In this edition of FOCUS In Sound, we meet Dr. Pardis Sabeti, a geneticist who won a Burroughs Wellcome Fund Career Award in the Biomedical Sciences in 2005, and has gone on to enjoy a very distinguished career, culminating this year in being named one of the 100 Most Influential People in America by TIME Magazine. That recognition follows her inclusion as one of TIME’s Persons of the Year in 2014, celebrating her role as an Ebola fighter. Although Pardis has a long list of accomplishments in her years of research on the genetics of infectious diseases, for this edition of Focus In Sound we want to concentrate on the incredible story of her work on Ebola. I’m sure everyone will recall how Ebola nearly spun out of control in 2014, threatening a worldwide epidemic. That didn’t happen, fortunately, but the deadly disease claimed more than ten thousand lives in Sierra Leone, Guinea, and Liberia before it was finally reined in by the heroic efforts of thousands of dedicated workers.
By rapidly sequencing the genomes of the Ebola Virus Disease particles present in the blood of dozens of West African victims, Pardis and her colleagues at the Broad Institute in Massachusetts played a central role in determining where the outbreak came from, how it was evolving, where it was likely to go, and how to bring it under control.
Transcription of “Interview with Pardis Sabeti”
00;00;03;08 – 00;00;28;17
Ernie Hood
Welcome to Focus In Sound, the podcast series from the Focus newsletter published by the Burroughs Wellcome Fund. I’m your host, science writer Ernie Hood. In this edition of Focus In Sound, we meet Dr. Pardis Sabeti, a geneticist who won a Burroughs Wellcome Fund career award in the biomedical sciences in 2005 and has gone on to enjoy a very distinguished career.
00;00;28;29 – 00;01;00;07
Ernie Hood
Culminating this year in being named one of the 100 most influential people in America by Time magazine. That recognition follows her inclusion as one of Time’s Persons of the Year in 2014, celebrating her role as an Ebola fighter. Although Pardis has a long list of accomplishments in her years of research on the genetics of infectious diseases. For this edition of Focus In Sound, we want to concentrate on the incredible story of her work on Ebola.
00;01;00;20 – 00;01;32;24
Ernie Hood
I’m sure everyone will recall how Ebola nearly spun out of control in 2014, threatening a worldwide epidemic. That didn’t happen, fortunately, but the deadly disease claimed more than 10,000 lives in Sierra Leone, Guinea and Liberia before it was finally reined in by the heroic efforts of thousands of dedicated workers. By rapidly sequencing the genomes of the Ebola virus, disease particles present in the blood of dozens of West African victims.
00;01;33;05 – 00;02;01;23
Ernie Hood
Pardis and her colleagues at the Broad Institute in Massachusetts played a central role in determining where the outbreak came from, how it was evolving, where it was likely to go and how to bring it under control. Pardis did her undergraduate work in Eric Lander’s lab at M.I.T. She got her doctorate degree in biological anthropology at the University of Oxford, where she was a Rhodes scholar and her M.D. at Harvard Medical School.
00;02;02;07 – 00;02;32;08
Ernie Hood
Today, she is an associate professor at the Center for Systems Biology and the Department of Organismic Biology at Harvard. And her lab is closely associated with the Broad Institute, which is a partnership comprised of faculty from M.I.T., Harvard and the Harvard Associated Hospitals. Despite her incredibly busy research life in her spare time, she is the lead singer and songwriter for the indie rock band Thousand Days produced Sabeti.
00;02;32;08 – 00;02;33;23
Ernie Hood
Welcome to Focus In Sound.
00;02;34;00 – 00;02;35;27
Pardis Sabeti
Well, thank you. And really, it’s a real pleasure to be here.
00;02;37;01 – 00;02;47;23
Ernie Hood
When and how did it become evident that the 2014 Ebola outbreak was going to be unprecedented in scope? And how did you and your colleagues respond?
00;02;48;26 – 00;03;06;23
Pardis Sabeti
As soon as we noted in March of 2014 and saw the alert that there was Ebola in West Africa? In our minds, we we thought that it could be unprecedented in scope. And so anyone who works in other viruses the way we do, you have to almost always assume the worst. You prepare for the worst, hope for the best.
00;03;07;04 – 00;03;28;24
Pardis Sabeti
And I think that as soon as we saw it in March, we prepared for the worst and we became involved because the centers that we work in, in Sierra Leone and in Nigeria have been working with another deadly virus, lots of virus for many, many years now. And we knew that we were positioned to be sort of on the front lines if these outbreaks were to hit the two countries.
00;03;28;26 – 00;03;36;11
Pardis Sabeti
We moved to put surveillance in this country at the start of the outbreak began. And our collaborators there were involved in the first diagnoses in the two countries.
00;03;37;07 – 00;03;58;12
Ernie Hood
I see. Well, the theory used to be that Ebola outbreaks would burn hot for a while in a contained area, but would quickly run out of hosts to infect and would basically burn out. What happened to make this outbreak different? How did this one spin out of control for quite a while, spawning such dire projections?
00;03;59;05 – 00;04;25;06
Pardis Sabeti
A lot of people like to think about what a virus might do, but the fact of the matter is viruses are very variable in how they behave. In instances, there’s probably a lot of Ebola infections that don’t even make people ill. This is every human being is different. Every virus is a little bit different. And so it may well be that some infections of Ebola virus don’t cause illness and maybe that some caused illness that don’t lead to other human transmissions and that some has properties that make them burn out quickly.
00;04;25;06 – 00;04;50;00
Pardis Sabeti
But there’s always the possibility that a version of the virus will come out that’s more effective in spreading, in addition to the viruses being different and not being able to know. Is there a biological underpinning to this change? There’s also just the fact that this virus outbreak began in West Africa, where you have not only dense population but a lot of road networks, good infrastructure that allows many individuals to interact with each other.
00;04;50;05 – 00;05;03;11
Pardis Sabeti
And you’re at this interesting space where this outbreak began at the border of the countries that have a lot of crossover between them. So you have this instant ability to move across national borders and escalate very quickly.
00;05;04;07 – 00;05;09;27
Ernie Hood
So what were the major questions that you and your team were tracking on an ongoing basis?
00;05;10;24 – 00;05;38;16
Pardis Sabeti
My team and I have been in Sierra Leone and in Nigeria for many years studying another virus called lots of virus. And it’s also another deadly virus like Ebola with very high fatality rates and the possibility of transmission that makes it a bioterrorist threat. And in 2012, we actually published a paper and perspective piece in science called Emerging Disease or Diagnosis, where we began to suspect that not just lost the virus, but also possibly Ebola to viruses.
00;05;38;16 – 00;06;04;25
Pardis Sabeti
We we portray in that article are circulating in these populations. And we are genomics is we use genomic data both to understand biology but also importantly in diagnostics and surveillance. And so we’ve been posing that we could do much better at detecting microbes that are circulating in populations now to help those populations as well, to be able to head off possible global pandemics, because the more we know, the better off we are prepared.
00;06;05;06 – 00;06;12;21
Pardis Sabeti
We really, as a group, are focused on using genomics for diagnostics and surveillance, as well as to get to biology.
00;06;13;26 – 00;06;25;22
Ernie Hood
So why is a quick diagnosis of Ebola so important to the disease outcome, or is it ultimately more important for containing the overall outbreak itself?
00;06;27;03 – 00;06;49;26
Pardis Sabeti
I describe diagnosis as an enabling technology. It enables you to know who the individual is and so that you can get rapid treatment and enables you to identify cases so that you can help stop transmission. And in that way, as to your question, it really enables both of those things. Extraordinarily, the diagnosis of that first key piece of information, you have to have to get every other aspect of care and prevention going.
00;06;50;05 – 00;07;02;17
Pardis Sabeti
Many people have also shown that for different diseases, the sooner, you know, an individual’s status, experience, initiate treatment, the better the outcomes. And so it’s critical to the patient and it’s critical to stopping spread to others.
00;07;04;07 – 00;07;17;15
Ernie Hood
I see. Well, part is why is tracking the mutations of the virus on an ongoing basis in real time, which I know is a major element of your approach. Why was that so important?
00;07;18;26 – 00;07;42;26
Pardis Sabeti
The thing is the diagnostics that you need to detect Ebola virus, as well as the vaccines and therapies that are used to prevent and treat it, are all based on targeting an entity as a virus. And the foundation of that is its genome sequence, which drives its protein sequence, which drives and sort of makes it itself. And so if the virus changes, it can affect those things in ways to make them less effective.
00;07;43;15 – 00;08;02;18
Pardis Sabeti
You always have to know what you’re targeting. And so we need to be aware that viruses in particular mutate quite rapidly. RNA viruses like Ebola virus are going to continue to mutate. And if they mutate, then all of the things that we’ve designed to an old version of the virus may no longer work. And so it’s critical to track that in real time.
00;08;02;28 – 00;08;26;17
Pardis Sabeti
It’s also very important just to the biology and other understandings of the disease. Epidemiology and understanding is genomic information can provide all sorts of really intriguing insights into the virus and how it spreads. And so it’s both critical to these diagnostics, vaccines and therapies, but also to understand the disease and its progression and its spread so that we can launch better campaigns.
00;08;27;16 – 00;08;41;00
Ernie Hood
Pardis. How will your sequence sing of the Ebola genomes, as you did through the course of several months? How will that contribute to an improved response to the next epidemic?
00;08;42;17 – 00;09;05;14
Pardis Sabeti
I think that there’s a couple of things that we’re sort of focused on what we were doing. One was showing that there’s nothing that these data and that we need to provide it in real time and we have that opportunity. Modern medicine is at the point where the technology is there to make a major impact in outcomes to allow us to know what the viruses are tracking at any point, develop the most rapid diagnostics and care.
00;09;05;22 – 00;09;32;14
Pardis Sabeti
But the other part that was really important is getting the data out and collaborating with others. And that is one of the things that I think most are surprised to see how there aren’t really things in place to really allow for open, positive collaboration. And fundamentally, as another outbreak strikes. The only thing that we have going for us is that ability to communicate, interact and work positively, that we then turn and work in silos or at worst, against each other.
00;09;32;26 – 00;09;49;22
Pardis Sabeti
That’s where the virus thrives and succeeds. And so I think that it’s not just the fact that there’s nothing that beats good rapid data in real time, but also that we need to set up an infrastructure and a culture by which everyone is sharing data and working together.
00;09;50;17 – 00;10;06;10
Ernie Hood
So could you have done what you did even five years ago, or did we just recently reach a threshold in terms of sequencing rapidity, reduced cost and increased computational firepower that allowed you to do what you did?
00;10;07;18 – 00;10;24;15
Pardis Sabeti
I think that the technology is definitely in a sweet spot where the technology is there and expanding. But we were doing work like this even five years ago, not within an outbreak, but within cases of loss of viruses in generating sequences. Lots of eyes for a long time. I think that the technology hasn’t been there and there have been some good instances.
00;10;24;25 – 00;10;40;05
Pardis Sabeti
But I think again, it’s that the technology is now very much there and this is about getting the culture to match the technology, to get us to have an understanding that data in real time research in real time is the way that we can prevent these things from escalating.
00;10;40;21 – 00;11;07;06
Ernie Hood
Pardis. We talked a little bit about the importance of mutation in in the Ebola picture. And I wanted to read you a quote from Richard Preston’s article in The New Yorker from October 2014. He, of course, was the author of The Hot Zone. And he wrote, and I quote, As Ebola enters a deepening relationship with the human species, the question of how it is mutating has significance for every person on earth.
00;11;07;14 – 00;11;10;06
Ernie Hood
Would you agree with that rather alarming statement?
00;11;11;09 – 00;11;35;16
Pardis Sabeti
Yeah, I don’t consider it an alarming statement. I consider it a very practical statement. And I absolutely agree that you always need to pay attention to things. And I have a lot of different mottoes and lines that come up over this. But I would say, don’t be scared, be prepared. We’re not saying these kinds of comments to alarm individuals in a lot of the ways that this has been interpreted as in the virus will go airborne tomorrow and all sorts of things.
00;11;35;24 – 00;11;58;05
Pardis Sabeti
Those are dramatic statements. But saying that a virus is changing and we need to pay attention to those changes is a very practical and important comment to make. We know viruses mutate. That’s what they do. All organisms do. And they have a very high rate of doing so. And most of those mutations will have no impact. But the fact is, the more we know, the more we can head off a single mutation that might have an impact.
00;11;58;08 – 00;12;03;17
Pardis Sabeti
I think that it’s important to think about that. Absolutely. We need to know how the virus is sitting at all times.
00;12;04;05 – 00;12;33;02
Ernie Hood
Produce As recently as last month, some new findings about Ebola and the 2014 epidemic were published. And I’d like to get your reaction. A group studying the recent Ebola outbreak in Mali showed that the Ebola virus is not undergoing rapid evolution in humans, with no major change in modes of transmission, suggesting that current methods of prevention, containment and treatment apparently are appropriate.
00;12;33;03 – 00;12;36;01
Ernie Hood
How do you feel about that piece of work that just came out?
00;12;36;20 – 00;12;58;03
Pardis Sabeti
Yeah, this is a paper analyzing for genomes from Mali and adding them to the 99 genomes that we sequenced and looking at an overall picture in the data actually that they used in the paper and the analysis they performed gave is very similar and gave very similar results, which is that the virus is mutating. It’s mutating at a rate similar to what is done in the past, and that’s what it also says.
00;12;58;03 – 00;13;19;24
Pardis Sabeti
It has a fundamental change in how it’s mutating. But what we said and what their data also supports is that there are many mutations that occur, which happens when an outbreak is allowed to have this many transmission. We think that it is very consistent with our our results as well. But it’s a matter of interpretation and it’s important to kind of stop people from saying, oh, the virus will go airborne or change fundamentally.
00;13;20;04 – 00;13;40;19
Pardis Sabeti
But we neither we nor they can say anything about whether or not there’s a biological impacted anything, mutations that accumulated. And at this point, there’s been hundreds of mutations that have accumulated. I think that it’s very important that we’re neither complacent nor alarmist, that we just continue to be very, very vigilant in what we do. And I believe that every one of those mutations should be investigated.
00;13;40;27 – 00;14;01;28
Pardis Sabeti
We don’t believe that this virus is doing anything fundamentally different. But all viruses continue to mutate and their mutation rates are much more rapid than, say, mammals like us. And so we have to pay extra ordinary attention to what’s going on. And and it’s very important, again, that we are neither complacent nor alarmist and that we continue to be vigilant and get down to zero cases.
00;14;03;02 – 00;14;08;16
Ernie Hood
I see. So what you’re saying really is that the jury is still out and vigilance is still very important.
00;14;09;20 – 00;14;18;21
Pardis Sabeti
Absolutely. Yes, absolutely. We should be all working collaboratively, collectively over time to understand what the process is. We get to zero.
00;14;19;26 – 00;14;33;07
Ernie Hood
So, Pardis, what are you and your colleagues working on now? Are you developing a method perhaps for rapid onsite Ebola diagnosis? What impact would a capability like that have?
00;14;34;14 – 00;14;51;18
Pardis Sabeti
Would you remember of things right now? And one of them is working very closely with our partners in Sierra Leone, Senegal, and then in Nigeria to make sure that they’ll have sequencing capacity for the work that we did in collaboration with them, that doing the sequencing to us now have going on in West Africa and that’s critically important.
00;14;51;24 – 00;15;15;19
Pardis Sabeti
There’s a number of other groups working with the families. We have a great paper that our colleagues and customers led coming out with the sequences out of Liberia. The more that we can move to doing sequencing on ground and capturing, the better off we all will be for global surveillance. And that’s one that it with at least all of our sequencing protocols for the community, are being used by others to do sequencing in-house.
00;15;15;19 – 00;15;39;29
Pardis Sabeti
We’ve not done a lot of work in cooperation with our partners, actually in our clinical data analysis. And we now have all that we’ve done showing how well we can start predicting prognosis based on clinical data and the policies. Again, the very important thing is we need more data. And my group personally, like all over the world, there are extraordinary people who are poised and ready to take advantage of any data and to come up with new insights.
00;15;39;29 – 00;15;46;10
Pardis Sabeti
And we need to make sure the community that data is available so that more science can move forward.
00;15;46;14 – 00;15;58;23
Ernie Hood
I see that. That sounds very promising. And it sounds like if there is another outbreak, significant outbreak, that is, that you’ll be able to turn around the sequencing much more rapidly.
00;15;59;16 – 00;16;20;24
Pardis Sabeti
I hope so. I mean, I think that there’s definitely progress in that direction. But I’ve seen a lot of heartwarming examples of collaboration and partnership and movement forward. But there’s, I think, a very long road ahead. And I think we should never be complacent. I think that we need to continue to develop that culture, develop the infrastructure and partner, most importantly, with our colleagues around the world.
00;16;21;02 – 00;16;43;14
Pardis Sabeti
This is a place where us as American scientists are not the ones that are leading anything. We need to partner with the local communities to make sure they’re best placed because they’re the hope for the future. They diagnosed the first cases in Sierra Leone and Nigeria. Without them, we would be in a very different position. And I think that is one of the extraordinary messages from this, which is the better we partner, the more strength we’ll have across the world.
00;16;43;24 – 00;17;07;08
Ernie Hood
Bernice, I know that beyond the compelling scientific questions at play here, this has been an intensely emotional experience for you and your people, including the deaths from Ebola of five of your close friends and colleagues. What has the whole experience been like? How has the emotional aspect affected your approach? Has it? Has it affected it in any way?
00;17;07;28 – 00;17;29;16
Pardis Sabeti
I think there’s no way that it could affect the way we approach. I think that’s what I would say, is that seeing the individuals that we work with in such risk, seeing the slow response that allowed this virus to escalate the way it did, it gave me this sense of purpose as well as a fight. And then my feeling it’s that it can never happen again.
00;17;29;17 – 00;17;49;20
Pardis Sabeti
And for all of those individuals, I think we as a global community owe it to all of those individuals who sacrificed their lives in this outbreak to learn something from this and work together in a very major way. We are continuing to feel that we are personally connected to all those individuals and to their families and that we are in this fight with them all.
00;17;50;03 – 00;17;54;14
Pardis Sabeti
And so I feel a great sense of purpose and resolve that we need to continue.
00;17;55;29 – 00;18;20;03
Ernie Hood
Well, you are certainly very much an inspirational example for all of us. Pardis. Pardis. I know that one outlet for your emotional response to the experience was to write a song in tribute to your fallen colleagues called One Truth. Would you tell us about the song and where it came from and what your you were trying to express in the music itself?
00;18;20;13 – 00;18;47;05
Pardis Sabeti
You know, I am a singer and a musician, the band, but a lot of times it’s not something I’m planning on doing or trying to do at any point. A lot of times things come out organically for me and as it turned out, during the summer that we were the outbreak, it happened. We were supposed to have our colleagues from Sierra Leone, Nigeria and Senegal with us doing a summer training program for two months and our colleagues from Sierra Leone couldn’t attend, but those are in Nigeria and Senegal did.
00;18;47;16 – 00;19;07;26
Pardis Sabeti
They have come year after year and when they come, we always have a sort of a tradition of singing together on a weekly basis and going and recording together. And so this is a wonderful collaboration that we have both in science and in music. But it was interesting because that was a one standing thing that we had going amidst the chaos around us.
00;19;08;02 – 00;19;29;05
Pardis Sabeti
And of course, you think you know that you should stop doing these things because you have to focus. But I’m glad that we did, because I think that sometimes you need this one outlet over the two week period was probably the height of the outbreak for us for a short period of time. We’d heard that a number of the nurses had been exposed to the kind of work at the hospital and soon after a number of them died.
00;19;29;14 – 00;19;50;17
Pardis Sabeti
And then Dr. Khan, our close colleague and the head physician at Kenema, also contracted Ebola. And then in that same time frame, our colleague Christian Hapi, diagnosed the first case of Ebola in Nigeria. So we were sitting in this period of immense devastation on the precipice of a potential cataclysm as Ebola might have struck a city of 20 million.
00;19;51;02 – 00;20;24;17
Pardis Sabeti
There is so much going on there. There was so much stress that we all felt that it was kind of unbelievable to sit in this room together to sing. But in that moment of great despair, there is this song that kind of came out of hope, and it just was born from the light and the smiles and the glances, as well as the fear and the despair of the individuals in this room and the lyrics of the song that kind of just came out of me while we were all singing together was the song is sort of about looking at the world and not understanding where you are, what your purpose is, why you’re here,
00;20;24;27 – 00;20;45;22
Pardis Sabeti
and seeing a room with Christian women, with Muslim women, with people from all backgrounds and saying, I don’t understand what what we’re doing here, but I have a lifetime to one truth that I’m alive and so are you. We are here. We are the proof. Yes, we’re here together. And it sort of says, you know, we write, we laugh, cry, we pray.
00;20;46;07 – 00;21;10;22
Pardis Sabeti
There’s a hunger in us that will never die. And I’m in this fight with you always. And that is really the sense I found myself speaking to our colleagues in Sierra Leone across the ocean, saying, I’m here with you always. We are. We are all here in this fight with you always. And it was an amazing moment. I’m so thankful that I have music in my life to be able to to give a voice to the feelings that are within me and within others.
00;21;10;22 – 00;21;22;28
Pardis Sabeti
And we kind of continue on with that. And those words will always ring true to me that I am in this fight with you always. And that’s where I hope to always be with these extraordinary individuals who sacrificed their lives on the frontlines.
00;21;23;29 – 00;21;49;10
Ernie Hood
Well, this is quite a moving tribute, and we certainly want to alert our listeners that there is a very compelling video of the song available on YouTube so they can just probably Google one truth and get right to that. And with your permission, we would like to end this podcast by sharing the song One Truth with our listeners.
00;21;49;10 – 00;21;50;23
Pardis Sabeti
I would be honored. Thank you.
00;21;51;25 – 00;22;00;09
Ernie Hood
Thanks. And Pardis, we wish you the best of luck for continued success in your very impressive and vitally important scientific pursuits.
00;22;01;12 – 00;22;03;02
Pardis Sabeti
Thank you so much. I really appreciate it.
00;22;03;23 – 00;22;13;06
Ernie Hood
Thank you for joining us on this edition of Focus In Sound. And now, please enjoy One Truth by thousand Days featuring Pardis.
00;22;13;15 – 00;23;21;29
Song : One Truth by Thousand Days
Getting sitting here in this room watching everything. You do not know how this city was at the same the sound like that. But you went on to write here and today and yay, yay, yay! We are gathered on the ground waiting for a sign to write, looking for the answers in the starry sky. But we were all alone And we are there speaking.
00;23;23;18 – 00;25;13;02
Song : One Truth by Thousand Days
Yes, yes, yes, yes, yes, yes, yes. Yay, yay, yes, that’s right. No, you’re right. We we and be friends. And we are making history. And we signed. We never got inspired by big. Yes, yes. Yay, Yay! Yeah. I like timelines in my time for quite a long time. And why?
