Mary E. Brunkow, Fred Ramsdell, and Dr. Shimon Sakaguchi have received the Nobel Prize in Physiology or Medicine for their incredible discoveries in “peripheral immune tolerance.” This refers to the vital system our immune system uses to stop wayward cells from attacking our own healthy tissues and organs.
The Nobel committee highlighted that their groundbreaking research has already led to significant medical advancements, especially in developing new treatments for cancer and autoimmune diseases, and holds great promise for improving organ transplantation.
These three brilliant minds will share the prestigious award, which includes a prize of 11 million Swedish kroner, roughly equivalent to $1.17 million.
Why This Award is So Important
At the heart of these scientists’ work is their profound understanding of T-cells, the body’s primary white blood cells responsible for fighting off infections. They successfully identified a unique category of these cells, known as regulatory T-cells, along with the specific genes that govern their function.
Their findings solved some of biology’s most perplexing mysteries: How does our immune system intelligently distinguish between invaders and our own healthy cells, ensuring it doesn’t attack itself? And, if some immune cells mistakenly slip through, what mechanisms are in place to prevent them from causing widespread damage?
The Nobel committee lauded their research as “fundamental,” emphasizing its critical role in unraveling the intricate workings of the human immune system.
Following the prize announcement, Rickard Sandberg, a distinguished professor at the Karolinska Institute in Sweden and a member of the prize committee, shared in an interview that this research offers a “new handle” – a fresh perspective and method – for tackling autoimmune disorders, developing new treatments, and improving the success rates of organ transplants.
He noted that over 200 clinical trials are currently underway, directly leveraging the insights gained from their pioneering work.
The Journey to Discovery
Dr. Sakaguchi, currently a distinguished professor at the University of Osaka in Japan, meticulously unraveled a complex medical enigma centered on the thymus. This small, crucial organ located behind the breastbone acts as a filter, identifying and preventing immune cells that might target the body’s own tissues and organs from ever entering the bloodstream.
His journey began in the 1970s as a student, delving into the thymus, and continued with research in the U.S. during the 1980s. A particular experiment by his colleagues presented a baffling paradox: The thymus is known to educate the immune system in the initial days of a mouse’s life, ensuring T cells that could attack the body’s own cells are stopped before they reach the bloodstream. However, the experiment’s results contradicted this understanding.
In this puzzling experiment, scientists had removed the thymus from newborn mice just three days after their birth.
Logically, the thymus should have completed its crucial training phase within those three days, preventing any harmful T cells from reaching the body’s tissues. Yet, the opposite occurred: the immune system spiraled out of control, launching devastating attacks on the animals’ own organs.
The question remained: why?
Through over ten years of dedicated research, Dr. Sakaguchi unveiled that the thymus isn’t a flawless gatekeeper; some harmful cells inevitably escape into circulation. While most dangerous cells were contained in the mice, a sufficient number slipped through to initiate attacks on the body’s own tissues.
Crucially, he found that the thymus would have rectified this issue if it hadn’t been prematurely removed. He discovered that the immune system possesses a sophisticated backup mechanism: a specialized group of immune cells designed to halt misguided attacks. These were a novel class of T cells, which he aptly named regulatory T cells. The mice whose thymuses were removed so early simply hadn’t developed these essential regulatory T cells.
This raised another critical question: what genes govern this intricate regulatory system?
The missing piece of the puzzle emerged from the work of Dr. Brunkow and Dr. Ramsdell, who were researching at Celltech Chiroscience, a British-owned biotechnology firm near Seattle. They focused on a particular strain of mice that suffered from a severe autoimmune disease, where their immune systems violently attacked their own cells, leading to lives of only a few weeks.
These afflicted mice lacked crucial genetic instructions that, in healthy individuals, instruct the immune system’s T cells to refrain from attacking when they enter the general bloodstream.
Following years of painstaking effort, the pair successfully identified the responsible gene: FOXP3. This gene shared similarities with others that regulate genetic activity. Their breakthrough came in 2001 when they announced that IPEX, a rare human autoimmune disease, was genetically identical to the condition observed in the mice.
Their findings revealed that without the FOXP3 gene, regulatory T cells fail to develop. Consequently, the body cannot produce the specialized T cells necessary to instruct other T cells not to attack its own healthy cells.
“This is a profound acknowledgement of the critical importance in understanding how the body differentiates between its own components and foreign invaders,” stated John Wherry, director of the Colton Center for Autoimmunity at the University of Pennsylvania.
Understanding the FOXP3 gene’s role has opened new avenues for cancer treatment. Cancers often evade immune attacks by drawing in a dense cluster of regulatory T cells. Now, with this genetic blueprint, scientists can design drugs to disrupt this protective shield and unleash the immune system against cancer cells.
Conversely, in autoimmune diseases, the challenge lies in either a deficiency or defect in these regulatory T cells. By leveraging FOXP3 as a foundation, researchers are actively developing therapies to re-educate the immune system, teaching it to cease its harmful attacks on the body’s own healthy tissues.
Dr. Wherry confirmed that “significant new drug candidates are advancing to clinical trials” for initial testing in both cancer and autoimmune conditions, a direct result of these discoveries.
Meet the Nobel Laureates
Dr. Shimon Sakaguchi is a renowned immunology expert and a distinguished professor at the University of Osaka.
Hailing from Nagahama, Japan, Dr. Sakaguchi initially had a passion for art and philosophy. However, his father, a high school teacher, gently guided him towards a career in science. He pursued immunology at Kyoto University and honed his research skills at prestigious American institutions like Johns Hopkins and Stanford in the 1980s before returning to his home country.
Mary Brunkow continues her vital research in genomics and autoimmune diseases at the Institute for Systems Biology in Seattle. Fred Ramsdell currently serves as a scientific adviser at Sonoma Bio, a company located in San Francisco.
Laureates React to the Prestigious Award
During a news conference at the University of Osaka on Monday, Dr. Sakaguchi expressed his profound gratitude, describing the award as “a surprise and an honor.”
He shared that securing funding for his early work was a significant challenge. Japan’s Prime Minister, Shigeru Ishiba, even called into the conference, directly asking Dr. Sakaguchi what fueled his perseverance despite early skepticism about his theories.
Dr. Sakaguchi’s humble reply: “I believe my sheer stubbornness ultimately led to these remarkable results.”
Last Year’s Physiology or Medicine Laureates
Last year, Victor Ambros and Gary Ruvkun were celebrated for their groundbreaking discovery of microRNA. These minuscule RNA molecules are vital in controlling how organisms develop and function, and understanding them helps explain when these processes go awry.
Upcoming Nobel Prize Announcements
The Nobel Prize in Physiology or Medicine kicks off this year’s series of six prestigious awards. Each prize acknowledges monumental contributions by individuals or organizations in their respective fields.
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The Nobel Prize in Physics will be announced on Tuesday by the Royal Swedish Academy of Sciences in Stockholm. In the previous year, John J. Hopfield and Geoffrey E. Hinton were honored for their discoveries, which laid foundational groundwork for advancements in artificial intelligence by enabling computers to learn more like the human brain does.
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The Nobel Prize in Chemistry is scheduled for Wednesday, also presented by the Royal Swedish Academy of Sciences. Last year’s awardees, Demis Hassabis, John Jumper, and David Baker, were recognized for demonstrating how artificial intelligence and advanced technology can revolutionize our ability to predict and design new protein structures.
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The Swedish Academy in Stockholm will announce the Nobel Prize in Literature on Thursday. Last year, Han Kang, celebrated for her novel “The Vegetarian,” made history as the first South Korean writer to be bestowed with this honor.
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On Friday, the Norwegian Nobel Institute in Oslo will present the Nobel Peace Prize. In the previous year, the Japanese grass-roots organization Nihon Hidankyo, composed of atomic bomb survivors, was recognized for their tireless dedication to achieving a world free of nuclear weapons.
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The Nobel Memorial Prize in Economic Sciences will conclude the awards next Monday, presented by the Royal Swedish Academy of Sciences. Last year, Daron Acemoglu, Simon Johnson, and James Robinson were celebrated for their research elucidating how societal institutions influence national wealth and prosperity, and the historical origins of these structures.
All Nobel Prize announcements are broadcast live by the Nobel Prize organization, offering a global audience the chance to witness these historic moments.
Additional reporting for this article was provided by Javier C. Hernández, Kiuko Notoya, and Hisako Ueno from Tokyo.