Is embryo selection allowing parents to ‘build-a-baby’?

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0:44That's schwab.com slash Washington Wise. If you could pay$2 ,500 to genetically test an embryo and know whether your baby had a rare genetic condition. Would you do it? Would you do it just to be able to pick whether you could deliver a boy or a girl? Well, people are. In fact, the richest man in the world, Elon Musk, has at least 14 children. And according to the Washington Post, for at least one of those kids, Musk and his partner genetically screened the embryo through a California biotech startup that's been getting a lot of attention for promising to map 99 % of an embryo's genome. So what Orchid does is it upgrades the amount of information that parents get access to.

1:29The company is called Orchid Health, and it's one of a handful of fertility startups that's offering similar services. They can scan for thousands of diseases that previous technology completely missed. That's Orchid's founder, Noor Siddiqui, speaking on a podcast. Diseases like pediatric cancers, adult-onset cancers, birth defects, neurodevelopmental disorders, genetic forms of autism, more genetically complex diseases where it's not just... Now, we reached out to Orchid Health for comment, but have knocked her back. And the company has not confirmed whether or not Musk and his partner were indeed clients.

2:02But this story is not just about Musk and Orchid. It's about our society as a whole. This question of whether we can stop genetic diseases before birth and how far we're willing to go in the quest for the so-called perfect baby. From the BBC, I'm Asma Khalid in Washington, D.C. And today on The Global Story, if you could change your baby's genes, would you?

2:31My name's Professor Adam Rutherford. Professor. I only say that because I got promoted today. Congratulations. So I'm a professor of genetics at University College London, where I specialize in the history of genetics, but specifically the history of eugenics. Well, just the man we wanted to talk to you then, we want to dive into the development of genetic testing, specifically genetic testing for expectant parents and all of the moral and ethical complexities that exist in that conversation. And I want to understand, when you have a company like Orkid Health, they say that for the cost of$2 ,500 per embryo, they can map 99 % of an embryo's genome.

3:17You are, as we say, a trained geneticist. So what exactly does this mean? I don't really know what the answer to that question is. And I don't mean that in the sense that I don't know because I haven't looked at it. I don't know because the way it's phrased is deliberately opaque in order to sell the product that they're selling, which is, which claims to be, I should say, the ability to make predictions about certain biological traits that can be selected for in prospective children that have not been born yet but will be conceived through the IVF process. So what they're doing there, they're taking a cell from the fertilized embryo as it's growing, and then they sequence the entire genome.

3:58And from that, you can tell what type of genes throughout the whole genome of the 20 ,000 or so genes that a human has in every single cell. They can read on digital file which says you have this version of this gene and this version of this gene. So from an embryo selection point of view, in the old version, you'd be looking for disease genes and choosing not to include them in the implantation of IVF, right? what these types of companies, and I won't speak to ORCID specifically, but there are a few of these companies and they all offer roughly the same service, is they're offering to genomically characterize these fertilized embryos so that you can choose what versions of what genes you implant into the mother that then turns into a child, right?

4:42So for diseases, there's a sort of fundamental problem with understanding what the relationship between complex diseases and genomes is, right? Because it's very difficult to predict polygenic diseases, which is that there is a huge influence from not just one, but multiple genes. And that applies to most types of diseases that affect most people. So things like cardiovascular disease or mental health diseases, schizophrenia. Monogenic diseases are diseases where the root cause of etiology is one single gene, which is characterized by one single mutation in that gene. Everyone has the same set of genes, but they are slightly different to each other in individuals.

5:21And sometimes, mercifully rarely, there are mutated versions of individual genes, and those genes are the cause of specific diseases. There's something like 8 ,000 or 9 ,000 monogenic diseases that have been identified. Okay. Most of them are extremely rare. But when you do a normal genetic screening, whether you're in the U.S. or the U.K., they're presumably not checking for all 8 ,000 to 9 ,000 of those, are they? No, no, no, they're absolutely not. And mostly when you're going through the IVF process, you only invoke that genetic testing if there's a history of that disease in your family. And we've been offering that service since the mid-80s.

6:02It's free on the NHS in the U.K. where we have socialized healthcare. That is available through IVF clinics all around the world, and I do not disagree with that. The problem is when you get to polygenic complex disorders, which are much more difficult to associate the genetic variants with the actual manifestation of the disease. Orchid and other companies in the States, because this is largely a US-based phenomenon due to regulatory reasons, they purport to offer services for the selection of complex diseases, the reduction of complex diseases, not just monogenic diseases. So for that reason, people like me look at this and go, well, you know, I'm not in the business of telling you how to spend your money, and I understand going through the IVF process is traumatic and important, but I think these companies are selling something which is scientifically spurious.

6:49What they're actually buying is a negligible, almost immeasurably small, if it exists at all, probabilistic increase for those traits or diseases that would be overturned instantaneously by environmental factors. Let's go back in time a bit. And I just want to understand the context in which we are having these conversations, because the ability to test an embryo is more common nowadays because of IVF. And it is easy to perhaps forget how just frankly novel and new IVF technology is. This began, I believe, just in the late 1970s. That's exactly right. So we've been doing IVF since 1978. Louise Brown famously was the first IVF baby.

7:38As everyone knows now, I think something like five or six million people have been born through the IVF process. And that is the external fertilization of an egg and then implanting it into a mother, either the same mother or a surrogate mother. The next stage in this story happens a couple of years later, which we sort of broadly refer to as embryo selection. So it is choosing fertilized embryos whilst going through the IVF process in order that those potential children are free from specific diseases. The first time this was done was in, I think, in 1980 in the Hammersmith Hospital, not far from here in the BBC studios in London.

8:17and it was a selection of embryos from a family who had a history of a particular type of developmental disorder which only occurs in boys. So the first wave of embryo selection to prevent disease in children through the IVF process was simply to select female fertilized eggs and implant them. So you only select girls, therefore the disease isn't going to manifest in their children. And I think we can agree that that is a positive step in alleviating individual suffering in children and their families, right? Through the course of the 80s, this form of embryo selection begins to develop for specific diseases that we understand the genetics of.

9:03And they include things like Huntington's disease or cystic fibrosis or Duchenne muscular dystrophy, the first types of genetic diseases that were characterized in the late 80s and into the 90s. As we get into the 90s and the 2000s and now the 2010s and into the 20s, the technology keeps developing. Our understanding of genetic disorders becomes hugely enriched after the Human Genome Project in 2001. Then it was published again in 2003, 7, 9, 15, and the final sequence of the Human Genome was published last Just last year. Just last year. So throughout the 2000s, we've been able to more, sort of with more direct insight, look, you're saying, at the human genome.

9:44And in mapping that human genome, it provided us with the ability to understand genetics further of ourselves, but also the genetics of an embryo. That is correct. But there's lots of caveats within that. So the first rounds, the stuff I was talking about a minute ago about the first diseases are monogenic. But as we got into the 2000, the post-Human Genome Project era, what we began to find is that for most diseases, they are polygenic. And not just that. It's not just the genes. It's also the environment as well. So, you know, you and I could have exactly the same versions of genes involved in some complex disorder like diabetes or cardiovascular disease or schizophrenia, and we could have exactly the same genes.

10:24But one of us might get the disease and one of us might not, and that would have been heavily influenced by the environment in which we're raised, the food we ate, the levels of poverty. Because, you know, the biggest correlating factor for most diseases is poverty. I see. Adam, it does seem like we're living in this age of optimization, whether we're talking about self-optimization, right, and in terms of trying to optimize our human body, trying to optimize our offspring here. The CEO of Orchid, a woman by the name of Noor Siddiqui, she had this to say. I think basically sex is for fun and embryo screening is for babies.

11:00I think that it's going to become insane not to screen for these things. It's an interesting quote, isn't it? An interesting sideline in this is that almost no sex that humans have results in babies. We have successfully as a species decoupled sex from reproduction. So I didn't disagree with that bit. But I mean, the first thing is this is only available to wealthy people in very limited areas of the world. So that's one aspect to it. The second thing is, even though we have successfully decoupled sex from reproduction, and most of the sex that we have is for fun, most babies are conceived through that old-fashioned method.

11:39And I don't know whether they are seriously proposing that all babies should be created via IVF and then we can just have sex for fun and not think about babies at all. But it's a strange sort of science fiction dystopian idea that we are not only going to decouple sex from reproduction, like statistically, but absolutely. Well, Adam, I want to understand what traits we are actually able to test and select for scientifically at this point. You mentioned a number of diseases. Can you actually test for things like, I don't know, hair color, height, intelligence? Yeah, no. Well, sort of. I mean, one of the problems with this whole conversation, I mean, not the conversation with you, but the sort of public discourse conversation is that this stuff is wickedly complicated.

12:26But, you know, instead of answering the question about whether we can predict intelligence or height, which are really complex, let's take a more simple one, right? Eye color. Yeah? Okay. So eye color is the first trait that school children are taught in order to understand human genetics. I remember this vaguely. Okay. Yes. And you'll remember that all the listeners will remember that in order to have blue eyes, you have to have two versions of the blue eye gene. And if you've got one version of a brown eye gene and one version of a blue eye, the brown eye is dominant and therefore you'll have brown eyes, right?

12:57You've just passed like, you know, basic high school biology. It's not true, right? Interesting. It isn't really true in any meaningful sense. It was a scheme that was first described in 1909 by the leaders of the eugenics movement in the States who wanted to show that every characteristic, even the most simple ones like eye color, are monogenic. They are caused by one gene in a statistically predictable way. So you're saying eye color is not a monogenic trait? Well, the first thing to point out is that eyes are not blue or brown, right? There's a full spectrum of eye color in humans, from very, very pale to almost black.

13:37If you look at the eyes of someone you're looking at, you will see that they have different colors within their irises. Some people have what's known as heterochromia, so they have bits of the eye one color and bits of a different color. Some people have one eye that's different color to the other one. So the whole notion that there is blue and brown and they're inherited in this very particular binary way, which is understandable and therefore actionable from a eugenics point of view, is total nonsense. So the way we teach genetics, we start by teaching children a fiction, right? A fiction which we've inherited from the history of genetics.

14:13So when you say like, okay, we know how eye color works, and therefore you could do an embryo selection. If you do an embryo selection, exactly, yeah. Right. You can't do that. That is impossible to do. I've had my genome sequenced, and based on the genes that I have that relate to pigmentation in my eyes, there is a 67 % chance that I have brown eyes. Okay, I've got to look. Adam, I can't see. We're on a Zoom screen. Yeah. I mean, I've known the color of my eyes for a while now due to the technology of mirrors. And if you were to dig me up in a thousand years' time and get some DNA out of me and make a prediction about what my eye colors were, you'd be right two out of three times.

14:57Now, that's eye color, supposedly the most understood trait that humans have. So now you ask me about, can we make predictions about the genetics of intelligence? IQ, let's say. All right. So we do know that intelligence or cognitive behaviors, or IQ specifically, have a large genetic component to them. And an equally big part is influenced by your environment. Okay? We know that there are hundreds of genes that make a very small cumulative contribution to the variation in those traits. And we know that because we sequence the genomes of literally millions of people and pool them together, and then we can extract meaningful statistics from them.

15:36So intelligence and height are heavily influenced by hundreds of genes with tiny variations. You take things like IQ, which I do think is a valid metric, although there are complexities within that, and understanding the history of IQ is really important, but we'll park that for a minute. IQ tests have an error margin of five points, right? So you take the same test ten times over the course of a month, and your range will be plus or minus five. We know that you can increase your IQ in a test if you have a cup of coffee before you start it. It's heavily influenced by the time of day. All sorts of factors like that.

16:13Now, the calculations of how much you can increase your IQ by selecting an embryo which had genes associated most closely with higher IQ is about two points, one or two points. It's about the equivalent of having a cup of coffee before you take the test. We know how to make more intelligent babies. You do that by reading them books or having access to healthcare or free education or access to sporting facilities. Well, Adam, let's talk about one thing that you say you can test for. And I know you can test for as well because I had one of my children through IVF. I happen to not have the other one through IVF.

16:53And that is sex, as you say. Certain diseases might be more applicable to one particular sex. And so there was a reason to select that for health purposes. But presumably nowadays, people can genetically screen and they are told the sex and they can choose which one they want. Well, this is a real, you're absolutely right. And that's a real ethical question, Adam. I mean, yeah. We know that this happens in countries where there is a financial and economic premium on having male children. It's not legal and it's, I don't think it's ethical either. But yeah, I mean, it's one of those cases where the technology that we've invented has inadvertently created these moral and ethical conundrums that we then have to deal with.

17:41We repeatedly do this, invent technologies which pose new societal questions. And I think often there is deployment of those technologies to the people as services and sometimes as commercial services, which we haven't really fully contemplated what the moral and ethical ramifications of those things might be.

18:29When we talk about the tricky ethical predicaments some of the screening raises, it makes me think of another term that I'm hearing quite a bit in our current context, and that is eugenics. It is a term that's kind of thrown around by critics around some of this advancement in genetic screening. Now, before we get to whether or not this is a fair comparison, can you just define for us what eugenics is? It is the process by which you try to maximize particular characteristics in the next generation through reproductive control. So it's a longstanding phenomenon. All societies have engaged in this type of behavior since the records begin, mostly through arranged marriages and infanticide.

19:18But in the late 19th century, following Darwin's discovery of natural selection, his half-cousin, Francis Galton, sort of formulized the concept of eugenics for the improvement of the, I'm using air quotes for people who aren't watching, for the stock of the British people. And so it was the idea that you could improve the quality of the population by controlling reproductive rights of primarily women. It was instantly very popular in the UK and particularly in America, in the USA. But in the UK, for various reasons, we never had any eugenics official policy. But in the States, from 1907 onwards and throughout the course of the 20th century, enforced sterilization of people deemed unworthy of reproductive rights was perpetrated through eugenic laws in 31 states.

20:12And the estimates vary, but somewhere between 70 ,000 and 500 ,000, mostly women, mostly working class or descendants of the enslaved or Native Americans. Most African Americans, right? were sterilized against their will or knowledge in an attempt, a government-sanctioned attempt to improve the quality of the people. And that's the basic premise of eugenics. Adam, what do you make of the comparisons between embryo selection that we're seeing now and the kind of eugenics that was being practiced in the early 20th century? Is that a fair comparison in your view? I don't think it's a useful comparison.

20:54And I think it's not useful for a couple of reasons. The first is that by my definition, which is mostly held by scholars in this area, eugenics is a state-imposed authoritarian regime, right? So it's the state. It's the powerful saying these people can reproduce because we like them. These people can't reproduce because we don't like them, okay? The second thing is that the types of technologies that we're talking about now, more often than not, are individual choice. They give parents the choice about the babies that they're going to have and hopefully the health of the babies they're going to have.

21:28So I don't think it's eugenics in that classical definition. A lot of discussion occurs where people say, well, that just sounds like eugenics. I find those semantic arguments quite uninformative. So I tend not to use eugenics to describe the current technologies. But I think they are technologies which would have been of great interest to the eugenicists of the earlier 20th century had they been available to them. It's worth remembering that we don't mate randomly, right? We choose our partners. We have children with people, hopefully, that we want to have children with. We're always choosing what type of babies we're trying to have because we don't mate with random strangers, thankfully.

22:08And when we talk about testing for various genetic conditions, it does sound to some degree futuristic and, as we've said, raises all sorts of ethical conundrums. But there are diseases, conditions that have substantially declined in prevalence as a result of being able to genetically test. Many folks who work in this field, right, wouldn't they argue that this has been really beneficial for society as a whole? Yes, and I make that case very explicitly. We've got good evidence for it over the 20th century before there was genetic testing. So diseases like Tay-Sachs, which was when it was first identified, it was in Jewish families in the 1880s.

22:52And as a result of genetic counseling, which is simply advising that parents who have Tay-Sachs running in their family should not have children with these people. As a result of that, Jewish communities, particularly in New York and America more broadly, have massively reduced the incidence of Tay-Sachs without any molecular genetic intervention, simply by understanding the inheritance pattern of those diseases. In various Muslim communities all over the world, there has been this form of genetic counseling for centuries through specific imams, like recognizing that diseases emerge in particular families as a result of first cousin marriages, for example.

23:31So genetic counseling is not new. We're just much, much better at it these days. And absolutely, our purpose as geneticists is not just to understand the human genome, but to use it to alleviate human suffering. In the modern era, through gene therapy, there are now diseases that have been cured. So there are people with sickle cell anemia who've had it all of their lives, who now do not have sickle cell anemia. And Adam, to be clear, gene therapy is when you are essentially able to fix or replace a faulty gene? Insert a corrected version of that gene. Into the, wow. Into the cells where the disease actually manifests.

24:09I mean, I will say again, in full transparency, when you have one child born through IVF and the other not, there's an element of like relinquishing control that you have to learn when you don't have an IVF child. because when you do the genetic testing, they tell you if a certain chromosome is missing a portion or if it's been deleted, and they will advise you that it's probably not worth implanting that embryo because it will likely lead to a miscarriage. And I don't know, I think so many women have gone through so many miscarriages. It's a sense of like emotional relief to be told some of that information.

24:46You know, we've talked about the pros and cons of this technology. and I want to understand from you as somebody who studies genetics what makes you hopeful about this sort of genetic screening technology I think that the advent of gene therapy which has really only happened in the last two years and so this has been a question that we've been trying to address for the last 50 years when I was an undergraduate in the 90s we were talking about gene therapy but it never really took off it turned out to be a much harder nut to crack than we'd initially thought. So the idea that rather than dealing with the symptoms of a disease, we actually treat the underlying cause.

25:24Now, there were reports just after the Human Genome Project was published that we would know all human diseases and cure most of them within a few months or years. Now, I was doing my PhD at the time, and I remember seeing this and going, really? I wrote a book in 2016 in which I was making the point that the number of diseases that had been cured as a result of gene therapy was zero. I've just published, like last month, the 10-year anniversary of that book, and that number has gone from zero to 10. And the next sentence says, and by the time you read this, that number will be out of date, and that is a good thing.

26:05Over the next few years, more and more diseases that were previously uncurable will be fixed through gene therapy. The problem with the commercialization of this type of product is that they create false hope based on spurious marketing and incomplete, immature science. And we have to be cautious because we're not talking about experimenting on mice or fruit flies or zebrafish, which are the animals that we use to test and design and invent these things. We're talking about people. And the history of this subject is people taking scientific ideas before they're ready and using them on real people, and the result has always been disastrous.

26:53Well, Adam, thank you so much for joining us and walking us through all this complex information. I really appreciate it. My pleasure, Asma. It's nice to talk to you.