Radiolab - Update: CRISPR

Episode Date: February 24, 2017

It's been almost two years since we learned about CRISPR, a ninja-assassin-meets-DNA-editing-tool that has been billed as one of the most powerful, and potentially controversial, technologies ever discovered by scientists. In this episode, we catch up on what's been happening (it's a lot), and learn about CRISPR's potential to not only change human evolution, but every organism on the entire planet. Out drinking with a few biologists, Jad finds out about something called CRISPR. No, it’s not a robot or the latest dating app, it’s a method for genetic manipulation that is rewriting the way we change DNA. Scientists say they’ll someday be able to use CRISPR to fight cancer and maybe even bring animals back from the dead. Or, pretty much do whatever you want. Jad and Robert delve into how CRISPR does what it does, and consider whether we should be worried about a future full of flying pigs, or the simple fact that scientists have now used CRISPR to tweak the genes of human embryos. This episode was reported and produced by Molly Webster and Soren Wheeler. Special thanks to Jacob S. Sherkow. Support Radiolab by becoming a member today at Radiolab.org/donate.     

Wait, you're listening. Okay. All right. You're listening to Radio Lab. Radio Lab. From W-N-Y-S. See? See?

Let me tell you, there is nothing like the sheer elation of discovery. And I was thinking, you know, this is the end of malaria. This is the end of everything else. Mosquitoes spread. Wait a minute. You know, tick spread Lyme disease. We can probably get rid of that too. So in the morning, you were like, who-hoo.

You were singing to the turtles in the park. Pretty much. And I give myself a full day of being who. And then I started thinking, but, but, but, but, what if something goes wrong? I'm Jedd aboumrod. I'm Robert Krollwitch. This is Radio Lab. And the guy that you just heard is Kevin S. Felty.

He is a scientist. He was talking to our producers, Storm Wheeler and Molly Webster. About CRISPR, which is a technology. Actually, it's a new, it's a gene editing technology that can reshape life, actually. Yeah, and we ended up doing an entire show about this. Yeah, and we called it Antibodies Part 1. I do remember that. As if there was going to be a part 2.

And that's like, name that. It's like telling someone you got them a birthday present, but you haven't yet. Yeah, that's true. Maybe we should just own up. Radio Lab listeners, we did not get your birthday present. Let's just, let's just, that seems mean. No, we meant to. We meant to have a part two.

But, you know, we were doing a story. It fell apart. Life doesn't always work out. The tape sucked, frankly, and we thought it was going to be a story. It just turned and turned out to be a story. But now what we're going to do is we're going to pay you what you do. This is the part two. Yeah, this is the part two.

Finally, part two, because CRISPR in the time that we did the thing till now, has gone banana crazy. So much has happened, really. Yeah, like every day in the science section, which I know we all read religiously, there is a CRISPR thing. Yeah. So just to get us started, we're going to play you the original piece for those. of you who never heard it just to sort of set the baseline and then we're going to come back and tell you all the stuff that has happened since yeah yes All right, so let me explain to you how I got started with this. You were some kind of an affair?

Yeah, so I'll tell you how I was at a party. Party. It was a conference where a lot of different people of different disciplines come together. You know, one of those. There are panel discussions and various things. So we were at one of the functions, and it was a situation where, like, dinner hadn't yet been served, and there was a lot of booze being served. Everybody was, like, drunk on an empty stomach.

So I was standing there. with some biologists. Oh, they're the fun ones. The junk biologists, yes. As my people, apparently. And they started to lose their shit, like genuinely lose their shit about this thing called CRISPR.

And like, I have never seen scientists this excited about anything. So I was like, what is this thing? What is CRISPR? And they were trying to explain it to me, but they couldn't slow down enough for me to get it. I gathered it had something to do with genetics.

And then at one point, one of the biologists turned to me and he was like, I'll tell you what it is. I can use CRISPR to take a little dog and poof make it into a big dog give me a chihuahua I could turn it into the size of a great dane and I was like no you can't he's like yes I can I could do it with CRISPR I was like what the hell is this thing

you want me to sit here as usual yeah if you sit here I will get out I didn't mean to imply in any way we'd be sitting here together so what happened was I came back and I immediately called science writer Carl Zimmer because I just figured for this kind of thing this is a Carl thing. I got to talk to Carl. So I basically asked him, like, why all the fuss? Maybe it was just the alcohol, but maybe there's something really happening here. Oh, there's something totally happening here.

I mean, it's big. He started at the beginning. So you can actually find, like, the first reference to CRISPR in a 1987 paper from some Japanese scientists. They basically described something weird in E. coli, and they said, we don't know what this is. E. coli are bacteria inside humans. And like all living things, e coli is made up of DNA,

A's and T's and C's and G's. And what happened was that these scientists were reading a chunk of that genetic code when... They found this really strange stretch of DNA. Strange how? Well, so basically what it was was five identical sequences in a row. And then they were separated by very short sequences

in between them that were... all different from each other. These little blurbs would be like, and they looked at this and they're like, what? This is nothing like we've seen before. Repeated sequences in bacterial genomes are kind of unusual. Seems very strange. Some biologists felt that, you know,

there must be a purpose for these. Among those purpose seekers? Jennifer Dowdna, University of California, Berkeley. She's a cell biologist. Yeah. So it's Dowdna, not Dudna. It's Dowdna. I used to be called the dude sometimes in school.

In the movie, she will be played by Jeff Bridges. Right. Anyhow. As time goes on, scientists start seeing these little repeat, blurp repeats everywhere. Yes. Or at least in bacteria. Lots and lots and lots of species of bacteria. They say, okay, wait a minute. That's kind of cool.

They're finding it so often that they decided they had to give it a name. Is this where the name CRISPR comes from? Yes. The full official name is clustered, regularly interspaced, short palindromic repeats. Oh, my God. I don't know why they called it CRISPR. It's kind of a... It's like a furniture manufacturer or something.

It sounds like an app. Yeah. Crispur. Chrisper. But now, scientists have this puzzle. If nature at this level preserve something intact here and here and here and here and here and here, and some of these here's are creatures that have been around for hundreds of millions of years, you figure, well, whatever this is...

It's doing something. It's doing something. But what? It doesn't take very long before the first big clue comes up. All right, fast forward. 2005, now scientists have these big, searchable databases of DNA sequences. So some scientists think, well, let's do a search. Let's see if these repeating patterns we keep finding match anything else that's out there in the world.

And these scientists are using computers to just line up these stretches of DNA with thousands upon thousands of different species. and then click. All of a sudden, they discover that those bits of DNA between the repeats, the stuff in the middle, those blurps. These are matching virus DNA. Like, you can find viruses with genes

where these little, you know, these little... To the bacteria had virus inside of them? Yep. Does that mean that a virus brought it into these cells? Does this tell you anything about the origin of it? The first recognition was, this is virus DNA. Somehow, all these bacteria have little snippets of virus DNA wedged in these particular places in their genome. Which is a little weird, if you think about it.

I mean, these are totally different creatures. It would be like inside a human finding a little bit of mosquito DNA. How do we interpret this? Well, actually, there was one scientist, his name is Eugene Coonin, who looked at these results and just said, okay, I get it. It's a defense system. What? Why would he think that? Because he's a brilliant man.

What do you mean? If I went to a large sanitation dump and I found a teeny bit of human hair, why would I think, oh, I get it. It's a defense mechanism. I wouldn't know. It's just like a bit of human. Right. Well, you see, that metaphor might sort of betray your lack of skill in microbiology.

I'm just saying, like, this is not a dump, all right? This is bacteria are not going to just let virus DNA get into their genes willy-nilly. Okay, remember, viruses are the big enemy. Right. If you're bacteria, viruses make your life a nightmare. Think about it in the ocean, okay? The ocean is full of viruses and viruses kill up to 40% of all of those bacteria every day. Really?

Every day, yeah. And we know that they have. have defenses. What Eugene Kuhnan said was, okay, I'm going to bet that these bacteria are somehow grabbing pieces of DNA from viruses, and then they're storing it, and now they have a way of recognizing those viruses if they come in later. It's like little Polaroid shots of the enemy. Right. Know thy enemy. Yeah, like a most wanted poster. What you call the mugshot. This is Eugene Kuhnan.

leader of the evolutionary genomics group at the National Center for Biotechnology Information. He's the guy that Carl referenced who thunk up the whole idea that maybe these bits of virus DNA inside the bacteria is the bacteria trying to defend itself. But really, if I would credit myself with anything here, it was not so much guessing this, because, you know, when you see these identical sequences, that gets pretty obvious. It is figuring out. how the mechanism was likely to work. So can you walk us through how the mechanism is likely to work?

All right. What happens is... You know, when a virus comes in to a cell, it just kind of explodes and just kind of releases naked genes, basically. If you're this bacteria, these things might take over your cells, so you've got to respond. Most of the time, you have multiple weapons of defense. If you've never seen this virus before, usually the first thing you're going to, you do, says Eugene, is you send out these enzymes.

To attack the viruses, they're sort of like the ground troops. And they fight really hard. But much of the time, they fail, and then no one will hear about you again. They're not terribly sophisticated fighters so very often. The virus takes over. The bacteria dies. But there is some non-zero probability that you actually survive the attack. If you do, then what the bacteria will do is send in some new enzymes to basically clean up,

to go out, find any stray viruses. And then cut the enemy DNA into suitable small pieces. And here, he says, is where you get to the storage part. Those enzymes will then take those little bits of virus and shove them into the bacteria's own DNA, right in those little spaces between the repeats. Right there and nowhere else. So I use those spaces in my own DNA.

DNA as a storage facility? Yes, if you will. You use it as a memory device. Because here's what happens. Next time that virus shows up, sprays its genes everywhere. Now you are prepared. And this is where the CRISPR store really gets going.

Because instead of sending out the ground troops who are probably getting at their asses beat, now you can actually send out the big guns. And in fact, what the cell does it will manufacture these special molecular assassins. And we'll give those assassins a copy of that little bit of virus DNA it has in storage, basically saying, here, take this mugshot. If you see anything that matches this pattern, kill it.

Ew. And these attackers, do we know what one of them looks like? Yep, so we know what the protein looks like. It actually looks, I would describe it a little bit like a clamshell. Sort of imagine Pac-Man, but kind of misshapen and rough. And each one of these guys... What it has is a copy of that virus DNA. It's got the mugshot.

That it's kind of waving around. What then happens is that... Whenever the Pac-Man bumps into some virus DNA... It pulls apart the DNA. Unzips it. Reads it. If it's not the right one, it goes on. Nope.

Mm-mm. And if that RNA has the... the same sequence, then click, click, it just locks in. And if that happens, then the DNA is trapped and molecular blades come out and chop. Cutting its head, they're the mighty blow.

Yeah. Wow, so this is smart scissors. So it's like, are you like the thing I got? Are you like the thing I got? You're like the thing I got. Snip! All right, now we're going to kill. Oh, I see.

And it has to be an exact match. When scientists first discovered this whole system, they were fascinated. They were like, they were working it out. They were like, oh, okay, then this happens, and this happens, this happens, cool. But then, in walks. The dude. Jennifer Dowdna, with a crazy idea. I don't know if it's crazy, but radical.

This could be an amazing technology. This is a tool. This is a tool. Right. This is a tool that we can use to cut DNA where we want to cut DNA. Her basic thought was, why don't we turn this defense into offense? Because these things, they seem to be really good at cutting, and yet they only seem to cut the things that are on their mugshot.

So maybe I could just replace what's on their mugshot. So instead of them going after viruses, maybe they could go after a gene that causes Huntington's disease or hemophilia. For example, and this is actually something that's been done, say you've got a mouse with something like hemophilia. Okay. This is a disease that's caused by one bad gene. So what you do is you take these little surgeons, you give them the mugshot for the bad gene,

then you stick the surgeon with the new mug shot in a mouse. Then you set it loose. And just like it's programmed too, it will find that gene. And click, click, chop. The scissors will end up cutting exactly the gene you wanted to cut. So the bad gene's gone. Now the question is, how do you put in the good gene? Right.

It turns out, actually, according to Jennifer Dowd, now that that's actually not as hard as you would think. Really? Yeah, apparently what you do is just throw this new good gene kind of in the neighborhood of where the old gene used to be, just in the general vicinity. You don't have to get super precise. I mean, it turns out that, you know, there are repair enzymes that are probably continually surveying and checking for breaks.

She says what will happen is it inside the cell? These repair crews will come along, they'll see the break. They'll see the good gene just sitting there next to the break. They'll be like, all right. I'll just stick it in. Put the pretty guy in this space. Exactly. So we take advantage of a natural repair pathway that cells have.

They trick both the cutters and the fixers. Yeah, now we're not assassinating anymore. Now we're actually engineering. We've gone from killing to refashioning. Although, haven't we been designing genes, doing a form of genetic engineering for, I don't know, like 30 years? Yes, but not like this. genome editing technologies have been around for a long time, but none of them have been as powerful as CRISPR is.

That's Beth Shapiro from UC Santa Cruz. She was actually one of the biologists that I drunkenly talked to at that thing. Was it a modern art museum? I can't even really remember. I don't remember either. Must have been quite an evening to have the setting be so vague. Anyhow, here's how she put it to us. Back in the day, this was just like two years ago, you would have these gene editor things, you would take one,

Put it in a cell. And what happened before was you would give it some instructions about where to go. And it might go there, but it might go to somewhere that's kind of related to where that was. So it's like, you just take it right at Staten Island, but it takes a left. And not only would it take a left at Staten Island and not find there, but it would have cost you a fortune and taken up six months of your time to get that thing. And now, you know, it's really easy. You just give it that mugshot? And it goes, I'm going to find that guy, exactly.

So it seems to be pretty precise. It's cheap. Like the old tools would set you back about five grand just to use them once. CRISPR, about $75. And here's the kicker, says Carl. It seems at the moment that you can take these things out of bacteria, stick them into almost any other creature. And it still works.

You can use the same CRISPR system on anything. Can you like do it if corn is vulnerable to a certain pest, you can do it in corn? Do it in corn. Do it in corn. I am waiting for someone to say, CRISPR doesn't work in species X. And I have not heard of that.

So basically what you have for the first time in science is this gene editing technology that is cheap, precise, and possibly universal. And Jennifer Dowdna says the moment the full impact of that landed on her? I literally had, you know, the hairs on the back of my neck were sanding up. Just processing the fact that this thing exists, you know, and that you could actually program it to cut DNA. and just like this molecular scissors, and I can just program it and it cuts DNA wherever I want.

It is amazing unless you think about it further, which we will do in just a moment. I feel a cloud coming in over the horizon. Just over there. Do you see those clouds in the horizon? I see it's getting sort of dark over there, but we'll be right back. Hi, this is Lauren from Atlanta, Georgia. Radio Lab is supported in part by the Alfred P. Sloan

Foundation, enhancing public understanding of science and technology in the modern world. More information about Sloan at www.sloan.org. This is Radio Lab. I'm Chad. I'm Boomer. I'm Robert Crowicz. Okay, so clearly the possibilities are there to use CRISPR to treat disease, right? But what if you could get a little more fanciful, right? Like, what if you could actually go back in time and resurrect long-lost creatures? I mean, this is something that Best Shapiro has talked about a lot. We could reconstruct using a computer what the genome sequence of the ancestor of all birds was,

and that would have been a kind of dinosaur, and then we could use crisper's to turn a chicken into that thing. Or what if you could take an elephant, and snip, snip, snip, gradually turn it into its long-lost relative, the woolly mammoth. No. Because they're related, but if you, their genes are similar. Well, right, but if you know the woolly mammoth genome, which they do, because they apparently got it off some bone or some hair,

then you could compare the number of differences, use CRISPR to CRISPR out the different parts of the elephant and put in woolly mammoth instead. If you can, in effect, go backwards in time and make changes, then obviously I think you can go the other way too, right? I mean, humans are good at design. We're designing animals. So it doesn't seem to me to be a crazy notion

to imagine parents all over the world wanting, I don't know, taller children, so silencing the short genes and favoring the taller genes, getting rid of weak muscles and going for stronger ones, and on and on and on. And I don't know where the designing stops. We sort of got into all this with Carl Zimmer, science writer. If you can be very, very gene-specific

and you learn more and more about genes over time, why couldn't you invent a creature? Why couldn't you make a pig with wings? You might one day get some. sophisticated enough to do that. There's no winged pig lab. You know, the best you're going to hope for right now is a willy mammoth lab, and that's down the hall from where the real action is at.

But now there's a hall, and at the end of the hall is a winged pig lab. It hasn't been built yet. It may be 20 years from now, but that's what you're looking at. Well, I think, but the thing is that... Well, what's wrong with this thought? Why shouldn't anyone realize that that's really what we're talking about here? Well, because you can't make winged pigs, just because of sort of evolutionary barriers, okay?

Well, there's no real reason for breaks to fly, except for the joke. Calm down. Calm down. I'm just soaking. I mean, okay, I don't think that we need a federal department of homeland pig with wing security. I think we're okay there, all right? What we do need is, like, we do need to, like, figure out what are we going to do about CRISPR in humans?

I mean, they're going to be using CRISPR for cancer, okay? They're going to take people's immune cells out of their body, and they're going to use CRISPR to basically allow them to make proteins. They're going to be able to grab onto cancer cells and attack their own cancer. Yeah. But you have to be for that. I mean, you have to be. Well, I don't know. I mean, are you for, that is.

Well, you're, you are tinkering with someone's own body. You are altering their own cells, you know. Dude. Where do I... It's just, I tell you, this is me, I don't know if it's a religious thought or just the thought of a conservative person, but, I mean, I grew up in the test tube baby era.

I now know many wonderful adult formerly test tube babies, and I remember being astonished that, no, so I can't, I don't know where the sacred begins and ends anymore on that particular turf. I guess what I'm instead on is I'm on, on a Hobbesian view of human beings, that there is something about human beings, including scientist human beings,

all human beings, that there's a darkness and a light. There's an angelic side to being human, and there's a very, very difficult side. And as the human beings get more and more power to create and design and essentially create a future, that future will include the imaginations,

both light and dark of humans. and that will be new in the world. I don't think it is new because if you go back to the start of the scientific revolution, something like Francis Bacon would say explicitly, like, science is going to be both about learning about how the world works and using that knowledge to control it. You know, this has been discovered. This has been published.

Everybody knows it exists. If you're going to say, like, okay, now we're going to all, we're going to outlaw this. I'm not suggesting that. Well, what are you suggesting that? I think we should cringe a little. supposed to just have a big part. All right, that's all cringe. Ready?

One, two, three. Don't make fun of it. You, no, no, that's not fair. What, we've cringed? And now what? What do we do now? I don't know. We all cringed.

If that's what you're arguing for. No, you cringe. We cringe, you cringed. You cringed meanly and, and you cringe with attitude. I'm cringing with, with. I would like to know. Because you're afraid of like dragons. You're sorry.

You're saying, oh, my God. Yes, I'm afraid of dragons. Okay, so that conversation with Carl was four months ago, and a lot has happened in that time. Because to the question that you asked, like, where does the sacred begin and end? Well, one of the lines that had been drawn by Jennifer Dowdena and others was that we should not use this technology on humans who haven't been born yet,

meaning not on sperm cells or egg cells, because if you CRISPR, say, an embryo. That is a permanent change. Right, that is a change to the DNA that will be passed on to their children. And their children's children's children's children. And you can't ask the person if that's okay because you're doing it before they're born. Consent becomes a real issue. And if you imagine making these changes and they cascade through generation after generation, you could affect the evolution of organisms.

And it's, I don't want to say trivial, but it's fairly easy to do it. Wow. It's kind of profound. I feel it's really profound. Profound, but it was just an idea. That is, until... For the first time in history, researchers in China have successfully edited the human genome in an embryo. Just two months ago, it was announced that a Chinese team...

From Sunyotson University used a technique called CRISPR... To edit DNA in human embryos, it's a way of hacking evolution itself. Well, this is hugely controversial. Now, these embryos, the Chinese team had edited, they were created through IVF and they were not viable. These are embryos that are not going to actually develop into a person, so they're going to be discarded anyway. But still, if they could figure it out with those embryos, what's to stop any of us from going further? Biologists and bioethicists are sounding an alarm. The scientists face accusations that they crossed an ethical line.

This sort of thing could be sort of a slippery slope towards designer babies. Essentially genetically engineering the human race. Sure. To kind of test your levels. Okay. Now that the cringe party had spread, and Robert didn't seem like such a loon, We called up Carl again. Well, we have to revisit.

We have to revisit because in our Armageddon conversation, in which I believe I was extremely alarmist and you were extremely downputting, I feel that I should do a small little parade called the... I thought, remember the Alamo. It's like, remember China. And you have to, so you should just begin any time you want, like getting on your knees and saying,

how sorry you are. I can start from there. I'm sorry. Are we actually surrounded by an army of clones with superpowers? Not yet. Not yet. But I think the dyke has been open. I believe I'm going to quote somebody who said maybe a few weeks ago, I think he was.

Maybe it was last week even writing for National Digress. I think it was. Maybe it was somebody named Carl who said that the news from China and that news was probably the beginning of an entire new era. I think I actually said it was a historical moment. That's right. Yes, and I still stand by that. Do you feel differently now than the first time we talked? Yeah, that's really the question.

I don't feel different, actually, because there's really no scientific surprise here. He says people have been doing all these CRISPR experiments on all these different mammals. We're mammals. This is bound to happen. And in fact, it may be happening more than we think. One account in the journal Nature has said that four other Chinese labs are doing this kind of work as we speak. But Carl also told us, which he said, was unsurprising too, but I actually find it kind of surprising, that the CRISPR work this

Chinese team did didn't work very well. It worked kind of. I mean, in only a few of the cases, did they really get exactly what they wanted? They tried using CRISPR in about 86 embryos, and they only got to work right in maybe 28. And in a lot of them, CRISPR's made the wrong cuts and screwed up the cells. And that led them to conclude that this is a technology that's not ready right now. for application in the human germline. And I agree.

Oh. We still are in this kind of fortunate position where we can say, oh, well, it's dangerous. So we shouldn't use it on human embryos. I just don't think that we're going to be able to sort of find refuge there in like 10 or 20 years. In 10 or 20 years, you know, CRISPR will be so sophisticated that people will be able to say,

I can get you the change you want. and I can do it safely. I can guarantee you that you will have human embryos that have the alteration in the particular gene you want. So then what? In fact, Jennifer Dowdna told us that this experiment, or similar experiments, have been repeated in mice with more advanced CRISPR systems because apparently there are many different kinds. And there it was done with almost no errors. Sometimes I feel like we're sort of displacing all our ethical concerns onto something that hasn't happened yet. If we really are concerned about what we're doing to the human gene pool, you know, it's already here.

Take, as an example, in vitro fertilization. About 60,000 kids are born a year through IVF, and it's probable that some of those parents chose whether they wanted a boy or a girl. And when people started doing IVF, there was a huge controversy. People said this was dangerous, this was unnatural. I don't see people who are unable to sleep at night because of the existence of IVF. Yeah. You know, now I'm going to sound like I'm on Robert's side of this. I mean, okay, so, so.

It won't hurt. It won't, it won't. Okay, all right. Here we go. So, okay. So, okay. So. Deep breath. So you guys know about all the stuff going on Iceland where they're looking at people's DNA and, you know, they're looking for disease genes and so on.

And when they were looking at these Icelandic people, they found that some people had a gene that protects them against Alzheimer's. It reduces their odds of getting Alzheimer's. Let's imagine your doctor said, now, if you'd like, for an extra thousand dollars, we will take these IVF embryos and we will use CRISPR to give them the Alzheimer-protecting variant. Would you like that? Do you want to add that to your procedure? Sure, yeah. Or would you like your child to face a future of, uh, uh, future of, uh, Alzheimer's. Your choice. See, here's my thing. Here's my thing with this whole thing. I'm a little bit haunted by the thing you said, which is that when it's not dangerous anymore, what will we do? And I'm afraid we've already answered that question. That it's not a

question that's open anymore. Because if we're already doing this kind of stuff, and who's going to say no to that? Who's going to say no to that? That's what he just was demonstrating. Yeah. We've already answered the question. Yeah. We may have. So that's how we ended our piece, which is now two years old. Roughly. Roughly.

And the drunk biologists at Chad's cocktail party couldn't have been more prescient when you think about it. You know, this is one of those strange cases where, like, you do a story. Usually, like, we just kind of leave it behind. We move on to other things. But in the last almost two years, so much has happened. Unbelievable. That we figured we need to update this thing. Yeah.

And so what we did is we asked our producer editor, Storn We, and our producer Molly Webster to sort of just go out, ask around, make some calls, and tell us, you know, what's been going on. Well, for one, Molly, do you want to give them the big news? Jennifer Lopez is going to do a television show

based on CRISPR. No. It takes an active role in the fictional narrative of the show. Oh, okay. Oh, like, she's a cough or something. She's like some sort of, I don't know, a medical something and CRISPR is involved.

Really? Yeah. Let me show you these. Let me show you these scissors. Wow, it's crossed over to that extent? That's the thing. It's like, it's, yeah. I was like, Jennifer Lopez knows about CRISPR and she was like, this is such a hot button issue.

We're doing a show. That's amazing. Yeah. Okay, so moving, putting J-Lo aside. Yeah, let's do some science developments. There's got to have been quite a few of those. We know there have been a few of those, right? Yeah, what do that run us through those?

I mean, I guess I would just say that it's being used. everywhere now. So it's being used in crops. It's being used in medicine. It's being used in basic research. It's being used in humans. In cows. Really? It's being used in eyeballs. And eyeballs. Yeah, they want to start a clinical trial where they're actually injecting a syringe full of CRISPR carrying viruses into your eyeball to overcome a genetic condition that lead to blindness. So this would be like the viruses injecting the CRISPR that then goes and cuts out the bad genes? Yeah, exactly. Just take, you know, a big syringe full of viruses and just Stick it in people's eyes.

Ah, da, da, da. Yeah. So, of course, when we did the update, Soren and I called Carl Zimmer. Yeah, it's, uh, things are moving very fast. And what kinds of things? So they are doing things that look like curing diseases. So Carl told us about one study where it seems like they cured a certain type of muscular dystrophy in mice.

Cured muscular dystrophy in mice? Wow. Well, then mice don't become normal mice, but they get. much, much stronger than they would have been. Yeah. So in your body, you have a gene that makes a protein that gives your muscle strength. But with muscular dystrophy, there's like a typo in that gene, a mutation. And so that protein's not made.

And the result is that your muscles start to turn into sort of a fat-like substance. That's how it's been described. No power. Yeah. Okay. So your diaphragm gets weaker and weaker. Your heart gets weaker. So in this case, they use CRISPR to fix that gene so you get the protein in these mice.

And they actually saw like the heart gets stronger or the mouse was able to push with more force on a button. And so they said over weeks they just saw like strength building up. Really? Are they going to do that in humans? Pretty first stepy at this point. Yeah, this is literally like one of the first experiments to show that this approach could work in muscular dystrophy. But, I mean, that's not a disease with a cure, is it? Not until potentially in mice now.

Yeah. Wow. And there are some human trials that have either started or are probably going to start soon, treating cancer. For example, people are talking about one in lung cancer. They think they can, what, cure lung cancer? Well, no. What they want to do, though, is they want to use CRISPR to go into immune cells where it would cut out the part of the DNA that kind of puts the break on the immune cell. And so you're taking your immune cell off

the leash and it can attack tumors more aggressively. I see. So the folks who invented this then must stand to earn a fortune. I mean, I think. Oh, billions. There's actually a big patent dispute that's happening right now. So one of the... Right now? Yeah. This is the one thing that I have heard about a lot. If you had been checking your CRISPR inbox, you might have seen. last week. There were two teams, Jennifer Dowdena's team out at UC Berkeley. Oh, the one we just heard from. Yeah. Sort of the West Coast team. And then on the other side is this group of researchers at the Brode Institute, which is on the East Coast. And so basically they both filed for a CRISPR patent. Okay. So there was sort of this like East Coast, West Coast for the last year showdown.

Yeah. And just last week, the U.S. Patent Office. decided that it would indeed go to Brod. This is the not doubt in the team. The not doubt in a team. But there are more patents to be awarded and there will probably be appeals. So I don't think anyone thinks it's settled yet. So in the Civil War over CRISPR patents,

there has been a Gettysburg. There's been a battle. But there are many more battles, I think, that will happen. Gotcha. Yeah. Is there anything else on the list of like what's happening now, exciting stuff happening now? Oh, yeah.

Can I, oh, can we do favorites, sorry? Can I do, can I do my favorite? You can do your favorite. So my favorite came from Carl. Yeah, yeah. They're actually trying to use it as an alternative to antibiotics. Wait, how did I didn't even understand what that means? What are you saying?

I was like, an antibiotic to me is a pill that I take. So what would CRISPR? How would CRISPR replace that? Well, your pill would have CRISPR in it. How would it work? You know, in the same way you would take your amoxicillin or your antibiotic pill, you would actually take a pill that was filled with CRISPR, and then it would go out and it would fight bacteria that is attacking your body.

So you could pick out, you know, some super essential gene that it has and chop it, and that will kill the bacteria. Oh, so you would have. You would turn the assassins on the bacteria. Exactly. So there you go. Wow. Yeah, the antibiotic thing seems huge, right?

That's pretty amazing. at this moment where they're like what happens with the next super bug. If you could actually just go in there and kamikaze the DNA of like staff or whatever, you'd be solving a lot of illnesses. Yeah. Well, what's, what's, uh, what's, soren, your favorite? Yeah, what's your favorite? So the coolest thing, I guess for me.

Hello. Maybe the scariest too. Hi, Kevin. Hey, sorry. How are you? I'm doing great. How are you? Came from a conversation that we had with this guy, Kevin.

I'm Kevin Esfeld. Esfelt. He's very sveld. I'm at the MIT Media Lab. He was sort of on the early edge of thinking about Chris. I think of myself as an evolutionary engineer before anything else. Got into biology because when he was a kid, he went to the Galapagos. Yeah, my parents took me there when I was 10 or so.

And I was just captivated, just looking at all of the creatures. And I thought, I want to make organisms that are as beautiful as that. You actually thought I want to make organisms as beautiful as that? Yeah. But then that's like the childhood vision. And then it's so hard, right? It wasn't possible. And so you sort of forget it.

But now with CRISPR, like almost like all things become possible. So anyway, to get to the crazy part, Kevin, a couple years back, he's working at the Harvard Medical School. And one day he's walking to work through this park. This park called the Emerald Necklace in Boston. It's beautiful. And there's a small river flowing through it. And you have these ponds. There's turtles and whatever.

Geese. And, you know, he's thinking about CRISPR and what it can do and all these different animals that are around him. And he has this thought. What if we could encode CRISPR in the genome? What if we program the genome to do genome editing on its own? Wait, what? I'm not sure I follow that. What is he saying?

Well, the first gene drive system. Here, maybe this is a way to think about it. Let's say that you want to tweak a mosquito and make it so that the little parasite that carries malaria, terrible, awful malaria, either can't get into the mosquito or can't. live in it. And so that mosquito will no longer carry malaria. That would be great. That would be a great thing because malaria is a bad thing. So you could now take CRISPR, send it into the mosquito and change a gene inside the mosquito. So now that mosquito either doesn't let malaria parasite in or kills it or whatever, but basically doesn't carry it. And that's great. But then I put it out

to the wild and it's got to fend for itself amongst all the other mosquitoes. So my mosquito has a special gene, but it's going to mate with some mom mosquito, and that mom mosquito is going to have the normal old gene, and the baby's going to get my special gene, but it's also going to get the normal gene, and that means that your baby has like a 50% chance of having your special treat. Oh, because only one of those two genes gets expressed. Right, in the baby. And then in the next generation, the grand baby, there's only a 25% chance, and, you know, on and on and on. So you're exponentially losing crisper powers. Your chances, just each generation, get less and less that this gene is going to stick around.

That's right, because regardless of what we do, natural selection wins in the end. Until Kevin is walking to work through the park and has his idea, which is to use CRISPR to create something called a gene drive. Gene drive. Gene drive. Yeah. Instead of just snip the DNA and insert the gene that we want, we also insert the genes that encode the CRISPR system and tell it to make that particular change. Here's how it works.

you go into the mosquito and give it the new gene that makes it resistant to malaria. And then right next to that, you put the genes for the CRISPR system you just used to make that change. Like you're putting like a spare scissors or something? Yeah. And here's how that plays out. Your first mosquito has this gene with the new change and it also has the scissors. Yeah. And then it meets a normal mosquito, which has the normal gene. The two end up side by side in the baby.

And now the new mosquito gene makes the little scissors, which go over. to the normal gene, snip it, and turn it into itself. So now there's two copies of the new gene. In the offspring, without any human assistance, CRISPR will cut the original version and copy over the change. That gene does the work that I used to do in the lab on its own inside the baby. Oh, interesting. So, okay.

It's like I set it on autopilot. So you're basically allowing the mosquito parent to pass the scissors. to the baby, which then snip, snip, snip, snip. And then that baby passes the scissors to the next baby, snip, snip, snip. And it is literally like a chain reaction. Yeah. And so, you know, from baby to grandbaby to great grandbaby,

now instead of letting that gene disappear, you're driving it into the next generation. And then that just keeps going down the line, down the line, down the line. Yes. This is something that spreads indefinitely. This gene is going to spread like wildfire through, the entire wild population. So you don't change just one mosquito.

You change all of those insects probably everywhere in the world. According to Kevin, this is the kind of change that could, given enough time, spread across an entire species. Huh. So this idea of the mosquitoes and watching it rampage through a population, have they done this? After we had first published the idea, we tried it in yeast. worked on the first try, you know.

They just plopped a little yeast, loaded with the gene drive, into a population to see if it would take over. One week later, yep. Kevin told us there are probably now, I think it's 10 different groups who are working on gene drive systems. Yes, they are doing it in mosquitoes and in parasitic worms and in rodents. It's all happening in the lab. But still, they are trying out, you know, this method for spreading genes. through a population. Yeah.

I just think that sounds terrifying. Like, honestly, I just keep thinking of it's like, oh, we've just hit over a domino and then walked away and aren't watching where the rest of them are falling. I'm very glad you think that. It took me one full day to reach that point.

Initially, I was elated. Let me tell you, there is nothing like the sheer elation of discovery. And I was thinking, you know, this is the end of malaria, this is the end of everything else, mosquitoes spread. Wait a minute, you know,

tick spread Lyme disease. We can probably get rid of that, too. So in the morning, you were like, woo-hoo. You were singing to the turtles in the park. Pretty much. I give myself a full day of being who. And then I started thinking, but, but, but, what if something goes wrong? And suppose, let's go back to your malaria case, making the mosquitoes malaria resistant.

Well, that seems pretty safe. I mean, malaria is a human pathogen. doesn't really affect other animals. But what if, say, the change you make to the mosquito makes it slightly more toxic to something that eats those mosquitoes? So then you have to consider what eats those mosquitoes and what eats those things. You know, it could be that all the frogs or the fish or whatever

start to die off and then that makes something else die off and something else die off. And that's an incredibly complex system and you just don't know. Or it could be that making a mosquito malaria resistant also somehow makes it do better in some environment, and then the mosquito population blows up, and then it turns out that it somehow makes it easier to carry some other disease.

So isn't anything likely to go wrong? You know. But how do you know? We should say at this point that Kevin is really thinking about all this stuff. He brought together a group of scientists to come up with some safeguards for this type of research, so it doesn't escape out of the lab. And his team is only working,

with this version of gene drive that they sort of rigged it so that it only lasts for certain number of generations and it sort of runs out of steam. But scientists can perfectly well start playing around with something in the lab that could affect a whole lot of other people if it happened to escape. I think what this technology forces us to reckon with is that now it's at least theoretically,

and again, we don't know for sure, but it's theoretically possible for one person to decide to change the local or possibly the global environment. And that's ethically problematic, right? Yeah. I mean, you know, if and when somebody uses CRISPR on an embryo and that embryo grows up into a person, that will be a momentous thing. But if you were to gene drive somebody, think about that.

You know, gene drive, like, say a few people and not tell them. And, you know, they have kids and so on. And you would be driving whatever gene it is that you were engineering into more and more people. And that's different. God, you know, and I'm thinking about the thing that Jennifer Dowdna said, I think it was her in our first piece about, like, if you make a change and say an embryo, like, okay, let me give this, let me snip, snip, snip, give this future child, make it taller. Right. Whatever. Like, you're doing that without the consent of that unborn thing.

Yes. But if you now do what you guys are talking about using this gene drive thing, well, now you're doing it without the consent of that unborn thing and all future generations of that unborn thing. And so the consent issues just become like unfathomable. Exactly. You know, I guess we're all for taller, but we're not all for taller. So in the end, it has something to do with democracy itself. Like, you sit there with a tool of change in your hand and you choose it. But in the act, with this gene drive, in the act of choosing it for yourself this way,

you choose it for an uncountable number of others who do not have the choice. Thanks you to Soren Wheeler and Molly Webster for the update. And so I guess all the people we thank the first time, because those thanks still stand. Many thanks to science writer Carl Zimmer, who's written many books. You can check them out at carlzimmer.com or at radio lab.org. This piece was produced by Molly Webster. We had original music this hour by Eric Kowalski, otherwise known as Casino v. Japan.

Special thanks to Anna Ruskwet Paz. Lee McGuire. Dr. Blake Widenhaft. Dr. Luciano Marafini. Dr. Sean Burgess. And Dr. Junway Shi. I'm Chad I'maumrod. I'm Robert Krollwitch.

Thanks for listening. One quick note of business. Some of you may remember we did a show about meat allergies a little while back with the inimitable Amy Pearl. We did that together with the Sporkful podcast, produced here WNYC. It turns out they've just done a little follow-up with Amy. She went back to get tested for her allergy one more time, and the results were not at all which she'd expected.

So you might want to check that out at the Sporkful.com. To hear the message again, press 2. To delete its start of message. Hello, this is Paul Zimmer. Hi, this is Beth Shapiro. Hello, this is Jennifer Dowdeno. Radio Lab is produced by Dad Apparack. Our staff include Brett O'Farrell, Ellen Horn, Dylan Keith, Matt Kilty, Lynn Levy, Nalve, Lateef Nasser, Melissa O'Donnell, Kelsey Padgett, Ariane Wack, Molly Webster, and Jayne Webster, I think I said Webster. Let me try it again.

With help from Danny Lewis, Kelly Prime, and Damiano Marquetti. Our fact checkers are Eva Dasher and Michelle Harris. Awesome. Thank you much. See later. End of message.