Getting malaria on purpose

Dylan got malaria on purpose. And he thinks you should, too. Guest: Dylan Matthews, senior correspondent at Vox’s Future Perfect This episode was made in partnership with Vox’s Future Perfect team. For show transcripts, go to vox.com/unxtranscripts For more, go to vox.com/unexplainable And please email us! [email protected] We read every email. Support Unexplainable by becoming a Vox Member today: vox.com/members Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

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• 0:38Speaker 01

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• 1:21Speaker 02

  One day last spring, my colleague Dylan Matthews drove out to the University of Maryland and made his way to a biosafety Level 2 lab there.

• 1:30Speaker 03

  Which sounds very fancy and whatever. It's not like that at all.

• 1:33Speaker 02

  There are no hazmat suits or anything.

• 1:35Speaker 03

  It's just like some plastic folding tables and some metal folding chairs.

• 1:41Speaker 02

  Basically like an ordinary doctor's waiting room. So Dylan's sitting there with a bunch of other volunteers waiting. And eventually, a nurse comes in with these cardboard tubes that are about the size of a peanut butter jar.

• 1:56Speaker 03

  And each one of those has a bunch of mosquitoes in it.

• 2:00Speaker 02

  Mosquitoes carrying malaria.

• 2:04Speaker 02

  Now, malaria is an awful disease. Without treatment, it can kill you. In tropical places with limited healthcare, it kills a lot of people. The global total is around half a million people every year. So just overall, this is not a disease that you want to be exposed to. And yet Dylan was here at this lab in Maryland to get exposed to it on purpose.

• 2:36Speaker 03

  The procedure is they go up to you. You, you put your arm out and they put the cylinder against your arm. And you sort of wait for the mosquitoes to bite you.

• 2:47Speaker 02

  Dylan was so determined to be exposed to malaria that he ended up having to go through two separate rounds of this biting. The first time around, the, the mosquitoes hadn't taken enough blood and another volunteer ended up giving him some tips.

• 3:00Speaker 03

  He was like, dude, take your socks off. I was like, what are you talking about? He's like, I, I don't know why it works. But you take your socks off. They have all your like disgusting foot sweat on it. You rub that against your arm.

• 3:14Speaker 02

  No.

• 3:14Speaker 03

  Mosquitoes love it. They love it, bird.

• 3:20Speaker 02

  Now, at this point, you might be wondering why? Like beyond even the, the sock sweat of it all, why did Dylan decide to voluntarily expose himself to this deadly disease? Well, this is unexplainable. I'm Byrd Pinkerton and today on the show, we will tell you why Dylan did this to himself. In some ways, it's actually kind of simple. Dylan once gave his kidney to a stranger. So he's just unusually down to put his body on the line to help other people. But he'll tell us why this specifically is the approach that he took. Why he thinks that getting exposed to a disease like malaria can be a good way to help people.

• 4:14Speaker 02

  The first thing to know is that Dylan's exposure to malaria was part of a study, this trial to test out a new technique for fighting off malaria that's kind of like a vaccine.

• 4:25Speaker 03

  I would sometimes like tell people I was testing a vaccine, just for simplicity, but it's not actually a vaccine.

• 4:31Speaker 02

  Oh, ho, ho.

• 4:32Speaker 03

  Oh, ho, yeah.

• 4:34Speaker 02

  A vaccine basically teaches your immune system to defend itself, to produce antibodies it needs to fight off a disease. But this thing that Dylan was testing was just the antibodies. Like, instead of showing your body how to make the tools that fight off the disease, it was kind of just pumping you full of those tools.

• 4:55Speaker 03

  Vaccines teach your immune system to fish, and this just gives your body some fish.

• 5:00Speaker 02

  And there are effective cures for malaria out there, but in places where healthcare infrastructure isn't robust, it can be hard to diagnose people or get them that care if they need it. So the ideal is just to prevent people from getting malaria in the first place. And while there are also already some malaria vaccines out there, they don't work as well as we would like them to.

• 5:24Speaker 03

  Maybe 70% effectiveness. And if you're in a place like the Sahel, the sort of region just below the Sahara, where on average, kids are getting malaria three times a year, 70% is good, but you're still going to get malaria a bunch of times.

• 5:39Speaker 02

  So the hope is that this new approach, this "give a man a fish," and by fish, I mean antibodies, this kind of strategy, the hope is that it will do better. It will be more effective at staving off malaria. And there are a couple of different ways that you can test out an intervention to see how effective it is.

• 5:57Speaker 03

  You could test drugs like this, and people do, by going to a region where malaria is endemic, like West Africa. You could offer people the drug, and then they are probably going to get exposed to malaria in their daily life, and you could see how well the drug works at preventing infection.

• 6:15Speaker 02

  This is what's called a field trial. And it's really important to do these. They give you a sense of how your intervention works in the real world. The problem is that this kind of test requires a lot of resources. Like, in this West African example from Dylan, right? You would need a big group of people from that region because you'd need to have enough people in your study to be sure that a significant number of them would be exposed to the disease at some point as they went about their daily lives. But then you'd also need to keep track of all those people, potentially over a long period of time. And that can be hard.

• 6:52Speaker 03

  Because you're doing it in a community, and often in a very poor community that sometimes doesn't have the best communications infrastructure. It can be hard to follow up with people. It just takes longer. It takes more time. It takes more money.

• 7:06Speaker 02

  Which means that studies like these can be pretty expensive. Dylan says it can be hard to get exact numbers for the cost of field trials, but he was able to find some specifics.

• 7:16Speaker 03

  There's currently a big tuberculosis vaccine trial happening right now. And it costs about $550 million.

• 7:24Speaker 02

  Oh, my god.

• 7:25Speaker 03

  This is a field trial of one vaccine.

• 7:27Speaker 02

  Half a billion dollars for one vaccine?

• 7:31Speaker 03

  Over half a billion dollars.

• 7:33Speaker 02

  That's a huge price tag. It's not necessarily the exact price for every field trial, but still, it's a lot of money to think about. Especially because, remember, a trial can fail. The researcher who's testing this new "give a person some antibodies" approach could go through this whole process, spend all this money, and then realize that they didn't have the exact right recipe for their antibodies, for example. So, these researchers decided to do a different kind of trial first. A smaller, less expensive kind of trial that would show them essentially if it was worth doing a bigger, more expensive field trial down the line. Something called a challenge trial.

• 8:18Speaker 02

  These are used for all kinds of diseases, from malaria to Zika, cholera, even the common cold. And literally, they're called "challenge trials" because they challenge a drug directly. What that means is, in a challenge trial, researchers give people a drug, like this drug that will hopefully prevent malaria. And then, instead of waiting around to see if they happen to get exposed to malaria out in the world, they just expose those people to the disease directly. In this case, by applying mosquitoes in a tube to Dylan's sock-sweat-covered arm.

• 8:53Speaker 03

  And a major advantage of challenge studies is you can do them anywhere. So, in this case, a team based in Maryland can do this with volunteers from the United States, rather than going to a country where malaria is common. And also, you can use a much smaller pool of people.

• 9:12Speaker 02

  If you can guarantee that everyone in your study is going to be exposed to malaria because you're the one doing the exposing, you can study fewer people. You also have control over when they're exposed, so you don't have to monitor them for as long or work as hard to keep track of them. And the amount that you pay participants, in Dylan's case, about $5,000, that money is not going to break the bank.

• 9:36Speaker 03

  So you can get a sense of whether these things work much more cheaply than trying to do a full-scale field trial.

• 9:43Speaker 02

  So remember, that one TB study is going to cost around half a billion dollars.

• 9:48Speaker 03

  By contrast, a challenge trial can cost as little as $1 or $2 million.

• 9:53Speaker 02

  Which means that if a challenge trial fails, it's a setback, but it's not a half-a-billion-dollar setback.

• 10:02Speaker 02

  This all felt pretty worthwhile to Dylan, which is why he volunteered his body for a challenge trial, for this, like, beta test to see if these antibodies were effective. But I was curious what the results were. Like, did this mix of antibodies work and keep malaria at bay?

• 10:24Speaker 03

  So it did not work in my case. I was going in every day and testing and kept hearing that I was negative. And I was on a call with my editor at Vox and I was saying like, yeah, it's going well. I don't, I don't seem to have malaria. And then I got a phone call and I was like, one second. And so he heard me be like, uh huh. Oh, it's positive. That's interesting. All right. Well, I'll see you soon. And I hung up and I was like, Brian, I have to drive to Baltimore and I have to take some anti malaria medicines is what I have to do. How was your Friday?

• 11:02Speaker 02

  Again, in a healthcare context like this one, where Dylan was in an actual lab, he wasn't at huge risk. Right from the start, researchers told him that they would be able to cure volunteers if they had breakthrough infections. That was part of their study design. And so basically all he had to do was take an anti malarial drug and then go home and deal with what was either malaria or the side effects of the anti malarial drug.

• 11:28Speaker 03

  I came down with what felt like sort of a stomach flu. Like I felt nauseous. I think I had a temperature. I was kind of tired and wanted to sleep. So it wasn't pleasant, certainly.

• 11:41Speaker 02

  But it also wasn't the end of the world.

• 11:45Speaker 02

  And similarly, it wasn't the end of the world that this approach to fighting off malaria didn't prove to be 100% effective. Dylan says the, the full results of his challenge trial aren't out yet, but his sense is that he was not the only person who had a breakthrough infection. So the researchers maybe want to make a few tweaks to the recipe of their antibodies and, and see if they can do better, basically make them more sophisticated or, or more effective somehow.

• 12:12Speaker 03

  And I think that's one of the things that challenge trials can help with is if they'd done this study and absolutely none of us had got malaria, I think a reasonable reaction would be like, wow, this is, this is a really effective thing. We should do a bigger, larger field trial of it. By contrast, if you do it and it's less effective than you hoped, then you, you have a reason to try some other things first.

• 12:37Speaker 02

  And that cheaper price tag means it's more financially realistic to try some other things.

• 12:44Speaker 03

  And I think for diseases like tuberculosis and malaria, like bluntly. Rich countries, or at least rich people in rich countries, just do not get these diseases. There's no political urgency to develop better vaccines for these within the countries that have the money to develop better vaccines for these things. And so money is scarce. If every vaccine candidate costs half a billion dollars to test, we're just like never gonna get effective vaccines against these things. And I think that's why challenge trials are so exciting to me is that we can find cures anyway. And all it takes is a few people in rich countries being willing to step up and put their bodies on the line. And at least in the case of malaria, it takes some not very large risks.

• 13:30Speaker 02

  So this, basically, is Dylan's case for challenge trials. I found it compelling, but I also still had questions about these not very large risks. So that's after the break.

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• 17:15Speaker 02

  How about new Michelle? That's a challenger. Yeah, I know that.

• 17:20Speaker 02

  So Dylan, before the break, we were discussing your challenge trial. And it basically sounds like it was kind of a low risk for you, high potential reward for humanity kind of situation, right?

• 17:32Speaker 03

  Yep.

• 17:33Speaker 02

  But is that always the case? Like, have volunteers ever died doing something like this?

• 17:38Speaker 03

  So the history of deliberate infection to study diseases goes back to when the smallpox vaccine was invented in the 1790s. So this is hundreds of years. And it will not surprise you to learn that not every study over that period was conducted with the utmost in ethical rigor. There was a famous case where an army doctor in Cuba in 1900, so this was two years after the US had invaded Cuba and was occupying it after the Spanish-American War. There was a horrible yellow fever problem, and he wanted to prove that mosquitoes transmitted yellow fever. And so he got bitten by mosquitoes. And I know I'm not prepared for this twist. He died of yellow fever.

• 18:23Speaker 03

  And sort of afterwards, his boss, who was a guy named Walter Reed.

• 18:29Speaker 02

  Like the hospital?

• 18:30Speaker 03

  Yes, that one. Decided to do his own human trials, and he wrote up an actual ethical code. And I don't think it's an ethical code that I would sign. It's a

• 18:42Speaker 02

  Wait, what's in this ethical code?

• 18:45Speaker 03

  It says, "The undersigned understands perfectly well that in the case of the development of yellow fever in him, that he endangers his life to a certain extent. But it being entirely impossible for him to avoid the infection during his stay on this island, he prefers to take the chance of contracting it intentionally in the belief that he will receive the greatest care and the most skillful medical service." It's like, you understand that this is a risk. However, you also say, "I'm gonna die anyway, because there's so much yellow fever here."

• 19:16Speaker 03

  And I have gotten this awesome deal from Dr. Walter Reed, and so I'm going to take that. But he did pay them, and he did demonstrate that mosquitoes transmit disease. And the result of that was a eradication campaign that dramatically reduced the level of yellow fever there. So I think that's a situation I look back at. Was it perfectly awesome? No, like, the US was occupying them. You could not have full informed consent in that circumstance, full stop. But it did work. And they did learn important information that led to saving many, many lives. In the modern context, there's a review that went over

• 20:01Speaker 03

  about 308 challenge studies that took place from 1980 to 2021. So this is sort of the modern period of challenge studies.

• 20:09Speaker 02

  We have left Walter Reed in the past.

• 20:11Speaker 03

  Left Walter Reed in the past. So they found that there were 24 serious adverse events out of 15,000 patients. So less than 0.2% had a serious side effect of any kind. And it didn't seem like any of these were life threatening. They were just some kind of medical side effect. And not a single out of the 15,000 people died.

• 20:36Speaker 02

  Okay.

• 20:37Speaker 03

  So that seems like a pretty good safety record to me. Like, it's not perfect.

• 20:42Speaker 02

  Is this just on malaria, or this is all challenge trials?

• 20:46Speaker 03

  This is all challenge studies, regardless of passage. And malaria is, I think, the longest running one. But there, flu is the other major category that we've done a number of challenge studies on.

• 20:59Speaker 02

  Are there steps that have been taken, you know, to sort of make sure that this is fully ethical, I guess?

• 21:07Speaker 03

  Yeah, I think the, all of these things run through IRB panels for ethical review. I think there's much longer and more detailed disclosures, like all the documents I got at the start of the study. Every day that I went in, even just to sort of get my temperature taken and my blood drawn, the first thing they would ask is, do you still consent to participate in the study? And they made it very clear that I could drop out at any moment if I wanted to. So like, things are better now.

• 21:36Speaker 02

  Are there any arguments against challenge trials that you do find compelling?

• 21:41Speaker 03

  So I think the best argument against challenge trials, which is not so much against them, but is sort of pointing out their limitations, is that getting infected in a lab in a rich country is not the same thing as getting infected the way that people get infected with malaria in West Africa, the way people get dysentery from unclean drinking water in poor countries. You're sort of mimicking the way that this disease transmission happens in real life, but you're never going to mimic it perfectly. And what's more, you're doing this with mostly young, healthy volunteers. And so this was a big issue during COVID where the people who were dying from COVID tended to be old, have underlying health conditions.

• 22:27Speaker 03

  And they were never in a million years going to get like an immunosuppressed 75 year old in a challenge trial for COVID.

• 22:33Speaker 02

  Right.

• 22:34Speaker 03

  That is just way too high risk. But at the same time, because of that, a challenge study wouldn't have been able to tell you necessarily how effective a vaccine was for that person. And that was the person who needed a vaccine the most. So I don't think that's a, that rules it out, but it does mean that it's a complement rather than a full replacement. So challenge studies are sort of quick and cheap first step before you, you do broader field testing.

• 22:58Speaker 02

  So they're not a replacement for a full field vaccine trial. Can we, can we use them for every disease?

• 23:08Speaker 03

  So I think generally places will only do challenge trials for diseases for which we have ready and available cures. That the thing people are worried about ethically with challenge trials is what if we expose people to an illness and then we can't cure it from them if they get it and the vaccine we're testing doesn't work. So for example, we haven't had challenge trials for TB yet because while you can cure TB, sometimes it's drug resistant. Curing it often takes like six months of antibiotics rather than like a week of anti-malaria drugs that I had to take.

• 23:42Speaker 02

  And having tuberculosis for six months could actually be like an issue.

• 23:47Speaker 03

  Right, right. It could have long-term health consequences. So that's considered too dangerous. And I think in particular, New diseases, new pandemics, things like COVID that feel like they come out of nowhere are going to be hard to do challenge studies on just because we probably don't have a way to fully cure them yet.

• 24:08Speaker 02

  Did we do challenge trials on COVID despite that?

• 24:13Speaker 03

  We did not in 2020 during vaccine development. There have since been some challenge studies on COVID investigating various aspects of it, but only now that we have vaccines, now that we have Paxlovid, other highly effective treatments for it such that we can be reasonably sure that the people on the challenge trial will be okay at the end of it.

• 24:38Speaker 02

  Overall, why did you think it was important that you do this?

• 24:42Speaker 03

  So I think I sometimes when I was doing it, people would ask, like, isn't it like scary to expose yourself to malaria? Like, isn't that, this is just too much, like, like, like, you'd have to be a pretty extreme person to do that.

• 24:58Speaker 02

  And you'd have to be the kind of person who gives a kidney.

• 25:02Speaker 03

  I would just like to remind them that in countries like Nigeria, on average, you have kids being infected with malaria two or three times a year. And like, that's on average. Some kids get it six times a year. That it's, it's like the flu or RSV or the cold. It is something they're being exposed to every single day. And I think the question I asked myself is like, what does it say about me if I'm not willing to face what they face every day, just for one day on a one-off in a much comfier environment? And I think that centers it a bit for me of this isn't about me. This is about specific people

• 25:44Speaker 03

  who are suffering and they're suffering specifically because they are against their will being exposed to a very dangerous illness. And it's better that I consentingly be exposed to a dangerous illness in a context where it's made as safe as possible than that they keep being menaced by it day after day.

• 26:10Speaker 02

  I think that's a really great answer. It makes me feel like it's a long drive to Baltimore, in my defense.

• 26:19Speaker 03

  It is. You can't, no. If you live in New York, absolutely not.

• 26:25Speaker 02

  All right, great.

• 26:26Speaker 03

  If you feel bad, yeah, like, on the scheme of things, I'll bug you about kidney stuff before I bug you about this.

• 26:36Speaker 02

  Great.

• 26:47Speaker 02

  Dylan Matthews is the head writer for Vox's Future Perfect. If you want to read more about challenge trials and malaria, he has a great piece about all of this on our site. Also, this particular trial was funded by a foundation, but Dylan has done some reporting on what the loss of federal funds could mean for anti-malaria efforts worldwide. We will link to both of those in the transcript. This episode was produced by me, Bird Pinkerton. It was edited by Meredith Hodnot, who runs the show. Noam Hasenfeld is our host. He did the music for this episode. Christian Ayala did the mixing and the sound design. Anuk Dusso checked our facts. Anuk, thank you for everything. You have been amazing.

• 27:30Speaker 02

  And thanks also, as always, to Brian Resnick for co-founding the show. Meanwhile, have you participated in a study of some kind? Or do you have other thoughts on this episode? Please tell us. Write in to [email protected]. If you want to support the show and help us keep making it, I cannot tell you how much we'd appreciate it if you'd join our membership program today. That is at vox.com/members. vox.com/members. You can also support us by leaving a nice rating or a review, or just by telling people in your life to listen. And thank you for listening. It means a lot.

• 28:13Speaker 02

  Unexplainable is part of the Vox Media Podcast Network, and we will be back next week.

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