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Obituary: Emil Raphael Unanue, renowned immunologist, 88

Former department head and noted scientist altered course of immunology research

December 24, 2022

Emil Raphael Unanue, MD, an internationally renowned immunologist at Washington University School of Medicine in St. Louis, died Dec. 16, 2022, surrounded by family in St. Louis after a two-year battle with glioblastoma. He was 88.

Head of the Department of Pathology & Immunology at the School of Medicine from 1985 to 2006, Unanue built the department into a preeminent research powerhouse in immunology, and did so while making major discoveries about the immune system that transformed the field.

“Emil Unanue was an extraordinary scientist whose work reached well beyond his own field of immunobiology and impacted many other biological fields, including cell biology, microbiology, neurobiology and genetics,” said Richard J. Cote, MD, the Edward Mallinckrodt Professor and head of the Department of Pathology & Immunology. “We have lost a titan of science whose breadth and depth and understanding of life will be impossible to replace. Although he is gone, his passion for excellence and discovery will continue to stimulate us to be the best scientists that we can be.”

The Paul and Ellen Lacy Professor of Pathology & Immunology, Unanue is well-known for his work to understand how the immune system identifies foreign protein fragments, or antigens — a first step in mounting an immune response — and how the immune system’s T cells respond. T cells, key components of the body’s response to infectious diseases and cancer, can be harmful when misdirected against the body’s own tissues and can lead to autoimmune conditions. Unanue’s work opened the door for research into therapies for autoimmune diseases such as Type 1 diabetes, multiple sclerosis and rheumatoid arthritis, which are caused by misdirected immune responses.

In the 1980s, Unanue’s research team discovered a critical component of how T cells recognize foreign invaders. Scientists previously had thought that the T cells were recognizing the shapes of intact pathogens, but Unanue showed that they were identifying parts of pathogens while interacting with another group of immune cells called antigen-presenting cells.

These cells pick up antigens and chop them into fragments, or peptides. Unanue and Paul Allen, PhD, now a Washington University emeritus professor of pathology & immunology, discovered that antigen-presenting cells bind these peptides to a special group of molecules known as the major histocompatibility complex.

Through his years of invaluable contributions as a researcher, Unanue spurred critical findings that have moved medicine closer to being able to improve the body’s defenses against diseases while preventing misdirected immune attacks on the body’s normal components.

“As busy and profoundly successful as he was as a researcher, teaching and mentoring were also deeply important to him,” said longtime colleague Robert D. Schreiber, PhD, the Andrew M. and Jane M. Bursky Distinguished Professor and director of the Bursky Center for Human immunology and Immunotherapy Programs at Washington University. “Through the Graduate Program in Immunology that he created at the university, he helped populate academia and industry with many of the most respected scientists in the field. His impact can’t be overstated.”

Unanue has been recognized on many stages over his career. His honors include the Albert Lasker Basic Medical Research Award; the Canada Gairdner International Award, Canada’s highest award in science; the Robert Koch Gold Medal Award in Germany; the Sanofi-Institut Pasteur Award; and the Gerold and Kayla Grodsky Basic Research Scientist Award from the Juvenile Diabetes Research Foundation. He also received the Lifetime Achievement Award from the American Association of Immunologists and was an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the National Academy of Medicine.

A native of Havana, Cuba, Unanue graduated from the University of Havana School of Medicine in 1960, a year after Fidel Castro overthrew the Cuban government. Wanting to be the architect of his own life, he left Cuba for the United States that year, before Castro imposed travel restrictions on residents.

He went on to complete an internship in pathology at Presbyterian University Hospital in Pittsburgh; a pathology research fellowship at Scripps Clinic and Research Foundation in La Jolla, Calif., with the renowned immunopathologist Frank Dixon; and then an immunology research fellowship at the National Institute for Medical Research in London, where he worked with famed immunologist Brigitte Askonas.

Unanue returned to Scripps and then was recruited by eventual Nobel laureate Baruj Benacerraf to Harvard Medical School. In 1985, he became head of what was then the Department of Pathology at Washington University School of Medicine, where he continued to define the process of antigen presentation in greater detail, with a special focus on Type I diabetes.

A true Renaissance man, Unanue also was known for his love and legendary knowledge of opera and was a longtime supporter of the Opera Theatre of Saint Louis, The Metropolitan Opera in New York, and the Santa Fe Opera.

Unanue is survived by his wife of more than 58 years, Marianne; his children, Marie Unanue (Chris Georgen), Rachel Rose (Scott), and David Unanue (Laura); his brother, Alberto Unanue; and six grandchildren.

A celebration of his life will take place in 2023.

Memorial contributions may be made to the Juvenile Diabetes Research Foundation or Opera Theatre of Saint Louis.