#510 Gene Drives (Rebroadcast)
The views expressed on science for the people are not necessarily the views of this station, its affiliates, sponsors, or advertisers. This week on science for the people. We're talking about new drivers for the genetic bus. We'll speak with Kevin s felt about what Jean drives are and how they can be used and with bioethicists Lori Zoloft on what it means morally to release them into the wild. Welcome science for the people. I'm Bethany Brookshire, a writer with science news and society for science and the public it's summer and the mosquitoes are out in force in North America. Now, they carry new worries about Zico, but they've always carried dangerous such as malaria and yellow fever. There's a new technology with the promise to kill off these mosquitoes with no spring or chemicals required. But what our Jeanne drives? How do they work? Why are people afraid of them to introduce us to Jean drives? I'm here with Kevin s felt an engineer at MIT. Kevin. Thank you so much for being here with us. Let's start simple. What's the gene dress? So gene drive is a genetic element. When that's transmitted from parents to offspring that can increase in abundance that is it can become more confident population. Even if it doesn't help organisms to reproduce. Now, you might imagine. How can it do that don't genes normally spread by helping the organism carries them reproduce? How could they do it in any other way? Will gene drive system has ways of increasing the chance that it will be inherited by the next generation of organisms most genes in sexually reproducing organism. Have a fifty fifty chance of being inherited by any given offspring. Gene drive systems can increase the chance that they'll be inherited by surviving offspring up to one hundred percent. And consequently gained advantage that lets them spread through the population. Even if they don't help the organism itself. Now that's tremendously important because whenever we alternate organism. We're diverting its resources to do something that we want. In other words, were we almost always reduce its ability to survive and reproduce in its ancestoral habita-, and that is prevented us from. Doing anything to alter wild population. Organises now, many would say that's a good thing. But when you consider the potential of mosquitoes and ticks to provide two notable examples to do things like spread disease that can be something of a problem. Style. Gene, drives are sometimes described as being kind of we talk about selfish genes, gene, drives kind of extra selfish, gene. How how does that work? How does gene drive increase its chance of don't want to say transmission, but I guess transmission across generations. Critical transmission anyway, so it's important to keep things in perspective. There are some viruses that not only transmit from person to person, but occasionally we'll get into the genes that are transmitted to the next generation. So in that context, a gene drive is like half of a virus? It's completely lost. The ability to spread from person to person can only be transmitted like a normal, gene, just slightly better than normal, gene. And get the thing is these are completely natural that is he ability to increase in frequency is exactly what natural selection selects for. So there's a tremendous variety of different kinds of gene, drives that nature invented hundreds of millions of years ago. What's different now is we have we now have technology that may allow us to harness gene drive to alter wild populations. And of course, this raises tremendous ethical challenges in terms of not just should we do it whether when and how but also who gets to decide. And you mentioned that we now have the technology to make gene drives ourselves. And you're talking specifically about crisper what is crisper and how does it work? Crisper is a protein that is a DNA encoded molecule that we can easily program to cut and therefore to edit just about any DNA sequence in any organism throughout all kingdoms of life. This is remarkable. Because before in order to edit it, gene we had to make an entirely new protein. In order to cut a specific DNA sequence. And this was a tremendous amount of work when we could do it at all with crisper. We simply need to express what's called a guide. RNA? Now are any is the messenger molecule DNA is typically transcribed to make Artan which then gets translated into a protein aren't aid has lots of other things around the cell. The point is that just like DNA has four bases. A c g t are in it has four corresponding basis. So DNA normally has two strands that pair to each other are in a normally has one strand, but it can also have two strands, and what's more. You can have a strand of Origny bind a strand of DNA. They're perfectly correspond. So to direct crisper to bind a DNA sequence. We just need to produce a corresponding RNA antagon- with a signal that tells crisper here, this is a guide us it too. And the target sequence. And it will out of the three billion base pairs of a human genome we can program crisper defined one unique sequence of just twenty bases of DNA. That is only found in one site. Chris Bobo go there and bind to exactly that sequence. And if we choose a carefully to nowhere else in the Gino. Now, how do you use that to create a gene drive? So when scientists I developed crisper for genome editing the way we did it as we introduced three separate pieces of DNA into the cell that we wanted to add it the first one in coded the crisper protein itself. So it produced the scissors the second one encoded the guide Arnie telling it, which gene we wanted it to cut in the third included the new sequence that we wanted to replace it with. Gene drive system like crisper. Gene drive system is just all three of those on crisper. Gene drive system is all three of those elements on the same piece of DNA. So instead of just putting in the sequence you want to change it to you also encode the instructions for making that change. If you do this and make an organism from that cell. That is if few edit a cell that will produce sperm or eggs, you can get an organism that encodes, your desire change and also be crisper components necessary to make that change in. Here's what the magic happens when that organism mates with a wild organism, the offspring will inherit one copy of the new, gene and the crisper system and one copy of the original sequence from its other parent, and in those offspring in the cells that will give rise to sperm were eggs and crisper system will cut the wild type version on the other chromosome and the cells will fix the damage by copying over the new sequence. And the crisper system that means the offspring now has two copies, which means that when it meets with a wild type organism its own offspring are guaranteed to inherit one and editing happens again, and again, and again, it's like releasing. An element into the population. That is a finding replace function. Whenever it finds a copy of your original target sequence encoded by that guide. Darnay he will cut it. And replace it with the new version. And you mentioned a little bit earlier that gene drives are not just laboratory creations. They actually do occur in nature. Where do we find them everywhere, including our own genomes, who's another kind of gene drive one that instead of copying itself from one chromosome to the same site on the sister chromosome because we have two copies of all of our chromosomes except for the sex chromosomes, which is a bit more complicated. In some gene drive systems. They simply copy themselves at random somewhere else in the Gino pleaser called jumping genes scientific name is transposed on. And what it does is? It makes a copy of all just insert self at random somewhere else. And the vast majority of the DNA in our own selves is broken transposons broken remnants of gene drive systems from the past that have just accumulated overtime. What's more gene drive systems can be essential to involving potentially important do traits? So the current best theory for how mammals evolved the placenta. To feed to feed the embryo in the fetus in the womb is that it required a transpose onto move essential regulatory elements to other sites in the genome that is mammals, and humans would not be what we are today. Were it not for an ancient gene drive that moved the elements necessary to let us become what we are. But now we have these gene drives on we can make them work in the lab. Scientists are working on ways to use this to reduce mosquito populations specifically mosquitoes, but also you've been working with nematodes, roundworms, etc. What are some of the ways that a gene drive could be used to reduce a population? So this seems kind of strange, right? How can you reduce the population by spreading announcement doesn't need to reproduce in order to spread will the way? You do. It is you target a gene that requires only one copy. For fertility. So it's most effective. If you target a female for Tillery g because for obvious reasons females are absolutely necessary for the species to produce. So if you want to reduce the population he want to reduce female facility. So if you build a gene drive system, but crisper gene drive system that cuts and replaces a female fertility g well females that have one copy of this gene inherited from a wild parent and one copy from a gene drive parent will be fertile. And that's because you only need one functional copy, but in their ovaries when they produce eggs. The gene drive system will activate it will cut the functional copy and replace it with itself. So these females will be fertile, and they will transmit the gene drive system to all of their offspring. But if you have a female that has two parents that carry the drive system, then she will inherit two broken copies and will be infertile. So the drive systems spreads rapidly went rare because most organisms are meeting with wild wild type organisms. But when it becomes abundant most females will inherit one copy from each parent and will consequently be infertile causing the population to crash, not to go extinct mind, you most scientists are extraordinarily skeptical that any combination of gene drive systems could ever drive species extent that's been commonly bandied about media in it is as best we can tell simply false. It cannot be done. Even if. The rest of humanity just sat on its hands. Which is another important when we need to get to if we have this technology to alter a shared environment. The shared ecosystem that we all depend upon. How can we ensure that no one person just decides to do something? And fortunately for us if you can if you can find and replace any wild population someone else can release their own find and replace that is using binding replaced it at it something in a in a word processing document, and you don't like it. You just run another finding replace and the same is true, gene because crisper can target any DNA sequence. No matter how agenda system is constructed. It's possible to build another one that will override it. And whatever change it made can be undone. So what that means is that everybody else has a veto over what is done to awhile population. As soon as you see it, you can override it and undo it. So the idea would be you take gene drive that reduces mosquito populations. The population crashes, presumably as a result of this malaria say goes away, and then you can introduce a another gene drive that makes the mosquito population fertile again. Although in that case, you don't even need another gene drive because any mosquito that can resist the effect. So you change the DNA sequence encoding that recessive female facility, gene. So that it can no longer be cut by the drive system that any female with that will be Hyun will always be fertile. And all of her descendants will always be fertile. And so they'll just rapidly to out compete, the ones that carry the drive system and the population will be restored. And because he's mosquitoes this would occur incredibly quickly. And how close are we to something like this? It feels like the whole gene drive research field is is just exploding. It's going so fast. Comparatively brand new the. I I thought of crisper gene drive a little bit more than four years ago. And now it's been demonstrated in numerous species, including two species of mosquito. But you're not going to see us anytime soon. And in fact, the kind of gene rod we've been talking about there's probably only a handful of applications in the world that could potentially be used for. And that's because it's a finding replace without limit. The drive system has everything it needs to be copied to the other chromosome, essentially, no matter what indefinitely you release a finding replace into the population. Eventually it's going to find him replace every copy and spread into potentially every population of that species everywhere in the world. So how do you program? Those mosquitoes to not spread over a particular international boundary. You don't her at least not with that technology. And that means that no one will be able to do this unless all of the potentially affected countries agree. So let's talk potential applications. If you want to get rid of mosquito borne disease, how common are these. Where do they exist? Is it possible that all the countries would agree while you mentioned Zeka there's two species that are that carry Zeka both are called eighties mosquitoes as a gypsy eighties? Albuquerque's and together, they are present in more than one hundred countries harboring more than four billion people. So how then are you going to get all of those countries to agree to release a gene drive system? To get rid of those mosquitoes. No matter how much we might dislike them, no matter. How dangerous they already human health. They are needed to someplace in the world. The may or may not be doing anything important for ecosystem. But whether or not they are you really think it's practical that all of those people are going to agree, especially because you can't test this in the what? That is how can you run a safe field trial? Given that it takes one organism that escapes, whatever containment you use to potentially invade the next population. So even if gene drive works as well as we hope. That means it almost certainly works too. Well to actually use for almost all essential problems cynic challenges you're talking about here are mostly sociological and cultural rather than scientific and diplomatic. Absolutely. There are international laws that essentially blocked this. Preclude most nations from even considering attempting? So where might you get enough countries to agree and the answer is probably malaria, and that's just because we had a lot of meetings and workshops, and so on trying to figure out what would happen if we suppress the level of a major malaria vector mosquitoes down to say one percent of their current level. Well in the African countries where these mosquitos live. There are many many many different species of mosquito. These are in fact in the minority, they're just concentrated around human habitations. And since they're in the minority that doesn't seem to be any other species that particularly depends on them. Yep. Shot is we don't think there would be. Really tensely any ecological effects? We came up with a whole list of them. Anyway, because we try to be creative that way. And if you assume that every last one of those potential expected side effects happen. Every last one of them, and you added together how bad that would be. They wouldn't be even a tenth as bad as malaria because in the time that we've been talking malaria has infected probably twenty thousand people and killed probably ten kids under the age of five just in the time that we've been talking. That's how bad malaria is. So if I lived in Africa and more to the point if my two kids lived in Africa because I have two children under the age of five I wouldn't care if we couldn't test this field trial. I would say go ahead and do it because malaria is just so bad that no combination of unwanted side effects could be anywhere near as terrible as malaria. But of course, I don't live there. So I don't get a boat. But if I did, that's certainly what I would vote mosquitoes are one possibility, but you've actually written about other species where this might come in handy. Can you talk about those? Well, another good candidate is the new world. Screw our. And this is an organism that lays its eggs in the open wounds of mammals and the larva eat their way out. Shooting painful and disgusting parasites that exists in all the world. That is the very life cycle of this organism involves agony for higher mammals. That is the organisms that at least we believe perhaps with a tad inflated self for God are most capable of suffering. This organism specializes in causing that as a default part of its life cycle, and partly because of that we have a radical it from all of North America. And we did so by deliberately raising millions of them starting in the nineteen fifties and irradiating them so that they're sterile and then releasing them. So a sterile irradiated scrim that mates they wild. When of course will not have any offspring, and because of this species is such that, you can Iran Kate the local population if you release enough so the US department of agriculture pays for a facility in Panama that every month releases millions of sterile skewer implies a cloud over Panama to keep the species from reinvading North America. And yet last year it did actually reinvade Florida. And so the USDA released a ton of sterile spree rooms in Florida now, it's gone again. So in this case, the geographical terrain of South America is such that we probably quit use sterile, or at least irradiated sterile squirms to remove them from South America as well. But we could if we wanted to use a gene drive system to genetic way spread infertility through the wild school population until it reduced to the point of being gone. If we're worried about any. Regular ecosystem being adversely affected by screw him. And again, the seems pretty unlikely because we did get rid of them from North America and didn't see any side effects than we have that facility that can make and release sterile screw already. So we could remove them from any ecosystem. We were worried about him and watch it to see what happened. So if we're worried about whether there'd be an ecological affects of removing squirms burning particular environment, we could always release irradiated squirms their remove them temporarily. And then watch to see what happens. So it's a case where we don't think there would be an ecological effects. We could use a gene drive to remove them. They're only twelve countries that would be affected not only with their profound animal welfare reasons to do something in this case. But there are also economic reasons, which is the reason why countries might actually act just because skirmish says he can imagine are absolutely horrible for livestock both from an animal of her perspective. And from an economic perspective they do about four billion dollars in damage every single year to the countries of South America. So that's a case where on both animal welfare and economic grounds. I care more about the former I bet a lot of governments in South America. Care. More about the ladder. We argue we ought to do something does that outweigh deliberately rendering species extinct from the wild. Bent depends on how you view the morality of the natural world than our responsibilities to it are we are we wildlife managers are we like Park Rangers trying to just protect what's already there. Or are we gardeners acknowledging that we have already played a profound role in shaping the composition of what we even what we think of as wilderness, and then taking on that responsibility. I think in this case this is a species where we should preserve it by feeding on dead meat in captivity. But I don't think that organisms should suffer that excruciating agony of screwing infection of literally being eaten alive by maggots for any longer. And this raises a particular ethical challenge beyond what I what I just said. And that's and that is we would all agree that if a child is drowning in a lake it's our obligation to dive in and save, and that's true. Whether or not we through the child in that lake we haven't ethical obligation to save the child, but we only have that obligation. If we know how to swim that is if you don't know how to. You probably can't save the child or at the very least you would endanger your own life by doing. So potentially accomplishing nothing other than your own debt. So if you do not swim, you're in the clear, but as soon as you learn how to swim. You are obligated to save drowning children's gene drive technology in this case is like learning to swim. We didn't create species like the new world screw worm that causes horrific agony through their very existence nature did that. But now, we are the ones who are morally responsible. What are we going to do? Now. You also mentioned earlier that hukou nations might be able to develop resistance to gene, drives is that true Sherm. So for population suppression ginger is like spreading female infertility. We've been talking about I mentioned that if you want to build resistance, you just need to Recode that, gene. So it can't be cut. Well, if you build a gene drive system, and it cuts the target south doesn't have to be the gene drive system. Some fraction of the time. It'll just jam the broken ends the DNA together creating a mutation of that site that mutation than can prevent the drive system from cutting it again that is gene drive systems naturally. Create resistant wheels that will block their spread. However, if you want to overcome that you simply need to program crisper to cut multiple sequences that are in a gene that is important for fitness. That's because deleting all of those sites so that they can't be cut than deletes that important region and deleting that important region is more costly drought. That is to say you just have to engineer at carefully. So that natural selection is on our side. There's a lot of papers coming out recently saying gene drive won't work in the wild. Because there are this problem of resistance wheels. Well, yes, we've known this for quite a long time, there are resistant wheels. Austin Berg who first proposed that we harnessed this kind of gene dry, this cut the other chromosome and copy itself over I proposed that back in two thousand three and he emphasized that this sort of thing was likely to be necessary. We couldn't do it until crisper crisper can readily be programmed to cut as many sites as we want. So we have to build drive systems that will do that. If we want them to work in the while. And no one's been doing that people have only built drive systems that use a single guide in and those ones. Of course, we. We know are going to create resistant Liles that will ultimately blocked. So there's been all of these all of these all of these stories saying, gene drive won't work in the wild. Well, yes, gene drive like that will not automatically work in the while. It's true. But no one has actually built them, according to the design that the model show will work. So if you think of crisper essay, a pair of scissors right now everyone's been doing crisper with just one cut in the paper strip of DNA assay. And you're saying that to avoid the animal just kind of gluing that cut shut you need to make a whole bunch of cuts. Yes. Gluing cut shut with a safe, adding a little paper clip there. You can't cut that site again. Okay. So make it too hard. So that the gene kind of runs out of paperclips. Yeah. In effect because keep in mind that all of those cuts are going to happen at basically the same time because the repairing them process is much slower than Christmas to be target five sites. It's going to almost always cut all five sites before any of them get repair, which means if it wants to Jimmy ends together as to delete all of the DNA in between as long as that's DNA is important than it. Just can't do. That natural selection will select against that more strongly than it selects against the drive system. Now, you've noted that there are some species where we really could find gene drives useful like screw worms or mosquitoes. But you've also written about gene drives places where Jeanne drives won't be useful like in crops or in humans. Why are there species in which Jean drives are not going to be practical for one thing any species that doesn't reproduce sexually or really can reproduce any way other than sexually so think plants that can reproduce vegetative early, but his grass just spreads without necessarily having sex. Similarly, some organisms primarily made with themselves that is some plants can sell Ponant anything like that. If you try to use a gene drive in it imposes a cost you're just going to select for them to reproduce without having sex because if they don't have sex than they can't acquire the gene drive system. So all species like that are essentially just off the table it won't work. The other thing is gonna keep in mind. This is a parent to offspring technology requires many generations to spread any meaningful extent in population. That means. She's like whales or elephants or humans. You would have to wait hundreds or thousands of years to have any kind of meaningful effect. What's left, and of course in humans. The reality is that everybody is going to be sequenced in a decade or two you would see it. And you can just imagine future generations laughing at us. You know, really dad you thought that you could tip the scales in favor of grandkids. That would be like, you you think that's really funny like we wouldn't notice that with your antiquated, gene drive crisper technology. The upshot is gene drive what we're humans it takes far too long. And that and that's true. Even if we didn't sequence everything and presumably have far superior technologies for doing anything in future. But people do get a little kind of queasy when we talk about manipulating species in this way, potentially playing God and driving them to extinction. What are some of the ethical questions that come up for you that you take into account when working with Jean drives? Here's the thing. I think the most important application of gene drive isn't even erotic getting malaria as important as that is. I think it's the gene drive could force. Us to change the way that we do science. Now, why is that? Well, almost all research right now is done behind closed doors, and that's just because scientists are afraid that if we disclose are brilliant new idea someone else might go ahead and do it in the lab, I publish first. And if that happens, they get all the credit and we get nut. So everyone keeps what they're working on secret from everybody else until they're done with it. And then you can present it all wrapped up with a nice Chinese the downside is it's really not much fun to live in paranoid that someone else might be working on what you you are. Because even if they don't hear about it from you. Well, there's a lots of brilliant people in the world and often they think like so there could be twelve other research groups working on exactly the same problem in exactly the same way. And you would never know every day you could wake up to see that your last three years work has just been wasted. It's not much fun and from the perspective of society, it's incredibly wasteful because ninety percent of projects fail it, gene. Dry. We don't know if it will actually work in the what we don't know it works in some species in the lab. Tori, quite well. But that doesn't mean it will work even in all populations of that particular species. I means it will work in the ones that we've sampled in the laboratory and since most research projects fail. Nobody publishes the ones that fail. Meaning somebody else who has the same idea waste their time. Trying to get something to work that will not work to take a step back. If you were to design a system for exploration, would you have all the explorers go out there deliberately keeping their plans? And where they're going in their record what they saw last time mostly secret from everybody else. Well, no that doesn't make sense. It's like saying you're sending out your explorers, and they come back and update the cartographers except perhaps for the juiciest findings because that's what their next expedition is that's the current system. But a few years back, we invented, of course, GPS and satellite phones. And it's like the explorers are still doing the same thing. Even though they could update the cartographers as they go and keep track of where everybody else is and coordinate their efforts compete to be sure but on an informed basis, but they don't because the incentive structure is such that they have to come back and report in order to gain any glory. That doesn't make sense. Let's think about this another way scientists and ecosystem, right? An ecosystem does not adapt to become better at being an ecosystem or doing any particular thing forest do not compete with prairies the trees compete with the grasses and the other trees so each tree species evolves to become better at reproducing as that tree species. But the forest itself doesn't evolve to become better in the same as truth, cultural institutions. They don't adapt particularly well to the conditions of the time, and unless there's some conscious human intent going on in there hasn't been much because it's hard to actually change a whole system away that people do things they don't tend to change much and a few years ago. The cost of sharing information went from too high to be useful. That is if you wanted to share what you were working on that didn't work you would have to print it out as ink on paper. And then send copies to all the libraries of all the other researchers in the world, and then they would have to go to that library and read it. Whereas recently the cost of information sharing dropped to zero system has definitely not update. Needed to account for that. We are wasting so much time so many resources pursuing a frankly obsolete model of how we do science. There are some efforts to make science open access that is when you come back enough. Dave Baker Taga Fers their maps shouldn't be kept behind lock in key only to those people who pay that's the battle where fighting nap L to respect. That's pathetic. We can do better than that. We should be disclosing what our plans are is should be faster because we win know what others are working on. And we can collaborate or compete on an informed basis. Fine. Who is the best collaborator? Who now has something new that we can consider jives with what we're doing. So you're interested in conducting this gene drive research, very openly, then will vote so phony continue a little bit. The other thing is suppose that someone comes up with something that is actually dangerous right now, we only hear about it when they publish it. If it's truly dangerous that's probably too late to do anything about it. So right now are blind discovery strategy is perfectly fine as long as there's nothing dangerous out there to discover what we know that there are nuclear weapons, and we know that they're dangerous pandemic viruses. There's a lot of worry about super intelligent artificial intelligence. So we also think that there are dangerous things out there. And yet we haven't changed our strategy for discovering things were still operating largely blind. If we want to open our eyes, we have to change the system somehow, but how do you do that you have to change the incentives of science, but for gene drive, the incentives could potentially be different. And that's because if you build a gene drive behind closed doors, you're denying people who could be affected a voice in those decisions, and that's different from all the other technologies because before we really haven't had any technologies that could allow a single research group to build something that would affect an entire ecosystem. Gene drive is in many ways, the first geo engineering potentially being the other one, and that means we have an opportunity here because what's more. If you're a scientist, and you're developing a technology to alter the Sheridan varmint, you're never gonna get to use it unless people want it to happen that, but why should they trust you? If you're insists on doing your work behind closed doors. There's just no reason. So there are moral and practical reasons to develop gene drive in the open. And so I. We might be able to change the incentives for researchers in the field of gene drive and thereby tryout a more open model of science. So we've been coughing for everyone to Preregister the experiments they plan to do in the field of g Andhra, and we're talking with journals with funders policymakers and even holders of intellectual property to change the incentives for research in the field of Jin. Dr initially the key incentives in science are the scientific journals for recognition the funders who respond to that recognition to give you money to run your next experiments. Be regulators who of course site whether you it's legal to do those experiments in the first place and nowadays holders of intellectual property. So we're working with all of these groups to try to change the incentives such that it is better for researchers to disclose their work in the open in advance of running those experiments and that ensures that everyone who might be affected by technology. Like, gene drive would have a voice as it's being developed critically important because frankly, science works by setting up the incentives for other people to challenge. Our assumptions to try to prove us wrong. That's really at the heart of science and yet right now that incentive system is largely confined to active professional scientists. And that silly, especially when it comes to technologies like Jane drive because I don't know nearly as much about the local environment as the people who live there. So not only do they have all of the moral power to decide whether or not this even should go forwards. They're the ones whose concerns and criticisms are most important not just morally, but practically because they know more than the people in the last. So the best way to perform gene, dry research by far is to propose a potential project. Let's suppress the local population of mosquitos as we're doing. Let's e Mian is heritable the local mouse population that infects most ticks with lime disease. So that most ticks are not infected with lime disease. We're not doing that with gene drive right now. But it's still an ecological engineering approach. And so we're not in charge where working primarily with the communities of man tuck it in Martha's, Vineyard and those communities their boards of health have appointed members of two steering committees. And the steering committee is run the project. We're. Just the technical hands of the communities, and that is should be because they have total say in whether or not the technology goes forwards and also what it looks like they decided, for example, that we shouldn't just make mice that are immune to live disease. We should also make them resistant to tick bites because that will block transmission of all tick borne diseases not just lying to these. That was a decision made by the community's not by the scientists in the lab, and I think that's more of what we need to see for research as a whole especially for these technologies was shared him backs. I think we will all be better off research will be faster will get new technologies to solve our problems more quickly. They're more likely to be supported and wanted and it's likely to be safer because he can keep an eye on what people are proposing to do than you could identify potentially dangerous synergies far enough in advance to do something. So I think Jin drive is the key to changing how we do science starting with a field trial in the field of gene drive to see how it works. And then if it works, well that could potentially change the rest of science. Well, kevin. Thank you so much. We are completely out of time. But that was. Amazingly eye opening or what we didn't get today's drive. Next time. So I have to be next time if you would like to learn more about Kevin assault and his work. We've linked to his biography and the great gene drive explainers on his website at science for the people dot c next. We'll hear from bioethicists Lori Zoloft who will talk about the bioethical issues surrounding sending gene drives into the wild. Science for the people is a weekly radio show and podcast that exploited everyday life from the scientific perspective, we are a member of the skeptic network clicks of blogs, podcasts and video content focusing on science and critical thinking to find out where science for the people areas near you. Or to listen to past episodes. Check out our website at science for the people dot CA. You also find links supporters that patriotic to connect with us on Facebook and Twitter and to subscribe to the podcast in items. And now back to the show. Welcome back Jeanne, drives are obviously something where scientific issues and our lives intersect, and there are some ethical questions to be dealt with. Are they moral to us? Why are why not to discuss the issue? I'm here with Lori Zola. She's a professor of religious studies bioethics and humanities at Northwestern University in Chicago, Lori. Thank you so much for joining us. Thank you for asking. We've had a little bit of background on what Jean drives are and how they work, but in some potential uses of gene drives this could actually involve gene driving species to extinction. What are some of the ethical considerations that scientists and the public need to think about an way with this technology? Well, let's start with what malaria is Bulgaria is one of the oldest and most significant human diseases on the planet. It threatens half the world's population. Last year, it infected two hundred million people and it claimed four hundred thirty eight thousand lives and most of those lives are little kids in sub Saharan Africa. The death rate for children under five is extra nominal more than thousand die every single day in their parents arms. Now, that's the background for why this is needs to be attacked. Why it needs to be considered seriously, and why serious efforts are warranted to try to eliminate it? The problem is that malaria parasite is clever, and it has developed resistance to every drug that humanity. His throne on that. So that's why crime doesn't work anymore. And that's why in some places the drugs that you take even traveling to work in some areas of of southeast Asia. And it's why it's so difficult to radical. So the best way to attack it is to think about about the host vector relationship. How Larry's Fred with his which is mosquitoes and the. The only mosquitoes are female the -squitoes they bite people only when they're only when they're about to lay eggs. So that's why it's only that's why the drive is is directed to female mosquitoes. And interestingly enough the drive is targeted so to eliminate the birth of females so only males would be born. And eventually there would be no females hence, there would be no there'd been a final generation. But here's the tricky thing. The drive doesn't have to even eliminate the species. It just has to reduce the binding rates below a certain level and find level, and then malaria could be could be eliminated to because of there's fewer people below a certain number being bit than the disease is not epidemic at some spread in the same in the same way. Now, there's thirty seven thousand kinds of mosquitoes. Right. And this drive is very localised. It would be delivered to a village there's big spaces in between villages. So the idea would be to see if it worked in one village. So there's the. The the the mosquitoes that they're looking at is one species of the thirty seven thousand -squitoes, which is anopheles Gambia. And that was that mosquito that one specific species is responsible for most of the worst kind of malaria in sub Saharan Africa. And that's the target of the drive. So no one's talking about eliminating all mosquitoes and people wanted to have ever head Miskitos. They could have them and no one's talking about eliminating even all the mosquitos in any particular village, just the ones that carry malaria. So the ethical issue is is complicated. Is it right to stop a practical solution to a deadly disease because of theoretical concerns about the future. And those concerns might be how would this affect the ecosystem in the villages now project malaria's is thinking about that? And what one thing they're doing is they're doing wide scale environmental research to find out what happens. When one particular species of mosquito is eliminated from ecosystem. And so they've thought about that. And they're they're doing research to answer that question does new species fill in that gap is what happens to the fish population that the mosquitoes all of this questions are being raised by this project. Now, people do get nervous about gene drives when they think about the power of science and kind of messing with the national world, why are people concerned about gene, drives is this a reasonable fear to have I don't think it's reasonable. I don't think it's thought through. So let's see what the worst case scenario might be. If if the fear is that somehow, this is Dr could leap over and eliminate all mosquitoes is what's the coherent fear? Actually. So I'm is it just this abstract fear of of manipulating nature. But of course, that horse is out of the born. Longtime ago, we've been manipulating nature since we became human beings that you could say the definition of what makes a human human being right about humanity itself is our curiosity or are are tricking around with with nature are are yearning to change nature are manipulation and taming and growing in harvesting and seating and and breeding natural world into an order. That is in fact, good for us safer us. And so this is a continuation of long held long long decisions about the fact that you should eliminate malaria from the world, we've eliminated polio, for instance, and the, and that's been altogether. A good thing for the children of sub Saharan Africa. Not to mention the children of waas Angeles in Chicago. So we do manipulate nature. We've made a decision that we don't like how the natural world rages, and is an and kills and we intervene whenever we possibly him. So the idea that we ought not do it. Suddenly when the the. The people that are being harmed our children in Africa. And suddenly, that's that point. We draw the line seems to me hypocritical. Right. I mean, this in any mosquito comes into my house bearing malaria, I would kill it. There's no question. So why would I deny that same moral gesture to a woman who who is in sub Saharan Africa doesn't have resources that the critics often have? So that's why that's why I'm I'm concerned about this. Because if you start with the science, and you understand the limited nature of this intervention, only, one species only species that causes the most of your cases of malaria, if you don't if you think about the actual science and don't have science fiction fantasy than I think most ethically ethical, and thoughtful moral people would say, of course, we should and this this terrible terrible disease. And this is this is a fish and good way to do it in a way, that's actually may have less of an impact than spraying and killing every living thing. In the village. The there's a fear about genetics, and I know it, and I know people are have enormous anxiety. It's normal to have exiled the about the power of science when there's been big catastrophic failures when there's been a linking of science with profit and people fear the intentions of scientists. But that's not going on and target malaria. It's nonprofit consortium of scientists who devoted a transparency who had voted in co-developing technology with the African people in the villages and with African scientists and university scholars from Africa. It's not a grand imperialist gesture in that sense. And we have to be careful about when we criticise science and technology that served could serve the good of so many people who don't have voice in public discourse. I said you talked earlier that I think oftentimes we are critical of right wing public disc-. Course that is mistrustful of the science that supports climate change. And we call to climate deniers when EMMY say them say this look at the science just look at the science science is very clear, and we are critical people who oppose climate change science. And I think that in fact, the progressive left, which I remember feels the same way about about Jeetan -nology. There's enormous progressive opposition to anything that has to do with genetic alteration and people need to look at the science, very carefully. Listen to what the scientists are saying and make the same sorta decisions that we've made around climate change respect the science trust, the scientists. And that's what the world a better place. Now, you mentioned, you know, people do have fears, and that's the thing there's a lot of logic. There's a lot of science, but when it's faced up against this kind of gut fear that we are, you know, playing God with you know, genetics or with the universe. What kind of? Of moral frameworks do bioethicists us to kind of deal with these questions. Well, I'm as scholar religious studies. And so I turned to the actual textual traditions in Judaism and Christianity and Islam that in fact, support support cultivation and support the notion that the natural world is left to its own devices can be cruel can be random can be capricious. And that the human task is to ring Justice and his to ring order and is to bring and his to being compassion into a natural world. That's the to the quite devoid of any of those of those moral moral principles that her what is not run by theory of Justice human beings, create a favor Justice. And so that's that's the framework that this work has to be considered within the framework of Justice would say, what should our scientific interest? What should our projects be directed to it should be the most vulnerable among us and. The most vulnerable among us seem to me to be for children without access to resources dying of disease that has used to be a problem in in the United States, but we eliminated every last species every last Petito of that species in the United States. That's why it's not a problem. Here we drained swamps, we sprayed every mosquitoes. We eliminated any mosquito that could be harmful to Americans as part of our project of of the -veloping America for for human beings. And now we've left rest of the world alone struggling with a very very very grim disease, and the solutions that that that are being tried have made a somewhat of an impact the death rate has gone down substantially. It's it's a good thing. But every one of the interventions is has problems, and that's why a combined approach including genetic approach is going to be needed to eliminate this disease. Now, you signed an open letter. That for a call for further, gene drive research in particular to target diseases such as malaria and that call for gene drive research. Actually, specifically talked about research that was vetted. Yes. Who should be vetting? Gene drive research. What are the things that they should consider while the people that one of the things that target Bulgaria does they put together a ethics committee drawn from physicians and scholars and bioethicists. Philosophers myself in religious studies who've can risk do the kind of research around the ethical considerations. That is needed in this case, the for me, the main people that should decide whether this is this prejudice. Advanced are the Africans were most directly affected by the disease. I believe that's true in general. I believe in the prep the premise nothing about us without us. So I think that this has to be this has to be a direct. This has to be vetted. This has to be approved. And it is by the villagers in. Mommy, were the the first mosquitos are gonna be are going to be sent. And it's only with their consent. They're full informed consent. It's only with respect for their their traditions. Their affiliations their their cultural decisions that the project should go forward. And you were mentioning target malaria the target malaria consortium, and they just did a vision and values statement regarding malaria and actually with specific respect to gene, drives, can you? Tell me a little bit about the group in general, and what it is that they've done here. Well, it is remarkable that scientists and social scientists sit around and think about how to undo ethical research. That's usually not a feature of big science. And it's it citing to me that that two of the leaders of the idea of gene drive one Kevin who had earlier onto program and Austin bird from Imperial College. London are both devoted to transparency to openness to public discussions to you know, going in and making sure that people who will be most directly affected strongly support and have consented to be a part of this project. So that's that's really remarkable. That's the the gene drive pioneers. Have taken our calls for ethics quite seriously. And it's not always true. It's Antilles stop the research to sit down and think what are we doing? And why and how we doing the manner in which they work. They claim is just as important as the results we achieve. I've rarely seen such a strong commitment to a respect for process of respect for Justice within a scientific team. And that that's part of it. Target malaria is a consortium. No, one takes full credit of the Austin Burke, who wrote the first book called jeans and conflict that put forward this notion of a gene drive, and I developed technology could in fact, take full credit, but he shares the credit. He says these committed to a co-development principal co-developing all the technology in co-developing all the research. So it sustainable and can go on independent of the particular one particular lamb, the idea of is is that such a big project take sharing knowledge. Dj investing in partnerships among many different disciplines, nanny difference itunes. A third principle is the notion that it should be done step by step by step. So I they're learning about how mosquitoes can be bred how they can be released in the wild. And they're doing all of these things with a self limiting with Strom hills. So whether the practicing all the techniques on males that cannot reproduce it all so they they're not they're not gene drive Miskitos. They're just stir home ales. And so they don't bite anybody. And and they don't they don't reproduce it make more mosquitoes. So they're using that doing that step. I before they use before the release the drive mosquitoes to make sure then that in fact, all the techniques are safe that all the release while the promises for safety can be maintained using I on an anon- drum species that step slows the search. But it makes the search more safe. And that's that's considering fort. And finally, they're open and accountable. They principle of accountability of transparency. They place trust at the center of the ability to deliver successful tools, malaria, control. And that's only possible if they're completely open about their work with the people in the village that every step is explained on the during a very massive education project. You know, in many parts of of Molly, for example, to use one of the countries in which they're working people don't understand the that malaria comes from mosquitoes. It's pretty they're pretty wild concept that this mosquito should have to do with a disease right emits, you need infected. Humans. You need you need. You know, you any mosquitoes were says certain variety, you need the transmission chain going so for many people it's much more logical that it's bad food or bad water or bad air or the season of the year or something. So I people have to stand that malaria comes from the CENA's malaria is carried around by mosquitoes and that we're the host species. And so that's that. Concept, I explained then they explained that. It's only females then they explained it. It's. Females by you because then your blood's to to lay their eggs that's part of their reproductive process. So that openness and that transparency and that ability to listen is key to target areas program, and they're very devoted with. They have a they have serious anthropologists and sociologists and people who've spent years studying community development, they've been in those villages for five years before any Miskitos have been released that's five years, and there's going to be it'll be another five years before they they do this ten years of an ongoing relationship with people who specific village, though, really they'll know what they're doing and they'll be able to participate. Are there any episode out? There who disagree who think gene, drives should not be used for this purpose? Ginger technology is very new, and the there has been a few people who have looked at it and said it's too dangerous. We. Shouldn't do it. Most of the attention of the field has been directed toward interventions with humans in particular reproductive genetic technologies like. In heritable, Nettie, changes modifying embryos with the so-called designer babies. People are very worried about that. And there's been a lot of literature. There's been a lot of the bait about that. Should we alter Argenta code? There's been much less anxiety around altering the genetic code of species that so profoundly dangerous to us. So the the kind has been a few questions about it. But for most people who've looked at seriously, and I would really argue for anyone who's seriously six down looks at the research. Sees it's limited to one species season couldn't spread beyond that Gambia species would think about it the way we think about polio. Right. A virus we've eliminated, and we didn't think oh, no what's going to happen in ecological niche. What's going to happen to humanity? If we don't have follow-up dimick's, we went ahead, and we eliminated that that. I'm causative agent. Madonna was smallpox rate. So this is. Another step towards a world in which this particular population is not tragically affected by this particular, this particular mosquito. Thank you so much Laurie. This has been really interesting. I'm glad I'm glad you asked. Because if the go considerations are so important, and it's hopefully people know that we've looked at the issues with great care. And they every time we've raised in issue. They have responded with a change in the protocol or giving us a thoughtful argument. That's that's addressed the issue or they've gone said. Okay. You're right. We need more research. We need to figure out a different way to do that we need to learn more about the ecology every single time the very responsive team. It's exactly the model for how how Dr technology should go forward hand-in-hand with partners across disciplines, including a discipline like mine, which is usually quite critical of science if you'd like to learn more about lorries Zola and target malaria. We've linked to her biography and some of the articles at science with people dot CA where we've also included links to a bunch of articles about gene drives their capabilities and their limitations. You'll also. Links to Twitter Facebook and tunes where you can listen to past episodes subscribe to the show or leave us a friendly review. You can also find our Patrie on page where you can support the work going into our weekly show with a monthly donation of any size. Thanks for listening. We'll see you next week on science for the people science for the people is produced by Rechelle Saunders. And edited by Ryan Bromsgrove. Helen, Yvonne is our publishing liaison. We get research help from Josh Witten and consulting support. From desert ratio are frequently seen guest hosts are marrying kill our, and he has RAV and Jessica euros. Our theme song is called binary consequence. 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