WEBVTT - A Genetic Engineer's Perspective on "Designer Babies" 0:00:15.396 --> 0:00:22.796 Pushkin from Pushkin Industries. This is deep background the show 0:00:22.876 --> 0:00:25.836 where we explored the stories behind the stories in the news. 0:00:26.276 --> 0:00:30.476 I'm Noah Feldman. Welcome to this week's program, where we're 0:00:30.476 --> 0:00:34.796 going to talk about gene editing, designer babies, and the 0:00:34.836 --> 0:00:38.716 future of science. These are all topics of importance all 0:00:38.756 --> 0:00:42.116 the time, but they've become more pressing since the announcement 0:00:42.516 --> 0:00:46.836 that a Chinese scientist had actually used Crisper Cast nine, 0:00:47.356 --> 0:00:51.836 the leading cutting edge editing technology, to edit the genomes 0:00:51.876 --> 0:00:55.876 of two embryos to assure that they would not be 0:00:55.956 --> 0:01:00.516 able to be susceptible to the HIV virus. This was 0:01:00.556 --> 0:01:04.316 good for the embryos, but it wasn't necessary scientifically, and 0:01:04.396 --> 0:01:07.596 it's led to lots of intense discussion about whether the 0:01:07.716 --> 0:01:10.916 era of designer babies was too close and needed to 0:01:10.956 --> 0:01:14.836 be headed off by regulation. To discuss these and closely 0:01:14.876 --> 0:01:18.476 related issues were super fortunate to have with us George Church. 0:01:19.356 --> 0:01:21.836 George is the Robert Winthrop Professor of Genetics at Harvard 0:01:21.876 --> 0:01:25.156 Medical School. He also teaches at MIT. He's been a 0:01:25.196 --> 0:01:28.716 central actor in the development of the technologies of gene 0:01:28.836 --> 0:01:33.076 editing and in applying them to the creation of new genomes. 0:01:33.116 --> 0:01:37.836 He sometimes, in fact calls himself a genome engineer. George, 0:01:37.876 --> 0:01:40.316 thank you so much for joining us. It's a great 0:01:40.316 --> 0:01:43.116 pleasure to be here. Noah, let's just start with the 0:01:43.156 --> 0:01:45.676 headline in order to make sense of what it really 0:01:45.716 --> 0:01:49.836 means and whether there are dangerous associated with it of 0:01:49.876 --> 0:01:53.516 the kind that many imagine. We read in the paper 0:01:53.876 --> 0:01:58.196 that Jan Qui, a Chinese scientist, says, or has it 0:01:58.276 --> 0:02:01.516 said about him, that he used Crisper cast nine to 0:02:01.956 --> 0:02:06.476 engineer the DNA of a couple of babies, and that 0:02:06.516 --> 0:02:08.916 they were then subsequently carried to term. That's what appears 0:02:08.956 --> 0:02:12.356 to be new here, and he's been The Chinese government's 0:02:12.356 --> 0:02:14.676 not very happy with him, and he has been under 0:02:14.676 --> 0:02:18.916 house arrest and radio silence more or less since. From 0:02:18.956 --> 0:02:22.916 the standpoint of the state of crisper technology, was there 0:02:22.956 --> 0:02:26.596 anything remarkable about the accomplishment, assuming it was accomplished, or 0:02:26.596 --> 0:02:30.316 is it relatively a trivial step compared to the scientific 0:02:30.316 --> 0:02:32.556 advances that had already been in place? Yeah, I would 0:02:32.596 --> 0:02:36.796 think similar things had been done by other groups, including 0:02:36.876 --> 0:02:40.916 groups in the United States and Oregon on human embryos, 0:02:41.716 --> 0:02:44.396 and even more amazing things had been done on other 0:02:44.476 --> 0:02:50.596 mammalian embryos, including altering dozens of genes. So is here 0:02:50.636 --> 0:02:54.596 the claim was only the altering of onengenee. You know, 0:02:54.636 --> 0:02:58.636 there's some interesting questions about choice of genes. You know, 0:02:58.676 --> 0:03:01.116 one of the things that's challenging in this field is 0:03:01.156 --> 0:03:05.036 picking a gene that even a few other people would 0:03:05.076 --> 0:03:08.556 agree is a good choice of gene, because you know, 0:03:08.596 --> 0:03:13.236 a fair number of genes could be fixed by other methods, 0:03:13.316 --> 0:03:15.716 Like you have to be in in vitro fertilization or 0:03:15.716 --> 0:03:18.276 IVS clinic to do this at all, and if you're 0:03:18.276 --> 0:03:21.116 in that clinic, you could fix it by just IVF 0:03:21.676 --> 0:03:25.196 prenatal genetic testing EGT. So when it goes to question 0:03:25.196 --> 0:03:28.996 of choosing the target of the intervention, what are the 0:03:29.116 --> 0:03:31.196 right criteria or what do you see as the main 0:03:31.236 --> 0:03:33.996 criteria people would consider. I mean, you've mentioned now one 0:03:34.276 --> 0:03:36.516 could you get there by some other means? Could you 0:03:36.556 --> 0:03:39.036 get there without without changing the germ line? But what 0:03:39.076 --> 0:03:41.796 are other criteria that you think would be relevant here? 0:03:42.476 --> 0:03:45.836 So in addition to could you get thereout altering the 0:03:45.836 --> 0:03:49.356 germ line, there's also the criteria of is it a 0:03:49.396 --> 0:03:53.276 net positive for that person or in a public health 0:03:53.276 --> 0:03:58.876 sinse on average on that positive and environmentally dependent. So 0:03:58.916 --> 0:04:03.196 if you're in an environment where everybody gets HIV and 0:04:03.356 --> 0:04:07.636 dies young, and that's a very different environment than or 0:04:07.716 --> 0:04:11.916 nobody gets HIV and China is not ground zero for 0:04:11.996 --> 0:04:14.076 the highest level of HIV in the world, who is 0:04:14.156 --> 0:04:18.436 highly stigmatized there, but you know places in Africa have 0:04:18.596 --> 0:04:21.036 higher incidence of it and it would be better candidates. 0:04:21.396 --> 0:04:24.356 Another one is, you know, is costs is a consideration 0:04:24.716 --> 0:04:26.956 if you want something that's going to be of true 0:04:27.196 --> 0:04:30.596 public health benefit for a disease like this impacts a 0:04:30.636 --> 0:04:34.516 lot of impoverished individuals because you have the alternative is 0:04:35.436 --> 0:04:39.876 drugs or safe sex. There there are a few alternatives, 0:04:39.916 --> 0:04:44.356 none of what you're working perfectly worldwide because a million 0:04:44.516 --> 0:04:47.636 people die for years, it's about two percent of all 0:04:47.716 --> 0:04:50.436 human deaths. So to claim that this is a solved 0:04:50.436 --> 0:04:53.996 problem is just as Naives saying that this is the 0:04:54.036 --> 0:04:56.436 only way to solve the problem. Right, it's not a 0:04:56.476 --> 0:04:59.636 self problem in real world descriptive terms, even though in 0:04:59.676 --> 0:05:04.876 principle it could be solvable. So what about the criterion 0:05:04.916 --> 0:05:11.436 that asks whether something is presently an immediate threat to 0:05:12.036 --> 0:05:15.556 either the embryo or the local population as opposed to 0:05:15.676 --> 0:05:20.716 offering some background improvement for the potential person who might 0:05:20.716 --> 0:05:23.676 come to be created, or for the environment more generally, 0:05:23.716 --> 0:05:26.116 does that seem like a meaningful difference to you? And 0:05:26.156 --> 0:05:28.676 I just to show that I'm why I'm asking that question. 0:05:29.036 --> 0:05:32.516 It goes to the broader societal fear about what are 0:05:32.596 --> 0:05:36.676 sometimes called designer babies, you know, babies who are who 0:05:37.436 --> 0:05:41.516 might have their genomes edited to give them some advantage, 0:05:41.676 --> 0:05:43.436 which could be a health advantage to begin with, but 0:05:43.476 --> 0:05:46.476 could also be other kinds of advantages, whether in esthetics 0:05:46.556 --> 0:05:49.356 or intelligence, or athletics or what have you. I think 0:05:49.396 --> 0:05:55.596 this is something that is very interesting entanglement of concerns. 0:05:56.796 --> 0:06:02.716 So the concerns are that we will create a monoculture 0:06:03.756 --> 0:06:07.316 number one, where everyone is the same, the way that 0:06:07.356 --> 0:06:11.276 you might have a you know, many square kilometers of 0:06:11.516 --> 0:06:17.196 identical crops. The second is that it will be inequably distributed, 0:06:17.236 --> 0:06:19.076 in no words, that some people have some people don't. 0:06:19.076 --> 0:06:22.236 That's a very different concern than you don't want anybody 0:06:22.236 --> 0:06:24.636 to have it, as you want everybody to have it, okay, 0:06:25.196 --> 0:06:27.116 you know. A third one is you could make a 0:06:27.196 --> 0:06:31.676 mistake that it could be a very popular fad, but 0:06:31.756 --> 0:06:34.556 it was a mistake that has long term consequences, either 0:06:34.636 --> 0:06:36.676 for the people who had it or the people who 0:06:36.716 --> 0:06:42.596 didn't get it. There could be stigmatization issues direction. Yeah, 0:06:42.596 --> 0:06:45.116 it could beat not to have had the intention or 0:06:45.196 --> 0:06:47.076 to have absolutely and there are a few more things 0:06:47.076 --> 0:06:50.156 that get tangled up here. Sometimes it's phrased as blondere 0:06:50.196 --> 0:06:53.596 blue eye, which doesn't make any sense at all. You know, 0:06:53.636 --> 0:06:57.476 that's not a public health threat. It's unlikely to have 0:06:57.636 --> 0:07:01.116 long term consequences even if it were a monoculture. It's 0:07:01.156 --> 0:07:04.716 not a monoculture that threatens society if it's not. But 0:07:04.756 --> 0:07:06.796 it's not an accident that people use that as the example. 0:07:06.836 --> 0:07:09.756 What they're invoking when they say that is there associating 0:07:10.236 --> 0:07:14.476 genetic engineering with the eugenics movement of the eighteen eighties, 0:07:14.636 --> 0:07:17.556 nineties or early twentieth century, which was not only by 0:07:17.556 --> 0:07:19.916 any stretch of imagination, popular in Germany but all over 0:07:19.956 --> 0:07:22.156 the world, including very much the US. Yeah, the United 0:07:22.196 --> 0:07:24.356 States kept doing it long after World War Two. I 0:07:24.356 --> 0:07:27.676 think it was into early nineteen seventies, and so eugenics 0:07:27.676 --> 0:07:30.156 though this wasn't the only line of eugenic thinking at all, 0:07:30.196 --> 0:07:33.516 but it married itself up at least in the European context, 0:07:33.636 --> 0:07:37.396 even you know now long discredited racialized theories. That's what 0:07:37.436 --> 0:07:42.796 people mean, I think when they say absolutely absolutely. And furthermore, 0:07:42.836 --> 0:07:46.676 there's all kinds of body image issues, shaming and so 0:07:46.716 --> 0:07:49.916 forth the en conjures up, which some of which are 0:07:49.996 --> 0:07:54.316 racially independent. You know that within a race you'll have 0:07:54.796 --> 0:08:01.036 you know, obesity shaming and many other features that determine 0:08:01.436 --> 0:08:06.716 your status of society, your socio economic status, enhance your 0:08:06.716 --> 0:08:11.716 health status. So even though it's not health explicitly, that 0:08:11.916 --> 0:08:15.596 has ramifications in that direction. So some of those can 0:08:15.636 --> 0:08:18.116 be addressed. So you know, equitable distribution, we could bring 0:08:18.116 --> 0:08:22.036 down the price as we have for various technologies like smallpox. 0:08:22.156 --> 0:08:25.996 Vaccine has made it extinct and so it's basically free now. 0:08:26.396 --> 0:08:30.116 So there are technologies that come down pretty quickly to zero, 0:08:30.836 --> 0:08:32.996 so that you can take some of these things at 0:08:33.036 --> 0:08:35.316 least not necessarily off the table, but you can put 0:08:35.316 --> 0:08:38.076 them aside in a separate category. But another one is 0:08:38.116 --> 0:08:41.956 that you could create It falls a bit in the 0:08:42.276 --> 0:08:46.836 equitable distribution, but you could create people that it's not 0:08:46.876 --> 0:08:51.036 necessarily racial. It's just a new capability right now, most 0:08:51.076 --> 0:08:54.316 new capabilities. I believe that the human population at present 0:08:54.516 --> 0:08:59.036 doesn't have right, and that enhancement is something that we 0:08:59.076 --> 0:09:03.916 should feel very familiar with because we are enormously enhanced 0:09:03.916 --> 0:09:07.676 relatives to our enhancestors. We're not actually fearful of enhancement 0:09:07.716 --> 0:09:09.556 as far as I can tell. But that do you 0:09:09.556 --> 0:09:12.156 mean incrementally enhanced? I mean so if you look at 0:09:12.196 --> 0:09:14.716 I don't know the fastest one hundred meter dash times, 0:09:14.756 --> 0:09:16.876 they're getting faster, though presumably they're also going to a 0:09:16.956 --> 0:09:19.716 mutual limit. But I can beat one hundred meter dash 0:09:19.836 --> 0:09:23.236 person any day in my jet. But that's a capacity 0:09:23.396 --> 0:09:27.596 enhancement that is not embodied. We have developed tools that 0:09:27.716 --> 0:09:30.196 enable us to do things, but they're not quite the 0:09:30.276 --> 0:09:33.316 same as being incorporated. It's an interesting question why we 0:09:33.396 --> 0:09:36.436 treat them differently because they are hurtable in a certain 0:09:36.476 --> 0:09:41.996 sense culturally culturally inheritable. But culture is an inheritance. I 0:09:42.076 --> 0:09:46.956 consider many ways more threatening and more rapid than DNA 0:09:47.036 --> 0:09:50.596 obsessed inheritance. You know, it's much more likely that my 0:09:50.756 --> 0:09:53.996 daughter will have my cell phone then she will have 0:09:54.076 --> 0:09:59.916 my facial features. Thankfully, so we get hung up on 0:10:00.396 --> 0:10:05.316 this sort of DNA obsession. If they actually knew less science. Oddly, 0:10:05.716 --> 0:10:08.876 we might draw less of a line between these, Right, 0:10:09.116 --> 0:10:11.436 we didn't know how we inherited these things. We didn't 0:10:11.436 --> 0:10:15.916 really understand culture and technology and DNA they would kind 0:10:15.916 --> 0:10:18.876 of look similar. Oh then it's your fault for helping 0:10:18.956 --> 0:10:21.076 us understand it, so well. Sorry, Well, you're making a 0:10:21.116 --> 0:10:26.556 really interesting observation that culture has a wide range of effects. 0:10:26.876 --> 0:10:29.756 It's in some broad sense heritable. But I want to 0:10:29.756 --> 0:10:33.716 add that it's also subject to the full range nearly 0:10:33.756 --> 0:10:36.556 every one of the serious risks that you described with 0:10:36.636 --> 0:10:40.676 respect to genetic editing. In fact, in many cases, the 0:10:40.716 --> 0:10:42.956 way we come up with our fear is we look 0:10:42.996 --> 0:10:46.436 at the distortions or the injustices produced by culture and 0:10:46.516 --> 0:10:49.156 we say, well, oh boy, you know, genetic editing might 0:10:49.196 --> 0:10:52.836 have the same effect, so you know, societal inequity. Check 0:10:52.956 --> 0:10:56.236 on that. Right. It can also these target effects which 0:10:56.236 --> 0:10:59.156 we haven't yet gotten to. But you know, that's broadly speaking, 0:10:59.516 --> 0:11:01.556 the idea that if we edit one thing, there will 0:11:01.556 --> 0:11:04.316 be unforeseen effects somewhere else in the genome. Check on that. 0:11:04.436 --> 0:11:06.556 In culture, all the time, we improve one thing and 0:11:06.596 --> 0:11:11.236 we make other things much worse, so certain consequences. Check 0:11:11.276 --> 0:11:14.276 on that. Go ahead, Yeah, I mean the early adopters 0:11:14.276 --> 0:11:18.596 sometimes they're more exposed to the unintended consequences the off targets, 0:11:18.636 --> 0:11:22.356 and so they're essentially be signing up with their extra 0:11:22.796 --> 0:11:26.716 dollars to become the first guinea pigs. So it seems 0:11:26.716 --> 0:11:31.476 like there's some meaningful debate within the scientific community about 0:11:31.476 --> 0:11:36.756 how concerned we should be that particular desirable genetic edits. 0:11:36.756 --> 0:11:38.956 This is assume it's we're avoiding a disease, that there's 0:11:38.996 --> 0:11:40.276 no other way to avoid it, that we fit your 0:11:40.316 --> 0:11:43.796 other criteria. There seems to be some disagreement between one 0:11:43.836 --> 0:11:47.756 campus scientists who say, because we don't know for sure 0:11:47.796 --> 0:11:50.676 what the off target effects might be of a given intervention, 0:11:50.916 --> 0:11:55.396 we should proceed extremely slowly and carefully, and another campus scientists, 0:11:55.436 --> 0:11:58.436 again this is a continuum, who seem to say, we 0:11:58.516 --> 0:12:01.396 can measure off target effects like we can measure anything else, 0:12:01.476 --> 0:12:04.556 and if we reach the point that off target effects 0:12:04.676 --> 0:12:08.556 are less likely to occur from a genetic edit than 0:12:08.596 --> 0:12:12.076 they are in nature, then it's absurd to be so 0:12:12.236 --> 0:12:14.556 worried about it. And I'm fascinated by this question because 0:12:14.676 --> 0:12:16.556 as a layman, I have no idea how to go 0:12:16.596 --> 0:12:20.836 about answering it right. Well, the probably the most glib 0:12:20.956 --> 0:12:24.276 answer to it is this is the responsibility of food 0:12:24.316 --> 0:12:26.756 and drug administration in the United States and equivalence in 0:12:26.796 --> 0:12:31.596 other countries. And it happens with every single technology to 0:12:31.676 --> 0:12:34.596 something expose. Certainly the medical technologies were the medical devices, 0:12:34.716 --> 0:12:39.476 or molecule drugs or protein drugs. Every category has all 0:12:39.556 --> 0:12:44.596 target effects which are physiological, so you need to do 0:12:44.636 --> 0:12:47.236 as much as you can theoretically, followed by as much 0:12:47.276 --> 0:12:50.876 as you can with animal models or human cells in culture, 0:12:51.596 --> 0:12:55.076 and then you move on very cautlessly to one person 0:12:55.476 --> 0:13:00.356 to do phase one toxicity and then efficacy, and then 0:13:00.636 --> 0:13:02.836 make sure that it's really ready for primetime, and you 0:13:02.876 --> 0:13:05.516 scale up the size of the cohort cautlessly so you 0:13:05.956 --> 0:13:09.036 expose the minimum number of people to risk for good 0:13:09.156 --> 0:13:14.236 theoretical reasons. So this combination of theory and testing cautiously 0:13:14.556 --> 0:13:18.436 is what protects us from all our new technologies. Is 0:13:18.476 --> 0:13:22.956 the timescale particularly challenging in the case of genetic editing 0:13:22.996 --> 0:13:25.636 because you're editing an embryo, but it might be that 0:13:25.676 --> 0:13:28.596 the off target effect doesn't express itself, you know, typically 0:13:28.676 --> 0:13:30.836 until much later in life, so that it might take 0:13:30.996 --> 0:13:33.556 much longer to find out what potential left target effects are. 0:13:33.996 --> 0:13:37.036 Absolutely you know, preventive medicine is a nice buzzword, but 0:13:37.076 --> 0:13:39.876 it's very hard to develop powerful preventive medicines because you're 0:13:39.916 --> 0:13:43.156 testing them on people that are healthy. And it's not 0:13:43.196 --> 0:13:49.996 restricted to embryo editing, its fetal surgery with actual microscalpels 0:13:49.996 --> 0:13:54.356 of things and monus sickness drugs like Blood of Mind, 0:13:54.436 --> 0:13:58.756 which which failed disastrous effects. Extreme caution is required when 0:13:58.756 --> 0:14:02.116 you're dealing with prevented in medicine. For example, you take 0:14:02.196 --> 0:14:07.916 chemotherapy as an adult woman, you could be affecting your 0:14:08.716 --> 0:14:12.836 German line in ways that you also won't see until 0:14:13.236 --> 0:14:15.356 your babies are born, and maybe their babies are born. 0:14:15.556 --> 0:14:18.196 Right used sub interesting words now, which I think are 0:14:18.316 --> 0:14:20.076 maybe they are characteristic give you, although I don't think 0:14:20.076 --> 0:14:22.676 of them as characteristic of you, namely the words extreme caution. 0:14:23.236 --> 0:14:25.796 So I want to ask you about your headge about 0:14:25.796 --> 0:14:29.676 the FDA. Of course, institutionally we assign those decisions in 0:14:29.716 --> 0:14:34.196 our democracy to the FDA, but that doesn't necessarily tell 0:14:34.236 --> 0:14:37.996 us what criteria the FDA ought to apply, or, more 0:14:37.996 --> 0:14:40.556 to the point, how cautious the FDA should be, or 0:14:40.556 --> 0:14:43.196 how risk taking the FDA should be. I mean, real 0:14:43.276 --> 0:14:47.316 human beings. Ideally, scientists and statisticians sitting in the FDA 0:14:47.436 --> 0:14:49.356 have to make these decisions on the basis of what 0:14:49.436 --> 0:14:51.796 data is known. So I guess what I wanted to 0:14:51.836 --> 0:14:53.716 ask you is, if I'm right that there is this 0:14:53.796 --> 0:14:56.796 continuum of how much risk we should take in the 0:14:56.796 --> 0:15:00.116 scientific community around gene editing, where do you fall on 0:15:00.156 --> 0:15:02.836 that continuum? The words extreme cautions sort of put you 0:15:03.076 --> 0:15:05.596 sound like they put you among the Really, let's not 0:15:05.676 --> 0:15:10.396 rush this side. I think tend to fall on the 0:15:11.196 --> 0:15:13.236 I worry about everything, and I want everybody else. I 0:15:13.236 --> 0:15:16.556 don't want to reassure people necessarily, I'm not in a 0:15:16.596 --> 0:15:20.076 big rush for most things, even aging reversal, even though 0:15:20.116 --> 0:15:22.636 I'm I'm not in a big rush show, so don't 0:15:22.636 --> 0:15:25.516 worry about it. I'm not in a big rush. But 0:15:25.596 --> 0:15:28.556 that said, I I don't fall into the camp of 0:15:28.836 --> 0:15:30.676 we should put as many barriers in the way as 0:15:30.796 --> 0:15:34.316 possible so that it never happens, or be so vague 0:15:34.356 --> 0:15:36.756 about it that we can never be satisfied as to 0:15:36.836 --> 0:15:39.916 what the criteria are for letting it go forward. And 0:15:40.276 --> 0:15:42.636 it is a continuum, and I think the FDA does 0:15:42.636 --> 0:15:45.476 an admirable job of prioritizing so if you have a 0:15:45.596 --> 0:15:48.156 very serious disease is going to kill you tomorrow, they 0:15:48.196 --> 0:15:52.596 have a different threshold. Then if you have a healthy 0:15:52.636 --> 0:15:55.956 baby who has every expectation of being healthy, and you're 0:15:55.996 --> 0:15:58.396 going to give it something that might extend its life 0:15:58.396 --> 0:16:02.036 by ten years eight years from now, that barrier is 0:16:02.156 --> 0:16:05.436 very hard to get permission to do that study. And 0:16:05.596 --> 0:16:09.676 rightly so, there's a line of thought that says, using 0:16:09.756 --> 0:16:13.116 the FDA as one pole of you describe pretty admirable 0:16:13.276 --> 0:16:15.996 cost benefit weighing, and then on the other side, looking 0:16:16.036 --> 0:16:19.156 at China, where at least in one instance, there seems 0:16:19.156 --> 0:16:22.756 to have been a lot of risk taking, it says, look, 0:16:22.756 --> 0:16:24.236 it's all well and good to say that the FDA 0:16:24.276 --> 0:16:27.316 should be cautious, but out there in the world, outside 0:16:27.356 --> 0:16:30.996 the reach of more cautious and maybe typically democratic although 0:16:31.036 --> 0:16:33.836 that doesn't have to follow governments, we're going to get 0:16:33.876 --> 0:16:36.196 lots of innovation, lots of risk taking, and that we'll 0:16:36.196 --> 0:16:40.036 fall behind if we listen to the FDA or we 0:16:40.076 --> 0:16:42.996 allow the FDA to be cautious, or alternatively, that says 0:16:43.236 --> 0:16:45.396 we ought to be very aggressively going out and trying 0:16:45.396 --> 0:16:49.196 to export our own limitations by pressuring foreign governments to 0:16:49.276 --> 0:16:53.236 make sure that they crack down to a greater extent. 0:16:54.036 --> 0:16:56.076 How do you think about that phenomenon? The science is 0:16:56.076 --> 0:17:00.156 increasingly globalized, as prices come down, as scientists train across borders. 0:17:00.796 --> 0:17:02.916 There's no in principal reason that a country with a 0:17:02.996 --> 0:17:07.476 reasonable infrastructure scientific infrastructure can't make all kinds of innovations 0:17:07.956 --> 0:17:11.316 under a very different regular environment. Well, and first of all, 0:17:11.316 --> 0:17:13.756 I would say that the Chinese FDA to c FDA 0:17:14.316 --> 0:17:17.476 is very similar. I think they have a similar risk profile. 0:17:18.116 --> 0:17:20.716 I think their government whether you want to call it 0:17:21.156 --> 0:17:26.276 capital hyper capitalistic, or less than perfectly democratic, it doesn't 0:17:26.316 --> 0:17:29.356 really matter. The point is they are capable and often 0:17:29.436 --> 0:17:32.156 do crackdown better than we do. So in the United 0:17:32.196 --> 0:17:35.756 States it's very hard to interfere with the industry, not 0:17:35.836 --> 0:17:39.076 because they run Congress or anything, but because there's an 0:17:39.076 --> 0:17:43.796 obsession with freedom. And in the Chinese government they can 0:17:43.836 --> 0:17:46.476 crack down on things that are unsafe in ways that 0:17:46.516 --> 0:17:49.596 are very difficult to do otherwise. So for example, cleaning 0:17:49.676 --> 0:17:52.596 up Pijing for the Olympics, and that's something that I 0:17:52.636 --> 0:17:56.556 don't think we could have done. And they're very technocratic too. 0:17:56.556 --> 0:17:59.516 I meant I'd heard that a huge faction, maybe eighty 0:17:59.516 --> 0:18:03.996 percent of their top politicians have degrees in science for engineering, 0:18:04.396 --> 0:18:07.236 and not because they're failed scientists or engineers, but because 0:18:07.276 --> 0:18:10.156 as politicians they went back and got those degrees because 0:18:10.156 --> 0:18:12.636 I felt it was important for understanding the issues. That 0:18:12.836 --> 0:18:15.236 is so far from where we are. We're more in 0:18:15.236 --> 0:18:18.036 a culture of if I need some facts, I'll give 0:18:18.076 --> 0:18:20.796 them to you, right. You know, this is a question 0:18:20.836 --> 0:18:24.276 that I've been very curious to ask you today. To 0:18:24.436 --> 0:18:30.436 be a cutting edge researcher as you are, it's also 0:18:30.636 --> 0:18:32.556 perhaps expect it is too strong a word, but not 0:18:32.676 --> 0:18:37.636 surprising when one also holds lots of patents and starts 0:18:37.636 --> 0:18:41.156 companies that develop those patents or that try to develop 0:18:41.196 --> 0:18:46.836 those patterns. So the entrepreneurial side seems to coexist very naturally, easily, 0:18:47.356 --> 0:18:52.956 almost normatively with being a leading scientist. How do you 0:18:53.036 --> 0:18:55.396 think about that relationship, because that's been an important part 0:18:55.396 --> 0:19:00.076 of your practice. So if you have an invention where 0:19:00.076 --> 0:19:05.156 you've gone from the vast cloud of scientific discovery to 0:19:05.436 --> 0:19:08.196 something that you think might be useful, it's not sufficient 0:19:08.236 --> 0:19:11.796 to write up academic ivory tower paper and hope for 0:19:11.836 --> 0:19:15.756 the best because nobody's going to use it. You know, 0:19:15.836 --> 0:19:21.396 sometimes there's some concern that capitalism in that form will 0:19:22.036 --> 0:19:26.236 infect us, you know, that affects us by manipulating us, 0:19:26.396 --> 0:19:30.236 or as market scientists entrepreneur cannot be as pure as 0:19:30.236 --> 0:19:33.676 the scientist who's received grants and does basic research. I 0:19:33.676 --> 0:19:36.756 think a lot of people fear that. Yeah, and they 0:19:36.796 --> 0:19:38.916 fear that even after the sign us steps away and 0:19:39.036 --> 0:19:41.556 goes back the Ivory Tower, a company that has been 0:19:41.596 --> 0:19:44.436 created as a life of its own, and it will 0:19:44.476 --> 0:19:48.116 be motivated to use marketing and advertising and operative lobbying 0:19:48.516 --> 0:19:52.636 to give us our opinion, run listen to us. And 0:19:52.676 --> 0:19:55.676 I think these are all valid things. On the other hand, 0:19:56.236 --> 0:19:59.316 if you're talking about companies going rogue, there's certain challenges 0:19:59.396 --> 0:20:03.676 to that, meaning that the CEO reports the bord of 0:20:03.756 --> 0:20:06.276 directors and to the stockholders in general, and so to 0:20:06.316 --> 0:20:12.716 do something blatantly irresponsible result in a huge public relations problem, 0:20:12.876 --> 0:20:16.916 your stots value and rash and so forth. While an 0:20:16.996 --> 0:20:22.556 academic with tenure who has acted responsible, they can go 0:20:22.596 --> 0:20:24.956 off and do whatever they want. They don't really report 0:20:24.996 --> 0:20:27.876 to anybody. So there's a danger in other words, also 0:20:27.916 --> 0:20:30.316 in having the pure scientists who can do whatever he 0:20:30.356 --> 0:20:32.596 wants or she wants, and it's not responsible at all. 0:20:33.156 --> 0:20:36.516 So let's take this then back to the question of 0:20:36.556 --> 0:20:41.996 the future of Crisper or other similar editing technologies in 0:20:42.116 --> 0:20:45.756 terms of the state of the science. Now, how credible 0:20:45.996 --> 0:20:51.676 is it that existing editing technologies could, if they were 0:20:51.676 --> 0:20:58.196 allowed to by regulators, actually make interventions at population level 0:20:58.196 --> 0:21:03.596 in a significant way. Are there actually traits enough traits 0:21:03.676 --> 0:21:08.596 that matter that are addressable by editing one or two 0:21:09.156 --> 0:21:12.116 genes or a handful of genes to actually make it 0:21:12.116 --> 0:21:14.636 make an impact. How much of this is science fiction 0:21:14.676 --> 0:21:16.756 fantasy and how much of this is within the reach 0:21:16.796 --> 0:21:20.716 of reality. So there's an interesting phenomenon. I would say 0:21:20.996 --> 0:21:25.516 a huge fraction of my colleagues would reassure you that 0:21:25.916 --> 0:21:29.156 human genetics is so complex that we are so far 0:21:29.196 --> 0:21:31.156 away we don't need to worry about it. I think 0:21:31.156 --> 0:21:33.316 that is false to some of them. I think that 0:21:33.436 --> 0:21:39.036 is false reassurance. So I think that we have sort 0:21:39.076 --> 0:21:44.476 of the textbook cases of complex genetics or things like height. Right, 0:21:44.876 --> 0:21:48.036 thousands of genes involved, possibly all the genes are involved, 0:21:48.756 --> 0:21:51.276 and they each have a very tiny effect along with 0:21:51.396 --> 0:21:54.796 hundreds of environmental effects. You know, why is it over 0:21:54.836 --> 0:21:57.876 the generations we've gotten taller and tallerance better nutritions. So 0:21:58.636 --> 0:22:03.636 this seems hard to predict, much less to manipulate. And 0:22:04.036 --> 0:22:06.636 when your colleagues just to flush out the argument for 0:22:06.996 --> 0:22:09.636 listeners when they say nothing to worry about, they often 0:22:09.836 --> 0:22:12.516 do use height and they say, well, look, if we 0:22:12.636 --> 0:22:15.076 know right now that there are four or five hundred 0:22:15.316 --> 0:22:17.676 genes involved in just producing a time percentage of the 0:22:17.756 --> 0:22:20.396 variants right in thousands to get you to the whole variety, 0:22:20.836 --> 0:22:23.076 we're never, or at least not in the foreseeable future, 0:22:22.956 --> 0:22:25.076 are going to be able to edit all of those 0:22:25.236 --> 0:22:28.276 different locations. So therefore, you know, don't worry your pretty 0:22:28.316 --> 0:22:31.116 little head about it, or that's what they say to me. Sore. 0:22:32.556 --> 0:22:35.116 There's three things wrong with that. One is, there are 0:22:35.236 --> 0:22:38.796 single genes that are so impactful that even though in 0:22:38.796 --> 0:22:42.756 the natural population they hardly add anything to it, in 0:22:42.796 --> 0:22:46.516 the medical situation, they have a huge impact, in particular 0:22:46.556 --> 0:22:51.676 for height. There's about seven different medical situations where physicians 0:22:51.716 --> 0:22:54.836 and patients want to do something about height. It isn't 0:22:54.836 --> 0:22:58.516 necessarily because they're genetically defective, and it's some other reason, 0:22:59.076 --> 0:23:02.036 And the answer is one gene. One gene product was 0:23:02.156 --> 0:23:05.916 somatotropin or sometimes called growth hormone. To me, that just 0:23:06.596 --> 0:23:10.596 really nails the counter arguments. So the counter argument is 0:23:10.716 --> 0:23:13.716 the geneticists who don't want you to worry, say there's 0:23:13.756 --> 0:23:16.036 so many different genes they're involved, and you naturally right, 0:23:16.076 --> 0:23:17.636 And you say, well, that might be true naturally, but 0:23:17.676 --> 0:23:19.916 that doesn't mean there isn't an intervention we could make 0:23:19.996 --> 0:23:22.836 exactly on a particular gene that would actually have the 0:23:22.876 --> 0:23:29.956 effect of overshadowing overshadowing the natural variations. So, in other words, 0:23:29.996 --> 0:23:33.996 and it's a mistake to reason from natural variation to 0:23:34.516 --> 0:23:38.076 the capacities of technological intervention exactly. And this is not 0:23:38.156 --> 0:23:40.956 an argument, and this is not hypothetical, because there are 0:23:40.996 --> 0:23:44.956 seven different so called diseases or medical treatments that are 0:23:44.956 --> 0:23:47.916 approved and are in routine use to involve this one 0:23:47.956 --> 0:23:52.716 genes a metatropa. Second, they'll say, oh, we'll have unintended consequences. Well, 0:23:52.756 --> 0:23:56.516 the fact is in medicine we always have unintended consequences. 0:23:56.676 --> 0:23:59.596 We almost always deal with them. We just say the 0:23:59.636 --> 0:24:02.516 benefits outweigh the risks. So that's an ethical argument that 0:24:02.516 --> 0:24:05.076 they make. That The first argument is a don't worry 0:24:05.196 --> 0:24:08.396 because it's not going to be practical to engage in 0:24:08.436 --> 0:24:11.596 these kinds of systematic edits. This argument set is the 0:24:11.876 --> 0:24:14.836