--:-- Sean Rameswaram: Support for Today Explained comes from the FIFA World Cup, of all things. The FIFA World Cup 26 is coming to North America next summer. It is the ultimate celebration of sports and culture. You can get closer to the beautiful game with a hospitality package, closer to the action, the best seats, the best suites, closer to match day and that world-class food and that world-class entertainment, closer to the experience of a lifetime. Book a hospitality package at fifaworldcup.com slash hospitality.
--:-- Sean Rameswaram: What do you think the deadliest animal on Earth is? I'll give you a hint. You hate them. They're tiny. You murdered many of them. Yes, it's the mother f***ing mosquito.
--:-- Kelsey Piper: [laughs] Yeah, that's right. In fact, the overwhelming majority of species of mosquito don't bite humans at all. And of the ones that bite humans, there's really only a couple, and really only one major one that carries the malarial parasite.
--:-- Sean Rameswaram: So scientists have been working really hard to develop a vaccine, and they're finally getting somewhere. Dear colleagues and friends, The World Health Organization announced on Wednesday that there is now a vaccine that they recommend to children in high-risk areas that'll reduce their odds of dying of malaria.
--:-- Kelsey Piper: Using this vaccine in addition to existing tools to prevent malaria could save tens of thousands of young lives each year. I started my career as a malaria researcher and I longed for the day that we would have an effective vaccine against this ancient and terrible disease. And today is that day.
--:-- Sean Rameswaram: Does it have a fun name like Spike Facts? Spike! Yeah, it's called Muskyrix. Muskyrix. Muskyrix, for when you can't kill mosquitoes like me.
--:-- Kelsey Piper: It used to be in trials, it was called RTS, S. That's not as good. Yeah, no, Muskyrix is a huge step up in branding, and the vaccine is a huge step up in the fight against malaria.
--:-- Sean Rameswaram: Malaria kills 400,000 people a year, and that's mostly young children and pregnant women. It tends not to affect adults and people with a healthy immune system. And of course, adults in high malaria areas have usually fought it off repeatedly and have some immunity.
--:-- Kelsey Piper: But it hits young kids really hard. Remind the good people how malaria makes you sick. So the parasite that causes the malaria disease is carried by mosquitoes. Here is the female Anopheles mosquito feeding with her body held high in a straight line with her long beak.
--:-- Sean Rameswaram: It infects the mosquitoes. When the mosquitoes bite us, it infects us. She sticks her beak through the skin, secreting saliva to make the beak go in easier. With the saliva, malaria germs are carried into the blood.
--:-- Kelsey Piper: And it completes its life cycle by reproducing in the liver, entering the blood, and then being passed along to the next mosquito to bite you. Recurring cycles of chills and fever sap the victim's strength. Along the way, it can cause intense fevers and kill young people whose immune system can't fight it off.
--:-- Sean Rameswaram: Why has it taken so long to reach this point where we might have a, you know, efficacious vaccine? So vaccines for viruses like COVID or like smallpox or like polio are just easier to develop than a vaccine against a parasite.
--:-- Kelsey Piper: A virus is very small. It's pretty compact. It has very few parts and it needs all of them. A parasite is an entire living organism. And so figuring out what part of it you want to counter, what part of it your antibodies need to recognize is harder.
--:-- Sean Rameswaram: And then making matters worse, malaria is not a disease where you get it once and you're immune for life. Like smallpox, you caught it once, you never get sick again. Malaria, you can get malaria up to like six times a year.
--:-- Kelsey Piper: And in fact, even among people who don't die of malaria, it can have huge long consequences just because constantly fighting off this serious illness leaves your body weaker means you don't have the chance to grow up as healthy and you know develop as a fully healthy person.
--:-- Sean Rameswaram: So beating that is a huge deal. And it's taken scientists sort of a long time to narrow down what part of the parasite life cycle we can most effectively target, what proteins we're going for, what antibodies we even want to teach the body to make, but they're getting somewhere.
--:-- Kelsey Piper: There have been efforts to develop a malaria vaccine that go back a century. Muskyrix actually work on it started in the 1980s. That's when GlaxoSmithKline, which is the pharma company that developed this, first put together the pieces that became RTS, S.
--:-- Sean Rameswaram: Okay, so a really long time. Yeah, it's an obvious one to go for as soon as you have the concept that we can use vaccines to control infectious disease. Malaria is really bad. It's one of the worst ones out there. And a vaccine is going to be a huge part of any strategy to control it.
--:-- Kelsey Piper: Currently, we do preventative prophylactic distribution of medications against malaria. We do bed nets. Those help a lot, but they can only get you so far. Whereas a vaccine, if you can make it universal enough, if the vaccine is effective enough can really just change the game.
--:-- Sean Rameswaram: So in early stages of figuring out how to fight malaria, there were efforts to target it at different points in the parasite's life. Like, do you want to target it as soon as it gets injected into the body? Do you want to hit it in the liver where it's multiplying? A lot of those turned out to be dead ends.
--:-- Kelsey Piper: RTSS and, you know, other efforts at a successful malaria vaccine try and hit it early, prevent it from getting to the liver and reproducing in the first place. And then that can stop you from getting as sick. And they've also gotten a better understanding of how to prompt the body to do that, like which specific things you need to teach the body to look out for so that it can mount a strong immune response when the parasite shows up.
--:-- Sean Rameswaram: So, unfortunately, not as effective as we'd like. It depends a little bit on how you measure it. But in general, for someone who's gotten the whole course of shots, you see like a 30% reduction in the risk of severe disease from a malaria.
--:-- Kelsey Piper: Now, when 400,000 people are dying every year, 30% reduction, that's still very real. But it's not the sort of dream vaccine that, you know, would just mean malaria was a thing of the past.
--:-- Sean Rameswaram: And now that vaccines are so top of mind for a lot of people, I mean, how does this one get delivered? Is it one shot? Is it two? Is it four? How does it work?
--:-- Kelsey Piper: It's four shots, three of them a month apart and then a booster a year later. That's obviously a lot to administer. But since malaria is so hard to teach the body to make an immune response against, it's kind of what you got to do.
--:-- Sean Rameswaram: Does that mean that this vaccine is presenting an additional challenge of getting someone to come back twice and then even a third time for a booster shot?
--:-- Kelsey Piper: So obviously that's a huge challenge in vaccine administration. But what the World Health Organization recommended Wednesday is that nations make this part of their normal childhood immunization program.
--:-- Sean Rameswaram: So this is something that like the measles vaccine, like the diphtheria or whatever else, you're administering to young kids as part of routine medical care.
--:-- Kelsey Piper: So a lot of the time that means you're traveling around in these communities frequently anyway in order to get those kids all their other shots, which hopefully makes it a little easier to add the malaria shot into the mix, you know, without having too many problems with uptake.
--:-- Sean Rameswaram: And they've had pretty solid uptake in the countries, Ghana and Kenya and Malawi, where they did a pilot program.
--:-- Kelsey Piper: So, you know, despite the four shots, they're really able to get people to get the care that their kids need.
--:-- Sean Rameswaram: OK, and this four shot vaccine for malaria, Muskyrix, it's the first one the WHO has ever recommended. Will it be the last?
--:-- Kelsey Piper: Hopefully not. So 30% efficacy, it's much better than nothing. It's not really good enough to turn around the whole fight against malaria. And there are vaccines in the works that look like they're a little bit better.
--:-- Sean Rameswaram: One study came out in April. It was a phase two clinical trial. So in a real population, but pretty small scale, that found something like a 77% reduction in severe malaria cases.
--:-- Kelsey Piper: That's a lot more. It's huge. It's really exciting. And that one is now in phase three trials, which are larger scale and will be more definitive.
--:-- Sean Rameswaram: And if that holds up, then we might only have Muskyrix for a few years before we're able to replace it with something even better.
--:-- Kelsey Piper: And I know of things that are earlier in the pipeline and, you know, obviously have a high chance of not panning out, but that have the potential to be even better.
--:-- Sean Rameswaram: So I do think eventually we have a shot at getting one of these vaccines that is as effective against malaria as vaccines against measles which is like 95 percent effective or COVID which is like 90 percent effective against the original variant.
--:-- Kelsey Piper: Well, that would be the hope. OK, Sean, we have to take a break because that's the nature of this show. But I have to ask, when we get back, can we talk about just killing all the mosquitoes? Would that help?
--:-- Sean Rameswaram: Oh, man, I would love to kill all the mosquitoes. That full plan, probably not going to happen, but there are some things sort of like it in the works.
--:-- Kelsey Piper: Uh, guys, uh, I'm still here. I heard that.
--:-- Sean Rameswaram: Support for today's show comes from Adio.
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--:-- Kelsey Piper: You'll see all your relationships in a fully fledged platform, they say, all enriched with that actionable data. And they say you can build AI-powered automations and use its research agent to tackle some of your most complex processes to seize so that you can focus on what matters, building your company.
--:-- Sean Rameswaram: You can join industry leaders such as Flatfile, Replicate, Modal, and so much more. You can go to adio.com slash todayexplained to get 15% off your first year.
--:-- Kelsey Piper: That's A-T-T-I-O dot com slash todayexplained.
--:-- Sean Rameswaram: We all have moments where we could have done better, like cutting your own hair. Oh, yikes. Or forgetting sunscreen, so now you look like a tomato. Ouch. Could have done better. Same goes for where you invest. Level up and invest smarter with Schwab.
--:-- Kelsey Piper: Get market insights, education, and human help when you need it. Learn more at schwab.com.
--:-- Sean Rameswaram: Kelsey, not all mosquitoes are malarial, obviously, yes?
--:-- Kelsey Piper: Yeah, that's right. In fact, the overwhelming majority of species of mosquito don't bite humans at all. And of the ones that bite humans, there's really only a couple, and really only one major one that carries the malarial parasite.
--:-- Sean Rameswaram: So the mosquitoes that can carry malaria are the ones of the genus Anopheles. This is the story of an outcast. You all know her name, Anopheles Annie, the malaria mosquito.
--:-- Kelsey Piper: And those live all over the world. It's just that in most of the world, they don't give you malaria. If malaria were introduced, there would be Anopheles mosquitoes, you know, in the U.S., in Europe, everywhere but Antarctica that could carry it.
--:-- Sean Rameswaram: But we've successfully wiped out the malaria parasite. To look at me now, you wouldn't hardly believe it. But back in the good old days, I was really some stuff.
--:-- Kelsey Piper: So this isn't really a question of getting rid of all of the mosquitoes. It's about getting rid of these kinds of mosquitoes that have malaria.
--:-- Sean Rameswaram: Yes. So obviously, if no mosquitoes ever bit anybody again, I think we would all love that. But in terms of minimizing the impact on the ecology and not having a risk of serious environmental side effects, most proposals to, you know, use gene drives or use sterile male mosquitoes to wipe out malarial mosquitoes have focused very narrowly on the specific kinds of mosquitoes that bite humans and can carry malaria.
--:-- Kelsey Piper: So we might still have other mosquitoes around, and, you know, the mosquitoes that only bite livestock, probably we don't care as much about those being around, and that way we just don't have to worry about, you know, majorly disrupting ecosystems by taking out an entire kind of animal, even if it's a kind of animal who we all hate.
--:-- Sean Rameswaram: You're answering a question I have for you here in advance of me asking it, which is, would it be bad to just get rid of all of the mosquitoes? We don't know.
--:-- Kelsey Piper: I think it might be fine. But since we don't know, and since it's a little bit hard to reverse, probably it's smarter to do something more conservative, like get rid of all the malaria-carrying or human-biting mosquitoes.
--:-- Sean Rameswaram: The Florida Keys Mosquito District has started releasing about 12,000 genetically modified non-biting mosquitoes, part of a pilot project the EPA approved last May.
--:-- Kelsey Piper: You know, which is narrower and almost definitely safe. The plan? Test to see if a genetically modified mosquito is a better alternative to spraying insecticides to control the type of mosquito carrying deadly viruses in the Keys including Zika dengue and yellow fevers.
--:-- Sean Rameswaram: I think we talked about some of the strategies here on the show before at least one maybe where Bill Gates wants to edit the genes of these malarial mosquitoes using CRISPR. Correct me if I'm getting anything wrong, but...
--:-- Kelsey Piper: Yeah, no, that is a proposal that's been put forward. And so we're working on genes that either reduce mosquito populations or eliminate the anophely mosquitoes.
--:-- Sean Rameswaram: What else is out there? All right. So one option, yeah, is putting a sort of genetic time bomb in some mosquitoes where maybe they can have children, but those children will be sterile.
--:-- Kelsey Piper: And you put those mosquitoes out there and then you have a next generation of mosquitoes that all have this gene for sterility or many of them carry it on. And then if you design your gene drive correctly, after a couple generations, you've wiped the species out.
--:-- Sean Rameswaram: There's obviously a lot of challenges in implementing this, but researchers have plans for it. And, you know, given that 400,000 people a year are dying, doing testing and figuring out how that works is definitely a priority and something I think we should honestly be investing more in.
--:-- Kelsey Piper: Another option, which is a little bit less scary to audiences, it doesn't have the phrase gene drive in it, is you flood an area with tons of sterile male mosquitoes. And then the female mosquitoes will mate with your sterile male mosquitoes instead of with the regular male mosquitoes.
--:-- Sean Rameswaram: Oh, no. And since the sterile males will die off, this is a temporary intervention. So we can sort of do it, wipe out the mosquitoes basically to a tiny fraction of their original population for one mosquito generation.
--:-- Kelsey Piper: They'll come back over time, but that lets us test. Like, okay, we wiped these mosquitoes out. Did that have any negative ecological consequences? Did it have the desired effects on malaria? We can sort of do things like that.
--:-- Sean Rameswaram: And there have been some pilots of projects like this and see, OK, wiping out mosquitoes seems to be going pretty well.
--:-- Kelsey Piper: So all these strategies are like based around tricky sex? That's honestly many of the strategies I've heard of basically amount to that.
--:-- Sean Rameswaram: Oh, yeah. You want to mess in some way with the mosquito life cycle. And in general, the easiest way to do that is either interfering with reproduction or interfering down the line with subsequent generations reproduction.
--:-- Kelsey Piper: Do we have any idea at the end of the day what the likelihood is that in order to eradicate malaria that we'll need both of these strategies, an efficacious vaccine and maybe some sort of tricky sex mosquito situation?
--:-- Sean Rameswaram: So I think when something is killing 400,000 people a year, you proceed on all fronts, right? You try and design a great vaccine. You try and design a great eradication plan.
--:-- Kelsey Piper: In principle, maybe the eradication plan would work without vaccines, but maybe we come up with something that partially works but doesn't fully solve this for us, and then the vaccines make a huge difference too.
--:-- Sean Rameswaram: Or maybe we end up doing so well with vaccination that we feel a little less urgency on rolling out a gene drive eradication type solution.
--:-- Kelsey Piper: It just gives us a little bit more opportunity to save lives and figure out the exact right way to do eradication.
--:-- Sean Rameswaram: I think just when the stakes are this high, it's worth sort of doing everything we can.
--:-- Kelsey Piper: And in the meantime, is it still cool if we just murder as many mosquitoes as we can?
--:-- Sean Rameswaram: I see no scientific reason why you shouldn't hate mosquitoes. They're the worst. They kill tons of children. You know, a grudge against mosquitoes is one of the most justified grudges you could possibly have.
--:-- Kelsey Piper: Blessings thank you so much Kelsey.
--:-- Sean Rameswaram: Kelsey Piper is a very evil staff writer for future perfect thoughts.
--:-- Sean Rameswaram: Will Reed and Miles Bryan produced this episode they seem okay and Sean Rameswaram farms the host it's today explained.
--:-- Sean Rameswaram: We'll see you next time.
