Outbreaks, Evolution, and Rock 'n' Roll: Topol Talks to Pardis Sabeti

; Pardis Sabeti, MD, DPhil


May 10, 2017

Editor's Note: Pardis Sabeti, MD, DPhil, is a member of the Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), and a professor at the Center for Systems Biology and the Department of Organismic and Evolutionary Biology at Harvard University. She develops algorithms to investigate evolution in the genomes of humans's most devastating and deadly diseases, like Ebola, Lassa fever, and Zika.

Fleeing the Iranian Revolution, Dreaming of MIT

Eric J. Topol, MD: Hello. I am Eric Topol, editor-in-chief of Medscape. I have the special privilege of having a conversation with Pardis Sabeti. She is an extraordinary scientist and physician at the Broad Institute at Harvard Medical School and MIT. We are going to talk about the arc of her life and career, beginning when she moved here at age 2 from Tehran.

Pardis Sabeti, MD, DPhil: Yes. We came to the United States around the time of the Iranian revolution and had refugee status here. Then we moved to Hawaii, New Jersey, Georgia, and Florida, and we settled in Florida.

Dr Topol: At one point you were not sure whether you were going to own a flower shop, be a novelist, or become a doctor. Is that right?

Dr Sabeti: That was when I was about 6 years old. I liked flowers a lot, so I thought, "This seems like the life." As a kid, I liked to write. As an immigrant and as a child of revolution, my dad amused himself by saying, "You can be anything you want to be in the world: a lawyer or a doctor." My sister became a lawyer and I became a doctor, but neither of us practice.

Dr Topol: Music has been a big part of your life. When did that become rooted?

Dr Sabeti: That was not until graduate school. I have liked music my whole life and played a little piano as a kid. I went to concerts all the time. That was how I enjoyed spending my time. When I was in grad school, I had two American friends and we were in England together. They would play "fantasy band" all the time and make up band names and that kind of stuff. One night I said, "Why do you keep fantasy-banding? Why not just start a band?" They said they at least had to have a rhythm section, so the next day I bought a bass and that started my journey.

Dr Topol: These days, you are a lead singer and writer for a rock band. How often do you get involved with that?

Dr Sabeti: It wanes and waxes. It's not very conducive to faculty life. I dropped it for a while and then I had an accident and picked it up again. Music is great, because every once in a while your soul just wants to speak and you have an opportunity to do it. It's pretty sporadic, but I have been writing some music recently.

Dr Topol: Somehow or other, you landed at MIT.

Dr Sabeti: In the 6th grade, the idea of going to MIT got sparked. My math teacher showed us a 270 competition: The MIT mechanical engineering department has a contest in which everyone builds robots that compete against each other. I saw that video as a kid and thought, "I need to be there." I was locked onto MIT as my dream school since then.

Dr Topol: You also became a Rhodes Scholar and went to Oxford.

Dr Sabeti: It was a bizarre experience right after college to be in this wonderland that was Oxford, and a lot of existential crises happened right after college. It was a very informative and great experience.

Dr Topol: Were you already starting to get into the whole selection, mutation, and evolutionary biology by then?

Dr Sabeti: No. I think that is what made that happen. I had gone to MIT and I loved all the engineering, but I still thought that I was supposed to be a doctor. I had intended to go to medical school, but I got this scholarship on a lark. I was planning to go to medical school when I came back. Along the way, somehow, I ended up getting a PhD. It was an interesting experience there. They had a shorter PhD track. That was when I started doing that work, and it changed the direction of my life.

In the Middle of an Outbreak

Dr Topol: And then you went to medical school—a big commitment. When you started your career, did you know that you were going to be leading the charge to do genomic epidemiology of Ebola and Zika?

Dr Sabeti: Definitely not. Because I never intended to be a scientist, I didn't have a very specific path for what I wanted to do. I feel like I am on a scavenger hunt; I don't know exactly where it's going, but this path has captured my attention for some time.

Dr Topol: This is quite a hunt. Just what you did with Ebola—you were named a Time "Person of the Year" in 2014 and one of the 100 most influential people in the world. You went to West Africa with folks in your lab, and many other people you work with, to try to get the knowledge that was needed to titrate the horrendous Ebola epidemic. Can you tell us about that?

Dr Sabeti: Sure. For one thing, I am just a bit player. At the end of the day, the Ebola fighters were recognized for the work that we all did collectively. I was privileged to be one of the people who were named as an example, but it was a collective effort. To us, the seemingly small part that we played was that we naturally come from the genomics world—I cut my teeth on the Human Genome Project—where sharing data and an open feeling about science was just a given.

This is an outbreak that we found ourselves in the middle of because it came to the site where we were working in Africa. As we were trying to do what we could to help our collaborators and partners there, and to get attention, we started publishing science on this. We started releasing our data to the lab. What was interesting is that we decided we didn't care about getting recognition; we just wanted to get the data out to the world. Paradoxically, that is what got us attention. It was apparently unusual to share data openly as soon as you generated it. It became a call to the community.

We didn't care about recognition; we just wanted to get the data out to the world.

Dr Topol: You were putting your lives on the line to do this work. What was that like?

Dr Sabeti: To be honest, as a scientist, that is the risk you take. We were working on Lassa fever for some time. I have been quarantined before. We take risks, but they are very measured, calculated risks. Fundamentally, in all cases, it was the clinicians who became infected. We saw that across the board in the outbreak. As the researchers, we work in a very contained environment and we can isolate things very well. We are really in the service of the clinicians. We take risks, but for us, there was more risk of being in a car crash than being infected with Ebola. We were honored to be there to support them.

Dr Topol: More recently, you have been involved with the Zika virus story. Where do we stand with that?

Dr Sabeti: Zika is different. Ebola was a rapidly escalating outbreak. It was one of those viruses that can transmit from human to human with very acute infections and a very high fatality rate. It was a frightening event. Zika is less fatal. It does not transmit as easily. It usually involves mosquitoes. But it is a more challenging virus to battle; it's more widespread, and mosquitoes are hard to manage. The virus hides itself a little at low concentrations in the blood for short periods of time, so the diagnosis is challenging. But it becomes really important because of the effects it can have on pregnancy and on children born to mothers who have Zika. Zika causes a visceral reaction in all of us because it affects a vulnerable population that we all care about.

Please Play With Our Data

Dr Topol: In 2015 you gave a TED Talk on how we are going to deal with the next deadly virus. Can you summarize what you talked about at the time?

Dr Sabeti: That was in the middle of the Ebola outbreak. I had been asked to give a talk at TEDWomen. I just discussed what was on my mind at the time. I had not really thought out exactly what the message would be, and I did not know, necessarily, that it would be posted online. In fact, I sang during my talk. It was good in the room, but they wanted to cut it out and make it the right length [for TED Talks online]. I just had fun with it. The message was about outbreaks and how frightening they are. But it's a war that we can win—but that we win by collaboration. It is very different from other types of threats to humanity. That was what I felt—the power of human capacity and love to overcome these kinds of challenges.

Dr Topol: Actually, that is one thing that I wanted to underscore in our chat. You have assembled a global collaborative engine that is exquisite in the real-time sharing of data in these Sherlockian investigations of the mutations in a virus that account for its movement. Through sequencing, we have this remarkable tool. But if not for the fact that you could assemble all of the people and parts around the world, it might not work too well, right?

Dr Sabeti: Absolutely. I have great people in my lab who are incredibly collaborative. At every point, we think about how to reach out to others. It's been fun. A lot of our collaborations happened when we released our data to the Web. Some of the greatest leaders around the world reached out to us and said, "Was this a mistake? Did you want to release this?" We said, "No; please play with it."

That is how collaborations form. Historically, the community has been very siloed and competitive. But there is a coalition of the willing who are begging. It seemed that as soon as we did it, a group of people really glommed on. We were excited to have an opportunity to work together.

Dr Topol: It has been an inspiration because I have never seen such effusive sharing, with such rapidity, and so globally distributed. It's a new model, and I wish we could do that across the board in all research in medicine.

No Shortage of Outbreak Puzzles

Dr Topol: You are quite young and have accomplished quite a bit. You have a National Institutes of Health Innovator Award, a lab with 34 people, and a lot going on. Where do you go from here? What is the next phase of your career?

Dr Sabeti: There is a lot to do in outbreaks. We're really just scratching the surface. At this point, we're identifying the problem. We're at a very exciting place for the technology. If we leverage it the right way, we can have a powerful network that can respond very quickly. I am dedicated to that. That is something that I have wanted to do for a long time. I am dedicated to the students in my lab. I love my job and what I do.

And I have moved around. That scavenger hunt has taken me to other projects I am interested in. Throughout my career, I have gone into areas where the unexpected happens or I am not necessarily chasing the obvious next big thing. Nobody knew about the Lassa fever virus, but I felt strongly about it. There are a couple of those kinds of puzzles that I want to solve.

Dr Topol: Do you think you will get involved with the notion that we should routinely be using sequencing early to diagnosis infections?

Dr Sabeti: We are already doing that. Michael Wilson gave a great presentation this morning [at Future of Genomic Medicine X]. We are doing very similar stuff over in Boston in our clinic. We diagnosed a number of cases through a research approach, but well in advance of clinical diagnosis.

Dr Topol: Are you almost ready to start using that clinically?

Dr Sabeti: There are still things to be put in place, but it's powerful data. We are creating a CLIA lab and rolling that work out. It's happening across the country. The research centers that do a lot of sequencing are trying to create the ability to do that.

Dr Topol: Do you see the day where MinION sequencing USB sticks will be used for sequencing in remote parts of the world, and somehow getting the data through the Internet to find out the bug that way?

Dr Sabeti: Absolutely. MinION is a really powerful model. Obviously, all of these things need to continue to advance. We see that the genome technology is far exceeding Moore's Law. It shouldn't be too long until we all have one in our houses. Frankly, no one should ever go to the hospital if they have an infection. It becomes a cesspool; you get another infection. Eventually, it will get to that point. Even if we can just get them into the main clinics and big cities, it would make a big difference.

Dr Topol: George Orwell called the hospital "the antechamber to the tomb." He didn't know it was because of nosocomial infection.

I would love to talk to you for hours and I know that the folks who are listening are very intrigued because you have done so much to change the face of medicine in these global epidemics. We are indebted to you. Not only that, but you have trained so many fine people. We are thrilled to have had a chance to help the people in the medical community get to know you, because there are not many people like you, Pardis.

Thank you for joining us, and thank you to everyone listening. This has been a fun discussion and I think we will be hearing a lot more from Pardis in the years ahead. Thank you.


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