Fifteen Questions: Steve Hyman on the Genetics of Mental Health, Mind Reading, and Speaking his Mind

This article originally appeared in the Harvard Crimson’s magazine, Fifteen Minutes (FM).

Steven E. Hyman is a professor of Stem Cell and Regenerative Biology and directs the Stanley Center for Psychiatric Research at the Broad Institute. He was the Director of the U.S. National Institute of Mental Health from 1996 to 2001, and then served as Harvard Provost from 2001 to 2011. This interview was edited for length and clarity.

FM: In your research, you work on the genetics of mental illness. Why is that an important topic to research?

SEH: The truth is, we have to do better in coming up with both preventive interventions and treatments for mental illness. We have very useful psychotherapies, especially cognitive behavioral therapy. But they have what’s sometimes called the therapeutic ceiling, meaning people improve, but these are not cures, and a lot of people relapse. The medicines that we have are mostly the chemical descendants of 1950s prototypes that were discovered by serendipity. While there are a few new drugs, none of them come from a deep understanding of what puts people at risk for mental illness.

The Broad Institute does genetics because they are clues to molecular mechanisms underlying mental illness. Genetics can be modestly useful for prediction of risk, but I wouldn’t oversell that. Genes are not fate for these conditions. What we hope to do is to understand those mechanisms with a view toward developing new treatments.

FM: What first got you interested in studying this and making this your research specialty?

SEH: I decided eons ago that the brain and what makes us tick was just the most important thing.

I was an undergraduate major in philosophy at Yale and then I got a fellowship to the University of Cambridge, where I did history and philosophy of science. But this was the mid 1970s, and there wasn’t all that much interest in the empirical world. And so I thought, I’m gonna be miserable if I can’t be in the trenches, figuring these things out. So I decided to be in the brand new field called neuroscience.

I realized that you could be a major in anything and go to medical school. I used medical schools as an avenue to get into research. I was very moved by the patients with psychoses, with bipolar disorder, with schizophrenia, and fascinated by them. I also was horrified by the predominant theories — that is, what the faculty believed. These were the dregs of psychoanalysis who were blaming the mother’s unconscious —the so-called schizophrenogenic mother — which was both implausible and sadistic.

I did a psychiatry residency, then did a five year postdoctoral fellowship in molecular biology and went into the lab.

FM: Was the history and philosophy of science your first academic interest?

SEH: I had a Ph.D. thesis planned out that I likely would have stayed at Cambridge anddone.

I wasn’t thinking at the time about mental illness. I was really thinking about how the brain gives rise to the mind, questions like that. But it was hard in the 1970s to find people really interested in that. And that’s when I decided — with utter terror, by the way, because I didn’t really know what I was doing — that I wanted to do neuroscience.

FM: How do you feel like that background in history and philosophy affected your practice as a scientist?

SEH: In ways that I wouldn’t have predicted.

It turns out that the ethics of neuroscience was remarkably unexamined. When I was NIMH director, I already was blindsided by profound ethical issues. The issue of treating children with ADHD with stimulants — it’s remained contentious, but it was very, very hot at the time. And people had a rather unexamined and rigid view that if you give medicines to a young child, you’re changing their brain, and you’re changing who they are. But people were not thinking about what happens to those kids if they can’t do well in school, despite their abilities, and they’re always being yelled at for running around, and they’re rejected by their peers. How do you decide what’s good, what the right thing to do is?

When we intervene in people’s brains, not only are the usual ethics of, “do they understand what we’re doing, do they consent, are we really concerned for their safety,” but also issues like, “are we thinking about personal identity, narrative identity, thinking about how a person’s personality might change and what that means for them, but also for their families and friends?” I think the world is not thinking enough about these things. That philosophy background has stood me in good stead and has contributed to a lot of what I actually do.

FM: What do you think is the biggest ethical issue that neuroscientists should be paying attention to right now?

SEH: There are a few. Although it’s really early days, the truth is, some form of mind reading, especially with the help of AI, is not implausible. I think the ethics of brain privacy are gonna be really important.

But for right now, 200,000 people in the world have deep brain stimulation to treat Parkinson’s disease. And a certain number of those people really have important personality changes.

People start gambling. People start engaging in risky behaviors very late in life. It really is changing the way people are, their relationship to their families and so forth. And as these procedures become more routine, and as they get developed to treat depression and OCD —which is happening —I don’t think that the medical establishment or people in general really have grappled with the fact that your sense of identity is not necessarily permanent and stable. It’s malleable and treatments that you might undergo for very good reasons might change that.

FM: Do you think these ethical issues are under examined?

SEH: Yeah. It’s very real, but yet to most people, it seems very exotic. It seems like science fiction.

FM: You were the director of the National Institute of Mental Health for many years. What are you proudest of from your work during your time there?

SEH: I was hired, and I had the temperament, to modernize it. It really was a mess. A lot of the work was wishful. The social determinants of mental health really matter. But having recognized — as I think we have —that living in grinding poverty can be causal for depression and anxiety and can exacerbate everything else, doctors are not very good at curing global poverty. We can advocate. I testified in Congress. But, just to give you an example, I moved our portfolio from a lot of large scale documentation of social factors that were worth documenting but that we couldn’t change, toward neuroscience.

And I could tolerate having a lot of people angry at me.

FM: In this New York Times profile of you in 1999, they write that you had “an alarming habit of speaking your mind, even when what you had to say was unpopular.” Do you think that’s like a fair characterization?

SEH: It is. It’s either a defect or a benefit at different times. People don’t like that. But people are sick, right? And this is taxpayer money. That’s what I kept saying.

We owe it to people with these illnesses, and we owe it to the taxpayers to do our very best.

FM: Then you took on another administrative position as Harvard Provost. You were in charge of Harvard’s academics, and you worked on some collaborative scientific initiatives. Can you tell me a little bit about what those were?

SEH: One of the things about Harvard is it’s relatively decentralized. But the problem was that the structure of modern knowledge is not necessarily something that would fit in a school or a department. Think about environmental policy, where you need lots of chemistry, engineering, economics, policy analysis, and actually many other fields because of the effects of climate change on agriculture, on migration.

We developed this program of interfaculty initiatives. The biggest one I negotiated the Harvard side of was the Broad Institute. That really was Eric Lander’s vision of bringing together Harvard and MIT and the Harvard hospitals to make good on the promise of the genome to make a difference for human health.

FM: On this kind of a topic of collaborative initiatives, I think right now, there’s maybe this feeling that STEM disciplines are kind of on the rise, while the humanities are more on the decline. What kind of work did you do to kind of balance the interests of these different academic communities while serving as Provost?

SEH: I don’t think I succeeded in what I really wanted to do. What I did do is support the humanities. I helped Homi J. Bhabha, the former director of the Mahindra Humanities Center, raise money, including trips to India, and tried to make sure that the humanities were involved in these important interfaculty initiatives.

But what I was really hoping was to develop more substantial kinds of collaborations, because many issues can’t be resolved within STEM disciplines alone. Let’s imagine that through enhancement, through better drugs and amphetamines and maybe a little brain computer interface and so forth, we pump up human capacities.The question then becomes, what was the purpose of life to begin with? Is it to be maximally productive until we drop? Are there other things we should care about? You find the answers in history and literature and drama and art. You don’t find them in science textbooks.

How do we confer moral status not just on people but on animals and other things? People are going to now ask this about AI — will some AIs deserve moral status? Again, this cannot be compartmentalized only within the STEM disciplines.

I didn’t succeed. Many humanists were afraid I wanted to instrumentalize them to be serving the needs of scientists to deal with these difficult problems. I think these are some of the most interesting and pressing problems that we’re facing. And we actually need humanists to help think in compelling and profound ways about these problems.

FM: What keeps you coming back to the classroom?

SEH: We think we understand things until an undergraduate asks you a hard question. It really does keep you learning. And that’s not a throwaway statement. It really is true.

FM: If you had to give a lecture tomorrow on a non-academic subject of your choosing, what would you make it be about?

SEH: What I do outside of academia, a lot with my family, is travel, cooking and gardening. I could probably give an amusing lecture on some of my travels.

FM: Where’s your favorite place you’ve traveled to?

SEH: I don’t know if I have a favorite. I think it’s so important to meet different people, have varied experiences. I think my favorite thing is to focus on human cultural differences and diversity.

I travel a lot for work also, because of our global genetics efforts. I’ve been in Asia three times in the last six months. We have a large NIH-funded grant on the genetics of bipolar disorder. People of European origin make up, I don’t know, let’s guess 15 or 16 percent, maybe less, of humanity, but more than 90 percent of medical genetics and medical research are done on people of European descent.

And so as we increase the number of people we study — for complex genetics you need very large cohorts — I felt that we should achieve those numbers by studying global populations.

We’ve completed a large study of psychosis, in Kenya, Uganda, Ethiopia, and South Africa. One of the medical school deans in Kenya admonished us ahead of time about what he called “safari research,” where Americans or Europeans would show up, take samples, disappear, write papers, and never be heard from again. But of course, while they were in Africa they would go on a safari.

The goal is, of course, to learn about psychosis across populations in this case, but also the goal when we leave is that the people who we have hopefully trained and helped with infrastructure will continue to do high level research that they don’t need us for. So that work travel is exhausting, but it’s very compelling.

FM: Are you still doing research these days?

SEH: The genetics and neurobiology of schizophrenia are far enough along that I thought it was time to start a serious study of biomarkers.

Industry has abandoned new research in psychiatry as too hard. That’s why we’re living partly on these drugs from the 1950s and their descendants. Without these biomarkers they’re not going to come back. So we’re involving industry. And with the industry scientists, we’re trying to get them hooked on the idea that schizophrenia and bipolar can be successful targets for treatment development.