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- [00:00]
A
Noor, welcome to the Network CI podcast.
- [00:02]
B
Thank you so much for having melodies is awesome.
- [00:05]
A
Awesome. Great. So I was thinking we could start by just giving an overview of what orchard is, what embryo screening is, maybe what DNA is. Just very, very basics. People don't know anything about this. And then also kind of what you're shipping. And let's get into the moral case, right? Why it's actually important that, you know, if you're on the left and you believe in my body, my choice, which I think you and I do, then obviously, you know, you. You're going to want that to extend to everything. And if you're on the right and you believe in deregulation, decentralization, you know, like allowing people, basically a libertarian kind of view, then again, you should come to this, to essentially the idea that people's personal choices or their own business, and certainly a parent shouldn't be forced to do something that another parent or person wants them to do is not really involved in their relationship. So why don't we, why don't we, though, start with the. The first part and let's talk about the technology and let's talk about the moral morality and then the society. So you got some slides, I got some visuals.
- [01:12]
B
So what ORCID is, is it allows parents to protect their children in a way that hasn't been possible before. And what we're able to do is we're able to screen the entire genome of an embryo to scan for thousands of diseases that previously parents didn't have the chance to know about until after the child was born, after symptoms already developed, after, you know, a doctor has a really, you know, awful conversation with the parent that sort of ends with, you know, there's not much that we can do. So we basically give all of that information at the earliest possible stage when there is actually something that you can do, which is to transfer an embryo that's unaffected. So let's kind of start. Start at the very beginning of the birds and the bees. You know, how does an embryo actually form? So what is an embryo? An embryo is an egg plus a sperm. Each egg, each gamete. You know, egg and sperm are carrying 23 chromosomes that combines to create a zygote, an embryo that grows. So you can actually see this is how an embryo develops over those five days that it grows in the lab. So what happens is that, you know, it divides into multiple cells. On day five, you have about 125 cells. Five of those cells are sampled from the outer membrane, which is called the trophectoderm and those are the ones that are actually used in orchids analysis. So this process of actually biopsying or giving a haircut to embryos has actually been happening for over two decades. It's just that in that five cell biopsy that only has 30 picograms of DNA, historically you haven't been able to get very much information off of that. You only got something called chromosome information, right. Which you can kind of think of as like chapters in a book versus what orcid's able to do is actually read every single letter, every single base in those chapters as opposed to just that.
- [03:01]
A
Here's the thing, the thing is this doesn't look, you know, at the, at the 1 or 2 or 4 or 8 or 16 cell or whatever cell stage. It really doesn't look human. Right? It is very much. You can, you can decide, you take a continuous process and every ethicist and every person will have a different point on that process as to when it's a human being. Right. But like, probably most would agree that. Well, actually, no, some wouldn't. That the sperm and egg are themselves. You know, there's, there's biblical injunctions against spilling one seed on the ground and so on and so forth. Right. So if you think it's actually a quote, human at the moment of an embryo, then you'll have one of moral intuitions. And if you think it's not really a human then, but it might become a human three months or six months or whatever, months from now. That's, you know, the whole termination debate or what have you.
- [03:55]
B
Yeah, yeah.
- [03:56]
A
It's important to put this on screen because that, what you just put there, it really doesn't look like a human. If you were, if you told machine learning to ask is, does, is that look like a human or not? It's not, you know, it's not, doesn't look like a human. Right. And whether it looks like something is on everything, but it's something, you know, in the sense of it's a, this, a microscopic little cluster of cells that it, you know, legal systems will differ based on whether or not you consider this to quote, be a human or not. Right. And many legal systems do not consider it to be a human. This is like one of those things where it's like.
- [04:35]
B
Yeah, yeah, I, I totally, I totally agree. I think it's like, it's very clear that, you know, this is not visible to the naked eye. It's, you know, there's, there's no organs.
- [04:45]
A
Oh yeah. And how small is it? You actually. You haven't indicated that on screen.
- [04:48]
B
Yeah, yeah, It's. It's not visible to the naked eye. Right. So this is under a microscope.
- [04:52]
A
You can't see this without a microscope.
- [04:54]
B
No. If you were to see a petri dish, you would. You would not be able to see anything. Right. It's like, smaller than a grain of sand. But I think even separate from that, like, the question of, you know, you know, is it. Is it, you know, human, is it not? Like, the core thing is that Orca doesn't actually change anything about the IVF process. Right. The way that IVF works, the way that it's worked for 40 years, is that you extract eggs, you create embryos, you create multiple embryos, and you have to choose one to transfer. Right? So if you're opposed to creating embryos, then you should just be. You. You should just be opposed to IVF in general, which is where, you know, 12 million plus babies have been born. Right, Right. The thing that ORCID is doing is saying that, hey, you have these, you know, 4, 5, 6, 10, 15 embryos, however many embryos that you were able to create during that cycle. And the question is, which one do you transfer? The previous method is that you transfer with extremely limited information. And then with Orchid, you have the opportunity to have much more information. So there isn't actually a new moral question of should we create embryos or not, or should we transfer embryos or not. Right. That question has already been decided by ivf. And this question of which embryo do we transfer is just inherent in every single IVF cycle. Right. If you create more than one embryo, then that decision has to be made. It's just that right now, it's made via kind of a beauty contest. So what will happen is that an embryologist will look at these images and say, okay, this one has a higher morphological grade, this one has a lower morphological grade. Or alternatively, they'll use really limited genetic information. So that's kind of chromosome testing what I'm gonna get into. Right. So, you know, humans have 23 pairs of chromosomes, and if you have a abnormal number of chromosomes, then it's frequently not compatible with life. Right? So chromosomes are organized from largest to smallest, meaning they know the of genes. The number of bases that are on chromosome 1 is much larger than on the sex. Chromosomes are much smaller. So most of you know, if you have a monosomy, meaning a missing chromosome or an extra chromosome on, you know, most of these chromosomes are just not compatible with life. A Sort of unique situation where it is compatible with life is down syndrome, trisomy 21. And I guess the key point here is really, you know, if someone asked you to proofread your book and the only thing that they could tell you is, you know, your book has an extra or missing chapter, you wouldn't really think that was a very good proofreader, right? But that's really all that existing genetic testing can tell you is do you have a, on embryos anyways, do you have an extra or missing chromosome? So what whole genome sequencing and what ORCID can do is go much, much further. It goes actually really deep into every single letter in each of those chromosomes or chapters, right? So any type of typo, whether that's an extra base, an insertion, a missing base, a deletion, those can all be detected. So there's actually thousands of different genetic diseases that have been cataloged by geneticists in the academic community over the last two decades. And you know what's really powerful is being able to actually scan for these ahead of time rather than after it's too late, right? Like you probably don't know a lot about, you know, the names of a lot of these conditions, you know, neuro, ocular disorder, like individually, each of these conditions is really rare, but in aggregate, if you add them up, a lot of people are affected. So you know, if you look at like the rare disease community, they'll say that, you know, 10% of Americans are affected by rare disease and the vast majority of those are genetic. The vast majority of those who are affected are children. And 95% of these conditions don't even have treatments, you know, know much less a cure. So you know what's really cool is that this is already happening, right? Like babies have already been born, you know, through orcid that have been screened for this, that have had their entire genome screened. And you know, the reason why this is really powerful is that if you look at pretty much every single outcome, whether it's pregnancy or healthy baby, a huge component, a double digit component, is actually genetic, right? So if you look at miscarriage, about 50% of miscarriages are due to genetic issues in the embryo, right? So there's people who have recurrent miscarriages due to genetics that if they do embryo screening don't have to suffer that same fate. If you look at infant deaths, over a quarter of infant deaths in the nicu, the neonatal intensive care unit, are due to underlying genetic diseases. Again, this is like a huge category of sort of the maximum Amount of suffering that you can imagine for a parent and a child, that could just be totally avoided via embryos screening. And if you look at another category, like moderate to severe intellectual disability, about 60%, there's about a 60% diagnostic yield for those folks. And a large fraction of these are caused by what's called de novo mutations. So that means that there's new or spontaneous mutations in the embryo that are not present in the parents. And a lot of these are paternally inherited, meaning, um, older fathers are contributing more de novo mutations.
- [10:02]
A
So just interrupt for a second. IVF already exists. Implantation diagnosis already exists.
- [10:07]
B
Yes.
- [10:07]
A
Most people who do this, Millions of people have done this. Millions of people are already screening, and they're already screening for, for example, moderate severe intellectual disability. Because if you're actually doing it, why would you. Why would you not?
- [10:21]
B
Right, so this screening, the moderatist, severe intellectual disability, this is happening in the pediatric setting, right. So a child will come in and they'll be affected. Right. With, with either, you know, autism or intellectual disability or epilepsy. And then geneticists will sequence them and find out what the cause is. Right. The only difference is that instead of waiting until after symptoms happen, we're. We're moving that timeline all the way up to the embryo. Because now we have this new ability which is we're able to actually sequence the entire genome of the embryo rather than just this tiny fraction, just the chromosomes.
- [10:48]
A
But yeah, so actually that's right. So some fraction things can be caught preconception or even pre, like even before people are married or what have you, because you can get, you can sequence or carrier test them, but many other things that are de novo, you can only catch post conception, but potentially post conception, but pre implantation.
- [11:08]
B
Yes, exactly. Yeah. And I think a really important piece here is that right now the situation is that, you know, we talked about chromosome testing, right? So via NIPT, pregnant mothers at 10 or, you know, 15 weeks are already getting information about chromosomes. Right. They're already finding out, okay, my child has down syndrome. And now they have an option, Right, which is either terminate or have an affected child. Right. They're already put in that position. Right. And people are already choosing to terminate or already choosing to, you know, continue those pregnancies. Right. So it doesn't, it's, it's fully sort of more compassionate from a emotional, physical level to just move that timeline forward to the, to the point of transferring an embryo as opposed to pre implantation.
- [11:50]
A
Rather than post implantation.
- [11:51]
B
Yes, yes, exactly. So that's what's kind of really surprising.
- [11:54]
A
Just, just to define terms, Right. There's like, you know, there's just screening an adult and giving them their genome before they're, you know, having any partner of any kind. Then there is, let's call it preconception testing, which is similar, except the difference being that now your genome and your partner's genome are being analyzed together to determine whether or not your children will potentially have, for example, a chance of having a double recessive if both parents have a Mendelian disease. Then there is post conception, when the embryo exists. But pre implantation, which is in the context of ivf, where you've got the nine embryos, for example, in your diagram, and there are these tiny, microscopic grain of sand things. And then there is post implantation, when you know, the embryo is actually in the mother's womb, hence developing, and then you're screening that E3 and.
- [12:44]
B
Exactly. And basically at each of those levels, different amounts of information are being revealed. Right, so.
- [12:48]
A
Correct. That's right.
- [12:50]
B
Only looks at recessive disorders. Right. But we're saying, hey, you know, you, you probably care about dominant disorders. Right. You care about cancer. Right. But that's just missing from carrier screening. Right. So it's sort of.
- [12:59]
A
Exactly. So in a sense, if you make a distinction between an embryo and a three month old fetus, which most people, I think do.
- [13:06]
B
Yes.
- [13:07]
A
By moving more testing. Now, of course, IVF itself is a procedure and a significant one, and so on and so forth. But if someone's doing ivf, then because you can screen pre implantation, you can catch things so that you don't have to screen post implantation when there's actually. It's actually developing in the womb. It's actually a more, as you said, more compassionate kind of thing.
- [13:29]
B
Yeah, yeah, exactly.
- [13:30]
A
Right. I mean, maybe it's obvious, but the main cost of that is doing IVF in the first place. And that's a whole separate topic. But we want to reduce the cost of doing ivf. We want to reduce, you see, overhead, a lot of people are working on that.
- [13:41]
B
And I think. Yeah, exactly. And I think even to focus on ivf. Right. So we've also already resolved the moral question of should people be allowed to do IVF electively? Right. So egg freezing and IVF are identical processes. The question is just, you know, do you freeze the eggs or do you actually fertilize the eggs? But essentially, women who are perfectly fertile, they have no infertility issue, are already using ivf, using egg freezing prophylactically. Right. Proactively to basically. Yeah. Preserve their fertility. Right. So this idea that IVF can be used electively without an infertility diagnosis has actually also already been resolved for the last 10 years. Right. So even that question of, you know, should people be using IVF who don't have an infertility issue, I think that question has already been answered. Right. It used to be the case that egg freezing was only recommended for women who had, you know, a cancer diagnosis. Right. They were going to be, you know, doing chemotherapy, and then it was. It was an option to preserve their fertility. Right. But, you know, over the last decade, it's sort of advanced beyond that. It's no longer experimental. Yeah. You know, millions of people have done, you know, that procedure as well. Right. And obviously gay parents are using ivf, you know, to form their families, too. So I think it's really sort of. I think at this point, it's already a personal decision. Do you want, you know, to use IVF to form your family? So again, it's sort of just like, okay, now once you've made that decision to use ivf, how much information do you want? Do you want a little bit of information or do you want sort of the maximum amount of information that science can provide? Yeah. So kind of just moving on. Right. So I really wanted to kind of focus on this monogenic case because this is sort of, I would say, you know, very clinically bulletproof in the sense that, look, all of these conditions are already screened for in the pediatric setting, in the adult setting. There's no debate about, you know, if you have this variant, does it lead to these disease. Right. They're all considered definitively associated with these diseases. So it's really just about, you know, moving that timeline forward. I'd say the second side of the testing is using what's called, I guess, sorry, just to kind of like hammer that point home on the monogenic side. Right. So we have users who've had, you know, children who have terminal disorders. Right. So this is a child that has this brain disorder called lissencephaly. You know, vast majority of children with this condition die before they're 10 years old. There's no cure. So I think it's. It's honestly, I think, quite cruel to in any way stigmatize these parents. Right. They've sort of given up their entire careers to be caregivers for, you know, these very severely affected children. And now they want the opportunity to have a child that is healthy, that doesn't have to suffer from the same way that their first child did. And I think that. That' you know, an extremely important vulnerable population to embrace rather than to somehow stigmatize. And I just feel, you know, extremely strongly about these families. I mean, this is kind of like the reason why I started the company. So. Yeah, I just think if people understood what it is that they're. They're going through, it's like a very human desire. Right. The idea that, you know, you want to, you know, see your child, you know, grow up, grow old, rather than having to bury them. Right. And this is a very. This is the reality.
- [17:01]
A
This is all the people who are like, just roll the dice. What about the people who didn't want to roll the dice? And they got a very bad roll of the dice and very bad luck. Right. You know, there's no point in, you know, just roll the dice is just some silly type of thing that people will say without actually thinking about the consequences of it for people they don't know. Like. Like Mrs. Crown over here.
- [17:25]
B
Yeah, exactly. I mean, they're not on the hook for the. For the lifetime, you know, of medical bills. Right. And I think that, you know, it's not diminishing, you know, you know, this, this baby's life or any. Anyone's life to, to screen and to say, hey, for my next child, I don't want them to be affected by that condition. I think that's kind of one of the tensions that I think people somehow don't understand that, hey, you know, if I choose not to drink during my pregnancy, that's not saying all people with fetal alcohol syndrome should be deleted. It's saying, for me, for my child, I don't want them to be affected by fetal alcohol.
- [17:56]
A
Of course, these arguments that the. Some of these folks are making are just so silly because it's like saying, you know, I think we should put on seat belts. So I was in a car crash. Do you think I shouldn't exist?
- [18:11]
B
Yeah, exactly. It's exactly the same as, like, it just makes no. Everyone is equal.
- [18:15]
A
I want fear people to be hurt by car crashes. You know, go ahead.
- [18:19]
B
Yeah, yeah, exactly. And if anything, it's sort of like even more unfair than a car crash because, hey, it's like, okay, there was like a clear human error, you know, 90% of the time for why that car crash happened. This is sort of like, okay, you just a random typo just, you know, got added to your DNA. And then, you know, you just, you know, your organs don't form, your limbs don't form, your, Your Skull doesn't form. Right. So it can just be very catastrophic.
- [18:42]
A
It's. It's like the. You know, the. The. There's a meme about, like, did you have breakfast today? They genuinely can't contemplate a counterfactual. Fundamentally, the. The concept, really, what it boils down to, I think, is misery loves company. People who have some form of bad thing happen to them just want other people to also be miserable. Some of them. Others don't. Right. Why don't we go to the next slide, Mark?
- [19:10]
B
Well, actually, I don't know about you. I kind of like, basically me saying something and then you doing your commentary over it.
- [19:14]
A
Go.
- [19:15]
B
So I actually think that's kind of good. Like, do you want to do this summary really quick of, like, what all this means? I actually thought that was really good. If you want to just, like, have one final.
- [19:22]
A
Yeah, I mean, my summary is. But we'll edit and pull everything out. Yeah, my summary is, a, we've got 12 million IVF babies. B, we already are doing diagnosis prior to implantation of IVF babies. C, we have the opportunity to improve that diagnosis by simply adding polygenic scoring on top of monogenic scoring. D, it's a parent's decision as to whether to do that or not. E, it is not somebody else's decision, really, as to obviously, whether those parents got married in the first place, how they choose to have children, whether they choose to have children. F, much of the hand wringing over this is based on bizarre, illogical emotionalism that doesn't encounter the reality of what it is to have a child with a genetic disorder and to make somebody else roll the dice of doing that. It's. It's kind of like, you know, I prefer a car without seat belts, therefore, you must have a car without seat belts.
- [20:30]
B
Yeah.
- [20:30]
A
You know, it's kind of like that. You're literally preventing somebody else from taking a precaution because you want to roll the dice. Okay. I mean, fine, if you want to roll the dice, be my guest. Why should somebody else have to do that again? Why? She's done with her hair.
- [20:43]
B
And I also think it would be good if you just did one quick recap of, like, what are the moral questions here? Right? Which is like, okay, should we create embryos? That's already been.
- [20:50]
A
Right. So. So moral question. Should I. Should IVF be legal? Okay. And by the way, we can reverse the same, you know, kind of argument. Do you hate all the IVF babies? You hate 12 million people. Do you want them all to be Eradicated because you're so anti ivf, you IVF hater, you IVF bigot, blah, blah, blah. Right. Like you can reverse all these arguments on them. Okay, fine. So number one, should IVF be legal? Okay, if. Yes. All right. Number two, should pre implantation genetic diagnosis be legal? Which it is. Which is basically like, if you've got. And by the way, you need that, because IVF embryos often have something, you know, wrong with them, aneuploidies or something like that. So you have to screen them before implantation. So screen them for aneuploidies, which are macroscopic chromosomal issues. Why wouldn't you screen them for microscopic ones, which are like monogenic scorers? And if you can do that, now that we've got the technology, why not polygenic? There's really no probably minimal added cost, I assume, the amplification step to actually get the DNA from there and screen it. It's like minimal biochemical added costs. Let me put it like that. There might be fixed costs in terms of doing the data analysis and so on. So if you get. If. All right, so if you're screening, should be able to do antiplates, Almost certainly, yes. Monogenic, absolutely. That's already really standard of care and many parents choose it. And polygenic. Guess what? First of all, it's already happening. And second of all, you can't. You can't draw the line for somebody else to marry somebody. So they're already picking the genes of the other partner. If they want a tall partner or a partner who's good at Frisbee. Like, that's already their choice. Right. They're already, in a sense.
- [22:27]
B
Right. The biggest impact on air embryos is going to be your partner. It's never, it's never going to be the case that your embryo screening is going to be. Have a bigger, you know, 50% of the DNA you're choosing right there. So. Right, yeah.
- [22:40]
A
So. So, you know, like, obviously that's not roll of the dice. You're completely intentional about partner choice. You know, and so this is just really, you know, editing around that equilibrium. It's like plus, minus, whatever percent, around that 50% that you've already got in there. So, you know, many medical procedures, by the way, you know, heart transplants, there are people who attack that as necrophilia. Right, right. Actually, recently, you know, fecal transplants, which sound gross, have actually been really valuable for people with IBS or other kinds of things to fix their gut microbiome. Um, and, you know, obviously there's a lot of people who are mad about not. The thing is, it's one thing to be mad, maybe specifically about a specific aspect of the COVID vaccine, but a lot of people have just turned that into being against the germ theory of disease writ large. Like they generally don't understand Cox postulates or transmission pathogenesis. They, they just don't just understand the immune system or how vaccines even work. And of course there's like, you know, stupidity on, on both sides, many sides on that issue. But the point being that many medical procedures, if you're just described them to like a medieval peasant.
- [23:58]
B
Oh, they'd be disturbed by them.
- [24:00]
A
Yeah, it's like it is extremely repugnant seeming. Right. Like, um, boy. Like, I mean, so first of all, just any organ, any organ transplant, you.
- [24:12]
B
Could basically make the argument that, you know, if you break your leg then, you know, didn't God want you to be, you know, unable to walk for the rest of your life?
- [24:19]
A
Yes, maybe.
- [24:21]
B
But you could also say, hey, look, why don't we put a cast on it and see if you can. If it gets better. That's like the.
- [24:26]
A
Yeah, so. So like, for example, organ transplants are an obvious one. Isn't that like defiling the dead or what have you. Right. Like, you know, necrosilic. Okay. You know, blood transfusions, very similar. Right. Wisdom of repugnance would not actually be that wise. Um, number three, epidural.
- [24:44]
B
People used to have a huge moral panic around epidural. Right, but that's right.
- [24:47]
A
Actually, doctors also not. Doctors used to not tell somebody, tell a patient if they had cancer. Yeah, right. They would keep that information from, from patients. Seems like a pretty big deal. Very, very, very in loco apprentice, you know, type of thing. I mean, there's, there's so many things like essentially modern medicine, you know, even hand washing was fought tooth and nail. Some. We used to have a huge problem with that. Like people didn't, didn't, didn't like him. You know, many, many things that are innovations in medicine. Even, even the analysis of. Go ahead.
- [25:26]
B
Oh, I was just going to say. Yeah, even, you know, urine samples, steel.
- [25:30]
A
Samples, blood samples, you know, analyzing all that stuff, analyzing all those fluids. There's a disgust reflex with that. Like a lot of medicine is gross. Right. Like if you.
- [25:41]
B
Surgery is gross. Right. The idea of cutting someone open, fixing.
- [25:44]
A
Something, surgery is gross. All this stuff. Of course, you know, you have. I mean, there's all kinds of blood everywhere in the operating room on a surgery. If you're just walking on that you're like, you're hurting him. Stop. Blah, blah, blah, blah, you know, and, you know, you wouldn't understand anesthesia. You know, basically these are just things where the intuitions of a medieval peasant can only really get you so far. Right. They really. The caveman mentality. Yeah. So sometimes there's a utility to it. Right. Where sometimes there's something that's. That feels weird and actually is bad or what have you. Right. But the problem, and one of the issues is that much of the modern scientific establishment has said, for example, like, XX and XY don't exist. Right. Like the chromosomes don't. Aren't functional and so on. So I actually understand where the sort of medieval peasant mentality came from or why it came back, because they just went back to extreme basics and just relied on their intuitions as a caveman. But those intuitions are going to be different from person to person also. Right. So they're not scalable across the site. They're very tribal. Yeah. Anyway, so it's coming back. So basically, I think what. What'll eventually happen with all of this, by the way. And let's go back to your. Your slides, but I think what's going to start. Yeah, yeah, go. No, no, no, no, you should.
- [27:10]
B
Yeah, yeah. I think I just have like five more minutes and then we can get into it. So basically.
- [27:14]
A
Sure.
- [27:14]
B
You know, if you. I think a lot of people really underestimate what the power of a base pa. You have a T, C, G. People are like, oh, maybe it doesn't really matter if you swap an A for a T. So I'm going to try to really illustrate and show you kind of what the impacts of a single base pair are. Right. So this is the tallest man in the world. This is the shortest woman in the world. And these conditions, gigantism and achondroplasia are really caused by a single letter change. So you're talking about a single letter in a single gene that results.
- [27:47]
A
That's a very good slide indeed.
- [27:50]
B
Dramatically different. Essentially, what happens in gigantism is that your pituitary system goes into overdrive and a massive amount of growth hormone gets dumped and you become extremely tall. And conversely, in achondroplasia, people who are much, much shorter, they have a critical protein that's broken that doesn't allow, you know, normal growth.
- [28:17]
A
Yeah. And actually, if. If I recall correctly, that particular variant is something that's more common among sperm of older men, that it's like a hypermutable 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.
- [28:40]
B
Way, which is like, I actually don't know, like 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, you know, these thousands of, of, of different diseases, a lot of these are honestly are, are, are fatal or extremely serious. People don't have an emotional reaction to it because they don't know someone with, you know, arterial calcification or any of these, you know, sort of diseases that have strange names are not very relatable. But I don't know, I guess what I'm trying to get across here is like, you know, it really matters, right? It could be the difference between your child having a terminal condition or not. It could be the difference between, you know, someone, you know, being, you know, very, you know, you know, three standard deviations from the norm in terms of height in either, in either direction. Right. So these changes do matter. And, you know, it's very reasonable for parents to want to scan for this information because it can have, you know, a very significant impact on, you know, their health trajectory. So we kind of already talked about monogenics. Now I'm going to get into polygenic. So again, monogenic is sort of that, you know, 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. So, you know, folks who have schizophrenia, folks who have bipolar. And then they're looking for enrichment. So, you know, basically which variants are, you know, more common in the, 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, you know, 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, the much higher percent. Right. The 95th plus percentile. Of risk. Right. So 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 that, okay, is my embryo in that low risk or average risk category or is my embryo in that high risk?
- [31:03]
A
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. You've got N more that are like that.
- [31:13]
B
Yeah.
- [31:14]
A
And so how do you, how do you think about the multivariable aspect of that? Because some, an embryo that's high on some of these will be low on others.
- [31:21]
B
Yeah, yeah, yeah. That's actually a great. So I'll actually get into that. So basically one, one thing that, because.
- [31:26]
A
You'Re doing best of N across a vector of K variables where K is usually much greater than N. Yeah, yeah, yeah.
- [31:32]
B
So I think one of the things that people are really trying to understand is that, you know, if I'm, you know, selecting an embryo that's low risk for, for one condition, does that mean that they're going to, you know, conversely be higher risk for another condition? And 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.
- [31:54]
A
Yeah, but you wouldn't, you wouldn't need to do it that way because you actually have, if I'm not mistaken, you have actually the raw underlying ACGs and Ts. 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 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.
- [32:28]
B
Yeah.
- [32:28]
A
And then you can just see, you.
- [32:31]
B
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, there's an aggregation with diseases that have, that are related. So 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's a, there, there is a shared genetic architecture for other mental health conditions. So rather than there being a trade off, what, what actually happens is that a lot of these conditions that are for similar systems end up actually having those, those shared variants. So 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.
- [33:26]
A
And how many conditions are you looking at there besides coronary artery disease?
- [33:29]
B
Uh, 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? 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. You know, these are one of the biggest causes of death, right? Like, and especially in terms of, you know, reducing the quality of life. Right. A heart attack, even if you survive it, it's sort of, you know, you aren't able to run as often a lot of consequences of this. Right? So the idea that parents shouldn't have access to mitigating the biggest vector in terms of mitigating risk for disease. Yeah, I just, I just think it's insane, right, because what you can see, right, you're just talking about, okay, you know, what are, you know, you're trying to quantify, like, from, from like the math perspective, how much risk reduction is actually possible. And it's, 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, 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. And if you're in. And this analysis, by the way, you know, wasn't done by orchidist, done by an independent statistical geneticist who just published this paper that. I just love these, these figures that, 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.
- [35:34]
A
It starts topping out. Wait a second. So the softer again is the difference between the triangles, the circles and the squares.
- [35:42]
B
Yes, yes.
- [35:43]
A
Okay. So just. And then once you get to about nine or so embryos. Yeah, right.
- [35:51]
B
Yeah, yeah, 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.
- [35:59]
A
On one condition.
- [36:01]
B
Yep, this is on one condition.
- [36:03]
A
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.
- [36:22]
B
Well, this one, this one is not looking at all. We can look into the methods, but this figure specifically is talking about reducing risk for one condition.
- [36:31]
A
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. Then conditions two through 12, you might have higher risk, so you have to sort of spend your optimization budget.
- [36:55]
B
Yes, exactly. So, so, 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, 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, that's kind of. Does that make sense? Did I explain that well?
- [37:24]
A
Yeah, totally. Keep going.
- [37:25]
B
Yeah, yeah, yeah. So, 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 and you still get this pretty massive, right. 30 to 55% risk reduction. Right. So people don't really have, again, a good way to conceptualize how massive this risk reduction is. So what I'm trying to compare it to you is, you know, this is more powerful than the most successful drugs on the market, right? Drugs that are making, you know, a billion all year, right? So here's, here's two drugs. You have, you know, a drug for copd.
- [37:58]
A
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.
- [38:08]
B
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.
- [38:16]
A
Or you, you prefer to be fixed at the genome level rather than Huber.
- [38:21]
B
Yeah, 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 leashed to that drug for life. And there's side effects, right? If you do this for your embryos, there are no side effects, right? Like 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? And then that, that risk level is the same for life. You don't have to like take a, you know, continually take a drug every single day, Right. Because the other thing is that when they do these studies, right? Like, you don't actually get the benefit if you're not perfectly adherent to the medication, right. And there's entire companies that are built around how do you get someone to actually remember to take a drug every day? Right. That's also not trivial. Even if you get, you know, a drug to work.
- [39:12]
A
Okay.
- [39:14]
B
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. Right. If you're in the situation where mom and dad are at average risk, you know, you're getting up to an 80% risk reduction. Right. And if you're in the situation where one is high and one is low. You're kind of, you know, topping out at maybe 70%, 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 surprisingly minimal cost for how big of a component the genetics is. And this is kind of what I was trying to talk about earlier, which was what are the genetic trade offs? Right. So you can build these correlation matrices where you look at which conditions are correlated to which other ones, and you can see that psychiatric conditions, you know, kind of are, 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 Orcutt, but the entire physical genetics community has done a ton of work to look into this and to, and to see, you know, what are the potential, you know, trade offs or shared architectures between these conditions. Yeah. 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 mitigate risk for schizophrenia. Right. There's nothing that can change 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. Yeah. Illogical arguments for why it should be stigmatized.
- [41:24]
A
Yep. Basically, the thing is. Go ahead.
- [41:28]
B
Oh, I was, I think, Sorry, I think this is the last point. Right. So sort of like people have actually already surveyed the public and said, you know, what is their opinion about embryo screening for, you know, childhood 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.
- [41:58]
A
Or that's a random sample.
- [42:00]
B
Yeah, yeah, it's, it's okay. This is a random sample and it's also Older folks. So I actually think that if you like, I think the average age was something like 40 or 45, which I think is. Was older than.
- [42:09]
A
Fascinating article.
- [42:10]
B
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 this actually.
- [42:19]
A
20, 24 paper.
- [42:22]
B
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. I would rather have babies, consider using, using IVF in order to mitigate risk for these conditions that I've been affected by.
- [42:38]
A
I think that that's extremely interesting nationally representative sample. Yeah. At least for. Yep, interesting.
- [42:47]
B
Yeah. So I think that this idea that, you know, IVF is somehow like, IVF is very different if you are, you know, 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 a, I mean, for a lot of people it's like a bad period. Right. I'm not trying to diminish, you know, what it's like to fight infertility. It is extremely diffic, you know, if you, you know, 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. I mean, it's extreme. Um, yeah, it's, it's extremely, you know, emotionally costly. So you.
- [43:45]
A
Oh, there, here I can, Yeah, 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, interest in polygenic ambulance screening by the. 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, just for the Twitter bubble, just for, just for people to know, just FYI, it's like 80% should be allowed. Okay, number one, then.
- [44:22]
B
And it's even higher for IVF, right. The idea that, like, there's like, yeah.
- [44:26]
A
IVF for the purpose of PSUs. 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 is 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 no opinion. If you delete. No opinion, in a sense. Right. These are close. You know, so it's like maybe it's 5 to 1 ratio or something. Like, what's that? Like, 80, 80 to 10, 8 to 1 ratio for some of these bars. And here it's like a one to one. Right. In the sense of close to 50. 50. But that's actually. That's. That's what I've called. This is non. Controversial.
- [45:14]
B
Yeah.
- [45:14]
A
And 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. Right, 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 obesity. And that's actually still pretty high over here. And it's only. Only when you get to skin color that it's like extremely negative. Even like, intelligence on. Again, this is. This is close, right? It's. It's more disapproved than approve, but it's not org de man. Do you add up the red and the yellow versus the blue and the other blue over here? Neuroticism. And so. And so BMI is basically very similar to obesity. So it's interesting that it's different. The phrasing of the question sometimes matters, and then, you know, concerns. Interesting, Interesting paper. Good paper.
- [46:12]
B
Yeah. So I. 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.
- [46:18]
A
Majority, FYI, 80% of people support embryo screening in a toy 24 SETI.
- [46:23]
B
Yeah, it's just important, actually.
- [46:26]
A
Send me your deck also, because I will preview this. I will preview this pod with the. With both that and the one base pair. Right. Like, is 8 foot 3 versus 2 foot 7. You know, literally one delta alteration.
- [46:46]
B
I want to give you just one asterisk on that one. So I don't have those people's genomes I just looked up for gigantism and achondroplasia.
- [46:53]
A
Okay, no, no.
- [46:54]
B
So, yeah, so basically, specifically, 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 or achondroplasia. 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 I.
- [47:21]
A
Well, well, first is. 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 some. That doesn't make any sense at all. Right? So just reap. 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. As for the right, I do understand the social conservative argument. I disagree with it because I think that the 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. Certainly past culture surgeries, like 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. We 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 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 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, 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. And then what are you going to do? You can reverse the argument on them. Are you going to discriminate against that IVF baby? Oh, huh. You know, well, you think they shouldn't exist, right? And so in general, I think 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 that is, that is a huge thing where the builders are in favor of this because we know life is hard enough. Life is. There's a lot of difficulties in life. And, 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 the 1800s, average life expectancy, because all kinds of infant mortality had not been solved. Right. So 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, not, 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. People 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, around the industrial revolution. And 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, and so, 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. We also had walkable communities and so there's a balance between them. And 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.
- [53:23]
B
Yeah, by a car. Why do you want to also have to go blind?
- [53:27]
A
Yeah, you can, you can already get hit by lightning. You get hit by a car, you can, I mean there's this 5 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 seatbelt, but why are they preventing you from putting on a seat belt? You know?
- [53:45]
B
Yeah. So what do you think is the steel man, like, what do you think is the most like I think we talked a lot about the arguments that kind of are just nonsensical. They 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. Sincere arguments?
- [54:04]
A
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 the, 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 capital S science. As if it has the same number of replications as Maxwell's equations. Because they equate prestigious citation with. And they basically substitute procedure citation for independent replication. Independent replication of what science is. Yeah, go ahead.
- [54:42]
B
Oh yeah, I was gonna say. Yeah, like.
- [54:44]
A
Yeah. And by the way, more than.
- [54:46]
B
Yeah, the replication matters way more than how prestigious the journal is.
- [54:51]
A
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 academia to be a social network where People post papers 2 or 3 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 git 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, but so, so because of that there's. And of course universities are like 99% democrat or something like that. And 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. So tech is in the US 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. 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, 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 overlying. Go ahead.
- [56:24]
B
Status quo bias is what you're saying.
- [56:26]
A
More than status quo bias. Unabomber bias. Right. What I actually think is going to happen, just to digress for a second, is not even digress. Many years ago, Many years, five years ago. Ish. I realized, and I wrote about this at the time, that after all the sturm and drawing, that after everything is said and done, the final political axis will Be. Let's call it futurism versus primitivism. Right? 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. 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, 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 Wrangham 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 hominids. And, you know, I posted that a while ago. It's like the first singularity. Did you see that? The original singularity.
- [58:29]
B
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 sort of like, if you compare that to, you know, GPUs and CPUs, it's like the timescales are very different. Yeah, biology.
- [58:46]
A
And by the way, Elon agrees. True. Right?
- [58:48]
B
Yeah.
- [58:49]
A
Boom. This is the original singularity. Right? And the thing about this is, 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 that took the gut enzymes, turned into fire, and pushed 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 push them into software. In the phone. The 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, 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 us human is the use of technology.
- [59:52]
B
Yeah.
- [59:53]
A
Because an ape can't use a spear. It can, it can jump, you know, along the woods or whatever. Right. But you know, or I mean they can use some basic tool use. We understand my point. They can't, they 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, the primitivism is essentially the new version of communism because communism also appealed to kind of the natural small group sharing and so 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. So instead of targeting capitalism directly, they'll target technology. And 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.
- [61:39]
B
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, primitivists versus absolutely primitive.
- [61:48]
A
Versus futurists will be the axis and it's going to be legal in some important jurisdictions probably certainly in tech forward jurisdictions around 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 and so forth. And the same kind 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. The 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. So even if they're rich, they're descending world. And whereas for, let's say India or you know, the Philippines, even if it's poor, it's ascending world. Right. So that's why like 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.
- [63:23]
B
Yeah, yeah, I know, yeah, that's a great point. Yeah.
- [63:25]
A
So I guess the ascending world will be pro all of this.
- [63:28]
B
Yeah. So do you want to kind of like just summarize what you feel like sort of the, like the moral cases sort of like what, 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. That's going to change over the next couple of years as it becomes more.
- [63:44]
A
Popular to reduce it to known moral principles in the West. For the left, it's just reproductive choice, period, point blank. For the right it is small government and why interfere with somebody's personal decisions? 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, 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 gets this, I can certainly quote Hinduism for it. I'm sure you could probably find someone who quote Islam for it because there's many people in the 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. So you could probably find scriptural arguments, I'm sure are usually for or against something, but in general, I think many of the major faith groups could be for it. Yeah, I think that'd be my. 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. They associate like a grain of sand. Embryo is the same as a human, is the same as this, 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 it just feels, you know, but feels. Can't build. Feels. Can at best, for them, ban, but feels like. Like doesn't know an A from a C from a T from a G usually. Right. So 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 fields.
- [66:11]
B
No, Yeah.
- [66:11]
A
I think the primitives.
- [66:13]
B
He made a great argument right 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. For death. Right. We treated epidurals for having, you know, a pregnancy.
- [66:30]
A
But the soldiers were. 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 and so forth. Like, 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.
- [66:53]
B
Right, yeah, exactly. I think basically pointing out, like, hey, what is lost? You know, from. From you know, having, having, you know, 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, I mean, you could make that argument for, you know, why don't we, you know, hunt our own food with a bow and arrow? Let's putting it at the grocery store. It's like something's lost. Sure. But what is gained? Right.
- [67:20]
A
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. And 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 and 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.
- [68:12]
B
Yeah. So what do you think is, is so threatening to people about it? Like, why is it, like, I am genuinely surprised by like, the amount of activation. I don't know, I'm just kind of curious if you feel like you have.
- [68:22]
A
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 at the Sydney Sweeney has great jeans 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. You 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, I, 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.
- [69:27]
B
Yeah, I mean, I think that's. That's the thing that I think is most. I don't know, I guess makes me feel the best about it, actually. It's like, basically, the benefit to each individual parent is so great that random negativity is not enough to convince them. It's sort of like for each individual parent, it's the difference between is their child 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 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, health care 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. And, 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.
- [70:20]
A
Yes, ma', am. I agree. Okay, cool. All right, so let me wrap there. And any last words, Any things you want the audience to come away with?
- [70:30]
B
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 rejigger them to whatever content that you want, that'll be great.