The First Gene-Edited Babies

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CRISPR is a groundbreaking genetic technology with huge promise.

But right now, it's caught up in a massive scientific scandal.

Right on the eve of an event to figure out the ethics of this technology, a researcher in China shocked the world by claiming that the first ever genetically edited babies have already been born.

Scientists and researchers across the field are saying that whether or not these claims are true, this is horrifying news.

What could it mean?

Why are scientists so upset?

And what is the future of gene editing?

This is Radio Atlantic.

Hello, folks.

This is Matt Thompson, Executive Editor of The Atlantic.

Alex is off gallivanting this week.

And here with me in studio are two

familiar voices Atlantic staff writers, Sarah Zhang.

Hi, Sarah.

Hello.

And Ed Yang.

Hello.

So, Ed, what just happened?

Tell us about this recent CRISPR scandal that has the genetic community all aflutter.

So roughly a week and a half ago, the world learned that a Chinese scientist named He Jiang Kuei

had allegedly created two

gene-edited babies.

He'd used CRISPR to modify a gene called CCR5

in two embryos which had been fertilized in vitro and which he then implanted into a woman.

who then brought the two embryos to term.

So those two girls apparently exist.

They're named Lulu and Nana.

And this would mark the first time that CRISPR has been used in this way.

So there have been past instances where people have used CRISPR to alter cells that are part of a person's body.

So you would take, say, there have been trials where you, for example, take immune cells from a person's body,

alter that same gene, CCR5,

and then put the cells back in.

And CCR5 influences our susceptibility to HIV.

So if you disrupt the gene, you theoretically reduce the risk of being infected or of sustaining the infection.

So this has been used

as a way of helping people who already have HIV.

But this is very different because in this case, you're altering embryos, which means that you then alter the sex cells, the eggs and sperm, or in this case eggs, that will be made from those embryos, which means that the modifications you made are not just contained within that person.

They transcend generations.

These are called germ-line modifications.

They will affect not just Lulia and Anna, but their children, their grandchildren, and so on.

And this has long been seen as a really significant

barrier, like

it's crossing an ethical Rubicon that no one has done yet and that was seen as a substantial moment in history that should only be crossed with incredible consideration, both for the technical side of things,

the ethics, the social implications.

It should only be done when the world, writ large,

felt that it was ready for it to happen.

And yet it apparently just happened.

This one guy decided to do it.

And

if his no one has verified his claims yet, we don't have a lot to go on, but let's assume it's true.

It does mark a huge scientific and ethical leap.

The significance of the moment combined with things like some of the shoddiness of the actual work, the secrecy behind the project, and the fact that this was done in contravention of what the world was ready for at the time has made this intensely controversial.

So before we dive into the details of why this is so controversial in the scientific community, Sarah, can you tell us just a bit about what CRISPR is, how it has been used?

Yes, well, so the metaphor that is used most often is that CRISPR is a pair of molecular scissors.

But the cool thing is that you can tell it exactly where to cut in your genome.

So the way you do that is you basically give it a little piece of code, something like, you know, ATC, GCC, or something, and it kind of searches along the entire genome, finds the region that corresponds with that code, and then cuts right there.

And it can do that with pretty good precision.

And once it's made the cut, it can do also a number of kind of interesting things.

One is if it cuts in the middle of a gene, you can deactivate that gene.

Or maybe you want to add a new gene, you can add it, splice it right in.

Or maybe you want to change like

an A to a T or something, you can make a tiny small edit like that.

So what CRISPR does, it just really opens up this toolbox, makes it really, really, well, I won't say really, really easy because it's not like someone in your garage can probably do it, but makes it fairly easy to make these edits in pretty much any organism you can think of, obviously including humans.

So CRISPR was discovered,

it was only discovered that it could do this maybe six years ago.

And since then, we've gone from cells in a dish to human babies.

So that gives you a sense of like, that is a warped seed feed for science.

That's how quickly this has moved.

It's been used in mice, it's been used in plants, and now obviously it's been used in humans.

Or so we think.

So we think.

That's right.

Before we step into the ethical minefield that we've entered, can you just paint a picture of some of the promise of CRISPR, what this technology could do?

Yeah, so part of what's interesting is that I think no one thinks that editing embryos is the best use of CRISPR at this point.

So what has been really promising is trials using CRISPR to cure genetic diseases in adults for the most part.

For example, you could take a, there's a trial that's about to start where you,

it's for blindness, a genetic form of blindness, and perhaps you can inject the correct copy of this gene actually into the eye.

This actually works.

And actually, so people could start seeing again.

Or there are other diseases like sickle cell anemia or beta thylacy, and these are blood disorders.

You can take the blood from a person, edit those cells kind of in a controlled environment, and before putting them back in.

So these were kind of the closest promises of CRISPR.

Got it.

And it's also made a huge difference to just basic scientific research.

Because it allows scientists to manipulate laboratory animals and other organisms with such ease and finesse, it means a whole category of studies are now available to them or easily available to them that they could just couldn't do before that would have taken years or a lot of money.

So CRISPR has been used to do everything from like

manipulate the fins of fish to understand how they evolved into limbs.

It's been used to change the wings of butterflies to understand how like the intricate molecular events that cause certain patterns to form.

So it gives an amazing ability to understand the world around us.

But of course, when used in human cases, it opens up this ethical minefield too.

This action by the scientist He Jean-Kui seemed to have brought a whole host of condemnations from researchers.

Ed, can you tell us why the scientific community was so upset?

There are so many reasons.

So the piece I read had like 15 different aspects to this that I think are troubling, but we can break them down into a couple of different categories.

So I think the first one is just the choice of which gene to edit and then the way the editing was carried out.

So as I said, CCR5 is this gene that affects our susceptibility to HIV.

And the idea is that by editing it out, you make these two girls theoretically resistant to the virus.

But there are loads of other ways of preventing HIV, everything from safe sex education to drugs.

The father was HIV positive, but you can wash sperm to prevent the infection passing on.

So there wasn't really an unmet medical need.

And certainly neither of these two girls were...

ever sick.

They just had the normal gene that everyone has.

So to argue that like you need to use this fairly extraordinary and extreme procedure to reduce the risk of HIV, it just doesn't make sense.

And then if you actually look at the results of the editing, which Her presented in slides at a meeting in Hong Kong, it doesn't really look as if it was done that well.

So there is one particular mutation called Delta 32 that in CCR5 deactivates the gene and is well studied and well known to increase resistance to HIV.

But that's not the mutation that you see in either of the two girls.

What you see are three very different mutations whose effects are basically unknown.

Like if you were doing this carefully, if you edited the embryos and saw those mutations there, what you would do is then use CRISPR to add the same mutations into, say, laboratory animals to see what would happen.

Or you would do it in like immune cells taken from a human person to see how they would react.

But that doesn't seem to be what happened.

It seems like Hurd just put the embryos into the mother, which means that these two girls are basically living experiments.

They are testing out modifications to their genes that we haven't even tested out in animals yet.

So that alone is, I think, pretty shocking.

And then if you look at the way this work was conducted, it was done in extreme secrecy.

Her didn't tell his university that he was doing this.

He took leave in February and conducted this work in secret.

The ethics board of the hospital,

which apparently was where this work was done, have denied that they were ever consulted.

Herr's University has denounced the work and is launching an investigation.

A few scientists were asked about it,

some of whom seem to have known about Herr's intentions, others may have caught some hints.

But in general, this was done in a fairly extraordinary amount of secrecy.

And it doesn't seem that the team really knew what it was doing in terms of the ethical side of things.

Editing CCR5 is not a risk-free proposition.

So originally, scientists thought that people who naturally lack copies of CCR5 seem completely normal, which is why some people had been considering modifying it in the first place.

But it now transpires that people who have problems with the gene are more vulnerable to infections with West Nile virus, Japanese encephalitis, and they seem to be more likely to die of influenza if they catch it.

Now, obviously, these diseases are big problems.

If flu in particular is a huge problem in China and in the rest of the world.

Now, the informed consent form doesn't mention any of this.

So there are so many different aspects of this, the way it was done, that have really rankled people.

And I think it's worth clarifying that it's not just people who are naturally like anti-genetic modification.

You know, it's not just people who think this technique should never, ever, ever be used in humans, full stop, who are against it.

It's...

most members of the scientific community as far as I can tell and people who have been actually pro-modification in the past.

Like a man named Julian Sivalescu is famously pro-modification and pro-human enhancement.

He called this monstrous.

So I think this shows

just

how much of a line people feel has been crossed.

All right.

Well, after the break, I want to step into why it horrified so many scientists.

So

stick around.

We'll be right back.

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Sarah, when I first heard the word CRISPR a few years ago, I think it came saddled with a lot of different anxieties about how the technology could be applied.

People were spinning dark visions of human-animal chimeras and things like that.

So, what are actually the most real and legitimate fears about CRISPR and how it could be used?

Okay, well, I think we just maybe saw one of them,

which is someone who does an experiment secretly to unclear ends, right?

So, one of the problems with using CRISPR in humans, you know, as Ed sort of alluded to this, is that we don't, we know where we can make it cut, but we're not, we don't have great control over exactly what it does.

So it may not make the mutation that we exactly want.

Maybe you'll create another mutation.

Maybe if you're doing it in embryos, right, like you're affecting every single cell in that person's body.

Maybe you'll create another problem for them.

Maybe it could hit a cancer gene and this is going to cause cancer or some reason.

So there's kind of lots of unintended effects of CRISPR.

I think there's a lot of fears also just about designer babies.

I actually think that technologically, CRISPR is probably not going to be creating designer designer babies anytime soon just because a lot of the traits we talk about when it comes to designer babies like intelligence or height, those are actually really difficult to genetically engineer because they might require hundreds or thousands of genes.

And CRISPR is really good, but it's not good enough to add that many genes at the same time yet.

Yeah.

What would it look like to start to undertake the work?

of using CRISPR in a human context ethically.

So I think we're starting to see some of that with trials in, first of all, not babies, but adults, right?

So starting with not germline, but actual just cells in people's bodies.

So I think one of the things you want is an unmet medical need.

And I think that's why

his choice of CCR5 for HIV was actually really telling.

Because if your goal is to just show that it's possible to gene edit humans, this is a great choice.

This edit is a much easier to do than a lot of other edits.

And,

you know, so obviously it was possible.

I mean, it doesn't seem to have worked perfectly, but it was possible.

But if your goal is to actually address an unmet medical need,

this really isn't it.

The news broke right before this big conference, and that means that the researcher, Hu Jean Kui, was questioned on stage by other scientists who study CRISPR soon after the news broke.

Sarah, what was that like?

Yeah, it was tense.

So I actually spoke to one of the organizers who questioned him, Matthew Porteus, and he had met with Hu about nine months ago, which is an ominous amount of time in retrospect, and had heard that He was interested in doing this.

He didn't know he had done it.

And Matt says that he was

extremely angry about this, told him he couldn't do it.

And I think everyone was really shocked when it happened, but the prevailing sense was like, we need to, we can't let him get away with it.

We need to question him on stage.

So I actually thought, you know, there were lots of good questions about consent and what he actually did and technical questions, but I think this question that really stood out to me is a woman asked him about what the lives of these girls are going to be like.

There was some question about whether one of them was maybe still susceptible to HIV, but not the other.

It's a little bit unclear, but basically she wanted to know, like, are they going to be treated differently in the family?

Because one of them might be immune and the one isn't.

And if I remember correctly, Hu's response was, I don't know how to answer that question.

And the sort of utter blankness seemed to suggest he really had not thought this through.

He had thought about what was going to happen maybe a year from now or five years from now, but these girls are going to be alive for 18 years, 50 years.

Who knows, right?

This is going to affect their entire life.

They're going to be around when he's not around, probably.

And it seems like he just really had not thought about those really long-term consequences.

Aaron Powell, and are there any formal prohibitions or restrictions that the scientific community or governments can enforce that this researcher broke?

Aaron Powell, it's a little unclear.

So, this work would have been clearly illegal in Europe, in many parts of Europe, where there are clear bans on germline gene editing.

In the US, it's a little trickier.

There are prohibitions, but not a clear ban.

So,

the FDA cannot consider research applications that involve germline editing, and the NIH and several other agencies can't fund work that involves the destruction of human embryos.

So through those restrictions, this work could not have happened in the US with federal funding.

If Herr had done his work in the US, would that have been illegal?

It's interesting that different bioethicists I've talked to have had different takes on this, but

Hank Greeley at Stanford made the good point that at the point when you put the embryos back into the mother, that counts as essentially,

I think it's an untested drug.

Like the embryo kind of counts as a drug in that case.

And you're doing that without FDA approval, which is a federal crime.

But

it's a little bit woolly, I think.

And

there's no international body watching for all of this with regulatory powers to control it.

So say you want to blow the whistle on something.

I mean, you could contact journalists.

Please contact journalists.

Yes, do that.

But who else do you call?

There's no phone that someone like Porteus can pick up and go, I've heard something truly troubling.

And that, I think,

is part of the problem.

David Baltimore, who chaired the summit at which her spoke, said that this represented a failure of self-regulation in the scientific community.

And I think that's absolutely right.

So this international group had convened the summit to discuss the possible ethical consequences of germline gene editing back in 2015.

And they had issued a report through the National Academies that summarized their take on it.

And their take was not an outright ban or moratorium, but that this should only be done under a set of quite stringent circumstances, including unmet medical need and widespread

global consensus or

widespread public consultation and a lot of other criteria that HUD did not meet.

It is interesting that the lack of a red light was taken by someone as a green light, which feeds into further discussions about how we should deal with this

thing going forward.

Do you think that this does suggest that the the scientific community will have a hard time regulating this type of thing itself?

I kind of suspect so.

I think the fact that this happened,

that this allegedly happened,

and that people didn't know about it is a problem.

And I think this is a problem

that extends not just

within the realms of CRISPR and gene editing, but across a lot of controversial and important areas of modern science.

The problem with modern science is that it is woefully untransparent.

So

the incentives of modern academia are not to

make incredible discoveries for the good of humanity, but to publish a lot of papers in high-impact journals.

And that might not be why scientists got into science, but that is what they have to do to play the game.

So, people do work largely in secret.

And, you know, they may talk to a few other people, but you then find out at the point when someone presents at a conference or publishes a paper, which is often too late when it comes to work like this that has massive social consequences.

And so this capacity for people almost unilaterally to make decisions that affect society and that might ramify across the world

is

huge.

Some folks might say, hey, you know, we've had this pretty powerful genetic toolkit for a while now.

And the fact that this is the first time that anything like this has happened is a sign of the robustness of the scientific community's ethics.

But Sarah, has anything like this actually happened before?

That's a good question.

I think yes and no.

So I think there's maybe like two issues that are kind of intertwined here.

One is can we edit the genes of a person?

The other is can we create like a responsible for human life, right?

Like now that we're talking about babies.

So with have we edited the genes of a person?

Yes, right?

So in the 90s we had something, the beginning of something called gene therapy, which which is kind of a precursor to CRISPR.

It's like you're adding a correct copy to a gene into the body of someone who doesn't have one.

And this was really exciting in the 90s.

This is like maybe the 90s version of CRISPR.

And then there was this one trial, not by rug scientists, but like a leader in the field, that just went horribly wrong when a young man died because he had a reaction to the virus that was part of the gene therapy.

And that really put a chilling effect on the field.

And I think it's, you know, kind of taken 20 years for gene therapy to get back to where you can actually start doing it again because that one action had such a chilling effect on the field.

And in terms of

this control of human reproduction, I think IVF was also extremely controversial when it first was used.

And that's actually become totally normalized.

I don't think people will even bats an eye at the idea of IVF anymore.

Yeah.

So it's worth noting that that gene therapy case where someone died,

Her actually mentions this in

a talk that he gave last summer in July 2017.

He ends that talk by saying this happened.

It had a chilling effect on the field.

If we were to do germline gene editing, we must be super careful and very transparent about it.

And he even published an ethics paper

saying roughly the same thing, which coincidentally came out two, like a couple of days after news of what he had done had actually broken out.

So it's not that he was blissfully unaware of all of this.

It just seems that he had passed it all, considered it all, and then gone ahead anyway, which is one of the more baffling aspects of this whole story.

How unique are the ethical

difficulties or issues that CRISPR itself poses?

So I think a lot of these questions have come up before, like, right, we've been talking about designer babies for decades now.

But one of the things that really is unique about CRISPR is that it's fairly easy to do compared to a lot of things that have happened in the past.

So Hu was a researcher who, you know, he was trained at some of the most prestigious universities in the US, Stanford and Rice,

but he

did not have a long-time experience with gene editing or with CRISPR.

He started doing this a few years ago.

He was able to order these parts off of the internet.

This fast and rapid spread of CRISPR and the fact that it is so much easier to do than almost anything else makes it really easy for someone like him, who's not a guy in his garage.

He's someone with a university.

He's an affiliate with a hospital.

He can work with doctors.

But he doesn't need a lot of resources.

He says he funded this space with his own money and some money from a startup.

So you don't, it's not that hard for someone like him to just do this without telling anyone.

What do you think are the likeliest impacts

of this event on the field?

It's sort of hard to predict.

I think the sense I get from looking at responses like at the conference and statements that have been issued afterwards is that it seems that people are very worried that this is going to have the same chilling effect that the gene therapy scandal had, that it's going to shut down legit possible uses of gene editing in the future.

And I think some of those statements are verging on the tone deaf, given the size of the public outcry.

And I don't know to what extent that chilling effect will actually manifest or to what extent the world will just shrug its shoulders and go, well,

this was a ridiculous turn of events, but we're just going to plow on.

I think we'll have to wait and see.

But I think it's important to take a bit of a reality check here, because like Sarah said, a lot of the more dystopian visions of what what CRISPR could do, so the creation of designer babies, like babies

that are smarter or taller or so on, are actually quite difficult to pull off because

the genome is so complicated, because those traits are the province of

a multitude of different genes.

It's very hard to edit all of those at the same time.

And even if you did, you have no idea whether those edits would then have knock-on effects with other genes or so on.

So I think using CRISPR for human enhancement in the way that I think most people fear it might be used

is actually

very tricky.

And

I think beyond the scope of what we can do now.

What should and shouldn't people learn from?

this catastrophe.

Aaron Ross Powell, I'm not sure that this dystopian vision of designer babies is actually going to come to pass in the way that most people expect.

I think if this kind of gene editing progresses, probably the most likely first thing that will happen is that people will opt to edit the genes of their embryos and babies in order to have these kind of enhanced traits.

And it probably won't work.

So you'll have a group or maybe even a generation of babies that are thought to be social, to be advanced in some way, but are not.

And so

what happens then?

And we see some of this in like basically almost any health-related technology.

There are people peddling products that don't actually do the things that they say they will do.

And there is obviously a massive consumer appetite for those products.

So I'm sort of interested in that space.

And I think in some ways what has happened here,

you know, even though it is a huge like ethical maelstrom, to me fits with that narrative because neither of these two children, Nano or Lulu, may be resistant to HIV at all.

So this, this sort of purported good

may not apply to them.

And yet here they are, the possibly the first two gene-edited babies in the world.

And what are their lives going to be like?

And that was the sort of part of the puzzle that her apparently hadn't considered and had no answer to.

And I think those kinds of social ramifications are unclear to me as well.

And I think that's sort of what

we need to grapple with now.

Sarah, I'm going to ask you this question.

Given this burst of news that's somewhat complicated, what do you think are the most important things for the ordinary person to just take away from this whole?

Yeah, I think just to understand what CRISPR is, I think now maybe most people's conception of CRISPR is now somehow tied with babies, but it's actually this thing that can be used in so many different ways.

It can maybe be used to make new vegetables, or it can be used to cure certain genetic diseases, or if we used to study butterfly wings.

It's just that it can do so many different things, and we shouldn't think of it only in the realm of designer babies.

Thank you very much for that, Ed, Sarah.

This has been an illuminating conversation, and I'm both slightly more pissed off and slightly less scared at the same time.

So

thank you.

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