Wired for DISCOVERY

Mark Bear ’75 is Applying Decades of Neuroscience Research to New Treatments for Brain and Vision Disorders

BY SARA C.P. WILLIAMS
[Top Portrait by David Sella]

Mark Bear ’75 has spent his career unlocking one of the brain’s most fascinating abilities: its power to change and adapt based on what it experiences. But long before he became a neuroscientist making groundbreaking discoveries, Mark’s own brain was shaped by his time at St. Stephen’s School. The curiosity, collaboration, and determination that drive his research today were already forming back then, sparked by inspiring teachers and challenging coursework.

“I learned how to learn at St. Stephen’s,” says Mark. “Then, the question was how does the brain learn?”

Today, Mark’s lab at the Massachusetts Institute of Technology (MIT) is testing new treatments for “lazy eye” and for Fragile X syndrome—a leading inherited cause of intellectual disability and autism. In both cases, he has developed drugs that work by precisely altering how the brain forms or weakens connections between brain cells.

“I’ve gotten a lot of joy over the years from tackling the challenge of understanding the brain at a fundamental level,” says Mark. “And it would really be the capstone of my career if we could advance these treatments into the clinic.”

The Spark of Discovery

Growing up, Mark was captivated by the brain. A Christmas list from his early childhood included a model of the human brain. When he was six, Mark watched the television coverage of John F. Kennedy’s assassination and listened to reporters speculate on the effects of a bullet to the brain.

“I remember sitting there being amazed, because I had never thought about what goes on inside the skull before that,” says Mark. “It initiated this lifelong interest in the brain.”

Throughout his years at St. Stephen’s, Mark continued to remain fascinated by science; he credits physics teacher and St. Stephen’s grad Marty Baumberger ’61 with showing him how even complex topics like the theory of relativity could be made simple. 

As an undergraduate at Duke University, Mark joined a research lab where he experienced the thrill of scientific discovery for the first time. Mark, working with a postdoctoral fellow, carried out research to show how brain cells connected with each other. The experiments revealed a previously unknown cluster of brain cells involved in vision.

“All of us were whooping and hollering and giving high-fives. I just remember vividly at the time thinking, ‘I can’t believe we didn’t know this already and I can’t believe I, as an undergraduate, could make this discovery,’” he says. “That is what gave me the confidence to keep going in science.”

Rewiring Vision

In graduate school at Brown University, and then when he launched his own lab, Mark’s research revolved around the emerging field of synaptic plasticity—the idea that the brain’s connections are constantly strengthening or weakening based on experience.

“Synaptic plasticity is fundamental to neuroscience,” Mark explains. “Experiences during childhood, or during high school, or any other time, shape our brains.”

Mark in the lab [Photo by Nina Palisano]

Mark, however, remained committed to the work—and to the idea that conceptually related treatment approaches could still work. Recently, he and his colleagues discovered a new molecular target that overcomes the problem of resistance with the earlier drugs, sustaining the effects on the brain for much longer. Results using the new compounds, in both mice and humans, are very encouraging.

Mark has founded his own startup, Allos Pharma, to try to raise money for clinical trials of the drugs. Many of the same molecular pathways important in Fragile X are also at play in autism spectrum disorders, and studies have shown the same drug improves social function in children with autism. 

“We’ve corrected Fragile X in mice many times over,” he says. “I still believe we can do it in humans.”

Lessons that Last

Despite publishing more than 200 papers, receiving prestigious national awards like the Julius Axelrod Prize from the Society of Neuroscience, and being elected to the National Academy of Medicine, Mark says his greatest accomplishment is the mentorship he’s provided to students. He has taught introductory neuroscience to more than 10,000 students, written a leading neuroscience textbook for undergraduates, trained more than 25 Ph.D. candidates, and mentored countless postdoctoral fellows in his lab.

“My individual contribution to science pales in comparison with the contributions all these people are making,” says Mark.

He believes much of his success can be traced back to the habits and values he developed at St. Stephen’s. He credits the school not just with academic rigor—teaching him how to write and think critically—but also with helping him feel comfortable around adults, behave professionally, and engage meaningfully with ideas, even those as complex as Chaucer or the Bible. “It prepared me to be an adult,” he says. “And it gave me really great examples of how to teach effectively.”

He adds that faculty members never disparaged students for failing to understand something; always patiently explaining ideas in different ways. That open dialogue taught Mark how to work with scientists and clinicians from all walks of life, including long-time friend and Nobel Prize winning physicist Leon Cooper.

“His theories really influenced my work on the brain and I would say probably my work influenced his ideas,” says Mark. “Even though we were speaking different languages, we had a super fruitful collaboration.”

When asked what advice he would give to current St. Stephen’s and St. Agnes students, Mark returns to the idea that the school taught him how to learn. That, he says, gave him the ability to figure out what career path he wanted to pursue.

“Don’t differentiate too early, because you don’t know as an 18-year-old what new things you’ll be exposed to,” he says. “St. Stephen’s and St. Agnes teaches you how to learn and conduct yourself, and when you get to college you can then take full advantage of this new universe of opportunities to learn different things. Professors love to teach those who love to learn.”

Ultimately, Mark’s own research was shaped by the colleagues, students, patients, and ideas circulating around him, just as his early fascination with the brain was shaped by the experiences and mentors he encountered at St. Stephen’s. And that, in a way, is the ultimate lesson of his work: our experiences shape us—and our brains—in ways both seen and unseen, every single day.