It was a staple of medical thinking dating to the 1910s that stress was the body’s alarm system, switching on only when terrible things happened, often leaving a person with an either-or choice: fight or flight.
The neuroscientist Bruce S. McEwen trailblazed a new way of thinking about stress. Beginning in the 1960s, he redefined it as the body’s way of constantly monitoring daily challenges and adapting to them.
Dr. McEwen, who died on Jan. 2 at 81, described three forms of stress: good stress — a response to an immediate challenge with a burst of energy that focuses the mind; transient stress — a response to daily frustrations that resolve quickly; and chronic stress — a response to a toxic, unrelenting barrage of challenges that eventually breaks down the body.
It was Dr. McEwen’s research into chronic stress that proved groundbreaking. He and his research team at Rockefeller University in Manhattan discovered in 1968 that stress hormones had a profound effect on the brain.
In studies using animals (five rats in the initial one), Dr. McEwen and his colleagues demonstrated that toxic stress atrophied neurons near the hippocampus, the brain’s memory and learning center. Their findings also paved the way for a later discovery by other scientists: that toxic stress also expands neurons near the amygdala, an area of the brain that promotes vigilance toward threats.
Describing the burden of continuing stress, Dr. McEwen coined the term “allostatic load” (derived from allostasis, the process by which the body seeks to regain stability, or homeostasis, in response to stressors).
Their discoveries, first published in the journal Nature in 1968, ignited a new field of research, one that would reveal how stress hormones and other mediators change the brain, alter behavior and impact health, in some cases accelerating disease.
At the time, only a few scientists were asserting that the brain remains malleable throughout life, challenging the dogma that the brain stops changing after adolescence. Dr. McEwen’s studies documenting how hormones alter neurons lent credence to this emerging idea.
“Everything in the field of stress bears his intellectual footprint,” said Robert Sapolsky, a professor of biology, neurology and neurosurgery at Stanford University and the author of the popular book “Why Zebras Don’t Get Ulcers” (1994).
“The most remarkable thing” about Dr. McEwen, he added, in a phone interview, “is that he started off as a cell biologist, with his first paper on muscle biochemistry published in 1959 in Science, and over the last couple of decades his work was more about why crappy childhoods make for adult brains that don’t work well.”
Dr. McEwen discussed allostatic load in 2000 in the journal Neuropsychopharmacology, writing:
“In anxiety disorders, depressive illness, hostile and aggressive states, substance abuse and post-traumatic stress disorder (PTSD), allostatic load takes the form of chemical imbalances as well as perturbations in the diurnal rhythm, and, in some cases, atrophy of brain structures.
“In addition,” he went on, “growing evidence indicates that depressive illness and hostility are both associated with cardiovascular disease (CVD) and other systemic disorders. A major risk factor for these conditions is early childhood experiences of abuse and neglect that increase allostatic load later in life and lead individuals into social isolation, hostility, depression and conditions like extreme obesity and CVD.”
By the end of his career Dr. McEwen had expanded his research to look at the impact of stress on communities, finding that chronic stress disproportionally affected marginalized people and increased their risk of illnesses.
Five years ago, he teamed up with his brother, Craig McEwen, a professor emeritus of sociology at Bowdoin College in Maine, to study the sociological implications of chronic stress.
“We know that environmental complexity changes the brain,” Bruce McEwen said in an interview recorded by Rockefeller University, and that it “comes to haunt us in terms of socioeconomic status, poverty and things of that sort.”
At his death — caused by complications of a stroke, a Rockefeller spokeswoman said — Dr. McEwen was the Alfred E. Mirsky professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at the university.
He published more than 1,000 scientific articles, and his work has been cited in others more than 130,000 times. He also wrote popular books, including “The Hostage Brain” (1994), about how the brain can be overtaken by both external and internal forces, written with Harold M. Schmeck Jr., then a science reporter for The New York Times; and “The End of Stress as We Know It” (2002, with Elizabeth Norton Lasley).
He had continued to lecture and write scientific articles (as well as draw and paint) until weeks before his stroke.
Huda Akil, the co-director of the Michigan Neuroscience Institute at the University of Michigan, said Dr. McEwen’s thinking had been “absolutely pivotal in key stages of how we think about stress.” Dr. Akil was a co-author of one of Dr. McEwen’s final papers. It was published in the Journal of Neuroscience on the day he died.
Bruce Sherman McEwen was born on Jan. 17, 1938, in Fort Collins, Colo., to George and Esther (Lenters) McEwen. He grew up in Ann Arbor, Mich., where his father was an English professor at the University of Michigan; his mother was a homemaker.
After graduating from University High School in Ann Arbor, he attended Oberlin College in Ohio, earning his bachelor’s degree in 1959. He received his Ph.D. from Rockefeller University in 1964 and did postdoctoral research at the University of Gothenberg in Sweden before returning to Rockefeller as a faculty member in 1966.
Dr. McEwen often collaborated with his wife, Karen Bulloch, a Rockefeller research associate professor and head of the university’s neuroendocrinology and inflammation program.
She survives him, along with his brother; two daughters, Carolyn McEwen and Sarah McEwen Kelly; his stepchildren Kimberly McGrath and Scott Muryasz; and eight grandchildren. An earlier marriage, to Nancy Ames, ended in divorce.
In recent decades Dr. McEwen became interested in how other hormones, like insulin and ghrelin (the hunger hormone), affect the brain, exploring why people with diabetes and metabolic syndrome are more likely to suffer from depression. He devoted his energies to understanding how factors like nutrition, physical activity and exposure to early-life trauma can also alter the brain.
Dr. McEwen was known for his enthusiasm in training young scientists. In 1993, he began an initiative at Rockefeller University for high school and college students to spend summers working with scientists. Many went on to fruitful careers in science.
“He was genuinely thrilled by the successes of his huge network of current and former trainees,” said Zachary M. Weil, an associate professor at West Virginia University who did postdoctoral work in Dr. McEwen’s lab in 2009.
Dr. McEwen was the recipient of many awards, including the Edward M. Scolnick Prize in Neuroscience from the McGovern Institute at the Massachusetts Institute of Technology and the William James Fellow Award from the American Psychological Society, recognizing a lifetime of intellectual contributions to the basic science of psychology. He was a member of the National Academy of Sciences, the National Academy of Medicine and the American Society of Arts and Sciences, and a past president of the Society for Neuroscience.
Last May, he officiated at his brother’s wedding, having been ordained online by the nondenominational Universal Life Church.
Prof. Craig McEwen said in an interview that Dr. McEwen had “relished the idea” of playing that role “and was delighted to become a minister on the internet as his last degree.”