The surprising beauty of mosquitos | Felix Hol

In order to actually understand the animal well, you cannot just think like, "Oh, it's a super annoying animal that I hate, right? You kind of like have to crawl inside the skin of the subject that you're trying to understand." I think a certain fascination, or maybe if you want to call it love, is at least in my case, required to really get deeply into understanding how it works. You're listening to Ted Tuck's Daily, where we bring you new ideas to spark your curiosity every day. I'm your host, Elise Hugh. That is mosquito biotechnologist Felix Hol. And yes, he really does mean love. Most of us have exactly one feeling about mosquitoes, and it isn't affection. But Felix's fascination comes with a serious purpose. He believes that the better we understand how mosquitoes find us, bite us, and adapt to us, the better our chances of stopping the diseases they spread, which take an enormous and growing toll across the world. About half a million people die of mosquito-borne disease each year, and the number is actually rising. Since they don't affect people in, for instance, Europe or North America that much, they seem to be getting much less attention than they maybe should. Felix is a Ted fellow, part of a program for early stage innovators that Ted supports. It's a community of more than 500 fellows around the globe, whose work reaches more than 200 million people a year. They're not just improving broken systems, they're building a better future for all of us. In Felix's case, he's challenging the idea that we can simply out spray mosquitoes. And in this episode, he takes us into his lab in the Netherlands, where his team builds cheap, open-source tools to film and study mosquitoes up close, and shows just how quickly they adapt to whatever we throw at them. Since the mosquitoes aren't stupid either, and they get hungry if they can bite people because they were sleeping on their bed nets, mosquitoes are now actually shifting their behavioral patterns, so they're biting early in the evening, later in the morning. After Felix shares his story, he speaks with Ted fellow's program director, Lily James Olds. They get into how a messy lab accident led to one of his favorite inventions, a surprising discovery about two malaria-carrying mosquitoes in Uganda, and why climate change and human travel are helping mosquitoes spread to new places. That's all coming up right after a short break. And now our Ted story and conversation of the day. I think a lot of mosquitoes are actually quite pretty. If you put a mosquito under the stereo scope, and you get to zoom in, you first see the whole body, and then you zoom in more and more and more, you get to the eyes, for instance. You know, they have all these little facets, and it's just really beautiful how those are arranged, and then you can zoom in even more on the mouth parts, and you see like all the scales in the hair sticking out. I think that just looks amazing. You know, it's a slender, beautiful insect. My name is Felix Hole, and I'm a mosquito biotechnologist. Everybody has some relation to mosquitoes, right? Most people hate them in a way they are scary and dangerous. Not the animal itself, but when a mosquito takes a butt meal from a person, and that person would be carrying a particular disease, then a mosquito can get infected by that pathogen, and it could transmit it to another human. So that aspect of the mosquito, yeah, of course, can be as dangerous, can also be a bit scary. They have this humongous impact on society, on humans, but while they're omnipresent, there's a lot of things that we really don't understand about them. In order to actually understand the animal well, you cannot just think like, "Oh, it's a super annoying animal that I hate," right? You kind of like have to crawl inside the skin of the subject that you're trying to understand. I think a certain fascination, or maybe if you would want to call it love, is at least in my case, required to really get deeply into understanding how it works. There's about three and a half thousand species, but only a small subset around 90 actually feed on humans. So basically, I'm sitting here breathing out a bunch of CO2, and mosquitoes can really smell that from far away, really like tens of meters, that activates them, they start flying, and then they kind of like surge and cast through a CO2 plume. When they get closer to me, they switch to more like smelling body odors, so basically just my sweaty smell. When you get even closer, a heat actually becomes, or you just, you know, the body heat that my body radiates, that becomes a much more important cue, and of course also visual cues. They also have taste and smell receptors on their feet, so when they're walking on your skin, they can actually just taste the surface of your skin. The mosquito will tap the skin with the proboscis, and then it will slide in both a foot canal and a slyvery duct, and the foot canal will then actually just aim your skin search for a blood vessel, and it will start drinking. Mosquitoes feed off of humans for about, you know, the quickest ones will be 20 seconds or so, maybe 30 seconds, and then other species may take a bit longer, like a minute or a minute and a half or so. They have an interest to do this quickly, right? Because we may just notice them, slap them, and then it's over. So that'd be sad for the mosquito. So they're really good at doing this very stealthily and very quickly. Whatever we'll do that was intended to prevent them from biting us, they will probably find ways around this, right? Mosquitoes are adapting really rapidly to the pressures that we as humans put on them. I think we really have to keep that in mind when we're trying to, you know, reduce the burden of mosquito-borne diseases. Insecticides, of course, are designed to kill mosquitoes, but given that they've been in an environment so much, mosquitoes are now being resistant to them, and we've actually done some recent work where we have preliminary data that suggests that mosquitoes when they don't die of some of these insecticides, it actually makes them hyperactive, so they start actually flying more. So we don't know yet if that actually translates into the mosquitoes biting more people, but you can totally imagine that when they're hyperactive, they may fly more and fight more people. So like that, you can see that sometimes an intervention that is intended to do one thing may even actually induce an auto-type of behavior in an insect like a mosquito that is actually counterproductive. The lab is located in Nijmeigen in the Netherlands at the Rabbat University Medical Center. We are trying to build new technology to really make kind of like unknown biology of mosquitoes visible. One of the interesting things that we build is this thing that we call the bidescope. It is a kind of like an imaging setup in which we build a thing that we like to think of as like a skin mimic. So to you and me will just look like a piece of plastic, but for a mosquito it actually just has all the key components that the mosquito needs in order to think that it's like real skin. So they can actually just land on this, they can walk around, they can bite it and then when they bite it, they actually slide their mouth parts into this artificial block meal and we can film them while they're doing this and we can get really high resolution footage and then we can really accurately study their behavior. For instance, like, you know, how do they bite? How often do they bite? Does that depend on whether they're infected? Does that depend on particular compounds that we actually can put on this fake skin surface? In the lab, those mosquitoes are very standardized. We can get lots of them and we know exactly under what conditions they were basically raised. But of course, they're a bit far from what we find in real nature. We really want to address these questions in as many endemic settings as possible. So when we do field work, we actually just collect mosquitoes straight from the field. So what we typically do is visit people's houses. We ask if we're allowed to collect mosquitoes at their houses. So we just go into a house early in the morning, mosquitoes are still kind of like resting on the wall. I come in with my little vacuum. We vacuum them mosquitoes off the wall and then we take them to the field lab. We practice everything in an open science fashion. All the code, we make all of that available open source and we just mainly use as cheap as possible components. It really works best if others just start using our tools. So open source and cheap, that's the main way to get it into people's hands. About half a million people die of mosquito-borne disease each year and the number is actually rising. My hope for the future is that we'll be able to use insights about how mosquitoes actually work to reduce the burden of mosquito-borne diseases. So while I find mosquitoes very fascinating and intriguing, I do want them to stop, like actually making people sick. So it's not just putting out the next insect aside that in a couple of years, they'll be resistant to it again. We can use everything that we learn about them to come up with strategies that allow us to really sustainably curb the spread. We've learned a lot over the past like decades or even longer, but with every single thing we'll learn, that will just pull open and order 70 questions, right? So in that sense, some, yeah, this is a never-ending story. Coming up, Felix sits down with Ted Fellow's program director, Lily James Oles, to talk about how a biophysicist ended up falling for mosquitoes. The strange things they can sense about us and what he hopes even the most dedicated mosquito swatters will take away from his work. Felix, I'm so happy you're joining us. Where are you calling from today? Oh, I'm calling from Nijmegen, the Netherlands. Amazing, and that's where you do your research. Is that where your lab is? Yeah, no, Andy, so the lab's here. Beautiful mosquito lab with a million mosquitoes. So that's where we do the experimental work, but then we also do a bunch of work in field sites in Uganda and Kenya. I am so looking forward to talking to you today and learning about mosquitoes. Unreal. So I want to hear how this love began. When did this love story start for you? For me, it started, I guess, by now, a little over 10 years ago. So I'm trained as a biophysicist, and I used to work on completely different things, like stir-frelated to microbiology, bacteria, and your gut in the soil, things like that. And I wanted to do something that was a little bit closer to problems in global health. And I tried a couple of different things, and then I just came across mosquitoes. There were so many basic things that were not known about mosquitoes. When I started working on them, so I was just super fascinated by the fact that there's something so ubiquitous, yet also still mysterious. So that's what I really liked. And I guess I just stayed because there's not that many people with my background in training that work on mosquito-related problems, so it kind of was a good match. I love that. There's not as many people in love with mosquitoes as you are, is that what you're saying? - No, yeah, no, I wasn't, but that's definitely true, yeah. - Okay, so what are three facts about mosquitoes that we might not have any idea about that you can illuminate for us? - I think fact one is that when they can taste with their feet, so when they're landing on your skin, they are actually tasting your skin with their feet. So they may think you taste knives, or you taste yucky or something. So I think that's fascinating. They have an insanely good sense of smell, so they can really get activated by the CO2 that we exhale, even when we're really far away, like tens of meters. So I find that fascinating. And yeah, I guess we always just talk about mosquitoes, but it's actually a huge group. I mean, there's over 3,000 species of mosquitoes. There's a lot of variety among that species. So it's also a really big and diverse group that can, yeah, I guess that keeps it interesting. - And are you one of those people who mosquitoes love as much as you love them? Are you one of those people that always gets bitten? - No, not so much. And I'm quite happy that the love is not the virtualness, yeah. - I also think it's really fascinating how you were saying there's so much that we clearly still after all these years that you've been studying mosquitoes don't know about them, you know? And you talked about how they're adapting to our attempts to thwart them, like becoming more, you know, resistant to the insecticides or you even said hyperactive. What are some other examples of solutions that humans have attempted that mosquitoes are now finding a way around? - So betnets are responsible for a huge drop in malaria cases over the past like decades. Betnets are being handed out all over sub-Saharan Africa in huge numbers. And that's really, really protecting people quite well because generally malaria mosquitoes are active during the night. However, you know, since the mosquitoes aren't stupid either and they get hungry if they can bite people because they're sleeping on their betnets, mosquitoes are now actually shifting their behavioral patterns. So they're biting early in the evening, later in the morning, there's clear evidence that that's happening, how exactly that's happening and whether there's other factors that may be important there as well that that's not really known yet. But the fact that we are basically depriving them of their meal during the night it seems to be really pushing their behavior. So I find that a fascinating example. - You know, you say that as if it's common knowledge but it really does feel like it shows their intelligence, resilience, adaptability in a way that I had no idea that mosquitoes could do. So that's pretty amazing. - Yeah, no, it's a great example of adaptability. I mean, it's like any animal, right? They're evolving and we're putting a lot of pressure. So then stuff happens. - Has there been a moment in your research where a tool that you've made has kind of backfired or had an unintended effect that made you have to rethink your approach? - I guess so far, luckily not a negative, unintended consequence. No, I mean, it is, I guess a lot of the stuff that we do is kind of serodipitous and just happens accidentally. So I got the idea of building a bidescope basically from an experiment going wrong. I was basically blood feeding mosquitoes in an artificial feeder. We do that all the time. We just get human blood from a blood bank. We stick it in an artificial feeder. And this thing kind of like ruptured all the blood spread out. It was kind of messy. And that really was the right, I guess the right setup to actually really nicely image them and film them. - That's wild. First of all, I love the name Bidescope. - Yeah. - I'm just imagining, I went through. I was just imagining you going to the blood bank to get this blood and then exploding all over the place. Your days look a little different than mine do. - I mean, luckily that generally doesn't happen, right? I mean, we don't want poor donors to think that their blood goes up the wall here. But yeah. - No, it's not good use. It's for science. - Yeah, yeah, it is. - So I know, you know, you talked in your film about how all the tools that you make are affordable with, you know, cheap materials, open source. Why does that matter? What impact does that have? Why do you think that's important? - So I think it's just a matter of accessibility, right? I mean, there's only so much science that I can do or I to get it with my team can do. And there's so many more questions that need answers or things that people want to explore. So by just facilitating others, that's one of the easiest way to have more reach and more impact. So yeah, that's why we do that. - Can you give some examples of other colleagues doing this work around the world that either you've been able to utilize, you know, their tools or they've been able to utilize yours just so we can get a sense of what it's led to that might not have been if it was privatized? - Yeah, so actually for us, we. So what we often do is that we film mosquitoes and we then try to extract behavioral data from those videos. For that, we need a lot of software and we build some of that ourselves, but none of that starts with tools that we build. We typically, for instance, for behavioral characterization of videos, we actually took a package that initially was made for tracking mouse, or basically processing mouse videos and we adapted it to our mosquito problem. So basically, we use a lot of open source software. So by others, just making that available that really drives our work. And likewise, for us, like for instance, the bite scope that I mentioned that is being implemented in different laps across the globe or we have another tool that we call the buzzwatch. It's like a device that you can basically use to get the activity patterns of mosquitoes throughout the whole 24-hour cycle. It's something that we recently made and that is now also being implemented in different laps. It's also super rewarding, actually, because when I get an email of somebody that I don't know and they're like, "Oh, I'm working on how mosquitoes sense humidity." Or I'm working on how mosquitoes hear and therefore I build the system. Can you help me figure this stuff out? Yeah, it's super rewarding. - That's so cool. What's a project or a tool that you and your team are working on right now that you're most excited about? - I'm excited about a lot of things. So that's part of the big one. But I think something that I'm really, really curious about is how mosquitoes navigate temperature landscapes. That maybe sounds a bit vague, but you can imagine that sitting in a house, the sun may be shining on a wall and the wall may get quite warm, whereas maybe the floor is much colder, right? And mosquitoes are actor terms, right? So there are animals that are just at ambient temperature. So when we're sitting on a hot wall, they're warm, when we're sitting on a cold floor, they're cold. So we don't really know very well how mosquitoes navigate these temperature landscapes and we've recently built a setup in the lab in which you can really mimic those temperature landscapes. So we can really make a user-defined landscape where here it's kind of cold, there it's kind of warm and then we just film where mosquitoes like to sit. If they like to sit somewhere else when they're infected with malaria and how all of that stuff works. And what I like also about that project is that we have a massive temperature landscape setup that we have here in the lab, it's super big, there's all kinds of electronics around it, like you can't carry it around, but then actually the PZ student that built that, she also built a portable version of it, that she took to Uganda and now she's using that to ask similar questions in the field. So that's something that I'm quite excited about the moment. - What sort of feedback have you been getting, what have you learned from that work there so far? - So we've talked about how mosquitoes may be shifting their activity patterns or actually like due to the use of batonets biting at different times more during the day. And what we've learned in Uganda that there's actually in this place where we work, there's two mosquito species that both transmit malaria and they seem to have very different responses during a day. So there's this one species that just, it's impossible to get it to wake up. When it's daytime, when the sun's out, it won't move, it won't do anything, you can breathe on it, you can do whatever you want, they don't respond. And then there's other species that's actually quite responsive during the day. So with more and more batonet use, you could imagine that species becoming more important for transmission. But yeah, that's something that we weren't necessarily expecting. That's not really like common knowledge in a field, so I think that was a really cool finding. - That's amazing. And maybe this is cart before the horse, but what could that eventually lead to? Is there a way to encourage? the lazy mosquito and reduce the hyperactive ones? - Yeah, no, that's a good question. So what we do there is, or actually everything we do is always, it's partly curiosity driven. We just wanna know how stuff works. And it's partly aimed at reducing disease transmission and mosquito-borne disease problems. Is it really true that the mosquitoes are biting at different times? Can we maybe get to the genetic mechanisms of that or how does that work? But at the same time, you know, when a government or any organization is trying to implement vector control, you know, you have a pot of money and you can go either buying betnets or you can buy insecticides that you spray in people's wall or there's these new things that are called spatial repellence. It's basically like a piece of plastic. You stick on the wall. They're just insecticide emanating out of it. And it basically works 24/7, or at least that's the thought. These things are just being tested now. So if you would find that you're in an area where the mosquitoes have completely shifted their habits and not biting during the night anymore, but everybody's getting bitten during the day, you could decide to stop handing out betnets but start handing out these spatial repellence or some other controlled methods. So I think that's where that knowledge then can come in. - Very cool. - Don't go away. We'll be right back with more of Felix's conversation with Lily right after a short break. I know you mentioned that half a million people die from mosquito-borne diseases every year and that that number is rising. From where you stand as somebody doing the research and the science on the ground, what do you think are the biggest hurdles in the way of us solving mosquito-borne diseases? - I mean, solving is a big thing. Yeah, so actually that number to half a million, that number was actually declining for quite a while. So already 2000s that number was actually going down, but then in recent years indeed it's going up again. You know, I think there's lots of things. There's drug resistance. So the malaria parasite is getting resistant to drugs. Then there's insecticide resistance in mosquitoes, right? So in mosquitoes we put betnets, we put spray on walls but they're getting resistant to that. And then there's other dynamics for instance, like because there's so much human mobility we're transporting mosquitoes from one place to the other. So one development that I think is really worrying is that it was a mosquito species that is normally vectoring malaria in Asia was introduced into the African continent. And that mosquito is actually really well adapted to urban places. Instead of the regular malaria factors in Africa that typically are thriving in rural areas. So because of a lot of shipping and dynamics like that, these mosquitoes get introduced into new places and they really spread over there. So I think developments like that are increasingly happening and I think they're a big problem. - And what do you think those of us in countries that have not yet had to deal with as many diseases from mosquitoes or in the case you just gave new kinds of mosquitoes being introduced? What can we learn from other regions in the world that are already dealing with these issues or dealing with those specific kinds of mosquitoes? - It's a great question. It's super hard to answer I think. Like for instance, so when I just moved to California the Zika epidemic hit, I don't know if you may be remember that it was huge in Latin America and then it was also actually getting into the US here and there, right? And from that I guess we'd learned that the local context and environment are really decisive in whether an epidemic actually spreads or not, because it's pretty much less in, for instance Florida than in areas in Latin America. So to actually transfer lessons from, for instance Ethiopia or Kenya to maybe Vietnam, it's I think it's hard. I think the one recurring lesson is that we seem to be learning that whatever trick we devise, like a new drug, a new insecticide or a new tool to keep the mosquitoes at bay, they'll typically come up with a solution that they will get around that, right? So in that sense we need to, we need to just, like wherever you are, it needs to be in approach that basically attacks the problem from many different angles. - I'm curious how much if any climate change has played a role in where the mosquitoes are living now, if they're expanding in certain regions they weren't before, how is that working? - Yeah, I think climate change is a huge driver in that because it's making all kinds of places that previously maybe were not suitable for a particular mosquito species that may be particularly nasty because it's good at transmitting malaria or something else. So it may make an area that was not suitable, suitable, given, for instance, warming or increased rainfall or something like that. Of course also the opposite sometimes happens, there's also regions where actually we think that maybe malaria transmissions going down if they would warm up. But I think overall the general projection is that by climate warming we will definitely get more spread. One big unknown there is that we don't really know how quickly mosquitoes are adapting to new temperatures, new thermal environments. So while there's this thought that maybe there's these specific regions at the edge of the Sahara where it's getting warmer and warmer and therefore maybe we won't get malaria there. I should say south of the Sahara. If mosquitoes actually would be adapting kind of at the same base as places are warming up or maybe cooling down, then actually we may just get more and more spread. So I think climate change and obviously mosquito evolution could go hand in hand in a nasty way in that sense. - Is there anything we can do to prepare for that or is it really just give you and your team more funding to help do that research for us? - I think that's an excellent starting point. - Yeah, I think whenever we see mosquitoes being introduced in a different area, the mosquito is not doing that so much in that. There's a little bit of long distance dispersal in mosquitoes probably in high-air current currents but the majority of long distance travel of mosquitoes is just by humans, right? But I also see it close to home here. Like I live in the Netherlands currently in the south of Europe we have the Asian tiger mosquito that has invaded over there. And like when people coming back from summer holiday there's always introductions of that mosquito in the region here, right? So people are really doing most of these introductions and there you could imagine that more awareness or more control on that front could actually help. - Okay, that makes sense. And how much do you think funding healthcare infrastructure, how much does that play a part? You know, I think again, it sounds like from where you said it's all of this at once, but you know, the mosquitoes are adapting climate change and as you said human movement is allowing them to move with humans. So how do we sort of pinpoint those greatest abilities I guess to affect change within all the different many pieces that go into it? - I mean both are super key 'cause we see that in a lot of African settings when the healthcare systems break down because of either for instance, some natural disaster or political unrest we also immediately see basically transmission of diseases go up, right? So in that sense it's a very multifactorial problem. Like there's people like me that are really focusing on the mosquitoes. Then there's like the guy on the other side of the wall is trying to come up with a new vaccine for malaria. But then you know, if the healthcare system is basically really under massive strain then none of that matter so much, right? Because you're still gonna have issues. - Yeah, well I think it goes back to your comment about open source, right? Like kind of just getting at how can we get better at collaborating across disciplines and sectors of thoughts? - Yeah, no and yeah. So that's, I mean for my work that's clearly valid and that's for bringing scientific tools to people, right? But if you look at malaria vaccine development for instance, just getting pharmaceutical companies to basically produce enough vaccines so that you can vaccinate that huge continent. That's not easy and if we close source everything and it's only about actually being profitable then that's probably a heart problem to solve, right? So they're open source and I guess like, yeah, sharing knowledge really comes in. - Yeah, so for someone who's listening to this who doesn't care about mosquitoes and always just kind of wants to swap them away, what do you hope that we leave this conversation understanding about these features that you love? - I'm not expecting people to be like, "Oh, that sounds like 260 herds that maybe like an 8 is female." That's great, oh, that's such a beautiful animal, right? What for me makes it interesting is that an animal that is deadly and annoying is also really like from a biological view is actually like, you can think of it as a pretty animal, you know? It has, depending on what your taste is, it can look beautiful. Also, it's evolution is quite interesting. It comes up with novel solutions for heart problems. And in that sense, we're kind of like, you know, we're living together with this animal on the planet, right? So we have to realize that whatever control tool that we will come up with, the animal's gonna respond, right? So I think that's something that we need to keep in mind. - Well, I do really appreciate this approach and clearly as in all of our conversations, the enthusiasm that you always bring to your work [BLANK_AUDIO] really encourages me to remember that even the things that I might not like or want to lean into are actually worth a kind of second or deeper look or thought. So I really appreciate that about you and how you approach your work. Thanks for joining us Felix. Thank you. It was super fun. That was Felix Hole and in conversation with Lily James Olds to learn more about the Ted Fellows program which supports a network of global innovators and to watch all the Ted Fellows films, go to felos.ted.com. If you are curious about Ted's curation, please visit Ted.com/curationguidelines. And that's it for today. Ted Talks Daily is a podcast from Ted. This episode was produced by Lucy Little edited by Alejandra Salazar and fact-checked by Eva Dasher. The audio you heard at the top comes from the short film made by Divya Gadongi and Owen McClain and story edited by Corey Hagem. Additional support from Lily James Olds, Leoni Horster and Allegra Pearl. Our team include Aspen Fitzgerald Dorsey, Oliver Friedman, Lucy Little, Shuhan Hu, Debbie Rolf, Emma Tobner, Connor Tittsworth, Tonsica, Sunglaar Nivong and Hannah Yu. Additional support from Isabella Aslorona, Danielle L. Ballerizo, Valentina Bohanini, Ban Ban Chang, Christopher Faisy-Bogan, Cinnamon Horn, Laney Lot, Matthew Poulis and Yachty Vazquez. Learn more at podcast.ted.com. I am Elise Hugh. I'll be back tomorrow with a fresh idea for your feed. Thanks for listening. [BLANK_AUDIO]