 Welcome to this early morning session, my name is Magdalena Skipper, I'm Editor-in-Chief of Nature which is a weekly science journal. And before I introduce my panel, I'll just very briefly set the scene for what we're going to discuss here. So of course you will well know that the focus of our discussion here is very beautifully framed with really an invitation to consider what happens when humankind overrides evolution. And it's an interesting thing to consider because of course when we think about it, we think about synthetic biology, we think about new biotechnologies, but in itself humans modifying evolution or trying to modify living organisms that are around us is of course not a new concept. For a very long time in human history we have engaged in trying to modify organisms around us, of course through classical breeding, you will be very familiar with examples from agriculture, be they plants that we consume today, our food crops, of course animal stock, but of course our very loved pets, they are all products of us trying to override and interfere with evolution in some way. But this is just the background in which to situate our discussion today. And so to discuss the much more rapid interference, if you like, with evolution, I have here today, I'm going to start from my right, Kevin Esvelt who is assistant professor at MIT labs and head of a sculpting evolution group. Next to him is Verna Baumann who is an economist by training and CEO of Bayer and over on the far right is Beth Shapiro, she is professor in the department of ecology and evolutionary biology at University of California, Santa Cruz. So thank you very much for joining in this discussion and I'm going to start with a general question to all of you actually. Why is it that we need to or we want to override evolution or engineer living organisms? I think, as you said, this is not something that's new to humans. The earliest records of us trying to change the way that species, the trajectory of different species evolution from the archaeological record date back some possibly 30,000 years with the first evidence of domesticated gray wolves or dogs in the fossil record. And since then, I think much of our motivation has been to come up with more efficient ways of turning carbon and nitrogen into more people. And the better we get at using what limited resources we have to produce enough food to keep us fed, the bigger our population is growing and the more we need to come up with newer, more efficient ways of going through this same process. And this has brought us to this stage now where we're using biotechnology which really is a step change, I think. It's not the same thing as we've been doing. It's not the same thing as classical breeding and I think it's a bit disingenuous to say that it is. But that's, yes, to meet our needs, our growing needs as a growing population. That's right. And so, of course, this is one particular avenue where we've been overriding evolution. There are other aspects of it. Would either one of you like to comment on this further? Yeah, I mean, I can only second what Beth has been saying. What we are doing is we are looking at your solving problems in order to actually benefit consumers and patients alike. And what we are trying to do is, of course, to do it in the most efficient way possible and then also to use new technologies in order to solve problems that were not solvable before or where problem solving took an awfully long period of time. If you look at traditional breeding on one side and then using, let's say, biotechnology to go and do precision breeding where we look at very, very specific expressions of a certain property of a plant that we can then precisely enact or actually deactivate. And that's what we are in for business, but that's also what the company is all about and many of our peers are about. We are trying to solve problem solving problems to actually serve the community and the people better. Yes. And that is what this is about. It's about attempting to build a better world. You say, why defy evolution? For the same reason we defy gravity. Should humanity fly? Well, evolution is similarly an emergent law of nature. That is, when you have replicating information with variation, you get evolution. But being an emergent law, it's amoral. If we expect the world to be a better place in line with our highest ideals and the journey that we have been bequeathed by our ancestors, not just turning matter into more people, but to making people's lives better and possibly making animals' lives better. That's an end to which we haven't always turned our skills with selective breeding is engineering animals to exhibit improved well-being in so far as we can tell. Is that something we should do? And in the past we've been limited to our domesticated animals. But now by looking to new technologies and learning tricks from nature, we think that we might be able to alter wild organisms too. Is that something that we should do for ourselves or for them? So this is very interesting. You've jumped in right at the very thick end of the debate here. Thinking about evolution being agnostic of morality. What we're talking about here is designing. So think about design being in some level opposed to evolution. I'm going to park this for a second because I'd like to come back to it. But let's take a step back and think a little bit more. Let's set the scene for the kinds of things that we're talking about and the kinds of tools that we have to play with essentially today. So in the examples that we've just used here, we mainly stuck to agriculture which touches on aspects of health, for example, through nutrition. But there are other aspects that we can talk about. Let's say specifically associated with human health and disease, spread of infectious agents. Would anyone like to comment, maybe give an example of what kinds of things we could do today or certainly advance further in the future? I think your work touches most closely on this kind of thing. I suppose although... I'll chime in. You can take some. Well, evolution of course applies to pathogens as well. And so many of you have probably heard of the crisis of antimicrobial resistance. Now this is one that we probably can solve. Most of our antibiotics we discovered in nature. They're the tools with which microbes wage war against each other and we've merely adopted that same strategy. And that's one where we do need to change incentives in order to reward companies for pursuing new antibiotics. But we also need to think about how we leverage our new discoveries to prevent those pathogens from acquiring resistance. And this also applies to viruses. So with respect to infectious disease, bacteria are frightening, but ultimately we do have reserve antibiotics against most of them. It's the viruses that we really struggle with. And there's a lot of exciting new therapies for viruses that could help prevent pandemics. And that's what I'm particularly excited about. That we might be able to avoid not just the repeat of 1918 influenza but of the far worse pandemics of the past. I mean, there are other diseases many of you will know that a lot of diseases are just driven by single gene defects. Monogenetic cause diseases such as cystic fibrosis, such as hemophilia. And the question is, we asked ourselves a question a few years ago, what would be the holy grail for us as a pharmaceutical entity in best serving our patients? And of course it's not the next best therapy for chronic disease. The holy grail is to move from a chronic condition to cure. And then the question is, are there new technologies out there that would allow doing that? Could we eventually cure people who are not curable today because they were born with a genetic defect that cannot be corrected? Today we have that possibility. But I think this brings up Kevin's point about incentives. I mean, what incentive does a large pharmaceutical company have to cure someone if this loses their income stream? I would not necessarily agree with that. I think the bigger question behind it is, what is the right system to incentivize research and development and pushing the boundaries for the greater good of humankind? And then how do we sustain a system that is actually dependent on sourcing that goes into research and development? Without the funding, we cannot move anything forward. And we are of course a for-profit entity, but beyond profit there's something that I would call purpose. And companies and organizations thrive when they know what they exist for. And we don't exist as many of our peer companies. We don't exist primarily in order to make profit. We exist because we help solve problems that we can solve with the expertise and the means that we have at hand doing that. So I do not necessarily think that it's a fair representation to say, well, you know, once you can cure a chronic disease which kills an income stream that spans the life of a patient, you would actually prevent doing that. Actually, the contrary is true. The question then is, what is the appropriate compensation for that? That is a much bigger question. I agree with you. So very interestingly, our consideration of overriding evolution in the context of health has now moved from, you know, I mentioned nutrition, so that was a sort of link with the first topic we touched on. Then we talked about infectious agents themselves, what we haven't touched on yet, for example, are vectors of disease, such as, for example, mosquitoes and other tend to be insect vectors that carry these pathogenic agents. But we moved through your contribution here to overriding our own evolution, engineering ourselves. When we're talking about chronic diseases, you mentioned monogenic or sometimes mistakenly called genetically simple diseases where you can modify cells in a body. But of course, I think most of us are aware of events that unfolded just over a year ago now when the general press, and there was much discussion about germline engineering of the next generation. So let's touch on this a little bit. You know, with your first comments, Kevin, you talked about you sort of woven morality into this conversation. Let's talk about engineering ourselves, and then we'll come out again to talk about engineering us and other organisms in a population context, because that's been quite an important aspect. Who'd like to pick up that particular thorny issue? Nobody, actually. Correct. With the notable caveat that my laboratory does not work directly with anything in humans, but I did play a minor role in developing a tool you may have heard of called CRISPR. So CRISPR is again one of those gifts from nature on a silver platter. It's a molecular scalpel that we can program to cut and therefore edit virtually any piece of DNA in any organism. And so theoretically with CRISPR, we could go into the genome of, say, an embryo and this is what was done in China a couple of years ago. So not theoretically. Not theoretically. But what is interesting, of course, is that most of these diseases that are cystic fibrosis and the like are single gene and they can be prevented using current technologies that don't require going in and editing. In fact, there's comparatively few genetic disorders that require us to go in and edit. And it's also usually unwise for technical reasons to edit an embryo. And that's why it was premature. Not only was it, I personally think it was unethical to do it in secret and there were questions about whether it was misleading to the parents, whether there was truly informed consent. But certainly it was a black mark on the entire field of science that it was done in this secretive way without public consent. Now that goes both ways because does anyone here know someone who was born through in vitro fertilization, IVF? Yeah. When IVF was first rolled out, about 90% of the public opposed it. So we do need to be careful because public attitudes do change. On the other hand, there's a difference between saying no, we won't do it because a lot of people disagree and being totally open about why we think it's a good idea, listening respectfully to people's reasons to do otherwise, and then concluding that this is really the business of, say, in this case, the parents. So I think one of the most promising aspects to come out of that unfortunate episode which really did decrease trust in science is that the World Health Organization has announced that they will host a registry for human gene therapy, that all clinical trials involving any kind of gene therapy in a human should be registered and therefore people will know what's going on. And that allows everyone to have a voice. Not necessarily a vote, but at least a voice. And of course it ensures transparency of the process. There's a few things that come to my mind on that topic. First of all, the question, does intrinsically good and bad technology exist? Can you really qualify the properties of technology? And I believe that that's not the case, very much the question on how you put it to use. You can put it to use for, I think, very, very noble courses, or you can do the opposite thereof. And what we need is, you know, we need actually both in academia and also in business. We need propaganda rails, you know, and you call that regulation. And the issue we have is that, and that's where I think academia and business are joined at the hip, that there is less and less trust in society for the advances of technology, which makes our lives miserable. And the only way to kind of get beyond it is that we do a better job in terms of explaining what we are doing, what it is that we would do, where the red lines are, where we actively solicit regulators and actually broader societal discussion in terms of what it is we should and should not do. And as Magdalena said, one of the key elements in it is that we create absolute and ultimate transparency. And only then will we be able to manage new technologies for, let's say, better solutions in whatever area, those solutions lay. So it's interesting what you said also about creating a dialogue with the wider society. One of my favorites, so I'm originally trained as a geneticist, one of my favorite examples of where an argument has been lost as a result of lack of transparency, but lack of dialogue and engagement with the broader society is GMO, Genetically Modified Organisms. This, of course, is not a new story. It has been with us for a very long time. But I think at the time when it was unfolding, there was the discussion was left to those who were not necessarily very well informed about the subject area and Beth has something to contribute here. You know, I think there's a lot of confusion around genetically engineered or genetically modified organisms and part of the problem is this lack of consistent regulation for different types of genetically modified organisms. There's lack of consistency within countries. In the U.S., there are three different agencies that regulate genetically modified organisms and some of them have decided not to regulate organisms that could be produced naturally. That includes the USDA's decision for agriculture, whereas the FDA has decided that any genetically engineered animal is going to be regulated as a drug, a new animal drug, which has made, especially in the academic world, where there's not that much money to go through these massive trials that you might need, it's difficult to make progress. There's a fantastic program at UC Davis where they've created cattle that are polled, dairy cattle that don't grow horns. It's an animal rights, it's a single change and it is one that could have evolved in nature. They've moved an allele from beef cattle into dairy cattle and yet these animals now will be regulated as new animal drugs and they won't be able to enter the food chain despite this experiment and it seems to be grinding to a halt, which I think is a real shame. Part of this is that the loud voices, the loud anti-GM voices, drown out the science and make it very difficult to communicate that the technologies that they opposed in the very beginning are not the same technologies that are being used now. There's no nuance to that dialogue and until we can have that nuance and different consistent international regulation that capitalizes on that nuance, I see that it's going to be very difficult to move forward. Maybe if I can add to it, you have hit on a particularly bad and sad example. GMO, I think if we look at AG, it's mostly about your transgenic technologies where you take your elements of one organism and into a resident to another organism and how that opposition came about is a fairly interesting story and there's an NGO behind it. It's Greenpeace at the time where Greenpeace for campaigning purposes looked at what it is that virtually affects everybody and where you can, excuse my German, scare the shit out of people and this was about food and food security. That's how they actually started to campaign against GMO technologies and what they did was they put millions of kids into misery because one of the things that had been developed is something that is called golden rice that carries vitamin A that helps people that are suffering from malnutrition to avoid developing blindness. That's how insane the dominance of some non-government organizations are if they are campaigning for the wrong reason and certainly far away from science. History always serves us interesting examples. The trouble is that we humans are not very good at learning from history and this observation is not just limited to our conversation but I think your example of hornless cattle is really a great example of something I wanted to discuss briefly here next and that is indeed as you say that particular variant which is being engineered into cattle I had the misfortune of seeing a video of what de-horning cattle involves and I will never forget that video until the day I die. This is a naturally occurring variant in the genome of wild cattle which could theoretically be bred into cattle using classical breeding techniques. Of course there are much faster ways which is what you were talking about. Today we have technology which allows us to make such precision engineering that actually the organism which is the outcome of that process is indistinguishable genetically and genomically from a naturally existing variant. Can you comment on this from the perspective of regulation and tracing of these designed organisms which have actually been designed to recapitulate what has evolved in some setting? This is exactly what I was speaking of earlier in the US. The USDA has decided that they would not regulate organisms that are naturally occurring in this way where you could have created that organism by breeding and with the example of the cattle you could do this but it would take 20 plus generations to rebread all of the beneficial traits of being a dairy cow back into that cattle lineage if you've used traditional breeding and crossed them with beef cattle for example. It's unclear why the FDA has gone a different route and decided not to deregulate. These are not transgenic organisms in any way and this is really what most people are most concerned about. It's actually essentially it's identical to nature so you can't tell the difference and we have seen different regulators in different places go different avenues. One is of course the question on have we re-understood all the risks that's certainly an issue in Europe where even in the eggspace gene editing technologies that work inside of the genome are not regulated as identical to nature but they are regulated under the GMO regulation. The other thing in that context is that if you look at current practice the question is is current practice better? You know how maybe you don't how we get mutagenesis going. You use heavy radiation or heavy chemical exposure in order to actually get variation and then you take it from there and then the question is isn't precision breeding if you want to call it that way or precision modification that could occur naturally isn't that the much better and much targeted way to go? I think one of the great ironies the popularity of the non-GMO labels that you see at the grocery store when you wander around, they're on everything they're on salt for goodness sake which doesn't even have DNA so how could it be modified? But you see it on the bottle of ruby red grapefruit juice which is an example of a citrus fruit that was created by this radiation breeding which is as much radiation as you could think of thousands of new mutations emerge and yet these are not considered to be genetically modified or genetically engineered. Your salt comment reminds me of a label which I saw on a packet of sugar which said this is a fat free food which is exactly analogous to what you just described. Kevin? Well the thing about this is it's punishing us for knowing what we're doing and this really speaks to something deep in the human condition and unusually unduly perhaps although that's arguable suspicious of applying technology to living things that is people are more comfortable with this notion that at random most people don't know we bombard our crops with radiation and chemicals in order to mutate them create thousands of mutations that we don't characterize that don't get regulated in anything other than the most cursory way for safety that's okay but going in and doing something where we know exactly what the change is and we're not making any other changes that's not okay that requires extra regulation it doesn't make sense but that's part of the legacy of mistrust so if we want to do differently we need to change our incentives and I think that's why I'm going to push a little bit on you Magdalena you're a moderator in academia publishing in high profile journals such as Nature being the premier journal is everything and if you tell us that we can only publish in Nature if we pre-register our experiments if we say here is what we're going to do and we need to find a community that is interested in the result of this new technology and we can only publish if we do that let me tell you we will we all will and if we want to be moral if we want to see improved consideration of morality and technology development when technology is going to determine the future of our civilization people respond to incentives if you want to behave morally put yourself in a situation in which you have incentives to do so very interesting so I've made a note of this I find your suggestion very interesting so we've had a suggestion of greater transparency increased dialogue with many different stakeholders a take home message from me on Nature to push for more pre-registration of studies which I completely agree with before I let you go however since you started the trend of putting forward suggestions of what should be done I'm going to ask you both as well what would you like to see let's say in the next three years change in terms of regulation legislation technology application and one thing you Beth work on a lot is aspects of conservation which we haven't touched on here would that be perhaps one of the things you the reason that I like thinking about biotechnology and genetic engineering for conservation is I think that people fear it less than they do biotechnology for their food what they're eating and I think we have potential there's a possibility that we can make some progress to be able to communicate the nuances of these new technologies to the public more effectively through conservation and maybe that will feed back then into the agricultural realm the public want new ideas and they want new things but they also want to feel safe obviously and if we can find a way of being effective in showing people that these technologies are not dangerous we're not creating monsters most of us Kevin possibly you think through communication would that be all through communication and transparency isn't that hard because we know that simply explaining to people what we're doing isn't enough if you want people to trust it you need to get them to trust something else they need to trust either us and that trust has to be earned and transparency is one way but you can also get them to trust the process yes but you do that by being effective communicators and storytellers and scientists that people learn to respect and then they'll hope you hope that they can I guess you can take it even one step further when it comes to regulation which for a lot of us if not the majority of us really are black box we open up our regulatory processes when it comes to the registration of new agents and make it a real participative process we invite people in and say hey we don't have anything to hide and we do not only represent it to you we invite you in so be part of the journey form your own opinion find people that help you form your own opinion because that is I think the only way transparency is good making it a participative process is better because you create ownership with the people that are ultimately benefiting from the things that we are doing and in that talk the last thing I would ask for is that we get back to having more courageous politicians because many many times they know better but they don't stand by the stuff that they know in particular in the regulatory area I've seen it happen in Europe where I have conversations where actually members of government tell me we know that technology is good because that is actually bad for my next election and they go against their own regulators so what I would really ask for is to actually have some more brave and courageous politicians out there that stand for the right thing this is exactly the right place to be calling for politicians to stand up and be braver but I think it's clear that the technology we have a lot of confidence in technology is very mature we do know what we're doing we can look to the future in which we will be increasingly modifying organisms including ourselves around us for a number of different purposes but we do need to engage a much greater number of stakeholders including the general public politicians, regulators as well as of course scientists and technologists themselves thank you very much Beth, Bernard and Kevin thank you all and I'm sure that panelists will be here for a few minutes for your questions if you have any remaining thank you very much