward, offering a genetic basis for the observations Sakaguchi had first made. Dr. Brunkow, 63, continues her work in Seattle, while Dr. Ramsdell has been a senior figure at Sonoma Biotherapeutics, a company working to translate the science of regulatory T-cells into clinical therapies.
A History of Elusive Winners
While Ramsdell’s case is memorable, the Nobel committee is no stranger to the challenge of contacting newly minted laureates. The time difference is often a factor, with calls from Sweden arriving in the middle of the night for winners in the United States. In 2020, the committee for the economics prize faced a similar, and widely publicized, hurdle. After trying to call Stanford professor Bob Wilson, they found he had unplugged his phone to avoid nocturnal disturbances.
Unable to reach him directly, they resorted to calling his wife. The story took another turn when they informed Wilson that his colleague and neighbor, Paul Milgrom, had also won but was not answering his phone. In a moment captured by a doorbell security camera and later shared with the world, Wilson and his wife walked across the street in the dark to knock on Milgrom’s door. The video shows a sleepy Milgrom being told the momentous news, to which he could only reply, “Yeah I have? Wow.”
Future of Immune Regulation
The discoveries of Sakaguchi, Brunkow, and Ramsdell have had a profound impact far beyond the laboratory. Their work has launched an entirely new branch of clinical research focused on harnessing the power of regulatory T-cells. Pharmaceutical and biotech companies are now developing therapies designed to boost Treg activity to treat autoimmune diseases. Conversely, researchers are also exploring ways to suppress Tregs in the context of cancer, where these cells can mistakenly protect tumors from the immune system. The research has already led to potential medical treatments that are being evaluated in clinical trials, holding the promise of a new generation of medicines for some of humanity’s most persistent diseases.
