Researcher comes back to BU to work on the science of memory

Because Steve Ramirez frequently attends neuroscience conferences around the world, he recently joined the Global Entry Program, which fast-tracks frequent flyers returning to the United States.

"I was telling my dad that when I come back to the United States now, I don't have to go through customs," says Ramirez (CAS'10), the son of Salvadoran immigrants. "And he's like, 'Wait a minute! I had to sneak into this country twice, and you can just waltz in?"

He laughs, but lots of doors are opening for him these days. His research into the nature and mechanisms of memory have made him a hot hand in neuroscience. His TED talk with research partner Xu Liu has garnered over a million views. He just signed a deal for a book combining neuroscience and memoir, to be published by Penguin's Riverhead Books in fall 2019. In December 2017, he won a McKnight Foundation Grant in Memory and Cognitive Disorders.

In summer 2017, the 29-year-old returned to BU, joining the College of Arts & Sciences psychological and brain sciences department as an assistant professor and settling into a lab at the new Rajen Kilachand Center for Integrated Life Sciences & Engineering.

"He has just rocketed to the forefront," says David Somers, (GRS'93), a CAS professor and chair of psychological and brain sciences. "I think the sky's the limit for him."

But it's the whole Steve Ramirez Experience—full of family, humor, and a deeply felt idealism about science—that makes you root for him.

He remembers where he came from

His parents, Pedro Ramirez and Delmy Moreno, came to the United States illegally with their older son and daughter to escape a murderous, decades-long civil war. The family settled in hardscrabble Everett, Mass., later becoming citizens; their younger son was born in a Brighton hospital in 1988.

He says he was a middling student in Everett High School's class of 2006, bright enough to earn As, Bs, and Cs, but lousy at standardized tests. "I learned to work hard. That's my parents, that's me channeling them," he says. "Because you see your dad working 100-hour weeks and you're like, maybe I should do my homework."

His father started in this country with jobs like waiting tables at a Howard Johnson's, then he took a janitorial position at a Harvard lab, eventually advancing to lab manager of the university's Concord Field Station in Bedford. His mother now works there too.

Ramirez's interest in the brain began as a teenager, when a cousin went into a coma after being anesthetized for a Caesarian section—a temporary lack of oxygen was apparently to blame—and has never fully recovered. At BU, he found his way to the lab of Howard Eichenbaum, an internationally recognized figure in the study of memory, who passed away unexpectedly in July 2017, at age 69. Eichenbaum was a William Fairfield Warren Distinguished Professor, a CAS professor of psychological and brain sciences, and director of BU's Center for Memory and Brain and the Laboratory of Cognitive Neurobiology. After two years in Eichenbaum's lab, Ramirez earned a BA in neuroscience.

"We did a lot of good science," Ramirez says. "We were working on really exciting projects, and he taught me how to think scientifically. So when I applied to grad school, I think MIT was like, 'Maybe the kid isn't as big a risk as we thought he'd be; who cares that he's from Everett or what his parents' background is.'"

Ramirez skipped a master's degree and became a PhD candidate at MIT's Picower Institute for Learning and Memory, where he and colleague Xu Liu first conducted newsmaking experiments changing the memories of mice.

"It's been a long-standing psychological question: what is a memory? What does that look like in the brain? How is it represented?" Somers says. "And we've had some ideas, but until you could actually demonstrate that you could activate one specific memory or change one specific memory, you have a theory that's not really tested."

Ramirez and Xu Liu did that with a variety of high-tech tools, including optogenetics: they inserted viruses into the brain cells of mice to make the cells respond to light. They identified cells in the hippocampus of the mouse that were associated with a specific memory, in this case a memory of receiving a mild electric shock on the foot while exploring a particular box. They then reactivated those memory cells with a laser while the mouse was in a different box, and it froze in fear.

"What he's done is to tag a specific memory in an awake, behaving animal and actually manipulate that memory and either make it stronger or make it weaker, to change it," Somers says. "It's really amazing technically."

In 2015, Ramirez earned a PhD in brain and cognitive sciences from MIT, and the same year he was named one of the Forbes"30 Under 30" innovators in science. He also won a coveted Director's Early Independence Award grant from the National Institutes of Health—$1.25 million over five years. He entered the fellows' program at Harvard, but left early to accept the BU faculty post after Eichenbaum told him about the opening and encouraged him to apply.

Complex questions, but the answers could help many

Coming back to BU was a no-brainer, Ramirez says. He'd always planned to stay in Boston. Work-life balance is a challenge he is determined to ace. A fan of good beer and Boston sports teams, especially the Red Sox and Patriots, he shares a Mass Ave apartment with two guys who have been his friends since seventh grade. He talks to his parents frequently on the phone and makes time for Sunday meals with the whole family. He'll do his best work where he's happiest, he says, and that will trickle down to his whole team.

He hopes to apply his techniques reactivating positive memories in mice to minimize negative feelings. He imagines that the techniques might someday be used to help people overcome anxiety, depression, post-traumatic stress disorder—even the memory loss associated with Alzheimer's disease.

Somers references Harry Potter to explain Ramirez's work: "Harry was very good at casting a Patronus Charm to ward off Dementors, which are really just sort of an embodiment of depression. To cast a Patronus Charm, one needs to recall a very positive memory. And one avenue of Steve's research is making this a real thing, using positive memories to ward off anxiety and depression. That has tremendous clinical potential."

"It's viewing memories not just as a mechanism in the brain," Ramirez says, "but—and put this in humongous quotes—viewing memory as a kind of drug, as a potential therapeutic."

Of course, for many people the idea of scientists meddling with memories has Orwellian implications. Somers says that's inevitable. "I think you can say that with any sort of fundamental breakthrough, like understanding how DNA works," he says. "We've got this new CRISPR technology, a gene-editing approach to be used for good, but you can imagine somebody else finding a way to use it for nefarious purposes."

Ramirez understands the issues well; he's prone to referencing the movie Inception when the moral aspect comes up. "Memory manipulation is something that's drenched in ethical dilemmas," he says, "and our job is also to start the conversation with everyone about what does it mean and start it yesterday. By having that conversation and setting that conceptual scaffold, we do our job."

His dedication to transparency is spelled out in detail on the Ramirez Group website, and he is more open than most scientists in posting results before they are formally published. His commitment was strengthened, he says, by the deaths of Xu Liu, who passed away suddenly in 2015, and Eichenbaum. "Life is too short," he says. "I don't have the time to BS my way to the top."

"People say, 'You're young and naïve and you're posting all your data, and to get tenure you have to do this and that,'" Ramirez says. "But you got here because you want to fundamentally change culture to what it can be at its best. It doesn't have to be The Hunger Games. Tenure is the last thing I'm worried about. We're going to do good science and everything else will happen along the way.

"This is what I love about research—you have to bust your ass, it doesn't matter if you're a genius or not," he says. "Whether you're a man or woman, gay or straight, from El Salvador or Canada, it doesn't matter. If you work hard in research, you're going to push forward, you're going to make discoveries."

Provided by Boston University