Don Mason: The Physicist Who Revolutionized Immunology

The Accidental Immunologist

Few scientists have bridged disparate fields as successfully as Don Mason (1934-2021), the physicist-turned-immunologist whose work fundamentally transformed our understanding of the immune system. Beginning his career working on controlled thermonuclear fusion at Harwell and Culham laboratories, Mason spent ten years studying plasma physics before a personal tragedy pivoted his life toward medicine ^{4 7} .

This unconventional background proved to be his greatest strength. Mason brought a physicist's quantitative rigor to biological questions at a time when such interdisciplinary approaches were rare ¹ . His unique perspective would eventually lead to foundational discoveries about how our immune systems are regulated—work that now forms the basis for understanding autoimmune diseases and developing cutting-edge immunotherapies.

Cracking the Immune System's Code

When Mason joined the Medical Research Council's Cellular Immunology Unit at the Sir William Dunn School of Pathology in 1973, immunology was undergoing a technological revolution. The recent development of monoclonal antibodies provided researchers with powerful new tools to distinguish between seemingly identical cells ⁴ .

Mason, with his physics background, immediately recognized the potential of combining these new tools with another emerging technology: fluorescence-activated cell sorting (FACS) ^{4 6} .

Mason was instrumental in bringing the first FACS machine to Oxford—a Becton-Dickinson FACS-II—and quickly began using it to unravel the mysteries of T cells, the orchestrators of our immune response ⁴ .

Modern flow cytometry equipment, similar to technology Mason pioneered

Together with colleagues, he used one of the first monoclonal antibodies (W3/25, later shown to recognize rat CD4) to identify functional subpopulations of T cells ¹ . This antibody was the result of a collaboration between César Milstein in Cambridge and Alan Williams in Oxford in 1975, and Mason showed it could inhibit mixed lymphocyte reactions—the first functional effect ever demonstrated for a monoclonal antibody ¹ .

Even more significantly, when Mason applied this treatment in vivo, it effectively inhibited a rat autoimmune model of multiple sclerosis ^{1 4} . These early experiments highlighted the potential of immunotherapy with monoclonal antibodies to treat disease—a concept that is now widely used in clinical practice, including for cancer treatment ⁷ .

The Discovery of the Immune System's Peacekeepers

Mason's most enduring contribution to immunology came from his investigation of what he called "controller" cells—now known as regulatory T cells (Tregs). While previous immunologists had focused on how the immune system attacks pathogens, Mason wondered why it doesn't always attack our own bodies.

He and his team made a crucial discovery: CD4+ T cells could be divided into two distinct populations using antibodies specific for high molecular weight isoforms of CD45 ¹ . One population (OX-22high) mediated immune responses, while the other (OX-22low) actively controlled those responses ^{3 4} . The OX-22low cells could prevent the pathogenic activity of the OX-22high subset—essentially acting as peacekeepers to maintain order in the immune system ³ .

These studies represented some of the foundational work in the regulatory T cell field, which has since grown into a large and active area of immunological research ¹ . Mason's work helped establish that these regulatory T cells are essential for preventing autoimmune diseases and moderating immune responses to foreign antigens ⁵ .

A Landmark Experiment: How Mason Proved the Existence of Peacekeeper Cells

Methodology: The T Cell Separation Experiment

In their pivotal 1990 study, Mason and colleague Fiona Powrie designed an elegant experiment to demonstrate the existence and function of regulatory T cells ⁴ :

Results and Analysis: A Dramatic Difference

The results were striking and clearly demonstrated the functional difference between these cell populations. Rats that received OX-22high CD4+ T cells developed severe wasting disease with inflammation and damage to multiple organs ³ . In contrast, animals that received OX-22low CD4+ T cells remained healthy ³ . Most importantly, when both cell populations were transferred together, the OX-22low cells prevented the disease caused by their OX-22high counterparts ³ .

This experiment provided compelling evidence that a specific subset of T cells actively suppresses immune responses—a concept that revolutionized how immunologists understand self-tolerance and autoimmune disease ³ . The work demonstrated that autoreactive T cells exist in healthy animals but are normally kept in check by regulatory T cells ⁵ .

The Scientist's Toolkit: Key Research Reagents That Enabled Discovery

Mason's groundbreaking work was made possible by several important reagents and technologies that became available in the 1970s and 80s. These tools allowed him to distinguish, separate, and analyze previously indistinguishable cell populations.

From Cellular Detective to Theoretical Visionary

Mason's physics background continued to influence his approach throughout his career. In 1998, he published a theoretical paper arguing that the T cell receptor had to be broadly cross-reactive rather than highly specific—contrary to what most immunologists believed at the time ^{1 4} .

Mason's quantitative approach also led to classic papers on antibody binding kinetics, applying rigorous physical principles to biological questions ⁴ . His 1980 paper "The kinetics of antibody binding to membrane antigens in solution and at the cell surface" has been cited more than 400 times and established foundational principles for understanding antibody-antigen interactions ⁴ .

A Lasting Legacy: Mentorship, Principles, and Permanent Impact

Beyond his scientific contributions, Mason will be remembered for his distinctive approach to mentorship and his strong ethical principles. He ran a small but effective research group, training students and post-docs over many years ¹ . His combination of intellectual rigor, empathy, and humility created a positive and nurturing research culture that influenced both his mentees and colleagues ¹ .

Mason's principles extended beyond the laboratory. He became a vegan in 1977 and discovered Quakers through CND activism in the 1980s while protesting against cruise missiles ⁷ . He spent a week in prison for civil disobedience, which informed his later work as a prison visitor and campaigner against poor conditions at the Campsfield immigration detention centre near Oxford ^{3 7} . In retirement, he published "Science, Mystical Experience and Religious Belief: A Personal View," reflecting his lifelong interest in the connections between different ways of understanding the world ³ .

Career Timeline