#35 - Noor Siddiqui

28:16Yeah. And actually, if I recall correctly, that particular variant is something that's more common among sperm of older men that it's like a hyper mutable region or something like that that tends to you tend to see more achondroplasia in children of older men that there's some sort of that part of the genome is actually more susceptible to mutation in that particular way which is interesting i actually don't know like you know the the full ideology of both of these diseases i just think that you know when you when you're looking at that previous slide where we're talking about um you know these thousands of of of different diseases a lot of these are honestly are are fatal are extremely serious.

28:55People don't have an emotional reaction to it because they don't know someone with arterial calcification or any of these sort of diseases that have strange names. They're not very relatable. But I don't know. I guess what I'm trying to get across here is it really matters, right? It could be the difference between your child having a terminal condition or not. It could be the difference between someone being very three standard deviations from the norm in terms of height in either direction, right? So these changes do matter. And it's very reasonable for parents to want to scan for this information because it can have a very significant impact on their health trajectory.

29:35So we kind of already talked about monogenics. Now I'm going to get into polygenic. So again, monogenic is sort of that single gene, single variant of a specific disease. Polygenic is trying to understand conditions like heart disease, schizophrenia, bipolar, where it's not just driven by a single gene, but rather it's the cumulative effect of many, many different variants across the genome. So, you know, the study design, the way that they actually, you know, build these models is pretty simple. They're looking for sequence variation. They have sets of people who are, you know, unaffected controls, and then they have people who are affected.

30:09So, you know, folks who have schizophrenia, folks who have bipolar, and then they're looking for enrichment. So basically which variants are more common in the cases as opposed to the controls. And in terms of the performance, this is what the shape of these curves often look like, right? So you're looking at how often do people get heart disease and what is the percentile of their risk score? So in the 50th percentile, that's about average. And then what you can see is that there's a really strong risk increase when you get to the much higher percentiles, right? The 95th plus percentile of risk, right?

30:44So that's kind of what the type of risk that we highlight. It doesn't really matter if, you know, the 30th versus the 70th percentile because a very small increase in risk. But if you're at the tails of these distributions, there is a very strong signal from that genetic component. So that's kind of what parents can learn. Is it, okay, is my embryo in that low risk or average risk category, or is my embryo in that high risk category? The thing about it is there's N variables on which you've got curves like this, whether they look exactly like this or not, because that is coronary artery disease.

31:11You've got N more that are like that. Yeah. And so how do you think about the multivariable aspect of that? Because an embryo that's high on some of these will be low on others. Yeah, yeah, yeah. That's actually a great... So I'll actually get into that. So basically one thing that... Because you're doing best of N across a vector of K variables where K is usually much greater than N. Yeah, yeah, yeah. So I think one of the things that people are really trying to understand is that if I'm selecting an embryo, that's low risk for one condition, does that mean that they're going to, you know, conversely be higher risk for another condition?

31:42And they've actually already built what's called correlation matrices where they'll say, okay, is heart disease correlated with atrial fibrillation? Is it correlated with schizophrenia? Is it correlated with bipolar disorder? They've done this across Yeah, but you wouldn't need to do it that way because you actually have, if I'm not mistaken, you have actually the raw underlying A's, C's, G's, and T's. So you can form, let's say you have N embryos and you have K conditions on which you're screening for, and then each of those K conditions has um m sub k underlying loci right that contribute to it which is a ragged list for each of them right yeah then you can you don't have to do the calculations you can actually go to the exact loci you can say let me calculate the pgs for this n by k table yeah and then you can just see you know how many shared variants are there yeah right yeah yeah so basically what i guess what I'm getting at is like what you see is there's an aggregation with diseases that are related.

32:42So basically heart-related conditions, you know, heart disease, atrial fibrillation, those aggregate together. They have a shared architecture. Mental health conditions like bipolar disorder, schizophrenia, they aggregate together, right? So what ends up happening is you get to actually reduce risk for multiple conditions at once, right? So an embryo that's, You know, high risk for schizophrenia is also, you know, likely to, there is a shared genetic architecture for other mental health conditions. So rather than there being a trade-off, what actually happens is that a lot of these conditions that are for similar systems end up actually having those shared variants.

33:18So anyways, I think that's, I'm trying to kind of just kind of respond quickly to what people usually, they're sort of immediate. And how many conditions are you looking at there besides coronary disease? We're looking at about 12. I'm going to give you the full list. But kind of thinking about this, you know, sort of from like the South Asian standpoint, right? If you roll the dice, you might get an average outcome, right? So what if the average outcome is chronic disease, right? So South Asians, we get heart disease at, you know, four times a higher rate than any other ethnic population, right?

33:48We're twice as likely to die. You know, 25 % of heart attacks occur under 40 for South Asians and 50 % occur under the age of 50. So we're getting heart disease 10 years earlier than the rest of the population. Right. So I don't want that to affect my child just because that's something that, you know, a lot of South Asians have. That doesn't mean that I want that to automatically be a part of. These are one of the biggest causes of death, right? And especially in terms of reducing the quality of life, right? A heart attack, even if you survive it, it's sort of, you know, you're able to run as off a lot of consequences of this, right?

34:27So the idea that parents shouldn't have access to mitigating the biggest vector in terms of mitigating risk for disease, yeah, I just think it's insane, right? Because what you can see, right, you're just talking about, okay, you know, you're trying to quantify, like from the math perspective, how much risk reduction is actually possible. And it's really remarkable how much you can get with a really small number of embryos. So this is looking at kind of the worst case scenario, right? So let's say you have two parents, both mom and dad are at high risk. And what you can see is that you can get a 30 % risk reduction with five embryos with, you know, a pretty poorly performing model.

35:10And if you're in, and this analysis, by the way, you know, wasn't done by Orkut. It's done by an independent statistical geneticist who just published this paper that I just love these figures that he produced. So then, you know, if you use a slightly better model, you get a 40 % risk reduction with five embryos. And then with an even better model, you get a 55 % risk reduction with just five embryos, right? So this is… Interesting. So it starts topping out… Wait a second. So the software gain is the difference between the triangles, the circles, and the squares. Yes. Yes. Okay. So just… And then once you get to about nine or so embryos…

35:49Yeah. Right? Yeah, you're seeing this behavior where it starts to flatten out, right? Because you sort of sampled from the distribution in terms of how much risk you can reduce. On one condition. Yep, this is on one condition. Right. But multivariate, the problem is if you're optimizing the minimum risk on one of your 12 things, the other 11 are loose and can have higher risk. Right. So you have some weighted sum of them that you're doing this on. well this this one is not looking at all we can look into the methods but this figure specifically is talking about uh reducing risk for one condition no i know i know but basically you would have this kind of figure for each of the 12 but opt reducing risk for let's say you picked the the best of five that got you the lowest risk on condition one right yeah then conditions two through 12, you might have higher risk.

36:50So you have to sort of spend your optimization budget. Yes, yes, yes, yes, exactly. So the thing you want to think about is that probably for those other conditions, if you're playing in this realm, it's not going to make a big difference. So you really want to be focusing on what is the condition that your embryos are at high risk for, where there's a really big delta, you know, right? You want to just get them out of that like 97th plus percentile, which usually for 12 conditions, you're not going to have multiple, where you have embryos like you're not going to have for multiple diseases that you're in the top three percentile of risk if that makes sense right because if you're playing that that's kind of does that make sense did i explain that less yeah totally keep going yeah yeah so um yeah so basically this is kind of like the worst case scenario right you have you have you're pretty constrained because both mom and dad are high risk um and you still get this pretty massive right 30 to 55 percent risk reduction right so people don't really have again a good way to conceptualize how massive this risk reduction is.

37:44So what I'm trying to compare it to is, you know, this is more powerful than the most successful drugs on the market, right? Drugs that are making, you know, a billion stalls a year, right? So here's two drugs. You have, you know, a drug for COPD. There's just basically one obvious point of this is there's just massive healthcare savings from this potentially if we can get IVF and so on out there because just like many - Yeah, yeah. Usually what I'm trying to get people to grok is like medicine is not very good, right? It costs a billion dollars and 10 years to get a drug to market. You prefer to be fixed at the genome level rather than the labor.

38:20Yeah, but even more than that, I mean, it only has a 30 % relative risk reduction. That's what we're comparing relative risk reduction to relative risk reduction, right? We'll talk about absolute risk reduction later. But the point is, is that some of the best drugs on the market only get a 30 % relative risk reduction. Then you're leased to that drug for life. And there's side effects, right? If you do this for your embryos, there are no side effects, right? You already decided to do IVF. You're picking an embryo. The question is just, do you want the embryo to be at higher risk or lower risk?

38:48And then that risk level is the same for life. You don't have to continually take a drug every single day. Because the other thing is that when they do these studies, you don't actually get the benefit if you're not perfectly inherent to the medication. And there's entire companies that are built around how do you get someone to actually remember to take a drug every day. That's also not trivial, even if you get a drug to work. Great. So, yeah, then if you kind of look across the other situations, right, like you might not be in that most constrained situation where both mom and dad are at high risk.

39:21Right. If you're in a situation where mom and dad are average risk, you know, you're getting up to an 80 percent risk reduction. Right. And if you're in a situation where one is high and one is low, you're kind of topping out at maybe 70 percent, depending on, you know, what the power of that predictor is, how well understood it is. So, yeah, all of this to say that I think this is like a huge area where people can potentially massively change the trajectory of their child's life with really kind of a like surprisingly minimal cost for how big of a component the genetics is. And kind of this is kind of what I was trying to talk about earlier, which is, you know, what are the genetic tradeoffs?

39:58Right. So you can do you can build these correlation matrices where you look at, you know, which conditions are correlated to which other ones. and you can see that, you know, psychiatric conditions, you know, kind of are the most correlated with each other, you know, cardiovascular conditions are correlated with each other. But, you know, schizophrenia is not correlated with height. It's not correlated with type 2 diabetes, right? So it's not the case that, you know, you're necessarily trading off risk for one thing, for another thing. And, you know, people, again, not just work at, but the entire physical genetics community has done a ton of work to look into this and to see, you know, what are the potential, you know, trade-offs or shared architectures between these conditions.

40:43Yeah, this is kind of the take-home point, right, is that having lower genetic risk at birth is likely more powerful than almost anything else that you can do later in life, right? There's no diet, there's no exercise that's going to, you know, mitigate risk for schizophrenia, right? There's nothing that can, you know, change, you know, the chance that your child has pediatric cancer if they have a specific variant that makes it extremely likely for them to have it, right? So I don't know. I think it's sort of like this massive benefit that's hiding in plain sight that people are, you know, instead of embracing, they're kind of, you know, coming up with these really illogical arguments for why it should be stigmatized.

41:25Yep. Basically, the thing is, go ahead. Oh, I think, sorry, I think this is the last point, right? So it's sort of like people have actually already surveyed the public and said, you know, what is their opinion about embryo screening for, you know, child's at onset, adult onset, polygenic, monogenic. And the American public is really strongly in favor of this, right? 72 % either strongly approve or approve of embryo screening. And here's a number that I think is actually even more surprising, right? So 30 % of Americans would either definitely consider... That's a random sample. Yeah. Yeah. It's OK.

42:01This is a random sample and it's also older folks. So I actually think that if you I think the average age was, I think, like 40 or 45, which I think is older than. Fascinating article. You know, the set of folks who are actually going to be considering having kids. If anything, I think this is an underestimate of how many people would consider, you know, doing IVF. And I think it's actually a 2024 paper. Yeah. Yeah. So I think that I think people should be really shocked by this number. Right. The fact that a third of Americans are considering, hey, I would not have babies the old-fashioned way.

42:31I would rather have babies consider using IVF in order to mitigate risk for these conditions that I've been affected by. I think that that's extremely... Interesting. Nationally representative sample. Yeah. At least for... Yeah. Interesting. Yeah. So I think that this idea that, you know, IVF is somehow like... IVF is very different if you are fertile and you're not struggling with infertility, right? It's sort of like, hey, it's like this inconvenience that you have to be on medication for two days. And, you know, it's like, I mean, for a lot of people, it's like a bad period, right? I'm not trying to diminish what it's like to fight infertility.

43:06It is extremely difficult. You know, if you have PCOS, endometriosis, a lot of these other conditions, infertility is like equivalent to a cancer diagnosis. But for fertile people, you know, it's an extra, you know, two to three weeks of discomfort compared to, hey, you're going to have a nine month pregnancy. You're going to raise this child for life. You know, do you really want to risk, you know, a condition that you've been affected by or kind of these random genetic typos affecting a child? And I think that a lot of parents are going to say no, right? I mean, even just if you think about miscarriage, right?

43:38I mean, it's extremely, yeah, it's extremely, you know, emotionally costly to have. Oh, there you are. I can share the screen for a second myself. So here is the article that you're just mentioning. I was pulling it up while you're talking. Here is the Approval and Interest in Polygenic Embryer Screening. This is a 2024 article. And so actually, this is a great figure. 45 % approve, 30 % strongly approve. Should be allowed 80%. This is an amazing graphic just for the Twitter bubble, just for people to know. Just FYI, it's like 80 % should be allowed. Okay, number one. And it's even higher IVF, right?

44:24The idea that there's like... Yeah, IVF for the purpose of PS use. Exactly. and then approval for various outcomes so you know for health conditions it's like overwhelmingly there right but even for and psychiatric conditions like mental illness overwhelmingly there but even here it's like close to 50 50 right like you know these are these are looking like you know in the sense of uh no opinion if you delete no opinion in a sense right these are close you know so it's like maybe it's five to one ratio or something like that what's that like eight 80 to 10 eight to one ratio for some of these bars and here it's like a one-to-one right in sense of close to 50 50 but um that's actually that's that's what i've called this is non-controversial yeah this is controversial but in the sense of 50 support and 50 opposition which means on the order of 50 % of states or jurisdictions may actually legalize it.

45:23Right. Yeah. So and then, you know, if you look at what conditions and traits and so on, so cancer, heart disease, Alzheimer's, diabetes, just basically overwhelming like this, you know, and you get to obesity and that's actually still pretty high over here. And it's only only when you get to skin color, that's extremely negative, even like intelligence. So and again, this is this is close, right? It's it's more disapproved than approve, but it's not orders demanding to you add up the red and the yellow versus the blue and the other blue over here, neuroticism and so on. So BMI is basically very similar to obesity.

46:00So it's interesting that it's different. The phrasing of the question sometimes matters. Um, and then, you know, concerns, um, interesting, interesting paper. Good paper. Yeah. So I think it's just people don't, you're, you're totally right. There's like a twitter bubble and people don't realize that you know the vast majority fyi 80 percent of people support embryo screening in a toy 24 study yeah yeah it's just important actually send me your deck also because i will preview this uh i will preview this uh pod with the um with both that and the one base pair right like is eight foot three versus two foot seven you know literally one delta alteration because just i want to give you just one asterisk on that one so um i don't have those people's genomes i just looked up for gigantism and achondroplasia okay no no so yeah so we're not giving them a diagnosis i'm just saying for gigantism and achondroplasia this is these are the single base pair causes of it so just i'll give you like exact copy if you want of like how what those mean but i just want to give the caveat it's like we're not giving them a diagnosis we're saying for people who have gigantism right contemplation so i think i want your commentary on like the moral necessity of this and then maybe a little bit of your commentary on the scientific side too because i think i might have gone too deep so i'd rather i would like for you to like summarize it because well well first is um i mean on the left the entire thing for the last 50 years has been my body my choice so how could i possibly not extend how could you how could you define reproductive choice so narrowly as to say it only extends like you can only terminate in some cases or not others or screen and so that doesn't make any sense at all right so just just choice alone so basically everybody who's in favor of reproductive choice on the left should obviously be in favor of embryo screening or certainly not pushing to ban it even if they don't do it themselves if it you know as they used to say, if you don't want it, don't have one, right?

48:05As for the right, I do understand the social conservative argument. I disagree with it because I think that the, quote, wisdom of repugnance could be applied to many, many, many, many things, right? And what we think of as normal, like, circumcision could be considered really bizarre and is considered bizarre in some historical cultures or what have you. Heart transplants would be considered bizarre in some cultures. um certainly past culture surgeries um like the screening of blood you know urine samples fecal samples all that stuff that's like completely normal in any biomedical clinic if you just go by oh that grosses me out you wouldn't do it and we have millions of ivf babies and we have millions of ivf procedures and we have existing screening for aneuploidies and monogenic disorders We have all the infrastructure set up.

48:57We have 80 % support from people, as your paper shows, for screening, even in the West. And it's almost certainly higher in the East, just given the numbers I've seen. And the whole point of the Human Genome Project, billions and billions and billions of dollars, was to use the genome for human health. Like all these taxpayer dollars went into this. So that's yet another argument that is, if you were a taxpayer on this, it's your right to use that information, right? And then you're also choosing your partner, that's 50%. And that certainly wasn't a roll of the dice. And this is like an edit around that.

49:34And then moreover, for many populations like South Asians, chronic disease is actually, unfortunately, the average outcome. Because in the modern environment, modern nutritional environment, we have very high rates of heart disease and of type 2 diabetes and other kinds of conditions. and so you put all that together and uh it is really something where people are some people are just reacting in this really stupid emotional way and you know that's their right for themselves you know for themselves whatever you know i'm not certainly not saying they should do it if They don't want to do it, but they definitely can't stop somebody else because at some place, you know, some point on the face of the earth, there will be, given that it's controversial, not in a 99 one way, but at most a 50-50 way, there will be 50 % of jurisdictions that do it.

50:36And then what are you going to do? You can reverse the argument on them. You're going to discriminate against that IVF baby. Oh, huh? You know what you think they shouldn't exist right and um so in general i think uh one of the most interesting things about this by the way is a dog that didn't bark which is that tech is in favor of this right and uh that is that is a huge thing where the builders are in fear of this because we know life is hard enough life is there's a lot of difficulties in life um and uh you know if somebody has chronic disease heart disease or something at 50 and they could have not had it why why would you you know it's this weird thing where life expectancy by the way as you know was quite low in day to under average life expectancy because all kinds of infant mortality had not being solved, right?

51:34So infant mortality is very high in the past. And as a consequence, some, you know, people used to write, and even adult mortality was high, depending on how far back you go, right? And I mean, people within our, I mean, great-grandparents' generation, all kinds of modern conveniences from electricity, running water, all kinds of things were just not present. And so, you know, really what it's related to, I think the resistance, not, I mean, the resistance to embryo screening is part and part, I think, of a broader anti-tech thing within the West, which is like people setting self-driving cars on fire, right?

52:14People getting mad about AI, people getting mad about crypto, people getting mad about immigrants taking their jobs, people getting mad about, you know, data centers and their electricity consumption or something like this people just getting mad about tech at all because tech is changing a lot of things and they just want you know no more stop you know i want to just i just want to stop i want to reverse the world and so on this is similar emotion in the late 1800s early 1900s uh around the industrial revolution and uh you know because the big belching factories all the pollution and so on and to be clear i'm not saying that there aren't some you know like we developed cars and then we developed walkable societies and we took away highways from some parts and so on so we developed the thing and we realized we had overdeveloped it somewhat so we removed some developments but we kept developing cars because we still did electric cars and self-driving cars and now flying cars but we also had walkable communities and so there's a balance between them and um you know my view is life is difficult enough why roll the dice doesn't matter why roll the dice when you'd have to there's going to be 5 000 more dice rolls yeah you could get hit by a car why do you want to also have to go blind yeah you can you can already get hit by lightning you get hit by a car you can um i mean there's this five million other things that can go wrong right why do you want to you know again this is this is the kind of person i think who maybe they don't want to put on their seat belt but why are they preventing you from putting on a seat belt you know yeah so what do you think is this deal man like what do you think is the most like i think we talk a lot about the arguments that kind of are just nonsensical.

53:51They just result from ignorance of not understanding how the genome works, how IVF works, how, you know, genetic screening works, right? So what do you think are maybe even the most sincere arguments? Yeah, sure. The steel man would be that far leftists have abused science, to call it capital S science. And they said masks don't work before they do. And they said that during the BLM riots that racism is a real pandemic after telling everybody to stay inside and they people ran outside and they call a paper that was published a day ago in nature they call that science capitalist science as if it has the same number of replications as maxwell's equations because they equate prestigious citation uh with and they basically substitute prestigious citation for independent replication independent replication of what science is yeah go ahead oh yeah i just say yeah like yeah but those are two totally more than yeah the replication matters way more than uh like a shop which is just a journalist yeah yeah exactly and so the thing is that the peer review basically means like two or three thumbs ups it's like if you imagine actually you need to be a social network where people post papers two or three likes from someone in that social network it's a peer-reviewed paper it's not like they're it's rare that someone goes and replicates the result where they replicate the result is on github where you get clone and then you try to compile it or build it right so that's actually where you get replications and that's actually the future of what academia is it looks a lot more like github and reproducible research and so on and so forth yeah um but so so because of that there's and of course universities are like 99 democrat or something like that and uh a lot of people have not gotten a share of all this technological progress and of course we're also demographically different from a lot of people you know we are uh so tech is in the u.s it's focused on the west coast it's focused in cities it's got a lot of immigrants got a lot of indians pakistanis chinese koreans japanese gays jews um that's that's how you know the right would consider it foreign and then for the left it has too many white men capitalists and you know so on and so forth right and um and so both the far left and the far right look at it as alien and different and the far left emphasizes the capitalism and the right emphasizes the immigrants and the left doesn't like the economic change and the right doesn't like the cultural change and they basically just wanted to go back to the way it was very roughly right and that is just an overwhelming go ahead that is quo bias is what you're saying more than status quo bias unabomber bias right what i what i actually think is going to happen just to digress for a second is not even digress many years ago i mean five years ago ish I realized, and I wrote about this at the time, that after all the Sturman drawing, that after everything is said and done, the final political axis will be, let's call it, futurism versus primitivism.

56:51Right? They will call it humanism versus transhumanism. Because they'll say, oh my God, transhumanism is so bad, blah, blah, blah. So, and we're just being human. We're being normal right now the thing is being a normal human means no electricity no running water no light bulbs and so on so forth in their heads okay yeah and so like there's no way that that societies cities could sat could have the carrying capacity to to have a unabomber lifestyle where he's literally living in the woods but we do have that as part of our dna in a literal sense because we uh you know our common ancestors were similar to chimps and so we do have millennia of you know the outdoors and and so on in our dna in a sense so there's some you know genetic yearning for that i'm sure however there's another interpretation which is that humanity is actually defined by technology for example richard rangham is this book which is like cooking made us human why because the fire allowed us to externalize metabolism so you could spend less energy on your gut and put more to the brain and then if you you take fire you take weapons like the spear you take clothes right the spear you don't need fangs with the clothes you don't need fur with a fire you don't need gut enzymes and all three of them freed up more calories for the brain and so encephalization quotient just rose across um hominids and you know i posted that a while ago it's like uh the first singularity did you see that the original singularity oh this is a good one yeah so basically it's like it's like basically it took you know millions of years for you know the human brain to evolve so it's sort of like if you compare that to um you know gpus and cpus it's like the timescales are very different yeah and by the way elon agrees true right yeah but this is original singularity right and the thing about this is um what that means is since humans began we have been pushing it into software it's the same process that took all of the you know took fangs and turned them into spears and took fur and turned into clothes and they took the gut enzymes turn into fire and push everything into the brain to manipulate all these tools is the same thing that's taken all kinds of devices from a camera to a recorder and so on and pushed them into software in the phone.

59:25The same kind of thing that's taken all kinds of tools and just pushes them into AI, right? That takes all kinds of stuff and pushes into the screen and into software and you have less hardware and it's more done in software, right? So we have been doing this concept of push everything into general purpose software has actually been a winning strategy for 10 million years. Right? And this also says, actually, what makes a human is the use of technology. Yeah. Because an ape can't use a spear. It can jump along the woods or whatever, right? But maybe they can use some basic tool use. We understand my point.

1:00:00They can't... Animals, unlike humans, basically can't use technology. Certainly not advanced technology. so actually technology is what makes us human and reversing technological progress you know stopping let alone reversing it actually makes us unhuman it's anti-human right so that's why i call them primitivists because they want to regress to something in the name of doing something natural they're doing something unnatural and they're stopping the singularity that actually defines humanity right yeah so that's actually the crucial reversal because it's actually you know primitivism is essentially the new version of communism because communism also appealed to kind of the natural small group sharing and so on and so forth primitivism has enough changes to its genetic code that conservatives don't recognize it as communism even though it's the same thing if communism was against capitalism primitivism is against technology okay but of course techno capitalism is a very correlated thing right so we have antibodies to communism because that's against capitalism.

1:01:08So instead of targeting capitalism directly, they'll target technology. The left will be against the capitalists and the right will be against the immigrants. And the center, a lot of well-meaning Jonathan Haidt type guys will be against the phones. And the problem is, I understand why they're against the phones, but basically moderated use of phones works in many other cultures around the world. The problem with the West is they don't have any moderation of use of phones for kids and so on and so forth. right so what what happens is you have a collision of values that just don't have any sense to them what do you think is how this is going to play out for reproductive technologies like do you feel like it's going to fall along these similar lines of like you know primitivist versus absolutely primitivist versus futurist will be the axis and it's going to be legal in some important jurisdictions probably certainly in tech forward jurisdictions around the world the same kinds of places probably that are pro-crypto and have digital nomad visas will probably have, you know, legal embryo screening and so on and so forth.

1:02:06And the same kinds of places that are falling to primitivism of the blue or now the red varieties will probably be against them. Or we don't know. It's unpredictable. It can be very...

1:02:22the future is fragmented and you will have a lot of different combinations of ideologies that make sense to those individual people versus just a clean left and right and so at least some of those tribes some of those jurisdictions will be in favor of technology and those will probably be some of the best places to be usually they'll probably be the places that are prosperous enough that, and not just prosperous enough, ascending. Ascending jurisdictions are also ascending at the same time the internet is ascending. So they have a positive association with the advance of technology. The West, minus tech, is descending while tech is ascending.

1:03:02So even if they're rich, they're descending world. And whereas for, let's say, India or the Philippines, even if it's poor, it's ascending world, right? So that's why developed and developing world is the wrong way of talking about it because that implies a static developed world and the developing world is me moving towards it. Instead, it's the descending world and the ascending world. Yeah, I know. Yeah, that's a great point. Yeah, so I guess - The ascending world will be pro all of this. Yeah, so do you want to kind of like just summarize what you feel like sort of the moral cases, sort of like what do you think, like how do you think people are going to see this like today and maybe like how do you think that's going to change over the next couple of years?

1:03:43as it becomes more popular to reduce it to known moral principles in the west for left it's just reproductive choice yeah point blank for the right it is small government and why interfere with you know somebody's personal decisions that's like that's a very short secular political case for it, right? Then you can go and you can quote, you make the religious case in terms of doctrine and scriptures and so on and so forth. I don't think many, you know, it may turn out that there's some people who can quote Christianity and so on and so on. I can certainly quote Hinduism for it. I'm sure you could probably find someone who could quote Islam for it because there's many people in Middle East who are very pro-embryo screening, many people in the Jewish community who are pro-embryo screening because of, you know, carrier testing.

1:04:34So you could probably find scriptural arguments, I'm sure are usually for or against something, but in general, I think maybe the major faith groups could be for it.

1:04:46Yeah, I think that'd be my concise moral argument for it. And then, you know, the thing is, one of the issues is some of the arguments put forward against this are just based on genuinely stupid, reflexive, like an AI, you know, like association, like this, right? Yeah. And they just get mad for the sake of getting mad, you know? And they associate like a grain of sand embryo is the same as a human, is the same as this, is the same as that. And these rhetorical equations simply don't map to the reality. And it's like, oh, isn't it nice to have some chance, the pitter patter of poems. and i think there's a great tweet that you had which is like this is like a guy talking about how great it was to pick berries that didn't like the rise of agriculture you know it's just i the thing is that kind of argument is to them very convincing because just feels you know but feels can't build feels can at best for them ban but feels like doesn't know an a from a c from a T from a G usually, right?

1:05:59So they can try to ban in those jurisdictions and then they just won't be able to do it globally because you can show the poll numbers and so on and so forth. So, so long as the feels, you know, the primitives. He made a great argument around that, right? Because it's sort of like, hey, we traded electricity for candles, right? We traded cars for horses, right? We traded, you know, organ transplants for death, right? We treated epidurals for having, you know, a pregnancy. But the soldiers for guns were considered really cowardly relative to like soldiers with, you know, knights with swords who'd actually go up and see you and chop you and so forth.

1:06:38Like, you know, today we think of a soldier with a gun as brave. But in the past, they were thought of as cowardly because they wouldn't just go up to you and hit you with a sword. Right. So moral intuitions do change over time based on the baseline of what people think is, you know, the right thing to do. Right. Yeah, exactly. I think basically pointing out like, hey, what is lost, you know, from from, you know, having having babies through sex is like it's basically kind of like the most standard cliche for anti-progress. Right. It's like if you only look at what's lost and you don't look at what's gained.

1:07:09I mean, you could make that argument for, you know, why don't we hunt our own food with a bow and arrow and putting it at the grocery store? It's like something's lost. Sure. But what is gained? Right. Like the macro argument, I would actually say, is not even really the moral argument. it's a correlational argument. If people feel that their fortunes are just in general declining, which they do in the West, outside tech, they'll just be against any kind of change whatsoever, especially from the tech guys. If you're in tech and change is generally being good for you, you'll generally be neutral or positive on change.

1:07:41And if you're in the East or more generally the ascending world, then you're also going to be more positive on tech. So we should look to tech and the ascending world to legalize this stuff. And we should not look to the descending world to support it and we just need to divide jurisdictions on that basis and then it just kind of you know like i'm not saying everybody in the descending world will support it everybody in the descending world will oppose it but that's the way that you you should expect things to to play out right that's actually the macro above even the moral intuition yeah so what do you think is is so threatening to people about it like why is it like i i'm genuinely surprised by like the amount of activation uh so i don't know i'm just kind of curious if you feel like you have any i mean you know well first is people have been inculcated to they literally don't understand what genes are like they got mad yeah at the sydney sweeney has great genes ad yeah right huge numbers of people got mad at this it's just a pun because they're like i can't believe you're saying genes could do something oh my god right so like it's you know in many ways American society is like twisted into knots over genetics, over all kinds of things.

1:08:52You know, it's, it's this bizarre kind of thing where they're, I mean, look, there's a lot of wars that kill a lot of people and they're much less, you know, I don't know. I feel that the concern is, one other thing about it is the concern is like, it's like, it seems like extremely angry on the day that it hits, and then they just move on to the next thing two or three days later, right? It is just very much a passing storm. And if you just keep building, they just don't have the attention span or anything like that. Yeah, I mean, I think that's the thing that I think is most, I don't know, I guess makes me feel the best about it, actually.

1:09:34It's like, basically, the benefit to each individual parent is so great that random negativity is not enough to convince them, right? It's sort of like for each individual parent, it's the difference between is their child, you know, going to be able to meet their developmental milestones, be able to walk, be able to talk or not. And then for these other people who are kind of, you know, being negative, it's like, you know, they don't really have anything at stake, right? So it is, it does feel like this like really unique part of, you know, you know, healthcare decisions where people actually get to, you know, vote with their feet and then decide, hey, like, this is the thing that's going to make a difference for me and for my family.

1:10:12And, you know, they'll be willing to do that, even if, you know, there's a lot of, you know, loud voices on the other side. Yes, ma 'am. I agree. Okay, cool. All right. So let me wrap there. And any last words, any other things you want the audience to come away with? No, no, I think it's great. I'll send you the slides and I'll even send you the slide notes too. And then if you want to like AI or rejigger them to whatever content that you want, that'll That would be great.