Whitney Pennington Rodgers: Hello everyone, and welcome back to TEDConnects. If you’re (Audio feedback) joining us for the — If you’re joining us for the first time, we’ve been bringing interviews all week with some of the world’s greatest minds to help us make sense of this unprecedented moment that we’re living in. I’m Whitney Pennington Rodgers, TED’s current affairs curator and one of your hosts. This week, thousands of you have tuned in to these live events each day, and hundreds of thousands more have watched these interviews after the fact. We’ve really loved seeing your questions. They add so much to these conversations. So please keep them coming. In a few minutes, I’m going to disappear to work with our team behind the scenes to monitor our Facebook feed, where you can leave some of your questions. I’ll work to figure out which ones are the ones that we can bring back to our guest, and I will ask as many of them as I can during the live interview.
Today, we’re going to be touching on a subject that I think is top of mind for a lot of people, so I’d like to turn things over to the head of TED, Chris Anderson, who will introduce today’s guest. Chris Anderson: Hello. WPR: Hi Chris. How’s it going today? CA: Nice to see you again, Whitney. It’s going pretty good here. Amazing days. WPR: That’s good. That’s great. We have sunshine here in the Northeast, which is nice. CA: So look, I am excited to introduce this guest, because I’ve known Seth Berkley for a long time. I count him as a friend. He’s a man who has really devoted his life to the most profound questions about public health. Vaccines are extraordinary. They save millions of lives. The quest for a coronavirus vaccine is, I think, the biggest single question that the world faces now if we’re going to get out of this. So it’s just a delight to welcome Dr. Seth Berkley to TED Connects. Come on in, Seth. Seth Berkley: Good to see you there, Chris, and delighted to be with you and all of the TED community. CA: Well, so look, on Tuesday, Bill Gates was here, and he mentioned that your organization, Gavi, is really at the heart of the quest for a vaccine.
So tell us a bit — what is Gavi? SB: So Chris, thank you for that. What’s interesting is that 20 years ago — we just celebrated our 20th anniversary — there were all these powerful new vaccines that were being used in wealthy countries, and the challenge is, they weren’t getting to the places that they could make the most difference: the developing world. So Gavi was formed as an alliance — WHO, the World Bank, the Gates Foundation, UNICEF — all working together to try to bring these vaccines to the developing world. And it’s been very successful. We’ve launched 433 new vaccines in the most difficult countries in the world, in the Somalias and Yemens and DRCs and Nigerias. But we’ve also set up emergency stockpiles for outbreak-based vaccines, so if there’s an outbreak anywhere in the world of yellow fever or of things like cholera or meningitis and now Ebola, we have vaccines that are available to do that.
And the last thing we are trying to do is build the health systems out to deliver these vaccines, but also to make sure that we can pay attention to new diseases that pop up in different parts of the world. CA: And just give us a sense of the scale of this. How many vaccines do you distribute in a given year? And how many lives do you believe that that may be saving? SB: So, let me give you a macro number. We’ve immunized more than 760 million additional children — 760 million additional children — and prevented more than 13 million deaths. In an average year, we give about a half a billion doses because we started out with six diseases, but now we vaccinate against 18 different diseases. CA: Yeah, the scale of that is incredible, and amidst all the bad news that’s happening, it’s kind of amazing that this intervention can save so many lives. I mean, help us understand what a vaccine is. SB: So, the original idea, the word “vaccine,” comes from “vaca,” or cow.
And the observation made in the 1700s was that milkmaids had beautiful skin, whereas everybody else had pockmarks from having gotten over smallpox. And the concept was that she was getting infected with a zoonosis, that is, with naturally occurring cowpox, not smallpox. That then protected against smallpox. And it was tested in those days: Could you artificially do that? They of course didn’t understand virology, they didn’t understand any of those issues. But what a vaccine is is something that you give to artificially stimulate the immune system, hopefully to not make you sick. But then later on, when the body comes in contact with the real disease, it thinks it’s already seen it and it is able to fight it off without making the person sick. CA: I mean, it’s kind of a miraculous thing to me that they work that way, that your body is always there looking for these threats. And a vaccine, I guess, the body perceives it as a threat, and therefore arms itself against that threat, right?
And that’s what gives the protection. So, is that why some people are sort of — irrationally, I will say — irrationally scared of vaccines and feel that they may be dangerous, because they are a kind of threat that you’re putting into your body in a very subtle way? SB: Well, of course, when this first started, there were two ways to make vaccines. You could grind them up and inject them, so-called “whole killed vaccines.” So you took organisms and you got an immune response, and sometimes those organisms, even though they were dead, gave you a pretty whopping immune response: your arms were sore, you got fevers. Then we moved to these weakened live viruses, and frankly, those are the best vaccines. That’s what measles is. That’s what yellow fever is. These are weakened viruses. They don’t give you disease, but because they look like the natural viruses, your body gets protection and, frankly, you get protection for your whole life.
Today, because people are worried about side effects, we’ve begun to use molecular biology and use little bits of it, and therefore, it’s moved forward. But the reason people are mostly scared is because, frankly, vaccines have been so successful. You don’t expect, if you have a child or two children, that those children are going to die of these diseases, unlike in the past, when three or four out of your five or six or seven kids would die. So today, people think, well, gee, these diseases aren’t around, they’re not that bad and, by the way, if I’m injecting these things, maybe they’re not organic, maybe it’ll make my child cry, maybe it’ll make them sick, and I don’t need to do it. And that’s the challenge. You don’t want to scare people to death on how bad these diseases can be, but at the same time, you want them to understand that these diseases are serious and can cause really bad disease and sequela. CA: So yesterday, you issued a really powerful call for this massive, coordinated global response to tackle the search for a coronavirus vaccine.
We’re going to come that in a bit, because I think that’s a very exciting topic. But I think we need some more background first. I want to go back five years to when you stood on the TED stage and you held up two candidate Ebola vaccines. This was just a few months after Ebola had been terrifying the world. It was basically amazing how quickly those vaccines had been developed. What happened to them? SB: It’s a great question, and let me tell a little bit of the story, but at the end, there were two vaccines. One, it turned out, couldn’t finish its testing, because the epidemic died down. The other one was fully tested. It had a hundred percent efficacy. We then went on to work with manufacturers to produce that vaccine, at least temporarily, in an investigational form, just in case there were more outbreaks. There were, and those are the vaccine doses that we’ve used in the DRC. In the last two outbreaks, 280,000 people have been vaccinated with this experimental vaccine, and today, there is a licensed vaccine, and we are now procuring a global stockpile of a half a million doses.
But let me just say, Chris, the reason they came so quickly at that moment is, after September 11th, there was concern in the US about bioterrorism. Remember, there were anthrax attacks. And so what happened was there was a list of agents, and Ebola, for a short time, was on that list of agents, so people started making vaccines, and later on, they decided that was not necessarily a good bioterrorism agent, so they dropped that off the list. But in the freezers were vaccines that had been started, and they were dusted off, and that’s why we could move so quickly in that moment. CA: And yet, how long was it from that moment on the TED stage with the candidate vaccine to actual deployment? SB: So, what happened was, the epidemic began to go down. The clinical trial I told you about was done. It was a heroic clinical trial done by WHO, and it showed that it had these results. That epidemic then stopped. We didn’t know if there were going to be more epidemics.
It took another number of years to finish the work on the vaccine to make sure it was pure, to figure out how to manufacture it at scale. It’s during that period that we put vaccine away and had it available in case there were other outbreaks. And it turned out, there were three outbreaks. One went away quickly, but there were two. I was there on day 13 of the second outbreak. We injected the vaccine, cases went up, then they went down, and controlled it. And then this DRC in North Kivu outbreak, which really was terrible because it was in a war zone. And that’s the one where we’ve been not only vaccinating in DRC but in surrounding countries. By the way, that is now, I believe, day 38 or 39 out of the 42 necessary to say it’s over. We hope it is. And that would be, again, an enormous example of what vaccines can do, even in a very difficult setting. CA: And yet, in one way, Seth, it’s kind of shocking that the outbreak that happened at the start of 2015, end of 2014, that it happened at all, because the world has known about Ebola for a long time.
It’s been sequenced and so forth. A vaccine could have been developed and got ready for a possible outbreak. Why didn’t that happen? SB: Well, there had been 26 outbreaks before, but each one of them was small — couple of hundred people or a couple of dozen people — in the poorest African countries in the world. There was no market for it. People didn’t know how to test it because they would just pop up and then go away. And so even though it was obviously a disease that potentially could spread, it had never really spread before. Of course, in West Africa, they didn’t have a good surveillance system; it spread for three months before people identified that it was Ebola, and by that time, it was too late. It had spread. What’s important about that lesson is that then caused huge disruption across Africa, across the world, because cases went to other places. And the challenge then was, and the reason we had to step in, was because there still was no market.
So the Gavi board said, “We will put out 390 million dollars. We’ll put it out there and tell companies, we’re open for business, we’ll create a market, we’ll buy the vaccine.” And that led to companies being willing to finish the investment to get us to where we are today. CA: Right, right. So it’s a real paradox, right? In a way, the very thing that makes vaccines so extraordinary, that once they’re developed, they are so cheap to administer, for a few dollars, I guess, you can administer this dose that will save someone maybe a lifetime of illness or save their lives, and yet so much of medical research and invention and development is done by companies who need to see a revenue stream, and so they don’t see it from those tiny little cheap things that might save a lot of lives. So it’s a real market failure that in this circumstance now — That’s one of the things I guess you’re thinking hard about, how on earth do we get round and avoid that market failure crippling the response this time? SB: Well, first of all, one of the reasons Bill Gates likes vaccines is, in a sense, it’s a little bit like software creation.
You put a lot of money and effort into creating it, but once you’ve got it, you can produce it pretty cheaply and use it in different places around the world. I don’t want to beat up the pharmaceutical industry here because they were heroic in Ebola, but I think realistically, they are for-profit entities, and they have to say to their shareholders, “Somebody’s going to pay for this, or we’re going to do it as a charitable thing.” And if we do it as a charitable thing, they can’t keep doing it. Since then, there is a new initiative called CEPI, the Coalition for Epidemic Preparedness Innovations. It was set up at Davos a few years ago, and its purpose is to try to make vaccines for the list of diseases that aren’t yet known epidemics but that can potentially be there. And the idea would be using public sector money to get us prepared. Of course, they jumped in on this coronavirus as well.
Last thing is, of course, I’m not worried on a coronavirus stage that this is a problem, with not having a market. One of the challenges here is that there may be too big a market for this, and therefore, how do we make sure there’s access for developing countries. CA: All right, so talk about this virus, Seth. How is it different from Ebola? How challenging is it to create a vaccine for it? SB: So what’s interesting about coronaviruses is that they are animal viruses, probably primarily in bats. They jump into other animals sometimes, and then they jump into humans. So this shouldn’t have been a surprise. This is the third coronavirus that has jumped into humans. We had SARS in early 2002, we had MERS a number of years later, and now we have this virus. What’s interesting is there is a database that shows there are 30,000-some-odd isolated coronaviruses in animals, and one of the things that people tried to do was say the way these coronaviruses work is they have a spike on them.
They’re called “corona” because they look like the sun. That spike is where it attaches to a certain receptor in people’s lungs. And so somebody said, well, maybe we can begin to look at those spikes and see if they’re similar to the human receptors and they can be predicted. But the problem is people don’t invest in those types of research. And, of course, I think that, given it’s an evolutionary certainty, we’re going to see this, that we should be. But one other point about this is coronavirus jumped into humans in ancient history as well, and so we have now about a third to a quarter of the common cold viruses are actually coronaviruses. And what’s interesting about those is they don’t make you deathly ill like these, but you also don’t have long-term immunity to them, so you can get reinfected with these viruses after 10 months, a year. And so that does raise an issue on vaccinology, because you want to ideally have lifetime immunity. CA: The reason why we get reinfected is because the virus mutates slightly, and so it escapes the antibodies? SB: No, no, not in this case.
Not in this case. So in flu, that’s what happens. The viruses are always mutating. In HIV, the reason we don’t have a vaccine is because they’re all mutating. In this case, the immune response seems to get weaker and go away, and people get reinfected with the same viruses. Now, that is potentially a solvable problem using vaccinology and many different techniques, but the point is, we just can’t assume. Some people now are talking about herd immunity as a way to deal with this virus, and the idea there is if you could get enough people infected — you know, forget for a moment that a lot of people are going to die and be miserable while that happens — but the idea is that you get a certain level immunity in the community, and then the disease will go away. Well, that is only true if you get long-term immunity. If you don’t, then you could go through all of that horrible experience, have all those deaths, and then not have the protection you need to protect against this disease. CA: OK, so in a way, the quest we’re looking for is a vaccine that will work for the long term.
I mean, I guess any vaccine that works at all will be a huge gift, but it could well be one that we have to retake every year, or something like that. SB: Right. That is certainly possible. Of course, we have to remember, though, that SARS and MERS both had even higher mortality than this virus does, and they give a much more profound immune response. So it may be that they react differently than the common cold viruses. The challenge, of course, is that we haven’t had the opportunity to study these over a long time, and this new disease — three and a half months, we’ve had it. More science has been done for this disease in this short period of time, but we don’t understand fully the epidemiology of the virus, the immune response, what’s protective, which is the best animal model. All of that is being worked on by science and at breakneck pace, but a lot to learn. CA: So talk about how the medical and the research community responded.
Because, the Chinese authorities — I guess we heard it yesterday — only found out about this sometime in December. Already, early in January — I think the virus started in November, they found out about it in December — by early January, they had already released a sequence of the virus to the world, and now here we are. And I think I saw that more than 40 companies are already claiming candidate vaccines. What does it mean to have a candidate vaccine? Like, have companies tested this already against animals or something? Or are they just looking at a computer model where they go, “That should work”?SB: Well, it’s an interesting question you ask there. So first of all, China was heroic on this. They did post the genetic sequence of it. Today, we have companies that can sit down with a computer and from that genetic sequence, make what is a candidate vaccine. Now, a candidate vaccine obviously means it’s not a licensed product. It’s something that somebody wants to work on.
But you’re right, you have to have the right nomenclature, because “candidate” can mean I’m working on something, it’s in my head, I’m just doing a little work on it, I’ve got something in a vial, I’m beginning to do testing on it. And so what we saw in that case was a company called Moderna. That was the first vaccine that went into humans. It’s a messenger RNA-based system. I actually visited the company, not in this outbreak but before, because the technology is interesting. And what they were able to do was, in 42 days, make a candidate vaccine from the genetic sequence. They didn’t need the organism. That now is in clinical testing. Now, there is no licensed mRNA vaccine, so we’re going to have to figure out, is it safe? Does it work in different age groups? How are we going to scale it up? All of that. But there are many others who are using conventional vaccinology. An example would be, the French are working on a measles-based vaccine.
The idea is to put the spiked protein in the measles vector, and it takes a little bit longer to do that work, but once you have that done, of course, we know how to make measles vaccine. We make hundreds and hundreds and hundreds of millions of doses and provide it to the whole world. If that was to work, that might be easier to scale up. So I think what we want in the race is to have multiple different vaccines moving forward. We don’t want one or two. We don’t want a hundred in the late stages, because it’s expensive and hard to do. But we want to have a diversity of science approaches going forward. CA: Which of the other candidates out there are you excited by or at least intrigued by? SB: Well, for me, the critical issue here is going to be we have to optimize for speed, and so that means, as I said, having examples of all the different new technologies that could potentially work, as well as conventional doses moving forward at the same time.
So what you’re going to want to do is have this bubble up. And it’s not just companies, or big companies. It’s also biotech companies. It’s also academic researchers that are working on this. You want all of those to bubble up. Then you want to be able to look at what’s the most promising, and that will depend upon animal results. It’ll depend upon being able to produce those vaccines, have a pathway, and eventually, you will want to put those into human clinical trials. That requires a certain amount of safety work. You can try to accelerate that. But then you need to say, OK, we need to know, do we need one dose, do we need multiple doses, do we need 50 micrograms, 100, 150? Do we need a chemical stimulant we call an adjuvant? Given that this disease, its big problems in outcomes are in the elderly, we might need to put some stimulants in to make it a more potent immune response. So all of that work has to go on. That’s what the clinical testing is.
Eventually you say, “Aha! Here’s the vaccine we’re going to use.” Now you test it in an efficacy trial. And that is to see, does it work? And at that point, you then have a vaccine that you know works. But there is a stage after that, and that stage is, you’ve got to work out the manufacturing, have it all worked out so that the regulators know that you can really make this, and that it’s pure, it doesn’t have any problems with it. And during that period, and that’s what we did in Ebola, we were able to use those vaccines to help in outbreaks under a clinical trial protocol while monitoring them and learning. So there’s a lot of steps there, and it’s complicated, and I’ve shortened it a little bit. CA: But summarize the steps that they basically need to go through. I heard probably an animal test, and then —SB: Well, for example, Moderna. They went into humans at the same time they’re doing animal testing. We don’t have a perfect animal model.
But normally it takes 10 to 15 years to do this, and that’s the compression you’re trying to do here. So the challenge is, we can compress all those different clinical trials. The basic way you think about it is, preclinical studies, animals, understanding it, purity, reproducibility. Then you move into human studies. You start off with a small number of healthy people. You then work on the dosing, how much, how often. Then you move into people at risk for the disease — that might be in this case the elderly or people with other conditions — and then eventually do an efficacy trial. Now, one of the cool new things we can do today is something called “adaptive trial design.” So rather than do these sequentially, what you can begin to do is enroll people and then, as you get the data you need, you can just begin to bring in the next set of groups, and by doing that, you can speed it up dramatically. CA: When you say enroll people, you mean enroll people who have their eyes wide open.
They have informed consent. I think that’s the term. SB: Absolutely. CA: And they’re willing to, I guess, take the risk that this isn’t a fully tested vaccine but it may well be efficacious, and so that obviously can help a lot. That’s crucial to this, right? SB: Absolutely. They are the unsung heroes of vaccinology, because people go out, they volunteer to take a substance, particularly early on, that don’t know how it’s going to react. Is it going to make the disease worse? Make it better? Is it going to protect them? Is it going to make them sick? So you try to predict that if you can with animals, but people do do that, and the informed consent says not only you may have these side effects or these problems, but also this vaccine may not work. And so it’s important for people to understand that, because you don’t want people to go and put themselves at high risk, saying, “Oh, gee, I had a vaccine, and so I’m protected.” We don’t know that until we get to the efficacy stage of trials. CA: But Seth, even putting together all those dots, what I’ve heard most people say is that it is likely to take at least 18 months before the world will have a vaccine available at any kind of scale.
Is that time line right? And can the world remotely afford 18 months on this? SB: Well, I think, you know, I’ve given you many questions. I could raise lots more questions. So part of it’s going to be luck: How easy is this particular candidate vaccine going to be? How lucky will we be in getting a good immune response? Which approaches will work? Will they be scalable? So I think there’s lot of questions there. The world will do everything they can to squeeze it down, but I think that’s the time line we’re talking about. And remember, it’s 10 to 15 years usually. In the case of Ebola, we did it in five years to a licensed product. In this case, we are hoping to squeeze it down dramatically, but there are many things we’re going to have to go through, and it’s really about making sure that vaccine works and it is safe for use in what ultimately may be billions of people. CA: Whitney. WPR: Hi. So we have lots of questions coming in, Seth.
One of them that’s kind of related to this is, you know, a lot of us right now are isolating, and we’re not building our exposure to this virus, so how will that affect us in the long term? Will this make us vulnerable to the virus until a vaccine is available? SB: So that’s a great question, and, as you know, we don’t fully understand the epidemiology of this virus, but there is some sense that there may be asymptomatics. Do they get immune protection? Are they afterwards resistant to infection? We don’t know that, but we do know that people do get sick, including young people, and that sickness can be quite severe. Obviously, a lot of it is mild, but some of it is quite severe, and then it gets more severe in the elderly. So I wouldn’t recommend that anybody go out and intentionally try to get exposed to this virus now. The whole idea of having isolation now is to try to stop the chains of transmission, protect health workers in hospitals, with the idea being that if you can suppress it enough — and Bill talked about this in his talk — and later on have testing available, you might be able to go back to somewhat of a normal life and then watch for reintroduction of this virus.
Of course, at the end of the day, we will probably need a vaccine to be able to completely control that, but the experiment is going on, in China … Japan has done an amazing job of controlling this with slightly less severe interventions. We’ve seen in Korea similar things. So the hope would be that if we take it seriously, we actually damp down the exposures and stop this epidemic now, we’ll be able to remove to some form of normalcy. And we also may have drugs, and drugs will change the dynamics as well, because people will then know that they are able to get treatment as well. WPR: Great. I’ll be back later with other questions I’m seeing. SB: Thanks, Whitney. CA: Thanks, Whitney. Thanks everyone watching. Keep those questions coming. Seth, this time line, I’ve been puzzled about this, because I get that there are so many things that have to be checked out, but I still worry that the rules are not adapting rapidly enough for the scale of the emergency.
I mean, my analogy would be: you’re going about your lives, and suddenly there’s this emergency, you see that there’s this enemy force approaching you from the horizon and coming your direction. You don’t, in that circumstance, spend a week trying to test all your guns and make sure they’re operating absolutely safely and in the right way. You galvanize and you do take some additional risk for the sake of avoiding the bigger risk. Is that thinking prevalent right now? Are there people trying to make those kinds of trade-offs? How should we think about that? Or do you really believe that the community is galvanizing and moving forward as fast as it humanly can and appropriately balancing the two risks? SB: I think we’re seeing heroics in moving forward here. Obviously, you’re right, and the reason we talk about going from 10 to 15 years down to something like 18 months is about squeezing those steps as much as possible. The regulators in the Ebola experience were really fabulous.
They worked with us and tried to keep any bureaucratic delays down to the smallest amount possible. And I think that’s what’s going to be important here, is we have to look at every single step and say, “Is it critical?” But you do need to answer a lot of these questions. For example, if you have a vaccine that works in healthy people, it very well may not give an immune response to the elderly. We may need to change that vaccine to make it work there. It may not work in young children. So you need a certain amount of studies done. Of course, if you work in areas that have big outbreaks, you’re able to also enroll more quickly and follow people more quickly. That’s one of the reasons we’ll have to think about this globally, because we don’t know in 12 to 18 months, or even six to 18 months, if we’re really lucky, where the epidemic will be raging and where we want to do the clinical trials.
We should be prepared to do them wherever in the world it’s possible, and also do some in different types of countries. Developing countries may have different immune responses than in wealthy countries. CA: What alarms me a bit is that on the models I’ve looked at, with the possible exception of what happened in China and Japan, by distancing, we can bend the curve, we can reduce infection. But as soon as you go back to normal, there’s this huge risk of a massive resurge, and until the vaccine comes along, it feels like your choices are: one, sort of recklessly expose the whole population to the bug and develop some kind of herd immunity, or try and do this scary dance of really cramping down on the economy and all the risks that are associated with that, and risking, if you lift the lid on that, risking these really dangerous second surges. So is that the right way to think about it? There’s a scenario where, until this happens, and if it’s 18 months, that’s an incredibly long time for the world to be in that sort of dangerous, scary dance. SB: Well, I think the issue here is that is a little bit the way to think of it, but the experiment is going on now.
China is now releasing its controls, and we will see what happens there. We’ll see where they have to clamp back down and what’s going to happen, and we’ll get a good idea of what that’s like. Right now, in many countries, we’re still in the upscale period when we’re seeing lots of cases. And so we have to break that transmission first before we can have that conversation. I’m the first person that would like a vaccine to occur quicker, and, of course, my job is to underpromise and overdeliver, not the other way around. And I think we have to be careful not to think about, “Oh, we can just have a vaccine in a couple of months.” It may be that we’re lucky. It may be that it’s easy to do. It may be the first few candidates will show promise, we get efficacy, we can scale those up for at least some limited use while it’s being worked out. But a lot of things have to fall in place for that to happen.
And that’s why we want to have an organized, global effort to absolutely incentivize the best possible chance for that to happen in the fastest way. CA: There’s some kind of debate out there about whether there might be way, way more cases, mild cases, basically zero-symptom cases of coronavirus out there that may have granted more people immunity than we know. Is that a credible suggestion? More cases and much lower fatality rate than we know, because so many of the cases could be invisible? SB: You know, Mayor Bloomberg used to have a saying that I loved. He said, “In God we trust. Everybody else, bring data.” And I think the answer here is we haven’t done enough testing to know, and we started out with PCR tests to look for virus, and therefore, if you had recovered, didn’t have the virus anymore, we weren’t able to pick it up. Now there are beginning to be antibody tests to look to see if you’ve been exposed and don’t have the virus now but have an immune response to it.
Once we have those tests operating at scale, we’ll be able to understand what the epidemiology is and what’s happening, and then we’ll be in a much better place to understand how this is playing out. Also, I mean, even the question: We don’t see a lot of cases in children — is that because the children get infected but they don’t get symptoms, and ther