RETROSPECTIVE RETROSPECTIVE

Bruce McEwen, 1938–2020

Huda Akila,1 and Craig McEwenb

The pioneering neuroscientist Bruce McEwen died on January 2, 2020 at the age of 81 following a brief illness. He was the Alfred E. Mirsky Professor and head of the Harold and Margaret Millikin Hatch Laboratory of at The . Born in Fort Collins, Colorado, Bruce grew up in Ann Arbor, Michigan, in an academic household; his father George was a Professor of English in the University of Michigan’s Engineering School. After graduating from , Bruce started graduate study at The Rockefeller University in 1959 and, after a postdoctorate in Sweden and a brief appointment at the , served on The Rockefeller University’s fac- ulty for 54 years until his death. He and his wife, the neuroimmunologist Karen Bulloch, collaborated in re- search and writing. Bruce remained active scientifically until the very end, with a paper published on the day of Bruce McEwen with Kobe and Buber on the coast of Maine. Image courtesy of Karen Bulloch McEwen (The his death. His friend and coauthor on that paper, Huda Rockefeller University, New York, NY). Akil, and his brother, Craig McEwen, remember him.

Huda factors. This led Bruce and colleagues to consider how Bruce has been a major force in . He steroid hormones might remodel the brain at the conducted groundbreaking research and inspired many structural and functional level, literally changing the of us to think differently about how we create science shapes of neurons and their connectivity. This dynamic and how we use it for the greater good. The central view of the brain was revolutionary for the time but was theme of his research—the brain biology of — entirely in line with Bruce’s views of the brain as an lends itself to every level of exploration, from the mo- organ for adapting, coping, and integrating information lecular and cellular, to the neural and behavioral, to the from various sources: its social setting, the rest of the societal and global, and Bruce explored them all. In a body, and other ongoing neural functions. He under- seminal 1968 Nature paper (1), Bruce demonstrated for scored that as the arc of our lives moves forward, our the first time the binding of glucocorticoids in the brain, experiences (positive and negative) are written in the specifically in the hippocampus. This was very surprising structure of our brains and become part of its fabric. as the hippocampus had been thought to be primarily “We can never go back,” Bruce emphasized, but relevant to memory. That discovery led to the unex- adaptive mechanisms could counterbalance, compen- pected notion that the response to stress is not simply a sate, and induce resilience to environmental demands. peripheral event related to “fight or flight” but rather He pointed to factors that stretch these adaptive mech- was integral to many functions of the brain, affecting our anisms to their extreme, be they genetic vulnerability, an cognition, memory, and . unhealthy body, or a toxic environment, increasing the Bruce also knew cell biology and understood that “allostatic load” to the point where it could lead to de- glucocorticoids have both rapid and long-lasting ef- pression, dementia, and other brain disorders. But this fects, even though this predated the characterization plethora of convergent factors is also a source of hope; of steroid receptors as ligand-activated transcription there are many ways to reset the system, lighten the

aThe Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109; and bDepartment of Sociology, Bowdoin College, Brunswick, ME 04011 Author contributions: H.A. and C.M. wrote the paper. The authors declare no competing interest. Published under the PNAS license. 1To whom correspondence may be addressed. Email: [email protected]. First published March 11, 2020.

6286–6288 | PNAS | March 24, 2020 | vol. 117 | no. 12 www.pnas.org/cgi/doi/10.1073/pnas.2003097117 Downloaded by guest on September 27, 2021 load, and call upon the remarkable neuroplasticity of medical students about brain research and its clinical the brain to rewire itself and bounce back. implications, supporting the RockEDU Science Out- But beyond this reframing of our thinking about our reach to K–12 science educators and students, and own minds, Bruce was also ahead of the curve in thinking Rockefeller’s Parents and Science Initiative. He be- about science as a team sport, not an ego trip. Many of lieved deeply in science, science education, and the my clearest memories of him are in my living room in Ann potential of science to change lives for the better. Arbor during the late 1980s or early 1990s. My husband Bruce’sfamily,aswellasfriends,graduatestudents, Stanley Watson and I, along with members of our labo- postdoctorates, and colleagues were all beneficiaries of ratories, are brainstorming with Bruce. We have a flip Bruce’s willingness and ability to share his knowledge. chart on an easel, and a postdoctorate is telling Bruce We were familiar with what his former students called his about his latest studies, not only the good stuff but also Big Mac attacks: Times when in response to a question the challenges. Bruce listens attentively, has very specific about a scientific question, he would pause, roll his eyes, and helpful suggestions, and points us to various rele- and then download a coherent rendition of research vant papers in the literature. We eat sandwiches from across disciplines, complete with citations. I experi- Zingerman’s deli and make a party of it. enced early indications of this capacity for encyclopedic This scene was to repeat itself over several years, as knowledge. In his teens he seemed to know extensive Bruce’s mother was still living in Ann Arbor, and he details about every airplane ever built and spent many visited her on a regular basis. During these gatherings, hours assembling plastic and wooden models. we told Bruce about our progress, and he updated us Over the last decade, Bruce came to describe about work ongoing in his laboratory. We discussed himself as a molecular sociologist. He developed that neuroscience more broadly: Gaps, challenges and ex- identity over several decades, starting in the MacArthur citing questions for the future. We also got to know Network on Determinants and Consequences of Health- each other’s families, including Bruce’s wonderful mom Promoting and Disease-Preventing Behavior and con- and her love of Gilbert and Sullivan; and his wife Karen tinuing with the MacArthur Network on Socioeconomic Bulloch and his brother Craig McEwen, with whom Status and Health. That engagement led to active par- we celebrated the University of Michigan Honorary ticipation on the National Scientific Council on the Doctorate that Bruce received in 2005. Developing Child. These and other commitments, such It was during these scientific exchanges that I dis- as membership in the Hope for Depression Research covered how Bruce’s personality played into his sci- Foundation Task Force, reflected Bruce’s wide-ranging ence. He had a deep and up-to-date knowledge of the interests and commitment to putting science to work for field and a prodigious memory to use it maximally. the common good. Bruce saw connections that were not at all obvious Bruce’s view of himself as a molecular sociologist that formed the basis of his new conceptual frame- may have been influenced a bit by my career as a works. And he made it all seem easy, probably because sociologist. Bruce was my older brother by almost it came easily to him. But more importantly, I began to 8 years, so our lives and careers diverged early on. perceive how remarkable he was as a person: His hu- Nonetheless, we talked often and learned from each mility, integrity, and generosity. Bruce always gave full other. Although I was in awe of Bruce’s extraordinary credit to others. He never spoke down to anyone. His accomplishments, he was not. He followed my career ego was never, ever, in the way. He made us feel like we with loving encouragement and openly admired my were all in this together, on a fantastic adventure to hands-on engagement in local communities, including discover important truths. Needless to say, we trusted work with the United Way of Mid Coast Maine to him completely, with our early data, our discoveries, our strengthen supports for early childhood development. successes, and our failures. An invitation for the two of us to provide the It is this remarkable combination of passion, intel- keynote at the 2011 Annual Meeting of the United lectual power, bone-deep integrity, and love of hu- Way deepened our conversations about early child- manity that explains why Bruce is such an inspirational hood and the impact of social inequality on life chances. figure. His science blended seamlessly with his essential This began an unusual and immensely rewarding pro- goodness and his life made it clear that knowledge is a fessional collaboration, as I came to understand through gift to be shared, not just among those who create it, Bruce that social processes and structures help shape but also with those who need it most. and reshape the brain, with consequences for behavior and life trajectories. After several coauthored articles, Craig our partnership culminated in a joint lecture on the Sharing his vast knowledge and insights with students, 111th anniversary of our father’s birth, shortly be- the public, policymakers, and practitioners was a central fore Bruce’s death. That talk on Inequality and Early feature of Bruce’s later career. A small sampling in- Childhood Adversity: Toxic Stress and Its Epigenetic cludes two books for the lay public—The Hostage Effects at the University of Pennsylvania’sAndrea Brain (2) and The End of Stress as We Know It (3)— Mitchell Center was part of their Reverberations of collaborating with researchers and practitioners of Inequality Series and represented well Bruce’s ex- mindfulness and meditation, sharing the stage with traordinary interdisciplinary reach, intellectual open- the Dalai Lama as part of a Mind and Life Dialogue, ness, and deep commitment to science and to social meeting with policymakers to deepen their under- justice. He was a beloved brother and a cherished standing of posttraumatic stress disorder, lecturing to intellectual partner.

Akil and McEwen PNAS | March 24, 2020 | vol. 117 | no. 12 | 6287 Downloaded by guest on September 27, 2021 1 B. S. McEwen, J. Weiss, L. Schwartz, Selective retention of corticosterone by limbic structures in rat brain. Nature 220, 911–912 (1968). 2 B. S. McEwen, H. M. Schmeck Jr, The Hostage Brain (Rockefeller University Press, 1994). 3 B. S. McEwen, E. N. Lasley, The End of Stress as We Know It (Joseph Henry Press, 2004).

6288 | www.pnas.org/cgi/doi/10.1073/pnas.2003097117 Akil and McEwen Downloaded by guest on September 27, 2021