 I'm Luke Alfie from the Pervrite Institute Arthropod Genetics Group and I'm going to talk about controlling mosquito-borne disease by releasing more mosquitoes. So what's the world's deadliest animal? You might think lion or shark or jellyfish or something like that, but according to this analysis from the Bill and Melinda Gates Foundation from a few years ago, it's mosquitoes and by quite a large margin. The World Health Organization estimated that something like 17%, 1 in 6 of all infectious disease is transmitted by mosquitoes or mosquitoes and ticks and these other small arthropods that transmit various viruses and parasites. Now malaria is probably the best known of those, but there are also many viral diseases. Dengue virus is very well known, Zika yellow fever was a huge scourge in previous times. We have very few ways to control these diseases, in fact they're getting worse. Yellow fever that I mentioned is probably the exception that there is a good effective widely available vaccine for it but it's really the only one. Dengue alone may be 390 million new cases a year and increasing. We have very few tools for dealing with these broad insecticide sprays and the like which are not very effective and not very environmentally friendly. So we're looking for something more precise and cleaner and more effective and many people are thinking about this but geneticists like me have of course think about a genetics based approach or synthetic biology approach if you like and so what if we can modify some traits of the mosquitoes and make a new trait for the mosquito, a heritable genetic trait in the lab in mosquitoes and then disseminate that into a wild population somehow. Ideas at the moment are really in two groups, one is what if we could reduce the viability or fertility or something like that of the mosquitoes and if we could get enough of the mosquitoes affected by that there would be fewer mosquitoes and therefore less biting and therefore less transmission and we might call that population suppression and if you think about it that's really what current pest control methods do try to reduce the numbers of pests but then the other approach would be what if we could make the mosquitoes less able to transmit and then go back to vaccines, let's do a thought experiment, what if we could vaccinate the mosquito population, now we can't for all sorts of reasons but if we could what would be the effect, well the vaccinated mosquitoes would still be out there still biting people looking really unaffected but less able to transmit the diseases so we would get less transmission of dengue or zika or whatever virus we're talking about with the mosquitoes looking otherwise unaffected and we might call that population modification because we're modifying the population without actually suppressing it and scientists including my research group at Purbrite are trying to do each of those things with quite a lot of success but then if you could make such a novel trait in your little mosquito colony in the lab how are you going to get it out into the field and that's that's another problem and again the obvious and simple way is to release lots of those mosquitoes and sort of overwhelm the wild populations so if you get enough of the wild females to make your sterile males the target population will decline and collapse so that's part of the population suppression approach that we talked about that I talked about a minute ago and it's really effective but you do have to release a lot of insects and it's not obvious not intuitive to anybody so when you say how you know you have a mosquito problem you have a mosquito-borne disease problem what if we were just to release a whole load more mosquitoes genetically modified ones in the same area that would be a good idea wouldn't it it's not sort of intuitively obvious to everybody that it would be but there of course there are a few details that I've skipped over one is that only female mosquitoes bite and so and males don't they just go look for wild females so if you release lots of those males they're really harmless and they're just trying to quarter make the wild females which is what you want them to do and another attractive part of this sort of approach which might call genetic pest management using genetics of the pest to try to manage the pest is that the insects that you release would only quarter mate with the other sex of the same species and not even with other species of mosquito of which there are many harmless mosquitoes out in the environment let alone bees and butterflies and the other insects the the earliest genetic pest management by a long way is the use of sterile males originally radiation sterilized males and that technology has been improved using synthetic biology and also some other approaches like what back here and so on to make better sterile males or effective ones for other species and in particular mosquitoes but the trouble with those approaches is you need to release a lot of insects you probably need to release every week and you need to release more sterile males than there are wild males out there so that most females will mate one of you or sterile males so that's a lot it's perfectly doable and it works really well but obviously it would be economically more attractive if you could manage to release fewer so how might we do that one of things a number of research groups including mine but around the world are working on is the potential use of genetic systems that will spread themselves so rather than you having to rear lots of mosquitoes and release them the genetic system will do some of the work for you we call those genetic systems gene drives and they're based on naturally occurring system systems of which there are many in nature so there are many genetic elements selfish DNA elements they're sometimes called that will spread themselves through a population and so synthetic biologists try to capture the essence of those and make artificial ones that will then go where they want them to go and not where we don't to spread these sort of traits and so these gene drives can be a sort of amplifier multiplier on our releases so that we can make the whole method much more efficient while still retaining the key benefits of having something that's species specific and clean and targeted and not affecting other insects or organisms in the environment at least not directly so for population suppression if we're going to reduce the number of mosquitoes and we want to put a novel trait into the population to do that what's that trait gonna look like when it could be fertility so they could just be sterile or less able to produce eggs or something like that but there are all sorts of other things that will do that and for the mosquitoes that transmit zika so 80s Egypti one possibility is to make them unable to fly so then as larvae in their little pools where they will breed together in little pools of clean water for this for this species the larvae will still be there and competing for food and stopping the other ones from getting enough food in the way that they do but then when they emerge if they can't fly they can't get away from that breeding site they can't fly and find you or me to take a blood meal as they would see it or bite us as we would see it and they also can't can't mate as it happens because the primary recognition signal for male mosquitoes whereby they recognize females of this species is the females wingbeat frequency so that's sort of annoying whining buzz that you hear from mosquitoes so if we want to put a novel trait into a mosquito how do we do it well the first thing is to think what trait you want to put in and then imagine or come up with a piece of DNA that will encode that trait and that's a sort of synthetic biology part but then there's actually getting it into the mosquito genome and by this I mean inserting it into the mosquito chromosome so this becomes just another gene amongst the genes we have and the modified constructs of the synthetic DNA that we put in is usually two or three genes on a piece of DNA that might be 10,000 nucleotides long and those nucleotides of the GATC of the famous genetic code mosquitoes probably have 30,000 genes we're putting in two or three and they and the mosquito that we work on has over a billion bases of nucleotides and we're putting in about 10,000 so that's significant but not huge modifications now to get it in we just inject DNA into the egg if we inject 100 mosquito embryos say then maybe 10% of them will survive that process and grow up to be mosquitoes and then the idea here is that some of the cells in that mosquito will have taken up our DNA into their chromosome so then they're what's called a genetic mosaic so they have some cells that have our modified gene and some that don't so to go through the numbers if if we inject a thousand hundred survive and we look at a hundred offspring from each of those so 10,000 something like that we have a pretty good chance of getting one that is what we want we have to be able to identify the modified ones pretty efficiently to find that needle in a haystack so we use one of the genes that we put in is always a marker so something that would like clearly identify the modified one from all unmodified ones so that we can pick it out but it's not it's useful not just in that first instance for picking it out but for subsequent breeding so that we can follow its inheritance and even if we get through into the field to be able to distinguish the modified mosquitoes from the unmodified ones so there's a few possible markers but by far the most common one that we use is a fluorescent so fluorescent protein the modified mosquitoes you might say they glow in the dark but really they you can only see it under a very special microscope but under that special microscope they do indeed glow and a very distinctive one the color that you choose we have red ones and green ones that look quite different from the unmodified ones so that we can recognize them very easily this whole group of approaches the sterile males I talked about but also the other ones of this type are very targeted to the specific pest that you're trying to control so very clean very controllable very very targeted to the particular person minimal off-target effects so there really is quite a lot to be said for releasing large numbers of mosquitoes to control mosquitoes