Okay, so let me set the stage for your audience. 2014 was in the heart and the heat of the Ebola outbreak in West Africa. So basically in March of 2014, an outbreak was declared in Guinea. Ebola hadn't really been seen in West Africa before and was quite terrifying for a lot of people because by the time they picked up that this was Ebola that was circulating, this mystery disease, it had already reached a large part of the country. We were working in Sierra Leone at the time. My team at Harvard University and our colleagues at Tulane and partners in Nigeria and Sierra Leone were all working together on another virus called Lassa virus. That's another hemorrhagic fever virus that circulates in that part of the world. So we recognized in both of those countries that there is now a risk of Ebola circulating in the region and if it was to come to those countries, our hospitals would see cases. So we quickly set up diagnostic testing there and the teams that we work with there on the ground were the first to detect it in Sierra Leone and in Nigeria. The more we set up testing, the more we identified cases and we started to realize that this idea of an emerging disease is not exactly the right idea, that this isn't emerging diseases. These are just emergent detection of diseases that are circulating. Right? I think Donald Trump once said, you know, if you don't test for COVID, you don't have it. And I think that's, you know, that's actually quite poignant. That's a true fact. If you don't test for something, you never see it. And as soon as you set up testing, you start seeing it. And that's basically what we were doing with these hospitals. And we started picking up more and more cases. You assume that every patient with Ebola is bleeding, you know, out of every orifice in this dramatic way that you see in Hollywood, right? Because the only time anybody bothers to run an Ebola test is when that's happening, right? So, you get what you look for. If you only look for Ebola in patients that look like that, you will only see Ebola in patients that look like that. And so he said if you looked at more people, you would see that actually a lot of other people are walking around with Ebola and you wouldn't know it.
Okay. So you decide that this is a problem worth solving. I mean, where do you even start with something like that? It's, you know, it's, I mean, do you have to build something new? Do you plug into existing systems? How much, what is the balance between those two things?
Okay. Well, I'll tell you how we started. We started small. We started with my Harvard startup funds and a call to Christian Happi, my colleague in Nigeria. I actually was a human geneticist mainly, although I always worked in infectious disease. And I developed an algorithm that could mine the human genome and identify signals of human adaptation. You may have heard of a story about sickle cell anemia and how it became common because having one copy of that trait protects you from malaria. So it's a classic signal of like adaptation that we adapted to malaria by having the sickle cell trait start to emerge. So I was studying that process of like traits that help humans survive. And when I was studying the human genome, the signal I found that was the strongest was a gene called LARG that was critical for entry of Lassa virus. And it was under evolution in Nigeria where Lassa is found. And so that made me be like, wait, what is this disease? Why have I never heard of it even having gone to medical school? And why is it one of the major drivers of our evolution? So I set out to just ask a question. Does having this trait protect you from Lassa? Not really knowing that much about the disease, but then when we set out and started working in Abuja, Nigeria, we realized, oh, this disease is everywhere. There's a ton of cases and it's not being detected because there's no diagnostics in country. It wasn't like, though there was an alert that Lassa was a problem. It was a weird signal I found in the human genome that made me be like, "Huh, could this disease be more important than I know anything about at least?" And it looked like that was the case. And so over time we started to study it more and more and we just went to this rural hospital in Nigeria. We started to help them set up capacity to test more cases and identify what could be going on. I spent seven years helping the community just start developing infrastructure to test for Lassa before I ever started any research questions because we just had to get the foundations and the fundamentals there. But what we found was that the more we set up capabilities, the more cases we found. And the hospital used to kind of be described as a cemetery because you would go there and they didn't have diagnosis and they didn't have good treatment. So they kind of just were there to witness the ravage that the disease did to you without any solutions. But once you started to set up diagnostic testing and got in early treatments, things transformed and so we saw a transformation at the hospitals. So we ended up writing a paper called "Emerging Disease or Diagnosis?" like asking the question, is this emerging disease or emergent detection of diseases circulating? And in that we basically said, hey, if we actually helped local hospitals set up the capabilities to test for the things that are circulating in their regions, we would not only help those communities and those doctors on the front lines, we would create sentinel sites for the whole world. And that was the premise. And so it is small, it's a small effort. It was really start with the local communities, start with the clinicians on the front line, meet them where they're at with the needs they had. And then from it grew a much bigger understanding of a problem.
This kind of different view, I suppose, of disease response, you know, one is responding to the disease, one is setting up a sentinel network. So responding to the signal, you know, trying to get the signal before it happened. How much of your hunch was correct? What ended up surprising you in that?
Honestly, nothing. I'm trying to think. Actually, I think we, I'm trying to think what did we not know? We actually knew everything. Like we literally, and that's the part where it's hard to explain because people are like, "Oh, how did you know COVID was coming?" I'm like, "Because you're just in the field and it's obvious. It's a matter of time before one strain gets away and kind of goes out of control." We wrote a paper in, you know, 2012 where we said Ebola is circulating. It's circulating all over Africa, all over that region of Africa, West and Central Africa. There's obvious evidence for it. You just have to look, you know, we just had to look. So, none of it was actually a surprise. And that's the frustrating part because we see all of that and we know exactly what needs to be done. And we see that another outbreak is coming and a major pandemic is coming because it's obvious because we're in an environment in which these viruses are having more and more opportunities to transmit from human to human than ever in history. That, you know, we are reducing our surveillance and our countermeasure capacity and we're increasing in a world where, you know, so much of this is about how we work. I just connected with somebody named Josh Akey at University of Michigan that's telling me fascinating things about how humans engage when they're sick and they're not telling each other when they're sick. So we have less trust in each other so we're also going to be walking around hiding our infections from each other and so it's just a matter of time. Nothing is really truly a surprise and we really need to start working now to deal with that better because otherwise we're only going to finally decide that we need to work on it again when we're in the middle of another pandemic and this time it won't be one that half the population can ride off, right? Like it will be one that we will all have to contend with because it could be fatal to major swaths of the population.
So you set out to, you're like, right, we have this problem, we can see it, this problem, we're going to try to do something about it. So in 2020 you launched Sentinel through the Audacious Project. The timing of this was amazing. The fact that you launched it in February 2020 before anyone had heard of COVID. Take us up from that moment, from 2020 up to the current day. You know, you've launched this thing. It's formal. It exists. What does Sentinel look like in 2026? What have you built?
Yeah. So, what's interesting about it is the first time we got like significant funding on this premise of, you know, an early warning system for pandemics was actually launched in March of 2014. And that was literally like we had the thing in early March and late March we were like setting up the diagnostics for Ebola and we were in it. And then we got the Audacious Prize in, like we submitted the application December 2019, got it in February 2020, and then March we were in the COVID pandemic and so I was pretty, I was like, I was submitting grants. Yeah. Yeah. Well, yeah. Now we got this MacArthur prize and I'm glad to say that like, you know, although I do feel like I'm in a pandemic, I feel like there is something brewing and we're just like not, we don't know yet, but it's going to sideline us. So yeah. So it is a little bit of like watch out if we ever get a grant we might be in trouble. And the interesting thing is, and the other way I describe it is, you can't always get what you want, but sometimes you get what you need. Essentially, Sentinel is forged through about two decades of work together with Christian Happi and I partnering on Lassa fever and malaria before that. The simple premise is that, you know, detect, connect, and power. You need to detect pathogens wherever they occur, you know, either characterizing them in genome centers or at home testing for things that are circulating threats. And also getting just everybody on their phone saying, you know, I see a cluster of symptoms or I have these symptoms and using that information to get them what they need. Then you need to connect all that because of the communicable nature of infectious diseases, that it spreads between person to person. It spreads from village to village. You have to connect that data for it to be meaningful. Right? Finding out that three people that went to this party, you know, each go somewhere and find out they have a disease or one of them does and the other ones don't, it doesn't get you anywhere. But once you see, oh, there's a cluster happening here, that's where you start to really understand how you get that intelligence that's going to help you respond quickly. There's something I often say which is that, you know, unlike other existential threats to humanity where, you know, you can tell people like you should vote in America, but unless you live in a swing state, you can't really convince them it matters. Pathogens, you know, have what we call exponential spread, right? So like one case can lead to two to four to eight. And so because of that idea of exponential spread, a single person can launch a pandemic and that means every person can stop it. Every person truly matters. There's like, there's no way around it. Like one person missed is, we're in a world of danger. And so within that context, we really think we have to empower every actor in the system to get the information that they need and to do the work that they need to stop the pandemic. And so so much of what we do is built around education.
I love that. All right, this has worked, right? I mean, I think Sentinel played a fairly large role, obviously not the only role, but a fairly large role in reducing the impact of the Marburg outbreak in Rwanda. Tell us a little bit about that. How did you use it? Why did it work? What went right?
Well, I mean, I think the biggest thing that went right is that we were there at the service of Rwanda, right? That's the thing that we always do. It's really important. It's like people sort of ask, like, how do you work well in countries? I'm like, we just ask them, what do you need from us? Right? That's how we work. We never try to come in and say like, we've got this, but that's not what we do. We, you know, we identify and find like all the terrific people in country who are leading the charge and we just provide them with resources to do what they're doing as best as they can. Christian's team in Nigeria are the ones that roll out to the different sites and work with them. For the most part, we also go there, but their team is the real leader in that. They went on ground, they supported the sequencing efforts of the country, helped them kind of establish reporting and identify what was going on and just worked closely with them to help them think about how to stop the outbreak, how to identify cases, how to understand transmission. And you know what was really great about that is that they stopped transmission quickly and they also had a, you know, got a very low fatality rate because they were able to identify cases quickly and help serve those patients and stop them from spreading to other people. The current outbreak in the DRC, I think, is now the fastest growing outbreak ever for Ebola and I think it has either become or is very close to becoming the second largest outbreak. And I think the UN and the WHO is warning that it could, you know, if it continues at this pace, it's going to become the largest. So what went wrong? Why did we not catch that? How does it go right in somewhere like Rwanda, but here we look like we've got a real problem on our hands.
Well, I mean, it's honestly a perfect storm. Basically, in regions where there's conflict, there's a dual problem, which is that conflict creates all of the circumstances that will lead an outbreak to escalate. You know, displaced populations, poor sanitation, you know, like lots of chaos, decay in health care systems, all of that is what's going to be more likely to cause an outbreak to happen, but then also more likely to cause an outbreak to go undetected. And so, as the world seems to be increasingly moving to kind of a constant drum of conflicts, we're really going to have to come to terms with that, of like how to build systems to weather those conflicts and not allow outbreaks to escalate. So, probably the biggest reason why we're in the circumstance we are in is the conflicts in the DRC. But in addition to that, there was, you know, the loss of a lot of global health funding, the removal of a lot of peacekeepers on the ground, the continual like difficulties in funding science and funding vaccine work, you know, funding diagnostic work. So it is a real perfect storm. And it's hard to see the way out without real international cooperation, which is something that is not great right now.
All right. Look, intuitively, I think people understand, you know, it's very, very difficult to provide health services or provide any kind of service in a conflict. I think what maybe is less obvious or less intuitive is, you know, this slashing of foreign aid and global health cuts that happened, that started about 18 months ago and, you know, we're really now starting to see that come through. What does that actually look like on the ground? What did that look like specifically for Sentinel?
Yeah, I mean, I think so much disappeared from the network. A lot of, you know, frontline testing, health workers, peacekeepers, like all of those things. I had colleagues on the ground who basically worked in DRC very successfully for many, many years who now, there were kidnappings. There were greater risks. Essentially, there was a sense that there's now no international force to protect the region. And so you had a lot more gangs and warfare and sort of terrorist acts that were happening all around. And so a lot of people lost the funding to work and a lot of people who had funding to work could just no longer viably work there. It's literally no surprise that this happened because of the number of people that I knew that either were withdrawn or had to withdraw based on what was going on.
All right. When you strip this funding away, which is exactly what has happened, what is still kind of left standing on its own? Like what is there in DRC right now? What does the response actually look like on the ground?
I mean, honestly, I would love to, I like to be honest with what I know and what I don't know. I don't have the best sense of it, so I'm not in the WHO, so I don't have visibility to anything outside of our own group. So I can tell you what our own team has been doing. Our own team has been sending people to the front lines kind of in a rotation supporting the teams on the ground. But there's a lot of challenges and restrictions that are more difficult than before. And usually our teams in Nigeria wouldn't think twice about going on the ground and our teams from the US would be able to join. Those things are all just a lot, there's a lot more friction to every part of that. But it's definitely, you know, you had said actually like, oh, it's something that's in the news and everyone knows it's in the news. I'm like, is it really? Like, when was the last time Ebola was on the front page? You know, for what we're looking at, I mean, it's not really in the news. There's so much other news. So it's, there's just, it's not really being followed that closely and there's a lot we don't know about how the outbreak will escalate.
