Oh, wait, you're listening to Radiolab from WNYC. Let me tell you, there is nothing like the sheer elation of Discovery. I was thinking, oh, this is the end of Malaria, this is the end of everything else, mosquito spread. Wait a minute, you know, text spread line disease, we can probably get rid of that too.
So in the morning, you're like... You're singing to the turtles in the park, and... Pretty much, and I guess I have a full day of being who... And then I'm sort of thinking, but...
but... but... but... What if something goes wrong?
I'm Janaboom Rudd. I'm Robert Kowich. This is Radiolab, and the guy that you just heard is Kevin S. Veltier.
He's a scientist. He was talking to our producers, Storm Wheeler and Molly Webster. About CRISPR, which is a technology experience, and you... 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 Antibody's part one. I do remember that as if there was going to be a part two. That's a name that...
It's like telling someone you got them a birthday present, but you haven't yet. Yeah, it's true. And they... Maybe we should just own up.
Radiolab listeners, we did not. Let's just listen to them. That seems mean. No, we meant to.
Yes, we did. Well, it doesn't always work out. Taping sucked, frankly. And we thought it was going to be a story.
It just 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 this stuff that has happened since. Yeah, yes. There's only 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 with different disciplines come together. You know, one of those. There are panel discussions, various things.
So we were at one of the, like, 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 drunk on an empty stomach.
So I was standing there with some biologists. Oh, they're the fun ones. The drunk biologists, yeah. It's my people, apparently.
And they started to lose their shit. Like, genuinely lose their shit about this thing called CRISPR. Like, I've never seen scientists this excited about anything. So I was like, what is this thing going on?
What is CRISPR? And they were trying to explain to me what they couldn't slow down enough for me to get it. I gathered. I had something to do with genetics.
And then at one point, one of the biologists turned to me. 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 was like, yes, I can. I could do it with CRISPR.
And I was like, what the hell is this thing? You want me to sit here as usual? No, no, no, no. We'll 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?
Or 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 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. 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 blurps would be like.
And they look 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 say they're like, well, what? They're like, what? They're like, what? They're like, what?
They're like, what? They're so unusual. Seems very strange. Some biologists felt that, you know, there must be a purpose for these.
Among those purpose seekers. Jennifer Doudna, University of California, Berkeley. She's a cell biologist. Yeah.
So it's Doudna, not Doudna. It's Doudna. I used to be called the dude sometimes in school. In the movie she will be played by Jeff Riches.
Right. Anyhow, time goes on. Scientists start seeing these little repeat blur repeats everywhere. Yes.
Or at least bacteria. Lots and 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. Oh my god.
I don't know why they call it CRISPR. It's kind of a furniture. It's like a furniture manufacturer or something. It sounds like an app.
Yeah. CRISPR. But now, scientists have this puzzle. If nature at this level preserves something intact here and here and here and here and here and here and here and some of these here are creatures that have been around for hundreds and 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. Pass forward. 2005. Now, scientists have these big searchable databases of DNA sequences.
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 structures of DNA with thousands and 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... Does the bacteria have virus inside of them?
Yep. Does that mean that a virus brought it into these cells? Does it tell you any of 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 named Eugene Kuhnen who looked at these results and just said, okay, I get it. It's a defense system. Why do you think that?
Because he's a brilliant man. What do you mean? If I went to a large sanitation dump and I found a teen bit of human hair, why would I think, oh, it's a defense mechanism. I wouldn't know.
It's just like a big human. Right. Well, you see, that metaphor might sort of betray your lack of scale and microbiology. I'm just saying.
Like, this is not a dump. All right. This is bacteria are not going to just let the virus DNA get into their genes willy-nilly. Okay.
Remember, viruses are the big enemy. Right. If your 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. What I'm going to do is I'm going to show you a couple of defenses. What Eugene Kunin 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 that they come in later. It's like little Polaroid shots of the enemy.
Right. Know thy enemy. Yeah. Like a motion-wanted poster.
What you call the mudshot. This is Eugene Kunin. 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, if I, if I would credit myself with anything here, it was not so much guessing this because, you know, then you see this identical sequence 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 it 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. You've never seen this virus before.
Usually the first thing 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, 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 as a storage facility?
Yes, if you use it as a memory device. Because here's what happens. Next time that virus shows up, sprays with genes everywhere, now you are prepared. This is where the CRISPRs really gets going.
Because instead of sending out the ground troops who are probably getting their asses beat, now you can actually send out the big guns. And in fact, what the cell does is it will manufacture these special molecular assassins. And it will give those assassins a copy of that little bit of virus DNA it has in store. It's basically saying here, take this mugshot.
If you see anything that matches this pattern, kill it. 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 and zips it. Reads it. If it's not the right one, it goes on.
Nope. And if that RNA has the same sequence, then click, it just locks in. And if that happens, then the DNA is trapped and molecular blades come out. And chop.
Cutting its head. The mighty blow. Yeah, 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 snip snip. Alright, 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, this happens, this happens. Cool. But then, in walks. The dude.
Jennifer Dabna. 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 off-eds? Because these things 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 hunting in its disease or hemophilia. For example, this is actually something that's been done, so you 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 a new mugshot in a mouse. Then you set it loose. And just like it's programmed to, you 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, 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 there are repair enzymes that are probably continually surveying and checking for breaks.
She says what will happen is it's inside the cell. These repair crews that 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.
What 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. Gone from killing to refashioning.
How have we been designing genes doing genetic, a form of genetic engineering for, I don't know, like 30 years? Yes. But not like this. Do you know, 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 with that thing. Was it a modern art museum? I can't even really remember.
I don't remember either. It was quite an evening. Good to have the setting be so vague. And yeah.
Here's how she put it to us. Back in the day. This was just like two years ago. You'd have these gene under 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 somewhere that's kind of related to where that was. So it's like, you just take it right. It's that island. But it takes a left.
And not only would it take a left it's that island and not find there, but it would cost you a fortune and take it up six months of your time to get that thing. And now, you know, it's really easy. You just give it that mug shot. And it goes, I'm going to find that guy.
Exactly. So it seems to be pretty precise. And it's cheap. Like the old tools would set you back about five grand just to use them once.
CRISPR about 75 bucks. 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? Do it in corn. You can pass it into it in corn. In corn, do it in anything.
I'm 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 Doudna says the moment the full impact of that landed on her.
I really, I literally had, you know, the hairs on the back of my neck were standing 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, 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. It's over there. Do you see? Mark, over there.
We'll be right back. Hi, this is Lauren from Atlanta, Georgia. Radiolab is supported in part by the Alfred P. Sloan Foundation, enhancing public understanding of science and technology in the modern world.
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I'm Jonathan Ron. I'm Robert Croweich. Okay, so clearly the possibilities are there to use CRISPR to treat disease, right? Well, what if you could get a little more fanciful, right?
What if you could actually go back in time and resurrect long-lost creatures? I mean, this is something the best repurios talk 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 CRISPR to turn the chicken into that thing.
Or what if you could take an elephant and snip, snip, snip, gradually turn it into an elephant. And then gradually turn it into its long-lost relative, the woolly mammoth. No. Because they're related.
But the woolly mammoth is over. Well, right. But if you know the woolly mammoth genome, which they do because they apparently got 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. So if you can in effect go backwards in time and make changes, then obviously I think you can go the other way too.
I mean, humans are good at design. We're designing animals. So if 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, or 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 supposed to get enough to do that.
Well, there's no winged pig lab. You know, the best you can hope for right now is the woolly mammoth lab. And that's down the hall from where the real action is. But now there's a hall.
And at the end of the hall is a winged pig lab. It has 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 anyone realize that that's really what we're talking about.
Well, because you can't make winged pigs just because of sort of evolutionary barriers, okay? Well, there's no reason for Mr. Fly except for the joke. Calm down.
Calm down. I'm just joking. Okay, I don't think that we need a federal department of homeland big-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 that are going to be able to grab onto cancer cells and attack their own cancer.
We have to be for that. I mean, you have to be. Well, I don't know. I mean, are you for...
You are tinkering with someone's own body. You are altering their own cells. You know? Dude.
Where do I... It's just... I don't know if it's a religious thought or just a thought of a conservative person. 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 a Hobbesian view of human beings, that there is something about human beings, including scientists, 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. 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 like, 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, some 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 can say like, okay, now we're going to outlaw this. I'm not just suggesting that. Well, what are you suggesting that? I think we should cringe a little bit.
Let's just have a big pause. Right. That's all cringe. Ready?
Don't make fun of it. I think you've cringed. Now what? What are we doing now?
I don't know. Are we all cringe? If that's what you're arguing. No, you cringed.
You cringed. You cringed. And you cringed. You cringed with attitude.
I'm cringing with. I would like. Because you're afraid of like dragons. You're saying.
You're saying. Oh my God. Yes, I'm afraid of dragons now. 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 be in an end? Well, one of the lines that had been drawn by Jennifer Dowden and others was that we should not use the technology of humans who haven't been born yet. Meaning not on sperm cells or egg cells, because if you crisper 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 and their 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 can affect the evolution of organisms. And 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. 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 Sun Yatsun 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, it was to stop any of us from going further. Biologists and bioethicists are sounding alarm. The scientists face accusations that they crossed an ethical line. That's a sort of thing could be sort of a slippery slope towards...
Sort of designer babies, essentially genetically engineering the human race. Sure. It's kind of such a joke. Okay.
Now that the cringe party had spread and Robert couldn'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 down-putting, I feel that I should do a small little parade called the... Not remember the Alamo.
It's like, remember China. And you should just begin any time you want, like getting on your knees and saying, how sorry are you? Can you start from here? I'm sorry.
So are we actually surrounded by an army of clones with superpowers? Not yet. Yeah, 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...
Maybe it was last week, even writing for a national degree. I think it was. Maybe it was somebody named Carl who said that the newsroom China and that news was probably the beginning of an entire new era. I think I actually said it was a historical moment.
Yes, right. Yes. And I still stand by that. Do you feel differently now than the first time we talked?
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. Where mammals?
This was bound to happen. And in fact, it may be happening more than we think. One account in the journal Nature 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 kind of kind of surprising, that the CRISPR work as 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 a lot of them, CRISPRs 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. We're sort of, 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. And 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 Doudna 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.
You know, now I'm going to sound like I'm on Robert's side of this. I mean, OK, so. It won't hurt. It won't hurt.
It won't hurt. OK, all right. Here we go. 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, you know, 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 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 demonstrated. 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 biologist at Jed's cocktail party couldn't have been more pressured when you think about it. This is one of the strange cases where you do a story.
Usually 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. And so what we did is we asked our producer, everyone, we learned 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's like it takes an active role in the fictional narrative of the show. Oh, okay. Oh, like she's a cop or something.
She's like some sort of 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.
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. Okay.
So moving, putting JLo aside. Yeah. Let's do some science developments. There's got to have been quite a few of them.
We know there have been a few of those, right? Yeah. 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 humans.
It's being used in 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 leads 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 syringe full of viruses and just stick it in people's eyes. So of course, when we did the update, Sorin and I called Carl Zimmer. Yeah.
Things are moving very fast. And what kinds of things? So they are doing things that look like curing diseases. Carl told us about one study where it seems like they cured a certain type of muscular dystrophy in mice.
Wow. Well, they might not 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 is 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. 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 step at this point. Yeah. This is literally like one of the first experiments to show that this approach could work in muscular dystrophy.
Wait, I mean, that's not a disease with a cure, is it? Not until potentially in mice now. Yeah. Yeah.
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. Do they think they can, what, cure lung cancer? Well, no, 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 Doudna's team, out at UC Berkeley. The one we just heard from.
The West Coast team. And then on the other side is this group of researchers at the Broad Institute, which is an East Coast. And so basically they both filed for a CRISPR patent. Okay.
So there was sort of this East Coast West Coast for the last year showdown. Yeah. And just last week, the US Patent Office decided that it would indeed go to Broad. This is the not Doudna team.
The not Doudna 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 of over CRISPR patents, there has been a Gettysburg, but the war is not won.
There are many more battles, I think, that will happen. Okay. Gotcha. Yeah.
Is there anything else on the list of like what's happening now, exciting stuff happening now? Oh, yeah. Oh, can we do a favorite story? Can I do my favorite?
Can I do your favorite? Can you do your favorite? My favorite game from Carl. Yeah, yeah.
They're actually trying to use it as an alternative to antibiotics. Wait. How did anyone understand what that means? What are you saying?
I was like an antibiotic to me. It's 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.
You would turn the assassins on the bacteria. Exactly. So there you go. Wow.
Yeah, the antibiotic thing seems huge, right? Because everyone's at this moment where they're like, what happens with the next super bug? Right. If you could actually just go in there and kamikaze the DNA of like staff or whatever, he'd be solving a lot of illnesses.
Yeah. Okay. So the coolest thing I guess for me, oh, maybe the scariest too. How are you?
I'm doing great. How are you? Came from a conversation that we had with this guy, Kevin. I'm Kevin Esvelte.
Esvelte. Esvelte. I'm at the MIT Media Lab. He was sort of on the early edge of thinking about CRISPR.
I mean, 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 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. It's so hard, right?
It wasn't possible. 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 called the Emerald Necklace in Boston.
It's beautiful and there's a small river flowing through it and you have these ponds and turtles and whatever. 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.
Maybe this is the 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. Fed 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 is 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 tree. Oh, because only one of those two genes gets expressed in the baby. And then in the next generation, the grandbaby, there's only a 25% chance and, you know, on and on and on. So you're exponentially losing CRISPR powers.
Your chances just each generation get less and less of 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.
Yeah. Instead of just sniff 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 put like a spare scissor 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 the 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.