 Okay, welcome everybody. This is our special consortia event. We're joining two forces. We're joining my ethics and research and biotechnology series with Aaron Kesselheim's health policy and bioethics series. The title of today's session is a new inheritance reshaping our environment with gene drives, but I want to just go over some logistics really quickly about the q amp a function and are in our chat box. So if you have questions along the way that you would like to post the speakers or to me as a moderator, please use the q amp a feature at the very bottom of your screen type in your question there. And we'll be happy to address as many of those as possible during the q amp a portion. If you have questions about technical support, then you might want to use the chat function to talk with one of us directly. So with that, let me introduce our speakers. Today we have two speakers because we're joining forces in two different consortia we have Omar at Barry and Jason Delborn. Omar is going to speak first, and then after that I'll introduce Jason Jason will speak second and then we'll have the q amp a session. So Omar is professor in the division of biological sciences cell and developmental biology section at UC San Diego. He received his PhD in cell and molecular biology from the University of Nevada Reno in 2008. And then he joined Bruce Hayes lab at Cal Tech as a postdoc, where he used principles of synthetic biology to develop population control technologies for animals. And in 2018 he co founded our good gene, just about technology based startup in San Diego. I'm your host in Sioux, Ken, I am professor of bioethics at Case Western Reserve University and director of research ethics at Harvard Medical School. So with that, let me turn that over turn it over now to Omar, and he will take us through gene drives, the scientific and some of the policy issues that it raises. Take it away Omar. Great. Can you hear me okay. Yes, we can see your slides. Thank you so much into for the kind introduction and also for the invitation to be here at this consortium today. I'm really delighted to be here and I'm looking forward to sort of present on this topic from a scientist side, you know, a developer side. That's working directly on developing the technology. Today I'm going to start off with a brief overview of my talk and I want to start off with with gene drives of course and I want to explain sort of some of the goals, the types and mechanisms of gene drives. I'm going to focus today's talk on mosquitoes because that's that's what we work on in our lab. There's a point here that gene drives can work in many other species to, and there has been development of gene drive in in animals like mice, also recently in plants. So, keep in mind that these technologies are are valuable for many controlling many other species beside mosquitoes. Of course I want to talk about some of the ethical issues related to gene drives. I want to offer some alternative solutions here to help deal with with some of these issues, and I think this will open up some of the discussion at the end. And there's two technologies that our lab is super excited about that we've been working toward developing. And I'll explain what these are. The first is a confinable homing based gene drive. The second is a technology we developed called precision guided sterile insect technique, and I'll explain what these are and why we're so excited about them. So I kind of want to start off just giving you a little bit of background so you know, there's many roads to gene drive, and I've been working in this area for quite a while. Of course, when I was a postdoc with Bruce hey, we developed a system called media which was a low threshold gene drive system. And then we moved on to developing an under dominant space system, which we called food mail, which was a high threshold reversible drive system. This is back in 2013. And then we moved on to developing another type of under dominant system called engine reciprocal transmissible translations. And these are a very stable way of controlling wild populations, and we did this in flies. So recently developed a system we call reproductively isolated species. And this is using CRISPR to develop this. And then, and then we've also been working in this area of homing based gene drug systems using CRISPR. And today I'll talk to you about confinable homing gene drives, and also this this pgs it system. CRISPR Cas9 obviously accelerated the excitement and the development of gene drives. And of course the the leading organism that people are discussing right now is is a use of gene drive for controlling mosquitoes in particular malaria and sub Saharan Africa that's that's pretty much the, the most discussed case study. I want to make the point that, you know, this, you know, CRISPR was was definitely essential for for getting the field to where it is now but but there was a lot of work prior to CRISPR on developing a gene drives. You know, prior to CRISPR, there was a paper that came out by Austin Burt and this is in 2002, which described this, this use of the use of using homing in the nucleus genes which are derived from bacteria to potentially control populations and he had a really great paper that came out back then. And, and following his his publication, there was a lot of work actually to use other type of engineered engineered endonucleases like tail ends and zinc fingers to actually engineer gene drive systems and there was some, some many papers that came out with was successfully able to develop gene drive systems with those with those platforms. Of course, when CRISPR Cas9 came out, we, we now had a tool that can be used to programmably target and make a double stranded break in DNA, and that was very simple to use and so the field basically transition to using CRISPR. And, and this is basically how gene drive is designed. So, picture here in a mosquito, you see that to build a gene drive. It has a small number of components actually. One of them is the Cas9 and the Cas9 is expressed in the germline. And then a guide RNA is also expressed which is going to direct the Cas9 to where it's going to cleave. And then you could also link a cargo gene. So, for example, like a gene that can confer resistance to malaria, or resistance to dengue fever in the mosquito. You link them together, you position these components opposite their target site in the genome. And you have these expressed in the germline. So, in an organism, when you have a heterozygous, so you have, you know, one copy of the drive one copy of a wild type chromosome, you have the cells are encoding this editing machinery. And so, when this organism mates out to a wild type organism, you know, 50% of the project you receive the gene drive as that's normal Mendelian segregation and inheritance. And because the cells encode this editing machinery in the germline, you can get copying of the gene drive to the opposite chromosome, thereby converting what was a heterozygous into a homozygous in the germline. So then when this organism mates out again, it passes on the gene drive to all of its progeny, and that just continues on and on thereafter, and that's how you get spread into a population rather quickly. So there's really two types of gene drive systems that are being developed and discussed. The first is what we call a population modification type of gene drive. And the way this works is you engineer your gene drive, and your goal is to actually modify the population so you release a small number of gene drive individuals into the population, and you expect the gene drive to spread that modification into the population. And the goal would be sort of at some point, you know, many generations later, everyone in that population will have a copy of the gene drive. The gene drive may carry a cassette that blocks malaria transmission, for example, and then you'll have no more transmission of malaria. And I want to point out here that in principle, the release of a single organism could result in the spread throughout the wild population. And that depends on a few things. Of course, the fitness costs that are associated with the gene drive, the efficacy of the drive, and the ability for it to generate resistant alleles. So for this type of system, ecologically, the wild population still exists, but it's been genetically modified, right? So this is going to have a different outcome than something that's going to suppress and eliminate a population. So the other type of system that's being described is a population suppression type of gene drive. And in this example here, you release your gene drive and it spreads into the population, it reaches a point of fixation, and when that happens, you know, the population then declines really quickly and gets eliminated. So ecologically for this, you know, you're essentially removing that species from that population, and so that could have some ecological consequences that we don't necessarily understand. That's something to think about. And again, for this type of system, the release of a single organism, if it's a perfect gene drive works great, it can result in suppression and elimination of that population. And there's a couple different ways of designing these and, and really the way this system works is that you're driving the gene drive is designed to target a gene that's important for female viability or fertility. So that when the, when it reaches fixation, the population, the females are all dead, or they're sterile. And so the population rapidly declines thereafter. So those are the two broad categories of gene drive. And the type of drive I just showed you is what we call a sort of threshold independent. It's a gene drive that can spread from very low release frequency into the population. And of course, this, these types of systems bring a lot of issues. Right. And I want to list a few of the issues here that we can, we can maybe discuss later. So the first issue is that these systems are invasive, right, they're predicted to spread into a population, and they're not going to respect borders. So if you release it in one location or one country, it's predicted to keep spreading beyond that country to basically everywhere where the organism survives. So if you think of mosquito, you're targeting survives in, you know, let's say it survives in all of sub-Saharan Africa, this is predicted to spread throughout all of that, all of that area there. This also makes it uncontrollable. We can't easily stop it. So once you do release it, it's, it's very hard to stop it from, from, from spreading. It makes the system somewhat non-reversible. The only way to really reverse this is to design an alternative system that then you could release to target that gene drive. And there's been a couple of examples in the literature that have come out. One of them is a system called an eraser, another one is a system called the E-Chaser. These are some of the reversal drives that have been described, and also using anti-Cas, CRISPR proteins have also been described. But of course, you're still having to release another type of genetic modification into the population that then could bring another whole another set of issues with it. These features make it very difficult to measure risks, right? If you can't, if you release it and you can't control it, how do you, how do you do risk assessment on it? And we talked about some of the risks in several papers. And this paper that I have here on the bottom, winning the tug-of-war between effector gene design and pathogen evolution and vector population replacement strategies, we talk about some of the issues in there. And one of the main issues that we talk about is for population modification. Here, if you're driving an effector into a population that's linked to a gene drive, let's say it's an anti-malarial effector gene that blocks malaria transmission in the mosquito. You're also putting selective pressure on the pathogen, right? So in the wild, you're kind of forcing the parasite to evolve to sort of overcome that effector. And so when you put that type of selective pressure on the pathogen, what is that going to result in, right? Can the pathogen become, you know, more, more virulent, for example, and cause more harm? And if that's even a possibility, shouldn't you test that before you move forward? The next thing is, you know, are these things regulatable? If you have a system that's invasive that you can't control, how can you go ahead and get regulatory approval in one country if you know it's not going to stay there, right? So is this something we can actually regulate? Do we need to go back and redesign the regulatory framework for technologies that are predicted to sort of spread into a shared ecosystem? What are the unintended consequences? What are effects on other species, right? Can this transfer to other species? Will removing a species, how will that affect the ecosystem? Will the public accept this technology if they understand how it works? Who decides on using such a technology? If you go into one location where they have a huge disease burden and they decide, okay, we're ready to move forward with this technology, but they know the technology is not predicted to stay there, can they make that decision? And then finally, will it even work? You know, there's been a lot of research that has happened over the last several years that show that pretty much all the gene drives that have been developed in the lab to date have this issue of resistance. So resistant to leels form in the lab rather quickly, and they can block the spread and persistence of the gene drive in a population. So if that's happening in the laboratory in a very small population in a few number of generations, what do you think is going to happen out in the wild, right? So that's kind of an open question. No one has done a release of a gene drive into the wild to date. So what we're really excited about is not this idea of developing gene drives that are invasive and uncontrollable, but instead taking principles of the gene drive and designing things that are self-limiting, things that give us the control that we need, make the system confinable so you can release it in a location and it can stay there. And make it reversible. So if something were to happen in unintended consequence, we can go back and reverse the system without the need of designing a new system to reverse it. Making the system safe, making it still effective. We want to develop technology to solve a problem that need to be effective, but we can't, I don't think we can actually, at this point in time, you know, go forward to the technology that we can't control. So how are we doing this? And so in our lab, what we focus our efforts on is, is developing homing gene drives in a species of mosquito called Adiz-Egypti, which is actually a species that's present all throughout the United States. It's invaded California. It's in my backyard. It's the primary vector for many different viruses like dengue virus, chicken gunia virus, Zika virus, yellow fever, for example. And it's present in pretty much, you know, all around the equator, around half of the world has a species. It's a huge problem in the world. So we're working on this species here and we're developing what we call split drives. So remember I showed you that a gene drive is a system where you have Cas9, a guide RNA and an effector all linked together. Well, it turns out if you just unlink the Cas9 from the guide RNA, then you can develop what we call split drive, where the drive doesn't function unless you create a, do a genetic cross between the two strains. And so we developed the first split drive in that species, Adiz-Egypti, and on the top here I'm just showing you some cool ifenotypes and mosquitoes. This on the far right is actually a wild type mosquito that have black eyes. And then we've targeted an ifenotypic gene to enable us to measure the drive efficacy basically. And we also had a fluorescent marker here, 3XP3TD tomato. So what we found, and I'm going to spare you of all of the, how we actually did this, but overall what we found is we were able to develop an effective split gene drive in Adiz-Egypti and our system had a 84% homing rate. What that means is, instead of the system being transmitted to half the progeny, it's being now transmitted to 84% of the progeny. So it's biasing Mendelian transmission, but it's not biasing it all the way to 100%. It's not perfect, but it's pretty good. And our cleavage rate was 100% in these. So with these numbers here, we teamed up with a mathematical modeler, John Marshall, he's at UC Berkeley, and he did this mathematical model to sort of model the behavior of our drive in a population. And so on the top here, what we're looking at is our gene drive system in Adiz-Egypti with an 84% homing rate. And what we're looking at here is actually 10 releases of our system into a population at a one to one release frequency. And what happens after you do that is the system spreads to really high frequency, this red line here, around 97% of the individuals in the population have at least one copy of this drive, and they persist in the population for three years above 85%. So this can provide you with a really high level of protection. If you were able to do this in a wild population and protect in that population for three years, you could potentially disrupt the disease transmission cycle and eradicate the problem. On the right here, we also looked at spread into a neighboring population because we want our system to be confineable. We don't want it to spread all over the place. We want it to stay where we release it. So he modeled a 1% migration rate and our system cannot spread into a neighboring population at that rate. And if you compare that to just releasing the refactor gene by itself, so if you had, let's say your anti-malarial effector without a gene drive and you did 10 releases at one to one of that, it spreads in and then rapidly kind of falls out. Also doesn't spread into a neighboring population. So you need the gene drive in order for the system to persist in the population and provide that protection. But this gene drive obviously doesn't enable these spread into neighboring populations. If you compare that to a linked gene drive, so a gene drive where the cast sign and guiding your link, having the same exact parameters, and you do a single release of that, then what happens is it spreads in and resistance happens, and it falls out of the population. But then it also spreads into neighboring populations, and it continues to do that, continues to spread that resistance to those neighboring populations. So what we think is going forward, we think these split drives actually can provide us with this self-limiting confineable behavior, but also provide robust control of that population. So I mentioned earlier that nobody has done a release of a gene drive into a population yet. And we've been thinking about this a lot about how one could go about potentially trialing a gene drive system. And we wanted to basically come forward as a group of ethicists, social scientists, gene drive developers, some regulators, and other stakeholders that are interested in gene drive. We wanted to put our minds together. There's about 50 different authors here and sort of outline what we think are the core commitments for trials of a gene drive organism. And this is to ensure that these trials are done scientifically, politically and socially robust and politically accountable and widely transparent. We didn't want, we just want to make sure it's done right. We want to make sure people know that we're actually thinking about the ethics and plan to do things as right as we can. And Jason is also an author on this paper. So what were our commitments? Oops, I think I skipped a slide. So we had four main core commitments that we outlined in this paper. And the first was a fair partnership and transparency. We wanted to ensure that we would engage the stakeholders for trial design and accountability. We will provide access to results regularly and make that information public and present trial data openly. We wouldn't be secretive about what's going on. We would ensure that we've undergone product efficacy and safety testing, and we would agree on acceptable performance parameters with the target location. And of course identify sources of influence and uncertainty and make all this efficacy and safety data public. Of course we would ensure that we do a regulatory evaluation and risk benefit assessment of the system before any releases. So that would involve working with regulators and to prepare for ethically and regulatory review. Develop methodologies to evaluate benefits and expand inclusivity of assessments. So basically we would do monitoring and mitigation. Monitoring would happen before, during and after a trial. And all this data would be presented openly. And this would involve also partnering with experts and stakeholders in the planning and defining conditions and preparing for infrastructure for mitigation. And if something were to go awry, we would have a mechanism in place and tested that could mitigate the technology from the site. So we came together and we outlined these commitments and, and I wanted to really make emphasize the point here that these core commitments that we presented in this paper. They're intended to address the field trials of localized gene drive organisms. And these are gene drive organisms that are genetically or molecular confined, and they will not spread indefinitely so so like the split drive I just showed you, we're talking about that type of system, not a link gene drive. So we've said that a non localized gene drive organism in an ecologically isolated location may also be able our, our, our commitments may also address that. And what we mean by that is a gene drive that's, that's released in like an island that that is completely ecologically isolated, and the gene drive will not get off of that. But of course, that will have to be, you know, the love the degree of ecological isolation will have to be sort of decided upon. At that time. And then we also made the point that introductions of non localized gene drive organisms into sites that are not ecologically isolated would be would be beyond the scope of these guidelines. And all the authors strongly agreed on this, it was, it was important to distinguish what we're committing to what we're not committing to. So we were not committing to the release of a non localized gene drive organism into the environment. So, you know, the, the National Academy of Sciences, they, they convened a panel and they came out with this, this article called gene drives on the horizon it's a really great article that talks about gene drives and, and, and all the different issues associated with them. And one of the things that it talks about is a stepwise approach for evaluating the safety and performance of genetic and gene drive technologies. And this is basically the conventional stepwise approach that they described in this, in this article. And the first step is to sort of take your gene drive and develop it in the laboratory. And, and then, you know, test it there. And then step two would be to try to do confined field trials so maybe something on an island, or in a cage in the field. And then they move it to a, an actual open field trial. And on the bottom here, I kind of show you that there's an inverse correlation between the persistence risks and geographical spread to safety confine ability and reversibility so as you transition from the lab you have really high level of safety confine ability and reversibility, but then as you move to the field, the persistence increases the risks increase and the geographical spreads increases. I think something to think about here is that for a non confine able gene drive. How can we make this transition from a lab to a field trial, either a confined trial or even an open field trial. How do you make that transition. And the stepwise approach, I think may not be applicable, since even the small scale introduction of a low threshold gene drive will result in spread and permanent impact on the environment. So maybe this is not the right mechanism for thinking about this. So, what we think is, is, is this kind of needs to be reconsidered and one way to think about this is to, to think about it as a technology based stepwise testing approach for gene drives. And what I mean by that is, is, if you start off with technologies in these first steps that are confine able. So on the far left you have a non gene drive system. And this is a precision guided SIT system and I'll talk about what this is in a couple future sites. And this system you have your cast nine and God or nay, separated, you have to cross them together, and you can get some population suppression. It's not predicted to persist or spread or invade other populations. So this is a very safe way of testing whether, you know, cast nine alone, and the God or nay alone will have an impact on the environment because we don't even know that no one's ever released these these things at scale before. And then potentially in the second step, you know, after testing whether cast nine and God or nays have any impact on the environment that we that we don't unintended consequences, then potentially move on to a split drive, which is an unlinked cast nine and God or nay. And this could be useful for either population suppression or population modification if you link to antipathetic effector. And this would enable you to safely test the, the effector in the environment. And also again the cast nine and God or nays in the environment to see if there's any impact and if there is, you can easily reverse it. And then finally, if, you know, if these systems alone don't give you the outcome you desire, right, if you don't get sufficient suppression or sufficient modification and protection, then potentially moving on to step three, which would be simply linking the cast nine gathering together, and then testing that in the environment so this is one way where the components can be tested safely before moving on to something where that we can't control. So, my last couple slides here. I want to talk about, you know, in suit asked me to talk about what we're really excited about. And I think in our, in our group we're really excited about this, you know, this idea of using combinable drive systems but also this idea of using non drive systems like this one here, which we call precision guided SIT. And we've designed this system and in flies, and also some agricultural crop pests and also in this case. So how does this work. It's actually very very simple technology and the way it works is you, you basically design two different strains. One expresses cast nine. And the other expresses Guidernays. The Guidernays are designed to target genes important for female viability and male fertility. So separately these lines, you can help as I go some, you could master them, they don't do anything. But when you cross them together, then what happens is you get female killing, and you get male sterility so you can you actually produce only sterile males by simply simply crossing these together. In a factory, if you're able to scale these two lines and robotically sex sort and cross them together, you can generate large numbers of sterile males that could be deployed as eggs. And these could be deployed, you know, via drawing a drone like system. And again, it's not a drive system. But it is a system that can enable you to test cast nine a Guidernate in the environment. It will not persist. It's logistically scalable in a facility in a factory. It's environmentally friendly because you're not using insecticides using mosquitoes to control themselves. It's evolutionarily stable because you basically have two lines that are mass rooted in the factory. They're not, they're not interacting with, you know, organisms in the wild until you release the sterile male, which is a dead end, because it's a sterile male it doesn't produce progeny. It's very, very safe. Also, it can be very effective we've shown that in our lab you can completely suppress and eradicate populations. And finally it's controllable. So it's a controllable way of modifying and a population. All right, so this is one of my last slides here. I just wanted to point out that, you know, there's been a lot of innovation in terms of technology so on the, on the far top left here we have the cell phone of the 60s. And on the right we have the cell phone of today. This is the iPhone, the new iPhone 13 I believe. And on the bottom here we have a mosquito control vehicle here that's spraying insecticide into the environment. And this is how mosquitoes were managed in the 60s. And on the bottom right here, we have an image of aerial spraying over Florida. When Zika virus was was happening in 2015 of insecticide out of airplanes over households. So I wanted to make the point here that there's just not enough innovation here with vector control. And I think over the next year is you're going to see more of this more of the use of engineered genetically modified organisms in the environment to control populations. So I think this is a really exciting area to follow. And whether it's going to be a precision guide to sit, or it's going to be a confineable gene drive or non confineable gene drive time will tell. But I think it's a very hot topic right now. So that's my last slide I just wanted to, of course, thank you for listening. Thank everyone from my lab and all of our funders that support our work. So I'll stop here. Thank you so much Omar that was fascinating I'm looking forward to the discussion to follow some questions have come into the Q amp a box, if you have other questions to submit to Omar please do so as we go along. This is our next speaker, Jason delborn. He's professor of science, policy and society, and yours, and university faculty scholar at North Carolina State University. He's an interdisciplinary social scientists in the genetic engineering and society center. He directs undergraduate science technology and society program. He focuses on public and stakeholder engagement surrounding emerging environmental biotechnologies, and he served on numerous expert committees focused on the governance of gene drives and synthetic biology. So with that Jason the floor is yours. Go ahead. I think you're on me. Yes, thank you I was just getting my screen shared to make sure that that works. Can you see the screen okay. Yes. Thank you so much for that nice introduction into and thanks to Omar for a great presentation. I really appreciate collaborating with Omar. We've had some great discussions over the years and that was a really nice introduction to some of the science of gene drives, which means I don't have to cover that which is great. So as you said I'm a social scientist at North Carolina State University in the genetic engineering and society center. And so I'll be giving a different perspective on the social science research around gene drives. And as you mentioned, I've been privileged to be a part of a number of committees that have worked at the science policy intersection. I was also an expert committee at the National Academies that published gene drives in the horizon in 2016, which was one of the first major reports to look at the science and broader social issues of gene drives. I was also asked to serve on an ad hoc expert committee for the International Union for Conservation of Nature, which had a task force on synthetic biology and biodiversity conservation. In 2019 and have been active in terms of helping the IUCN develop preliminary policies about synthetic biology for for conservation. And I was asked more recently to join a working group for the NIH, their, their next track committee, which is the novel and exceptional technology and research advisory committee. And our working group on gene drives published a report just this past September, focusing on gene drives and biomedical research. So I won't have time to cover all these reports but I just want to give you a sense of the kind of scope of work that I've done at the policy level as a social scientist active in the space. And I will start with a couple of lessons or ideas from the gene drives in the horizon report, because this was a really important start to my own career working in gene drives. This came out in 2016. One of the important conclusions that we had as a committee and this was a very interdisciplinary committee that involved ecologists and geneticists and social scientists and ethicists is that public engagement cannot be an afterthought. In other words, these technologies as they're being developed, we can't wait until they're finalized, and then go to the public and ask for permission. And in fact, our committee in our consensus reports stated that the outcomes of engagement may be as crucial as the scientific outcomes to decisions about whether to release a gene drive modified organism into the environment. And this was quite a statement for the National Academies to make. And I will assure you, we defined engagement as a committee as seeking and facilitating the sharing and exchange of knowledge perspectives and preferences between or among groups who often have differences in expertise, power, and values. And we also talked about different levels of engagement that could range from engaging communities to engaging stakeholders and engaging broader publics. In our report, we talked about the motivations for engagement surrounding gene drive research, including the incorporation of local knowledge knowledge that formal experts and scientists may not have about certain locations. Second principles of justice. So given that gene drives are meant to operate in the public environment issues of transparency and informed consent arise. And there are opportunities for mutual learning among different kinds of experts. And last and a hope is that engagement builds trust among experts among different kinds of stakeholders who may be surrounding these kinds of research and development. We also recognize as a committee the challenges of engagement. So who should be engaged. What are the goals of engagement. When should engagement occur. When should we manage cultural differences. When we engage different kinds of stakeholders and communities. There's well known patterns of polarization. When you get people together to talk about a controversial issue. And we also need to think carefully about how the results of such engagement actually influence decision king, and aren't simply an exercise where we talk, but the talk makes no difference. The sense of how those recommendations that that that came out in 2016 have continuously had an impact. The working group that I participated in on the NIH had a section of recommendations related to stakeholder engagement regarding gene drive modified organisms. I think the highlights are that the recommendation from our working group with is that the NIH should establish organize or conduct preliminary engagement activities that could inform future trials. That the NIH should require all requests for support of field release research and again to echo what Omar said, there hasn't yet been field release research of gene drive modified organisms. But that the NIH if it's supporting that kind of research should require a plan for stakeholder and community engagement. And that the NIH should even go so far as to support research on establishing best practices for stakeholder engagement recognizing the importance of this kind of practice surrounding the technical research that Omar described so well. So that gives you a sense of how these kinds of ideas and values around stakeholder and community engagement have continued to echo in the science policy space around gene drives for the last several years. So what does engagement actually look like. And I thought that I used the rest of my time today to give you a sense of how engagement happens around gene drive technologies. I'll be referencing three projects that I've been involved in over the last several years. The first, and they're also very different intentionally to give you a sense of the diversity of approaches that engagement can include. The first is a survey, which focuses on learning about public attitudes and preferences around agricultural gene drives. The second is a focus group project that was focused on learning about how we communicate about gene drives. And the third is a workshop that I organized among stakeholders and researchers in 2019 as a part of a particular project related to gene drive mice for biodiversity conservation. So the first project is the survey. This project was led by a PhD student Mike Jones and his advisor Zach Brown. I was a collaborator. And this project was a nationally representative survey of adults about their attitudes toward potential gene drives in insects that could be used in agricultural context. So specifically what has been proposed are a couple of species that are pests that are very difficult to control with existing chemical insecticides. So one of the ideas is to use the kinds of technologies that Omar was describing to suppress these populations or to change their behavior. Importantly for this project we began with a series of focus groups. Mike actually recruited people outside of different kinds of grocery stores, and he held focus groups to learn about the kinds of ways that we need to talk to consumers about gene drives and agriculture and what they would need to learn in order to offer a thoughtful opinion. So the survey that we developed was not a simple, you know, call someone up and say, do you support gene drives and agriculture. Because to be honest, most people don't even know about gene drives and certainly wouldn't understand some of the issues. And so our survey was very comprehensive and thorough. We had a lot of opportunities for learning about the technology as part of the survey. And we asked a lot of specific questions that allowed people to make comparisons, and to prioritize among different choices. During the survey, as the second part of the title of this article suggests, and what do they want to know. We were also interested in learning about what would consumers feel like they needed to learn more about to make an informed decision about gene drives and agriculture. And I'll just share a couple of the results from this paper. First of all, this is really important is that public support for gene drive is incredibly contextual. So in the survey we we presented and we described. So people would understand this a gene drive system that would control for spread and otherwise it would be localized in the way that Omar was describing. And it would be targeting a non native species of insect. And in that case, the support range from 57 to 60% and opposition was 14 to 16% so that that looks promising. If you're interested in a gene drive for agriculture, but we also found that support drops very quickly under a couple of conditions. So this shows that when there wasn't a control for spread of that gene drive. The support would drop quite quickly, 20 to 25% lower. And there was also a less significant drop of support if the target species was a native species. And so what's important here is just to understand that public attitudes about the use of gene drive drives are not going to be all or nothing. And people are going to be interested in the way that the gene drive behaves in the environment and the kind of targets that gene drives might be deployed against. And as I mentioned our survey also asked about priorities for what people wanted to know about agricultural gene drives. And so these were the kinds of uncertainties that would need to be resolved before we could make good decisions about using these technologies. And this, this figure gives you a sense of the fact that people think very differently about what the uncertainties we need to resolve are. There was general consensus that issues of human health effects and environmental consequences of pest removal were very important to a lot of people and selected as least important, very seldom by our by our participants. There were categories of the speed of the drive spread or changes in food taste or appearance so that was an interesting one that was selected least important by many participants. But notice, for example, horizontal gene transfer potential. People thought that was the most important issue to resolve about equal number of people thought it was the least important issue to resolve so there's, there's a lot of uncertainty among the public about how to understand these different kinds of uncertainties that will affect how we make good decisions about gene drives when they are potentially ready to deploy. The project I'll describe is a focus group project. This was led by Dr Sarah Hartley at the University of Exeter, and I was a collaborator in the US. This was a fairly broad project that looked that had partners in Africa, Europe, North America and Asia. I'll focus on just one element of this project which was a set of focus groups that we conducted in the US and United Kingdom. We were intending to be in all four parts of the world, but because of COVID, we were reduced to two countries, and our focus groups were virtual, which had actually pluses and minuses. So the focus groups we ran, we're focusing on gene drive communication. So we're interested in understanding how non experts and non gene drive experts would think about different ways to talk about gene drives. If we're going to make decisions with broader groups of stakeholders and communities, we need to think about these issues of communication. So we convened in the UK and the US focus groups of public high school teachers, and we separated them into science teachers and humanities and social science teachers. And we convened groups to talk about different aspects of communication of gene drive, which I will describe. So what we did was we took linguistic expressions from other parts of the project that were a media analysis and interviews of gene drive experts. And we looked for importance and diverse ways that we could frame gene drives. And so these are all phrases that have been used to describe gene drives either in the in the popular media, or by experts that we interviewed. And we organized these, roughly in two categories, actually four categories, so it's a two by two. We wanted to make sure that we had framings that were both promotional and critical of the technology. So you'll notice those two are the rows there. And the columns, we thought about a diversity of framings in terms of how they might explain what gene drives do versus framings that are focused on the application or implication. The frames that we used in our focus groups to talk with the participants were these eight frames so malaria proof, proof mosquitoes to bias inheritance, tweaking genes to save species, eradicate the world's deadliest creature, exterminator technology, GM on steroids, Jurassic Park, and we don't want to be guinea pigs. And I should just say that this research, we're writing this up so it hasn't been published yet, but we hope to submit it in the next several months for peer review. So what are the kind of preliminary lessons from these discussions that we had with public high school teachers about these framings of gene drives, in terms of their ability to communicate and have good discussions. And that we found that disciplinary differences were more significant than national differences in terms of how the conversations went, what people's opinions were on the different framings and things like that so in other words. And this was interesting to us because we noted that that you know they're very different discourses about GMOs in the UK and the US. There was higher prevalence of critique of GMOs in the UK and in Europe, more broadly. But even with that being the case, we found that the social science and humanities teachers had very different preferences across. And that those differences from the scientific teachers were larger than the nationality differences that we found. And what it says that these frames, which were very diverse really opened up to liberation, meaning that we had very fruitful and interesting conversations with people who did not know anything about gene drives ahead of these focus group activities that these different kinds of frames raised issues and perspectives that we didn't anticipate as researchers, the frames trigger very different meanings for different people. And that was really important to recognize and I was really pleased that we presented our participants with so many different framings of how we might talk about gene drive, because there were very different kinds of reactions. For example, in going into this study, the term that I always thought of as the most neutral was that gene drives bias inheritance. And like a very scientific neutral technical way to describe gene drives. But when we presented some of the focus groups with that term. Some of the parties participants heard biased inheritance as very negative that the word biased triggered for them, a lot of negative associations, and they thought of it as something that was possibly sinister or wrong. So, what this raises I think for us in the in the gene drive research community is that our ability to control the conversation is really limited. It's difficult for us to choose exactly the right language. There may be no neutral term to talk about gene drive. And so if we recognize that that's going to have an impact on the way that we try to communicate with broader stakeholder community audiences around gene drives. And the last project I'll talk about is something I've been involved in for a number of years this is the genetic bio control of invasive rodents program or G bird. This is an interdisciplinary and multinational partnership among many institutions that are interested in exploring the possibility of creating a gene drive mouse for release on islands, where mice are invasive. There's many islands mice attack native species, especially birds, and they're the current way to eradicate invasive mice on these islands is to use spreading rodenticides, which is both logistically difficult and problematic and a number of different ways. And so this consortium is interested in the possibility of using genetic bio control, including gene drives to explore whether this could be an alternative method of suppressing invasive mice populations. And I of course won't talk about the whole project. It's a really exciting partnership across many institutions, but I'll focus on the work that I did as the lead of stakeholder engagement for this project. So here, the goal here, rather than insects we're talking about mice. And so one of the possibilities here is to have a gene drive that passes on the characteristic of maleness. And if you imagine an island population of mice, if over multiple generations, all of the mice that are born are male, eventually that population would crash. And so that's one of the visions of the of the G bird consortium, although to be clear, we have not yet made a gene drive mouse. And so these are all ideas and strategies. The mouse work is behind the mosquito work that Omar described, but use some of the same techniques. So what I was in charge of doing for for a project that was funded through DARPA's safe genes project was to organize a workshop. And to me what was really exciting about this workshop was that we convened a group of diverse stakeholders to interact with our experts and experts in in the program, the G bird program itself. And so unlike a focus group, where we're talking to not experts, unlike a survey when we're simply sampling the perspectives and opinions of people who are not experts. This is a true conversation and an interaction between different kinds of experts stakeholders and project scientists. So we did this in 2019. And I'll just give you a flavor for how this kind of engagement was unfolded in our workshop. So as I said, we had many different kinds of participants, both in terms of discipline and also sector. We recruited from NGOs, from regulatory institutions, many scientists, other kinds of stakeholders. And that was really important to us to get a broader group of people in room, then, when we have our partnership meetings and the same scientists are on the call each time. This is a much broader group to have a conversation about the G bird technology. And our discussions ranged across many scales of research. So we talked about laboratory research different kinds of gene drive mechanisms and control methods, some of the methods that Omar described. We talked about potential testing in what are called simulated natural environments. We talked about the field trial risk assessments. One of the important parts for this project is to eventually identify an island where we would try out this technology if it becomes possible and safe. So we talked about that scale of research, as well as strategies for community engagement. So this, this is you don't need to read every cell of this of this matrix, but I'm showing this because this was one of the really fruitful exercises we did during the workshop. What we realized was that given that island selection is a really important part of the future of the G bird partnership. Yet we didn't have a we haven't identified a small set of islands to consider so we couldn't convene this group and say, Okay, here are the four islands were considering help us decide which one would be best. We're not there yet we don't even have a mouse that's working. But the partnership recognize that this this challenge of island selection is incredibly complex and will be incredibly important. And so we designed was a kind of a scenario exercise where we created fictional islands that had very different characteristics from each other and represented some of the kinds of trade offs that our partnership saw as emerging when we considered island selection. What enabled was a really interesting conversation among the people at the workshop about how they would make decisions, knowing that there wasn't a perfect island, knowing that there are many different kinds of issues for example accessibility, or human activity or regulatory that would matter to making a decision and those those decisions provided insight to our partnership project in a way that simply having the experts list the criteria separately had not yet. So what were some of the lessons for engagement from this workshop that we ran. But first that there was a great deal of enthusiasm among the stakeholders who invited for what we call upstream engagement. In other words, we were engaging stakeholders about this project before the mouse exists before we're ready for a laboratory laboratory trial or a field trial. And what was that the stakeholders we invited appreciated dialogue, having dialogue with what they saw as uncommitted developers. So the scientists involved in the G bird project. Also express their uncertainty about whether this, whether the gene drive mouse would work and whether it would be safe and whether it would be a good idea. And so these stakeholders were glad to be invited to a workshop where they didn't feel like the scientists were simply trying to sell them a technology that they had preordained as a good idea. So the scenarios that we developed, particularly around the island selection, allowed us to have conversation where both facts and values were integrated, where we could see how people deal with trade offs, and how they think about priorities under complex, under complex situations. It was difficult to discuss the different technical options that are being talked about for G bird without real safety data. So this is one of the drawbacks of upstream engagement is that if we don't have the technology in front of us, we can't present data on the safety. And there certainly is a tension felt by the organizers and the scientists in these kinds of events, the tension between seeking public acceptance and being what we might think of as an honest broker. So how do we manage our own identities and our own priorities, as we as we interact with broad stakeholders about technologies that we've been working on as a project team. I'll let you know that we've published an online workshop report about that workshop if you're interested in learning more details about some of the outcomes about how we put it together. And I definitely want to acknowledge my collaborators on that workshop who made it possible. I'll just end my presentation by mentioning that the G bird work is ongoing. And I've also been recently recruited to work with Mike's man ski at the University of Minnesota, who's working on genetic biocontrol of invasive common carp. So he's brought me into the project as a social scientist to help him think about doing stakeholder engagement early on in the project. And so it's really exciting to me to see scientists like Mike scientists like Omar, taking these social science issues really seriously, even as the technology is fairly early in its development. Thanks very much for your time. And I also just want to mention that I'm part of an interdisciplinary fellowship program in North Carolina State called ag biofuse or agricultural biotechnology, and our evolving food energy and water systems. And we are accepting applications for a limited number of PhD students for next year. So thanks very much. And I will stop sharing my screen now. Well, thank you so much Jason and both of you for your presentations and for staying right on time. I have questions that are trickling in right now in the Q amp a box but while I get that sorted out let me just post a couple of questions to the two of you. First to Jason. We have a pretty international audience right now for the webinar. And as an audience member if someone really wants to get engaged in this topic. How do they go about getting engagement do they sort of have to be lucky enough so to speak to live in an area where there's contemplation of gene drive and then they might get kind of sorted into a focus group or is there some like more proactive stuff that someone might take to say you know I'm really interested in this as a citizen. How could I get engaged. And I think I can think of a couple of responses. I mean one is that certainly there are a number of groups and organizations that aren't focused on gene drives per se but are focused on the kinds of issues that gene drives are meant to deal with. Conservation organizations, public health organizations are actively thinking about different kinds of technologies and so if you're interested in these kinds of technologies and how they might be applied in real environments one way to really make a difference in terms of our broader public dialogue. We get involved in organizations that are pursuing solutions in these spaces, and help inform them about these possibilities help them be ready to engage when we are at the point of making real governance decisions about the research and development of gene drives. Thank you. So this is another question just I think I'll just post it to the two of you. This issue is so complex and so fascinating because it touches on so many different elements public health environment, you know, CRISPR, you know, high end science is sort of kind of metaphor that kind of helps that you think would help organize are thinking about what type of issue and problem is this like, you might imagine I could sort of imagine it's the earth has an infection, and it's kind of like a patient and you're going through pre clinical studies in the lab and you're trying to see when can we go first in earth or first in human now. Is it is it a metaphor sort of like that, in which case the question arises, are there thresholds for intervention so who who sets that threshold you mentioned Jason invasive carb right and so that's different than malaria bearing mosquitoes. So certainly economic impact but not a super direct impact on on human health and survivability. So if we think about these ecosystems is like almost like a patient that has something out of balance, and we want to have some direct intervention that science based and developed through technology. Is there a threshold intervention that anybody talks about like what warrants going to this type of so called cure. I imagine many different types of ailments right so I'm just working off some metaphor I'm, I'm using to make sense of a lot of this, and it raises that question about the threshold. So either one of you can maybe address that. So that's, that's a really interesting and challenging question, I would say, I, the metaphor that I've been thinking about a little bit lately, it involves like, you know, COVID, for example, and the vaccine, right, and we're all sort of facing COVID and and we're deciding whether or not to vaccinate ourselves and our kids and I recently got my booster shot and my kids got their first dose like this week actually. And so we made that decision and some people are deciding not to do it which I don't think is the right decision but that's what they're deciding. And they have, they have but they have the ability to decide, right, they have the choice, right. And, and so I think, you know, COVID the COVID vaccine is a new type of vaccine right it's something that we haven't used before there is, you know, initially in the, you know, there is risks with it, right. Of course now we it seems like it's very safe and effective. But of course initially we were we were everybody was scared because it's a new thing, but you had the you had the choice to take it or not. And so with gene drive, you know gene drive is a whole different type of thing where, you know, one person is potentially going to, you know, a regulatory body is going to make the final decision, of course with engaging and things like that but you know a regulatory body is going to decide, and to go forward or not and then it's going to be released into the shared ecosystem, and it's going to affect all of us and what are the. What the unintended consequences are so we don't, we won't have the choice after it's the choice has been made for us. And so I think, you know, in some ways I think of it as, I can understand the the COVID vaccine and how it's been dispersed and and widely used and accepted in that and it's shown to be effective, but with gene drive. I think it's, it's going to be a lot more challenging than that, you know, because of the fact that the deciding body is deciding for everyone. Because it's a shared ecosystem and it's going to spread broadly and I think that needs to be taking that that decision needs to be taken very, very carefully. I guess that's that's kind of what I've been thinking about. I don't know if I answered your question. Thank you. Jason, anything to add. I think just building off of Omar's answer I think. You know the, these are certainly public health or or broad environmental challenges that are being addressed. And so I think what I would say is we just need to be careful about not using metaphors around medical consent, for example. But that the, you know, we don't have opt out possibilities for a gene drive that's introduced into the environment, unlike we would have in a patient doctor relationship. So there's been some important thinking about how we can expand notions of informed consent to issues to think, you know, to scales of community consent, things like that. And I think, you know, as Omar said, you know, there is, these are tough decisions, and especially given that we're at a stage where we haven't experimented even with field trials of gene drive modified organisms. It's, it's going to be hard to say exactly what the threshold will be. What I would expect is that the threshold will change over time, depending on the technology, depending on our familiarity depending on the results. Jason, in your slide where you showed people's survey responses about what they thought were very pressing issues and not so pressing or concerning. I was surprised to see that what was not high on the concern list was who deploys gene drives and who regulates them. Yeah, did you have thoughts on that or did that surprise you. Well, we actually did. There was another part of the survey that looked at who, who were trusted experts in this field. And there was a variety of opinions there that were quite important. And so, I didn't take that, that that ranking as an indication that it doesn't matter who's in charge of gene drives. I actually think that those are really important issues and the other other work I've done in other spaces but confirm that as well. Great. So we have a question that's coming from a mirror, she beta. Mayor says, for the gene selection and transfer, how will we be sure it's benefits based. It's benefits are based on real clinical health research and not other types of research that may be misleading. Either one of you want to take that on. I think this kind of gets the issue of trust and deployment and who's making the decision to use these I mean I don't know what exactly what the types of research that may be misleading but maybe not really aimed at. I think the mosquito malaria case is such a brilliant one to start with because that's the one that I think people think, well, of course, if you're going to eradicate this disease at such a major global burden, it'll be a great thing. But I think kind of gets back to the threshold idea and deployment who makes that decision I mean maybe there could be other reasons that people may think don't really serve the public interest. I may not exactly answer a mirrors question, but I think one of the interesting issues around testing the efficacy of these technologies for example the mosquito case. You know is it's one thing to show that that either with models or with field trials that we can suppress a mosquito population. It's a second thing to show that it has an impact on disease prevalence and health. We would, we would assume that those things are very closely linked, but it would be important for us to distinguish the kinds of outcomes that we're measuring. And in fact, you know my understanding of the US regulatory system is that when we propose, you know, a biotechnology product. We have to say what is it what is it going to be used for how is it going to be effective. And how we define that effect, whether it's population suppression, or public health benefits, that will change the way our regulatory framework views, the kind of testing that's required. I just want to build on this a little bit too so with the, the question for the gene selection and transfer I think, perhaps, Amir is mentioning the, like for the anti malarial factor gene that's in the mosquito. You know that that has been tested in the laboratory using a laboratory of your parasite, you know that's been allowed for over 20 years. So one of the things that needs to happen is, is that a factor needs to be tested with, you know parasites that are currently circulating in the environment to make sure that it is as effective as you know it isn't you know as it seems to be in the laboratory. And that kind of information needs to be sort of made available prior to to doing a release of something like that to make sure that it's going to actually be effective at blocking transmission in the population so I think, going forward. There are groups that are actually planning to do sort of field experiments in parts of Africa where they're actually collecting mosquitoes from the environment that are infected with malaria and then testing these effectors to see how effective they actually are. So I think that, you know, just more work needs to be done in that area. So let me follow up with that with another question just came in Terry bar says evolution is an ongoing reality selecting targets could be problematic. Might there be no end to these efforts. I mean, I think, I think he's spot on. I think evolution is something that's going to continue. And you're going to have to keep fighting against it and it's going to keep winning. I think, ultimately, one needs to think about, you know, try to develop the technology to sort of overcome that as much as possible and so I think some of the new thinking is to, to design gene drives to target essential genes. And so when you do that, when you actually generate a resistant allele in that gene, then that can kill the organism and so that's there's a lot of work in that area. And I will say that, you know, we think about this a lot too. And this is part of the reason why we're really, really excited about PGS it. It's because it kind of takes the ability of evolution to have an impact on the system out of the out of the equation because everything is done in a very stable environment and it makes it very hard for evolution to take an effect on that. So, but I but that is something that we think about quite a lot. I think this conversation right now is sparing several questions so Jonathan would just submit a question. Regulatory is often repeated in both repeatedly regulatory. Can someone speak to the global regulatory bodies do they exist. And if so how did they educate all this. Really great question. There, what I would say is that there are a lot of, there are a lot of institutions operating at the international level that will have an impact on research and development. And those range from the Convention on Biological Diversity to the WHO World Health Organization to the IUCN International Union for Conservation of Nature. Regulations are going to have significant impacts on, you know, what we require of gene drive research on the kinds of technologies that are pursued on the kind of engagement that needs to be done things like that. But regulation mostly happens at the national level. And so, in terms of what most people think about of a government requiring a permit for something to happen. We don't have international permits. And as Omar raised you know this is a really important issue with gene drives. If we do consider the release of a non controlled or non limited gene drive that could cross national borders. Then we need to think about regulation that isn't simply within a national context. And so some of the interesting conversations at these global institutions is about these cross boundary issues of gene drives and other other other organisms. Okay, so Jonathan Pugh has two related questions for the two of you. Although there has been no real world trials of gene drives, there have been a few releases of standard genetically modified mosquitoes, including now in the US. If we establish that split drives are sufficiently reversible and controllable. To what extent will split gene drive technology require new policy frameworks beyond those that are in place for the release of standard genetically modified organisms. Are there any mistakes to learn from policymaking in the release of standard GMOs. Very good question. I could I could probably jump in here first so I think I think there will need to be new new frameworks develop for for any type of gene drive. I showed you that split drive is is confinable and it's safer than a invasive gene drive. However, it's still a gene drive and it's still predicted to sort of persist and also spread into a population and because of that, I think you're going to need new frameworks because the the current currently released GMOs, like for example the oxy tech mosquito trial in Florida. That's a self limiting system so that that is not predicted to persist or spread in the environment like a gene drive would. So, even though a split drive is confinable and safe, it's still a gene drive so it's still going to require a new framework, I would say, what I'll add is, you know, I think I've been in conversations with a number of different regulators. And I think there's a there's a mix of caution that these kinds of technologies do pose new challenges so the ability to spread and persist in environments is is new, or at least somewhat novel. There's also a kind of confidence that the kind of risk assessments and the kind of approaches they have had for genetically modified organisms of different kinds could be updated to apply to the, you know, the kind of technologies that Omar is describing. So, you know, I am, I'm not optimistic that we'll see a brand new framework in the US regulatory system for gene drive organisms. I think people would even end up arguing about what constitutes gene drive and what's regularly genetically modified. So what we'll see what I hope to see is that the regulatory institutions that are active already, especially USDA FDA and the EPA takes seriously the new characteristics that are presented by any of these organisms. And think about what are the kinds of risks and management techniques that we need to deal with the novel characteristics of, you know, these organisms that are on a spectrum from being, you know, very uncontrollable versus self limiting. And also just I want to add another part of the question was, you know, what lessons can we learn from how we did the GM mosquito trials I think there's certainly a lot to learn from the way that we communicated with the public and different kinds of stakeholders. The backlash that we saw in the Florida keys in the last, you know, six years or so has been pretty intense. And there are, I think there, you know, we can find better ways for developers and scientists to communicate about their technologies we can find better ways to get feedback from communities and publics about how the technology should be tested how they should be deployed and things like that so there's a lot to learn there. But I don't know that it that it will be a specific new regulatory framework that we need. I'm wondering. So your SIT systems really quite fascinating kind of represented a new evolution and kind of approach to managing populations as technologies keep getting better maybe we get better and better control over over the technologies and and how they may behave in the wild. Do you think we should just wait a little longer for more technologies to evolve before we start thinking about field trials or do you think we're already at the point now where, in your view, it would be justified to go ahead with some kind of field trial. I think, I think, you know, people are suffering, right, you know, with with things like diseases like malaria, thank you fever. These mosquitoes are causing a lot of problems in the world and so if you have a technology that can address it, then I would probably, you know, if it's safe and can be effective I would probably go forward with it, knowing that there will be potentially new technologies in the future. So, you know, the PGS it is, you know, we think it can, it can actually be advanced to a field trial now, because it's so it's so effective in the laboratory. But of course we actually have many new ideas of how to how to improve it right and we're working on some of those already so will we have a new product before this actually gets used maybe, I don't know. I think, given that people are suffering and we have a technology that's safe and effective I think we should actually start using it. Now, if we can. So I have a couple of questions that I think touched back on this idea of what the right metaphor is because I think consent comes up in both of these questions. Okay, Chan asks, what about the issue of intergenerational ethics. Are we modifying the world without the consent of the generation that is going to be left with the consequences, if any, and one just said it's my belief that if genetic testing on humans is illegal, at least prior notice of the subject should be so they're both sort of playing on this idea of consent. But, but you know I'm Jason you said that that I think rightly of course that we shouldn't think of this in terms of like like patient consent for therapy or for for research. But, but I think a lot of the public love people kind of have this concern about consent, even the future generations, how do you address these concerns. I think it's a really important question to deal with. And I mean the first thing to recognize is that that this is not unique to gene drives or to genetically modified organisms that we make decisions about how we modify our shared environments, all the time that are going to have intergenerational impacts. So anything from development to construction to public health interventions. We do things all the time that affect people who are not yet born, or people who don't usually have a voice in the process. So I think that we can think creatively about how to have conversations that influence governance that bring those voices into the conversation. Because I think for for people to be representatives of more marginalized groups for us to organize stakeholder dialogues that privilege of voices that are often unheard. I don't know how we, I don't think there's a perfect way to bring future generations into the conversation, but we hopefully we can have people in the room around the table who are being thoughtful about the impacts that go beyond the next five years or the next business cycle. And that's a challenge for any kind of intervention that we have, and any kind of non intervention that we have as well so certainly, you know decisions to not deploy a public health measure. You know our debates about when to approve the COVID-19 vaccine. I'm sure that those experts were wrestling with both the safety, the kinds of impacts that it might have that would be negative but also the impacts that if we didn't release it. That's the kind of suffering that would happen so those kinds of trade offs and challenges and complexities are present in all sorts of interventions that are not completely sites, site specific or located in a particular time. I was wondering if either of you could take me through this a little bit more. In order for the research to go from the lab to, you know, kind of control settings and then eventual, maybe field studies. Who's in charge of that process like, you know, is there like an FDA like body. I don't have a clear idea of what what the actual steps would be to to go from lab to real world application. And you want to, I mean, so I think I think it's going to depend on where, like the location of where you're actually planning to do the intervention. So, you know, if it's if it's going to be in sort of somewhere in Africa, for example, then that country is going to have its own regulatory body that's going to ultimately decide on it. And I think, you know, that's, it's not going to be the FDA here in the United States is going to be that regulatory body. And I think, you know, they, they will obviously have to measure the risks and benefits and and to the engagement and all these sorts of things. But ultimately, they're, they're going to decide if they want to go forward or not. And, and so, you know, that thinking actually was part of the reason why we actually were, you know, came out with this article of the court commitments is because we wanted to make, make it clear that, you know, if we were to go forward with a gene drive intervention somewhere in the world that we would, we would follow all these court commitments who wouldn't bypass any of them. It wouldn't just go out and get a regulatory approval at that location and then deploy the drive because we understand that the drive is not going to stay there. It's going to, it's going to potentially spread beyond that site. So I think that's part of the reason why we went out and did that, but, but ultimately, I think it's going to depend on where you, where you actually plan to do the intervention, maybe Jason has some more thoughts on that. I'll just add, I think, you know, there's a whole network of institutions that govern decisions about gene drive research and potential deployment. And it ranges from funders. So for example, you know, the next track committee that that I worked with on the working group, the NIH has, you know, a kind of regulatory authority, given that it funds so much research in the biomedical sciences. So the kinds of policies that the NIH requires of investigators on institutions that receive NIH finding funding has a kind of governance power. So that's, that's present already. We have institutional biosafety committees. I'm sure Omar is very accustomed to working with them, even at lab scale research on genetically modified organisms or any kind of insects or pathogens or things like that. Regulatory institutions will get triggered in different ways for testing for transport of genetically engineered organisms and certainly for any kind of field release. So there's, you know, there is, it's a very complex field. You know, Omar could probably speak to the complexities, even when you're doing lab research. But when you're talking about taking it to the next phase of any sort of field release or field trial, there's going to be more organizations and institutions involved. So far, the paradigms we've been working with, I think, are about eradicating or getting rid of negative, undesirable traits, right, and invasive populations. Is anybody thinking of using gene drive technology to promote something like beneficial or thriving in an ecosystem? It's almost like pumping up some good rather than getting rid of something undesirable. So kind of like a positive kind of eugenics sort of spin on this technology. Is anyone thinking of that along those lines? And then kind of as a close follow up question, the funding agencies, are they worried at all about dual use of these technologies? And are there any ways to sort of address that in the early research stages? So even if you're developing this to get rid of malaria, what if somebody decides to do this to promote a species or really, you know, drive it up rather than drive it down, right? So those are the two questions I have. So for the first question about, you know, are there ideas about population replacement that would have been beneficial or positive characteristics? I think there certainly are those discussions. One area of that is in terms of conservation. So there are, you know, I don't know of anybody working on a specific project of using a gene drive in a threatened species or endangered species, but there is discussion about how, you know, with climate change and other kinds of threats to biodiversity, are there ways that essentially natural evolution wouldn't be fast enough to protect species? If that's the case, then there's all sorts of interventions that conservation scientists consider through translocations and other interventions. But one of those could be to, you know, choose a characteristic that would make a species that's threatened or endangered more fit in terms of Darwinian fitness in the environment and to spread that characteristic quickly through a population more quickly than if we just relied on natural selection. So one example of work there, I mean, you know, the other, you could also think about an anti-malarial mosquito, in other words, a mosquito that wouldn't transmit malaria is a kind of beneficial characteristic that could be spread in a natural population. Omar, do you have any comments on that before we take on the dual use question? Yeah, I think, yeah, I think you're spot on. I think, you know, there's a lot of different beneficial traits that one could spread into populations and I will add that there has been work at UCSD where they've shown that gene drives can also work in plants, right? So in plants, you could imagine spreading in, you know, pest resistance or, you know, depending on which planet it is, you could potentially produce like better crops and spread that into a population like, you know, more robust strawberries or more depends on what you're working on. But I think there's just a lot of gene drive is a very powerful technology. It can be used in a lot of different ways that could benefit the ecosystem. And there's a lot of a lot of thought going into it and work on that. So, and then, yeah, sorry. Okay, so in Sue, you raised the question about dual use and whether people are worried about this. Certainly there are conversations and our gene drive committee at the National Academies address this briefly in our report. We have to consider with a powerful technology, what would it mean for, you know, a bad actor to get involved with this technology, whether that's a bad actor as a kind of lone wolf in a garage or if it's a government that has bad intentions or doesn't care about health ecological or human health issues. So I mean those concerns are going to surround any technology. From the conversations I've been a part of, you know, that this technology is not advanced enough to present a new kind of threat that we need to become incredibly worried about. And I think that education already exists. There's a lot of, there's a lot of ways to cause death and destruction in the world. I'm not sure that gene drive is the is going to be low on the shelf, at least in the near future but I think there are people who are having those conversations. One of the things that I really want to try is that the the scientific community are on gene drives Omar and other colleagues are really interested in the responsibility of this field of science. So they're not, you know, I could, you can even tell just by Omar's presentation that even though he's working at the frontier of the technical research on gene drives, he's thinking about the broader social and political and ethical issues. I have so much respect for that and I feel like this community is interested in those kinds of issues in a way that other scientific scientific communities have not. So I don't know whether that protects us against dual use in the future but I think it, it bodes well for an ongoing conversation about how we govern this technology thoughtfully among within an expert community to promote the best uses and to avoid the bad ones. So that's what I'd like to conclude our session today. I wanted to thank Omar and Jason Del Mar for joining us and giving us your perspectives on these issues. I also want to thank Leah Rand and Ashley Trotman for your support and helping this webinar run as a success and Aaron comes behind I thank you also for sharing your consortium with me splitting that with me. And the last session for this semester after the break for the winter holidays will be back in January and actually in a nice follow up to today's session we're going to talk in January with Mary Haggadorn from this Smithsonian Institute about bioengineering approaches to preserving coral reefs. We have a session on solar geoengineering idea of putting particles in the atmosphere to cool the earth down. And then session after that will be with James Fishkin who's the director of the Center for deliberative democracy at Stanford to talk about deliberative democracy so we have a nice follow up to our presentation today coming in the next semester. And until then I want to thank you our audience for joining us. Thank you for always being there and being such an engaged audience with a series. I hope everybody has a great weekend and we'll see you in January. Thank you.