Hugh McDevitt, whose work unraveled genetic controls of immune system, dies at 91

The Stanford immunologist’s research on how our immune cells recognize pathogens — and what happens when this process goes wrong — paved the way to modern immunology.

- By Jennifer Welsh

Hugh McDevitt

Hugh McDevitt, MD, a professor emeritus of microbiology and immunology at the Stanford School of Medicine who unraveled the genetic controls of the immune system, died April 28 in Stanford, California, from pneumonia and sepsis. He was 91.

McDevitt was a dynamic leader and a pillar of the Department of Microbiology and Immunology, according to his colleagues, who added that he was generous with his time and intellect. He was a smart and effective negotiator who fought for his department, said Grete Sønderstrup, his wife of 38 years and a senior research scientist in the department.

“It takes a leader like Hugh to model collegiality that you need for a community to prosper,” said Mark Davis, PhD, professor of microbiology and immunology. “He played a major role in making Stanford such a thriving immunology community.”

“Hugh was both a fantastic scientist whose research made a big impact on modern immunology and someone who took the time to mentor people,” added Davis, the Burt and Marion Avery Family Professor of Immunology and a Howard Hughes Medical Institute investigator.

McDevitt’s research on how our immune cells recognize invading microbes — and what happens when this process goes wrong — paved the way for modern immunology.

“Hugh McDevitt’s research changed the field of immunology,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “Hugh possessed a boundless curiosity and an intellect to match. That’s a potent combination, and it enabled his breakthrough discovery of how the immune system fights infections. Those same traits made Hugh a gifted teacher and mentor — his enthusiasm for science and learning was galvanizing.”

McDevitt was born Aug. 26, 1930, in Wyoming, Ohio — a suburb of Cincinnati — the youngest of five siblings. His father was a urologic surgeon who wanted one of his children to be a doctor, and he imbued McDevitt with a love of science and medicine. Starting in the third grade, McDevitt’s father offered to let him skip church, taking him instead on rounds to check on his hospitalized patients.

When his father retired, the family moved to California, where McDevitt finished high school in Ojai.

He enrolled at Stanford University, where he earned a bachelor’s degree in biology with honors in 1952. As an undergraduate, McDevitt conducted laboratory research on fungus, learning genetic techniques that would prove invaluable to his career. Many immunology labs didn’t focus on genetics, McDevitt said in a Stanford Historical Society oral history, so the experience and knowledge gained as an undergraduate researcher set his approach apart.

McDevitt attended Harvard University Medical School, earning a medical degree in 1955. He did residencies at Peter Bent Brigham Hospital in Boston and Bellevue Hospital in New York, followed by two years with the Army, stationed in Japan.

Back in Boston, he had a postdoctoral fellowship and another residency before spending two years in London as a U.S. Public Health Service special fellow at Mill Hill laboratories. It was there that he became enchanted with immunology.

He returned to Stanford in 1966 as an assistant professor of immunology, becoming chief of the Division of Immunology in 1970.

Research discoveries

Pivotal research discoveries came quickly. He studied a set of molecules — the MHC, or major histocompatibility, proteins — on the surface of cells and discovered that they help the immune system fight infections.

He found that, despite being on a different chromosome, changes to the MHC genes of mice controlled the animals’ antibody responses. His work found that MHC molecules are essential parts of the immune system that bind to small pieces of other protein molecules left behind in cells by viral or bacterial invaders. They present these pieces to the immune system’s T cells, alerting them to the presence of an infection and sending them to help B cells produce antibodies.

“It was one of those shocking things that happens in biology — somebody reveals a relationship that nobody knew existed but is now a foundation of modern immunology,” Davis said.

McDevitt also mapped the genes related to this sequence of events in the immune system. He studied what happens when it goes wrong — how the immune system causes Type 1 diabetes, arthritis and systemic lupus erythematosus.

While building a research legacy, McDevitt trained the next generation of immunologists.

“Many people who are now prominent came through Hugh’s lab,” Davis said. “That doesn’t just happen by itself — people come because they know they’re going to get good advice, that they’ll have good colleagues and that they’ll be able to do their best.”

Hugh would be the center of attention in a room. Because when he said something, people wanted to listen.

“Hugh was very charming with a magnetic personality. He had a way of encouraging and inspiring these young people to ‘think’ and be creative. He would let them develop their own projects and help them back on track if or when they failed.” Sønderstrup said. “He also taught them very high standards about honesty and scientific integrity. He was adamant about valid positive and negative controls of their experiments.”

McDevitt retired in 2008, when he started developing mild symptoms of Parkinson’s disease, although he returned to the department for meetings and seminars. He worked with Sønderstrup on her research — always lending a helpful ear (and mind).

“He would study the literature and be a powerful opponent in the discussions around the dinner table,” Sønderstrup said. “He was an incredible partner to interact with every day, and he was fortunate to keep mentally healthy and engaged until the very end of his life.”

An endlessly curious mind

Outside of medicine, McDevitt enjoyed a cultured life: traveling the world, visiting museums, attending plays in London and the opera in New York — or simply going out to dinner with friends.

“Hugh would be the center of attention in a room. Because when he said something, people wanted to listen,” Sønderstrup said.

He was the eternal scientist, his wife said. “He was a little curious child, who always wanted to explore and know what comes next,” she added.

McDevitt won many awards and honors: He was elected to membership in the U.S. National Academy of Sciences, the Academy of Medicine and the Royal Society of London. He received the Paul Ehrlich and Ludwig Darmstaedter Prize, the Jessie Stevenson Kovalenko Medal and the Lita Annenberg Hazen Award for Excellence in Clinical Research.

In addition to Sønderstrup, McDevitt is survived by four children and two grandchildren.

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