MDI Biological Laboratory

Bruce S. McEwen (1938-2020): Understanding the Biology and Health Effects of Psychosocial Stress

  • April 19, 2020

Bruce McEwen, Ph.D., Alfred E. Mirsky Professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University and a member of the National Academy of Sciences, was to be the keynote speaker at this year’s Maine Biological and Medical Sciences Symposium (MBMSS), but died unexpectedly on January 2, 2020.

I was very much looking forward to meeting him. We had corresponded over the past few years, most recently about a review I wrote last summer, a pre-submission draft of which he read and commented on. Bruce had enthusiastically accepted our invitation to be keynote speaker at MBMSS, and always replied to my e-mails shortly after I sent them, testaments to his generosity and passion for mentoring.

Bruce was an intellectual giant who broke ground in the field of stress biology, over his career publishing hundreds of scientific papers as well as the popular 2002 book The End of Stress as We Know It, and training dozens of students and postdocs, many of whom went on to become leaders in the field themselves.

As a postdoc and assistant professor in the late 1960s he discovered that the hippocampus, a part of the brain important for learning and memory, is altered by circulating stress hormones (cortisol in humans) and contains high levels of the glucocorticoid receptor (GR), a transcriptional regulatory protein that is activated by cortisol. He and his lab went on to show that GR activity in the hippocampus and amygdala (another region of the brain involved in emotional regulation) plays an important role in regulating how the brain responds to stress, and contributes to the detrimental effects of chronic stress, including neurodegeneration with age as well as immune system dysregulation. He showed that sex hormones also affect the brain, causing males and females respond differently to stress.

He popularized the concept of allostasis, which refers to the concerted response mounted by multiple physiological systems to maintain homeostasis in the face of environmental challenge. He wrote extensively about how acute stress is both necessary and good, helping shore up the body’s defenses, whereas chronic stress becomes toxic by increasing allostatic load, sometimes leading to allostatic overload, a condition in which the body’s defenses and ability to adapt to stressors becomes overwhelmed and ineffective.

I learned of Bruce’s work a few years ago when the research focus of my lab turned to the long-term developmental effects of chronic stress and cortisol exposure. I wrote to him for advice on the project. By coincidence I discovered that in scientific genealogy Bruce is my “uncle”, having been a graduate student of Alfred Mirsky at the Rockefeller at the same time as my postdoctoral mentor Eric Davidson. My longstanding research interest on the regulation of gene expression, an intellectual tradition extending directly from Mirsky’s pioneering work on that subject, began in Eric’s lab. My lab’s current work on the GR and other transcription factors that regulate the stress response continues that tradition, building on the combined intellectual legacies of Mirsky and his students Davidson and McEwen.

I was attracted not only to McEwen’s work on the cell and molecular biology of the stress system, but also to his advocacy of non-reductionist system-level thinking, which recognizes that the health problems caused by chronic stress cannot be understood much less solved without addressing their socioeconomic roots. Bruce understood that one of the biggest causes of the public health problems linked to chronic psychosocial stress is poverty, and that the most effective remedy for the health-damaging effects of chronic stress are strong social safety nets. In pursuing this line of work he collaborated with his brother Craig McEwen, Ph.D., Daniel B. Fayerweather Professor of Political Economy and Sociology Emeritus at Bowdoin College. In recent years the two coauthored several papers exploring the connection and vicious cycles linking socioeconomic adversity, chronic stress, and poverty (most recently: Social Structure, Adversity, Toxic Stress and Intergenerational Poverty: An Early Childhood Model, Annual Review of Sociology, 43: 445-472, 2017).

Bruce McEwen accomplished an extraordinary amount in a career that was far from complete at the time of his death. He was a quintessential scientist, a generous mentor, and a true luminary, opening doors and shining a light on the path that biomedical research needs to take to address the growing array of public health problems linked to chronic psychosocial stress. I will miss him.

You can listen to Bruce reflect on his research and career in this excellent 2017 interview produced by The Rockefeller University.

Written by James A. Coffman and presented at the Maine Biological and Medical Sciences Symposium, April 23-24, 2020.