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- [00:01]
Craig Horlebeck
Hey, it's Craig Horlebeck here to tell you that the NFL is back whether you like it or not. And we are covering all the latest news, trades, rankings and more on the Ringer Fantasy Football show with my two co hosts who are both named Danny. Check the Ringer Fantasy Football show out on Spotify or on our new YouTube channel.
- [00:18]
Derek Thompson
This episode was brought to you by ServiceNow. We're for people doing the fulfilling work they actually want to do. That's why this was written and read by a real person and not AI. You know what people don't want to do? Boring, busy work. Now, with AI agents built into the ServiceNow platform, you can automate millions of repetitive tasks in every corner of your business, it, HR and more so your people can focus on the work that they want to do. That's putting AI agents to work for people. It's your turn. Tap the banner to get started or visit servicenow.com AI Agents this episode is brought to you by Zendesk, introducing the next generation of AI agents built to deliver resolutions for everyone with an easy setup that can be completed in minutes, not months. Zendesk AI agents resolve 30% of interactions and instantly, quickly giving your customers what they need. Loved by over 10,000 companies, Zendesk AI makes service teams more efficient, businesses run.
- [01:29]
Roxandra Tesla
Better and your customers happier.
- [01:31]
Derek Thompson
That's the Zendesk AI effect.
- [01:34]
Roxandra Tesla
Find out more at zendesk.com today the.
- [01:38]
Derek Thompson
Fertility dilemma and the Future of Fertility Science in the last few decades, men and women have been having children later in their lives. The reasons tend to be complex and easily simplified. Yes, it's about labor economics as today's.
- [01:53]
Roxandra Tesla
Young people are more likely to go.
- [01:54]
Derek Thompson
To college and use their 20 something years to become established in their careers before settling down and having kids. It's about housing economics too, as the cost of homes has soared in this country, which makes it harder for young couples to feel settled. It's about gender relations as young people.
- [02:10]
Roxandra Tesla
Are less likely to date or couple.
- [02:12]
Derek Thompson
Or marry than they used to be. And it's about biology, as young people delay family formation by spending more of their twenties working or prioritizing personal fulfillment. And as coupling is delayed and as marriage is delayed and as home buying is delayed, this unstoppable force of delay runs up against the immovable object of human anatomy. It is just harder for a 40 year old to get pregnant than a 20 year old. The best solution that we have for this dilemma is in vitro fertilization. IVF is a decades long practice which is based on Science. And so you might think that the procedure is highly predictable, something close to an act of precision engineering. But it's not. First, the doctors send the woman home with prescriptions for hormone shots. This is for the purpose of stimulating her ovaries. One might like to think that the exact dosage comes from a genetically and biologically precise calculation, but it's more like a rough guesstimate based on the woman's age and medical history. Second, doctors collect eggs from the ovaries. Again, you'd like to think that they have a clear sense of how many eggs they'll retrieve.
- [03:25]
Roxandra Tesla
But here again, the doctors are often.
- [03:27]
Derek Thompson
Just as surprised as the patient by what they collect. Third, the eggs are combined with sperm provided by a husband, partner, or donor. How many embryos will result from this lab dish fertilization process is, again, kind of anybody's guess. Fourth, the embryos are analyzed for, among other things, chromosomal abnormalities. But what these abnormalities actually mean is yet another mystery. There is, for example, intense debate among doctors and couples about how to think about mosaic embryos, meaning they contain a mix of genetically normal and abnormal cells. Many clinics and doctors simply don't know exactly what to do with these embryos. Fifth, embryos that are deemed healthy enough are transferred, as they call it, to the woman's uterus. Again, you'd like to think that at this point in the process, success is all but guaranteed. But the truth is, it's still basically a coin flip as to whether the woman gets pregnant. This is the best and most advanced common fertility procedure in the richest country in the world, in an age of scientific wonders. And yet the whole thing is just one long cavalcade of uncertainty. With an overall success rate well below 50% per round, some couples have to go through the process several times a year for several years, at exorbitant financial cost, not to mention emotional cost. Fertility is practically the most basic mammalian function there is. And yet the science of fertility feels awfully like a crapshoot at the very moment in our history when. When we need it the most. I know it might sound a little creepy to some folks to think about the science and technology of fertility. Perhaps a little bit matrix adjacent, but the one and only baby boom in the history of the modern world was, in part a revolution in science and tech. Many people assume that the baby boom, that which we associate with, say, the baby boomers, started after World War II, like a spasm of giddy horniness following America's smashing victory. This is simply wrong. The baby boom actually started in the 1930s. And it happened not only in the US but practically everywhere throughout the Western industrialized world. It was somewhat universal among richer countries, and so the only explanations that make sense here must be similarly universal. In fact, starting in the 1920s and 1930s, electric appliances like refrigerators and heating machines proliferated throughout American and European homes, just as advances in antibiotics dramatically reduced maternal mortality, which made giving birth much safer. Electric machines and medicines probably weren't the only factors behind that first baby boom.
- [06:13]
Roxandra Tesla
But they were critical factors.
- [06:16]
Derek Thompson
And if the last baby boom came from science and technology, perhaps the next one will too. Today's guest is Roxandra Tesla, a scientist and a writer. We talk about the fertility dilemma that exists, the fertility technology that doesn't yet exist, and how a scientific revolution in egg science could produce a second baby boom. I'm Derek Thompson. This is Plain Eng.
- [07:08]
Roxandra Tesla
Roxandra Tesla, welcome to the show.
- [07:10]
Thank you for having me on.
- [07:12]
We're talking today about fertility, the science of fertility, and even the future of fertility technology. And I know some folks find any level of attention paid to this topic a little bit creepy. Like, why should any stranger care about the number of children you have? The number of children I have. Why is this subject important to you?
- [07:33]
Well, so I think on a very personal level, I suffer from a condition called polycystic ovary syndrome, and I'm a biologist. And I think these two things combined led me down a path of looking a lot at fertility science and realizing that I had been sort of misled by doctors and by sort of, I don't want to sound conspiratorial, but society in general and like, sort of common medical knowledge in terms of, like, what my condition meant. And also, even with all of the sort of biological training, what I could find and how badly underfunded and under researched the topic of fertility was. And then it just turned into, like a broader interest, I guess, because, you know, I am a woman who wants to have a career, I want to have children as well. And, and there are all these conflicts that, as I'm approaching my 30s, I'm 28 now, are sort of like, becoming more apparent to me. And I'm also seeing women older than me sort of grappling with these kind of things.
- [08:38]
You touched on something that I think is absolutely critical here, which is this tension between modernity and biology. In rich countries around the world, birth rates have fallen to historically low levels. And a part of that is that many women, especially educated women, have been.
- [08:54]
Derek Thompson
Delaying fertility if they want to work.
- [08:57]
Roxandra Tesla
If they Want to build a career in their 20s.
- [09:00]
Derek Thompson
You've written that women who make this.
- [09:02]
Roxandra Tesla
Decision are looking at the data in.
- [09:06]
Derek Thompson
A very rational way. Women face a significant penalty in earnings after giving birth. Can you talk a little bit about that earnings penalty?
- [09:17]
Roxandra Tesla
There's a 16% gender wage gap on average. And in developed countries a very, very large part of that wage gap is a so called motherhood wage gap. So basically these sort of wage gap starts to appear when women start to have children. And this is particularly stark in professions that are like high pressure, high demand professions like medicine, law or. Yeah, medicine, law, academia, you know, all of this, all of these professions that we kind of as a society, for better or worse, hold in high regard.
- [09:51]
You call them greedy careers.
- [09:53]
Greedy careers? Yes, greedy careers. That's the term that Claudia Goldin, the winner of the Nobel Prize for economics in 2023 uses for these careers. So these are careers where the more work you put in, the more hours you put in, the sort of return to your input of ours is, is exponential. It's exponential, it's not linear. Can always work more and you can always gain more. And you know, probably entrepreneurship is like the perfect example, right? Like in entrepreneurship, you know, there's never enough that, you know, there's never too much that you can do, right? Like each, like extra hour that you take for a meeting with someone, it might lead to the next company, might lead to the next business partnership and so on. So I would say that's an extreme. But a lot of the other like sort of high stakes care like medicine and so on, also quite greedy.
- [10:44]
We could do a whole hour on delayed fertility and why so many people have fewer children today than they had in previous decades. We have done shows about that. And to circle some of the conclusions that I reach from those shows, I don't think this is a simple topic at all.
- [10:58]
Derek Thompson
I'm not even sure that we have.
- [11:00]
Roxandra Tesla
A simple way to describe how complicated it is. I think it's about economics. I think the earnings gap that you described is absolutely a factor here about technology. I think contraception allows people to control fertility today in a way that's historically unusual. I think it's about sociology.
- [11:18]
Derek Thompson
I think people date less, they get.
- [11:19]
Roxandra Tesla
Married less frequently than they used to. And you've touched on this as well.
- [11:23]
Derek Thompson
It's about trade offs.
- [11:24]
Roxandra Tesla
I mean, parenthood is sacrifice. You don't sleep, you can't parent hungover. Trust me, I've tried. You can't work full time with a baby.
- [11:33]
Derek Thompson
Trust me, again, I've tried.
- [11:35]
Roxandra Tesla
So I want to push even deeper into this core dilemma here, which is that the economics and the culture and the technology of the modern world are conspiring, you could say, to delay fertility.
- [11:46]
Derek Thompson
But this is running up against something.
- [11:48]
Roxandra Tesla
Else, which is biology.
- [11:50]
Derek Thompson
What do you think is the most.
- [11:52]
Roxandra Tesla
Intelligent, sophisticated, scientific way to think about how pregnancy gets harder as women get older?
- [12:00]
Yeah. So basically, we know that per month chances of conception for women, let's say in their 40s, decreased to 5% from something like 25% in their 20s. And we also know that a significant proportion of women, the fertility, starts to decline after 35, and that a proportion of those women will really struggle to conceive naturally. It's not just like a per month problem, it's like a sort of even if you try for a year, this is how infertility is defined medically. If you try for a year naturally and you don't conceive, then you're diagnosed with infertility, and that starts to increase after 35. The main problem here is the aging of the egg. Basically, women have a complex reproductive system. We have a uterus, we have eggs, we have ovaries, where we have the eggs. And a very important point here is that this aging, the aging of the reproductive system of women is driven mostly by the aging of the egg, not the uterus. And you can see this very clearly when you look at data from the chance of pregnancy using donor, Young donor eggs. And when women in their 40s use young donor eggs, their chances of pregnancy are quite high. They're very similar to the chances of pregnancy of women in their early 30s, late 20s, which clearly shows that a very good control experiment clearly shows that the reason why their uterus, the rest of the reproductive system, is quite capable of holding a pregnancy and having a pregnancy. But this aging of the egg is really what's driving the decline in fertility with age.
- [13:54]
I want to put a pin in that because it's obviously so important if we want to think about the science and technology of fertility the next few decades. The key here is egg health. Right? The key here is understanding the science of eggs. Before we get to the science, there's a large group of people, I think, who believe the best way to solve these kind of problems are with policy interventions.
- [14:18]
Derek Thompson
And if you look around the world, many governments have responded to declining fertility.
- [14:23]
Roxandra Tesla
By introducing this enormous set of policies. We have more maternity leave and paternity leave. We have preschool programs. We have tax benefits for parents. We have child tax credits here in the US which were Just expanded with the new Trump law. I think it's fair to say that if these programs worked, their success has been moderate at best.
- [14:45]
Derek Thompson
So why do you think in the.
- [14:46]
Roxandra Tesla
Big picture it's been so hard for government policy to increase fertility?
- [14:52]
There's complex answers to that. And I would also say that government policy, maybe even more surprisingly, has failed to decrease the gender wage gap. So there are a lot of policies that were targeted specifically at the gender wage gap to help women navigate this part of their careers. And especially, again, in these greedy careers, you can't really compensate for lost time, especially in your 30s. And this is the important part that I would also like to highlight how important one 30s are for these greedy careers. We have data to show that, you know, the more you delay, the better it is for your career. I'm not saying necessarily that the more delay childbearing, and I almost call it like escape velocity, there is a point in your career where you become established enough that you can afford to take some time off and you can afford to sort of. I mean, if you take 10 years time off, then it's not great. But once you become established enough, and I think everyone here knows this, for example, in academia is becoming a principal investigator, and that usually happens in your late 30s and so on. It's not that you can just take time off, but you have a more stable situation. But it's very, very hard to take time off or to not take risks in your 30s if you want to have one of these careers.
- [16:11]
I want to scope out here a.
- [16:13]
Derek Thompson
Bit, because you and I both went to college. We're both enmeshed in the culture of what we're calling greedy careers. We agree that the smart way to think about this problem is to create technologies that extend fertility deep into one's.
- [16:26]
Roxandra Tesla
30S and early 40s.
- [16:28]
Derek Thompson
But I want to acknowledge here an alternate viewpoint that says that what needs to change is culture. There are some folks who say no prioritizing work is the problem. People should just get married earlier. They should have children earlier. We shouldn't try to push against the biological limits of our bodies. What is your response to that?
- [16:53]
Roxandra Tesla
A lot of people are arguing on that point, that we should change culture to be much more sort of, that we shouldn't encourage women to the. We shouldn't invent these new technology to encourage women to delay childbirth because we're kind of like creating this, like, sort of negative feedback loop where they have, like, less and less children. But my point is that we're already seeing a decrease in you Know, a delay in childbirth. And like Gen Z, women are having less children than millennial women were having at their age. And unless we develop this, this is no longer a matter of like, encouraging women to have children later. Women are having children later. And unless we have this, unless we do something, unless we invent this technology that goes beyond policy, unless we do the technology, it's not about encouraging women to have children later. It's about helping those women who will have mostly chosen already to have children later actually have the children that they want.
- [17:47]
I think that's such a critical point that government policy can work at the edge to make it easier for people to take time off. It can make it a little bit cheaper to have a child by subsidizing certain aspects of childhood. But government can't change the fact that.
- [18:02]
Derek Thompson
Having children is no longer a norm.
- [18:05]
Roxandra Tesla
For young women and men in their 20s. So you and I are trying to execute something that might be a little bit unusual. I think a lot of people, when they look at this issue, fertility, they think about behavioral and policy solutions, right? They don't think first to how do we invent some new fertility technique through science and technology. But one really interesting point that I've heard you make is that there's other social dilemmas where behavioral and policy interventions.
- [18:30]
Derek Thompson
Kind of failed or at least did very little, and we needed a breakthrough.
- [18:35]
Roxandra Tesla
From science and technology to achieve real progress. Can you name a few of those examples where you see, maybe fertility can be like that?
- [18:44]
Yeah, so one of the very recent ones is obesity, right? So we have. Western countries have struggled with obesity and sort of associated comorbidities for, like, decades now. And we have had all sorts of programs, all sorts of social programs that promote healthy eating and so on. But it just turns out that our minds are kind of like, not adapted to resist to the sort of temptations of the kind of food environment of the modern world. And then you have this GLP1 agonist. So the new therapies, that people know them by different names like Ozempic, Semaglutide, Mounjaro, you know, all of these are kind of names for the same thing. So these new therapies that now pharma companies are like, racing to develop, and they're all like, you know, in a fight. There's this fight between Novo Nordisk and Eli Lilly for biotech geeks. These therapies work very well. And I think that's a great, great example because, you know, I know, I actually know personally people who have struggled for years with this obesity. And they have felt guilt and they have felt, you know, there's all sorts of like mental health issues associated with it as well. And then you have this drug and then, and we're making it better and better because like people were saying at the beginning, like, oh no, you're going to become dependent. It's just going to have so many side effects. And it turns out, like my parents, you know, I recommended to my parents and you know, they couldn't take the first version of it, but now they're making it better and better and they don't have side effects.
- [20:19]
Well, I think obesity is such an interesting example because with obesity, I love the way you framed it. There's a mismatch between the architecture of our calorie seeking brains and the calorie abundance of the modern world. And it turns out that while behavioral interventions are not often successful at fixing.
- [20:36]
Derek Thompson
That mismatch.
- [20:40]
Roxandra Tesla
A pharmacological intervention is very good at adjusting our minds or our brain gut balance.
- [20:46]
Derek Thompson
And in the same way, what we're.
- [20:48]
Roxandra Tesla
Talking about here with fertility is a.
- [20:49]
Derek Thompson
Little bit of a mismatch right between.
- [20:51]
Roxandra Tesla
The contour of the modern career, the shape of modernity and human biology. And so let's talk a little bit about fertility technology that exists and about fertility technology that could exist. First, what exists? We'll start with egg freezing and in vitro fertilization, otherwise known as ivf. Can you explain the science here? Why does egg freezing work at all?
- [21:19]
Yeah, so the reason why egg freezing works at all goes back to my earlier point about why women's reproductive system ages, which is the egg. Right. So the reason why, you know, and I just brought up that women who are in their 40s and they use young donor eggs, they usually can conceive at similar rates to women. Like very, very small difference between them and women in their 30s or late 20s. Basically, when you freeze your eggs, you act as your own young egg donor, more or less. Basically, the process of egg freezing used to be quite inefficient. The first reported birth was in 1986 from egg freezing. But it was very inefficient. It was only used for extreme cases, for example, during cancer treatment, but then in the mid-20s to protect the eggs from all of the, you know, damage that you could get from like cancer treatments. But, you know, in the mid-20s, 2000s, people introduced this new technique of freezing eggs. It's called fast freeze vitrification. And it kind of started to take off. It works very well. I mean, you know, most Studies show that if you do it at a clinic that knows how to preserve your eggs. And that's a big if. And unfortunately, clinics don't publish data on this. But, you know, if you do it well, frozen and thawed eggs kind of have the same type of developmental competence as, like, you know, fresh eggs.
- [22:56]
Unknown
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- [23:25]
Derek Thompson
Rated T for Teen.
- [23:27]
Unknown
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- [23:56]
You know that one friend who somehow knows everything about money?
- [24:00]
Roxandra Tesla
Yeah.
- [24:00]
Unknown
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- [24:23]
Roxandra Tesla
So IVF has been with us for a while. I think most listeners are familiar with ivf. How well does it work compared to, say, trying naturally?
- [24:33]
Yeah, that's a very interesting question, and it's quite a hard question to answer because usually people who try IVF try IVF because they have some infertility problem. Also, the rate of failure of conception in the human body is not really very well assessed because people just try and at some point they get pregnant or not. It's hard to say how successful it is compared to natural conception. But we do know. I can tell you how well it works for women of different ages. For women under 35, about 50% of cases of women under 35 do IVF. So in vitro fertilization, just to begin with what it is, it's literally fertilizing an egg in vitro with a sperm. And usually you do that for various reasons. If you're a woman under 35, in 50% of cases is because of male factor infertility. And basically that just allows you to artificially fertilize the egg with sperm and bypasses the problem with male factor infertility. In many cases for women under 35, only 50% of cases are related to female factor infertility. And that can range from stuff like polycystic ovary syndrome, which is a problem with ovulation. So you don't ovulate regularly. And actually in in vitro fertilization, you induce ovulation sort of synthetically. And actually women with pcos, which is what I have, and I didn't know this, actually do have good success rates with ivf. They don't have lower success rates than women with things that don't affect their eggs. So they don't. Yeah, they don't have. They have good success rates. And other factors are like tubal factors. I literally can't travel through your fallopian. So the fallopian tube thing that connects your sort of ovary to your uterus and like the egg has to travel to it. So some women simply just have some sort of blockage and the egg can travel through it. And again, that has nothing to do with the egg quality itself. It's just about like, you know, it can't travel. Then you have endometriosis, which is a bit more complicated because endometriosis is the inflammation of the uterus and it can actually affect the ovary as well. And that's a bit more complicated. And then you have women over 35 for which increasingly they use IVF because of the fact that their egg quality starts to decrease their egg quality and egg quantity starts to decrease. So then they're more like age related infertility.
- [27:09]
I will say. You know, the thing about IVF is that it is kind of terrible for a lot of couples who go through it. It's expensive. It's certainly more art than science. If you're the woman, you're stabbing yourself with hormone shots that can leave you feeling drained, bloated, or just gross. It's stressful, it's painful. The process of taking the eggs, retrieval, as it's called, is quite intense, requires anesthesia. And then after all that, it often results in no embryos, in no viable embryos. So there is a lot of room for improvement here.
- [27:42]
Derek Thompson
What are some ways we could make IVF better.
- [27:46]
Roxandra Tesla
They usually tell you that for embryo transfer success rate. So, for example, for women under 35, it's usually somewhere between 40 to 50% chance of live birth. For an embryo that. Yeah, for an embryo that you are transferring. But that's if you get any embryo at all. In General, women under 35 do get embryos from their cycle, but there is the possibility they won't get any embryos. And the number of embryos you get that are morphologically, people assess them morphologically, they're morphologically good. And assessed as implantable is directly proportional to the number of eggs that you retrieve. Obviously, if you're younger, it's easier. Then the rate of success of IVF decreases a lot with age after 35. For example, for women who are between 40 and 42, I think the national average in the US is 13% per cycle. And if you do PGTA, which is like, if you assess whether the embryo is chromosomally normal, then the success per embryo transfer is higher. It's like around. Again, around 40, 50%. But that's because you've already selected an embryo that is genetically normal, and your chances of having an embryo that is genetically normal are low for a woman between 40 and 42. So actually, your chances per procedure is itself the egg retrieval procedure. Per IVF procedure is more like 13%. So you have to be very careful when you look at these tasks, whether you look at. Is it per procedure, Is it per embryo transfer? Because if you do it per embryo transfer, they can just consider the best embryos that we tested. But a lot of women might not.
- [29:31]
Derek Thompson
There's a larger dilemma that we're circling here, which is that fertility and women's health don't receive nearly the same levels of funding that major diseases receive, even though fertility is the basis of life. And the trends that we described make it harder for many couples to consider conceive. The state of fertility science is surprisingly weak, Underdeveloped.
- [29:53]
Roxandra Tesla
Right.
- [29:53]
Derek Thompson
Advancing quite slowly. IVF is the best we've got in many cases. And it's essentially a process of trial and error rather than precision medicine. Why do you think fertility and maternal health are underfunded fields?
- [30:11]
Roxandra Tesla
Yeah, there are many reasons for this. So one of them is just kind of like cultural inertia. So I want to say the name of a book, the Emperor of All Maladies. And what disease do you think it is about?
- [30:27]
I happen to know that, yes, Siddhartha Mukherjee's book, the Emperor of All Maladies, is a book about the history of cancer.
- [30:33]
Yeah, exactly. And I think that this kind of shows how cancer is seen in the public consciousness, right? Like it's seen as this. Like the emperor of all maladies, and we had a war on cancer. And I don't think it's coincidental we have so much funding on cancer because it's seen as this. I mean, it is a very horrible disease. Not just seen as a horrible disease. But my point is that we tend to treat and we tend to fund things that are like, lethal, that like, sort of cause death. We. We have in general, much less. We don't see things that, in general, that affect life quality as. As important. So I think that we just don't. We haven't really invested a lot in women's health, and we haven't seen fertility as something extending fertility in the same way that we see finding disease. So that's one part of it. I think another part of it is just I've been digging deeper into the nitty gritty of this. It's just how hard it is to study it from a very, like, practical perspectives. So, for example, getting access to human eggs and being able to fertilize those eggs just to study in order to implant them, it's just very, very, very hard to get approval for that. Very few labs can do it. And I sometimes talk to researchers and I ask them, they have very exciting research that could maybe improve. We could learn how to improve egg quality. And as I'm like, why have you mice, right? You have to consider that they're first of all resource constrained because they don't get a lot of funding, as I just explained. But then they tried this thing in mice, and I'm like, why didn't try in humans? And they're like, oh, we just don't. I don't want to waste human eggs because they're so hard to get. And if you want to study embryogenesis and sort of the process which the embryo forms is even harder, and so few labs can get access to that. And there is so much legislation. People of different sort of cultural and political backgrounds will disagree on this. But the fact that we treat it with so much, in my opinion, over care makes it very hard to make progress because you kind of have to understand the process of fertilization, the process of how the egg develops and so on, and then how the embryo develops in order to be able to make IVF better. Because how are you going to make IVF better unless you understand how the embryo forms and you understand the biological basis of that and we don't really understand it.
- [33:21]
I'd like to depart now from the world that exists and enter the world that might exist if fertility science technology advanced tremendously in our lifetimes. Paint the picture here. What does the frontier of fertility technology look like to you? What should we hope to invent?
- [33:39]
Yeah, so I think that we can do at the moment a lot to make the IVF process itself better. So we know that even for women who have healthy eggs, it doesn't work very well. We can make the stimulation easier. We can get those embryos to develop at a much higher rate. We don't need like 50% success rates. We can take that higher. We don't need young women to go through multiple cycles as they sometimes do. So that's one thing that we can do. But then on the very sort of more like long term horizon sort of sci fi level, I think we can create actual new eggs from other cells of the body and have an abundance of eggs, and then you don't need to worry about anything.
- [34:23]
All right, and this is the sci fi part that I really wanted to talk to you about. And it involves a frontier of science called induced pluripotent stem cells. I would like you to bring this all the way down to science 101. What are induced pluripotent stem cells? And how could this science dramatically improve fertility rates?
- [34:48]
Yeah, so induced pluripotent stem cells, just to begin with a bit with the science, you have an eye cell and a skin cell, and they all share the same DNA. The difference between them, and they're all descended from the same embryonic stem cells. The difference between them is mostly epigenetic. They're epigenetically programmed to be an eye cell or a skin cell or whatever. It turns out that if you induce these things called Yamanaka factors, these four transcription, they're called transcription factors into fully differentiated cells from a human, you can turn back the clock and you can make them back into something that is more like a stem cell. And that's why they're called induced pluripotent stem cells. The inventors of this won the Nobel Prize in 2012 for medicine. These induced pluripotent stem cells then act as stem cells and then they can be turned back into other cell types. This is actually widely used in medicine now in cancer therapy and drug testing and so on. It's almost like in Harry Potter you have transfiguration here. You kind of transfigure one type of cell to another through the intervention of the.
- [35:59]
Let me slow this down because it.
- [36:01]
Derek Thompson
Truly is the most extraordinary thing if.
- [36:04]
Roxandra Tesla
This science moves forward. Several years ago, I went to a.
- [36:08]
Derek Thompson
Conference on the frontier of medicine, and one of the presenters was working on this field of pluripotent stem cells.
- [36:15]
Roxandra Tesla
And I had never heard of this, by the way.
- [36:17]
Derek Thompson
And he says, essentially, imagine a world where we could take a scrape from your arm. So we take forearm skin cells and we could use this science that you described, Yamanaka factors, to turn those skin cells back into stem cells, to almost pull the cells back into their stem cell state. And from here we could develop those stem cells to become other differentiated cells. After all, they are called pluripotent pluri, like plural, meaning many, because these are cells that can become any number of things. We could grow them into, let's say, a liver if what the patient needs is a liver transplant. And now this already sounds quite sci.
- [36:58]
Roxandra Tesla
Fi, the idea that if I need.
- [37:00]
Derek Thompson
A liver transplant that's a genetic match, I might be able to grow my own liver from induced liver pluripotent stem cells derived from cells just scraped from my arm. That's also, that's completely wild. But what we're imagining here is actually wilder. In the distant future, we wouldn't just grow pluripotent stem cells into an organ like a liver, we would grow them into an egg. And this would mean that older women could essentially develop youthful, healthy eggs from their own ordinary epidermal cells. Can you pull us back to reality here and ground us in where does this science exist now?
- [37:49]
Roxandra Tesla
Yeah, so I think, well, there is already a company called Gameto who actually is turning induced pluripotent stem cells into ovarian support cells. It turns out that's much easier than making them into eggs because you're just kind of like creating an artificial ovary. It's very hard to assess how far away we are from creating eggs from induced pluripotent stem cells. And the reasons are that most of this research is now happening in private companies and it's a bit hard to assess what they're doing. I think it is very hard because the egg has to go through these very specific processes called. It's a process called meiosis. It doesn't do the normal cell division that most cells in the body do, mitosis. It has to contain all of the proteins that a lot of the proteins that the future embryo will need in order to survive. It has to go through this epigenetic reprogramming process, just like a very complicated cell type. So I would say that this is A very, very, it's a very complex scientific question. I think we will get there. I think the question is like, how will we test it? How will we make sure it's safe? How will we compare it? And I think that it would be very useful if we had sort of public funding for this. And the reason for that is that I think it will rely on a lot of technologies that are not quite there yet.
- [39:23]
And so just to get a really clear understanding of how it would work. Because we'll end back in reality. I just want to play out the sci fi situation just one click longer is the idea that there's a 40 year old woman who wants to get pregnant, she goes into a fertility clinic and then in a world with what you call IVG in vitro gametogenesis, what happens next? Can you just tell the story of how this technology would work if let's say the year is 2040, it's a reality.
- [39:56]
Yeah. So she would just get one of her, this cell in her body that is in an egg and people are debating which cell is the best cell to start with. In a lab, someone would turn into and use pluripotent stem cell. It would share the same DNA with a woman and then they would turn into an egg and then they would do the normal IVF process that people do regularly. I think that's kind of how people envision it, but there are other avenues. People are also trying to do repair of eggs that are aged, so to sort of try to repair the DNA damage that has occurred. So that's another sort of maybe more midterm solution to aged eggs until we get to ivg. But yeah, that would be like. So there are other things besides IVG that we can do in the meantime as well and I think we should research it much more.
- [40:57]
Absolutely. So is it fair to say by summary that you see a sort of short term, medium term, long term technological solution to the fertility dilemma? In the short term we need better science, better experiments to improve the IVF process that actually exists.
- [41:14]
Derek Thompson
In the medium term we want to.
- [41:15]
Roxandra Tesla
Use the science of induced pluripotent stem cells to assist in the IVF process to essentially, you know, to repair ovaries or repair eggs, rescue immature eggs that would have been maybe discarded in standard ivf.
- [41:34]
Yeah. With the startup called Gamedo.
- [41:36]
Yeah, yeah, right. That's the startup Kamito. And then in the long term there's this sci fi idea of the 40 year old investment banker who walks into the fertility clinic and someone like scrapes her thigh and turns the skin cell into an egg that she can implant after it's been fertilized by her partner. Right, so is that the landscape here of short term, medium term, long term?
- [42:04]
In the medium to long term you can include other scientific solutions. So for example, as I said, like probably reversing DNA damage, which is DNA damage of the egg is the main source of why women can't have children. That's another thing that people are pursuing, for example. So that's another avenue. But it's also like medium, medium to long term. But again, that's how I would see it.
- [42:25]
Yeah, Big picture here. It does seem like these sort of advances require sustained scientific investment.
- [42:34]
Yes.
- [42:34]
What needs to change in the institutions of science and the field of science to support this kind of long term investment in revolutionizing fertility.
- [42:47]
So I think that just at a very basic level, making it easier for researchers to get eggs or just kind of these policy changes would be helpful. But in terms of the funding landscape, funding fertility research per se would be very helpful. A lot of the people who research fertility and a lot of the people who, they come from developmental biology and they just stumbled upon fertility because it's kind of related. Right. If you're studying development, it's related to fertility. But the people who discovered induced report on stem cells, they were developmental biologists. Very few people start out as fertility scientists. They start out like, oh, I want to study fertility. No, they started DNA damage or something else. And there isn't even like an institute as far as. I mean, I think there's one in the US now, but it's not like a proper field. In the same way that cancer, like cancer has like dedicated things. There are conferences for reproductive science, but they're very applied. The basics of how eggs age, all sorts of IBG stuff doesn't really get funded by the state. And I think it doesn't have to be the state. It can be like philanthropic money. I think a lot of people are very interested in all sorts of futuristic reproductive technologies, but somehow when it comes to the woman, they don't really think about how to do that. I think there's a lot of opportunity here for philanthropic funding. I think there should be much more of it. It's such a neglected area that if you want to have impact, you can probably have so much impact. If you're someone with money, you can probably have so much impact so easily because it's not like cancer again, where there's already so much investment that every marginal dollar is not going to do that much. But here if you just invest a bit, I think you could have a really big impact. So if you have money and want to fund fertility research, you should.
- [44:40]
Well, I think it's interesting because if what some folks seem to be interested in is what it would take to have another baby boom. If you look back at the first baby boom, what happened in the 40s and 50s, that was a technological revolution. In part, parenting got easier and cheaper because of the proliferation of household technologies. Washing machine penetration, quadrupled vacuums, refrigerators, stoves, electric power. All of that grew during this period, and it made it easier to raise children. At the same time, early antimicrobial medicines made giving birth much safer. And so, in many ways, the first baby boom was assisted by a revolution in science and technology. And it's interesting because right now, I think when a lot of people think about, how do we raise fertility, they think about policies, they think about money, they think about tax cuts, and they think about free services. All of that's fine. But I'm really happy that you came on the show to talk about reintroducing science and technology to this discussion, because science and technology might have been critical to the first baby boom, and they might be critical for another baby boom.
- [45:52]
Yes. Yeah. And I think people. I think there's a bit of almost like a political mismatch here. A lot of the people who want to help women don't want to think about fertility, and a lot of the people who think about fertility think that it's bad to invest in fertility because women will be more or will delay more. And I just kind. Kind of want to say that you can be interested in fertility and also care about women. They're very convergent things. And also, if you want a baby boom from the fertility perspective, you shouldn't be worried that you're further encouraging women to delay childbearing, because they already are doing it. And this is about saving. This is literally about allowing these women that are already delaying childbearing to have.
- [46:38]
Children to have it all. Right? This is about letting women have it.
- [46:42]
All, in a way, from whatever perspective you're coming. Please be interested in fertility, because I think both sort of, like all cultural stripes, I think, should be interested in that, and I think it's a mistake to think that it's at odds with their goals.
- [46:57]
Ricksandra Teslow, thank you very, very much.
- [47:00]
Thank you so much for having me on, Sam.