Fifteen Questions: Pardis Sabeti on LS1B, Computational Genetics, and Holiday Cards

Pardis C. Sabeti is a professor at the Center for Systems Biology and the Department of Organismic and Evolutionary Biology at Harvard University, a professor in the Department of Immunology and Infectious Disease at Harvard School of Public Health, institute member of the Broad institute, and a Howard Hughes Medical Institute investigator. She does work in computational biology, medical genetics, and evolutionary genetics.

FM: You teach Life Sciences 1B — the flagship introductory genetics class — along with three other professors. Some LS1B alumni I talked to said they were surprised that you taught it, given your qualifications. What do you like about teaching an intro course compared to the smaller graduate classes you teach?

PCS: I just love all teaching. I love teaching in the small group, where there’s such personal connections.

But I love teaching in the big group, and trying to figure out how to make the big group experience seem personal.

LS1B has been one of the greatest highlights of my career.

I’ve never not taught it, even during the Ebola outbreak. After I shattered my pelvis and my knees, during SARS-CoV-2 … No matter what’s going on, it just grounds me to come back to LS1B.

It’s such a privilege and an honor to get to teach, to introduce amazing, young, brilliant minds to this topic in their college education.

FM: What are you most excited about right now — in and out of the lab?

PCS: So many things. It’s hard to say what I’m most excited about. I love my days. I really do. I’m working on four papers right now with my students, running the gamut of so many different topics. On every one, I’m like: this is my favorite project! Every project is my favorite project.

FM: How would you define computational biology or computational genetics, your primary areas of study, to a lay person?

PCS: Eric Lander, my mentor, once described genetics as ‘biological information as described through math.’ Basically the genome is one big code to decipher. And we can use computational tools to really understand them, and understand the logic, and build on that, and build new tools based on that.

Being a computational biologist is someone who uses mathematics and computer science to mine the genomes of humans and other organisms on this earth to understand how they work and to use that to the advancement of life on Earth.

FM: It seems that computational genetics is an inherently interdisciplinary field. But your research has also spanned other disciplines, including statistics, information theory, and medicine. How do you keep up with such a wide range of fields, and how do you decide what to work on?

PCS: I have always been somebody who’s just very curious about a lot of different fields.

I surround myself with brilliant people who can bring a lot of the expertise that I don’t have.

I usually find where there’s nobody else working, where my being there might make a difference.

I’m not in it to win a race. I’m in it to find what races aren’t being run.

FM: What’s your next big project?

PCS: It’s the big project we’ve been in for a decade, but we’re really picking up momentum on it, which is building the future of surveillance systems.

In the next several years, it’s really putting our money where our mouth is and taking the research and really implementing it to try to build resilient systems and early warning for outbreaks.

FM: Since at least the sequencing of the human genome in the early 2000s, as you talked about, using algorithms and statistical tools to study biology has become commonplace. Now the advent of artificial intelligence-based technology like AlphaFold and the possibility of genome editing with CRISPR seems to open up new frontiers. Where do you think the future of biology lies?

PCS: Yeah, we’re generating genomes from every organism on this planet, and every individual of different species on this planet. And we’re starting to understand the logic of how these genomes work. And then with these new generative AI models, we can actually create completely novel sequences that have their own properties.

It’s exciting to know that we could really have a lock on every infectious disease spreading, and we could use that to then build precision therapies that really target the thing that’s making you sick, and nothing else. So all of that is really exciting. But it’s also terrifying, because there’s so many ways that we can misuse this.

And, you know, I’m an M.D., and I literally am the last person you know that will take a medicine. Literally everything is natural. If I get sick, I take avocado and water. That’s it, you know what I mean? I will not take an antibiotic. I don’t think that most of the medicines we’ve created make us healthier.

FM: Why is that?

PCS: So far we’ve made them pretty poorly. Antibiotics blast our entire microbiome, and we have no idea the doggone effects of that.

I do think that medicines are powerful and transformative. But I do think that they should be more of a last resort choice, not the first go-to.

FM: Your lab has a tradition of making extremely elaborate holiday cards. The one in 2021, for example, featured members of your lab dressed up and photoshopped onto the covers of popular board games, like Candy Land and Operation. How did this tradition start, and how does it work now that the lab is so big?

PCS: It was my first year as faculty: 2008.

I started getting this whole slew of family holiday cards. And I was like, ‘Oh, I don’t really have a picture to share, but I do kind of have a family; there’s this really cute lab, you know, delightful lab that I’m making. So just one night on a whim, I drove to a local K-Mart and bought a lot of ugly holiday sweaters and a menorah and some different multi-denominational things. And I just was like, let’s just take a photo.

And then we got the bug.

We had a completely underwater holiday card where I ended up renting scuba gear. We just started getting really intense about every part of this.

We’ve got celebrity guest cameos; we had Chris Martin from Coldplay and Seth Meyers from SNL in our SNL card.

Longzhi Tan — who is a former undergraduate with me, and now professor at Stanford — I need to give him a shoutout. He started photoshopping for us as an undergraduate, and he’s still photoshopping for us through graduate school at Harvard and postdoc at Stanford and now professorship at Stanford.

FM: Which was your favorite?

PCS: You can’t do this to me. I don’t do favorites. Like literally every one is magical in its own right.

FM: What was your biggest setback on the way to becoming a leading genetics researcher?

PCS: So many. Like I can’t pick my favorites, I can’t pick my biggest setbacks. They’re all pretty big.

I think the one thing I’ll say that you should know is that a successful life is not one that is free of setbacks. It’s defined by setbacks.

Probably the most important setbacks were just being lost in graduate school and having my project not going anywhere.

In a way, college is your childhood for being an adult, and graduate school is your adolescence for being a professional. It’s a time where there’s a lot of existential angst.

And if you don’t really have good support and people there to make you feel like you’re on the right track and tell you when you’re not, in a healthy way, then you could get lost.

FM: When you graduated Harvard Medical School in 2006, you were only the third woman to receive summa cum laude honors. What are the difficulties, as you see it, for women pursuing careers in science and medical research?

PCS: It is not to say it is not difficult to be a man, and to be a good person in society today. I actually feel for all of my students very much. Even at this age of now 47 years old and a tenured professor, I’m still asked to clear dishes at conferences where I might be the keynote speaker, and shushed when the men are talking. That happens all the time. And overlooked for grants that I proposed that are given to junior faculty who have never done the work before.

It’s pretty relentless. Because people are innately suspicious of women and their ability to manage things.

Or just the fact that I’m a computational biologist who has written a lot of papers myself as first author, that are developing new algorithms. And yet, most people literally don’t think I know the math.

It’s laughable, but it’s also sad. It really doesn’t bother me that much. I clear the dishes. I clear the dishes. That’s what a nice person would do. Sometimes I think I shouldn’t, because that’s not helping the cause. And sometimes I think I need to be more forceful. I know that that impacts other people that don’t have a voice more. I’m always trying to balance like, when do you say something?

During Covid, the same thing happened: I got kicked out of every room.

All these women who were just brilliant scientists, like the people that were in charge in outbreaks before, were all told to sit this one out, and I was told to sit this one out.

Essentially it was being told that the men take charge here.

And it’s why you saw most of the prominent voices during Covid were men, even though a lot of the people I know and I work with are women.

The world is not fair. It’s just not fair. None of these races are run equally in any way. So for me, I keep going because it’s important for the people that come after me and for everybody else that’s in it with me.

FM: Aside from your teaching and research, you’re also the lead singer of indie rock band Thousand Days. Is there a new album in the works?

PCS: There are a lot of songs we haven't released yet, some of which are so old that it’s almost silly to release. And there is new music being written but I’m pretty focused on a few other things right now.

FM: What are you listening to right now?

PCS: You know, really everything. Every spring I make a mix for LS1B, so I make a LS1B study mix. So I just started listening to a lot of tunes and trying to find new gems for the mix.

Two bands that I’ve re-fallen in love with are Petit Biscuit and Walk off the Earth.

FM: Your resume is practically exploding with academic achievements — a Rhodes Scholarship, multiple publications in Nature, a winner of the prestigious Howard Hughes Medical Institute Investigator award, and, on top of that, you’re one of Time’s 100 Most Influential People of 2015 for your work on Ebola. Yet you also played varsity tennis in college, started bands at Oxford and Harvard Medical School, and you continue to sing for Thousand Days even as a full-time professor and researcher. How do you balance all your commitments?

PCS: If you really do things you love, it’s not like commitments. It’s just like, I love playing music. I love playing tennis. I love the kind of work I do.

You’re actually finding the path of least resistance. People waste a lot of time working really hard in something they don’t actually care about, but that some external driver made them think they care about it. I just make things move faster by doing things I really like to do.

FM: Follow-up question: Do you sleep?

PCS: Yeah, I do.

— Associate Magazine Editor Hewson Duffy can be reached at hewson.duffy@thecrimson.com.