Daniel and Kelly’s Extraordinary Universe - How do we control mosquito populations?

Episode Date: December 4, 2025

Daniel, Kelly, and Katrine chat about how mosquitos find us, and what we can do to protect ourselves from the diseases they transmit.See omnystudio.com/listener for privacy information.

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If you live in most places in the United States, mosquitoes are a massive annoyance. They've ruined a good hike. They've ruined a beautiful night camping under the stars. They've ruined delicious picnics. And they ruin breathtaking sunset. They are the worst. But if you live in an area where mosquitoes carry deadly diseases like malaria, dengue, yellow fever, or Zika, they're also potentially deadly. According to the Centers for Disease Control, malaria alone killed 597,000 people in 2023.

So what are our options? Mosquitoes have developed resistance to our insecticides, and insecticides in general aren't great for ecosystems because they all. often kill a bunch of other stuff as well. But what if we could use new genetic tools to drive some mosquito species to extinction or make those mosquitoes resistant to diseases so they can no longer transmit those diseases to us? Today, we're going to respond to some listener questions about mosquitoes.

We'll chat about how mosquitoes find us, how genetic engineering could be used to combat mosquitoes, and how you undertake the tricky task of estimating how mosquito population sizes are changing, over time. Welcome to Daniel and Kelly's mosquito infested universe. Hi, I'm Daniel.

I'm a particle physicist, and I have a top five list of animals I'd like to see genocided off the planet. Oh, man, start in an episode with the word genocide. I'm not loving that. Hi, I'm Kelly Weiner-Smith. I study parasites and space, and I was going to say I'm buzzing with enthusiasm for this topic,

but Daniel started with genocide. So my enthusiasm has been shot through. Did that sting you a little bit? Scratching the wrong itch over there. I can't. I can't. All right. What are the five insects that you like the least, Daniel?

We could put it that way, too, you know. Yeah, number five mosquitoes, number four mosquitoes, Number three mosquitoes, number two mosquitoes, and number one, coming in at the top of the list is mosquitoes. Oh, yes, predictable list. Yeah, I'm not a mosquito fan, really either. Absolutely. And so I'm fascinated today that we're going to be talking about the science of mosquitoes and learning about everything that biologists can do to improve our quality of life. Yeah, I mean, biologists and engineers, a variety of folks for many decades have been trying to do battle with mosquitoes. And, you know, in the last few decades, we now have some genetic tools that we can use that might give us the leg up. And your focus, of course, is on eradicating disease-carring mosquitoes because that kills people and all that stuff.

And all that stuff. But along the way, I would eradicate Daniel suffering from mosquito bites. Because that's what it's really all about in the end. It's about me and my itches, right? No. I'd say no. Yeah, I don't actually know. that I would advocate for eliminating mosquitoes that are annoying but don't transmit disease.

Although I guess in California, do your mosquitoes transmit West Nile? I don't know. I have heard of cases, but I'm not sure. But really for me, it's just all about the itches. I'm not a great sleeper and I'm very responsive to mosquito bites, which means if I get too many mosquito bites, then I'm up all night scratch at them. So it's really a bummer. I would happily actually donate my blood to the mosquitoes if we could make a deal. Like, if I could just put out a little, like, saucer of blood every night and be like, here's your blood meal, leave me alone. I would make that deal.

No trouble at all. So if the Mosquito's lawyer wants to reach out and negotiate some sort of settlement like that, I am open for business. All right, yeah. So you give your fecal sample to your wife and your blood sample to the mosquitoes. Everybody needs a part of Daniel. Come take a sample, exactly. Matt will take an audio sample.

Here we go. All right. Well, then you will be very excited to hear. here today that there are a variety of cutting-edge techniques for, in some cases, straight-up eradicating mosquitoes, and in other cases just trying to make it so that they can't carry disease anymore. I like the sound of straight-up eradication. Well, we, I reached out to our extraordinarily and asked them what they think the most promising techniques for eradicating disease-carrying mosquitoes are. And let's go ahead and hear what they had to say.

Treat the water where they breed. Kill the larvae. Someone far smarter. than I am, must have a technique to get them to stop breeding. I like what they've done in the past with releasing genetically modified ones so that it reduces the population and potentially targets those disease-carrying ones because the generic sprays kill all sorts of insects, and they are beneficial for the ecosystem. Does the Geneva Convention apply to mosquitoes? If it does, I'd have to say some bioengineered aerosol that wouldn't harm other living creatures. The one technique I know right now is that some larvicide is spread during mosquito season.

I'm not so sure that is the most promising technique since that's been done for a long time and we still get a lot of mosquitoes. It appears the sterile insect technique is the most promising method, though I'm not sure if that will eradicate or just vastly reduce population numbers and is nowhere near as fun as an electrified racket swatter. We would genetically engineer some very attractive but sterile mosquitoes, dispatch them to the affected areas, let nature run its course, and over time the population will fade away. Do the thing they're doing with the screwworms and doing like sterilized ones. And I really do hope that you kill all mosquitoes because they love me. I am foreign food here in the UK, even though I'm half English.

So kill them all. I think a lot of people are on the same page with you, Daniel. eradicating mosquitoes, they are on board. It sounds like somebody else spoke to the mosquito's lawyer because they're referencing the Geneva Convention and like getting all legal about it. Oh, my gosh. I know. I know.

These things are intense. And, you know, in the United States, if you do want to release some method for eradicating mosquitoes, you do need to go through like the USDA, the EPA. We'll talk about this a little bit more later. There's some legal stuff involved. I think that probably makes sense. Somebody should think about whether these are good ideas before we just like let scientists do things willy-nilly. I'm for that.

I'm going to let you in on a little secret. We've messed things up a few times in the past. Yeah, I know. I know, right? We can't be trusted to make our own decisions. Well, I think some oversight is warranted. That's a good way to put it. We get a little over-enthusiastic. We do because the universe is amazing and we just want to learn stuff and we think we

have it figured out. And so, yeah, we just want to press the big red button sometimes. Well, today we're going to be learning specifically about answers to questions that we got from listeners, and we called in a little bit of backup because any biology topic is improved by having Katrina Whiteson join the podcast. So let's invite Katrina on the show. It's my great pleasure to welcome back to the podcast, our most popular, our most frequent guest, also winner of the Whiteson Unable to Say No to a Podcast Invitation Award, Dr. and Professor Katrina Whiteson. Wow, thank you for the glamorous introduction.

Thank you for being willing to come back on the show again. We always love having you. Well, thanks all around. All right. Let's dive right in. So we have a couple questions from Robert Shackleford, who is a high school teacher who wanted to know about mosquitoes. So let's dive in. Hello, Daniel and Kelly.

This is Robert on San Juan Island in Washington State. And I'm curious about mosquitoes. Well, it's probably more accurate to say they seem to be curious about me, unfortunately. and where we live there's a pond nearby and if you're anywhere near the pond you will get bitten right away further from the pond it's not so bad unless you're stationary and then they will find you and when they find you they really find you and that has to be wondering if they are coordinating their attack somehow if they are watching each other or if they are little mosquito walkie-talkies i don't know, or are they just acting individually on the same clues to find the victim? And then similarly,

I would love to know how many mosquitoes I'm up against, right? It's important to know your enemy. And how would you ever estimate a mosquito population? I know there's some techniques for estimating wildlife, say birds by tagging them and then recapturing them later. But I can't imagine doing that with mosquitoes. Sorry, Kelly, I can't imagine even the best biologist having the ability to take little tag number 42 and glue it to a mosquito's leg and be able to capture it later. So I'm curious, is there a way? Is that number even knowable? Is there a way to make a good estimate of mosquito population? Really curious. Thank you so much for taking on my question. Look forward to hearing from you soon. Wonderful question. I love hearing from high school teachers. And thank you to

all the teachers out there working on the front lines of education to make society a better place and everybody smarter. Y'all are heroes. Thank you so much. And I am thrilled to get to, you know, educate folks about mosquitoes, which I have to admit I hate. It's not hard to admit you hate mosquitoes. It's joyful.

I guess. I don't know. I'm an ecologist. I'm supposed to like almost everything. But I have to admit dipterins, which are like mosquitoes and flies. I'm not a big fan of. Well, you know, I used to say all the time that mosquitoes are the one thing you could, like, erase from the planet and not have any negative effects.

But then some listener sent me an article about how mosquitoes help chocolate, help cocoa beans pollinate each other. And I was like, uh-oh, I'm not sure if I had to give up mosquitoes if I would also give up chocolate. It sounds a little bit tough at first. But when you consider that mosquitoes transmit malaria, which kills almost 600,000 people a year, I would give up chocolate for that. I mean, I hear you, but we're talking about chocolate here, Kelly.

We're talking about children, Daniel, but I have to remember that you are willing to give up all of humanity to get one answer from an alien. We had that discussion the other day. I made a juicy answer, but yes, yes, I am. That's true. All right. I'll note that his wife was also shaking her head in disbelief. I don't like this new number of podcast hosts where I can get outvoted. We'll go back to mosquitoes. Mosquitoes are often listed as the deadliest animals on the planet. Wow.

And one of the problems caused by mosquitoes is that they transmit malaria. There are over 500 Anopheles mosquito species, so this is like a genus of mosquito, and about 60 of those species are able to transmit malaria. Mosquitoes also transmit denge, West Nile, Zika, lymphatic filariasis, and so mosquitoes are estimated to kill indirectly up to a million people a year. But I've never felt like this is super fair to pin on mosquitoes, even though. I hate mosquitoes because it's like, isn't it the individual responsibility of all of those diseases? It's not necessarily the mosquitoes, but, but I get, I get it. They were unwilling

partners. Nobody, like, they didn't say, yeah, bring on that plasmodium. They were just like flying around. Right. But they do drink blood. I mean, I don't know. I mean, Kelly, if I came over to your house and drank your blood and gave you some weird disease, I think you'd blame me for anything you got, wouldn't you? You would not be invited again. That's true. And you would be breaking a lot of social mores to do that. Yes, and laws.

And laws. Right. But does anybody want to guess? This surprised me a little, but it shouldn't have. On the list of species that kill humans, mosquitoes are at the top. Wow. What species is second? The next most killing-y species kills about half as many humans each year.

But what would you guess that species is? Raccoons. Oh, come on, Daniel. Those are ferocious. Have you heard that story about raccoons? Don't have a pet raccoon, FYI, and don't Google what happens if you leave a raccoon in a room with your baby. Definitely don't Google that. But I would guess it's microbial.

I mean, it has to be microbial. Microbes rule the world. So now I've got to pick from microbes, and I really should know this. I mean, it could be tuberculosis, bacteria. That is still a problem. Which infects a threat of humans. or it could be microbial raccoons

some kind of parasite some kind of eukaryotic parasite is that what it is? It's humans oh my gosh oh that's so good I think Katrina gets points because we are eukaryotic parasites

right so there you go there you go so Katrina essentially got it right one point for Katrina zero points for raccoons from Daniel I'm not going to I can't take any points I was going down a totally wrong road there

And I really thought it was microbial, you know? I also felt like you could just blame bacteria across the board. But anyway, the list right now has humans. I guess we kill about half a million of each other every year, which is depressing. Wow. But all right, let's talk about the mosquito life cycle real quick, because understanding the life cycle is necessary if you're going to understand how you can try to eradicate mosquitoes by breaking part of the life cycle. So first, let's note, there's lots of mosquito species like over 3,500 mosquito species.

They don't all bite humans. Oh. The ones that do bite humans are females. The males actually don't take blood meals. And the females apparently need the blood to make eggs. Ooh. Okay, so if you get bit, it's a female. Don't blame the female.

They're just doing what evolution made them do. But anyway, so they do the blood meal. So they get a blood meal. They lay their eggs in a body of water. The eggs hatch in the water. And then they've got this aquatic stage where they look like these sort of like frilly little specks of dirt that kind of move around like crazy all over the place. Sometimes you might see them in like a bird feeder in the middle of the summer or something. And then they have another

stage where they essentially like stay near the surface and they're kind of getting oxygen from the surface. And then they emerge out of the aquatic environment as adults and they go off and, you know, mate with each other and go off in search of blood. And all this happens in hours or days or? Depends on the species. There's a lot of variability. But an egg can take something like seven to ten days to develop into an adult. And then when they're an adult, I think they've got like a week or a few weeks. They don't live for very long. So when a mosquito is biting you, it's like one of a few dozen meals it's going to have in its lifetime. Or how many blood meals does a mosquito have in their whole lifetime? They must be taking more than one blood meal,

but I think they only mate with a male once in their life and lay eggs once. And that has to be the case for a bunch of the techniques that we talk about later to work. Well, I know that in Southern California, we have two different kinds of mosquitoes, so the ones that come and give you one really big juicy bite and then move on, and another tiny version that come and bite you like four times in a row. Oh, they're all awful, though. They're all awful. Yeah, thumbs down. Well, so then how do they find you? Yeah. So Robert wanted to know if they're like communicating with each other so that they can swarm and get to you. And I don't think that that's what's happening. I didn't find any evidence that a mosquito is like altruistic enough to be like,

hey, there's a snack over here, fellas, or I guess ladies. Hey, ladies, there's a snack over here because it's all females do in the feeding. I think that the only times they swarm on purpose is when they're trying to mate. And so usually they're not sharing information, but the way they find you is a multi-step process. First, they detect the carbon dioxide that we breathe out, and then they follow the carbon dioxide trail until they get close to us. When they start getting close enough to us, they start detecting some odors that we give off. And these odors can be things like ketones, lactic acids.

And Katrina, I read that a lot of the odors we give off are related to our microbiome. Exactly. I even had a whole grant once. I didn't get it, but I wrote a grant with a bunch of people. It was a military grant. And the goal was to make soldiers invisible to mosquitoes. And we were going to do it by changing their skin microbiomes. And, you know, some people are just so juicy to mosquitoes.

And they get bitten all the time and others don't. And we don't know why, really. but I think it could be related to the microbiome and the volatoles that the microbes are emitting that the mosquitoes can detect. And so, anyway, it might be that that's something we could change. Like, that's pretty amazing. Hold on a second. I just put two and two together. I live in a house where I'm the one getting bitten by mosquitoes all the time.

And I also live in a house where somebody knows how to manipulate people's microbiomes. And I just heard that microbiomes are the number one influence in who gets bitten my mosquitoes. Hmm. Hmm. Okay. I'm going to have to think about that. Okay. This mosquito preference thing has been going on since way before I learned about microbiome. I see. So you've been guilty for a long time. Got it. Got it. Got it. All right. But it could be a life goal. But for the individual mosquito, Kelly, this is not like, you know, they have complicated sensors. I'm imagining they're like flying through the air and they sort of veer towards the CO2 instead of away from it. It's sort of like moths being attracted to light. Is that how it works? Yeah, I mean, I think it might be underselling it a little bit to say that they don't have complicated sensor.

So, like, moths, for example, the males who have to find the females, they have super feathery antenna and nobody can see, but I have had to have hand antennas right now. You're looking very mothy. I have to say, thank you. And super, they have an incredible surface area, and they're able to detect chemicals that the females put into the environment and follow that chemical trail to find a female. And so, you know, like insects, you know, they might not look super impressive, but they do have pretty important. impressive ways of detecting cues in the environment. Like, I can't detect CO2 and use it to find my dog when she's not coming in the middle of the night when I call her. So anyway, I'm impressed. But, but yeah, it's not super complicated. I mean, I think there's a lot of sensors that we actually don't know what they are. That's something that I'm so fascinated by that apparently, you know, we have these sensory receptors that we know about in our nose and our tongue, like you hear about the sense of taste. But actually, we have those kind of receptors all over the place. They're in our skin. They're in our guts, like babies have them when they're developing. And so I think those receptors are binding molecules. We don't even know what they are yet. And I would not be surprised if mosquitoes

have a lot of that going on too. You're saying we can taste with our hands and stuff like that. Exactly. I see. So when I swat a mosquito and I feel that like moment of satisfaction, it's like literally delicious. Let me just back up on that. I'm saying there's receptors that are sensing those molecules and you're having a response. The response is not lighting up the taste receptors in your brain. At least not for me. I mean, I don't know about you. But I think it's like lighting up something that we, not necessarily that we're even aware of it in our brain, but it could be like affecting our physiology, you know? We had Stephen Munger on the show to talk about taste and smell, and he was talking about how we have receptors for things like even in our

hearts, and it's not quite clear why we have them. So if folks want to learn more about that, they should check out the Munger episode because we talk about that for a little bit. It's totally fascinating, in my opinion. All right. So we were talking about how Mosquitoes find hosts, and you're saying at first they look for clouds of CO2, and then as they get closer, they're looking for skin odorants that give them cues to where you are. And then what? Walk us through all the way to the bite. And then they're looking for heat and humidity. And so I don't think we know exactly how they decide, like, I'm going to bite their arm as opposed to their leg. It might be whatever they encounter first because you want to get the bite in there and get out. But yeah, those are the cues that they use. The cues change depending on how close they are to us. Some people give off more cues as Trina mentioned. That could be because of their microbiome. There's some evidence that women in their third trimester are also more attractive to mosquitoes. And the idea there is that we are breathing more and more heavily and we give off more CO2 so we're easier for mosquitoes to find. I certainly was breathing heavily. I remember my mom being like, do you have to be so loud? And I was like, I do. I'm breathing for two. But yeah, the mosquitoes apparently love that. all right so now we know how mosquitoes find us but now how do you figure out how many mosquitoes are in an area so robert had this great insight which is that often when we are trying to figure out how many of a certain species is in a particular environment we use this technique called mark recapture and it would be really hard to mark and recapture mosquito so mark recapture is a procedure where you essentially go out into an environment twice to collect animals the first time you go out

You collect, you know, as many animals as you can with whatever technique. So, for example, I used to go sample fish, and I would use what's called fight nets. You essentially put a net that goes, one side of it is in, like, the middle of a lake. The other side goes to the shoreline. As the fish swim along the shoreline, they hit the net that hits the shoreline, and they follow it essentially into a funnel that they can't get out of. And then you sample that once a day. Does that make sense? Mm-hmm.

Okay, so we trap fish. We take the fish out. we tag the fish in a way where we will know if we've seen them before or not, and then we release them back into the environment. And then a week or two later, we go out again and we use another technique to catch as many fish as we can. In this case, we're using an electrofishing boat where you stun the fish temporarily. You bring them into a live well on the boat, where it's got a lot of water circulating so that they can, like, come to and stay safe. And then you count how many fish you collected, and you look to see how many of them you're catching

for the second time. So how many of them showed up in both of your samples? And so then you're making this assumption that the proportion of animals that you recought in your second sample is similar to the proportion of animals that you caught the first time in the entire population. So for example, if I caught 50 fish in my first sample and marked them all, and then I went out and I caught 100 fish in my second sample, 10 of which were already marked individuals, The way that I would capture this is I would say 50 times 100, which is the number of fish I captured in both of my samples, and divide by 10, which is the number of individuals I caught twice. And that would give me an estimate that there's 500 fish in the population. All right.

So the goal here is to get a sense for how many animals there are total. Of course, you can't measure all the animals. And so you measure twice, and then you look at the overlap because, like, if you have 100 percent overlap between your two measurements, that means you have a smaller population. If you have no overlap between your two measurements, then you have a bigger population because you're getting like different subsets of the whole population. Is that the way to think about it? Exactly. Yes. Yeah.

Like if you mark 100 fish and then the next day, every single fish is marked, it suggests there's not really any other fish out there. But if only 10% of them are marked, then it suggests that the population has another 90% out there. Right. Cool. All right. So that's how mark and recapture studies work to get a sense for like, how many birds are there or how many cheetahs are there? But what do you do for mosquitoes? You can't capture and mark mosquitoes, can you?

So first of all, thanks, team. It was very helpful to have your input on that. Yeah, so marking and recapturing mosquitoes would be kind of nuts because they're so small and so delicate that when you go to catch them and count them, well, maybe not unfortunately, you usually kill them in the process of counting them. And so how could you mark a mosquito and release it? And the answer is they usually don't. So when a lot of companies are trying, for example, to see how many mosquitoes are out,

there, what they'll do essentially is grow males in the lab and they'll throw out all of the females because you don't want to put any extra mosquitoes out there that will be biting anybody and taking blood meals. But since the males don't take blood meals, they hatch them out of eggs in the lab. And then when they go to emerge to go from the water to their like air phase, they put a powder on the surface of the water. And it's a fluorescent powder. So as the mosquitoes emerge through it, they get covered in this fluorescent dust. Wow. And you get fabulous mosquitoes. And you get fabulous mosquitoes. You can also genetically modify them so that they fluoresce green based on a protein that they're making themselves. But one way or another, you're

making it so that the animals that you've released into the wild are detectable in some way that didn't require you to like handle them, which could kill them. So now instead of doing mark and recapture, you mark in the lab and then when you go out, you can put, for example, a giant tub with dry ice, which releases CO2, that attracts the mosquitoes. And so you find a way to capture them. And then you look at the proportion of mosquitoes that you recapture that fluoresce when you look at them and you'll say, okay, those are the ones we added to the environment from the lab. And then you compare that to the number that didn't fluoresce, which were the wild animals that you're catching for the first time.

And this process does kill them while you're doing the counting. Does that make sense? Yes. So if you attract and capture a bunch of mosquitoes and they're all. all your fluorescent ones, it suggests that your fluorescent ones are dominating the population. And if they come back and you see almost none of your fluorescent ones, it means that they're a tiny fraction of the population. So there's a bunch out there.

Exactly. What I wonder is, like, how many other crazy ideas did they come up with before this crazy idea that they made work? Like, I love the experimental creativity of science this way. You know, like, this is a hilarious idea, but I would really love to see the whiteboard where They came up with all sorts of bizarre ideas, including, like, you know, laser pointers or who knows what. There are some more complicated methods. So, for example, you can, like, look at how many batches of eggs appear to have been laid in, like, some water that you put out.

And then you can try to extrapolate from the batches of eggs, how many females likely came by to lay those eggs. And it's much more complicated. And there's a lot more guesswork because you have to, like, have an estimate for the average number of eggs laid by a female, for example. But yes, I think it is a beautiful technique to release fluorescent mosquitoes who can't bite you and then see how many of them you get back. And this is important because it's like a basic element of mosquito science. It's just like to know what are the populations and where are they, right? Because without basic knowledge, you can't do anything. But I think a lot of people underestimate like how much work goes into just getting some basic information.

Like we had our episode about weather and like just knowing what is the temperature everywhere on the, Earth would be hugely helpful. And we can't know that. We don't know that. And so just like knowing where the mosquitoes are would be massively beneficial, I imagine. Yeah. And actually, I don't know if you guys have ever talked about the citizen science projects that are the reason we have information about insect population size. But for example, many of us have noticed that our windshields are not covered in bugs when we go on a road trip these days. And that's because the insect populations have declined so much. And there are citizen science projects where people will like put nets kind of like the one you described on the top of their cars and drive around and just catch all

the insects and count them. And there were people that were doing that in Germany throughout the 20th century. And that is a big part of why we know about the insect decline. Like if they hadn't done that, we just wouldn't even know. Wow. I didn't know about that. Yeah. That's amazing. Thank you weird German insect capturing people. There are people out there who have enthusiasm for everything. It's incredible. It is. Well, I need a break from all these mosquitoes. I got to go scratch some itches. And when we come back, we're going to talk more about how mosquitoes do what they do and how we do what we do best, which is kill mosquitoes. Wow. Thank you for those answers, Daniel and Kelly. What a relief knowing that mosquitoes

aren't able to coordinate their attacks. Let's hope they do not evolve that ability anytime soon. Also, so amazed that biologists have figured out a way to estimate mosquito populations. Sorry, Kelly. I will never doubt biologists. again. Let's get whoever came up with that idea working on quantum gravity soon. Love the show. Thank you guys so much. Shout out to my Spring Street students. Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google Doc and send me the link. Thanks. Hey, just finished drawing up that quick one page business plan for you. Here's the link.

But there was no link. There was no business plan. It's not his fault. I hadn't programmed Kyle to be able to do that yet. My name is Evan Ratliff. I decided to create Kyle, my AI co-founder, after hearing a lot of stuff like this from OpenAI CEO Sam Aldman. There's this betting pool for the first year that there's a one-person,

a billion-dollar company, which would have been like unimaginable without AI and now will happen. I got to thinking, could I be that one person? I'd made AI agents before for my award-winning podcast, Shell Game. This season on Shell Game, I'm trying to build a real company with a real product run by fake people. Oh, hey, Evan. Good to have you join us. I found some really interesting data on adoption rates for AI agents and small to medium businesses. Listen to Shell Game on the IHeart Radio app or wherever you get your podcasts.

I'm Robert Smith. This is Jacob Goldstein. And we used to host a show called Planet Money. And now we're back making this new podcast called Business History about the best ideas. and people and businesses in history. And some of the worst people, horrible ideas, and destructive companies in the history of business. Having a genius idea without a need for it is nothing. It's like not having it at all.

It's a very simple, elegant lesson. Make something people want. First episode, how Southwest Airlines use cheap seats and free whiskey to fight its way into the airline business. The most Texas story ever. There's a lot of mavericks in that story. We're going to have mavericks on the show. We'd have plenty of robber barons.

So many robber barons. And you know what? They're not all bad. And we'll talk about some of the classic great moments of famous business geniuses, along with some of the darker moments that often get overlooked. Like Thomas Edison and the Elections Chess. Listen to business history on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast.

For 25 years, I've explored what it means to heal, not just for myself, but alongside others. I'm Mike De La Rocha. This is Sacred Lessons, a space for reflection, growth, and collective healing. What do you tell men that are hurting right now? Everything's going to be okay on the other side, you know, just push through it. And, you know, ironically, the root of the word spirit is breath. Wow.

Which is why one of the most revolutionary acts that we can do as people just breathe. Next to the wound is their gifts. You can't even find your gifts unless you go through. the wound. That's the hard thing. You think, well, I'm going to get my guess. I don't want to go through all that. You've got to go through the wounds you're laughing. Listening to other people's near-death experiences, and that's all they say. In conclusion, love is the answer. Listen to sacred lessons as part of the My Kutura Podcast Network, available on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. Hey, I'm Kelly, and some of you may know me as Laura Winslow. And I'm

Telma, also known as Aunt Rachel. If those names, ring a bell, then you probably are familiar with the show that we were both on back in the 90s called Family Matters. Kelly and I have done a lot of things and played a lot of roles over the years, but both of us are just so proud to have been part of Family Matters. Did you know that we were one of the longest running sitcoms with the black cast? When we were making the show, there were so many moments filled the joy and laughter and cut up that I will never forget. Oh, girl, you got that right. The look that you all give me is so black. All black people know about the look.

On each episode of Welcome to the Family, we'll share personal reflections about making the show. Yeah, we'll even bring in part of the cast and some other special guests to join in the fun and spill some tea. Listen to Welcome to the Family with Telma and Kelly on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Okay, we're back, and I'm very excited for this segment of the podcast, where we get to take scientific revenge on all the mosquitoes that have caused me to suffer so much. All right, so we have this question from a listener, James, and let's go ahead and listen to James's question. Hi, Daniel and Kelly. I was wondering if you could cover gene drives. It seems like this technology has been out for a long time, but hasn't been deployed. It seems like a magical technology for wiping out invasive species. When you have invasive, Evasive mosquitoes wiping out the last native Hawaiian songbirds with avian malaria,

you have to ask why you wouldn't test this out on such isolated islands. What terrifying scenarios are keeping them from deploying gene drives in the outside world? Are those scenarios realistic? Or is the pesticide industry just bumping off gene drive researchers? Thanks. All right. So we have tried lots of things to kill mosquitoes with varying success. One of the things we tried initially was spraying a bunch of insecticides.

And that worked for a while, but eventually the mosquitoes that happened to be resistant to the insecticides had a lot more babies. And now we have populations of insecticide-resistant mosquitoes. How does that even possibly work? I mean, I see, like, trucks driving around, spraying insecticide. But I'm like, you know, what fraction of the mosquitoes are they going to be hitting with that? It seems like, you know, shooting individual pigeons in the park or something. It's like hopeless, right? Yeah.

And sometimes they release it airborne. Other times they'll specifically release insecticides into, like, waterways where mosquitoes are breeding, and that's a little bit more targeted. Either way, you're probably killing a bunch of stuff you don't intend on killing as well, because a lot of these things are not specific just for mosquitoes. And then aren't people going to end up drinking insecticide? Yeah, or breathing it in. I remember whenever the insecticide trucks would come through in California, I would run inside the house or I'd bring my baby inside of the house. And yeah, so you breathe it in, presumably. I mean, they try to make it so that these chemicals are specifically focusing in on things mosquitoes and other insects do and not things that happen inside the human body.

I don't know how well we're often able to do that. Katrina, do you have any insights there? Yeah, oh, exactly. That's the idea. But I think that's extremely hard. I mean, when it comes to viruses and microbes, it's easier to come up with targets that are totally orthogonal to what would happen to a person. but that's so much harder for insects. Like, we're a little more closely related, believe it or not.

To insects than we are to microbes. Yeah. Yeah, exactly. So it's harder to come up with distinct targets. But yeah, that's definitely the goal. But I think there's all kinds of off-target impacts. Like, I'm sure you guys remember hearing about the Peregon Falcons and the compromised egg structure that came from all the insecticides being sprayed in the 60s.

Yeah, right. The DDT. Yeah. I think Rachel Carson wrote about that in Silent Spring. Yes. So we use these insecticides. And we're trying to use them in a little bit more specific ways. So, for example, you can dip a bed net in insecticides, and then you can put the bed net over your bed.

And then at the time of day when mosquitoes are most likely to bite, you're protected inside of the bed net. And because it has already soaked into the bed net, you're not breathing a lot in or you're not drinking it in water. But the problem is that there's very strong selection pressure for mosquitoes to find routes around this. So, for example, if you've got mosquitoes that bite at night, if there's variability in some of, mosquitoes are biting a little bit earlier in the day. The ones that bite earlier in the day are going to catch the early birds. And then they're going to have a lot more babies that go early in the day. And now the bed net isn't as helpful. And we've actually been finding that in some parts of the world, mosquitoes are changing the time of day when they're most active so that

they are now going after people when they're outside of the bed nets. Wow. And this is why when I came back from a trip to Tahiti where we had to sleep with bed nets every night and I loved waking up that any bites. I just set up the bed net on our couch. And then for weeks, I just like, anytime I'm hanging on the couch, I'm under the mosquito net. No big deal. I'm like impervious. I'm like laughing at all the mosquitoes. Ha, ha, ha. Wow. It was a very interesting sight. Daniel, like, watching TV while sitting inside the bed net. It's amazing. Amazing. Because I don't feel any social pressure to, like, be bitten by mosquitoes so I don't look like a weird under a bed net. I was happy. It was great. And now I know that ecologically,

I was, you know, suppressing mosquitoes in a balanced way. So, yeah, I was being responsible. Way to go, Daniel. Thank you. Pat on the back. All right. That's what I wanted. Thank you very much.

All right. So mosquitoes essentially are constantly providing a moving target where there is selection for them to, you know, route around whatever methods that we are using to try to keep them at bay. People also use things like they'll dump mosquito fish into waterways. These are tiny little fish that eat the aquatic stages of the mosquito. My new favorite fish. Yeah, but then the problem is they also out-compete a bunch of native fish.

they cause problems in the ecosystems that you introduce them into because they're not, they're not native there. So it's not a perfect method, but it's a method you can use in some areas. At your own house, now that you know that there's an aquatic stage, maybe you already knew that, but you can make sure that you dump any standing water. And if you want to, like, have a bird bath, just dump it out every day or two and then refill it because that won't give the mosquitoes time to hatch. But trying to like up the complication level a little bit, the next thing that we started in the 1950s was using sterile insect technique. And folks might remember that we talked about this a bit for the screw worm episode. And the idea here essentially is that you blast mosquitoes with gamma rays or other chemicals that sterilize them.

And then you release just the males into the environment. Female mosquitoes mate once and they'll mate with one of these sterile males. And then if they're able to lay eggs, those eggs won't hatch. And so essentially you are taking females out of the population reproductively by having them mate with males where it won't result in successful offspring. But this method has a couple problems. First of all, if you are just like

randomly bombarding insects with gamma rays, yes, you're going to sterilize them, but you also might beat them up in a bunch of other ways. And so sometimes these males that you release into the environment aren't as good at attracting the ladies as the wild males because these males have all sorts of other

things wrong with them. But Kelly, I read a bunch of comic books and if you blast something with gamma rays, it usually gives it superpowers, right? Yeah. Are you telling me that particle physics isn't really connecting

with biology there? Is that what's happening? I think that's what's happening, Daniel. I'm really sorry. Or maybe it's a statistical thing. Sometimes it works out that way, but the mosquitoes just, there hasn't been the Spider-Man

equivalent for mosquitoes yet. Yeah, I'm glad that we haven't turned any of these mosquitoes into the Incredible Hulk mosquito. Yeah. That would be really a sight to see. That would be bad. Yeah.

I bet the fabulous mosquitoes do great, though. Yeah. The ultra-barland mosquitoes. Yeah. And actually, I have a colleague at the University of Hawaii who's working on the microbiome. It's actually in the context of gene drives, but they are working on making the microbiome of the mosquitoes robust to help the mosquitoes that they're engineering to go out there and succeed with the ladies, as it were. Nice. Is this Wolbachia? No, it's mosquitoes. It's a malaria project. It's Nicole Hinson at the University of Hawaii.

By Wolbachia, I meant the bacteria that they're adding. But anyway, we'll get back to Wolbachia soon. Oh, no, I think that they are, like, more roundly making the microbiome of the mosquito robust so that in general the mosquito is robust. I'm not sure. Who won't? But again, with this method, I wonder, like, how many males do you have to put out there to have this have any efficacy? It's not like the males are reproducing and making more of themselves, right? So, like, every one you put out is one that you essentially manufactured. Is it really possible to have an impact on the population? Yeah, great question. So there was an experiment done in Havana, Cuba. Sorry, I said that wrong, but that's what we expect out of me. where about one and a quarter million irradiated mosquitoes. In this case, the species was 80s Egypti, were released, and again, all males, and they did a 20-week trial, and they looked at a 50-hector area, so a pretty big area, and they put out what they called overtraps, essentially just like areas where mosquitoes could lay eggs. And they didn't find any eggs in that 50-hectar area, suggesting that one-and-a-quarter million mosquitoes, which is a lot of mosquitoes, is enough to essentially not. a population down in an area.

But the problem is you've got to keep doing that over and over and over again every year. So it's an expensive process that needs to be maintained. But it turns out it doesn't work well for Anophilies mosquitoes. So we talked about 80s mosquitoes. There's another genus of mosquitoes called Anophiles that also tends to have a lot of species that transmit diseases to us. And that species, it looks like it's a little bit harder at the early stages of their life to figure out which ones are males and which ones are females.

And if you can't be sure, then maybe you're releasing a bunch of extra females into the environment who are going to, like, go and start biting people and possibly transmit diseases. So it works okay for 80s egypti if you're willing to release it over and over again over a large area. But it works less well for Enophiles because there's this step where you need to figure out if there are boy mosquitoes or girl mosquitoes. And because that's hard to do in the lab, that makes this technique a little harder to use. So next, let's talk about bacteria. so I suspect to have Katrina's attention. So Wolbachia is a gram-negative bacteria

that's carried by a bunch of different kinds of insects. It lives inside of insect cells, and it only passes down the female line. And so it's found ways to manipulate a lot of different insect species to help it transmit from one generation to another. So if a male who has the bacteria mates with the female who doesn't,

the eggs that she produces won't hatch. But if the female has Wolbachia and the male doesn't, then she will lay eggs that all carry Wolbachia. And so essentially the bacteria has a way of sort of manipulating things so that eggs are produced in ways where the bacteria can transmit. And in instances where the bacteria wouldn't be able to transmit, it just sort of like stops reproduction dead so that there's a line there where nothing's happening.

So in this way, it can permeate the entire population. That's mind-boggling, this sort of like genetic engineering by the bacteria to ensure that only lines that have the bacteria continue. That's incredible. It is incredible. Yeah, I remember when I first learned about this, it's kind of like blood types or something that there's like this incompatibility. But I know it's given people a real handle for engineering the populations. So I can only imagine what you're going to say next. So what I'm going to say next is that Scott O'Neill at Moines.

Monash University noted that a different lab had found that viruses and fruit flies have trouble growing when they're infected by Wolbachia. So this has nothing to do with reproduction. This is just if Wolbachia is there, it prevents the growth of viruses that otherwise would have killed the fruit flies. So O'Neill was like, well, what if we take Wolbachia out of fruit flies and put it in mosquito eggs and then see if mosquitoes carrying this Wolbachia are less likely to transmit dengue, which is another mosquito transmitted disease that can be lethal.

And so essentially they did the incredibly difficult job of extracting a teeny tiny bacteria from a fruit fly, sticking it into a teeny tiny little mosquito egg. Apparently they had to do this like thousands of times before it worked, but they eventually were able to get a strain of mosquitoes that were infected by the Wolbachia that was found in these fruit flies. So you're telling me that they found a strain of Wobokia. that kills viruses. And since dengue is a virus, they were like, maybe this strain of Wabakia is going to also kill dengue. That's crazy. It doesn't necessarily kill the virus, but it makes it so the virus can't reproduce. And if the virus can't reproduce, it can't go from mosquito to mosquito.

Right. And so they did some lab experiments, and it was working well in the lab. And in fact, one of our listeners, Joe, sent us an email that included a link to an article where Wobakia infected mosquitoes had been released in Florida. So we're trying this, like, out in the wild. Wow. And so the question is, does it work? And I looked for a really long time to try to find studies that had quantified this working. And I was able to find one study. And it was in Indonesia, and they released Wolbachia infected mosquitoes, and it reduced the spread of dengue by 77%. Wow.

So not 100%, but, like, man, those are much better odds. I'd take those odds. But then I found a 2024 review paper that was trying to aggregate. all of the Wolbachia-infected mosquito results. And they reported that essentially the only paper they were able to find was this paper from Indonesia. There were two other ongoing studies collecting data, but they hadn't published results yet. And so I would say at this point that this is super promising. I'd like to see evidence that it's working in some other areas before I could say like,

oh, we, this might be the key. But for Dengay, there's some preliminary evidence that this method is promising. Well, I'm a big fan of anything that's anti-mosquito, and I'm a big fan of preventing dengue or other kinds of diseases. But the idea of, like, intentionally infecting mosquitoes with some kind of bacteria seems dangerous. Like, how do we know this thing isn't going to, like, mutate, and then all of a sudden it's some new horrible face-melting disease or something. So, you know, this bacteria is pretty widespread in nature. So it's not like we're introducing something super weird into the environment, but it is a different strain. I don't know, bacteria expert.

What do you think, Katrina? Well, I guess I was just going to say that this Wolbachia bacteria, I think it's present in like 40% of insects. And so, of course, there's going to be very individual relationships that each bacteria has with its own insect. But I don't know. Of the things that humans do to manipulate the environment, this seems like a relatively innocuous one. I think it's really cool. It's like not so toxic to just kind of scramble things around a little and hope for a better outcome. All right.

Well, if people's faces get melted, it's on you. Oh, no. Well, I think it's on OxyTech, which is a company that is releasing some of these mosquitoes. I don't know that we can blame Katrina. She didn't release them. But. Thank you for looking out for me, Kelly. Yeah, you're welcome. I like when we can team up against Daniel. So, I'm sure. Well, you know, then maybe I need you to chime in on a topic that's been discussed heatedly at the Whiteson Institute board meetings recently. Oh, really? Which is, you know, what is the source of all the mosquitoes at the Whites and Institute compound that are biting Daniel?

And, for example, I'm against having sources of freshwater near the house, but Katrina is growing vegetables hydroponically in our backyard. Hmm. What do you think, Kelly? I need a ruling. There's no, like, way for a mosquito to get into this hydroponic growth chamber or for a mosquito to get out. So I just really don't think it's possible for them to be in there. But there is sometimes, like, a bowl of water that collects from rain. that I don't notice, and I'm sorry if that caused any mosquito growing to happen.

I mean, I'm hearing all of your fancy engineering explanations for why this can't happen, but I'm taking measurements of mosquito bites, and I'm telling you, it's high. It feels like there's been a lot of mosquitoes lately, but I thought we could blame that shipping container of the Port of Long Beach, isn't that way? Well, what do you think, Kelly? I think that I like every opportunity that I can have to side with Katrina, enough, but I don't really want to get in the middle of a marital spat, so I'm going to run away and call a commercial break and pretend none of this happened when we get back.

Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google doc and send me the link. Thanks. Hey, just finished drawing up that quick one page business plan for you. Here's the link. But there was no link. There was no business plan. It's not his fault. I hadn't programmed Kyle to be able to do that yet. My name is Evan Ratliff.

I decided to create Kyle, my AI co-founder, after hearing a lot of stuff like this from OpenAI CEO Sam Aldman. There's this betting pool for the first year that there's a one-person billion-dollar company, which would have been like unimaginable without AI and now will happen. I got to thinking, could I be that one person? I'd made AI agents before for my award-winning podcast. Shell Game. This season on Shell Game, I'm trying to build a real company with a real product run by fake people. Oh, hey, Evan. Good to have you join us. I found some really interesting

data on adoption rates for AI agents and small to medium businesses. Listen to Shell Game on the IHeart Radio app or wherever you get your podcasts. I'm Robert Smith, and this is Jacob Goldstein, and we used to host a show called Planet Money. And now we're back making this new podcast called business history about the best ideas and people and businesses in history. And some of the worst people, horrible ideas and destructive companies in the history of business. Having a genius idea without a need for it is nothing. It's like not having it at all. It's a very simple, elegant lesson.

Make something people want. First episode, how Southwest Airlines use cheap seats and free whiskey to fight its way into the airline business. The most Texas story ever. There's a lot of mavericks in that story. We're going to have mavericks on the show. We're going to have plenty of robber barons. So many robber barons. And you know what?

They're not all bad. And we'll talk about some of the classic great moments of famous business geniuses, along with some of the darker moments that often get overlooked. Like Thomas Edison and the electric chair. Listen to business history on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. For 25 years, I've explored what it means to heal, not just for myself, but alongside others.

I'm Mike De La Rocha. This is Sacred Lessons, a space for reflection, growth, and collective healing. What do you tell men that are hurting right now? Everything's going to be okay on the other side, you know, just push through it. And, you know, ironically, the root of the word spirit is breath. Wow. Which is why one of the most revolutionary acts that we can do as peoples just breathe. Next to the wound is their gifts.

You can't even find your gifts unless you go through the wound. That's the hard thing. You think, well, I'm going to get my guests. I don't want to go through all that. You've got to go through the wounds you're laughing. Listening to other people's near-death experiences, and that's all they say. In conclusion, love is the answer.

Listen to sacred lessons as part of the My Kutura Podcast Network, available on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. Hi, I'm Radhi DeVluca, and I am the host of a really good cry podcast. This week, I am joined by Anna Runkle, also known as the crappy childhood fairy, a creator, teacher, and guide helping people heal from the lasting emotional wounds of unsafe or chaotic childhoods. We talk about how the things we went through when we were younger can still show up in our adult lives, in our relationships, our reactions, even in the way we feel

in our own bodies. And Anna opens up about her own story, what helped her notice the patterns she was stuck in, and how she slowly started teaching her body that it is safe now. When I got attacked, it was very random. Four guys jumped out of a car and just started beating me and my friend. And they broke my jaw on my teeth. I was unconscious. Then I woke up and I screamed. And I screamed because even though I didn't know who I was or where I was,

something in me was just like, hold on, wait, they could kill me. And I'm not going to let that happen. I'm not going to let that happen. I'm going to get through this. And I did. Listen to a really good cry on the IHeartRadio app, Apple Podcast, or wherever you get your podcast. And we're back, and we are talking about genetic engineering techniques for controlling mosquito populations this time around. We're about to get to gene drives, which was the listener's question.

This is the most roundabout way of getting there. But first, let's talk about some genetic engineering where essentially you take males and you make it so that if they don't encounter tetracycline, they will die. What is tetracycline? Tetracycline is an antibiotic, and essentially you make it so that the males are making a protein that when it's made, it messes up the cell's activity. But in the presence of tetracycline, that protein is suppressed so it doesn't get made. So males in the lab are given tetracycline, they act normal. But when they produce suns in the wild, the suns start producing this protein like crazy.

It messes up their cell activity, and they die. And so the females do lay eggs, but their eggs don't tend to survive. So you genetically engineer mosquitoes to be dependent on this thing that you can give them. So when they go out there in the wild, their bodies are making this protein. And since they don't have this magic powder, they end up killing themselves. They end up dying, yeah. Wow. These are pretty complicated strategies.

And they also are strategies that tend to make a lot of people uncomfortable. So, for example, this has been tried in the Cayman Islands, Panama, Brazil, and Florida. In the Florida Keys, for example, the initial response was, like, massive backlash against the release of these GMO mosquitoes. They ended up getting released anyway, but there were people who were saying, like, I'm going to find the boxes where these mosquitoes are supposed to hatch from, and I'm going to dump them out or pour bleach in them. And I think in general, it's really important that you have public buy-in for these sorts of things, because otherwise you just get, you know, you get people who are justifiably upset. They don't understand what's being released. They're worried that the genes that got put in the mosquitoes might jump into them. Is that what the concern is, that they're going to end up dependent on tetracycline also?

Or is it just a generic, like, I'm scared of GMO stuff? I think it's more of a generic, I'm scared of GMO stuff. You know, folks don't want GMO foods. I think they don't necessarily like the idea of getting bitten by GMO mosquitoes. I think they also don't like the idea of putting an engineered gene out in the environment and not knowing where it's going to end. So like these island capture experiments where, of course, the idea is that it's an island, so it's somewhat contained, are still unsettling because the world is so connected right now. So it's hard to know what the reach of an experiment like that will be.

Exactly. And so while these releases do first have to go through like a complicated series of approvals through groups like the Food and Drug Administration, the United States Department of Agriculture, the Environmental Protection Agency, it is still the first. time we're doing something like this. And so Oxitech did release mosquitoes that had this tetracycline thing happening. And some of the genes from the mosquitoes did end up being found in wild mosquitoes. So like those genes had escaped into the population. There were some headlines at the time that sort of were way overblown. They said things like these genes are going to make the wild mosquitoes even better at biting us. And now we've just made our problem worse. There wasn't necessarily any evidence for that, but there was evidence that genes that were essentially

manufactured in a lab are now part of the wild population and might be there forever. And we don't really understand if that is going to do anything at all. I understand the concern that these genes that you put into one mosquito might end up in a wild mosquito and you don't know exactly what's going to happen. Maybe it turns them into Incredible Hulk mosquitoes or whatever. But how does a gene go from that mosquito to the wild mosquitoes? Does it have to breed with those mosquitoes or is there some other weird horizontal thing happening? So I think what happened in this case is that one of the mosquito babies that was supposed to die did not. And so it survived, had some of the genes that it got from its genetically engineered dad, and then is passing that through the generation. Okay, so it's

through breeding. Yeah, you could imagine some compensation that allowed it to survive with that toxic protein and then the toxic protein would stick in the population. I mean, I guess, In my mind, there's so much evolution and transfer of genetic material all the time that any tiny little drop that comes from a lab feels insignificant to me. But I do understand why it feels unsettling. That's my gut feeling also. Like horizontal gene transfer happens between insects and our food and just all sorts of different transfers are happening all the time in nature. I'm less worried about a genetic sequence that seems pretty benign, getting out into the wild. But on the other hand, I'm somebody who is totally fine eating genetically modified

foods, but I understand that that's not true for everybody. And so I can understand why this would be upsetting to some people. And I think generally, you know, biologists don't know how everything works, and we're pushing buttons and pulling levers on a big complicated machine. And it does feel like one little button on a huge machine. But, you know, you release the right pathogen, and it can definitely have a big impact on a population. Yeah, I think it's important to be humble. So let's get to gene drives, which is probably the most like ethically controversial thing that we'll be talking about today. And, you know, we bring Katrina on the show because we generally love Katrina's input. But she also understands gene drives. And I spent a day smashing my head against a paper I could not understand. And so Katrina, could you explain gene drives for us, please? So a gene drive refers to when you use genetic engineering to force a gene through a population at a really high rate. So normally our genes are inherited approximately 50-50, so the chances of inheriting a particular trait

are not weighted in one direction or another. What a gene drive does is it ensures or drives that a particular trait will be more frequent in the population. And we've actually been using this technique in the context of mosquitoes with a few different strategies in mind. It could be something that affects fertility, so then you drive the population to extinction, So that would lead to, you know, fewer mosquitoes is the goal there.

But then there's also strategies where you try to prevent the mosquitoes from spreading malaria. So there's some mosquitoes that are naturally resistant to carrying the malaria parasite. And so spreading that strategy is another gene drive technique. So can we dig a bit deeper? Like I understand sort of the basics at the sort of P-Pod level, you know, from Gregor Mendel. And you have a 50% chance of getting the gene from one parent. or from the other, how does the gene drive affect which genes you're going to end up with? Well, okay, the one really cool strategy that people use to make gene drives work

is to borrow the phage defense system called CRISPR-Castnine. As you guys hopefully know all about, there are these viruses called phages that can infect bacteria. And the bacteria defund themselves in all kinds of interesting ways. And one of them has been co-opted for all kinds of genetic engineering. it's called CRISPR Cas9. And it turns out whenever the phage infect the bacteria, the bacteria keep a little record of little snippets of the genes that the phage was trying to infect the bacteria with. And then they put a little pair of scissors, a gene that can chop DNA up next to the little memory bank of all the little phage genes that were left behind. And then when

the phage tries to infect, the scissors, the gene that has the DNA cutting enzyme on, it will match up with the pieces of the phage gene, and it'll chop up the phage as it tries to enter. It was just the Nobel Prize last year to Jennifer Doudna and Emmanuel Charpentier, because they had the idea of taking this tool and using it to engineer genes in any system. So just to back up and make sure we're understanding, the CRISPR idea is some sort of like bacterial immune system where it remembers the viruses it's seen before and has a bunch of floating around, which will recognize those viruses, plus it comes with scissors so that when the viruses come near, it latches on, and then it chops them up, and then the viruses can't

infect the bacteria anymore. So the basics of how the CRISPR system works? Yeah, that is exactly the basics. But the idea of using it as a tool is really cool because basically now you have a system that can go and find a particular DNA sequence, and then it's got scissors right next to it so it can go cleanly chop things out exactly next to whatever sequence is next to it. So with the phages, the bacteria were using it to chop up phages. But now imagine you wanted to go in there and slice and dice a mutation that was causing sickle cell anemia. You can do that. That actually is happening in people right now, which is amazing. So people with sickle cell anemia now can have some access to CRISPR-Cast-9 genetic engineering technology where you use the same scissors,

this time you match it to the gene causing the sickle cell disease and you have the scissors go in there and snip out the problematic gene and replace it with a healthy gene. And I mean, that's to me amazing that that is actually working in people. The idea is not that old. I mean, the discovery is somewhat recent. And so that's the same strategy that's been used to build mosquito gene drives. So I understand how CRISPR can let you edit your genes, which On one hand, it sounds like, why is that hard? You know, you just, like, go in and edit the data, but, like, this data stored on DNA, you can't just go in there and, like, manipulate it with tweezers.

You need some sort of, like, microscopic manipulation tools, and that's what CRISPR is giving you. But how does that connect to gene drives? How does CRISPR let you enhance which genes get passed down in the population? Well, you engineer mosquitoes that contain a CRISPR-Cast-9 gene set in there. And so you could put the scissors right next to, a gene that's important for fertility, or you could put the scissors right next to a gene that controls whether the mosquito is able to be infected by the malaria parasite. And so if you put that in there, then the CRISPR-Cast9 scissors will go around spreading

that gene even after the mosquito is born. So it's throughout the mosquito's life, the gene drive will be active, and it will continue to spread that gene. So your opportunity for picking up your genetic traits will not end right at the moment of Mendelian inheritance. The gene drive will continue to be active after that. In the same way that you go in and edit somebody's genes when they're alive to remove the bit that's giving them some condition, you're basically giving these mosquitoes a little bit of genetic engineering during their whole lifetime. So it's not just what they inherit. You're like changing them after the fact. That's cool.

So basically, if that gene drive is in there, every time the little cassette that has the scissors on it encounters the gene that it can match to, it will swap things around. So you can, like one of the examples that I really loved that I read about was where they had a naturally malaria-resistant mosquito, and it was just caused by one snip in a gene, a single mutation, and they made a gene drive that forced that mutation through the population. But it's a naturally existing gene, so they're not making a Frankenstein mosquito here. And it made it so that the malaria infectivity rate of the mosquito population could go down. I found another paper where they were tinkering with the gene that they called double sex. And essentially what happened is they made sure that everybody got two versions of double sex. And if you're a female that has the double sex genes, you're sterile. And you also look a little bit male-like, but males who get it are normal, and they can go on spreading the gene drive.

So essentially, every baby that's produced that's a female is not going to make any more babies. And males that are produced are going to be able to go on inmate, but they're going to pass this gene drive onto their offspring. And so they'll create female babies that die and male babies that go off and continue to pass the gene drive until it gets through essentially the entire population, I think, is the goal. Wow. Yeah. And so this has not yet been released into the environment. And so as Katrina noted, there's two different methods. You could try to either kill the mosquitoes directly or you could do something to the mosquitoes so they can't transmit the disease anymore.

There might be some other options too, but those are the two things that people are working on right now. But this, I think this technique in particular is a little scary or ecologically because, you know, like what if that gene drive jumps to, I don't know, another mosquito species? species. Maybe having two mosquito species eradicated doesn't sound so bad. But what if somehow that gene drive is able to jump to, I don't know, a ladybug that helps control pests in agriculture or something? And now we've got this thing that could lead to extinction and there's some concern that if you release it, you know, where is it going to end up? But how do these jumps happen? Earlier, we were saying that the genetic engineering that you manufacture and your mosquitoes can spread to wild mosquitoes through inheritance, but we're not having mosquitoes like having babies

with ladybugs. How does that jump possible? So as we're going to talk about in a future episode, the definition of a species isn't always entirely crisp. Sometimes you can get, you know, individuals that are in the same genus, for example, mating with each other. I don't know if they get confused or they have very particular interests, something they're looking for in a partner. No judgment, no judgment. No judgment. But if, you know, the mosquito species you put the gene drive in, mates with another mosquito species, now you're wiping out that species too. And you can imagine yourself jumping around the tree of life. And whenever you get some, you know, cross-species mating, you've now got that species wiped out too. So crisper can move because species aren't crisp is what

you're telling me. That's right. I mean, yeah, that's definitely one way is through mating partners that might be a little bit less related. But I mean, another big strategy is that some Sometimes there are big leaps in genes that get transferred across the tree of life, and that often is facilitated by viruses. So, for example, 8% of the human genome is in the form of endogenous retroviruses. So that means that one of our long-ago ancestors had a virus infect one of their germline cells, one of their sex cells, and we have inherited that to the tune of literally 8% of our genome. most of them are pretty dormant and haven't really affected us that much, but some of them have led to the biggest innovations in biology. So, like, for example, did you guys know that the gene that led to the placenta evolving came from a virus? So an endogenous retrovirus that infected one of our ancestors back before mammals existed had a gene in it that helps with membrane fusion.

So, like, that gene in a virus is great for helping the cell membrane fuse. But in a mammal, it allows for the fusion between the uterus and the placenta. So cool. So those kind of jumps can happen. And to me, that's a really big question about gene drives, because what if this CRISPR gene gets transmitted farther afield? I think that's the real concern. But keep in mind, in your own gut right now, you have thousands of bacteria that contain all kinds of CRISPR systems, and I'm not worried about those transmitting into human cells.

And I should note there are labs that are working on anti-gene drive techniques, like a gene that you could release into the population that would sort of stop the gene drive. And so there are some folks who are forward thinking about this problem and are trying to stop it. But then we can return to Daniel's earlier point, which is that biology is complicated, and biologists don't necessarily know what's going to happen. So, like, what if we knock out one mosquito species, a different mosquito species fills that niche, and that species is even better at transmitting the disease. Now we've, you know, maybe we can release gene drives again to control the problem,

but, like, it's hard to know what's going to happen to a system when you remove an animal that has, you know, a large number of individuals out in the population. And we don't really understand the ecological impact. So Daniel mentioned that some mosquitoes pollinate chocolate. You know, what if you have a mosquito species that ends up being an important food source? for example, for a fish species that is an important source of protein for the local community. So, like, there's a lot of, you know, ecological stuff that might happen that we don't understand very well.

And so making the decision to knock out a species because we've decided we wanted to do that, you know, could have some other implications. But if, on the other hand, you're talking about, you know, more than half a million people dying every year from malaria, my tolerance for taking risks goes up a little bit, but those risks should be well thought through, in my opinion. And I hope that you're including my itchy ankles from mosquito bites in your calculation. I'm not. I'm not. Nope. And of course, Katrina's going to vote with you, so I'm not voted again. So where we are on this right now is that some genetically modified mosquitoes have been released, and we're doing tests on those.

But no gene drive mosquitoes have been released yet. There was Target malaria was working in Bakina Fossa to try to get community buy-in, to get people, on board with this idea of releasing gene drives. But recently their facility was essentially raided, and they were told that their project is being shut down. It was a little bit unclear what happened because it seemed like the Target-Belaria group was in good with the local community, in good with the government.

There have been some, like, think tanks that think that the problem actually is Russian disinformation, where this message has been spread that we are using genetic modification to make people sterile and, you know, releasing these genetic mosquitoes will sterilize the local population. So it has become a complicated, ethical, geopolitical problem, and that's where we are right now. We are sort of trying to decide as a society what we're going to do when we have this technique that could be used to save a bunch of lives from malaria, but has, you know, potential implications some of which we know about and some of which we might not even understand unless we were to actually try the experiment.

So it's complicated because it's biology. But it's worthwhile because these are people's lives and it matters. Yeah, and I think it's so interesting that it's more controversial when we understand what we're doing better. I mean, for example, in agriculture, we've been selecting for traits for thousands of years that have all kinds of ecological impact, and we don't find that to be controversial. But as soon as we use molecular biology tools to genetically engineer things, it's less understandable and somehow scarier, although the implications could be the same. So I think that's really interesting. All right. So we have had a fun, complicated discussion about mosquitoes and genetic.

engineering. And Katrina, I have no doubt we'll bring you back on the show five or six more times before the end of the year, which is only a couple weeks off. Thanks for coming back on the show. Well, thank you for having me. Thank you to our listeners for submitting their questions. Let's hear what they had to say about the episode. I really appreciate you getting to my question and in the most relevant episode. I can't say that I'm entirely convinced that the reason gene drives haven't been tested yet aren't nefarious. After all, if your goal was eradicated, and you released enough mosquitoes on a small island, and considering the length of the mosquito life cycle,

how long would it take to eradicate the species entirely? A short time period leaves very little time for the genes to jump. If the gene drive did jump species and eradicate another species of mosquito, Hawaii has no native mosquitoes to worry about. In fact, the six to eight invasive mosquito species on the islands would make a great test case to see if the gene drives do jump species. Maybe some diligent pesticide use by the ports could keep any measurements. modified mosquitoes from leaving the island before total eradication.

Overall, it seems much less risky than Uruguay's plan to use gene drives to eradicate screwworms, given the biodiversity of South America. Maybe the answer is in Wobakia, which you covered. Perhaps it's just less risky. It looks like they started attempting to use it to eradicate Kulex mosquitoes on Maui to save native birds. Thanks so much. Kelly's Extraordinary Universe is produced by IHeart Radio. We would love to hear from you.

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