What Embryo Selection Means for Humanity - Dr Jonathan Anomaly

I've been advising you guys now for ages and I think I became convinced that this could be a technology for good probably ever since our first conversation a few years ago now. >> Few years ago. Yeah. >> Why do a lot of people still have such an issue with embryo selection do you think? >> Um let's see. There's probably a few issues. One is it's still a new technology. any new technology that hasn't been fully explained to the public, even to doctors, is going to have some, I think, justifiable skepticism. Um, another reason is people worry about tinkering with the human genome, which we're not doing. But people, um, often, I suppose, confuse embryo selection with gene editing, right? So, what we're doing, um, the company Herasite is when women do IVF, they they can already get a bunch of different genetic tests. They could test for Down syndrome, that's called annuployy. They can test for single gene disorders, that's PGTM, pre-implantation genetic testing for monogenic conditions. We're just doing polygenic conditions. All we're doing is revealing more information about the the natural genetic variation that exists in your embryos and letting you choose which one to implant. But when we explain that to people, sometimes they think that what you're doing is you're adding new genes or you're editing the existing genes. And so I think they worry about that. So what's going on? How much do we know about the genome? Um what are you doing to tinker with it? But in fact, we're not tinkering with anything. So that's probably the main reason people worry. But Scott Alexander did a great blog post on this. He had this wonderful example. He says, "A woman goes in for IVF. She produces 10 embryos. The usual technique for deciding which of these 10 embryos to implant is for a doctor to look them over and see which one looks generally the most normally shaped and healthiest. Is this right?" >> It is. And it's not that there's no correlation whatsoever between, let's say, the morphology or the shape of the embryo and its viability, but there's probably not a huge correlation. >> Right. But my my point here is that there is already if you're doing IVF, and I think between sort of 1 and 3% of babies in the US are born through IVF at the moment, sort of. >> Yeah, I think it's at least a few percent. In Denmark, it's 10%. So, >> right. So you're going through IVF and currently if you do IVF you have this batch of let's say maybe 10 fertilized embryos. Somebody's already eyeballing them using some kind of scrutinous like is is it eugenics to look at the one that looks the roundest or healthiest? >> Yeah. That has the fewest. And uh he sort of finishes the example off and he says this time the doctor tells the intern to make a decision. The intern chooses embryo number five, but a few hours later, the doctor gets nervous, decides to double check, disagrees with the intern's assessment, and picks embryo number seven. Embryo 7 gets implanted, and the woman gives birth to a healthy baby child. Like, that is what we're talking about here, but just with way less information. >> Yeah. Although to to steal me on the other side, I mean, I think what they're worried about is we're taking away some of the mystery of childbirth. So there is something you know of romantic about meeting somebody and you know having sex the natural way and having kids the natural way and I think what people worry about is every step along the way of you know you're selecting your partner or your sperm or egg donor and then you're selecting an embryo and there all these dimensions you're selecting on somehow like removing romanticism. But the truth is if you have you know a really bad disease in your family schizophrenia, Crohn's disease etc. All we're really doing is saying, "Look, there's a set of embryos. As you said, there's already a morphological score that that's being given to them. This one's more likely to be viable, less likely." And we're just revealing more information. It's just it's the kind of information people really want >> specifically to minimize disease. And of course, the the controversial one that's not controversial in every part of the world is intelligence. And of course, we can talk about that, but that probably also scares some people a little bit. The Harvard HMS study says 70 75% of Americans support embryo screening for disease and about 40% for intelligence. So there's a pretty big gap there, almost double the acceptance. Uh talk to me about the difference between screening for disease and screening for traits beyond disease, not negative versus plus positive. >> Right. Yeah. Yeah. And it's interesting because if you do the same study in Singapore and it has been done, it's about the same. It's it's it's equal. So people equally support screening against disease and screening in favor of psychiatric traits including intelligence or low risk of various psychological disorders. So what I like to say is both the winners and the losers of World War II um basically took on a set of taboss about genetic explanations especially for the trait that makes us most human which is which is our brain intelligence. Um, and I think those who were sort of outside of that, you know, Germany, the United States, England, etc., those in Asia especially, and South Asia in particular, they just don't seem to draw this distinction between selecting in favor of a positive trait and selecting against a negative trait like like a disease trait. And so I think what's going on here is there's a set of taboss after World War II. They arose at least in part because of the eugenics programs in Germany and this idea that we could rank humans by their relative worth and the worth was never in terms of I don't know how tall you know Swedes are versus banttos are or something. It was how smart they are or how creative they are and those are all sort of things that have to do with the mind. And so I think that there's this kind of this mysterious taboo around mental traits. I don't think it's deserved. I think we can understand the genetics of mental traits just like we can bodily traits, but that probably explains the distinction where some people are uncomfortable selecting for intelligence or against mental health disorders, but they're perfectly fine selecting against diabetes or Crohn's disease. So, >> what is the different is it a more of a sense a judgment on who you are on a a value of your worth? >> I think so. That's probably exactly the right answer. I mean, what what distinguishes you from another person? I mean, we do look at looks and strength and, you know, how fast you run and all of that, but what really distinguishes you, your friends, you know, the people you love and so on, it's it's the mind more than the body. >> And so, when you think about it, I mean, as as people decay, as they get older, maybe they have Alzheimer's degree disease or something like that, and we say, you know, the person is starting to fade away because their mind is. And so I think we attach moral judgments and and that sort of thing with mental traits more than than physical. >> Yeah. It's it's an interesting challenge that people people do lay an awful lot at the feet of what's the landscape of this person's mind. And you're right, if somebody ages and becomes a little bit more forgetful or scenile, they feel less like themselves, right? >> So yeah, there is this sense of self. It's the soul being portrayed through your behavior and your actions and [snorts] stuff like that. So, what what do you say about the slippery slope toward eugenics? Like, this is a a term that gets tossed around a lot. And then I've heard you use the word liberal eugenics, whatever that means. >> Yeah. >> How do you come to how do you ensure that this doesn't end up being just 1944 all over again? >> Uh, well, I'm not wor really worried about the terms that we use, whether it's eugenics or genetic enhancement or genetic selection. Um, I think what people worry about, of course, is government control of these kinds of reproductive technologies or maybe the social pressure that you would feel if everyone else was using it and then you would feel some pressure >> to use it as well. I think there's just a big distinction we need to draw between individuals making choices informed choices in particular to reduce disease risks among their kids and and governments forcing people to to do these kinds of things. This is why I don't know there's an interesting trade-off here between people worry about genetic inequalities. We've talked about it before. Maybe if if only the rich, for example, for a generation or two could afford to use these technologies, there would be some genetic gaps that would increase between, you know, the really bright and and the not so bright and that sort of thing. And one obvious solution to that is governments might, you know, force insurance companies to cover it or subsidize this technology. And I think that's true. We could sort of ensure that there's more equality by doing that. On the other hand, there's a lot of people who don't like technology like this. And I wouldn't want governments to to basically redistribute their income in [clears throat] such a way that other people, you know, got subsidies to do this. And so I think there's this trade-off between, >> you know, governments getting more and more directly involved and and equality, which in that case I tend to opt against equality um and I worry less about equality and more about individual choice and information because the more we try to solve >> the whatever kinds of gaps we get between people because of their choices, the more you're going to have to use governments to solve it, right? And that will bring you more toward kind of coercive eugenics rather than against it. M what what is your answer to the concern people have about rich people being able to have smarter, taller, better looking kids? Uh further worsening the gap. The not only is the inequality now wealth, the inequality is now genetic. >> Yeah. Well, part of the wealth inequality already is of course genetic. We already have strong assortative mating as you know and and we've talked about this as well, but intelligence is one of the main traits that people assortively mate over height, intelligence, athleticism. So I think um you know what we're going to get is we are we're already getting more inequalities along various dimensions and this could ramp it up a little bit but I think in a generation or two you know what can embryo selection get you it can get you a few points in terms of IQ it could get you a couple inches maybe for height but it's not going to lead to dramatic inequalities look over a thousand years if we had embryo selection plus you know IVG which we can talk about gene editing that sort of thing you know the world is going to be a very different place. I think people are going to go in lots of different directions and different states will have different solutions to this sort of thing, right? So some governments probably will, you know, enable people to use this if they can afford it. Others will have a more libertarian approach. So I don't really worry about that too much. What I would worry about is governments really directly controlling the technology. >> And I mean I can add, you know, in the Middle East, um, governments already cover, they already subsidize a lot of genetic testing. So, it's not really that big of a deal to necessarily just cover genetic testing. What is a big deal is if you're covering a broader and broader swath of this and you're forcing everyone else to pay for it. And so, that's >> okay. Just just to put it into language that I can understand, what you're suggesting is uh if only the rich people can afford it, that means that there is an unfair advantage being given to the rich people. >> Sure. in order to make it more affordable for the poor people to be able to keep up with the rich people genetically uh their progeny genetically. Uh one solution would be to have it subsidized or paid for by insurance. But insurance is paid into by everybody both people who want to use it and people who don't. people who agree with it and people who disagree, people who are rich and people that are poor. And that means that there are people who fundamentally disagree with this sort of technology being forced to pay for it so that people who do agree with it can get to use it. >> Precisely. And whether it's an insurance mandate or a direct subsidy that the government gives you, well, they the government is us. They get their money by taxpayers. And so that's why I sort of say like a lot of people, you know, say, well, the obvious solution to inequalities of anything, genetic inequalities, wealth inequalities is just give the poor money or give the poor access to whatever. And it's like, yeah, that sounds good, but the money comes from somewhere. And in the case of wealth wealth redistribution, you know, you're not forcing on people necessarily views they vehemently disagree with, but there are some religious people who really don't like IVF, like they really don't like abortion, >> which is different than IVF. Is this not this is this not the case with a bunch of treatments at the moment? >> Yeah. You know, there's some people who don't take their kids in when they've got cancer and they're going to pray the illness away and stuff like that. Surely this is a situation that we've already encountered are in good. Yeah. Jehovah's Witnesses and blood transfusions. Um so Jehovah's Witnesses I guess don't you know I don't really understand the religion well but they don't agree with blood transfusions. They don't want to intervene in you know what they regard as natural or God's will or something. And so some of them have refused their children blood infusions when in fact their life depends on it. >> And um so the Supreme Court, other governments have basically ruled no no you have to whether you like it or not because the children can't really make their own choices. They're not old enough. >> Fascinating. >> The same thing happened with a famous case with vaccinations in 1905. I believe it was. A Swedish guy didn't want to get his kid vaccinated. But, you know, vaccinations then were not against like COVID, which isn't necessarily deadly for kids, but polio, you know, which could disable or kill you. And so, yeah, the Supreme Court actually said, you know, you should be forced to vaccinate your kid in some circumstances. I actually agree with it in that case. Um, but I recognize these are contentious issues and the more you get governments forcing people, everyone to do things for their kids that some are going to reasonably disagree with, you know, the more you ramp up kind of basically people's appetite for civil war. People really kind of warring over these these culture issues. >> Yeah. How what an interesting uh circle to try and square here. Yeah. Yeah. Exactly. You got this inequality on one hand and government overreach on the other. People's desire to have autonomy. Actually, autonomy is on both sides of this, right? The autonomy to be able to choose Y, which is limited by your ability to pay, but also your autonomy to be able to choose where your money like what you subsidize with your health insurance. Uh, so >> welcome to politics. So, in in that sense, like there's no really there's no really new principles here at stake. It's just that when you think about genetic inequalities as opposed to wealth or housing policy or healthcare or whatever, there's just a a new dimension along which we're thinking and it's like part of us, right? This is what >> freaks people out. I mean, we are in some ways our genes. Yeah, we're shaped by our family, our environment and all of that, but genes are kind of fixed and so you know when you're talking about redistribution so to speak of genes or genetic endowments, people do worry and and they're not completely crazy to worry about that. Have you thought about a way to make the discussion around the impact of genetics on people's outcomes in life less icky? Every time that I have a conversation about this, whether it's with Robert Plowman or Paige Harden or you or who Rosie or whoever, >> whenever I speak to somebody about this, Paige Harden is like hardcore on the left. Like she is very very left-leaning. Plowman. I have no idea, but he was what, the fifth most cited psychologist in the 20th century, I think. Um, no matter who I speak to, there is always this [ __ ] spectre in the back of there's this big elephant in the room, this big genetics is eugenics. Uh, this is uh judgmental. It's breeding. I it's it's determinist. It's reductive. Um, it's right-wing. It's Nazi policy. It's overbearing. It's there's always this sort of lurking. And um ultimately anybody that reads a single book on behavioral genetics is going to find out that the raw materials that you're made of is highly predictive of some of the outcomes that you're going to get in life. Not all of them, but some of them. Have you thought about how to make this message more palatable to the sort of wider audience? Sure. I think I think we all have people in this domain, but actually you said people who have read a book know about this. The reality is everyone who's had a family who's got brothers and sisters or children know that a lot of what forms their their personality, the the differences between them and athleticism, musicality, all this stuff is obviously involuntary. They grow up in the same environment, same family, same teachers in many cases and they end up very differently. And so the reality is most people know this. It's more of again back to taboos and kind of public signaling and that sort of thing. Um, you know, you're supposed to signal that genes don't do very much. And part of this is like we live in a meritocracy and we want to believe that you can be anything you set your mind to. And, you know, we look like we're kind of reigning on the parade of, you know, telling people actually, you know, it turns out genes are going to constrain part of part of your outcomes in life. But I think actually it's an optimistic message too because the truth is the more you know about genetics the more you realize like first of all they're not deterministic. There's still a lot of space for for what you can do with them. But secondly we're all good at different things. And so you know figuring out that you're you're better at some things than others doesn't mean that therefore you're I don't know inferior or you should never try to do those other things. Maybe you try to do them precisely because it is a challenge. But you also you grow up as a human and you realize you're not equally good at everything and and you do the things that you're good at and those become sort of exaggerated. And so yeah, I don't think it's necessarily a bad message to understand genetics. But you know, one way to soften it is precisely, especially when we're talking about genetic selection. People spend all this money, resources, you know, selecting a mate, getting married, you know, buying a house, sending their kids to the right schools and that sort of thing. And I think, you know, one thing you can do is you can stack the deck ahead of time. the genetic deck by just kind of minimizing disease burden. You know, making sure that to to the extent possible they have a a decent level of general cognitive ability, low level of, you know, psychopathology uh um proness, that sort of thing. And yeah, that's probably going to be as effective or more effective than a lot of things parents already do. And I think that's an optimistic message, not a pessimistic one. There's there's definitely a a strange sort of duality that I hear in some of the criticisms around embryo selection. Um, one being that I I don't think I've ever heard anybody anybody from the embryo selection camp use words like um better as in the worth of a person. uh preferable, more optimal, etc. Um, which is the outcomes typically that most people are looking to get in life will be predicated by this sort of uh collection of genes as opposed to this sort of collection of genes. Uh, you know, if if you had the choice between a gluten intolerance and no gluten intolerance, like presumably even if you don't want to eat gluten, it would be better to not be wrecked by it if you accidentally get stealth glutened in a a restaurant somewhere, for instance. Let's say uh or myopia, right? I don't need to deny the personhood of everybody that needs glasses, which includes both of my parents, by saying it's probably preferable for people to wear fashion glasses if they want to, but to not need them in order to be able to read a piece of paper or a menu in a restaurant. >> Exactly. >> But when you hear a lot of the criticisms, they seem to be about Well, what you're saying is that somebody with a higher IQ is sort of more worthy, a better person, better person, more of a person somehow. And uh I I don't think I've ever heard that come out of the at least anybody that's well. I'm sure that there's [ __ ] tons of people who actually do. [laughter] I'm not going to [ __ ] hitch my wagon to every person that's talking about behavioral genetics, but you understand what I mean. >> Yeah. Most people don't think that someone who is healthier is morally superior to someone who's less healthy. There are degenerate societies where that's true, right? We can think of 1930s Germany and the eugenics laws that they passed which is you know before the Holocaust something like 300,000 Germans were murdered um because they were considered morally inferior because they had psychological disorders or you know sexual deviants you know some some homosexuals were killed by the German regime. So there are people who have kind of made that conflation in the past, but that doesn't mean we need to make it. And and the truth is, as I like to say, I mean, we have fewer disabilities over the last 20, 30 years simply because medicine's gotten better. And you could say, therefore, the disabled community, you know, whether it's deaf people or people in wheelchairs, you know, there are fewer of them around and so they have less solidarity with each other. Um, there's going to be more discrimination. But the reality is the opposite, right? We have, you know, stronger laws that protect them. we have more tolerance as we've understood the source of their disability etc. So >> yeah, I think you said what's basically correct, which is you can on the one hand respect disabled people, including intellectual disabled people, and to not just tolerate them, but actually say like, yeah, they're perfectly fine morally, but nevertheless want your your own kids to have various advantages. And I guess I should probably say something about, you know, the way in which what we're doing is going to make this conversation inevitable. So, I probably haven't said much of this to you so far, but you know, I'll just give you a quick history. How about that? Of >> of IVF and and how people go about kind of selecting embryos. So, IVF is 50 years old now. It started in your your home country, right? Um, in vitro fertilization, when you hormonally stimulate women, typically it started with infertile women, they generate a bunch of eggs, and the younger you are, the more eggs you get. fertilize them with sperm, then you have a bunch of embryos. And you know, since the 1990s, they've been able to test for Down syndrome and chromosomeal problems, test for monogenic disorders. I mentioned that. Um, but here's the thing. I mentioned, okay, now what we can do is we can scan the whole genome. We have these polygenic predictors. Most diseases, most traits we care about, height, diabetes, intelligence, even a big part of eye color is highly polygienic. hundreds, thousands, even tens of thousands of genetic variants are influencing these things. So that's a new thing we can do. But the thing that my company is doing, which is not just okay, we have better polygenic scores than other companies. That's cool. But the really really fundamental thing that we're doing which is going to make this technology accessible to everyone basically in the world. There's no blocking this is we can now take the test for Down syndrome which basically it's just meant to to count chromosomes but it gives you a small snapshot of the genome of the embryo. What we can do is take that data and then whole genome sequence the parents and because the embryo is just a function of the parental genomes, we can then we have an algorithm to recreate the entire embryo genome. Each embryo has a discrete genome, right? Different risks, different risk profile, different genetic profile. And we can do this using again these two sources of common commodities, two sources of data. Anyone can hold genome sequence themselves, any parents. We do it at our lab but you can do it elsewhere too. Anyone who does IVF can ask for that downs test and then request the raw genetic data from that test or we can do it for them and then we can use that data to understand the entire genome of each embryo. Why is that important? There are lots of countries and lots of clinics within our country where it's completely legal but some doctors you know they don't necessarily want to do it. um they don't necessarily understand how polygenic uh selection works. They don't understand the science of it. And this is totally understandable. I mean, doctors who went to medical school 20 years ago, they can't keep up with all the latest developments in genetics. But now, because of this innovation, they don't really need to. I mean, we'd like them to to know and support, you know, what we're doing. And we have lots of clinics that we work with who are perfectly supportive. But the truth is, you know, it's going to be really easy for individuals to go to clinics to request data from from this test, this downs test, PGTA, get sequenced, and then understand the whole genome of their embryos. And that means they can get these polygenic reports that we offer. They thought they were getting a D down test, but they were also getting a schizophrenia test, a test for intelligence, a test for height, a test for all of the the kind of disease traits that they care about that we can offer. >> So that's of enormous significance because it means that in a way there's no stopping this technology and it democratizes the technology. I think the optimistic point is people worry about inequalities of access. Well, we're giving them access. We're kind of removing the gatekeepers. So as you started, you know, people worry about eugenics in the sense of governments controlling these things. Well, what we're doing is saying not only can governments and should governments not control it, but actually clinics and doctors, although we respect them, we respect their choices, they shouldn't be, you know, infinitely powerful to to be gatekeepers either. I mean, modern medical ethics is premised on basically informed choice by the patient. You go into your doctor, you get diagnosed with cancer. In fact, one of our star scientists right now, he's only 36. He's a Brit. >> You told me about him. >> He has cancer. This is Alex, Alex Strudwick Young. He's at UCLA and he's the one who, by the way, sort of inspired this this algorithm I just talked about. And yeah, diagnosed with cancer at age 36. There are people with cancer who are diagnosed much later who don't want to be treated. Why? Because it can be really, really rough. You know, you're 91 years old, stage 4 cancer. the probability of success is really low. It's going to be extremely painful. And you just say, you know what, I understand that what will keep me alive a couple more months is chemotherapy and radiation, but I don't want to do it. >> And you know what? The law and modern medical ethics says you don't have to do it. Now, if you're Alex Young, you should do it. And and he did it, of course, because there's a good chance of recovering from it. But anyway, the point is if we want to take seriously individual autonomy and respect what individuals want to do with their bodies or with their genetics or their embryos genes, you know, this technology is a godsend because now we can reveal all this information about embryos. It's no longer a completely random roll of the genetic dice. And all of these kind of, you know, these nannies who want to say, "Oh, no, no, no. You know, you may want to choose in that way. You know, you want to choose whether you get chemotherapy or not, but I know what's better for you, Chris. Like, I know you should get the chemo even though you're 91 years old. >> You say that you want to choose which embryo to implant. But, >> but I say, you know, I in my academic ivory tower, that's eugenics, so you don't get to. Well, what we've done with this technology is basically liberated people from the nannies, from the people who want to tell them what to do. So, I think it's pretty cool. What would happen? I I keep on thinking about the current process of IVF because it seems to me like this has already happened. It seems to me like there is some sort of selection. There's a a harvest 10 eggs. Somebody looks through a microscope. If you're the mother or father or both, can you go to your doctor and say, "Hey, um before we implant, what what did you see over those 10?" Is this a conversation that sometimes happens? Well, the doctor would usually say, "So, look, we've got, you know, there's two or three here that I think are they're non-starters. I don't think that they're going to take as it's known. Um, they're non-starters. We've chosen this particular one. Could you say, well, what did you see?" And then from those, well, actually, I feel I feel a little bit a little bit more number five than number seven. Is that is that conversation sort of happening at the moment? Do you know? >> Not very often. >> But is it something that you could have, do you think, if you could ask? >> Yeah. And people do. And we've had customers, you know, we we were in stealth operating for a few years here. So we've had about 80 customers now. We're just kind of coming out of stealth and we're we're going to take on thousands in in the coming year. But you know, early days a couple years ago, what we would do is because this technology is new, we' we'd explain to people like this is how it works and you know, we can give you various information. You could discuss it with your doctor. In some cases, clinics, doctors are very open to it and they say, "Yeah, look, I mean, if you know what you're doing and you know, you understand the relevant information, like you get to choose." But there are others who would just say, "No, like we're not going to let you do this. We're going to say this one is morphologically better. So, we're going to put we're going to sort of think >> eyeballing it rather than using tests and data." >> Exactly. And in many cases, this is the bizarre thing and this actually raises some interesting philosophical issues. um they will let you choose based on monogenic disorders. So let's take something like hemocromattosis, t-ax, um cickle cell anemia which is more you know west Africans and and some in the Middle East right you know famously if you have the one variant you have protection against malaria but if you have both of them you know both copies then you get cickle cell anemia those diseases have been understood for a long time and since the 1990s you could the parents could get a carrier screening they get a blood test to see if they carry one of those variants >> and they could also do the same for the embryo and doctors are perfectly fine if you have that one gene that's known to cause that disease. Okay, then you could pick an embryo based on that or based on morphology. But what you can't do is pick based on polygenic diseases, which are the huge majority of the diseases that afflict us. I'll give you an example. Everyone's heard of the BRCA genes. There are these variants. They call them B, but it's kind of like brooka or whatever, right? BRCA. um these these uh mutations that significantly elevate the risk of breast cancer, right? So, if you have one of these variants, you're like 60% likely to get breast cancer or ovarian cancer, but yet that's 3% of all the breast cancers are caused by that. The rest of them are polygienic plus environmental in origin. And so, the crazy thing is what these doctors who are acting paternalistically are saying is look, >> you know, for this 3% of cases, sure, we'll let you choose. And yet, even in those cases, it's only probabilistic. They're raising the risk of breast cancer. They're not guaranteeing you get it if you have the BRCA genes. But for all of these other cases, you've got significantly elevated risk of breast cancer or schizophrenia or Crohn's disease. We know it runs in your family. We know this genetic data is real. We know that you validated your results. But you know what? You don't get to choose based on that. It's kind of insane, actually. And I'll give you another example that's kind of in between these. We're offering for the first time something that we're calling neurorisk. And it's an interesting thing. Basically, a significant portion of the population has genetic variants that interfere with neurological development. They don't guarantee that you're going to have a really bad outcome, but they're often associated with things like dyslexia and even low functioning autism. And these are just rare genetic variants. we can track them and we can give you a score and say look some of these embryos have these variants known to cause neurodedevelopmental disorders and some don't and um you know again these doctors because they haven't kept up on the science and you know fair enough it's hard to keep up with the stuff they're going to say you can select against a monogenic disorder but this neurorisk thing or these polygenic disorders were uncomfortable with that but the real question is why and you know again it may be just like well the latter you know, polygenic disorders, they're probabilistic. They're not guaranteed, >> you know, to produce these outcomes, whereas the others are. But it's it's like, no, they're not actually because again, these monogenic traits like like the Brack variants, all they do is you have this one gene, it elevates the risk of breast cancer, ovarian cancer. It doesn't guarantee that, right? And so what we're doing is we're just introducing complexity. And what I found interestingly is doctors don't like dealing with probabilities yet they're already dealing with probabilities. Every treatment that you go in actually you know this as well as anyone. You go in for a diagnosis and they say based on your symptoms we think it's X and you're like two months later you go to another doctor and it's like no way dude it's why. >> And then it's like okay now we've got three doctors who believe it's why and you're like okay cool I'm pretty secure it's Y. Now how do we treat it? And then you go to two or three more doctors and they disagree about how to treat it. All of medicine is probabilistic and indeed all of life is, right? Should you take a driverless Uber or a Whimo or you should take the one with the driver? And it's like, well, let's weigh up the probabilities, right? People do this all the time. But I think what's happened is there's this illusion that medicine is about there there's truths, there's facts, and what I want is the doctor gives me the facts and then the doctor tells me, do I have the disease? How do I treat it? And doctors have gone along with this illusion in a way. But it's an illusion. It's just false. And so what we're doing, I think, is we're introducing a little bit more complexity and a little bit more in terms of probability. and they worry that it's just it's just too much to explain to people and they don't want to do it. >> That doesn't feel like a particularly moral stance, but it is moralized what's going on there. >> Yeah, fair enough. You know, you made the criticism, not me. I mean, that is Yeah, it's in in in some ways they really are projecting. I mean, not all of them are. Some of them have legitimate worries. Um, I I will say this, for example, there are some companies out there that are doing polygenic prediction either to give you health scores for yourself so you can diagnose what's the chance I'm going to get Alzheimer's when I'm older, right? There's a >> one of those Intel XDNA. They're based here in Austin and they're great. >> Yeah. So, there are many companies out there and I'm not going to name names because some of them are actually pretty good and some of them are horrendously bad. >> Okay. >> Like like no better than chance. this is astrology what they're doing and shockingly moving from the academy to to the the the private market. You know, I used to be a bit more of like a kind of libertarian economist like markets will eventually get, you know, the right information. And so, you know, the best companies will get the best investors and the most money. And what I found in this in this realm, oh my god, some of the worst companies are the the best capitalized. Like people who have been good at, you know, maybe charismatic CEOs are are often good at raising money even when they have a [ __ ] product. >> And because there's so much um what we call in economics asymmetry of information, they can often con both customers and even venture capitalists. >> Well, I mean, look, the the world of health and fitness is replete with this, right? like how many how many uh products are superfluous in claims, not clinically backed, not tested for >> contaminants and all the rest of the stuff. I suppose the difference is >> one dose of a uh slightly overcaffeinated preworkout, it doesn't have lifelong implications. >> Exactly. >> A company coming in and saying you should choose embryo 3 instead of embryo 5 or you have a a disposition for this or that results in a literally an alternate human being born or you adjusting your entire lifestyle for the rest of your days. >> You just hit on the most important point and this is what I want to stress because you know of course I have a product to shell or whatever but don't believe me. I mean you should you know science is science and so for any company that's offering polygenic scores whether it's for your own health prediction there are lots doing it you just mentioned one or for you know embryo screening the first question you should ask is how did you get your polygenic scores how did you create these scores you know have you accessed various bio banks and so on and mainly how do you validate these scores how do you know they work how do you know how much predictive power they have and how do you justify that claim and then finally and I can tell you how this works. But finally, how does this work across different ancestry groups? And this is of fundamental importance. And I I'll just tell you an anecdote and then I can get into how how these claims can be validated because you should anybody should ask these of these companies, right? Including my own. You should challenge us and say like, you know, seriously, skeptically like what are you doing here and how do you validate this? So let me give you an anecdote which is we had one couple come to us in early days and they had done some genetic testing on themselves and they had polygenic scores for schizophrenia and they were really worried about having kid. They actually had some embryos in the bank already and they were worried about whether they should have a kid at all because they both scored according to this company really high in terms of risk for schizophrenia and schizophrenia is a highly heritable condition. And if both parents have it or if neither parent has it but they have a high high polygenic score for it u meaning you know high risk for it there's a decent chance their kids are going to have schizophrenia right >> what did we do we retested the parents and then we simulated embryos based on parental DNA >> and what we showed is you know based on our predictors and our predictors do work better than this other company I can say how that works I'm not going to name the company they actually had very low risk in terms of their poly ogenic risk scores for schizophrenia. That is [ __ ] wild, right? That means people are making decisions about, as you said, their health, >> if they're going to have kids at all, let alone which embryo to implant based on >> stay with this particular partner. >> Yes. Based on [ __ ] data, right? >> Now, let me tell you how we would know it's [ __ ] Um, and this is what you should be asking for any company. How do you validate your results? And I'll just sort of say this high level. Well, first of all, what is a polygenic risk score, which is what's guiding, you know, um, your choice of embryos or what's guiding your health decision? A polygenic risk score is basically just an indication that given your genetic endowment, you're going to be at higher risk or lower risk of whatever it is we're talking about. Schizophrenia, you know, uh, having, you know, light eyes rather than dark eyes. Blue is a specific variant, but if you just want to know kind of hazelish or greenish, you know, there's a few variants involved. Uh, how tall you're going to be, etc. Those are highly polygenic, many genes at stake and a risk score basically just indicates your probability of this. How do we derive these? We access biioanks that have scanned, you know, half a million, million people in some cases. They've looked across the entire genome >> and they've matched up the the specific genetic variance that you can see across people with a particular trait. So it could be again it could be schizophrenia, it could be diabetes, it could be how tall you are. and you you you create a polygenic risk score based on this genetic information, but that still doesn't mean it works. I mean, you know, you've kind of generalized from all this information. Now, how do we know if it works? Well, the ultimate way of testing whether it works is to do the following. We know that embryos in a petri dish, the kind of embryos that you're going to implant, have the same genetic relationship to each other. They're basically unrealized siblings um as sib adult siblings do to each other. and they have the same genetic relationship to their parents as of course adult siblings do to their parents. And so if we could take a bunch of siblings and we've done this right there are big you know banks of siblings where we know their gna DNA we know the traits that they have if we can predict the differences in height between siblings adult siblings right where we know their DNA we predict their height or we predict across large numbers of people do they have diabetes or not you know etc. then we know that this is going to work for embryos. And so the key then is to use these kind of sibling studies and we call them within family studies when we're talking about embryos. And if you can predict just based on DNA the differences between adult siblings, then you know that's also going to apply for embryos. But you want to add one more thing which is can you do it across ethnic groups? And what we do in our our papers, you can see them on our on our first white paper at herite.com. We've got a bunch of papers coming out in the coming weeks for disease traits, intelligence. We have the best predictor in the world for type 1 diabetes now. And what we show is how much loss is there in terms of predictive power for different ancestries. And I can get into why there would be a loss of ancestry. >> Polygenic scores trained on European data lose up to 80% of accuracy in African ancestry samples. The humroad update. >> Yeah. Not for not for ours but in some it depends on the trait in question >> and it depends on yeah exactly which polygenic scores you've done. So for us we do have some loss in ancestry for all non-European groups but it's a lot less than other >> is that just because the data set for Europeans was way higher. >> Yeah. Exactly. So >> and it's just another dice roll of like another uncomfortable element as a part of this that now race is being brought into it for no reason. >> Yeah. Although, you know, it's I mean, race is not a discreet thing, right? So, we like to talk about ancestry groups cuz there are, you know, continental clusters, you know, so subsaharan Africans do cluster together and they're quite different than North Africans and well, if you've been to Egypt and you've been to the Sudan, you can just see it. Of course, they're quite different genetically. Um, but the reality is a lot of these groups do in many cases bleed into each other, right? So, like Bangladeshies and Indians are pretty genetically similar, but there are some differences in ancestry. Same thing for Europeans. And so basically what's happened is the earliest, this is so typical, right? The richest countries fund all the R&D. And in a way the poorest countries are lucky because the rich countries are doing this and poor people in poor countries their descendants are going to benefit from what the UK and Sweden and the US is doing now. But yeah, the UK is p primarily of course Anglo and and of course there there are some South Asians, there are some East Asians and so the biioank naturally is going to reflect the demographics of the country that does this. And there are biioanks now everywhere in the world practically. But the UK is just much more open >> to people using their data than the Chinese bio bank is. No surprise, right? So if you want to study Chinese people, which of course we'd love to, you know, we do have access to some of that data, you know, it helps if you're a Chinese citizen or something like that, whereas the UK, what are they trying to do? Promote health for the world, right? They've got this kind of cosmopolitan healthpromoting mission. And so yeah, if your data is trained primarily on Europeans, of course, the scores are going to work better on Europeans, but there are some statistical techniques and some other things you can do to increase the effective sample size of non-Europeans and try to get the polygenic scores more to par than some companies can. Just going back to what you said there about the predictive power. Um, obviously one of the questions that I I have is unless you're going to do a longitudinal study to say we thought that this embryo would be X and then 5 10 15 20 25 30 years later you work out this was what happened with the immune system. This was what happened with height. This was what happened with IQ or schizophrenia risk or whatever it might be. Um, you're saying you don't need to do that because you can treat existing adults as just genetic samples. Ignore the fact that they're adults. Take the samples, work out what that predicts for, and then compare that to the real world person. Is this one taller than this one? Is this one more schizophrenic than that one? etc., etc. And that validates the model. And from that you can infer that it would also work for this batch of embryos. Is that correct? Is that >> Yeah, exactly. And if if you want to take the the dimension of human bias out of this entirely. You could just imagine some AI bot, some AI model just developing, you know, accessing a bio bank, developing polygenic risk scores and then asking itself, how do I know if these work? And the the first thing that AI would do is say, well, you know, again, embryos in a petri dish are a lot like siblings in terms of, you know, your genes don't change over time. You're from the same parents. So, how would I know if these would work? And the first thing an AI would do is say, let's look at 70-year-old siblings and let's run the polygenic scores on their DNA and see, do they in fact have Alzheimer's disease or not? Right? >> And that's why you need truly huge samples. This is why like most of subsaharan Africa, you know, they're not represented well in bio banks because those countries don't have the the medical infrastructure, the scientific infrastructure. You have to genotype, you know, let's say a million people and then phenotype them well, right? You have to measure all these traits. >> How do you do the measuring of that? Who's doing that? Who's going in and measuring? >> Well, the cool thing, you know, the the the one good thing about socialized medicine, there's a lot of bad things about it, right? you know, the NHS is it's it's pretty inefficient. But the one good thing about the NHS is they keep meticulous records of, you know, who's got what. And in the in the the UK bio bank, you can just match >> and that's correlated to >> Yeah. You could just you can pull the records from the NHS. They have to opt in, of course. Um well, I shouldn't say of course anymore. You know what's going on with your country? There's more and more big brother going on with the UK government. But but in reality, yeah, with with something like the UK Bio Bank and the Swedish Bioank, the Icelandic Bio Bank, people opt in to participate. And the cool thing is you don't have to do a lot of work because you already have these health records. >> And so you don't have to, you know, bring them into the doctor for a week and do every possible medical exam because they've already got them. So you can correlate the genes with the health records. The only thing that you need to do and you know especially if you want to get good intelligence predictors the UK bio bank has a kind of IQ test. It's just not very good. It's a quick one. You know it's worth something but a lot of what we get are intelligence scores or polygenic scores for you know we have to go across different bio banks some of which are a lot smaller than the UK bio bank. It's you know the sample size of maybe 10,000 people or 20,000 people. it's not quite powered up enough to give us the best score that we could get, you know, where they've sat down, taken a proper intelligence test, etc. And so we're correlating all these things where you have smaller biioanks that are properly IQ tested, but that takes a lot of time and resources versus bigger bioanks where they're not really well IQ tested, but we can also look at things like educational attainment and, you know, some of these other coralates with intelligence. >> Oh, that's interesting. just run that through, you know, and then and then the ultimate thing is again not sort of how you do this, it's how do you show this works, right? You can do anything you want, right? Let an AI machine just just go at it and try a bunch of things. What really matters is did you validate your polygenetic scores and did you do it across diverse ancestries and that's the key that we've done. >> Okay. So, what's the efficacy like? Does this work? Does your thing work? >> Yeah. Um, yeah, it's it depends on the trait. So, all of them work well that we offer. I mean, we have like an endless list of traits we don't offer, and that's because we want to be sort of we want to be extremely scientific, scientifically rigorous. What we don't want to do is offer a trait where we're barely better at chance at predicting this. We want these to work robustly. And I can give you examples, but basically, you know, when you think about something like, let's just take schizophrenia because it's a bad disease. It's something nobody would want, right? um you know the predictors work reasonably well but they're going to be more effective in a sense for people who have a family history of it right it is true that a random person could get it with no family history but if you have and we do this when we when we give um parental reports to people first we give a simulated report based on their DNA here's what you can expect your embryos to look like we actually do 500 simulations and the idea is let's like recombine their DNA 500 realistic times give them a a sample of what their embryos probably will look like on average. >> And then when they do IVF, they might they might have actually gotten genetically lucky and everything shifted a little to the right or unlucky and to the left. And this will guide them. Do you want to do another round or not? >> Um, etc. >> Oh, how far or close from the bullseye did you get? Or did you beat your odds based on our prediction? Exactly. You under sell them. Yeah. >> Yeah. And if you just want one kid and you've already got a couple of embryos that are doing pretty well, like, yeah, why do another round of IVF if you want three or four kids? And we've got a lot of pronatalist customers that want to have a lot of kids, you know, maybe they want to, you know, do do more rounds of IVF based on that. Um, but the other thing that tells you is, you know, there may be risks you didn't know you had, but based on your DNA and your partner's DNA, we can reveal kind of new information. And whether or not you know your family history, that can show up in those scores. But if you do know your family history, what you can really see is like, you know, something like schizophrenia for example, depending on the number of embryos you have, you could reduce risk by by half, right? So it really depends on what your family history is, how many embryos you have, but I'll tell you what we can do for intelligence. And maybe we can talk about some of the coralates because they're pretty cool. um you know for intelligence if you have 10 embryos we can predict about a 15 and a half point spread which is about a full standard deviation so the average IQ of of the population is going to be 100 not by magic because we just define the average IQ as 100 and so any deviation from that is going to be above or below average but think about the difference between someone that has 100 IQ and 115 or 100 or or 85 or if you want to really go down 85 and The army will not let you serve if you're below 85. And for good reason, right? You can't learn quickly. You can't process data and you can't be relied on to fight a war effectively. If you're below 70, you can't be executed in I think the state of Texas because you're considered basically incapable of making rational decisions. So think about that. A 15point spread is big. Now the the real spread between 10 embryos is about double that. It's about 31 or 32 points. we can predict about half of that if you have 10 embryos. And that's wild because, you know, think back to uh, you know, I don't know about your grandparents, but, you know, I have an Irish Catholic side and my my grandmother had 12 brothers and sisters. And if you if you see a big family like that, you really do see differences >> in in height, in intelligence. You know, this guy, he's going to stay on the farm. You know, everyone kind of accepts that. You know, you might not talk about why, but, you know, he's a he's a great guy. He's athletic. he's good-looking, but you know, this is going to be a farm boy. This guy over here, you know, he's, you know, maybe not so athletic, but he's he's heading to Yale. And everyone kind of understood that you've got big variation between siblings. And all we're doing is we're saying, look, if you have a bunch of embryos, we can reveal a large part of that variation. In the case of intelligence, about half of it, >> and you can choose accordingly. And and a lot of people, by the way, we have a customer who, you know, she has type 1 diabetes. She's really bright. She went to medical school and she decided not to be a surgeon in part because of type 1 diabetes. She doesn't want to pass out. I mean, you know, you've got a a good patch now that regulates blood sugar, but there are certain limitations. And she went through and she looked at her report and some of her embryos were really shifted high on diabetes and some were lower. And she had a real dilemma, which is the smartest one, projected smartest anyway, was also highest risk of diabetes. >> What's she going to do? she's not going to she's not so obsessed with one or two points of intelligence that she's going to impose that risk on it. And so she chose, you know, one that's a little bit shifted to the left on intelligence, but also on diabetes risk. So >> yeah, I've got I think this is a really good point. What about buyers remorse? >> Yeah, >> with regards to this, I had a dude on the show, Finn Taylor. He does this great podcast, Finn Versus the Internet, and another one called Finn Versus History. And I briefly mentioned this topic and this conversation to him and he's a father of two I think and he brought up well imagine the strange kind of regret or resentment or what ifism that a parent might have if they choose from a harvest of 10 eggs and they say I'm not going to get the one that's got diabet that's got the high diabetes risk even if they're not going to be quite so clever I'm going to pick another one or whatever any outcome that that child has in their life, the parent is going to feel even more culpable for. Not only a parent's already swimming in this, well, if you don't raise them, right, and what about attachment theory and what about nutrition, natal nutrition, fetal alcohol syndrome, and it was because of you, the house had mold in it and so on, and then it's the way that you raised them and it's, you know, you cried out other not all of these things. Parents are already overloaded and burdened with this guilt. Yeah. >> And now the guilt of I chose wrong partner child, right? How do you think about that? That seems to be a unique problem that we've never had before. >> I agree. Although actually the never had part I don't agree with. So I'll give you an analogy. But first I'll start by saying you know several people you've interviewed are customers. I can say that now. Um, well, I can only obviously we don't reveal names of customers unless they really want to be revealed. And I can say, you know, Diana Fleshman and Jeffrey Miller, who you've interviewed, >> they haven't used us yet. Um, you know, they've they're they're good friends of mine, they are planning on using us, but they had two kids the natural way first, and now they've got embryos they'll probably use in the coming year or two. >> Not surprising that they would they would be customers or that they would be open about that. But Diana is actually the one who first posed that question to me like 2 years ago. And I thought that's a good question. Um I'm going to write something on our website. We have like an ethics fact FAQ. You know, it's kind of '90s term, but you know, are we playing God? You know, and uh will what about you know, buyer's remorse or you know, her question, the way she put it, uh what, you know, what if I feel guilty that our original kids didn't have the advantage of being selected, you know, for low disease burden or high intelligence in our later kids? And I mean the answer that I came up with, you know, maybe it's satisfiable, maybe not, is first of all, like, you know, there's only so much you can do with embryo selection, right? We're not creating the perfect kid. There's every kid's a trade-off. Every embryo is a trade-off. But also, imagine, you know, that the polio vaccine was invented, you know, after you had your second kid and you're about to have your third kid and, you know, the kid is grown and, you know, you didn't vaccinate the first couple of kids and, you know, they grew to adulthood. one of them got polio and they've been crippled and now later you have a kid and you could vaccinate it in time right before it gets polio. Would you say like I'm not going to vaccinate because I feel guilty like giving this kid an advantage that the first one or two didn't. And it's like that would be morally insane, right? You would actually be a moral monster if you chose not to vaccinate your kids when you know just because the vaccine wasn't available to the first one but it is to the second. I think the same thing goes with this. So, you're giving a slight to maybe a potentially large advantage. But even if the advantage is large, as it is with the vaccine, >> or maybe um you would have implanted an embryo that had really bad prospects because you were doing it blindly um and you did it blindly when you just had sex and had the kids the first time. Does that mean you shouldn't give the next kids advantages? And I think nobody really thinks that. You know, there might be an irrational and I will say it's irrational guilt that you might feel over it, but I do think you should just push that aside. I don't think it's really a legitimate guilt. >> I understand Diana's question. I don't think it's precisely the same as the one that I was asking. >> Okay. >> I think the one that I was asking was you choose. It's not the comparison between the natural child and the selected child that you have. Let's say that you've done it in the way that Diana and Jeffrey have done it. It's more the outcomes that my child gets in life I am more culpable for than I already was >> and and that is because of the choice that I made and I chose wrong. >> It's a good point. I mean in a sense you could say that um about any of this. Did you choose to do IVF at all? And then if you chose to do IVF did you choose which embryo? And in a sense that is true. I I suppose the more you take control of any domain of life, >> um, and and in this case, it's another person's life, >> the more culpable you are. But you could argue, I'm not going to make the strong argument, but you could conceivably argue that you're culpable for not doing it and actually potentially morally bad. And I don't mean like people who don't do IVF are morally bad or people who don't select are morally bad. But if you knew just hypothetically you have a family history of all kinds of horrible diseases and you you're already doing IVF. Let's just put that on the table and then you decided I'm not going to select an embryo based on you know minimizing this this terrible disease that runs in my family. I mean I would actually I would make the claim that there's something wrong with you. That's actually a bad thing. And so I would say that, you know, whereas some people might say you're now culpable because you've made an active choice to do a thing, I would say that you're also culpable for not making that choice under certain circumstances. I don't want to be too strong about that. You know, again, >> it makes it obligatory that everybody is supposed to now start using >> Exactly. Exactly. And I don't think that's true, especially if you're young and healthy and all of that. There's there's really no reason. I will say however you know we get criticized sometimes like this is going to create you know a kind of cultural norm whereby more people do IVF electively in order to optimize various genetic traits and >> I don't think that's wrong I think it's true and I will say like half of our early customers probably not our future ones but the early ones who are really into it you know probably half of them were doing it electively they didn't have a family history of disease um I don't think there's anything wrong with that I think it's cool but you know it's not wrong to say there is going to be some externality in the form of maybe as it becomes more accepted to do this. It will be, you know, some people will feel a little more pressure to do this. I don't think that's necessarily a bad thing, but I'd be pretty uncomfortable with it if it if it became so strong that somebody wanted to codify it as policy >> or it created a new kind of norm whereby you're considered just a terrible person if you don't do it. So, >> how do you stop that from happening? The >> norm you you you can't. I mean, the only way you can stop certain things is with cultural norms. And I like to say this, I I always reference this this novel that was actually it's a play very formative when I was in high school in my my Nichi years. Um, you know, I went through and read a lot of a lot of Nichi and then the first Nichi play which is called Man and Superman by George Bernard Shaw, the Irish playwright. And in that play there's a dialogue in act three and it's occurring in hell you know for a reason and it's between um a couple of characters and first of all they're debating like is hell or heaven cooler you know because it's like h heaven is where all the boring people are hell is where it's at you know >> um apart from that debate they have this debate about technology because the guy that's >> you know sort of um defending the devil you know and standing up for sort of Lucifer is saying well you know technology is just a more efficient ient means to to engage in warfare and death and dismemberment, you know, and the and the other side is saying, well, wait a minute, hold on. Like technology is a tool, you know, we can use nuclear technology to build these amazing forms of power that has like almost no carbon footprint and makes nuclear energy and therefore AI and everything energy powers >> um easier, better, more efficient, you know, makes cars cheaper to drive, etc. So in other words, like what Einstein was up to, you know, which is like the basis of in a way nuclear power, right? This could make the world a lot worse or it could make it a lot better. And it depends not on the technology. Technology is a tool. It depends on the norms. Similarly with genetics, you could misuse genetics in the way that the Nazis did. Or you could use genetics, the the the power of genetics, the knowledge about genetics to allow people, in this case I say allow, not force, to improve the welfare of themselves and their kids. And and there's no magic bullet. See, people want an argument that that we can somehow stop this, right? That, >> you know, we we either are for it or against it. And as you know, I wrote a book about this. I've written a lot of articles on this. And you know, I I I hate this kind of utopian thinking like you could somehow get the state to to start or stop this and somehow that's going to work. Laws are just going to police themselves. They don't, right? Incentives are powerful and you know, people are going to do this. They're going to travel to other countries. If some states outlaw it, you know, with our technology, they're barely even going to need to do that because it relies on two commodities, right? Parental sequencing, which anyone can do, and embryo PGTA testing, which anyone can do, right? And then we can give them predictors >> for polygenic traits. >> And what this means is it's imperative to devise societies, social norms, and yes, to some extent laws that encourage toleration that do draw some lines in terms of like what you should and shouldn't be selecting for, >> but you not be selecting for. >> Yeah. Good. Um, I'm glad you asked. Uh, I I got asked this by a journalist yesterday, and you know, are there are there lines that you draw? or there are things you wouldn't select for. And the the the first thing that came to mind is think of the worst in humanity. Sadism, psychopathy, the combination of those dark triad traits, right? Machavelianism, >> you know, dark triad, basically sadism, psychopathy, machavelianism. If we had a good predictor for those, which we don't now, but I think that's coming in the future, would you allow people to select against those things? And I think the answer that I would give is yes. and I would be happy if they did. Would you allow people to select for those things? And my answer is no. And that any company that allowed that should be shunned. And should it be illegal? I'm not so sure. And the reason I say I'm not sure, even though that's the most extreme case, is I think social norms are more powerful in many ways than government regulations. >> Yeah, they are. And if people were shunned for doing that, and furthermore, if we look at the the psychology of a psychopath or a narcissist, do they really necessarily want to invest a lot of resources and I don't know, doing IVF and embryo screening and all the other things? Probably not, right? They want to get away with petty crime. You know, they want sex, drugs, and rock and roll. That's why they always end up in prison, right? They they tend to be normal levels of intelligence, but sort of fast life history strategy. They're always committing crimes and, you know, getting momentary pleasures. I doubt they'd even want to use IVF, but if they did, I think that we should as companies basically not let them select in favor of those kinds of traits. >> Wow. >> Um, but here's I mean, do you want to talk about the complexities? Because I think this is more complex. You know, there's the sort of PR angle where I could say like, well, this is wrong and this is right or whatever. But I mean more interesting is stuff like well you know these are all spectral conditions just like height just like intelligence there there's a spectrum right there's not just tall and short and there's not psychopath and not psychopath the truth is probably some degree of some of these traits are are both adaptive and even good >> for either the individual or society. If you had zero machavelianism, I don't know whether there's a scale of machavelianism. Uh if you had no machavevelianism, then you're not particularly shrewd or canny, you're not able to play the game when you need to. You're probably going to get walked all over at work. And yeah, there's a bell curve, right? There's an optimal zone. And maybe there's a couple of little bumps in it. There's a little bit here. Oh, that's good. But this is not so over there again. We go and then it falls off the end. Um that's really interesting. I I I looked on uh a bunch of announcement posts that have been going on on Instagram. I think I sent you one of them a little while ago. Uh and a few of these have trended because this world your world herite plus a bunch of other companies. It it seems like this is kind of the space race now kind of the the starter pistols. Is it fair to say that? >> Absolutely. Right. Okay. So, starter pistols being fired on polygenic risk scores for embryo selection. And uh I was having a look through the comments. I I was finding out what what people's thoughts were. There was some of the sort of boilerplate stuff that that I thought was perhaps unsurprising. There's a couple of really interesting ones. Uh diabetes and cardiovascular disease run in my family and if I could select an embryo that had a reduced risk of it of getting it, I 100% would. I thought that was really interesting. this sense that if you knew I I I thought about the potential of that woman, I think it was's kid. >> Uh knowing mom, you had the option to select against this. You didn't and I got it. That's the first one. Um well, do you have a moral obligation to sort of give your kids? That's an interesting question. But the second one being uh where was it? [gasps] Um suppose that you got cancer and your mom admitted that she selected you for pretty eyes and didn't even check the cancer column of the embryo selection report. How would you feel? Um so this potential we talked about uh buyer's remorse but what about birther's remorse right the potential that you feel like you were born and we get into the question of personhood which I want to get into in a second >> but um yeah these these these two worlds the one where somebody knows that they've got family history and they think I would love to do this for my kids uh and if as a kid you realized that you had the opportunity for this thing that you're now suffering with to be selected against and you didn't. Again, it's so it's so novel and messy and I don't I'm struggling to navigate the ethical landscape here. I feel like I'm sort of clunky. I'm trying to learn a new dance and I'm clunky and falling over my own feet as I try to work out what I think about this. Good. Yeah. Well, yeah, this is a bit mind-blowing. Back when I was a philosophy professor, I I had written a couple papers on this topic and I encountered a little niche of of law of legal doctrine and it's called wrongful life. You know, there are wrongful death lawsuits, right? Obviously, someone is >> a big part of this, right? >> Yeah. Well, and and there's a woman at UCLA law school, Shauna Shiffron, who wrote an article called wrongful life, and it's about someone who sued their parents, but you know, because or somebody >> never asked to be born. >> Exactly. or somebody sues on behalf of the kid, but in this case because they have severe disability like the the the >> the kind like think of Tay-Sax. So you might not know what it is, but it's a it's a protein folding disorder and basically if you have the two copies of that of that gene, that variant, um you're either going to die in the womb as as a fetus or if you are born your your life is typically very short, extraordinarily painful, just deformities. Think of, you know, proteins are basically what constitute your your body just like cells. And so imagine if you have generalized protein folding disorder. You you just basically >> body can't make a body very well. >> No. And and you're just going to die a miserable, painful death. It's horrific. And so this disease is actually going away because people are screening for it. It is one of those monogenic diseases. And people are either coupling up. They're not marrying if if you're known carriers, if both of you are, or if you are, they're screening for it. in terms of embryos. Um, but imagine if you you knew that you had this risk and maybe even deliberately implanted it. I don't know who who would do that, but >> strangely enough, there are these wrongful life, you know, lawsuits. It's kind of strange, but >> better never to have been born kind of thing. >> Yeah. If the kid dies so young, who's doing the >> law? >> Yeah. Yeah. Exactly. It's got to be on behalf of someone else. >> Okay. >> And this this is an extreme case and and Yeah, >> I I understand on that. Uh, would you let somebody select for T-Saxs or something like that? >> No, I don't think so. So, any anything that's clearly and demonstrabably antithetical to a healthy life or that's antisocial. So, I think the antisocial one's easy like again extreme sort of sadism, psychopathy. If somebody told us they wanted to select for that, >> we would say no. Just to interject there, uh, desktop DNA printers have a similar sort of system in there. The red, green, yellow system. I'm Yeah, I'm guessing you're familiar with this. Um, that all of these DNA sequencer desktop things. It's like the size of a, you know, big computer you can just have literally in a lab on a table somewhere. Um, if you try to sequence anthrax or smallox or some [ __ ] uh, a big warning goes off and guys in black kick your door down, right? Um, I imagine that you're suggesting a kind of moratorum within particular brackets of >> Yeah, but again, I'm not sure there needs to be laws because I think it would be so rare that somebody would select for it. So I think norms and and uh you know moral responsibility companies would be sufficient but yeah if we somehow start seeing a rash of people selecting for extremely antisocial traits or tayachs which again I can't imagine sure we could justify a lot but actually let me say something else about the disease bit. So something we just published yesterday and more is coming um in the coming weeks here. I guess by the time this airs it'll be already be out. Um, one of the worries that I used to have about this and and I often hear it from scientists and some bioethicists is, you know, it's this question of plyotropy and that's when you've got one gene or a small set of genetic variants that code for multiple phenotypic outcomes. So you could imagine a case where I mean I already gave you one example. So the gene that causes cickle cell anemia, you know, if you have one copy you get this beneficial effect but if you have both you get a harmful effect and it's it's totally different, right? One is on the immune system, the other is on blood. But there could be in principle lots of these situations where you select for one trait like you want to reduce the risk of schizophrenia, but for whatever reason those genes are connected in such a way that you increase the risk of diabetes or you decrease IQ or something for some unknown reason. And until you know the whole genome, it would be dangerous for you to to select against one of these traits because you'll get the other one as a side effect. We did a comprehensive study on this and the interesting thing is when you talk about plyotropy again multiple phenotypic effects outward expression of genes for for one gene or a small set of genes you have to distinguish between what you would call positive plyotropy neutral plyotropy or negative or antagonistic plyotropy. The idea being that sometimes when you select against one disease you're actually going to get a lot of other diseases being lower risk as well. That would be positive plyotropy where there's multiple effects but they're they're all good actually. And then there's neutral where it's just there's nothing or it cancels out and then there's negative. We did a huge study on this with thousands of traits and we tried to genetically correlate these different traits whether it be diabetes or heart disease or any of these other things um even mental health disorders and their manifestations like eating disorders. And we correlate those with things that people would select for intelligence, you know, selecting against diabetes. etc., etc. And what we found is the huge majority of plyotropy is positive. >> And this is really [ __ ] cool because what that means is, you know, you go in and you get polygenic scores and you say, "Okay, well, I have a a family history of severe depression or something like that. We're going to have a a risk score. We don't have that yet, but that's coming soon." And you say, "Yeah, I'd like to select against that because it was crippling to to my grandmother or something." As it turns out, you select against severe depression, you get less bipolar as a side effect. You get less schizophrenia as a side effect. And and and in fact, we know the answer. We know the reason for this. Just as there's a G factor, there's a general factor of intelligence that unites all the different ways in which we can be intelligent, right? You can you can have spatial reasoning, verbal reasoning. There's some positive correlation between these different tests. We call that the G factor, and that's general intelligence. There's also the P factor, the aforementioned Scott Alexander, you talked about him earlier. I had talked to him about this three years ago. He's a practicing psychiatrist, famous blogger in Silicon Valley. Um, and I had mentioned this to him and he said, "Yeah, the P factor is is is pretty real." And so you get this this genetic overlap between all these different psychiatric disorders. And the same thing goes for intelligence. Intelligence is positively correlated with all kinds of good things. And there are very few if any negative things that it's correlated with. >> And this didn't have to be the case. I mean, I went in actually worried about this. Like, what are we going to find? Um, but it turns out it is. So, this is actually really good news for embryo selection. >> Talk to me about the problem of personhood when it comes to this. >> Oh, yeah. That's that's a good question. Um, getting deep here. So, um, a Brit named Derek Parett, a famous philosopher, wrote a book in 1984 called Reasons and Persons. And part of the topic that he was he was going on about this is really really big topic in the 70s is you know what makes you the same person across time and this goes back to David Hume John Lockach these old British Scottish philosophers they were you know debating is there a thing is it is it your body you know is it the same body over time and they'd say oh no but a baby is very different than a you know a middle-aged man or preubescent postpubescent the old man that you become you know your your body is different your cells are changing so like is there anything that unites you over time. And you know, guys like John Lockach, David Hume, and eventually Derek Parett, they would say, "Actually, what makes a human the same person over time, if there's anything at all? It's psychological continuity." But then they would have all these these interesting thought experiments like, "Yeah, but what if you had amnesia? You know, you had a head injury or something like that." And and they would just bite the bullet and say, "You're actually not the same person. You're quite literally a different person in the same body." Right? Because what makes a person uniquely a person is going back to our earlier discussion, you know, there's so much based around our brain and our psychology, right? Cuz that's what we identify as, you know, and Derek Parett even said, you know, a brain transplant is the only the only operation where you know the the donor, you'd rather be the donor than the recipient, right? You are the donor, right? Because you are the brain essentially in a new body if if if you could do that. And so so Parfett had all these really interesting puzzles and they're ultimately ethical puzzles that revolve on this kind of metaphysical discussion about personhood and identity and you know he starts with some cases of you know you imagine a teenager who gets pregnant you know accidentally and she thinks to herself man I could have waited maybe had a career or whatever else and if I did wait maybe I would have found a better a better guy right you know he had lower risk of disease or he smarter, he had some other advantage. And he asks himself, you know, from an impersonal standpoint, would the world be better had she had she waited? >> And he more or less answers, well, yeah, from a utilitarian standpoint, which is what what he was committed to. Sort of costbenefit analysis impersonally. >> Is it better for the person who's born? Well, no, because like they wouldn't exist or they or they would exist if they were, you know, selected later. And and this is exactly what embryo selection raises. this problem of personhood and I've seen this objection too. You know, they say something like um you know, I'm glad this technology didn't exist when I was born because surely I would have been selected against >> my bad eyesight, my short height, my >> Yeah. But of course, you know, it would have been a different world and different sperm and different egg. Let's say your parents did it naturally would have, you know, had they waited a minute longer or done it 5 minutes earlier. >> I think about this all the [ __ ] time. I think about this. Hey, if you're a guy that is struggling to uh keep it up or is worried about coming too quickly or too slowly, let me throw the worst curveball in history as well. If you're trying to get your MS pregnant, every thrust is a different child. If you do it this thrust versus the next thrust versus the thrust after that versus half a thrust before versus this one's a tiny little bit less deep, a little bit more deep, that's enough to kill an erection, right? 100% that's enough to kill an erection. Holy [ __ ] >> This is a new source of erectile dysfunction, by the way. I was thinking about this problem. >> Widely available. No one needs to worry. Um, but I I I thought about this. I was like, "Holy [ __ ] >> if you're trying to get pregnant, >> every We decided to put the fan on before or didn't." Yeah. >> We decided to drink an extra sip of Sprite before we got down to it or not. I got up on time or I >> put a different song on, you know, get her in the mood a little bit. >> Everything results in a different child. So the question of personhood sort of comes up. It it seems to me to be the question of culpability. >> Yeah. >> It it's it's how much did you choose this to happen? >> Yeah. Um and what this raises is what Parfett called it the nonidentity problem, but it doesn't really matter what we call it. We all kind of get it intuitively. you know, when you're doing, you know, he called it population ethics, we call it reproductive ethics, you know, whether you're selecting an embryo or again putting on a different song or whatever, different thrust, you know, you're getting different people. And so what you can't say is um if you are born in some way, whether it's through IVF or regularly, like, man, I wish my parents would have done a different thing. I would have been better. You can't really say that because what would have happened? You are who you are. it would have been a different person with different genes. >> Yeah, there's a a wonderful example here uh a couple of things I took from Scott Alexander's fantastic blog post breakdown on this. So, the concern about selecting against certain potential humans chances of being born like is it really correct to say that you have reduced someone's risk of breast cancer by 46% when what you've really done is closer to replacing them with a different person with 46% less likely to have breast cancer. And uh this great example here, I think it's such a funny story. I love the way he writes. I think Scott Alexander might be he might be the greatest blogger of all time. Yeah. I don't I can't Tim Urban good but not as prolific. Um [ __ ] who else would I be thinking about in this world? Like Scott Aronson like old stuff. Robin Hansen old stuff. I'm thinking very much sort of rationality pill like some AliEads stuff's good but like who has been as consistent as Scott. >> No, I agree. And he's he's one of the most trustworthy people. He's just really honest. He calls it as he sees it. And so >> and actually that post he he asked our one of our employees, Alex Young, the guy I mentioned earlier, to help him with some of the understanding some of the, you know, statistical genetics. So >> he does his research. He's he's [ __ ] great and he's very charming the way he writes. Anyway, so this is this is from Scott's uh blog. A woman is planning on getting pregnant. She talks this over with her doctor who asks her some screening questions and discovers she is a heavy drinker. The doctor warns the woman that her child is at risk of fetal alcohol syndrome and advises her to quit alcohol before coming pregnant. She goes to rehab for 3 months and quits alcohol. Then she becomes pregnant and has a healthy child without fetal alcohol syndrome. In common language, we would say that the doctor's intervention prevented the baby from getting fetal alcohol syndrome. But a woman produces one egg per month. So the postrehab egg that produced the healthy baby was different from the egg that would have produced the baby if she'd gotten pregnant right away. They're different babies. She has essentially replaced a baby who would have had fetal alcohol syndrome with another baby who doesn't have it. And this choice of selection, this is the three monthlong version of the what pump you do is determining the child you have argument. >> Exactly. Yeah. This is the ultimate great replacement. We're replacing, you know, chance with choice to some extent. And that's not necessarily a bad thing. I mean, so if what you're doing is I mean, people are deciding, do I want to have kids? Who do I want to have kids with? I mean, this is just going on all the time. And all you're doing with this kind of technology is narrowing it down a little bit more. And in my view, you know, on average, you're creating a life with better prospects. And and the word better makes people uncomfortable cuz you know in modern liberal society we're uncomfortable making moral judgments out loud. I'm not um people make them all the time. They're just uncomfortable expressing them. The reality is you know if you know anyone with a severe disability and you ask them would you rather not have the disability? They would say yes. I'd rather not have it. Um, and if you are choosing between embryos, one of which will have a disability that's severe and one won't, >> they themselves, I mean, they're almost more likely than anyone else to choose the embryo without the disability. And so, >> but the embryo that wasn't chosen that did have the disability would probably presumably have rather been chosen. >> Exactly. And actually, this goes back to that point. So, what did Parfett say, and also Scott Alexander, and I think we'll probably agree, that's not to say the person who was born with a disability has a life that's not worth living. there going to be very few of those. Maybe the Tay-Sax baby, you know, that's possible. You could make that case there. But if you think that most human life is worth living, and I certainly do, um, then you're not going to say that this is regrettable that this person exists. What you're going to say is, you know, it's perfectly justifiable beforehand if you want to minimize the chance that this person exists and maximize the chance that a different person exists that has better prospects. And I, you know, I'll say it. You know, you're not you're not supposed to judge here, but I think everyone privately does judge. And I will tell you this. What do >> you mean by judge? >> Well, judge in the sense of okay, you don't think that a person with without a disability is morally inferior, right? Like I don't think that I think you don't think that. But what you do think, what most people do think is, would it be better to have a life where you have uh, you know, more prospects because you have a healthier immune system. You're just going to get sick less because your immune system works better. >> I have a shitty immune system. I get sick all the time. You and I travel all the time and I'm constantly getting colds, you know, and the people around me don't get them. And it's like, would I rather have a better immune system? The answer is clearly yes. >> And again, >> but it wouldn't be you with a better >> It wouldn't be me. it would be a different person with a better immune system. But, >> you know, I'm comfortable doing that. I exist and I'm determining who will exist in the future. So, what I'm not doing is letting someone, you know, implanting someone, letting them grow up, seeing they have a bad immune system and then murdering them and then replacing them. I'm not doing that and I'm not advocating it. But from an impersonal standpoint and from my standpoint, you know, as a potential parent, yeah, I want a kid with a better immune system than me. >> Question. Is it difficult to be somebody who is pro-choice and anti-ambrio selection? >> Yeah, good question. Um, there are some people like this. >> Well, there'll be lots of people like this. >> Well, are there I don't know. >> I would imagine. So, how many people how many I I there's tons and tons of people a lot of the people that were in those comments will be pro-choice, ardent, but also this is furthering the distance between rich and poor. This is soft eugenics or [ __ ] I think it's a lot of signaling. So um >> you understand my point though right around the fact that you are saying I have control over life and death of this baby but I don't have control over life and death of this pool that I can predictively work out whether or not they're going to >> what sort of a person they're going to grow up to become. But often the people who are doing who who say these things, you know. So, first of all, I can I can say I'll never identify who these people are, but I can say that there are some people >> who we would both know who publicly are against this who privately are willing to use it. >> Um I know that for a fact because they've come to us >> and or they're publicly very ambivalent, but privately they're absolutely not ambivalent. >> And that strongly suggests, you know, some of the ambivalence is real. I mean some people are morally uncomfortable with it but a lot of it is signaling they you know and and and when you look at people we talked about this before when when we were talking about intelligence and life outcomes associated with it I think in our last episode you know a lot of people who are who are bright and who are healthy you know they they're the ones who talk about how well intelligence isn't real or it's not genetic or I would never do embryo selection it's like yeah you're bright and healthy your partner's bright and healthy your kids are all like reasonably good. But if you had a genetic predisposition to something really bad or if you were infertile like you know and you you had to produce embryos and choose one anyway really are you going to do it random or are you going to take this information to account? Again if it's credible information maybe some companies have I know some companies don't have credible information. Do your research there but >> if it's credible I mean these people are going to be the first to do it. I'm I'm sure of that. So some of this is like reasonable ambivalence and some of it is just [ __ ] social signaling. >> What happens to ideas like look or merit once parents can literally choose abilities? >> Man, that is a good question. I mean, in a way, we've been struggling this with this since the enlightenment. Um, Baron Deolbach, a French philosopher, wrote a book called man the machine. and Newton and others, you know, as we discovered calculus and, you know, understood more about physics and and chemistry and even, you know, what is a rainbow other than refracted light, you know, um, as we've kind of reduced, you know, the mystery of the world to its constituent parts, you know, atoms, uh, chemistry, genes, you know, that's the kind of latest one with Mendele and Darwin and and the genetic revolution of the last 25 years. You know, people have worried like, are we just this bundle of things and is it going to disillusion people and and make them feel like they have no free choice? And I think to some extent the answer is is yes. Um it, you know, it does do that. It can also reveal the staggering complexity and beauty of the world. Like holy [ __ ] like a few, you know, different combinations of chemicals at the the beginning of the Big Bang, you know, could produce this like staggering complexity. And now that we understand these processes, we could actually harness them, take them into our own hands, and actually produce something even more beautiful. I actually think that's really cool. So, in a way, you could have this this fatalistic attitude like atoms, chemistry, genes, you know, these are the things behind, you know, the flower or behind, you know, this beautiful smile that this woman has or this beautiful creativity that this poet has, you know, and so we're just reducing it to these parts. But >> fine, we can reduce it and still appreciate the beauty and take that further. I know you you interviewed Richard Dawkins. One of the books that he that he wrote was on this topic and it was it was called unweaving the rainbow. And this is again a phrase I think it was from from Alexander Pope. He had a poem where he's just saying like Newton all these people they're just they're unweaving the magic of the rainbow. And Dawkins argued I think plausibly that actually science unveils this new layer of beauty to the world. But it does it does cause a kind of double think because we also realize that there's some truth to the statement that you take like a pedophile or a mass murderer, a psychopath, let's say, and you ask yourself like, did you wake up every day resisting your urge to just like molest children or kill people? And the answer is like, I've never even had such an urge. >> It's disgusting. I don't even know what that would look like to to be motivated that way. And then you ask yourself, are you proud of that? It's like, not really. I just don't I'm not wired that way. Right? And so in some ways it causes us to I don't want to say like forgive you know a psychopath or a pedophile >> but actually what it does is it sort of says it can it can guide us and say well now that we understand that's partly genetic and even largely genetic in those cases. We should also not just like let them out of prison based on good behavior. we should keep them locked up, you know, and maybe you don't torture them in prison because maybe to some extent it wasn't under their control and so retribution is not the right concept here. >> But isolation >> definitely, right? >> All roads lead to determinism and a little maybe a little bit more altruism as well or a little bit more sort of understanding. I remember this was when I was at at uni and uh I asked this this girl that I was dating uh super smart doing a med degree and um I said what's an opinion that you have uh that most people think is disgusting and she's like um uh non-offending pedophiles need sympathy. That was her position. And I'm like I'm young, dumb, and full of unpronouncable small bags of white powder from running nightclubs. I'm 22 and even that even like through my bro fueled [ __ ] fug haze thing that pierced through and I was like that is a [ __ ] spicy opinion and that is worth investigating for a long time. My point here is just that people get cursed a lot of the times with things that they didn't choose to somebody with really really deep deep dark depression. Winston Churchill like unbelievable depression basically his entire life the black dog that followed him around. Y you go. Wow. How unfortunate. Like how how how how with that context, how much more impressive some of the things that he managed to achieve. Uh and on the flip side of that, look all of the benefits that this person got and how sort of short they fell, how much they squandered the the opportunity. I mean, if you're a full [ __ ] determinist, right, then none of this matters at all. Um, but I I just think it's really interesting to like think about these questions and um, yeah, I I know what you mean that as you begin to understand the mechanisms more and more. This is something that I realized when I did my genetic test. I can't wait for you to tell me whether or not this company that I used is [ __ ] or not. I'm going to have to use you should have [ __ ] just come to you. What do you mean way easier? Um, uh, doing that, I fed it into Chat GPT and had a bunch of conversations with it and I said, "Pretend that you know nothing about me. Wipe your memory briefly for the rest of this conversation. Tell me the sort of person that this genetic profile would be likely to become. What's their disposition? What are the jobs that they do? And it was [ __ ] in the middle of the bullseye. And I was like, holy [ __ ] Doesn't like uncertainty, doesn't like ambiguity, would uh optimize for peace, not war, would be great for focus and obsession as long as things are relatively controlled. um uh thinks deeply, feels deeply, would be a horrible uh soldier in a firefight, but a fantastic um psychologist and therapist. I'm like just all of these different things. I'm like, how much am I the [ __ ] author of the [ __ ] that I've become that I've decided to do? My preferences like you and it's done two things to me. It's first off made me feel um more compassion for people and the way that they show up. Uh somebody that's really annoying permanently having to overt talk other people or always having to uh seek attention in a sort of very transparent and shallow way or whatever like you know some some something that's kind of obviously like usually pretty annoying. I'm like how unfortunate. like I wonder what combination of genetics and lifestyle caused you to be this way. Still [ __ ] annoying, but it it it at least gives me a little bit more perspective. And then on the other side, it made me feel more >> justified in my preferences. >> Like not only do I like this thing, I was kind of built to like this thing and that's cool. And I this isn't just as it made, this is a way to put it. It made my preferences in life and my desires feel less flimsy. It made them feel really justified and secure. It almost actually made them feel like a calling. And um I suppose that that can run both ways. You say, "Well, my calling is to molest children. I'm a children molester, you know, d I'm a bogey picker. I'm a I'm a athletes futter or a fart or whatever, you know." Um okay. But for me, it made me think, well, I quite like talking about deep stuff. And not only is that something that makes me feel good, so I'm allowed to like what I want to like, but also this was kind of like my inheritance. This was sort of your Yeah. Yeah. Yeah. Yeah. >> Yeah. And maybe the other flip side of it, you know, the the the positive side of knowing that we're not genetically determined, so to speak, but genetically influenced, >> predisposed. predisposed is take your family members, your partners, and maybe if you have a blank slate view of human nature, maybe you're frustrated, you can't change them, and that's not good for you or for them because people are more or less who they are. And it's kind of nice to just chill a little bit and realize that. I have this example in a paper we we released yesterday on the the ethics of embryo selection. And you know, we're sort of talking about tig tiger parenting, you know, in in Korea and places like that. And we're sort of saying, you know, some object that, you know, there's already tiger parenting, now it's going to go down to the genetic level and they're going to obsess. You know, my kid has to be perfect. >> On the other hand, you know, once your genes are sort of there, the real solution is to just chill the [ __ ] out and don't be a tiger parent because actually a lot of that parenting is not having the effect you think it is. And a lot of the nagging that you might do of your partner, you know, is probably not going to change them very much. So, you know, either switch partners or learn to love the person for who they are. >> That is Jeffrey Miller's uh insight. I think maybe it was Plman that said this too. I think it was Plman actually that said this to me and then Jeffrey Miller disagreed. Uh every parenting book in history could be replaced with one behavioral genetics book. >> Yeah. >> That that is the the summation of all parenting versus one book and how behavioral genetics works. Like the the single biggest determinant of your child's future is the raw materials of the other person that you make them with. >> Exactly. >> Presuming you're going to have the kid, you can't change yours. >> Like >> exactly >> 50% of So you could say around about 25% of everythingish roughly that this person is going to become >> is because of that person opposite you. You can choose wisely. But in an and I've thought about this a lot as well. uh in an ever aging society of first childhood. Um I appreciate uh Scott Galloway and Warren Buffett and all of these guys that say it's the most important decision that you make in your life. It's not where you work. It's not who you work with. It's the spouse. You know, all of these videos that go super super viral online. I think that they're actually applying more and now perhaps undue weight to the pressure of the decision of finding a partner. And I think that the sort of people that are likely to see those videos and resonate with them actually need to be told >> satisficing, not maximizing. >> Yeah. >> Um like it's good, not perfect, but it's good. There's no major red flags and you can work through this and got a good growth mindset. You guys going to be fine. Um because precisely the sort of person that will watch that thing and resonate with that thing is the sort of person who's already thinking, "Oh, I I can't deal with the shape of their ears. How ever could I have a a child with the shape of those ears? You know, >> Chris, it always ends up with dating on your show. Everything >> all all goes back. >> It's autobiographical. No, but it's true. I mean, I think, >> you know, and this is another issue. You know, you've talked about it more than I have with other guests, but we've just got infinite choice in our society, whether it's dating apps or just the kind of general liberal norms. You know, I'm a bit of a conservative about this, like a traditionalist, where you you take Indian society, and I don't mean the cast part of society, but where where you've got parents, they don't choose your spouse for you typically, but they do kind of narrow it down. And there's something to that. Your friends and your family often are better than you are probably >> at sort of figuring out like who's really compatible with you. And yeah, I don't know, maybe we should go back to some of that where other people have a bit more influence over who we again, not like determining it for you, but kind of >> take Yeah, taking their input. >> Yeah. Uh, the Society for Psychiatric Genetics said screening for embryos for psychiatric conditions may increase stigma surrounding these diagnoses. What do you think about that? >> Yeah, I don't think it necessarily will. Well, I think quite the opposite because back to the determinism point, when we know that there's a kind of genetic cause to something, what it typically does, at least in a decent society, is it makes us realize, oh, we can't blame people for this, right? You might run into a schizophrenic in the street and if you don't really know what's going on and he just randomly attacks you, you're just like, what an [ __ ] you know, like what a jerk this guy is. But if you know it's schizophrenia and you know it's like genetic predisposition toward it, which pretty much always is, are you going to be more hostile to that person or less? And so I think I think they're exactly wrong with that. >> Maybe in a sick society again, you know, you can think national socialism 1941 in Germany, whatever, >> sure, um, you know, you've got a shitty theory of of morality, then okay, let's dispose of these people. But actually, I think in general, it's going to make you more compassionate. That is an objection which could be used to justify a ban on pretty much all medical treatment. I think if you were to say screening for X condition may increase stigma surrounding those people who still have it. It's like um >> the fact that laser eye surgery exists increases stigma around people that wear glasses. >> Exactly. Yeah. So I Yeah, I have nothing to add to that because that's exactly right. I will say the the one thing I will add is it's funny when some of the kind of you know activists talk about this they'll say something like it's wrong to select against you know poor hearing or something like that right uh it's it's it's good to select for deafness >> and you think first of all probably most people wouldn't do that well there is there there have been you know academics have said actually the deaf community are offended by this and it's or denial of their personhood >> yeah it's just another way of being to be deaf and so on. But I find it really interesting in some ways. There's some truth to it, of course, right? Like a deaf person can get on in modern society pretty well. But it's precisely that latter part that you have to emphasize. Modern society. In a more primitive society like like our own 300 years ago, deafness would have been a death sentence, right? You get run over by a tractor or eaten by a lion or whatever. So they they often will pick those traits that are sort of only marginal disabilities and say, "Oh, well, how are these people going to feel about that? It's not really a disability." But then when you pick the real ones, Tay-Saxs, you know, breast cancer, schizophrenia, like nobody thinks like it's we should keep the the same pool of people prone to breast cancer because there's more solidarity with the breast cancer community or something. >> It would be interesting. It would be interesting to speak to communities like that, you know, huge huge uh amounts of investments and fundraising going into breast cancer awareness, people with the little pink ribbon, stuff like that. Uh and saying, well, what if we could do preventative medicine before birth? Um what would that look like? And would I would be interested to know, this is another one of those can you be pro-choice and anti-mbbre screening? uh can you be um like pro- breast cancer awareness and anti-ambrio screening too because if what you're trying to do is reduce the prevalence of this disease and it comes down to it comes I think the personhood it's a it is a little finickity to get your hand to to grasp to understand well it's not a reduction it's a different person you're choosing a different person >> um and in some ways I actually bet that there would be a group of people that would be more comfortable with uh em genetic editing than they would with embryo selection. >> Is that because they you wouldn't be discarding embryos? Yes, >> I think that's probably true. >> Be a maybe a a small minority of people, but I think that there would be a well no no you choose the one and then you make the best that you can with that or some some something of that that sort of >> that's probably true. and they have an implicit theory of person or maybe explicit where they think an embryo, you know, has a soul and it's exactly like, >> you know, the fetus at 3 months and exactly like the person at 3 years and 30 years. I think that's completely wrong. Um, I actually think the case can be made for fetuses having a certain degree of personhood because they develop the relevant traits that, you know, maybe at 6 weeks you've got a heartbeat. It's it's primitive, but it's there, you know, and at 8 or 10 weeks the brain is starting to form and develop. Um I might be getting the timeline wrong but you can understand that. I mean this is becoming a human but an embryo is just an undiffer literally an undifferiated cell right so some some people will falsely say that about about fetuses right oh it's just a ball of cells that's not really true you know after a few weeks it starts differentiating but an embryo is not like that and unless you want to sacriize every cell in your body which also has the full comp >> embryo different embryo is different to just a skin cell surely >> yeah barely I mean not much it's it's an undifferiated cell it's you know I just mean it's It's the kind of cell that can become really any other kind of cell, >> but it is going to become a human if allowed to proceed under normal circumstances. >> Under normal circumstances, maybe. But I mean, here's a relevant fact. So, if you just do things the natural way, some large proportion of pregnancies, I think it's something like 40 40% >> within the first two weeks >> are spontaneously aborted. >> Crazy. Dude, when I found that stat out, I could not believe that that was the case. Can you just dig into for people that have never come across this before can you just explain that and the implications? >> Yeah. And the best evidence is because you can do this kind of post hoke you know analysis of this look at what's going on in almost all those cases they have annuployy it's exactly the thing that we're testing >> rejecting some sort of genetic >> abnormality. So the body is rejecting you know some kind of tricome condition whether it's down syndrome or something much more severe and it's doing that regardless. So either you think that God is creating this condition where your body is just constantly aborting you know embryos um and and you know that's okay but what God is not doing is allowing you to do the same thing before it's even implanted. It just it's a mystery to me. I mean these are things that are again they don't have there's no circulation there's no brain activity. I'm I'm sympathetic to the view that once you have those things, they have some moral status. And abortion is a pretty it's a horrible thing to do. I I'm conflicted about it myself and I'm pro-choice, but I also realize this is not just it's not just a choice. I mean, if you're eight months pregnant, you know, that's a viable kid, right? I mean, you could you could take that kid out and and somebody will adopt it and it'll be fine, you know? And so, I don't think it's just like a random choice and there's no moral status to the fetus. But an embryo is very different. And if it weren't, you know, again, people should be really upset about these spontaneous abortions following around these women, collecting them, and then trying to reimplant. >> It's called a spontaneous abortion. >> A spontaneous abortion. Yeah. Exactly. >> And that is a within the f within cycle. >> Yeah. Within the first few days or even couple weeks, women are doing it all before you even know you're pregnant. Happens all the time. >> Well, what a what a fascinating question, you know, to say, um, we're trying for a baby, but as of yet, we haven't got pregnant. and you go, "Well, maybe I did." Yeah. At what point do we call pregnant pregnant? >> Yeah. >> You know, within a couple of days and then your next presumably just at the next period this is this you wouldn't notice any difference. You just assume didn't get pregnant this month. It's like it was a different kind of oh man. Wow. That is so every time I think about that I think how clever the human body is and like how sad how how unfortunate it is especially for couples that are trying um and and and struggling >> and the older you are the more likely that's to happen. So basically >> the more genetic abnormalities the older that you get. So >> exactly and this is specifically on the female line. There's problem with older sperm of course and you know there's some correlation with autism and later life children but for the female side you're not only going to produce fewer eggs you're going to produce more damaged eggs and specifically annuploites these kinds of uh chromosomal problems and so you could say again like if you were a 40-year-old much more likely to have quote spontaneous abortions than a 20-year-old simply because you're going to have more annupoid embryos. If you were if you were regulating this space, what um what red lines would you draw? What what what you've mentioned before that there are some promises being made that aren't legitimate? You've mentioned that there are certain traits that shouldn't be that maybe should or shouldn't be allowed, etc., etc. Um it seems to me like your libertarian bonafidees are coming back in a little bit like I want government out of this but also there should be some perhaps not enforced top down but almost expected norms within the companies so on and so forth. What are there any are there any actual hard red lines that you would draw possibly? So um yeah we can talk about things selecting for against but I think the main thing is transparency. So, you know, governments, you know, make companies say things all the time. I mean, sometimes it's annoying like you have to, you know, when you have a software program and you have the 30 pages of legal ease that you don't read and then you have to consent to it, right? You don't really know what's going on with drugs and so on, you have to make them disclose side effects. I think we should do something much simpler, which is you should at the very least publish on your website and then hopefully publish in scientific journals, which is what we're doing. your validation studies. Um, how much of the genetic variation for any condition can your best predictors explain and how do you prove that to us and how does it work across ancestry groups? >> What's the likelihood that this is going to get open sourced at some point? Because obviously you guys have you guys have got proprietary this with that, this with that and this is your moat. This is the moat that you currently have, right? algorithm that's able to predict it and assessments between what this means and what that results in genotype phenotype expression versus gene. Surely someone's going to steam in and just [ __ ] open source this for everybody and then it means that it's basically a marketing race. >> There's already a public catalog as it's called for polygenic predictors. Most of the stuff in the public catalog aren't very good. There is one company that is exclusively relying on those which is absurd because that's a very well- capitalized company and instead of doing proper research which is what we're doing we're like buying as much talent as we can to access as many bio banks as we can and to actually turn that data into real predictors that we can validate. Like that's one way to expend your energy. Another is to do flashy marketing and then rely on this shitty public catalog of polygenic predictors. And some companies are doing that. Um, I take it as those cataloges get better, which they they certainly will, right? Um, yeah, it's going to be a way for everyone to access these and what's going to happen is there's more of an arms race between the best companies. Right now, it's us, but surely there's going to be good competition coming. And um, I think those scores are going to get better and better. But, you know, it's like with every innovation, you know, we're going to be fighting at the margins 10 years from now with slightly better predictors where the public catalog at that point will probably be like 80% of the way there and almost free or or completely free. And so, actually, this is another thing where it's like if you talk about inequalities, you know, there's always this innovation access trade-off where it's like, yeah, at the beginning you've got this innovative thing. it works really well and only the richest people can can access it. But what they're really doing is just subsidizing poor people 10 years from now to have a really good product in some cases much better than what you had 10 years earlier. >> Whatever the first cell phone was $12,000 and for now 50 bucks you can have something hundred times better. I mean it it's it's infuriating when you know the US or Switzerland is blamed for drug prices in Africa and it's like well those drugs wouldn't exist if we didn't spend billions of dollars you know inventing them and then we give them away to to foreign governments for free and then in some cases people are still unhappy about that you're g either you're not giving them away free or you're not giving enough of them away free and it's like guys like we've already taken on all these costs like you should be grateful for this actually and you know you can accelerate in that to some extent it's going to happen in this realm I'm sure >> I think what's going to happen I mean for what it's worth you know everyone always asks oh China surely they're doing this they're ahead of us no they're not like we we know the talent in this field it's very it's a small pool it's very very difficult to develop good polygenic scores and then validate those things it's extremely difficult so we know all the people in the field and they're not Chinese however I will say as with so many things the Chinese will take notice I'm sure now that we're coming out >> say I hope your data security is very [laughter] good >> yeah no but but also I mean even legitimately doing it not just with like leaked data yeah we do have really good data security but but I think China the government doesn't really know how powerful this is right now and um I think they will know >> you haven't accounted for how many of the uh Chinese government officials listen to the modern wisdom >> yeah of course yeah exactly well in a few weeks they'll know when we release this >> but Um, I do think they're going to take notice and what they're going to do is there is a Chinese bio bank and they're going to put more traits in it, including cognitive ability, including try to get personality traits down, all these things that explain maybe even aggression. I had this discussion yesterday with someone and, you know, in some populations maybe they'll like try to weed out aggression and select for empathy. In China, you know, if the government is controlling it or >> they might tune it up. Yeah, they might tune it up, you know. And so I I again back to George Bernard Shaw, man and Superman, technology is a tool and you can use it for good or bad and you can decentralize it to the maximum extent or you can centralize it. And um I think I hope we have it mostly decentralized where we have norms policing it plus laws that require transparency for companies because I do support that. I want everyone to be able to show their work and be forced to do it so they don't manipulate consumers. But with China, yeah, I think they're gonna, you know, they'll end up building like a bigger bio bank with more traits and maybe hiring up poaching some of the best scientists from from Europe who's going to continue for the first few years whipping themselves, flagagillating themselves over World War II. This is eugenics. This is what the Germans did while China just takes off. And then some some years from now, all these European countries are going to radically shift course, right? Why? Because first of all, people don't want to pick a sperm or an egg at random. They don't want to pick an embryo at random. Right now in Spain, we've had customers who are Spanish and they have to leave Spain or France or Germany or whatever to do this. >> I was going to say it's banned in Europe. Basically, what you're doing >> for the most part. Exactly. But not only that, it's much worse. If you want to know you're you're a lesbian couple or you're a heterosexual couple, but the guy is infertile, so you want to get a sperm donor, for example. What can you know about that sperm donor in Spain? Nothing. nothing. You can't even see pictures of them. That's insane, right? And so, like, people want to know, you know, at the very least, is my sperm donor like mentally stable, >> you know, like what did they do they have any accomplishments? What do they look like? And obviously, they'll want to know the same for embryos. And I think the more real this gets, and it's about to get very real, the more that's going to put pressure on Europe to really reverse course. And one of the facilitating mechanisms is always going to be well India, China, these other countries, the Middle East, they have zero moral qualms and we have the evidence for that. I mean you could do opinion surveys I can tell you about those. They have no moral qualms. They actively think this is a good thing. >> And that I think is going to lead Europe and and of course the US to sort of move along with this. Well, when you talk about uh wealth inequality evolving into genetic inequality, here we're talking about almost geographic inequality, right? That the countries that have a culture which is pro- embryo selection and is prepared to accept the reality of behavioral genetics is going to end up with a very different future to the other ones. So I guess what what do you think looking to your crystal ball what do you reckon the next 5 to 10 years looks like with the is it going to be everywhere is it going to be accepted is it still going to is there going to be re are there going to be [ __ ] marches in the streets against this what what's everything going to look like and how widespread is it going to be >> I think there are going to be some religious extremists who are going to be really upset and you know threaten IVF clinics in the west and that'll be you know on the one hand some kind of right-wing religious extremists and also the woke left because they're immune to genetic explanations and you're >> whole shoe continues to horseshoe. We've exactly we've ti we've we've we've mentioned this I think in both episodes we recorded before but you know progressives have made a huge mistake a catastrophic error in tying their worldview to the blank slate theory of human nature because that view is about to be unraveled partly by technologies like this and the incentives it creates where people are now forced to confront like okay this is real like if I'm having kids even if I don't use this technology I'm going to think about it because like it exists. and and consciously not use it or when we have these explanations for the human past, you know. So, for example, if you want to know when did human migrations happen and why do populations look the way they do, you you use polygenic scores in ancient DNA to explain that. So, I have this thesis now actually that polygenic scores are going to be this, you know, not arguments, but technology is going to break the break the blank slate more than anything else. And it's just going to be a huge mistake where some people again on the left and right for different reasons are going to vehemently oppose this. Other people and other countries are going to push this hard. And here's one here's one possibility. In the next 5 to 10 years, China, Israel, and a few other countries have already announced that they want to subsidize IVF in order to boost birth rates. That's going to naturally make the relative cost of embryo screening go down. There's going to be more pressure. That'll create more pressure for people to, you know, pressure the government to to have polygienic traits subsidized, including potentially intelligence and, you know, these disease traits. And then that's going to have effects on their neighbors. Oh, China's doing this. Okay, now I'm going to do it. Israel's doing this. You know, Lebanon's going to go, well, we better do it, too. And in fact, this is happening in the Middle East right now. Um, we've discussed this before, but because cousin marriage is so high in well, actually in the UK now, partly because of immigration, but you know, cousin marriage is so high in in the Middle East in in specifically Muslim majority countries that some of these countries have responded by banning cousin marriage. Others have responded by making genetic screening either cheaper, free, or mandatory. And so, >> question on that. Actually uh I I'm I can ask this question because I'm an only child. Would you be able to produce viable children from brother and sister with your s with >> Yes, you you would um still be incredibly inadvisable and if you take first or cousin second cousin marriages especially, you could do that. Like there are going to be some embryos that are at much higher risk than others. And um yeah, indeed this is going to be a use of this potentially. And like if I were in Emirati, um, and I guess I'm going to the Middle East soon to to meet with some of these people. >> Mhm. >> You know, my my policy would be banan cousin marriage and enforce that. But for the existing people who are married, they're probably not going to get a divorce. >> Um, and you should probably encourage them to do IVF to try to >> to try to minimize these problems. And actually, indeed, you you can pretty much eliminate them if you have enough embryos. eliminate the problems associated with that. Brothers and sisters, it's going to be a little harder and uh yeah, it's pretty [ __ ] up. Pretty inadvisable. >> Well, I mean, look, the Lannisters, if the Lannisters had known about the opportunity. >> Who are the Lannisters >> from Game of Thrones? >> Oh, I didn't watch Game of Thrones. >> I did not know. >> There's a there's a male female twins who keep on having kids. >> Wow. >> And uh Yeah, it's hilarious. Anyway, >> it's fantasy, so you know, anything goes in fantasy. >> It does indeed. But they didn't have access to Herasite. Johnny Anomaly, ladies and gentlemen. Dude, uh, I have been fascinated by this topic ever since we first spoke about it. Um, Plowman teed me up. Paige Harden came in after, and then you, and you know, I continue to I continue to get be fascinated. Um, it's certainly something that I I feel is an inevitable part of our future and I'm like cautiously positively disposed to. I'm like moving toward it bit by bit and I think I'm a good avatar for kind of the normal inquisitive person and uh every time that we speak I feel a little bit less icky about it. So uh hopefully you can keep going on that track. >> Yeah. in in a virtuous society, you know, whether it's ancient Greek society or now, you know, if we if we think the good, the true, and the beautiful are things that are worth, you know, revering and promoting. I mean, this is just one more way of doing that. So, I'm actually quite optimistic about the tech. >> Okay. Why should people go want to check out more of the stuff that you >> Yeah, come to herite.com and that is after the Greek goddess Hera, which is the goddess of fertility and and childbirth. So, herite.com and you can look at our embryo IVF calculator. you can look at what gains you can get in terms of disease reduction, even intelligence gains. And we're also going to put on there a bunch of videos and stuff like that. But one of the coolest things is the associations between intelligence and and all the different life outcomes. And and that's kind of the cool stuff. It turns out like selecting for IQ is not just a thing you do selfishly to have smart kids. It makes them more likely to live longer, healthier lives. Makes them more likely to be cooperative. It's really cool [ __ ] So yeah, come to herasite.com and and check out our website. >> Heck yeah. Thank you, man. >> Thank you. Thank you very much for tuning in. If you enjoyed that episode, you will love this one with Mr. Naval Ravakan. [music] It's first episode in six years. Go on, press it.