ORNL research links to 2025 Nobel Prizes in medicine, physics and chemistry

From the discovery of a mutant mouse to the frontier of quantum computing and new molecular frameworks, ORNL research connects to three of the 2025 Nobel Prizes. The honors in medicine, physics and chemistry underscore how curiosity-driven research continues to drive global breakthroughs.

Mouse House discovery shaped Nobel-winning immunology

The 2025 Nobel Prize in Physiology or Medicine, awarded to Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi, honors landmark research that revealed how the immune system prevents attacks on the body's own tissues. Central to their work is FOXP3, a master regulator gene that controls the activity of regulatory T cells - key defenders against autoimmunity.

The roots of this Nobel-recognized discovery trace directly to ORNL's Mouse House, established in the late 1940s by husband-and-wife geneticists William (Bill) and Liane (Lee) Russell. The Russells built the facility to study how radiation affects mammalian genetics, pioneering a large-scale breeding program that would yield generations of scientific breakthroughs.

In 1949, they observed an unusual mutation in male mice - later named scurfy - that caused distinctive symptoms including enlarged lymph nodes, scaly skin and premature death. (The name scurfy comes from an Old English word for flaky skin.)

Because it only appeared in males, the Russells suspected a mutation in the sex-linked X chromosome; Liane Russell would later use the strain to investigate sex determination in mice. Recognizing the mutation's scientific potential, they maintained the strain for more than 40 years. Read more about the legacy of their scurfy discovery here.

"The Russells' decision to preserve and document this line for decades, alongside their seminal sex-chromosome work, created a rare biological resource whose significance would only fully emerge later," said ORNL's Biosciences Division Director Jesse Labbé.

In the late 1990s, Brunkow and Ramsdell began looking for the gene on the X chromosome responsible for the scurfy phenotype, ultimately pinpointing FOXP3 as the culprit.

Their discovery revealed FOXP3 as the genetic "switch" that keeps the immune system in balance - a breakthrough that, combined with Sakaguchi's discovery of regulatory T cells, reshaped modern immunology and paved the way for new treatments for autoimmune disease, allergies and cancer.

The long arc of discovery - from the Russells' foundational genetics work to modern breakthroughs in immune regulation - highlights how fundamental research can spark transformative insights years later.

"ORNL's role is a classic case of how long-horizon stewardship of model systems, by careful phenotyping, keeping pedigree records and persistence with 'curious' mutants, help lead to breakthroughs decades later," Labbé said. "The scurfy story showcases the enduring value of federally supported basic research and curation."

Quantum prize recognizes pioneers whose discoveries transformed computing

The 2025 Nobel Prize in Physics was awarded to John Clarke, Michel Devoret and John Martinis for pioneering experiments that revealed how quantum mechanics persists at larger, macroscopic scales. Their research demonstrated how superconducting circuits could exhibit quantum behavior - work that became the foundation for modern quantum computing.

"It is very exciting news about the Nobel Prize in Physics being awarded for results that have been essential to quantum technology. This year is the international year of quantum science, and the award is a remarkable statement of how far the field has come," said Travis Humble, director of ORNL's Quantum Science Center.

"Fundamentally, their research demonstrated how cryogenic electronic circuitry made from superconducting materials realizes the effects of quantum mechanics," he said. "They incorporated techniques, like Josephson junctions, to demonstrate that quantum physics rules even in these mesoscopic systems - and the demonstration that electrons can tunnel through energy barriers is not something we expect classically."

In 2019, Humble and several ORNL staff collaborated with Martinis on a seminal quantum supremacy paper, demonstrating that a quantum computer can outperform its classical counterpart on certain tasks. Martinis, then at Google, pioneered the quantum computer hardware development, and the lab supported their studies by validating the calculations through numerical simulations on the Summit supercomputer, which has since been decommissioned.

Martinis later visited ORNL to deliver a Wigner Lecture on quantum supremacy and spoke to the lab's Sound of Science podcast about the team's research. He also served on the Science Advisory Council for the Quantum Science Center, advising on new directions for quantum science and technology.

Humble noted that the foundational research by Martinis, Devoret and Clarke led to the current paradigm of quantum computing known as superconducting transmons now being implemented commercially by Google, IBM and IQM. ORNL recently acquired an IQM quantum computer that will be integrated into the lab's high-performance computing systems.

"ORNL is now studying how the impact of this Nobel Prize-winning research will create a new frontier of quantum computation," Humble said.

Shaping molecular chemistry through collaboration and neutron science

This year's Nobel Prize in Chemistry was awarded to Susumu Kitagawa, Richard Robson and Omar Yaghi for their development of metal-organic frameworks (MOFs) - a new class of porous materials featuring precisely engineered internal cavities that can capture, store, separate or release molecules.

In the mid-2000s, Yaghi's work on MOFs caught the attention of Sheng Dai, a Corporate Fellow and section head for separations and polymer chemistry at ORNL. Dai's research focuses on mesoporous and porous carbon materials used in separations for gas capture and the absorption of minerals and metal ions, among other applications. Recognizing the potential of MOFs as a new separation medium, Dai, Yaghi, and Bangling Chen, a visiting professor to ORNL from University of Texas, collaborated to test the idea - publishing their results in Angewandte Chemie.

"Our paper back in 2006 was one of the earliest ones to use this class of materials for separations applications, especially for energy-related separations," Dai said. "And we're still doing it." The work helped bridge Yaghi's foundational MOF chemistry with ORNL's long-standing strengths in chemical separations - a field Dai added has "a long history at ORNL."

A decade later, the lab's capabilities in neutron sciences brought Yaghi back to ORNL to further explore the potential of MOFs. Yaghi's team used the Spallation Neutron Source, a DOE Office of Science user facility at ORNL, to study the properties of MOFs designed for industrial catalysis applications.

"Neutrons are exceptional probes of both material structure and dynamics, with a unique sensitivity to light elements that lets researchers unravel the complex architecture of metal-organic frameworks and directly observe how molecules adsorb and react within their porous networks," said Jon Taylor, ORNL associate lab director for neutron sciences.

"Instruments such as POWGEN, NOMAD and VISION at the Spallation Neutron Source provide complementary capabilities - ranging from precise structural refinement and local atomic environment analysis to vibrational spectroscopy - enabling a comprehensive understanding of how framework structure and chemistry govern functionality."

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UT-Battelle manages ORNL for DOE's Office of Science. The single largest supporter of basic research in the physical sciences in the United States, the Office of Science is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science. - Morgan McCorkle