John (35:23)
Yeah, yeah. The marketing claims are a big, big piece of this. I think the scientific claims are potentially just as important. But it's both, they're both understanding where the science actually is, both broadly and then also within the companies and then how it's marketed. Like all of that is important to get like a complete picture of what's going on here. So for her site, it's a polygenic longevity index. They don't give exact risk reduction numbers for each disease, saying that it depends too much on a couple's specific family history. But say that most people gain one to four years of healthy life. When I test it on a set of 20 embryos, the healthiest gets an extra 1.66 years. And so how much would you pay to give your children an extra one to four years of healthy life? This is no longer a hypothetical question. Here are the costs. Genomic Prediction is around $3,250, Orchid is around $12,500. Nucleus is around $9,249 and Herasite $53,250. That is expensive compared to the rest, five times the price. Is it worth it? Well, if you're already doing ivf, the claimed risk reductions are accurate. You value your kid's health as much as your own. You have low time discount rate, you're well off enough that these aren't extraordinary sums of money to you. You're okay using expected utility calculations where 50% chance of preventing X is half as good as fully preventing X. Then I'll go out on a limb and say, yeah, it's obviously it's worth it. Consider genomic prediction, which costs $3,500 for five embryos and claims to lower absolute risk of type 2 diabetes by 12%. That implies that not getting type 2 diabetes is worth $27,000. Ask anyone dealing with regular insulin injections, let alone limb amputations, whether it would be worth $27,000 to wave a magic wand and not have type 2 diabetes. It's not a hard question, and that's just one of a dozen conditions you can lower the risk for. Other ones, like not getting breast cancer, might be so valuable that it's hard to even attach numbers. So what about IQ6? Extra IQ points, which is Herasytes estimate with 5 embryos is about a quarter of the gap between the average person and the average Ivy League student. The benefits of intelligence are hard to quantify, but it's been shown to have probably causal positive effects on income, mortality and achievement. Probably the income effects alone make up for the cost of the intervention, again assuming total parent child altruism and a low discount rate. So if we accept all of these claims and assumptions, the choice seems obvious. It probably even accounts it's probably even obvious for governments to pay for all citizens to get these, given how much they'd save on health care costs, says Scott Alexander. But in practice, it's complicated. Critics have raised both scientific and ethical objections to polygenic embryo screening. Most significantly, it's been condemned by various bodies, including the Society for Psychiatric Genetics, the European Society of Human Genetics, and the Behavioral Genetic Society. Their statements are not good. They tend towards vague language about how people are more than just their genes, or how no genetic test can be perfect, or how embryo screening is not exactly the same thing as some other form of screening, which has a longer history and more proponents Although quote although in general, higher scores mean you are more likely to have a condition. Many healthy people will have higher scores. Others might develop the condition even with a low score says the Society for Psychiatric Genetics, as if they have just blown the lid off of some dastardly conspiracy. Screening embryos for psychiatric conditions may increase stigma surrounding those diseases, they continue. An objection which, taken seriously, could be used to ban every form of medical treatment because if you take care of something, you remove them from the population. That might increase the stigma, but we should still treat these. So, he says, we will mostly ignore these people and try to imagine the implications of the objections that mildly competent critics might raise, some of which will coincidentally overlap with the content of the non hypothetical statement. So the big question he wants to answer is scientific objection. The scientific objection around efficacy does this Are we sure where this works at all? Are we sure this works So a typical polygenic score is created by collecting thousands or millions of adult genomes, then matching genetic information with surveys about who has the traitcondition of interest. Reputable studies then test these scores on holdout samples, adults who were not used to make the score to see if they still accurately predict who has the trait condition. Polygenic embryo selection depends on an assumption that the scores which work in these kinds of retrospective tests will also work prospectively on embryos. This assumption hasn't been formally proven in studies which would require years or decades to conduct, but seems commonsensical. The strongest challenge to the application of polygenic scores for embryo selection comes from a recent body of research showing that most scores combine causal genetic effects with population stratification and therefore can be expected to lose much of their predictive power when comparing two members of the same family. There is an increasing agreement in the field that unless scores are validated within families, headline results like Decreases risk of X by Y percent will be large overestimates. When I talked to company representatives, they all said that they took accuracy extremely seriously and had various white papers and journal articles where anyone could double click could double check on their methodology. But I attended an industry conference a few months ago and the gossip level was comparable to a high school cafeteria.
