 So I'll just kick things off. I had one just reflection that connected the two talks and then one question for Jacob. So the reflection was just going back to that Pew Research study, the second set of statistics, the one that you pointed out how current parents of children under 18 are less likely to want somatic editing than people without kids. And for me, that connected up with Marsha's talk because in some sense you can think of people who don't have kids and all of the kind of anxieties and fears that are projected onto what it would mean to have a child with a particular illness or disability and kind of the need to wanna control what that's gonna be and parents just knowing like you don't have any control of any of it. But also more seriously the idea that the experience of actually having children informs this different perspective on what it would mean to try to make that choice. So thinking about experience as a form of knowledge that should be part of the conversation that's then put into conversation with the kind of statistics you might get from a genetic counselor that would kind of counter the over-determined aspect of taking on these technologies. So I just thought about just those things in conversation. The question that I had for Jacob goes back to the idea of the democratization of gene editing that's brought on through CRISPR-Cas9 and other techniques. And just the idea that we think democracy has a kind of positive valence, right? Like good, it's good to democratize. But one of the things Phenomenon I was thinking about within this sort of democratization of gene editing is the proliferation of kind of community-based, do-it-yourself gene editing labs. For example, in my neck of the woods, I can go to a Brooklyn lab called GenSpace and pay $400 for four sessions to do some tinkering with gene editing. And so the question is really basic. Can you just help us think about what's the upside of that version of democratization? What are the things we should be worry about, cautious about to help us understand it from sort of different angles? Yeah, so I think, so there are Kickstarter campaigns and Indiegogo things where you can go out and you can buy CRISPR kits that will let you do these things in your own home. And I think that what I wanna point out is that these kits are, the things you can do are things that you would do in a high school biology lab, right? So I think in some ways that's actually a very powerful positive, right? You don't have to be in high school, you don't have to be in college, you can access and engage with science just as a hobbyist. And I think that's a positive thing. The negative side of things is that these things tend to be very overhyped and they potentially have a over-regulation component to them. So when these kits came out, some of the three-letter agencies came to me and to other gene editing scientists and said, should we be worried about these? Like, is this something that is gonna explode and be really dangerous? And we had to tell them, no, this is like, all high schoolers basically do this type of stuff. And I think that the challenge is that it's difficult to make regulation that's subtle and so there's a chance of, again, throwing the baby out with the bathwater where someone would get over worried about something and say, nope, everything is done. This is just totally done forever because of the possibilities. I mean, I should point out that there are legitimate dangers that could come from this type of gene editing. I mean, gene editing right now is currently classified as a so-called dual-use technology. The same way nuclear power is, right? You can use it to make a bomb, but you can also use it to make power. Gene editing, same way, right? You can use it to potentially cure a disease, but you could also do something really bad with it. And I think we have to be very upfront and acknowledge that things, technologies in general can be used for good, but they can also be used for bad. Can I follow that up with the question too as well, Jacob, because we talk about gene editing and we think of it in terms of clinical treatment. And obviously, when you get into clinical treatment, you're not in your garage in the back door. You're in a totally different scenario. We think of it in terms of sci-fi, which scares everybody. But the bit that I find the most interesting is the research potentials, which you talked about, Kathy Nijken's work, for instance, but just the use of this technology to do some really good basic research into a whole load of different conditions, which is going to be beneficial in different ways. And that's something that I think was sort of slightly played down, maybe, but that's really important. Yeah, I would completely agree. I mean, I think in some ways that sort of snowball of impact is going to be bigger than the impact on people with genetic disease. I mean, just understanding the world around us, it's all these unexpected discoveries that you make using the technology. I had a question that I think crosses between the two somewhat. Marsha, one of your recommendations at the end was to ban germline gene editing in humans. But my understanding is biologically that the two are much less distinct than the idea that you can just approve somatic and not approve germline would make it out to be particularly along two lines, one that unless you're dealing with post-fertile people that it's not necessarily impossible for some of the edited cells to make their way into precursor cells in the germline. And the other point of view being that we already have proof of principle that you can take a somatic edited cell, induce pluripotency, turn it into a germ cell, and in the mouse model we already have, then fertilize that and produce a live offspring with that, so that we have at least two front ways in which the somatic and germline boundary has been crossed recently. And so do you think that in practice it still is a very robust line or is it slightly disingenuous? And are we setting ourselves up for trouble down the line in the same way we did when we called adult stem cell research and then people were horrified to find out that often adult stem cells are sourced from aborted fetuses? Are we setting ourselves up for that kind of trouble and then also can you take a principled ethical stand on that line given that it has now been breached? You go ahead, separate them. Okay, I mean I think that it's really about, it's a little bit about intention and what you want to do. I mean I think that for example you made the point about somatic cells can be turned into germline cells, that sort of thing doesn't happen accidentally and so if you say we're not going to do germline editing, then you wouldn't be able to accidentally take an edited somatic cell and accidentally turn it into a germline cell. So I think there is a line there. But it could just, for one second, it could very easily become part of a suite of privatized reproductive technologies and in this country in particular reproductive technologies are almost entirely unregulated and carried out in the private sector. Again, a difference that you keep saying between the two systems. My point just being that would be an explicit decision someone would make. I think the thing that ends up being more porous is when you put in an edit and it goes to a place that you don't want it to go to, you try to edit an adult cell and it goes to the germline. So I think that right now people are focusing a lot on places where that doesn't happen. So ex vivo editing, you take the cell out, you edit it, you're not anywhere near the germline. Other people are trying to cure blindness and the eye happens to be this enclosed space and it doesn't go anywhere else. But once you start delivering, editing your agents into the bloodstream and hoping they go to the liver and not to the germline, I totally agree, things get sort of porous and if we really wanna say no germline, we would have to have some kind of safeguard about that. Thank you. Yeah, my great concern is the unknowns in impacting future generations with no controls for that, that seems like a line to be drawn. Can I just check this with you, Jacob, with you talking about germline, if you correct a somatic cell line because the oocytes in a woman are laid down in her fetal life, if you correct a somatic cell when she's an adult, it can't affect her germline. It can't affect her oocytes because they've already been made. The sperm haven't. Yeah. Well, sperm, the germ, the spermatogonial stem cells are also set down in fetal life as well. Yeah. I think the worry that people have is, you know, if you edit the sperm, you edit the egg, things like that. No? Can you edit the sperm? I think spermatogonial sperm cells are not laid down. The spermatogonial germ cells are laid down in fetal life and then the spermatogonial are made from that throughout life. But you then have to imply that you're going to incorporate a new gene into the spermatogonial stem cells and into the primordial oocytes that are laid down in fetal life once they've already been made. You're not going to go in and change them. To change the germline, you're really talking about doing things to the embryo. Yeah, I get your point. So, yeah, I think that's a really good point. I mean, this sort of gets into what's possible with current technologies and things like that. So, I think, I mean, I think you're... Okay, I see your point. You're completely right. But I think that people are still going to worry about it until we come up with ways to show that things are not happening. The onus is going to be on us, the scientists. We'll talk a little about tomorrow with the mitochondrial stuff. And of course, with the mitochondrial side, we are going to change the germline. And that was discussed ethically in the UK before permission was agreed that we could do it because we are very specifically dealing with embryos and we are very specifically aiming to change the germline, too. So, we've been talking about, you know, we need to have these conversations and if this is what we decide we want to do as a society, I was wondering if you could talk a little bit, just clarify who's the we in the deciding and when does that decision get... I mean, could you explain to our audience what are the structures or the bodies that set these guidelines and is it professional, you know, professional, I guess, organizations or are they just kind of the general community of scientists or is it like a policy, you know, on the policy level with the government? So, where was that? Where did those things come from? So, at least in the United States, to do any kind of research whatsoever, you need to have ethical approval and that means even if you're doing something like, you know, you want to grow a bacterium and you want to get a little piece of plasma DNA out of it, that has to be approved by a governing body. And you can imagine that the regulations around doing any type of gene editing research are much higher than that and, you know, I think you could probably speak much more to the regulations, for example, around Kathy and Naikin's work. You know, it was required for that. When you're dealing with embryos, it's covered by legislation in the UK that relates to what you can and can't do with embryos, which I'll talk, again, I'll talk a little bit about tomorrow. When you're talking about somatic cell... Somatic cell genetic modification, that again is covered by legislation that starts in the EU. European legislation covers that. I'm not an expert on it. Tissue directive. It's the Advanced Medical Advanced Therapist legislation, the Tissue Directive, yes. So it is tightly monitored. I serve on a few committees where we have a couple of stem cell ethics committees. And one interesting thing about those is who serves on them. And again, in different countries, they think about what kinds of expertise or general public ought to be represented. And this is a point that comes up in relation to the disabilities, is that it's a patient advocate on US committees who stands in for... So there isn't somebody from a disability justice point of view. And sometimes the patient advocate is not actually the person with the conditioning question, but a spokesperson for that raising this issue of spokesperson-ship, again, a parent or somebody who works in an organisation and very often a sort of moral pioneer who's a parent as well. So there are a lot of interesting questions around who's on those committees and what kinds of expertise should be represented. But it would be great to just broaden the membership of those committees and to have them do more substantive work. Yeah, they're just beginning... Medical schools are just beginning to have instructors with disabilities so that the medical students get to meet disabled people with chronic illness who are not in the patient role but who are communicating as peers and educators. It's just beginning. It's very slow. I'm gonna jump in here, Yorah. There are several questions coming in that are about some sort of basics, questions about what are some of the diseases and issues that seem to be tackled by CRISPR-Cas9 in addition to sickle cell disease. So maybe just a little bit of discussion about that. And then also, how is it possible to think and talk about possible side effects of this kind of technology? Or is that the sky's the limit? It could be anything under the sun. So I wonder if either or both or any of the panelists would like to just talk a little bit, because as I said, a number of questions are coming in about that from the audience. This voting reminds me of a study done in the 90s. Dorothy Wurtz was a social researcher. She passed away, but this was a long time ago. And she posed a similar kind of question around prenatal testing to medical professionals in all the range of fields related to baby making from genetic counselors to clinical geneticists to laboratory research and so on. And she posed the question, which of these prenatally testable diseases should be the priority if we can draw a line somewhere? And it was a very well done study. I wish I could cite it for you, I'll look for it. And she sent out these questionnaires to, you know, many, many, many professionals. And the results were that there was absolutely no agreement. And it shows that the life experience of disability is in the context of that person's life and family and community. You can't make a decision. This is the issue of reducing humans to their DNA. We can't make a clinical decision based on looking at a test. And so these votes that we got are not gonna help us think about the impact of these technologies in the real world. It's not about voting, it's about lives. Right. So what are some of the lives or conditions that could be impacted? You talked about sickle cell disease, Jacob, and we've got a lot of really interesting questions I think we can tie all of this stuff together. What are some other things that are on the horizon that we should be having all of these conversations about? Well, I think in, so in that context, you might say, okay, what should we do? And then once you've figured that out, the question is what technically can you do, right? And I think it's important to put it in that order, not what can we do, but what should we do? And then try to figure out, can we do it? I think right now gene editing is still very early days. And so I don't, I wanna make sure that we don't over promise. One of the things that is extremely limiting right now is the ability to get gene editing reagents where they need to go. So people like blood disorders because you can take bone marrow out, do something with it, and then put it back in. But think about, you know, one example might be cystic fibrosis, right? You can't take lungs out, do something to them and put them back in, right? You have to have some way to get things there. And that doesn't work very well right now. So right now people are going for pretty low bars. So blood disorders, we can get to the bone marrow, the eye, the ear, things that are pretty readily accessible because getting that kind of delivery is easy. One example might be muscular dystrophy. So you can get to the muscles, you can inject something into the muscle and try to do something in a local area. But that still has problems too because you might affect one place of injection but how do you make sure that you get all the muscles, right, so sure you affect this one part but you don't affect over here, that's a problem. So I think it's important to recognize that theoretically you could do any genetic disease. Realistically, right now we're talking about like three, maybe four, that's kind of it. So we can't trust everything that we read on the internet? Yeah, exactly, exactly. Because we've been hearing about all kinds of things. And so thank you, that's really helpful. Can I make a comment about the risk issue because you talked about there is a risk of a new treatment, we don't know what the complications are likely to be but this is when it comes down to an individual patient benefit. You've got to look at the problems that that patient has, explain to them what the risks might be and it's their decision then based on their problem, their suffering if they're suffering, whether they want to decide to take that risk and any time you do anything that's new you're going to have to do it under something in the UK with ethics approval with appropriate written consent to explain to people. Ultimately the decision about whether they want to take the risk is going to depend on their perception of the benefit they're going to get from it. No one is going to insist that they have to have it. That's important bit. And I think that's something that, you know, a scientist, that's one of the things that really motivates us, right? Like we, as scientists we don't go out looking for just any random problem, try to solve it, right? We're driven by patients and advocates that say, here's a problem that we have and you know, we would really, we feel like we would benefit from a solution to that and that drives us as scientists to try to solve, for example, problems of delivery to a given tissue. You know, we don't just go out looking for any random thing we can do, we're driven by people that say, I'm having this problem, please develop something that will help solve this problem. The one thing I would add is that people's perception of the risk is mediated through their interaction with healthcare professionals alongside a whole host of other individuals and media and communities. So we know, for example, from the work of Rainer Rapp around amniocentesis is that so much of the perception of risk was mediated through the language and framings of genetic counselors that were very dramatically. And so it's not as if people are making the ideas around risk in isolation from that communicative process. And so one of the things that Marcia brought up is really thinking carefully about what is being communicated, not even just explicitly, but in all kinds, the ways of framing the kind of deficits, the kind of tragedy that's involved because you are already in many ways sort of seeding a particular perspective, guiding people towards particular conclusions about what to expect that then is re-inscribed in whatever calculus they're making as an individual. Yeah, that's very true. In some states that set criteria, they set goals to achieve certain numbers of abortions of certain categories of disease conditions. My disability and downs are particularly targeted. And if the parents don't elect to have the selective abortion, it's considered a failure for those counseling professionals. So there's tremendous pressure in the culture to use the prenatal tests into abort. But back to the three diseases you said there's some progress with. Are they driven by families? Typically, yes. So for example, Huntington's disease. People are very interested in Huntington's disease. There are problems of delivery there and people are now being pushed to try to deliver or to try to find better ways to treat neurological diseases. And in part, it's because the way those diseases work, it's really this problem of fear. If you have a certain number of repeats, when you're born and early in life, you basically have no symptoms, but you know that at some point in your life, cognitive decline is gonna happen and things are gonna start going bad. So it's driven by the patients, especially to try to develop treatments for them. One of the things I appreciated about what you said, Jacob, in the talk is really heating the heterogeneity among even one particular patient group. I know from my study of the California Stem Cell Initiative that both the group that was promoting stem cell research and the group that was trying to squash it, both sides invoked sickle cell disease as being helped or harmed by the research. They got different organizations to sign on. And so sickle cell disease in particular, among all the different illnesses we can think of, is often used strategically to make claims about the benefits or harms of many new innovations. And so I would point you to the work of medical historian Keith Weilu, who wrote a text called Dying in the City of Blues in which he documents historically how sickle cell disease has been a celebrity disease of sorts. Celebrity in the sense that with each new iteration, new set of techniques that are meant to bring us closer to kind of medical utopia, sickle cell is employed. And I don't think it's a coincidence that part of the circulation of sickle cell in this way is exactly what Jacob described about the utility of being able to take the blood in and out. And so that should be recognized as a distinct factor and not this idea that we're gonna help black people because that's often the way it's used. We're gonna help black people by doing this, this underserved population, but what we know through the work of Alondra Nelson and others is that black illness and sickle cell in particular has both been neglected and over-surveilled. You have this duality in which you are on the margins, but you're always at the center as well, especially when it comes to experimental techniques. And so I think I appreciate it just being cognizant of that duality, that it's not one or the other, and that we should be very wary of the way that particularly neglected populations are used as a kind of moral prophylactic for innovation or for experimental research and think critically about whether communities and patients are really being served and in what ways by new techniques. I would probably take challenge with you a little bit on that because I think sickle cell has been used by scientists, by clinicians, and by the media particularly, just as an example that you can easily explain what the clinical issue is because relatively common people know about it. The inheritance of it is relatively straightforward. People understand it. So you're reading things into it, which I certainly think at the start when it's been used has not been the intention of doing it now. How it might have been then interpreted and used on, okay. But to try and explain to lay people, people don't know how this sounds, a simple example of what this is doing, take it to a disease we know about. And sickle cell is common. I guess it was just that one. I appreciate that, but I also urge us to disaggregate the intention versus the effect. So you can have the good intention to do it, but the effect can be the feeling and the sense of being used. Okay. And the, and Marsha kept using the expression or used a couple of times, I don't mean to say kept using, of well-intentioned, that the point is not that people doing this are bad people. The point is that the ambient society is structured with deep inequality at every level of design. And we really need to be cognizant of that and get outside it to approach it at the same time as we approach the technical issues. I wanna interject here also, this discussion has prompted some folks on Voice Hive to say, I'm disturbed by the anti-science perspective of some of the speakers and I'd love for you to speak to that because I'm imagining that what's, I'm imagining that something else is going on here. So I'd love to have you all have a chance to talk about that among yourselves. So I was going to ask that question of some of the panelists. Cool. What diseases would you want to try to cure? Because there are many diseases from which people suffer and die, particularly children and all that are very tragic. And I'm not sure that we wanna celebrate that. I think we wanna try to fix that if we can. So let's take that one. And then if we can come back to my sort of more umbrella question first, but please take Dr. Blythe first. Because I can understand how perhaps some of the things that I'm saying can be read as anti-science and I would encourage us to think about the fact that when we question something, we shouldn't conflate that with being against it. When you care about something, you want it to be better. And so to my mind, what we're talking about in terms of social justice, when we're talking about equity, it's about making science better, not about being against it. So that just to coddle something and celebrate something and be cheerleaders of something, we shouldn't conflate that with being for it either. Because you're satisfied with where it's at, you're not trying to improve it. So I would challenge us to embrace questioning in a critical faculty as part of improving ourselves. And I would also encourage us to remember that the social sciences are science too. So if I'm drawing upon social scientific insights and conversation with science, I'm also for science. Did anyone else want to speak to that matter? I'm gathering my thoughts. People in marginalized communities have been used by science targeted in research in shocking horrible ways. The field of ethics grew out of the need to protect vulnerable populations, the Tuskegee Syphilis studies, for example. So yeah, we're pissed off. And in my community, the medical deficit model is also called the medical model, and it's a bad thing. Because a lot of the oppression has been associated with the medical profession. And I don't blame doctors for this. They just happen to be there when this evolves in the culture. But a lot of medical school training, for example, and training of researchers does not address the real needs of the people that are supposedly trying to be helped. This is a big problem. I'm alive today because of medical research. That's probably true of half or more of the people in this room, not related to disability, but just vaccines and antibiotics and public health and good stuff that keeps us healthy. So we don't mean to criticize medical science and research as being a bad thing, but I like the way you said that. We want to improve it. We want to make it more representative and more useful to the broadest population of people challenging the discriminatory aspects of the distribution and the research and all the things that get it off track. Great. I certainly think as a scientist on this panel, I don't feel attacked in any way, and I certainly feel as a scientist, science and scientific progress is not a priori inherent good. I should be able to explain and defend why I'm interested in what I'm doing the same way anybody should be able to explain and defend their position on any issue. So I certainly think that these kinds of discussions are, I mean, they're for the good, right? Yeah. Yeah. This actually brings us to one of the questions that was turned in by one of the audience members here, actually, Diana's question about, you know, so what are the conditions that would be acceptable to edit for, and then this question, how is gene editing for disease prevention different from other medical treatments for disease prevention, such as vaccines? And so I think that raises a really interesting question about diseases versus conditions, and the lines get really fuzzy, and so what are the, is there a difference between gene editing to prevent diseases and vaccine is to prevent diseases? And what are the specific ones then, I guess, that would be okay? I mean, in some ways, there's not a lot of difference, right? For certain diseases, Huntington's would be a good example, right? If you would induce a gene edit to prevent Huntington's, that's a disease that is so-called penetrant, which is if you have the mutation, you're going to get that disease, right? So you would be preventative and that you would introduce the edit when someone didn't yet have the disease and prevent it. Kind of the way vaccines would work, right? You're probably going to get exposed to flu at some point in your life and so you get a flu shot because you're probably going to be exposed to flu and so you get the shot. But there are other mutations that are not very penetrant, and so it just carries an increased risk of getting the disease, and I think that's where lines get really fuzzy. There are certain mutations that carry an increased risk of heart disease. So do you try to prevent heart disease by making that mutation backwards? At what point do you draw that line? What if it's a 50% risk? What if it's a 10% risk? So that spectrum is almost endless and I would say at some point decisions need to be made. Would you cure muscular dystrophy if you could? I would think you would. I don't think there's an advantage to having muscular dystrophy. It's very debilitating the children die young. If you could cure diabetes, would you? Because many people live their whole lives fine with diabetes, but would they prefer not to have insulin if they didn't have to? Sure, I would think they might. And so I think there are many, for each disease that's out there, one can ask the question, would it make their lives better? What would they choose if asked? I would try to approach it. I think this is one of the big challenges. You had a great picture of Congress. Imagine trying to legislate around that gray area. That's going to be really tough. At least to me, it seems like what would make sense is you introduce a general framework and then, like you said, it has to be individuals, patients, individual diseases. I can't imagine some sort of congressional law saying 50% risk of diabetes is the line at which we do this and other diseases, it's this risk. I think it's a very interesting you mentioned that the deaf community, many of them are opposed to something that might introduce hearing, but others might prefer. I'm sorry, that would introduce like a cochlear implant or something to cure deafness, if you will. Some parents might want that for their children and some might not. But it's not uniform even within a disease or a condition. That's right. This actually gets back to one of these other questions that someone, you know, some of the discussion about sickle cell disease, someone asked, you know, Dr. Korn alluded to some geographic correlation between sickle cell disease and malaria. If I recall, Dr. Benjamin mentioned that the condition of sickle cell also confers some benefits in terms of malaria resistance. Could any of the speakers get a little deeper into that? Does sickle cell have known benefits? And then this is the part I thought was really interesting. Is there a sickle cell community which fears eradication because of gene editing? And so we're talking about an identity, right? An identity, a culture with its own set, with its values and vibrancy and all of that. Does that apply to communities of people who have a disease, right? That's something that we tend to think of them as different things. Are they different or is it a blurrier thing? Is there a sickle cell community? And I know we've already kind of talked about how it's very heterogeneous. I can take that side of it. Do you want to talk about the malaria trait? Yeah, I mean, so okay. So the malaria traits, I'm going to get out in front of, because that was the only thing that I jotted down in your talk. So the evolution of the sickle trait is thought to be evolved and retained in the human population because it confers resistance to malaria. And so that's a good thing over the life of the human race. And so some people have said, what if we got rid of the sickle trait? Would that be bad? Bed nets currently cost 10 cents and they actually provide much more protection against malaria than the sickle trait. And so I think, again, there's this, right? Do you want to retain this in the population and then a quarter of the people will get sickle cell disease? Or do we just want to pony up the money so that bed nets are very widely accessible throughout the entire world? Personally, I would vote for bed nets, but unfortunately, even those are really hard to do, right? So I think that we're generally bad at helping people that are, you know, we're generally bad at helping people that live in areas where malaria is a problem in general. And so technically, I'm not very worried about getting resistance to malaria out of the human population. We're worried about getting wide access to bed nets throughout the entirety of Africa. Yeah, the question, that side of the question around is there a sickle cell community? You know, there's been some great work, both sort of ethnographic and medical sociology studying this, that the idea that there is not a community, right? So we have to think about what constitutes a community, a sense of belonging or sociality. Yes, you share a biological condition that then often leads you to have all kinds of experiences in the world that you connect around, right? Difficult experiences, but also kind of shared meaning around what it means to have this trade or this illness. And part of that sense of community that exists in some areas is this idea, especially in the United States and Brazil and other places in Central and South America, where, you know, people of African descent are having a kind of shared social-cultural experience. This idea that this illness ties you back to a shared motherland, right? So there's meaning around being a trade, someone with a trait or the disease that also goes beyond the biological condition to a cultural social cohesion. And so one scholar, Melissa Creary, who's done some great work around this in Brazil, where she's interviewed and talked to people with sickle cell in Brazil, she finds that not only is there a sense of a way in which this biological illness conjures a sense of collective identity as people of African descent, but also it's used strategically to make political claims against the state or vis-a-vis the state, a state that purports to be this kind of multicultural democracy where people are saying, no, you know what? I know that's the brand of Brazil, but as black people in this country, we have a very different experience beyond this multicultural utopia. And so the trait and the illness is often used to lay claim to this distinction, this distinct experience within the body politic that says, you know, this is biologically real that we're a distinct group. Look, we have this illness. And so it not only doesn't have all these layers of cultural meaning, which you can read as a community, which kind of flattens the dynamic a little bit, but it's also used politically to say that you need to recognize this experience that we've had in this country that is not all hunky dory vis-a-vis this multicultural democracy. And in different societies and different communities, different regions of this country, depending on how much of a critical mass you have in terms of people with sickle cell, you have different dynamics at play. For some, it's like any other patient advocacy organization, right? It would be like, you know, any other illness where there's not a sense of, you know, community in the sense of going beyond being patients together. But in some areas, for example, the Bay Area, where you have beyond being patients, people get together in the sickle cell community to have cultural events, right, throughout the year that isn't simplifying the experience to being patients, but it's a sense of shared experience beyond the medical that I think needs to be recognized. And that's not to say that people want the debilitating aspects of the illness, but it's to say it's more complicated in terms of your connection to other people that share this illness, right? Yeah. So, again, I would kind of ask, is it worth preserving it forever and having the people suffer with it as opposed to curing it and not having them suffer with it and not getting malaria because of fixing that somehow, too? Which would you go with? And I think that no expert, none of us on this panel, are in the position to answer that for an entire community or set of communities, right? I think that that's part of what we're trying to think about is how do we innovate around democratic structures that would allow people to give voice to their own answers to this question, right? I think too often we are in the position of answering four people are presuming we know what would be in people's best interests, and I think we want to sort of shake that up a little bit. Well, so let's take polio, for example. Polio is not something necessarily that you're born with, but you wouldn't want to promote it if you could eliminate it. So I think this might be the same thing or similar. I'm not sure what you gain by keeping, and maybe the people with sickle stuff could give me a better answer. Like, what do you gain by having that problem? I think they would give you a better answer than I'll give you. The one thing I do know is that especially sickle cell, this is not as true of other illnesses, genetic illnesses, but there's great variability in the biological experience of the illness, right? There's levels of severity from, you know, people having strokes at 10 or needing hip replacements at 5. Great variability. Too much milder symptoms, right? So to say that this is the experience would be inaccurate. It wouldn't characterize everyone. And one of the things that we know is that often that experience is mediated through environmental factors. So although it's a genetic illness, the severity is also not for everyone, but also mediated by levels of stress and hydration and social experience that bring on the symptoms of pain that doesn't necessarily have to happen to that degree, right? Especially for those whose symptoms tend to be less severe. And so to say that definitely you wouldn't want to get rid of it, perhaps the answer is yes, but you would also want to say what about also trying to mediate all of these environmental factors that make the experience so difficult, right? But in the meantime, the science has to carry on so that we can give these people the choice. I'm sorry. We're having a discussion up here, sir. I'm sorry. The reason the science is continuing is because what we want to do is to develop the possibilities that we can give these people the choice. No one is saying if we have the way to genetically help them, they have to have it. But if they don't have the choice, if they're denied the choice because of some of the things that you might say, then that's not good for them either. It's to do with them being given the choice. And you can agree that there are a lot of the social things that need to change as well. That's almost a different line. Both those things have got to move at the same time. But we have to allow the science to proceed as well to give people the choice. So I'll go back to the polio example. We don't give children the choice would you like to have or not. We vaccinate them so they don't have it. And I would say most people might think that eliminating sickle cell or some other childhood diseases from which children suffer would be a good thing. And I'm not sure that I see the opposite point of view that eliminating it would ever be a bad thing. You might lose some cultural pride, but isn't there something else that doesn't cause people to suffer that would allow cultural pride to still exist? I think we need to deconstruct suffering. It seems a little bit too easy to say we want to help them because they're suffering and therefore we have to pursue this cure. It's what Ruha said. You're pointing out that the complexity, the history, the culture, the environment, the stress levels make it much more complicated than we just want to help those people feel better. And I actually do in my mind make a distinction between vaccines for polio and genetic engineering. I think it's quite different. And I need to think about what it is that's different, and I'm not quite ready to articulate it, but we're messing around with a much more fundamental level of humans with our big question at this conference. And to offer a vaccine operates on a level that gives us that community a lot of control. Intervening in genetics has a lot less control for the people who are affected. That's true, but there's some bad stuff that happens genetically, and you could fix it and wouldn't you want to in some instances? And I think Tasex might be a good example. Hypothetically. Muscular dystrophy is a very good example. Cystic fibrosis is a good example. There are a lot of genetic things that aren't necessarily happy for the person who suffers from it. Sure. I think what Allison said about choice resonates a lot to me, and I think that having a treatment available induces a sort of pressure, but not having it there equally also, it gives you no choice, right? If there's no treatment available, you have no choice. But would you choose it? Let's say, I mean, right now, you can with some techniques, you can choose whether or not to have an embryo that has the disease or not have the disease. Would you promote that, or would you say, oh, that's a bad thing? What I'm saying is it takes a chance. What I'm saying is it's a good idea to have multiple options. So if one option is have the child, not have the child, I'm saying if gene editing is pursued from a therapeutic point of view, it introduces a third choice, right, in which you can have the child, and then after the child, after you have the child, you then have a choice, you know, the child, you don't have to do anything, right? You can have a child with a disability, or there's another choice, which is if the technology is available, you could do gene editing to remove the causative mutation. So to me, it's not about forcing choices on the people. It's about trying to widen the number of options available to individuals, because everybody's life experience is different. And so you shouldn't just say, do this, do that. It's each choice in each situation. I take issue with saying that eugenics, which is a pretty bad thing, I think we can all agree to say, well, what's a little bit of eugenics, where you make a choice whether or not to have an embryo that has a disease or doesn't have a disease. Maybe that's genetic eugenics light, but it seems to me that at least that decision shouldn't... I wouldn't criticize anyone for making that decision. I would certainly criticize the Holocaust and much worth, much for clear examples, I'm sure I can come up with lots, but that one, I think... We need to talk about eugenics, because eugenics is a state-sponsored theory. When you're talking about an individual deciding to have a genetic test on their embryo for their individual family, that is their choice. I think that's not eugenics. We really need to sort of say, whole eugenics movement is a different issue. Would you agree with that? I mean, because I'm not sure. No, only because the lines are so gray. When we say someone has a choice, but she's been pressured by a genetic counselor or her partner or her family, ideally it is absolutely her free will choice, but it's always in context. Has she had exposure to families, for example, who have a child with that condition? Generally speaking, the patients who we see who come for pre-genetic diagnosis of an embryo, so this is not genetic manipulation, this is they're having IVF, they have a choice of embryos, they do a genetic test on the embryo to decide if that embryo's got a problem. First of all, these are all families who already have experience of genetic disease, so these are not people who are pressured because they don't have any previous knowledge. This is not screening, this is not saying, out of the blue, you have got a down syndrome in a child with no previous experience. These are people who are coming to us for the test because they've already decided they do not want to pass it on, and that is a different issue than just routine screening blindly for everything so they don't know. For their individual couple, the severity of that condition is going to be very different. There are some couples who might decide, well, I'm quite happy to have a child with that, might have that problem, I've experienced it and it's no problem. For other people, for the same condition, they might say, in our particular circumstances, we do not want that particular disease. I'm not sure that I'm in a position to make that value judgment for them, I think it should be there, they've got to live with the consequences, and if you want me to sort of make that decision for them, I don't feel competent to do it. I'm just lucky not to have that bad gene being passed down by my family. Well, I think it gets back a little bit to the previous panel discussion where we were talking about, there's a difference between intentions and top-down regulations and that's how you want to define eugenics or that it's a state-sponsored program or something like that. And then there's the coercive aspect, but then there's also, I think, the last time that the network of decisions that people make together, right, so individually they each have their choice, but then if enough individuals, as a group, as a culture and a society operating within certain kind of expectations is the effect of it going to be minus regulations and official policies, kind of eugenic. And so I think it's really tricky to think about the individual choices and we're talking about the many factors that kind of press upon the decisions people make and then also kind of how just not intentionally, you know... I mean, I think partly what happens is that in hindsight, now we've painted eugenics as the big bad boogeyman and so we kind of have a distorted understanding of how it functioned, how the genetic imaginary functioned and when we say state sponsored, we think someone knocking on your door and forcing you to do something, which perhaps it happened, but the way that power works is to make you think that you're making the choice yourself. And so in terms of, you know, at the height of eugenics, partly what was at play was, for example, staging the fitter family fairs at fairs throughout the country, in Minnesota including, right, where people were going to the fair, you were going to normal fair, hanging out with neighbors, doing things, and then you were also being encouraged to cultivate this genetic, eugenic imaginary, where you internalize the same kind of norms and standards and you are making decisions for your own family. You're encouraged to make the best decisions for your family. At the height of eugenics, the function was not to sort of beat you over the head with it and to make you feel forced, it was to make you feel like you were making the choice, right? White families, we need to cultivate the best white families and you need to get rid of all these molados and these poor kids and these disabled kids and it was never simply a kind of top-down phenomena where people felt like they were being coerced so I think in some ways we want to not think about the epitome of genetics as the Holocaust, where we understand that it was the height of coercion, right? But to think about the origins, which were American, which was a much more diffuse cultural eugenics that didn't feel necessarily like this state-mandated thing that we associate with it, right? That's just something to keep in mind as we think about how power operates and how it may operate now in terms of the binary between choice and coercion. To bring this conversation back a little bit to CRISPR, because we have some questions about that, we have one question that one person asked, do any of you believe that we'll look at these technologies and collectively say no to one or more? Has there ever been a case where we as a species have developed a technology and then chosen not to use it? So we're having these great conversations. Is it kind of moot? Is the genie out of the bottle? I think for a long time we tried very hard to suppress stem cell research. The government certainly had prohibitions against it. Then eventually they allowed a few lines to be used and so forth. So sometimes they put impediments. It's not always a clear sailing path. We have a lot of treaties for weapons of mass destruction. They're not perfect. The testing periods, Ruhar talked about this morning, and we're often suspecting that rogue governments are using them, but by and large they do a very good job of holding at bay a reckless use of weapons of mass destruction, nuclear and chemical and biological warfare. So we have a lot of regulatory standards around transportation. By and large people follow traffic lights. They don't just do what on earth they want to do and in all kinds of areas, computing and so on. They regularly fights. It always bubbles up again and people have to contest it again, but absolutely we live in a world where every single step we take is mediated by things that we've said enough for this way, not that way. Often problematically, in ways that are extremely life-promoting as well. This week's New Yorker has an article, it's a book review actually, that describes fire as one of the first technologies. And it's a nice example of how something so useful to human beings, which according to this writer was a huge step forward in civilization, gets us in big trouble as well. So is it not true of any technology that there are huge drawbacks that we have to examine and figure out how to contain? There's this very specific technology in the IVF field, some techniques to achieve fertilization that you probably have never heard about because they tried them and it didn't work and so they never did them again. You don't hear about those. They were done as a controlled trial with very good intention. It didn't work, so you stop. So there are safeguards in place and this is part of the process, yes? Yeah. At the same time, it's probably worth not adopting the just say no as your fight because people, not everyone will. And I always think it's worth saying not should we, but how should we? Because how should we, this comes back to an earlier point actually, the how should we is an invitation. It's additive, it's not mutually critical. It says how can we care about inequality? How can we care about social justice? How can we have not excess mortality and morbidity for some groups, but equal more vitality for all groups at the same time as it says what's the best possible science and technology we can have? How can we do that in a way that's additive? It's really a challenge to try to develop something that will never have any side effects on anybody ever. And I think the female pill for birth control may be a good example of something that had a wonderful intention but they didn't realize that the amount of ethanol estradiol was too high until lots of women took it and they started dying from venous thromboembolism and that caused them to realize that and to lower the level of that hormone. That's not something that necessarily shows up in some of the preclinical toxicology so that was a very large experiment in the population of women which you could say is a really bad thing and we would try to prevent that if we could by ruling that out but oftentimes something doesn't show up in the population until you get into the population. But on the other hand things like that is to do with risk benefit because what you're doing was preventing them from dying from unwanted pregnancies and backstreet terminations so it swings around about... There was a period of adjustment Yes, ups and downs but yes, you've got to start somewhere. But some of the very technologies we're talking about are part of the new generation of model systems and more things can be done on human model systems in vitro than used to be able to be done and the chances are that we're going to have a lot... We're actually using some of these technologies to have a much better chance of avoiding that kind of catastrophic set of side effects although I totally agree that everything has side effects and we also another slogan we like to use in the history of technology field is that every technology is a dual use technology. We have another question submitted by one of our audience members here who would like to know can gene editing technologies be patented? I know this is a big question and why and if so how will this affect access? So our last year's Nobel conference was on economic inequality and so I kind of wish that we could like do a reunion or something like that and bring them but can anyone on the panel but Jacob I think you in particular probably would have some insight into this that you could share with the general public about the role of money in all of this and who owns this technology? So the answer to the first part is really easy can they be patented? Yes and they have been patented. I think the bigger question is for something that's this sort of bedrock technology should it be patented or should it be shared in some way that incentivizes companies to invest a huge amount of money that are required to maybe make a cure out of it while at the same time ensuring that everybody gets access to the technology and that is I'm not a lawyer I have no idea how one would do that yeah it's tough but I think the goal would be just what I said you need to make sure that everybody has access to the technology so that everybody can work with it and innovate on it but at the same time you need to incentivize people to pour in the huge amounts of capital that's necessary to make a drug out of it that can eventually go into a person as an example of an application. Is there any way to try to figure out how to say this is it only market forces? that is going to drive how far this technology can go and who gets access like what are the are there other forces that can come into play that can say you know maybe yes pharmaceutical companies sure we need to incentivize them to putting the money because we need the money governments don't have the money to do it or the will or what not right and so there is that relationship that needs to be there but is there any way for that not to be the only thing dictating how these things get developed and who has access then? so I think that that's I mean that's a really interesting question of how can governments and societies incentivize drug development in a way that is non-commercial there have been some interesting examples of that One World Health was one there are a couple others and in fact in California CERM has this big thing where it's state money and in the budget and they try to incentivize stem cell technologies that eventually become therapies but even those require I don't know require might be the wrong word but they you almost always have to have some sort of commercial partner just because CERM can only put in so much money and then you still need another 70 million dollars to get something into the clinic so actually getting something into a drug costs a huge amount of money and it's really hard for the state or even a federal government to say yeah we'll just pony up all of that so I don't really know exactly what the right answer to that is I mean from the basic technology point of view if your question is how do we incentivize that that's easy because basic research fundamental research is actually quite cheap comparison to going through a clinical trial and doing all that stuff so we can incentivize all that in a very non-profit way and people can just do basic fundamental research using these technologies but going through the regulatory process of proving that something is safe has acceptable side effects like we were talking about no technologies completely without side effects figuring out what all of those side effects are when it can be indicated when it can't be indicated all that it just costs a lot of time and a lot of money and that raises this much bigger thing that's not just private to gene editing but in general with drugs is there a way that we can make drugs in a non-profit model that does not involve corporations should we do that what's the best way to do it maybe other people on the panel have it's a really expensive process and then the post-marketing problems are that again you get into the population even if you've tested thousands of individuals for the drug whatever the condition that might trigger a problem might not show up in that population so I think vaccines was a good example where the government actually passed a law to indemnify the companies so that they couldn't be sued up to a certain limit in order to get vaccine development because otherwise no one would have done it I see it from a slightly philosophical, moral viewpoint in that someone has got to pay for developing new treatments there's no question about that what concerns me though is people making profit out of it and coming from the UK which where the health service is considered more as a service as a fundamental core thing that should be provided by the state we still do have a problem with pharmaceutical companies making profit I feel uncomfortable about making profit about other people being ill and that's very idealistic but then on you've got to decide who is going to pay for it and if the people paying for it are only doing it to make profit I don't actually feel very comfortable with that and just putting that into conversation with some of the examples we have in the states where if you think about the different sets of actors researchers, patient advocates and kind of commercial actors in the context of California where we created this agency and this initiative and the state agency that was giving out grants to universities and other public sector actors to encourage collaboration with private actors so that the idea was that a portion of the royalties if something profitable were to develop should feed back into the state because this is taxpayer money so this collaboration a small percentage should go back into sort of benefiting everyone regardless of if you can access the therapies and I recall that many of the most vocal patient advocates in this context who are cheering on the desire for cures were often vigorously opposed to increasing that amount of royalty that would go feedback into the healthcare system so they wanted the cures but they were not as invested in the redistribution of access to it and so I think we have to think about those tensions and the way that your desire for medical treatment I think needs to be paired with also this idea that it should be available and so what mechanisms how do we prioritize that and in this case it was actually pitted against each other the idea was it would actually deter companies from working with researchers if they thought they had to increase the percentage of royalties even by a little so that was seen as a deterrent to want to develop these cures because a little more money was going to funnel back into the state and so no we shouldn't we shouldn't increase that because that will dampen you know the pursuit of cures and I think that's part of what we need to begin to question and actually become a little more idealistic I think it seems to me whoever was on the panel making that decision might have had some connection to the drug company because I would think the general public would have been in favor of that well this goes back actually to Charis's point earlier about who was represented on these committees that were purported to be independent oversight committees representing the public and the kinds of interests that were really represented in you know and as a social theorist I can't resist saying that there is a big an underlying question which is what is the social contract with science why in the post war era do we believe that taxpayer funds should go to support basic research well partly because we get all kinds of wonderful just incredibly intrinsically interesting stuff is found out about the world but also because we do a lot of useful and amazing things about science but when you hone a little closer in than that there are competing models so one view of what we're mostly doing in allowing inputting public money into basic scientific research is that we're de-risking part of the translational the bench to bed side the innovation pipeline we're having it happen in a context where it isn't yet it isn't up to a company won't rise or fall on the basis of what happens there so it's been function is to be is to take the risk make the risk public to democratize the risk of you like and to de-risk it another model would be the one that you were alluding to which is the idea that we pay for it we should get something back and that isn't just the few but that it has intrinsically that idea must have a justice dynamic to it because everybody pays taxes so they should come back to everybody in a way that's representative of all and those lead to very very different people as the right people to be saying how this social contract should be carried out if we could close with just one final question this is again about CRISPR I think people are really they want to learn as much as they can about it because it's been all over the news and this person asks about actually there were two questions one that was talking about kind of you know how will this affect evolution and how will evolution kind of like interfere in some of these attempts to kind of gene at it maybe that's thinking a little further ahead but this person asks doctor corn brought up the potential to introduce widespread genetic resistance to HIV theoretically that could eventually create a strain of HIV that has mutated to overcome their resistance and operate on a different mechanism thus developing a resistance to current or future treatments how do we weigh the potential of the risk so it's kind of you know it's not that you fix the problem and then it's done about to stop moving in the arms race so CRISPR often gets talked about as this oh it's this magical thing and it's going to solve all the problems it's not going to solve all the problems forever right I think that certainly when it comes to infectious disease that's going to be the case there are other uses of CRISPR that involve for example eradicating diseases like that and people have already started to show that when you start to deploy these things malaria finds a way right around the technological solution so we shouldn't think of these technologies as panaceas and magic bullets they come with their own sets of drawbacks and you always want to think very carefully about will the cure be worse than the disease any final thoughts from our panelists before we break this okay okay all right Lisa has a couple this is a fire hose and it is it is clear that there's a million things being thought and discussed and worried about among the among the gathered here and I want to really encourage you to leave this hall and talk with each other I made an executive decision we are not we don't run this as a town hall forum for a variety of reasons which we've chosen so I apologize if I came across as rude to the gentleman but we really choose to have the questions come through this you know still it's a fire hose but nevertheless through this mechanism so I do want to encourage you all to take advantage of this time that you have now to talk with each other about the really challenging issues and questions that our panelists have brought up these are hard topics we've had a hard discussion I very much appreciate their forbearance they're careful listening to each other I think it's been a real model of those things and I want to thank them for that because this is difficult so thank you and I thank you for submitting your questions and I encourage you to continue to do so and I'll put the I don't know the regulator on the fire hose please remember the events this afternoon and this evening and enjoy the rest of your of your day