If We Can Make Genetically Engineered Designer Babies - Should We?

0:00No one goes to Hank's for his spreadsheets. They go for a darn good pizza. Lately, though, the shop's been quiet, so Hank decides to bring back the$1 slice. He asks Copilot in Microsoft Excel to look at his sales and costs and help him see if he can afford it. Copilot shows Hank where the money's going and which little extras make the dollar slice work. Now Hank's has a line out the door. Hank makes the pizza. Copilot handles the spreadsheets. Learn more at m365copilot.com slash work. In 2018, two girls were born in China who were the first ever genetically modified humans. They were followed a little bit after by a third girl who'd also been gene edited.

0:39They'd all been grown from embryos gene edited with the intent to give them immunity to HIV. But the process didn't work out as planned. And the scientist who made those embryos, Hei Zhang Kui, he was jailed for three years. He was fined. And it's illegal to modify human embryos in most of the world. but there is a lot of funding nevertheless a lot of funding flowing into this area this week we're going to report on research that has a direct bearing on this because it gets rid of some of those problems that occurred in 2018 with those three girls so the question is are we getting closer to being able to safely gene edit babies to make designer babies so called and when might that happen if so from New Scientist this is the world, the universe and us I'm Dr Rowan Hooper i'm joined by michael page michael you've been reporting on this for years let's start with this new work that you've uncovered now about crisper gene editing that's an an improvement on that technique which already is has a claim to be the most important biotech revolution of the 21st century yeah so just standing back there these two big questions about gene editing children which the first of all is can we do it safely and then the second of course is if we can do it safely should we do it at all now up until this point there's just been no doubt that it's not safe at all when those kids were created in china the main objections were not necessarily that trying to make them hiv resisted was wrong but that the technology wasn't there to do it safely so that was a big problem and of course but this was done using an older form of crisper and now people are starting to use you know more updated and better forms of crisper so because that old form introduced like unwanted mutations into those children right it didn't work as as intended and is this new sort of base editing way of doing it that's got to get around that yeah so the the original form of crispo was actually more like a sort of targeted destruction rather than precise editing so uh try not to go into too many details but basically you know we've got these strands of DNAs in our cells, you know, they sort of double-stranded bits of DNA, and the original form of CRISPR cut right through them, so you had two ends floating around, and then when the cell tries to repair them, it can introduce these mutations, and, you know, there might be a sort of a couple of letters changed, which would sort of knock out a gene, which is what you want to do, but then also what can happen is those ends of DNAs, they can be joined up to the wrong things, and then you get these big rearrangements.

3:16And of course, the other issue is that that DNA can be cut in the wrong place and then you get these unwanted mutations. So there are all these things that can go wrong. Now, if you're just sort of trying to sort of edit a plant and you can do it as many times as you like to get it right, that's fine. If you're trying to edit children, you don't have that luxury. It should never have been tried. Yeah. And actually, I know you've reported on different variations of CRISPR that are trying to get more precise. And now base editing is even more precise. And as it suggests in the name, it can edit a single base pair of DNA.

3:52Is that right? That's right. So instead of cutting the DNA, these are modified forms of the CRISPR enzyme. They sort of chemically alter one of the DNA letters. And then at the same time, they make a little cut, a single cut in the opposite strand of DNA. And then when the repair enzymes come around, They go, they see that altered form of DNA, think, oh, that's a mistake. And they correct it and they change the DNA letter in the process. And so because you're not, you're never cutting completely through the DNA, this is much safer. It's much rarer for things to go wrong. And so that precision means it's a lot safer.

4:32And it's already been used, but not in the germline, not in sort of in an embryo or in sperm or eggs. but it's been used in children to correct leukemia, cells with leukemia, right? Yeah, this is quite complicated. So I'll try and explain it simply. So most forms of leukemia are caused by cells called B cells, those antibody making cells, they start dividing out of control. And so one way of treating that, you can take another kind of immune cell called a T cell, and you can program that to go off and destroy those B cells. And that's known as CAR-T therapy, and it can work extremely well in some cases.

5:09Now, there was a girl called Alyssa and now what she had was a form of leukemia caused by T cells. So if you modify T cells to destroy T cells, they're just going to kill each other. So they couldn't use a standard therapy. So what they did is they used base editing to change the T cells that they're using to kill the B cells. They changed those T cells so they didn't recognize each other as T cells and they didn't destroy each other. So Alyssa was treated in 2022 and I interviewed her just a few weeks ago in fact and she's doing she's doing really well no signs of recurrence. Amazing. Most of us worry about memory lapses as we age but how do you know when it's something more serious?

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7:04So we're all happy with that way of doing it. What about using this precise base editing on an embryo? Well, that's now been done in the U.S. This team, they haven't created children, to be clear. They've just tested it on human embryos that were donated by couples, I should say, having IVF. They've just tested it on those embryos to see how well it works. And so they tried making two different changes. With one of those changes, they got a few off-target mutations. That is, the letter, when I tried to change a specific letter, it sometimes changed letters to either side of that target, so it went slightly off-target.

7:47With the second change I made, they had no off-target mutations. Now, why did it work in one case and not the other? So the key thing with CRISPR is you have the sort of, the protein hooks up with what's called a guide RNA and that guides the protein to the precise point in the genome that you want to change. So I think in the first case, the guide RNA was not ideal and that's why they've got some off target mutation. So if you can get your guide RNAs right and you don't get these off target mutations as in the second case, then this is looking very promising for avoiding those issues we had with the children in China where there are lots of undesired changes.

8:24Okay. And what sort of age are these embryos? They're probably, I don't know how many days you're allowed to muck around with embryos. They were two-cell embryos. Oh, so very early on. Very early on. Very early on. Yes. So if this is starting to work, does it suggest that we can start to think about actually making edits and bringing these embryos to term? them well there's another issue uh and that is in in these embryos they didn't always succeed in making the changes they wanted in every single cell so why is the two cells of the well of the two cells and if they'd advance a bit further yeah so why why is that a problem so you think about if suppose you are trying to correct a disease that someone might inherit you edit the embryo you succeed in making that change in some cells but not in other cells that embryo then develops into a baby into a person some of those cells will have that correction some of them won't now depending on what disease it is they might still go on and develop that disease and then you'll have failed your your gene editing will have failed because you haven't got corrected it in all the cells of the embryo so this issue of some cells in the embryo being different to the others is called mosaicism.

9:40And it's a big problem for gene editing applications because there's no way of tailing if it's happened. So when people have been sort of, if parents have a risk of passing on a disease and you do IVF and then you can test the embryo, if that embryo has come from, there's no gene editing involved, then all those cells should be the same. You can take a single cell from the embryo, you can test it and you can be sure that child or that embryo will not develop into a child with that disease if you're gene editing and you've got a mosaic assume you can take a single cell from that embryo but it might still the wrong part of the mosaic yeah it might be the wrong part of the mosaic so you can't be sure okay so this is a huge problem so so we have to solve the mosaic problem but i don't know it's not really holding back the money the flow of money going into the industry is it and there's a lot of hype and talk about what is possible why is it all this money going in at this very early stage.

10:38Yeah, I mean, I wouldn't be sitting here talking to you if I was an expert on investments and things like that. But what I can say is that fertility treatments, it's a huge business. I mean, globally, I checked it, and it's something like$40 billion a year around the world. So if you think, and if you can add something on top of that, that parents, if you know, you can persuade, would be couples who want to be parents, if you can persuade them to pay a sort of few thousand more dollars in order to edit an embryo and have something extra, which I think a lot of parents do want, then there's a potentially huge market there.

11:15Well, we'll get on to whether that's going, let alone the morals of that, but whether the claims are going too far. Because, you know, you do start to hear about, you know, not just, you know, have a taller child or have a more intelligent child. But we'll get on to that in a sec. But what about how to get around this problem of the mosaic? Yeah, so the reason why you get mosaicism is you put your gene editor into an egg after it's been fertilized, and it may not act until after the embryo starts dividing. Or in the case of this recent study, the embryo had already divided, and they were trying to edit it at a later stage.

11:52so the way you can avoid that if you can sort of gene edit the egg before it's fertilized or the sperm before it's fertilized then that change is already there and it's going to be in all those cells now we can't do that at the moment but there's a company which is just an answer it succeeded in taking sperm stem cells from people's testes and growing them into sperm in the lab now if you can do that if that's true and we don't know that it is yet they haven't provided in the evidence. But if it's true, then they should be able to gene edit those sperm stem cells and create gene edited sperm. And of course, there's potentially a good reason for doing this, because one thing you could do with this would be to treat infertility.

12:35So there's some men who have mutations that prevent any sperm developing, but they still have sperm stem cells in their testes. So potentially, you can take those out, gene edit them so they can now turn into sperm, and you then have a child that's completely normal except that you've corrected the mutation of course in infertility in the father yeah and as you say the the market is huge of no doubt that this this will happen because there's a there will be a lot of pressure to do it and then as you say once that's dead for to to treat infertility it can then be co-opted for for gene editing i was just looking at a website for a u.s company offering ivf screening and the tagline says have your best baby the modern way to plan and have a baby driven by science guided by love and they claim they came to you to say they get the ivf embryo they can test it for 2 000 diseases so that's quite common that way of um you know what's it pre-implantation genetic diagnosis yeah testing but then they also say they they'll they'll test for eye color um because you wouldn't want your child to have a certain color you know you might make you know You want your child to have a certain color eyes, height and weight, even intelligence, they claim.

13:49So this is not with gene editing yet. This is with embryo selection. So you can see the appetite is there. There is this market for designer babies. Absolutely. So embryo selection, the options, because women generally have very few embryos available to choose from, what you can do with that is very limited. Of course, if you can edit them, the options are going to be much greater. Let's step back and look at the bigger picture here. So if you think about who we are, you know, what we are, you know, we're these products of mindless evolution. Our genomes are a complete mess. I mean, you know, they consist mostly of the rotting remains of genetic parasites.

14:29I mean, it's just... Speak for yourself, Michael. so you know and it's also you know we tend to think oh it's normal to have healthy children that's the norm but evolution doesn't work that way evolution doesn't care if all children are not sort of healthy and happy so if you come at it from that perspective of you know we've got this sort of real mess of a genome i do think that it's inevitable that we are going to start to use gene editing in the future and in fact it's going to become routine and and so on the question is, have we got to that point yet? And I'd say not even close, not even close.

15:05To start with, you know, even the case of like trying to improve the health of our children, we don't have a great understanding of genetic variants at all. So, you know, there's a chance that you sort of tweak a gene because you think it's going to make your child healthier. It might have that desired effect, but it might also have some adverse consequence that we haven't anticipated at all. Yeah. I mean, we've got really our understanding of the genome is in its infancy. You know, most genetic variants have got no clue what they do. And the ones that we do know what they do or we think they do, that's based on these sort of statistical studies where you sort of look at 100 ,000 people and go, oh, well, if they've got this genetic variant, they've got sort of a 10 % less chance of developing heart disease.

15:46It's not like a cause and effect at all. You know, this is sort of, you know, statistics that could be wrong. Maybe you're talking about the limitations of our knowledge of genetics and development. and that's one objection. The other objection, of course, is that this would lead to this two-tier or maybe even speciation amongst humans because rich people would be, let's say we did solve all those problems you just said, you know, rich people will avail themselves of this technology because it would be very expensive to do all this tweaking and then you do start to get, you would start to get children with genes, maybe protect them against certain diseases or would help them with their nutrition.

16:27maybe then maybe down the line you get other things like maybe like intelligence or something but then you know those children wouldn't want to mate with children who are unmodified so you could get this two-tier system it's just the objection of inequality as well as the yeah i mean it doesn't have to be that way i mean you know we could have for example we've got the national health system in the uk if that decided to offer this as a service then you could potentially avoid that inequality. I mean, yes, that could happen. I think we're a long way from happening. That's a long way from happening.

17:02I mean, the more immediate thing is, you know, are we going to get people going or I want to sort of, you know, have more intelligent children or smarter children or I want them to look like X. I mean, personally, as a parent, do you actually want to have that degree of choice? I mean, can you imagine the arguments that you have a sort of like someone saying you know i've got blonde hair and blue eyes but i wanted to have brown hair and brown eyes like mummy and and you're going to get these you know do you really want to be in that world and have those sort of choices to make i mean we've got enough hard choices to make as it is without going into the nitty-gritty of what our children are like yeah so let's uh let's leave genetic engineering uh of our babies for the for another time please yeah none of that none of that We're not there.

17:52We're not there at the point yet. It's going to come, but hopefully not for quite some time. Probably not soon enough to get your investment back on those gene editing companies that you might be tempted to invest in. Yes. Okay. We'll leave it there. That's all for this week. Thanks to my guest, Michael LePage. And do subscribe wherever you get your podcasts. And we'll be back soon. Bye for now.

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