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--:-- Sean Rameswaram: It's Friday, April 17th, 2020, and Michael Cohen is free at last. Well, I mean, not yet, but soon. This is your coronavirus update from Today Explained. President Trump's former bully, Michael Cohen, will be serving out the rest of his prison sentence from home. I guess we should expect a podcast soon. Be sure to not subscribe wherever you listen.
--:-- Noel King: The president is also having quite a Friday in a show of solidarity with a rather vocal minority of Americans who have been protesting social distancing. He tweeted, Liberate Minnesota, followed by Liberate Michigan. And then he wrapped up the trilogy with, Liberate Virginia and save your great Second Amendment. It is under siege. Worth noting, all three of these states have Democratic governors. Also worth noting, the president told states last night to call their own shots.
--:-- Sean Rameswaram: For the record, in a Quinnipiac poll, over 80% of Americans support a national stay-at-home order. The same poll found that about 31% of Americans would give the president an F for his handling of this pandemic so far, while 25% of Americans would give him an A. You can grade the president yourself this November.
--:-- Noel King: Of course, there isn't a state in the union that doesn't want to open back up, as we established on yesterday's show. First, we have to dramatically increase testing capabilities. Public health workers say we are not ramping up fast enough. And the president's own task force coordinator, Dr. Deborah Birx, told CNN last night that testing needs to be expanded in concert with contact tracing and surveillance.
--:-- Sean Rameswaram: Over in China, they are revising the COVID-19 death toll, raising it by 50% in the city of Wuhan. This comes after lots of questioning of how legitimate the original numbers were in the first place. China's economy sank for the first time since 1976 in the first three months of the year because of this novel coronavirus.
--:-- Noel King: Though kids have largely been spared, the UN is warning about the pandemic's long-term impacts on the world's children. Secretary General Antonio Guterres acknowledged that closed schools and lost jobs will affect all countries, but the world's poorest countries and poorest children will suffer the most.
--:-- Sean Rameswaram: Many of you have emailed us to ask what you can do with your stimulus checks because you don't necessarily need them. Consider charities that focus on global poverty. Ireland is giving a little more in light of President Trump's decision to suspend funding to the World Health Organization. The country's foreign minister tweeted, so many countries rely on UN expertise and capacity to save lives. Ireland is quadrupling our annual contribution to WHO for 2020.
--:-- Noel King: Today, Explain wants to do more for kids. Wherever you are, get your favorite kids to call us and tell us about their coronavirus experience and ask questions about this pandemic if they've got them. The number is 202-688-5944. That's our listener voicemail line.
--:-- Announcer: Today, Explained wants to do more for kids. Wherever you are, get your favorite kids to call us and tell us about their coronavirus experience and ask questions about this pandemic if they've got them. The number is 202-688-5944. That's our listener voicemail line.
--:-- Sean Rameswaram: Thank you from Sean, 35, District of Columbia. Thank you.
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--:-- Noel King: I spoke to Zeke Emanuel about the path forward. It involves, in the immediate future, sticking with social distancing, but then seriously ramping up how much PPE we have for frontline workers and how much testing we're doing of Americans and contact tracing.
--:-- Sean Rameswaram: Noam Hassenfeld has been reporting on how it ends for Today Explained. Noam?
--:-- Noam Hassenfeld: Yeah, the only way this all really ends is with a vaccine. The big problem with coronavirus is that there's so many asymptomatic cases. You know, people walking around with coronavirus, they don't even know they have it. They're infecting other people. And so the only way to stop this isn't with treatment. It's with prevention.
--:-- Sean Rameswaram: And when we talk about ending, we're talking about what? Getting back to the place where we can go to Coachella and feel cool?
--:-- Noam Hassenfeld: Yeah. I mean, we're talking about things that we used to take for granted. I mean, bars, clubs, sporting events. And there's a recent poll that said that even if live sporting events start happening again, about three quarters of Americans would not go to them unless there's a vaccine.
--:-- Sean Rameswaram: So let's talk vaccines. I mean, people are working on this across the globe, right?
--:-- Noam Hassenfeld: Yeah. I mean, according to the WHO, there's at least 70 coronavirus vaccines in development all over the world. But coronavirus research didn't just start in 2020. For the last decade, our vaccine center has been working on a SARS coronavirus vaccine that currently sits in a freezer.
--:-- Maria Elena Bottazzi: Hi, I'm Maria Elena Bottazzi, co-leader of vaccine development at Baylor College of Medicine in Houston.
--:-- Noam Hassenfeld: And there is a great chance that vaccines that were initially developed for SARS could provide partial protection against the COVID-19 virus, and most importantly, even future coronavirus outbreaks.
--:-- Maria Elena Bottazzi: Now, she and her team are taking what they learned from working on the SARS vaccine, and they're bringing it to a vaccine for the novel coronavirus. The vaccine is designed to retrain your immune system.
--:-- Sean Rameswaram: Here's how it normally works. We produce little cells. T-cells, B-cells. We also know that cells produce other enzymes and proteins. Like antibodies. And this is what we call our human immunological army cadets, right? You know, so it's our army.
--:-- Maria Elena Bottazzi: When your body detects an outside invader, like a virus or another microbe. These little cadets, which is our whole army, get together. And like when you're in a war, you create a strategy to go and try to combat this microbe. That's the battlefield.
--:-- Sean Rameswaram: Here's where the vaccine comes in. A vaccine is a molecule that we inject into the human body that mimics some virus. And therefore, the body can then produce antibodies against it. The vaccine is weaker than the real virus, but to your body, it looks just like the real thing.
--:-- Maria Elena Bottazzi: So the vaccine gives our immune system a trial run at fighting the virus such that when we get the real infection, we already know that you know that is a foreign entity and our body can produce antibodies against it.
--:-- Sean Rameswaram: The first vaccine dates back to the 18th century, when a British doctor named Edward Jenner noticed that milkmaids weren't getting smallpox. Turns out they had been exposed to cowpox, which is pretty similar.
--:-- Maria Elena Bottazzi: When you had smallpox, you already were protected because both organisms were very close. So Jenner started exposing people to cowpox on purpose. Using cowpox postules that you would inoculate patients, and then they would prevent smallpox.
--:-- Sean Rameswaram: But getting cowpox was still pretty bad. Not as bad as smallpox, but still not fun. Eventually, though, scientists started to realize that they didn't need to expose people to live viruses. You can take a virus, manipulate it. Either inactivate it or kill it. And because the virus has the same shape, the immune system gets the practice it needs.
--:-- Maria Elena Bottazzi: But still, you have to deal with an actual live virus before you can kill it. Not ideal. And so therefore, there are other strategies where you then kind of like take apart the virus. Looking for that one thing that can get your body to jumpstart the immune system.
--:-- Sean Rameswaram: And it all leads to this point. Can we just pick a single protein within the virus? This protein, actually just a piece of it, is what Maria Elena wants to inject into people's bodies. You may have actually seen it already. It's been plastered all over. That grayish ball with red triangular spikes.
--:-- Maria Elena Bottazzi: The spike protein is essential because that's what the virus uses to get inside the cells. Maria Elena needs to figure out a way to make that spike protein in the lab. Correct. We are brewing a vaccine.
--:-- Sean Rameswaram: To start, you need a base. In our laboratories, we love the yeast expression system. And the reason is because they're very avid producers. It's a process that actually looks sort of familiar. Maybe you are familiar on how, in fact, yeast is our producer of beer.
--:-- Maria Elena Bottazzi: In fact, when you go to a brewing company, the way that you produce beer is through these humongous stainless steel machines that, you know, allowing these yeast to just grow and you're feeding them food, right? So what do you feed them? You feed them sugars that then gives your alcohol like a taste and whether it's an amber ale or whether it's, you know.
--:-- Sean Rameswaram: So we do exactly the same in our laboratories. But instead of telling our yeast to produce alcohol, we change the way that we code the yeast and we tell the yeast, forget about the alcohol. But I need that beer now.
--:-- Maria Elena Bottazzi: Then Maria Elena and her team give the yeast the genetic code for that spike protein. Ultimately, what the yeast is doing is actually secreting all these proteins in this broth, right, in the liquid. It gurgles and bubbles and burps for a bit. Usually it lasts, I don't know, three, four days, and we get a nice broth that has our, you know, vaccine protein.
--:-- Sean Rameswaram: Believe it or not, this is sort of the easy part. Because after this comes lots and lots and lots of testing. Unfortunately, it requires time, right? Because first you have to look for safety. A rushed vaccine could create something called immune enhancement, which could make the immune system supercharged.
--:-- Maria Elena Bottazzi: Attacking kind of randomly, right? You want this attack to be very specific just to the cells that maybe have the virus, but at the same time not start affecting all the normal cells that are around you.
--:-- Sean Rameswaram: On top of the safety, you obviously need to make sure the vaccine works, that it actually makes someone immune. So how long will it take? You know, we've been hearing that it may take a year, it may take 18 months, it may take longer.
--:-- Maria Elena Bottazzi: And that 12 to 18 months is aspirational. The fastest way that we have ever been able to develop a vaccine has been four years. And if this aspirational goal is somehow met, it'll raise a whole new set of questions. Then we have to turn around and say, OK, who's going to make it? How quickly can it be scaled up? How quickly can it be delivered?
--:-- Sean Rameswaram: And then the aspiration is that we don't do things in a non-equitable manner. We want to have vaccines for everyone that needs it. All of these unanswered questions, it's a lot to handle. So indeed, it's a pretty high responsibility.
--:-- Maria Elena Bottazzi: I mean, I have to say, we wake up with, you know, that heavy, heavy weight on our shoulders. It's very stressful for us, and I wish we could do more. It's especially heavy for me because I've been through this before. We've already had seen two other prior coronavirus-related outbreaks with SARS and MERS.
--:-- Sean Rameswaram: So it was a huge disappointment, frustration for our group that has been working on a coronavirus vaccine program for more than a decade. And all that research, that's what's sitting in her freezer. Funding dried up, other things, of course, getting the attention of the world, you know, dengue, Zika, Ebola.
--:-- Maria Elena Bottazzi: And everybody thought, you know, maybe this will never come back. And as you can see, that was not the case. You know, the reality is this will continue to happen. And so this brings to the attention that we cannot just go and invest. And then just because at one point or another, you know, that priority is not there, that we just leave them halfway.
--:-- Sean Rameswaram: If we would have had evidence of prior SARS and even MERS vaccines, we may already know a lot more than what we know now.
--:-- Maria Elena Bottazzi: The vaccine's going to take a long time, no one's arguing that point, but there is a radical way to speed it up. That's after the break on Today Explained.
--:-- Announcer: Support for Today Explained comes from Built Rewards. These days it seems like everybody has a rewards program. You swipe your card and you get one cent on the hundred dollars. But with your rent, frequently, you just pay month after month. You never get anything from it other than that roof over your head. Not anymore, says Built Rewards.
--:-- Sean Rameswaram: Built Rewards says it lets you earn points on your rent. By paying rent through Built, they say you can earn flexible points that can be redeemed toward hundreds of hotels and airlines, perhaps a future rent payment, your next Lyft ride, and so much more.
--:-- Noel King: Your home isn't just where you sleep, it's your community, and Built wants you to go out and do things in the community. You can eat at your favorite local restaurants, then earn more points. You can get VIP treatment at certain fitness studios. You can enjoy exclusive experiences just for Built members every month.
--:-- Sean Rameswaram: When you're ready to travel, they say Built points can be converted to miles or hotel points all around the world. You can earn points on rent and around your neighborhood wherever you call home by joining built.com slash explained.
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--:-- Sean Rameswaram: Now you're going to tell us about a way we can speed this whole vaccine process up. How does that work?
--:-- Noel King: Yeah, so once you make the vaccine, the testing takes a long long time. Usually the way it works is you randomize people into two groups. Group A gets the vaccine, group B gets a placebo. And then you just wait and see if more people from group B get sick.
--:-- Sean Rameswaram: If that happens, it's a sign that the vaccine's working, but this takes forever because researchers have to wait and see if those people naturally get exposed to the virus. And that takes even longer when everyone's social distancing.
--:-- Noel King: So we won't know for many months, and it might just be too late. Nir Eyal is a professor of bioethics at Rutgers University in New Jersey. We propose instead to do a challenge study.
--:-- Nir Eyal: In a challenge study, you deliberately expose people to a virus, in this case, to coronavirus. And you compare the two groups, the vaccine versus the control, knowing that everybody was exposed to that virus.
--:-- Sean Rameswaram: This could save a lot of time. We hope that a human challenge could shave off several months. We're talking about savings of thousands, if not millions of lives.
--:-- Nir Eyal: But there's a trade-off here. It's not every day that doctors give germs to people deliberately. The first dictum doctors like to say of medicine is, first do no harm, primum non nocere. Giving somebody a deadly virus doesn't at all look in line with that.
--:-- Sean Rameswaram: It took some weeks to convince one co-author and eventually a second co-author to jump on board. Initially, they also thought that I was crazy. Even though a human challenge isn't a totally unorthodox idea.
--:-- Nir Eyal: We do human challenges a lot for diseases like seasonal flu, typhoid, malaria. But it's unusual to conduct human challenges for something that is killing so many people.
--:-- Sean Rameswaram: So that's why initially it might create the impression that there is an ethical problem. On the other hand, just because something is risky doesn't mean it shouldn't be allowed.
--:-- Nir Eyal: It's legitimate to allow people to, say, volunteer to be EMS workers in this crisis, although it's risky for them. It's legitimate to ask people to donate kidneys to others. We let them do it, although it wasn't in their own best interests.
--:-- Sean Rameswaram: Why should we stop people when they try to do something that we need in a very dire way in order to save potentially millions of lives?
--:-- Josh Morrison: My name is Josh Morrison. I live in Brooklyn. When I read Nir's article about human challenge trials, I was really excited by the idea, and it was one that maybe could make a difference.
--:-- Sean Rameswaram: So I created this website to organize volunteers who are interested in participating in a challenge trial. And since then, we've gotten more than 1,000 people signed up.
--:-- Josh Morrison: As a young and healthy person, I think participating in a vaccine trial would have pretty limited risks in comparison to the enormous potential upside.
--:-- Sean Rameswaram: Philosophers in my religious tradition, Judaism, teach that to save a single life, it's as if you've saved the entire world. This is a pretty unique thing to be able to donate your health.
--:-- Josh Morrison: So I wanted to share that, if at all possible. I was involved in a head-on collision, an tractor-trailer accident, back in 2014. Ever since I've been put on permanent disability, I would love to be involved in the study mainly to be able to help and protect others.
--:-- Sean Rameswaram: Especially my 13-year-old daughter, who I absolutely adore and would rather me be the subject to this virus in her stead.
--:-- Josh Morrison: I'm a third-year medical student, and that means right now I'm not far enough along in my education to actually be able to help out with patient care. To me, a challenge trial is a way that I can contribute to help speed up vaccine development and other aspects of patient care.
--:-- Sean Rameswaram: I'm young, I'm healthy, I don't have kids, and I'm a historian. So while the things that I teach, the critical thinking skills, these questions about how we know what we know, while all the things that I do are really important at this moment in time, it's not the same as doctors and nurses serving in hospitals.
--:-- Josh Morrison: This felt like a contribution that I could make and that my willingness to do so would be really important because it's not something that everyone would want to do.
--:-- Seema Shah: So there's this history of challenge studies that have been done on vulnerable populations with high risks that have been really controversial.
--:-- Sean Rameswaram: So one example is the Willbrook hepatitis study. So these were studies where children who were institutionalized in the 50s and 60s were deliberately infected with hepatitis.
--:-- Seema Shah: And even though the researchers got consent from the parents, parents didn't have as free of a choice as you would want because they may not have been able to get into the institution if they didn't agree to the study.
--:-- Sean Rameswaram: Many of them were otherwise waitlisted to get their children into the institution. The study did produce valuable information and obtained consent and the researchers thought carefully about risk.
--:-- Seema Shah: But this episode is widely considered highly controversial and something that damaged the public's trust in research.
--:-- Sean Rameswaram: Nir understands these issues, which is why he concedes that his human challenge trial needs to pass a high ethical bar.
--:-- Nir Eyal: This study must be done with the highest standards of informed consent, so certainly no children, no prisoners. No paying participants.
--:-- Sean Rameswaram: I don't want people who would join just because they are in dire need of a job in this economic recession. We should triple check comprehension of the risks.
--:-- Nir Eyal: This is a study that should be done in the way that respects the autonomous will of the participants the most we can.
--:-- Sean Rameswaram: And Nir wants to recruit young, healthy participants to minimize risk.
--:-- Nir Eyal: Still, there's no denial that there could be a fatality in such a study as there could be in other efficacy studies.
--:-- Sean Rameswaram: My main argument, however, is not relying so much on how small this number is. It relies on the fact that these people would benefit from being in the study.
--:-- Nir Eyal: Participants might actually be better off being exposed to coronavirus in a human challenge.
--:-- Sean Rameswaram: What biologists think is the relevant number to measure is not so much the likelihood that somebody will die, but the gap, the difference between your chances outside the study and your chances inside the study.
--:-- Nir Eyal: Coronavirus infections and deaths continue to rise, and hospitals continue to be overwhelmed.
--:-- Sean Rameswaram: And this is the thing that demarcates coronavirus from a lot of other diseases, because with coronavirus, we know that so many of us will be infected in a few months, and we know that so many of us, should we, heaven forbid, require our life support, will not be able to find it.
--:-- Nir Eyal: It will be better to be treated in state-of-the-art facilities with the best researchers, sometimes accompanied by the best clinicians around.
--:-- Sean Rameswaram: And the minute you get infected, before you're even symptomatic, they can direct therapy to you.
--:-- Nir Eyal: But even with young people, this can be risky. There are significant numbers of young people who are dying, and we don't fully understand why.
--:-- Sean Rameswaram: And they don't seem to have other conditions that are causing them to die. And there are questions about whether a trial like this could be definitive.
--:-- Nir Eyal: Maybe a healthy 20-year-old who doesn't have any other comorbidities isn't going to tell you how well the vaccine will do at protecting someone who's older or who has a lot of other conditions.
--:-- Sean Rameswaram: But even Seema thinks something like this is worth considering.
--:-- Seema Shah: It would be a mistake to rule these studies out and say, you know, it's too risky, we just shouldn't even consider them at the present moment.
--:-- Sean Rameswaram: We've just never seen anything quite like this. This is a pretty extraordinary circumstance.
--:-- Nir Eyal: So we might think differently about risk because what we can learn might be considerably more and considerably more valuable than it has been in almost any other case we can think of.
--:-- Noam Hassenfeld: Noam, where does this leave us? We have this way to expedite the process, but it's an ethical quandary. People say it's dangerous. What's going to happen?
--:-- Sean Rameswaram: Well, I'm not sure to tell you the truth. But one thing I can tell you from my reporting is that because these things have such a long timeframe on them, because a decision you make now maybe won't come to fruition until months, even years later, people are starting to consider making decisions from a place of uncertainty.
--:-- Noam Hassenfeld: What kinds of decisions are people making? Well, take vaccine manufacturers, for example. They're starting to talk about making vaccines at risk, meaning manufacturing vaccines before they even have testing finished.
--:-- Sean Rameswaram: So they're basically going to have to take a bet on which vaccine is going to work before really knowing.
--:-- Noam Hassenfeld: And how big a bet is that? Well, according to one CEO, if they do this sort of manufacturing early idea, if the tests come back and it turns out the vaccine that they chose doesn't work, they'd be out about $30 billion.
--:-- Sean Rameswaram: But he's talking about doing it anyway. He's talking about putting $30 billion on the line, which means it's definitely crunch time?
--:-- Noam Hassenfeld: It's definitely crunch time. And at the same time, there's so much that's still unknown. We don't know how many people are infected but asymptomatic. We don't know how the virus might mutate and what that could mean for a vaccine.
--:-- Sean Rameswaram: And as far as the human challenge, this potential key that could speed up the whole process, we don't fully know its true potential.
--:-- Noam Hassenfeld: But we're talking about months and years-long timeframes here, so we're going to have to start making decisions really soon. And some of those decisions might be uncomfortable.
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--:-- Sean Rameswaram: Noam Hassenfeld is a reporter at Today Explained. The rest of the team includes Afim Shapiro, Amina Alsadi, Jillian Weinberger, Bridget McCarthy, and Halima Shah.
--:-- Noel King: Cecilia Lay is our fact checker, The Mysterious Breakmaster Cylinder is our heartbreaker. Liz Nelson is the editorial director of Vox Podcasts.
--:-- Sean Rameswaram: Special thanks this week to Josh Morrison and Natalie Wren for their help.
--:-- Noel King: Today Explained is part of the Vox Media Podcast Network. If you don't know, now you know. Listener.
--:-- Announcer: I'm Liz Nelson, editorial director of Vox Podcasts.
