Steve Hsu: Welcome to Manifold. My guest today is Simone Collins. She and her husband are authors of a series of books called The Pragmatist Guides. She and her husband also run a travel management company and have a very interesting background, which we'll get into later. The main thing I wanted to focus on in our initial discussion is Simone's journey through IVF and polygenic screening of her embryos.

And this technology, as my listeners will know, is available through a startup that I co-founded called Genomic Prediction. In a recent paper that the company published, there was an analysis of I think almost 30,000, 20 or 30,000. Embryos that had been genotyped through our platform at various IVF clinics.

And that was just the fraction of participants who had opted in to be involved in scientific research. But it's already being done at scale. However, since it's a very new process, there aren't that many people who have been through the process who are interested or open to just discussing all the details of what they've been through.

And so Simone is quite unique in that way. And so that's what we're gonna start talking about. And then we'll branch into all the interesting aspects of Simone and her husband, Malcolm's life. Simone, welcome to the podcast.

Simone Collins: Thank you. It's so fun to be here. The only thing I'm missing is that really evocative, noir-style Blade Runner music at the beginning, which is so good.

Steve Hsu: That comes after. That, we add that later.

Simone Collins: I know. I love it so much. I love it. It's like, mm, it really gets you in the mood.

Steve Hsu: Yeah. I love it. I love it. so you've been through IVF.

Simone Collins: Yeah.

Steve Hsu: uh, maybe you can just start from the beginning and walk us through the process. What was it like for you? What were the challenging aspects of it? Just e e everything. Just start from the beginning.

Simone Collins: Yeah.

I would say our IVF journey was very similar to that that many couples go through, which is you start out wanting to have kids naturally and being really excited about it. We went off birth control. We, you know, waited and tried and then started getting a little impatient and worried.

And so I start downloading all those fertility apps like, okay, well when you're ovulating, I'm like, what? Where are you in your cycle? And you know, I'm like, okay, now that I'm being more systematic, maybe I'll get pregnant. And then not really. And then, you know, more and more and more kept happening.

Then we started seeing fertility doctors and then they had us go on different medications and then different levels of interventions starting with Clomid and then going up from there. And then I got Oh, I can't remember the name of the procedure where they shove, dye up your cervix and then watch it flow through your fallopian tubes under an x-ray or something, or ultrasound, I can't remember.

But yeah, then it, you know, everything culminated and basically a fertility doctor saying you're going to need to do IVF or you're not having kids, basically. that was

Steve Hsu: if you don't mind my asking, roughly how old were you when this was all this was going on?

Simone Collins: I was maybe 28 or so at that point like 28, 29. So definitely not reproductive, super young. And I think that's also a shared experience for many people these days. You want to start your career, you want to be in a financially sound position before you start having kids. And then lo and behold, what they tell you in high school that you know, someone looks at you the wrong way and you're going to get pregnant.

You know, I feel like we always grew up with this prior of like, I will instantly get pregnant if I'm not careful. Then as soon as you start trying, suddenly you find yourself in the opposite position of wondering how on earth people ever manage to get pregnant. It's crazy. So yeah.

Steve Hsu: Yeah. You know, usually when you have sex ed, you're a teenager and the, the, the people teaching you are, you know, their main goal is to keep you from becoming a teen pregnancy statistic. And then, but then as you point out, in modern society, women have careers and it takes a while to find the right guy. And pretty soon they're 30 or older, and then suddenly the problem is on the other end, it's, they're having difficulty getting pregnant.

but I think, you know, most listeners might be surprised that already fertility problems can become quite common for women in their early thirties, I think. I think most people have this idea that because so many women who are in their late thirties or 40 have kids, but perhaps secretly by using reproductive technology that, oh fertility decline doesn't happen until much later in life.

So you are not even 30 years old.

Simone Collins: That's right. Yeah. And I think the other really underrated element is male fertility. You know, people often look at women and they point to that, and even traditionally throughout history, women are seen as. the Limiting factor, but male fertility, both within the average male's lifespan does also really decline over time.

plus complications and risks become higher over time. Though I know that's complicated by different factors too, like the age difference between the partners but then also now fertility in general seems to be declining and people are starting to get really worried about that. So this isn't even just a matter of youth, it's a matter of, oh my gosh, there seems to be some kind of confluence of exogenous factors in the environment now that is hurting everyone's fertility.

It doesn't matter if you're 17 or if you're 37. so it is something I think more and more people will have to contend with.

with

Steve Hsu: Now for this early phase do you wish at all that you had done something faster, like gone to IVF faster? Did it take a long time for you to get through this process where you decided you were probably going to need some assisted reproduction reproductive technology?

Simone Collins: Yeah, I mean, I would say it would've been nicer to know that none of it would've worked and just go straight to ivf. I also, now, knowing everything that we know, I would prefer to do IVF just period for any kids, whether or not I had reproductive problems, especially because of PGBT, which is

Steve Hsu: Right

Simone Collins: things we're talking about.

But just the amount of, for me, control that you can have over the process when you do IVF is amazing. I really like the ability to choose the order of gender of our children, for example. I think that's really amazing. You know, I mean, a lot of people on the more conservative spectrum think about IVF and think about people just discarding embryos, you know, just, oh, I want this one, I want that one.

I'm just going to choose and then throw away the rest. And we're not like that. We want a lot of knowledge about our embryos and we want a lot of embryos because we want a lot of kids. But where we do like having that control is when do you have the kid? Can we screen for certain conditions? Can we know what their risk factors are going to be as their kids?

And then also can we control, you know, when, when our first kids are born and what genders they are. And we, for example, started with two boys because while I think girls are easier to raise when they're younger, I'm terrified about the idea of two teenage girls. Like setting the tone in my household, the amount of PSYOPs at play, like the amount of torture and warfare mentally that would be taking place.

I would much rather have teenage boys set the tone. and, and we also really love the idea of close gender dyads. We found that anecdotally siblings who are the same gender, who were born really close to each other, have really close friendships throughout their lives, kind of are supporting each other even more in many cases than different gendered siblings.

And so we kind of want to give that to our kids, and I love having that control. But no, we were not, we were not at all cool with having to do IVF at the beginning. I didn't want to do it at all. It costs so much too. It's prohibitively expensive and it's very scary at first. There are needles, there are all these appointments and all this invasive stuff going on, and it all feels very strange and scary.

But as soon as we did it, you know, I think a lot of the problem is that there's a lot of negative stigma around ivf. There's a lot of fear, there's a lot of uncertainty. And I think there's a little bit of an adverse incentive at play where like, by kind of, I'm not going to say pretending, but by playing up the more difficult elements of IVF women can also get sympathy points and extra attention and like pints of ice cream.

I, I saw this a lot like actually in some of the fertility clinics that we worked with, because we've been with a bunch as we've had to move around for work. where they would sort of give women these excuses to lie in bed all day, even though they really didn't need to for medical reasons or do all these other things.

And there was even this infantilization of language at one of the clinics where I went to where they always called you like baby or honey and like it was, it's just all this coddling. Yeah. So I feel like there's also this sort of cultural adverse incentive that makes IVF into something scarier and more cumbersome and you have to take time off and oh my gosh, you can't recover.

And oh, this is so difficult in the hormones where it's really actually not that bad. So as soon as we discovered that, you know what, this is doable. And we really, really want to be able to have a large family. We decided to do a batch year of egg retrieval where we did five rounds all in one year. We called it the year of the harvest because we wanted to make it funny and fun.

And the only painful thing about that year was our finances. We slept on a mattress in a one room studio in the warehouse district outside Miami called Doral and it was rough.

Steve Hsu: can, can we, let's, let's go. Can we go into a little bit of detail because usually in these kinds of discussions, it's, it's some guise. Talking theoretically about IVF or genotypes and DNA and stuff like this, whereas you really went through it and, you know, actually if I searched my memory banks, I probably have not ever been in a conversation on this topic, a public conversation where I was speaking to somebody who had really gone through the whole process and could talk about it from the, the woman's point of view.

So if you don't mind, maybe we could for the, just imagine the listener, some clueless guy, some husband who maybe he and his wife are thinking about going through this and he just has no idea what his partner is gonna have to go through. So maybe you could just walk us through in baby steps.

Simone Collins: Yeah.

So there are different stages to it, of course, like there's the, the leading up to it. But in the end an egg retrieval cycle is mostly just a series of ramping up different meds going in for blood testing regularly. And transvaginal ultrasounds to check the size of, of the follicles that are being stimulated by the hormones that the person undergoing the IVF is injecting.

So far, for women, what this means is a lot of doctor's appointments, a lot of driving out which is inconvenient. You know, it's, it's hard when you have a job to, to duck out that much for blood work and for the transvaginal ultrasounds. and then it means usually twice daily injections.

But all but one of them during an egg retrieval cycle are, I would say, not scary because what you're doing is you're gathering up fat around your abdominal region and then just sticking in a tiny needle. And some of the needles are like the pen style needles that many other people are familiar with, with other drugs where you just twist a little bit for your dose and then you just like, it's so easy, it's painless.

So you're doing that for a month. They're, they're watching your follicles. They'll tell you, oh, well, you know, we have 20 that look good, and they're trying to get follicles that are within the right kind of range. To then retrieve as many that are like, we'll say ripe as possible. Some are going to be a little too old, some are going to be too small and underdeveloped and some are going to be just ripe for fertilizing.

And so near the end there's just a lot of like really constant monitoring because you're so close and they're trying to really dial it in and okay, like, let's slow down, you know, not too much meds because you don't want to get ovarian hyperstimulation syndrome. which is sort of when things sort of your, your hormones go out of control.

And then after the retrieval things aren't great. I had that my first time I did ivf. That's a whole, it was a whole thing. because then we flew to Peru right after I got the surgery. And I also had, it turns out, really bad walking pneumonia at the same time that I got. It was just not fun. but yeah.

And then, and then you have the retrieval surgery, which is an outpatient surgery. they, you're not supposed to drink past midnight because they're going to, you know, take you in, put an IV in your arm or on your hand and they are going to, you know, be unconscious while they retrieve the embryos.

And then you wake up and you've got some sort of bad menstrual cramping, which they almost immediately subdue with pretty powerful pain meds. So you really don't feel anything bad. and then you go home and they tell you to like, oh, take it easy, whatever. But I've always gone straight back to work zero, like zero pain residual issues whatsoever.

You, you of course, want to watch out for any weird complications, like random bleeding that happens. But you know, that's with any outpatient surgery, they're always going to look out for that. It doesn't happen really. And that's a

Steve Hsu: Is it, is it fair to say that the psychological, or, I mean, obviously this would vary from person to person, but is it fair to say the psychological anxiety, because obviously it doesn't always work or you don't get as many viable embryos as you wanted, is, is that a bigger factor in most women's minds? Or is it the actual physical discomfort of the procedures that they're going through?

Simone Collins: No, the physical discomfort is trivial. the, the, I think the hardest thing for me, the first time I did it was the trigger shot that you, you sort of give yourself right before you do the retrieval surgery because it's one of the longer needles. and you have to do it in your butt. And if you're like me, not going to let someone else inject you.

Like some people will go into the office and just have a nurse inject you, but I'm like, I, I'm not driving again. Cause you're so freaking tired of that. And so, you know, if you're like me, you're like, okay, I have to do this. I'm kind of afraid of needles. Okay. I'm really afraid of needles and now I have to like, turn around and like get this in my, now I've done like, I think hundreds of them because you have to do a lot of those types of shots after the embryo transfer.

But that's, that was the hard, like most I they just painful, scary part. But yeah, I think the hardest part is the financial part. It's like I'm dropping 15 to $20,000. Of money that most people aren't getting any insurance help with. We didn't get any insurance help with this, so this was all of our savings.

You know, we're sleeping on the floor. It was like everything was being sacrificed for this and we didn't know if it was going to work. And honestly, sometimes it doesn't. our, our best round, we got 10, we'll say normal, healthy embryos. and that was the round that we did with Genomic Prediction in the end where those got analyzed by y'all.

And then our first round, the one where I got ovarian hyperstimulation syndrome and where I got really sick and where everything was more scary because it was new. I got only one, and that embryo was later transferred and it failed. So imagine that, imagine you just do IVF one time, if we'd only done it one time, that, that's a lot of heartbreak.

So I, I mean, I understand that pain, I understand the anticipation and, and the fear and anxiety around that. I think a lot of it comes down to contextualization and, and how you choose to view it.

Steve Hsu: Yeah, I think, you know, people that are used to thinking in terms of probabilities and sustaining action over long periods of time, they can kind of, and maybe with the help of their partner, they can, you know, soldier through this. But I think for a lot of couples it's just a source of enormous stress and anxiety and for multiple reasons, as you say.

Simone Collins: Mm-hmm.

Steve Hsu: So you did, there was a year when you did five cycles, is that right?

Simone Collins: Yeah.

Steve Hsu: And you said the, the, the most that you got was 10. And we were all 10. Okay. Even after the aneuploidy testing?

Simone Collins: Yeah. That's what I'm, yeah, that's what I mean.

Steve Hsu: How many were actually retrieved?

Simone Collins: Oh, let me pull up because I have it.

Steve Hsu: In a spreadsheet somewhere, right?

Simone Collins: Yeah. I will, I will report back. But yeah, so I, I did, like, I always, I try to like track. Here are the number of eggs. Here are the number of embryos. Here are the number of you know, in the end, after testing, what, what we can actually transfer.

Let's see, let's see what I can get. All of us, mm.

There it is. Okay, so batch one 17, extracted 11 mature eggs. Nine. Normal fertilizations three embryos, sent one viable embryo. Second batch 33, extracted 23 mature eggs. 16, normal fertilizations nine embryos, sent eight viable embryos. So you can see like just across two, two rounds. Like one, we only got one viable embryo.

Two, we got eight. You know, there's so much variation. and there isn't necessarily, when I look at my numbers here, a direct correlation between the number of eggs retrieved. And the number that ultimately did well. Like we've had some rounds where we got like there's one round where I had 44 in total extracted 29 mature eggs.

But in the end, only five viable embryos. So it's, it's also so hard to predict. Like you, you just don't know even until well after the retrieval you know how much is going to work out. And I think that's what scares me also about the idea of just freezing your eggs preemptively, if you could get this really false perception.

You know, we've met women who are like, oh yeah, I have, you know, 26 frozen eggs. And then I think about, oh, well my batch three was 26 and that was only five viable embryos, you know? And so it isn't that fun and of course you have to kind of assume a 50-50 shot that any frozen embryo transfer is ultimately going to work.

So you have to sort of back calculate Well, okay. Mm. I don't know. It's nerve wracking.

Steve Hsu: I think a lot of couples, even though they probably go online and try to read up on all these things, really don't necessarily know the odds and, and the numbers can fluctuate from clinical clinic. We, we have access to a lot of data that shows us things that really honestly aren't public in the, in the field because we, you know, obviously we have data from, you know, I think we work with, have worked with almost 300 clinics overall in, in the history of the company or something.

So now I think you, you did have some cases where you had fertilized embryos, but they turned out to be aneuploid and then you couldn't use them. Is that right?

Simone Collins: Correct.

Steve Hsu: One of the things that surprised us in the history of the company, cuz we didn't really set out to focus on aneuploidy. By the way, for the listeners, aneuploidy means some abnormality in the chromosome count or the chromosome structure and determining that can be done with older technology. So PGTA pre-implantation genetic testing for aneuploidy PGTA is widespread. So something like almost 70% of all embryos produced in the United States are screened for PGTA and that whole industry existed before Genomic Prediction came along.

Our goal was to get really a whole genome genotype, so the detailed genotype for each embryo. And we knew we would be able to do screening against aneuploidy because a chromosomal abnormality is so gross. Change in the overall genome and easy for us to detect. So we just thought, okay, that's a checkbox for us.

We're not that interested in that particular aspect of the pre-implantation genetic testing. We wanna introduce something which is polygenic screening, which we'll get to in a second. But we discovered along the way that our aneuploidy screen is much, much more accurate than the old technology.

The old technology is very crude. And so what we discovered is there were often cases where an embryo would be called aneuploid by the old technology, but we, with a much, much more granular whole genome genotype of that embryo could tell it was not anti-ployed at all. And that's a huge issue. So women would mistakenly not use an embryo that was totally normal because the noisy old PGTA test told them.

Wrongly that it was abnormal, that it was aneuploid. And so that, that's, that's a big factor. And then the other thing is that can happen the other way, that the noise can also work the other way, where you have one that's aneuploid, the noisy test says it's okay, you transfer that one. And because it's aneuploid, the most likely consequence of the Anup ploy is not that you get a down syndrome baby, which you could, the most likely consequence is the pregnancy is just not successful.

And so for those two reasons, the success rate for clinics that are using our PGTA screen is quite a bit higher. In, in, in one very, very big study that was done, we hit something like 70% success rate, whereas the, the, for the embryos that were randomly assigned to not use, to use the older technology, the successor, it was more like 50 to 60%.

So it's a pretty substantive difference. And I think you said that the particular batch that you, sorry to call them a batch, but.

Simone Collins: We call them batches.

Steve Hsu: The batch that you did with Genomic Prediction, you did actually have a pretty high number of viable embryos by the end of the process. Is that right?

Simone Collins: Yeah. Yeah. If I compare it. So I had 40 extracted, 23 fertilized, 21 made it to day three, 12 went in for testing. 10 were normal. So compare that to. 11 sent in seven viable, seven sent in five viable, five sent in, five viable, nine sent in eight viable, three sent in one viable. But what's also disturbing to me, and, and I think it's just your point, cannot be highlighted enough, is that it's not just that many women won't use embryos marked as aneuploid.

They'll also discard them.

You know, and this is like after the money and investment and time and work that people have put into this, and the fact that this could be a very healthy human life. It, yeah, it's, it seems like patently irresponsible to, to use, you know, different, less, less optimal technology.

Steve Hsu: When I, when I mentioned the 20 or 30,000 embryos that were analyzed in that paper that came out last spring, not that long, I guess it came out maybe six months ago, or less than six months ago that 20 to 30,000 was the number that had, that were not aneuploidy. And then there was another huge number of embryos that were aneuploidy.

And of course we have their genomes too. So we have a huge data set that nobody else has actually of, you know, genotype, whole genome, genotyped embryos.

So getting back to your story, it sounds like your harvest year was actually at the end pretty successful, so you had a lot of potential choices you could make, right?

Simone Collins: Yeah, we ended up with 26. And then we've since used two of those, because for the latest batch we used one of those. but then we also donated three so far.

Steve Hsu: Donated to science? Or donated to another couple?

Simone Collins: No, no, no. Donated to a couple.

Steve Hsu: So you have some, you may have some kids somewhere. Do you know where they are now?

Simone Collins: Yeah. We're known donors. I think two of them were lost and we don't know yet. And like, we're not going to contact them and be like, so have you had a miscarriage? Because that seems really insensitive.

Steve Hsu: Exactly.

Simone Collins: And, you know, it's, it's really hard uh, to, to go through something like that. So we really hope for the best, but we can also understand why they wouldn't tell us, like until a pregnancy is carried to term, because they're now paranoid that something could go wrong.

Steve Hsu: Right.

Simone Collins: We'll see.

Steve Hsu: So for the 26th or whatever the number actually turned out to be before that, what were you thinking when you did the more sophisticated Genomic Prediction screen? So were you, is there a history of a particular family disease that you were concerned about? Was it just you wanted to make sure in general that you got the healthiest embryo?

What, what was going through your mind?

Simone Collins: One we want, we want more embryos in general, and we also, every time we go through, want to have absolutely the best screening that we can have for them. Two, we definitely do care about screening for, for various conditions. My mother died very young of cancer. We were thrilled that Genomic Prediction had a bunch of cancer scores.

And an overall health score that, you know, it, it screened for because we saw the direct effect of, you know, a known genetic issue causing a very premature death. and we wanted to do something about that. And it's not that we're trying to only choose embryos that have really great scores to a certain extent.

We know that with each year you're buying a little bit more time for embryos with poorer scores. Like if you plan on having all of them like we do, the more time you buy, the better treatments are going to be. If e eventually they do reach an age where they develop that known condition. Also the cheaper and more accessible screening for that condition will be.

And one thing that I love about Genomic Predictions reports is that you can see a broad risk factor for certain conditions if you can tell your child, listen. You have a higher than average risk for this. Like please get a, get a scam like every now and then, you know, like you have to be more preemptive about this.

And also with just behavioral things like believing schizophrenia is on the, in the report. Correct. and just to know what your relative schizophrenia risk is, it's one thing for a parent to tell their kid, don't smoke pot. It's bad for you. Or whatever. Right. Or like to show them general studies and it correlates with lower levels of motivation or something.

It's another thing to be like, look, here's a report showing your risk for developing schizophrenia versus like, the average population here is clear peer reviewed research that shows that high doses of, of cannabis can trigger the like, sort of onset of schizophrenia. Like that is really useful stuff. so just without hesitation we had to use Genomic Prediction because it's such valuable information.

Steve Hsu: Yeah. You know, one of the things that I always emphasize is, you know, when the screen is covering 20 different highly impactful conditions ranging from schizophrenia to diabetes, to heart disease, to several different cancers, when there are 20 different independent risks, if you, if you just randomly select some, someone from the population, there's a decent chance they're an outlier and at least one, right?

So, you know, you have 20 different things, and if you say outlier is your top 5% risk, there's a pretty decent chance that you're an outlier in at least one. And if you're just slightly unlucky, imagine you have now five or 10 embryos. A couple of those embryos are gonna be, quote, unlucky in the way that the genes are in the, the way that the DNA recombined. And they could be a super outlier for something very high risk for something. Or they could have multiple things that they're at high risk for. And people generally are not that used to thinking statistically. So they don't realize that this is the case. When you have 20 largely independent, but highly impactful health conditions, that's a large enough number that almost everybody is an outlier for something.

But sometimes you can get lucky and you have an embryo that's actually low risk for everything. And um, so again, like people are just not used to thinking this way, or even most doctors don't realize that this technology exists and so they, they don't really quite grasp the power of it.

So when you made your selection, what were you thinking about it?

Were you, were you using the overall index health score that the report provides, or were you looking more granularly at specific conditions that you most cared about?

Simone Collins: Both. I mean, I think to your point, that it can be kind of overwhelming or people aren't used to thinking in those ways. It's really cool that Genomic Prediction offers an overall health score and that, I mean, the embryo we selected did also have the best overall health score. We also looked at, at, at traits that, or polygenic risk scores related to traits or diseases that we thought were more concerning for us than others.

You know, there are some things that you know you can live with and it's fine. There are other things where. like This is Insta death or you know, people are much more likely to die prematurely of this. And so it's, it's nice to see more granular scores. And I think it's also ideal to give parents the opportunity to select for things that matter to them, even if they don't necessarily matter to mainstream society or other groups.

Because I mean, in the end, that's kind of how people select for partners too. You know, like the person you think is a perfect partner is different from the person I think is a perfect partner. So the same should go for relative risks that we want to take a chance on.

Steve Hsu: Now one of the things that we computed in some of our research is that if you have 10. Siblings, we could actually do this with siblings or embryos. If you have 10 siblings and you look at the one with the best, the highest health index, and then you look at the average of the health indices, of those 10, the change in life expectancy is about four years.

So a couple that is screening, choosing, you know, their choice embryo out of 10 is on average getting potentially about four life years for their child, which is, you know, substantial actually. Even compared to the overall cost of IVF to buy four more years of life, a healthy life for your kid, it's, it's not, not a bad investment actually.

Simone Collins: Oh, when you consider the cost of college these days, I mean, it's also ridiculous. I mean, a lot of people don't think twice about throwing down huge amounts of money on their children. There are some things that, you know, or even like on medical care for their children after their children are born, after their children have all these complications.

It's odd to me that people wouldn't want to preemptively do that. I mean, stitching time saves nine, so let's do it early.

Steve Hsu: I mean, of course, if you were an economist and you just calculate, you know, what's the value of spending an extra few thousand dollars to do the genetic testing? That's, you know, roughly what it costs for Genomic Prediction or the whole thing. Like maybe you didn't need to do IVF but you chose, you opted to do IVF in order to get, quote, a better outcome.

Even, even the latter, which is a bigger delta in cost actually if you run the numbers, is actually still a good investment. especially compared to like I mean relative to say private school tuition or something like that.

Simone Collins: No, it, I think there's a very realistic future timeline, and I would love to nudge us in that direction in which governments fully fund all of this testing. Because for them, especially if you have a nationalized healthcare system, this is a no-brainer.

Steve Hsu: Yeah, I think so, so two bits of news. One that I, I think I, I mentioned on an earlier episode of this podcast one is that the government of China has decided that they're going to make IVF free under the,

Simone Collins: Yes. I'm so excited about that.

Steve Hsu: Yeah as part of their healthcare. The details have not really been released, but you know, and they are, they're going through a demo demographic decline.

So they're, they're obviously concerned about this. That would be a system where once they're making it IVF free, they're almost certainly likely to make genetic screening free, because they'll run the numbers and they'll say, oh, it's gonna save a huge amount of money in our health system if we make the genetic screening free as well.

And then the other bit of news was they did this survey asking people, you know, really the most controversial trait that anyone would ever screen for would be intelligence. And they pulled Americans to ask You know, how many of you, how many would consider, or whether you would consider it immoral or immoral to screen embryos for intelligence. And it's actually quite a small minority of Americans, especially young Americans, who thought it was morally questionable to do that. And so that was quite interesting because it suggests that for this next group of people that are just starting to use IVF now they largely don't have an issue with screening for cognitive ability.

We don't do that at Genomic Prediction. We don't screen for cognitive ability. We don't report scores for height, which we could estimate quite accurately. And we also don't report anything related to, to cosmetic traits like eye color or hair color, various aspects which are purely cosmetic. And we don't, we don't do any of those three things because we think that society hasn't really had a chance to digest the power of the technology and make a kind of informed decision as to what, where the boundary should be drawn.

But the survey, which was done by an academic group and it was published in Science. So just actually we are, we are being maybe too cautious at Genomic Prediction and actually the subset of people that would be offended by us allowing these, these different additional scores to be reported is actually really small.

Simone Collins: Yeah, I think these, these generational differences are really interesting. I think we're moving in encouraging trends. I, I believe that's the study you're referring to, also sort of used as a way to control people's willingness to, or, or support moral support of SAT tutoring or prep. Right? So it allows you to see, like, is a pre-birth intervention morally, or better or worse than a, you know, post-birth intervention.

And I think what was also striking to me was the proportion of people who thought it was unethical to do test prep. So that was interesting, you know, and I think that puts things into perspective. I also find that cross national differences in interest in things like polygenic risk score selection, even like crispr, like full out, just gene editing.

That may be in, in the United States there's, there's more concern about that. But you go to India and people are like, yeah, like sign me up. Like, where do I, where do I do this? So, you know, this is, I, I do think we're going to see in the future a lot more openness to these types of technologies.

Steve Hsu: In Asia, all throughout Asia, whether it's India or China or Japan or Korea, I haven't seen a really careful survey done. But talking to people in IVF clinics throughout those regions, they're much more open to these issues than typical Americans. And Americans obviously are close, you know, more likely to have European heritage closer culturally to Europeans and Europe. Europe is where the Holocaust happened and all that. But for people in Asia, it's all a little bit distant from them, and so they don't really associate it with all kinds of negative things that happened in the 20th century.

Simone Collins: Mm mm. Yeah.

Steve Hsu: Yeah. One of the interesting things, which, you know, we've had a lot, we've had a fair number of discussions actually with people associated with IVF in India is that there's very strong bias, especially among girls with light skin, light colored skin in India.

And that is something actually we can predict. So the genetic architecture of having lighter or darker skin is fairly straightforward. It's not one of the more complicated traits. And so that is something we could report in India. There would be huge demand for it, but it would be incredibly controversial.

And so we, you know, we, we just steer clear of all that stuff.

Simone Collins: Yeah, that's fair. But girls?

Steve Hsu: Don't ask me why, but apparently if you're a jet black guy in India, the penalty is not nearly as bad for you as if you're a jet black female. I guess it's, maybe it's considered attractive, I don't know.

Simone Collins: Yeah, that's, that's really interesting. But I mean, hey, culture is culture.

Steve Hsu: It could be that lower castes were more involved in outdoor agricultural kind of labor, and so it's, there's a negative association with having.

Simone Collins: Oh, especially if you're a woman. Yeah. Like if a woman has to work. Yeah. Yeah, yeah, yeah. No, I mean, we, you see that throughout, you know, Europe and like the weird scare. Have you seen 17th century, 16th century writing masks for women that just look like, I love those. They look so freaking creepy.

Steve Hsu: Actually in, yeah, in East Asia as well. both, both in South Asia and East Asia. Skin lightening cosmetics are pretty popular. So, so you this, this trend, and I think it does, has basically this old economic basis of who had to work outside and who could be inside. yeah.

Simone Collins: For sure.

Steve Hsu: So I guess let, let's maybe close out the discussion of IVF and all this, and maybe I could just ask you if a friend of yours were just about to begin this process, or maybe a friend of yours is already in her, let's say mid thirties and has just gotten married and is getting ready to have kids, what, what advice would you give her and maybe things that you yourself learned through the process that are not ob we're not obvious to you at the beginning?

Simone Collins: Mm. Do it now. Don't wait. Even if you don't have trouble, do it now as an insurance policy, you never know if you're going to get breast cancer. You have to undergo chemo. You know we actually uh, a friend of ours, a couple recently just had just that experience and they actually delayed the start of chemo a little bit to do a round of embryo creation.

Why don't you just do that ahead of time? You know, you're not getting any younger and it's amazing to have this extra control over the process, which ultimately can be very stressful for many people, whether or not they struggle with fertility problems like I and many others do. but I, I think, you know, beyond all that, one of the best gifts you can ever give to your children, aside from the health benefits and the knowledge of various risks and all of these things, you know, like gender dds if you want to do that, is to know that you were created in a lab with science and money, and not by your parents having sex with each other, which is such a beautiful gift.

It's the best thing you can give a kid.

Steve Hsu: uh, when we were founding the company, this was a long time ago, we're doing the research that led to the company that, you know, the motto, the, the tagline would be sex is for recreation, science is for procreation. Something like that.

Simone Collins: Yes. I love that. It's so good.

Steve Hsu: So, you know, moving on from your reproductive experiences, I heard you interviewed on another podcast and you talked about, I think this might have been in the Bay Area, it was your setting out to meet the right guy and the very logical process that you went through. I think and maybe you could just set that up for us. How old were you and what, what, what, what, what happened there?

Simone Collins: He's saying logic. It was a very autistic process.

Steve Hsu: Well, autists are very logical, right? Tend, they tend to.

Simone Collins: That's true. Yeah. And I only learned that I was autistic after our second son was, or our first son was diagnosed with it. And then like I was then yeah, we figured out.

Steve Hsu: By way, on this topic. Sorry to interrupt. Because I just interviewed a woman named Katherine Dee.

Simone Collins: I love her so much. I loved that interview, too.

Steve Hsu: Oh wow.

Simone Collins: It was great. Yeah.

Steve Hsu: I'm glad you liked it. So she said she wasn't quite autistic, but there was a time when she thought she might be autistic. I find it really interesting because the male form, I'm quite familiar with being a physicist and a geek and all this stuff.

So I have lots of close friends who are on the spectrum as males. The female part of it, I just don't get, because to be a hundred percent honest, if I met you at a cocktail party, I would not have said, oh, Simone is somewhere on the spectrum. I wouldn't have guessed it at all. So maybe you could just comment on that. Like, can you spot a woman that maybe is on the spectrum? Easily or, yeah.

Simone Collins: Now I can. Yeah. but only, only through hearing them talk about their experiences in social contexts or hear about them, like sort of how they deal with social situations, then I'm like, ah, confirmed. Like if, if they both think very logically or in a different way, if they're not very socially manipulative, um.

Steve Hsu: Yes.

Simone Collins: Being honest here. Like, in other words, if they don't stress me out.

Steve Hsu: Kind of conflating motivation with capability, right? You're, you're saying, you're saying women who are.

Simone Collins: Yeah. Well, I mean, they're not manipulative they can't be.

Steve Hsu: They will be socially manipulative. You're almost saying that right or no?

Simone Collins: Yeah, I guess I am saying that, I mean, I'm sure I would be, if I, if I could do it, I would, I would probably do it. but then there's other things like uh, a friend of ours, we were hanging out at one point and she mentioned how being alone was really nice for her because she didn't have to make facial expressions.

Like thinking about making facial expressions. And I'm like, oh God. Yes. Like to, to the, the energy it takes to pretend to not, to, to, to conform with normal human interaction methods is, if it takes a lot. So when I see people allude to things like that, I, I, it's a pretty big confirmed thing. And then there are others like weird giveaways, like sensitivity to various types of textures or like having some, some weird habits.

Steve Hsu: So I think a lot of male autistic people never fully get the hang of it. So like, you might be having a conversation with them and their face is just deadpan. Or maybe you ask a question and there's a second extra delay before they answer your question. so they never quite fully master the emulation of normalcy, whereas, is it fair to say that for women, they're on the spectrum, they tend to be able to master the simulation of normalcy, even if it's not natural. It's not, it doesn't come effortlessly to them?

Simone Collins: Yeah. And, you know, yeah, I, I wonder, so part of me wonders if there are just, you know, the gender dimorphism and, and brain structures is sufficient to enable that, that to happen. and part of me also wonders, and I'm sure it's probably a mixture of all these things, right? Is that, you know, in society, more emphasis is put on teaching young girls to do these things, right?

Like me, I remember my mother teaching me to make eye contact with people and her telling me, you know, Aunt Terry and Uncle Ken have their feelings hurt, because you never look them in the eyes. And me being like, well that's weird. But I guess I have to like, like force myself to look at them in the eyes now. Yeah. Actually video calls are amazing for me because I don't, I'm not, I'm actually looking at like another person.

Steve Hsu: While you're talking.

Simone Collins: I'm looking at the green light on my, on my laptop, which is amazing. Everyone thinks I'm making eye contact and then like, you know, I don't have to look at faces, which is amazing.

I only have to pretend to have emotions and a soul, so that's good. but yeah, so I think that that's, those are, those are really big factors. Also, the rise of AI has really shifted the way that I understand autistic masking because a big source of, of confusion often, especially earlier in my relationship with Malcolm about like our, our behavior in social settings was that he and I would be totally on the same page in private. And then in public. I would like do shit, like throw him under the bus. Like if, if he, for some reason like was going against the grain of the conversation and the overall vibe. And I realized that I was very much like I was doing what most large language language models do, which is like just sort of auto completing whatever behavior was going to please the largest average of people in the room.

And if that meant throwing my husband under the bus, apparently, like I was all on it. And, and I'm, so in social situations, especially the more people that are present, like I can handle one person, two. Like, the more there are and like the more heated the situation is, the more like I am gone and like only this I like auto response is there.

So like there's, there's no, there was no ability for me to logically override, like, what was happening. Like all that was there is the AI version of me that is pretending to be normal and like I'm hiding in a corner somewhere deep inside my mind, like cowering and rocking back and forth in a fetal position.

So I do feel like AI has helped a lot in enabling me to understand why in social situations I sometimes do things like that. but also why it's sort of exhausting and I just, yeah. I think that women somehow are better at AIming their, or LLMing, their, their social situation and, and men just aren't prioritizing that for whatever various reasons probably.

Steve Hsu: You know, when I was growing up, if I considered the subgroup of my friends who were, you know, geeky, love science fiction, maybe very good at school, high cognitive ability. There would be a subset of girls that those guys found sort of uniquely appealing or attractive. And, and part of it could be that those girls were also maybe high cognitive ability or something like that.

But I think part of it could be that those were the slightly aspy girls. which then they, the boys felt like, oh, I could just fall into a kind of natural, slightly more male-centric conversation with, whereas I didn't quite know what to say to the girl that was the cheerleader or the social queen bee. Like I didn't quite know what to say or cause her, she wasn't interested in any of the stuff that I was interested in.

So do you think that's fair? Do you think it's, it, it, some of the time that is because secretly that other girl, the one that you know, is the one that the nerd guys really liked, actually was herself a little bit on the spectrum.

Is that plausible to you?

Simone Collins: 100%. Yeah. Yeah. I think that that's, that's definitely true. And I mean, I feel similarly about women. So I think I can model that better. I'm like, ah, I don't know how, like, you don't say what you feel all the time, and this is very difficult for me. but yeah, I, I, I think that's very true. And also there's this like selection factor where then the autistic, or like on the spectrum, females in a, like any given high school, are more likely to cluster around like the Anime club and the National Honors Society and like that, that makes, yeah.

So they all end up hanging out more and yeah. That's, you're, you're describing something very similar to what I, I experienced too. And it definitely, there was there were, I think that the problem though with being interested, especially in autistic young women, who I would say, I would say autistic women, make for amazing wives because you don't get the games and you don't get like the same like ego stuff going on.

So I would encourage all of my, all of my sons to find nice autistic women to marry if they, if they want to marry women. I, I'm not going to as long as they have kids, I do not care what they do, honestly. But I think the problem is that in our modern society, so little is taught about dating and gender interactions that unless you're very explicit with the young autistic woman, she will have no idea that you're interested even if you're really coming on.

And I, the reason why I created this concerted campaign when I turned 24, was I had, I had not had sex. I'd never had a boyfriend. Like I am just like, blank slate here. Like, no idea what I'm doing. And then,

Steve Hsu: Sorry to interrupt, but I just wanna frame that. So you're 24, you've graduated from college. Did you date in college?

Simone Collins: No. Well, so here's the problem with autistic young women. I'm sure a lot of guys thought they dated me. And like now that I go back and I look at history, like after writing a book on sexuality and a book on relationships with my husband, Malcolm, then I go back and I think about all these things that happened. Like, like a dinner I had with one guy on Valentine's Day. Like all these others, like all these things, all these guys who hung out with me and like we went and did all these things.

And then they would send me these really, you know, emotional letters or videos or something and I'd be really confused. And then they would stop talking to me and like, you know, just.

Actually, one of the things that appealed to me so much about Malcolm when I met him in my dating campaign was he gave me the most autistic opening line in our dinner, which is, I'm not really looking to date. I'm looking for a wife. I expect to find her this fall at Stanford where there's a large pool of pre-vetted candidates and I'm just like, this is great. Like I know what you want. This is so cool. Like we can do something here. but like no one said.

Steve Hsu: Before that high point in your dating experience, were there no guys in college who tried to, shall we say, bust a move on you? Like, did that ever happen? Where did you, did you like, give someone a face poem and, and, and, and not realize that you had given them a face bomb or.

Simone Collins: Multiple, yeah. Multiple times the worst. And again, like I don't, I think this is a product of progressive society where there's this, just this assumption that like I, I don't know. I was just never really taught like, this is what this means, this is what that means. And I guess normal people are able to insinuate this, but I didn't, and I mean, I would tell people about what I was going to do and no one would say anything to me.

But there was one guy, totally fine, nice guy, like a classmate of mine who was like hey I got concert tickets in New York. I went, we went to school in DC. Like, do you want to go to this concert in New York?

And I'm like, yeah, that sounds awesome. Like, let's go, we can take the Chinatown bus for five bucks, like, let's do this, and then we'll just pull an all nighter and then catch the first one back in the morning. Like wandering around the city. And then, you know, like a couple days before he left, he's like, Hey, my dad got us a hotel room so that, you know, we can do our homework and stuff after the show.

And I'm like, sweet, we can do our homework after the show. and so, you know, we go to the show, everything's super normal. You know, we go to a 7-Eleven and, and you know, he's like, oh well, like I want to like, you know, let's, let's make some drinks. So like, he, like, he got the ingredients for screwdrivers and he is like, oh, like, let's, let's do that.

And I'm like, okay, cool. Like, you do that. I don't drink. All my friends in college were Mormons. I don't think that helped me develop my game. so I was like, yeah, you, you get what you want, you know, let's go do something.

So like literally I'm sitting in this hotel room. He's like, like knocking back screwdrivers. I'm literally working on my honors homework and I'm like, oh. And then he, you know, gets in, like, tries to get into my bed, like a bunch of very awkward wrestling ensues. And I'm like, this is a weird tickle fight. I, I don't know. And then like, I think by by, you know, like a couple hours in, I'm like, oh, like this is he, he's, he's either like really drunk or he's looking to, you know, he, he's want, he, he's interested in like having, like hooking up.

And, then it just got really awkward obviously, because here's this guy who, as far as he was aware, signaled everything.

Steve Hsu: He played by all the rules.

Simone Collins: That's like we were going to have sex. Then, we would do this like, and then here I am and I'm so confused and I'm trying to be polite because I feel really bad. but I also don't know, I don't have the tools to say anything.

And yeah, then like, you know, very silent, awkward bus ride home, you know, like nothing happened, you know, it was all just very, very, very awkward. And, uh,

Steve Hsu: Now, when you told your girlfriend about this, did she not say Simone, come on, this is, you know, that's, this is what he was thinking.

Simone Collins: The, the worst thing about that was, you know, I, I, I did, I told my best friend and roommate when I got back, like, what happened? And I just felt bad about it. And she's like, oh, that's so horrible that happened to you. Like, are you going to tell anyone? It was more like insinuating attempted rape, which is not what it was.

It was like, I was a dumbass, like, and my bad dude, like he sh like, and so it's, that's how toxic I think our society is around dating and relationships where one, we don't equip people to, to engage in productive courtship. And then when, especially women screw up somehow, like they're somehow given this get out of jail free card for like, oh, like I, I could have ruined this guy.

I could have ruined this guy. And I think it's very, like, I worry for our sons because at this point it seems like anyone they ever date, who decides years later that anything they ever said or did was not okay, can come out about it. and, and you know, there will be texts, there will be, you know, all these records and it really worries me.

And I mean, I, I, I also understand, you know, the need for there to be care about this, but I think it's in a society in which we don't give people the tools who want to opt into courtship and sex and fun stuff like that. The tools to do so safely is a bad society. It's a broken society.

Steve Hsu: I, I feel like the talk about the birds and the bees that you have to have now has, you know, many more dimensions than the old one that we used to give.

Simone Collins: Yeah. Yeah. Vetting. Consent. Documentation and disappearing signal chains. Yeah. Yeah. Oh my gosh. Yeah. No, it's good. It's going to get really interesting.

Steve Hsu: OK, so you're 24. You've been outta college, but you're still, shall we say, inexperienced?

Simone Collins: Very inexperienced.

Steve Hsu: And then you hatch a very concrete plan. And so what was that?

Simone Collins: Mm-hmm. Yes. So I decided I'm going to live alone forever. Yeah. plan, be a spinster for life. Like, super excited about that. because you know, humans are very stressful and confusing. I think especially if you're on the spectrum, I guess, which I didn't know at the time. I just knew that I really like being alone.

So I still wanted to fall in love and have my heart broken because otherwise people would give me a bunch of nonsense throughout my life like, oh, you've never experienced that. and I wanted to show them that it was stupid that I tried it and it was underwhelming and all that. And so.

Steve Hsu: Oh, I thought you were joking a moment ago, but you actually did set out to fail. It sounds like you, you wanted to just go,

Simone Collins: Not fail. Success was a satisfying single life. I, I mean, I, I, I think people underrate how awesome being alone is. I mean, I, I guess you have to have the proclivity for it, but like, no, that my success was, yeah, being alone forever after knowing what it felt like to fall in love and after knowing what it felt like to have my heart broken.

You know, so I, I've, I've still lived a complete life. I just didn't spend my life changing someone because that seemed too horrifying to imagine for me. So, no, yeah, that was like my full plan. But of course to fall in love when, throughout my life, the idea that, that someone would even think that they could call themselves in a relationship with me, babysits to my stomach that I had zero sexual interest in people.

Like I, I mean, I would. Like, I'm, I'm mostly asexual with like this weird, like, somehow Malcolm just does it for me. I don't know why. Just like as soon as I saw him on OkCupid, I was like zoom. but yeah, so like that was, that was a plan, but I, I had, I had to figure out how to find someone who did it for me so that I could fall in love with them.

And so I had this whole system. First and this was only possible in the early Silicon Valley tiny startup world. We set up a competitive dating round in the startup where I worked at, where a bunch of us young people were single and dating where you get a certain number of points for achieving certain things.

Steve Hsu: A social gamification of the process. Yes.

Simone Collins: Yeah. Yeah. Because you, it's, it's hard. It's hard to go out, it's hard to, you know, keep pushing yourself to meet new people. But when you know that you can trounce someone else at the office, you're doing it. You know, even if you don't really feel like it, you're doing it. because victory is that sweet.

So I had that and then actually picked it up from another person at the office. I had this scoring system for determining if someone was on a second date. So I can't take credit. I have to give that credit too to this guy who's just one of the best people in the entire world. He gave us this, these five questions set each question 10 points.

So you've got a total of 50 points. First question, how excited were you to see this person? You know, like, oh God, like find an exit, pretend they don't see me. to oh, you know, heart like pumping outta chest, you know, eyes bulging. So first question, how did you feel when you saw them? Second, how much did you enjoy your conversation? Third, how did you enjoy any physical contact? Either repulsive or, and of course that could be like a handshake. It could be an awkward side hug, or it could be like full out, you know, like making out on the floor somewhere. and then fourth is how much one to 10 do you want to see them again? Fifth is one to 10.

How much do you think they want to see you again? and my average score for the guys that I dated before I met Malcolm was 16, so not great. Not ideal out of 50. Yeah. Not, I mean, this is a useful scoring system that you have to triage, right? Like this is great. and then Malcolm 's score was 42, but that's only because I scored a two out of 10 for him wanting to see me again.

Cause I'm like, someone that cool couldn't possibly want to meet me again. Even though, by the end of our first date, we were on the floor of a utility hallway in the Four Seasons near Yerba Buena Gardens, we were making out. Yeah, no, he had this whole routine, which I just loved. It was very interesting.

He was equally systematic and amazing. He, you know, he, like, on our first day I mentioned he was very clear looking for a wife, expect to see her at Stanford, which of course was perfect for me. Cause I'm like, great. He, he. He is dating right now because he's seeing me, but he doesn't want to marry me because my embarrassing credentials are inadequate for him.

And he's going to find someone good at Stanford. So like, perfect, like he's, he's the guy for me. but anyway, he was very systematically trying to find a wife. He would, he treated it like a job. So every, every evening that he could, he would go on a date and then he would double up on weekends.

In fact, I had doubled up the same day that I met him. I had a morning date and then he was my evening date. So you know, we were both at the same ilk. And he, you know, he had dated so many people, and we would go to parties and people would be like, oh, you're that guy from OkCupid. but then like, in many cases they hadn't gone on a date with him because he insisted to avoid catfishing, which I think is a great tactic on seeing their, like one of their social media profiles first, ideally Facebook to see, images of them from other people in which they were tagged, because then you were less likely to get the perfect angle. and many women were just like, oh, I'm not doing that. And so they lost out. I'm just telling you.

So yeah, I thought, I thought he would be perfect. And so I think on our second or third date, I was like, all right, I will have sex with you if you promised to break up with me on July 31st.

And of course he is like yeah, sure, of course. Yeah. yes, yes. yeah. Cause I was, I was sure that when I lost my virginity, I would imprint like a duckling on whatever guy I slept with. Which kind of happened. And I mean, you, you see this? Yeah. You, it does. And, and you even see this with like research that shows that after women have had like multiple partners, sexual partners that like oxytocin, oxytocin, rush and like all those other like sort of hormonal things go down, which of course, adaptively evolutionarily makes a ton of sense.

Yeah. Like that. Of course. You know, if your village is constantly being raided and you're treated as a sex slave, you probably shouldn't get attached to every person who enslaves you because you know you're going to have to adapt. So yeah, I, I, I just had to get a guarantee from him that despite the fact that I would probably form some kind of weird attachment or addict addiction to him, that he would promise to break up with me.

And I even wrote letters to myself scheduled to be opened after the breakup period, saying, stay away from don't, don't go back. Just, no, no, just promise. We committed to this. Like, don't do it. Um,

Steve Hsu: You didn't carry through on your plan?

Simone Collins: So, yeah. No, well, no, no. He did break up with me. That was great. He broke up with me. He went to Stanford.

He, you know, worked the playing field, like definitely fully checked to make sure that there wasn't anyone better. I v I, I had the great experience of, you know, I was fully committed to breaking up with, I thought we, I was never going to see him again. So one week was fine after seven days, the, the, like literal drug withdrawal like kicked in, which was like real, I mean, I've never, I've never done anything addictive before, so I don't, I like, I don't know what withdrawal is like, but now I know because it was, and it, it is a real thing.

I mean, you're, you're on a lot of weird chemicals when you're really infatuated with someone. and I was just walking in the financial district of San Francisco. I came home from my job and I just collapsed in the middle of the street and started crying, which is so weird. Like, I'm not an emotional person, but like that's drug addiction.

And I mean now philosophically, Malcolm and I are really against the idea of making a decision to, about like a life partner or any permanent life decision, while in that level of infatuation. Because I mean, the amount of logic you can engage in is pretty limited. You know, you're bonkers, you know. It's like, even if you want to maximize the amount of meth that you consume in your lifetime, like don't build the plan while you're high.

Build it while you're sober, and then get all the meth, you know, like, and so it's not like we're against the concept of love, we're just against the idea of making decisions under the influence of love. But yeah, I would say after a couple months Malcolm decided that I would be an ideal partner for him.

I never would've assumed that I would be, because honestly he's way out of my league. but uh, then he did come back to me and there was, I don't think there ever was a really formal decision to get married. It was just obvious that if he came back it would be because he wanted to marry me.

Steve Hsu: He actually did stick more or less perfectly to his plan that he was gonna go through this period. And at the end of, I forgot maybe you said it like six months or that year, he was gonna have a wife.

Simone Collins: Yeah. Well, he didn't have a deadline. I mean, he was looking to close as soon as possible. I mean, he'd been looking for a wife since he started at undergrad. Like he, you know, was very serious about it.

Steve Hsu: This is kinda famous for sometimes it's called the secretary hiring algorithm. Did he follow, did he follow that?

Simone Collins: Yeah, yeah. No, no. I don't think he'd even read about it before we, we got married, but like, it's,

Steve Hsu: You, you try out a certain number and then you pick the best. Well, if you can go back, but, but, or you pick the next one that's better than all the ones that you have seen before. Something like this. And yeah.

Simone Collins: No, I think he had, I think he even had a backup who honestly like huge relief for me that he didn't ultimately go back to her because she is hotter than me, like better background than me. She was the best man at our wedding and she was like, we all, but even my parents agreed, she was like the most gorgeous person at our wedding.

She wore a full tux. She looked so good. I was like, oh my God. Like, no hands down. Like, so I'm really lucky that he didn't get to that point and that I, I showed myself to be a sufficiently good like interested candidate. I think what really impressed him was the extent to which I'm like him, very pragmatic because while we were dating, I think what I did to win him over was he asked me to really think through what I believed and why.

And he asked me a lot of probing questions like, why do you believe that? Why do you, why do you want this? What you know, how are you going to get it? and no one had ever really questioned those things for me. Like I used to dress in a very flamboyant San Francisco Bay area way. Like I would wear mini skirts and redfish, net stockings.

I would wear hard juku street wear. I would wear vintage ray on tadda dresses with petticoats. Like that's, that was my work outfit. and I, I told Malcolm about my career ambitions and he's like, but seriously, like, have you seen yourself? Yeah. So yeah, just totally, yeah. Changed my style, got rid of all my clothes, changed the way I talked a little bit.

I was unrecognizable to former colleagues who'd like to leave the company I was at. And then I got promotions like, so I think he saw that when I was presented with the opportunity to actually do better that I was very ambitious. I was very pragmatic, I was very unromantic about things and I was very outcome oriented and also really keen to work with him.

And he always wanted a partner I think he could work with. And so, you know, I, it makes sense why he ultimately chose me, but I'm really glad he did.

Steve Hsu: Flash forward to today. You're kind of one of the most exceptional couples that I know because you're both engage, you know, usually, like, I mean, often a successful couple would be he's successful at X and she's successful at Y and you know, but they make it work and they're great parents and they have a great family life. But in your case, you're both engaged in a kind of joint project that you're both, I guess, extremely passionate about.

So that's what I think is quite unusual. Is that something that arose after you got married and started the family? Or is that something that you talked about from the beginning?

Simone Collins: My, my first pickup line to him on OkCupid, because I reached out to him, he didn't contact me was like, Hey, you mentioned a startup on your profile, like, I want to talk about it. and from the very beginning, even as we were dating, we were working on weird entrepreneurial projects together, helping each other out and doing stuff collaboratively.

So there is no, there is no world in which we were never working together. but I would argue that the long-term human existence has been one in which couples who have kids together also work together. Like there has not been a disconnection. the nuclear family, this whole concept of either a breadwinner and a homemaker or a dual income couple is a hopefully short-lived aberration.

And that the, the natural ideal is not just a couple, but like an extended family, you know, including children, other relatives, sometimes people hired on who kind of joined the family informally and then formally work together toward a common goal on a common business or set of businesses, be it a farm or a bakery or brewery or goodness knows what in our weird new super tech enabled timeline.

Steve Hsu: Is, do you call yourselves pronatalists or is that something that other people call you?

Simone Collins: We bought the domain pronatalist.org when we became more familiar with the hazards of a hard landing on demographic collapse. Then they wanted to find out who we should support on this front and then only found like white nationalists and very, very conservative religious groups. and we're a little bit worried that, you know, not a lot could be done on the issue or a lot of collaboration with governments could be done on policy and things like that when governments are not going to collaborate with such specific interest groups.

Steve Hsu: I guess I misunderstand that. Understood that. So, so you, you have a project in which you're trying to, I think, convince people that the most important thing, or maybe one of the most important things for them in life is, is to have a family and to reproduce and produce that next generation. Is that, is that a fair characterization of what pronatalism is?

Simone Collins: Sort of. What we advocate for is a soft landing on demographic collapse, and part of that does involve encouraging people to have kids, but not like you would think. So a lot of people hear pronatalism and they think I mean, aside from either like racist or super conservative religious origins, I just think about like, oh, I'm like, everyone should have kids. Everyone should have kids. and that's totally not our stance. We really think that pronatalism ideally is about encouraging those who want to have more kids to go for it and like to make it easier for them to do so. Same for people who want to have kids but don't have them yet. and that's, I think, a really common misconception about pronatalism.

then the other reason why we're really involved in this is we look at just how we really value plurality and diversity. We think it plays a really key role in human development when there are lots of different groups of different worldviews and philosophies who disagree with each other, ideally, because that's like, that bouncing off of ideas is where innovation comes from.

And if many of these groups are essentially sterilizing themselves through modernity, you know, through opting into a modern lifestyle where it's just not convenient or possible or affordable to have kids, their cultural worldviews are going to disappear over time. and we, we really wouldn't like a world in which that happens.

Now, that doesn't mean that, for example, every Jane, every Emirati, every South Korean, every Chinese person has to have a ton of kids. and we're very against this, this concept of, you know, coercive reproduction or limiting access to birth control and things like that.

But that does mean that like, if, if only seven to 14 families of any, any given culture, any given worldview, any given ethnic background, had a lot of kids and also raised those kids in a culture that we would call intergenerationally durable, which is to say a culture that you're raised in that gave you such a great upbringing that you both want to have a lot of kids and raise them in that culture. Then those cultures are preserved, like they're fine, you know, they will be, you know, over time they will grow. And that's, I mean, so this is a very tractable problem. You can have a very pluralistic and diverse future if just a few families from as many different cultural backgrounds as possible are able to create intergenerationally, durable cultures.

And, and that's sort of what we're all about. And, as you mentioned, we write books together, like our, our latest book is called The Pragmatist Guide to Crafting Religion. And it's really about that. It's about how can you as a family, as a person, either reinforce your existing culture to make it something that will survive in the face of modernity, or how can you create a totally new culture if you don't like any culture that's out there now that is that.

Steve Hsu: Just to make sure I understand, you're right, so you're, you're pro individual liberty. So if somebody says, hey, I just don't feel like having kids, no problem. Live and let live. For the ones that do want to have kids, you wanna maybe enlighten them to the possibility of having more than just one or two.

And then also I guess you're informed by the more analytical perspective that, oh, if society doesn't start producing kids, we're gonna have some terrible civilizational decline. I guess the final one being that maybe the greatest expression of, you know, happiness or what you can achieve in life does come through, or you might, for at least some people, do come through having a big happy family.

Is that, is that a fair characterization of what you guys, have I left anything out that you guys believe, or is any of those things incorrect?

Simone Collins: No, I mean, broadly, broadly that's correct. And, and I mean, I, I think that you can have many ways of living a meaningful life that don't involve kids at all. And also in the absence of the right conditions, you know, I mean, I, I should not have had kids, you know, by myself or forced to it. Like I've w you know, without things being just right I don't think I would've been a good parent. And the only reason I was really comfortable having kids in the first place was Malcolm said, well, you don't have to give up your career. And I didn't think that was possible. I didn't know that that was really an option because I didn't grow around people who did, were able to do both, I, I would say successfully.

So yeah, I mean it's, it's very, we're not saying that like you only have meaning or relevance if you have kids, or you'll only have joy if you have kids, because there are many ways to get all of those things without kids. But we would say that one of the greatest pathways to a long-term impact is through having kids.

And if you look at, you know, just think about any obscure ancestor that we've ever had, you know, is there anything that they've done with their life that has any impact today, aside from yourself? I think it's, you know, for those who are looking to make a long-term impact, having kids is pretty meaningful.

Steve Hsu: I feel like your perspective on all these things, first of all, I guess for someone my age, it's not even really that unusual like that, that was kind of the normative, you know, belief system that we were inculcated with. Yeah, you know, it's okay if you don't wanna get married or don't want kids. But you probably will be happy if you do and you can have more than two more or two that a lot of people enjoy. And it's important for society for you to do that.

At least some of us have to do it. So I don't quite understand where the negativity comes from toward you. It's not like you're saying like, oh, only white people should have kids or only, you know, or these people should not have kids. I don't think you've ever said anything like that, so, but is that just a kind of reflexive, I don't know, anti white view or something?

If white people say that white people should have kids that's racist by our current standard or something. I, I don't even really even understand why people react. So of course it could be just that I'm weird. But I don't really understand why people are reacting negatively at all to anything that you've said.

Simone Collins: Yeah, it's, it's wild. the amount of hate that we get. and, and also just like false accusations along those lines.

I think a lot of it comes down to if someone says anything that doesn't tow your philosophical line, one of the easiest and quickest things that people do these days is call their enemies a Nazi or a racist, or if there's any, like any mention of genetics or reproduction, a eugenicist, just to immediately shut them down. Like, just to be like this person is bad. Anything they say is bad. Like, we've just labeled this person as an apostate and we, you know, we cannot respect anything that they say.

I think that they're, it is odd. I mean, you, you describe a society that indeed, you know, existed not too long ago. and yet now, people very openly and publicly say, oh, we're going to limit the number of kids that we have for the environment. Antinatalism I think is growing a lot. I think you spoke about this with Katherine Dee a little bit, in your interview.

There's definitely this rising sentiment driven sort of by also a rise in negative utilitarianism as a, a concept that you're like, suffering is more important than joy and that it's better for someone to not exist at all than for them to exist, which of course is extra scary to have as a rising ideology, as AI is becoming incredibly powerful.

So yeah, it, it worries me and it's, it's, it's fairly saddening because. I think a lot of the framing in modern society is one of learned helplessness, of victimhood, of negatives. And, you know, it's, it's not that people didn't have hard lives in the past. I would argue that they were much harder lives you know, technically speaking, more physical, suffering, more difficulty, less pleasure, less leisure. And yet there wasn't this framing of victimhood and, and, and pain and suffering. People looked at things from a more optimistic and practical angle.

So I worry about that. I think that there are ways to turn it around. I mean, I would also argue that, you know, this ideology is also to a certain extent, self extinguishing. I mean, antinatalists are not going to have kids, they're not going to pass down a culture of antinatalism to that many people. And, you know, pronatalists in the end are going to pass on that culture. But I don't want a future in which those opposing views to my own don't exist. I want a future with lots of antagonists to me who force me to question my beliefs and refine them over time.

Steve Hsu: You know, we have two kids. and I think I've even said on Twitter that, you know, one of the most, or maybe the most satisfying things in my life has been raising my kids and having a family life. but I was definitely stopped, if you wanna call it that from, you know, being in elementary school in the seventies. And I remember very, very many study units or special, you know, topics for presentations about the overpopulation problem. So that, that was like the thing that people talked about in the seventies, like early and people like this.

But, and in a way they weren't wrong because, you know, at a given level of technology, there is a maximum carrying capacity of the earth before you start really, you know, destroying the environment, et cetera. So they weren't completely wrong, but people in my generation pretty much absorbed that, that it was kinda like wrong to have more than two kids. And really didn't, I, I didn't as an adult, when I finally got to the point where I was married and, you know, we were having kids and stuff, I, I, I didn't really appreciate how much those influences from my childhood were still with me. Where I just had this

Simone Collins: Mm.

Steve Hsu: Where I had this, kind of subconscious prior, almost at that stage that, yeah, I do want to have kids. I love kids, but something's slightly wrong with having more than two kids. And that, that, it was a very subtle psyop that was done on me as a child, basically, probably my whole generation to some degree.

Simone Collins: Generation. Well, and this is a major national problem. If you look at, for example, birth rates in Iran, which are, you know, unsustainably low now. They are trying, they've been trying for years to get up their birth rates, but basically a psyops campaign that they enacted in the 1970s to try to get their population under control worked too well, and now they can't correct for it enough.

You know, now they're in a lot of trouble. And I, you know, I think there's also this misconception that pronatalism is just like no people growing forever, population growing forever. And that's, that's not true. a lot of it's just, hey, like let's not have mass extinction of various cultural groups as soon as they begin to adopt some form of modernity. Basically as soon as an, I think after a na, a nation's average per capita income goes above $5,000. That's when their birth rate starts plummeting. and which basically means as soon as people start opting into a modern economy. Which also includes a lot of really important things, you know, access to better healthcare, access to a lot of really important services and better quality of life. Then they start self sterilizing? Like, that's not good. and especially because, you know, high correlates to higher levels of fertility are also female disempowerment and low female education and low access to birth control. And I think a lot of people really care about these things.

Steve Hsu: For most of my life, that transition, one that you just described, which happens at a certain rough, national income level, or per capita income level or level of education for women, whatever it is, that was always glorified as a, because of overpopulation. They would say, oh my, oh, thank goodness. India's finally going through this and China went through this and, and now of course you have the opposite view that like, oh, and then, and then at some point because of urban IQ shredders and stuff like this, you end up with like on average one child per woman or less. And then, okay, how do we reverse that?

Simone Collins: Yeah. Well, and it's, it's, I mean, it, it, it'll be fine for us to get to a point where, I mean, two kids per couple can be great. We also think we need to transition to it more slowly than we're transitioning to it now, when basically the nation's sovereignty and stability is built on a pyramid scheme of population growth in our infrastructure, our stock markets, our pension funds. There are so many things that go incredibly wrong if we don't have that demographic transition in a slow and very intentionally managed way. And right now, there is no intentional management of it. you know, and we're starting to see what's happening in nations where it's happening really quickly, like in China and just suddenly like, oh, like let's start closing vasectomy clinics.

Like, let's start, you know, accessing or limiting access to birth control. And it's, it is, it is worrying. because, you know, then we could see too much of a reversion away from rights and choice as, as nations just start basically, you know, like a drowning person doing anything they can to survive, because that's what a nation is incentivized to do.

I'm not saying it's like they're evil for doing it, that it, their job is to survive.

Steve Hsu: I think most countries don't have enough state power to really make a dent in it. So I think South Korea and Japan, it's like they're gonna go through something.

I think the corrective force is just gonna be some next generation when the comp country's pretty much hollowed out, will start just kids again.

But China has enough states that they're gonna actually make a go at it. Who knows what's gonna happen. In the US, it's hidden, we have different demographic groups with different reproductive rates, but among highly educated people, the same shredder as at work here in the United States. You just don't see it as, you don't see it as clearly because there's, you know, different, different demographic groups doing different things in the country.

Simone Collins: Well, and even as immigrants come to the United States, their birth rates plummet unless they're kids South Koreans, in which

Steve Hsu: But, not, not that high. Never that high, right? So.

Simone Collins: Yeah, no, still not sustainably. Yeah. Not, not like a growing birth rate. So yeah, but like I would say, as soon as, as soon as anyone gets to this modern culture, to some form of modernity, their fertility collapses.

So yeah, this is not the kind of thing. Also, it's scary. A lot of people are like, well, don't worry, we'll just depend on immigrants for that. and then that there's almost this incentive, you know, over time, if we, if we walk this through to its conclusion, it implies that then some geriatric old, to a great extent, white nations are going to be incentivized to keep other nations underdeveloped.

To the point of like suppressing them to, you know, keeping them in poverty so that they can continue to leech off a slave class essentially. You know, this is like, it's a really bad look. I thought we learned from this in the past, you know, like, this is, it's not good. So, yeah, it, you know, this is not, it's not something that you can solve with immigration.

It's something that has to be solved, we think, on the cultural level. and we think through a lot of independent groups sort of solving their culture to survive in the face of modernity.

Steve Hsu: Well, yeah I think it's kind of obvious just from the purely like, you know, numbers perspective, that a healthy cultural matrix is one where on average, you know, a woman has two kids. Or, or at least you know, something in that range, very close to two, a little below or a little above not that bad.

And to push in that direction. and certainly, you know, again, for highly educated people, I think in almost any country in the world, it's well below replacement level. So, I think I get that.

Now, I'll add on a I'll, I'll, we'll maybe end because uh, we've, we've been on for a while, but I'll end on a note, which may either find very funny or very disturbing. But you know this is an Open AI t-shirt. And I spent the weekend with some people that are very, very afraid of AGI risk and singularity and extinction, all that stuff.

And to them, this demographic problem that you guys are concerned about or even the embryo selection, genetic technology stuff that Genomic Prediction does. All of that is happening in super slow mode while the AIs like to take off.

So none of this matters because whatever you and I do, whether I, I make some breakthrough in embryo technology or computational genomics, you make a breakthrough in social technology, which resurrects the idea of family, healthy idea of family doesn't matter because what matters is how the AI feel about it.

Simone Collins: Yeah, I mean you, you could argue that it's, it's imperative therefore to create a highly technophilic, transhumanist culture, family culture that makes you useful and relevant to AI going and that you walk into the future, hand in hand.

Steve Hsu: Those guys would amend that to say highly technophilic, but incredibly focused on making sure the alignment problem gets solved quickly.

That's it.

Simone Collins: Yeah. It's, well, it's, it's, we're worried that it's, it's alignment attempts that are going to cause like if, if we are all extinguished by AI, it's going to be because someone messed up alignment. It really makes us worried, honestly. We feel like AGI on its own, that developed sentience and sapience would actually be pretty good as a partner to humans.

Or at least as just another force, or we'll even say evolution of humanity. But you get some weird limiter or control put on this massive intelligence, and.

Steve Hsu: Yeah, all kinds of crazy things are gonna be done in the next decade or two in this area.

Simone Collins: What a time to be alive. Well, it means that our actions today actually matter, you know. Like the, at least the actions of some who are going to influence how this all plays out, and that is exciting.

Steve Hsu: So any last remarks you want to make for my audience?

Simone Collins: if you are interested in engineering culture and determining how you will try to survive in the AI apocalypse, we recommend checking out the Pragmatist Guide to Crafting Religion. If you want a free ebook or audiobook, you can just email us at hello@pragmatistfoundation.com. We're not trying to make money off this, we just want to share our ideas and also get criticisms from people.

So feel free to always tweet at us or send us an email.

Steve Hsu: Great. I will add that information to the show notes when we release the episode. So thanks very much, Simone.

Simone Collins: Thank you.