Transcript

Speaker 2: Hey, you're lis-

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Speaker 3: You're listening-

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Speaker 3: ... to Radiolab.

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Speaker 2: WNYC.

Speaker 3: C?

Speaker 2: Yeah.

Kevin Esvelt: Let me tell you, there is nothing like the sheer elation of discovery. And I think you know this is the end of malaria. This is the end of everything else, mosquitoes spread. Wait a minute, tick spread Lyme disease. We can probably get rid of that too.

Soren Wheeler: So in the morning, you're like woo hoo.

Molly Webster: You're singing to the turtles in the park and ...

Kevin Esvelt: Pretty much and I give myself a full day of being woohoo and then I started thinking but, but, but, but what if something goes wrong?

Jad Abumrad: I'm Jad Abumrad.

Robert Krulwich: I'm Robert Krulwich.

Jad Abumrad: This is Radiolab and the guy that you just heard is Kevin Esvelt. He is a scientist. He was talking to our producers, Soren Wheeler and Molly Webster about CRISPR.

Robert Krulwich: Which is a technology. Actually it's a new... it's a gene editing technology that can reshape life, actually.

Jad Abumrad: Yeah. And we ended up doing an entire show about this.

Soren Wheeler: Yeah. And we called it Antibodies part one.

Jad Abumrad: I don't remember that.

Robert Krulwich: As if there was going to be a part two.

Molly Webster: That's [inaudible 00:01:33]. It's like telling someone you got them a birthday present, but you haven't yet.

Soren Wheeler: Yeah.

Jad Abumrad: Yeah it's true.

Soren Wheeler: May be we should just own up. Radiolab listeners we did not get your birthday present.

Jad Abumrad: Let's just- That seems mean. No, we meant to.

Robert Krulwich: Yes we did.

Jad Abumrad: We meant to have a part two. But we were doing a story it fell apart.

Robert Krulwich: Well, life doesn't always work out.

Jad Abumrad: We got it on tape, sucked frankly. And we thought it was going to be story. It just turned out to be a story.

Robert Krulwich: But now we have ... what going to do is, we're going to pay you what you're due.

Jad Abumrad: This is the part two.

Robert Krulwich: Yeah, this is the part two.

Jad Abumrad: Finally, part two. Because CRISPR in the time that we did the thing till now has gone banana crazy.

Robert Krulwich: Yeah so much has happened really.

Jad Abumrad: Yeah. Every day in the science section, which I know we all read religiously, if there is a CRISPR thing. 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.

Robert Krulwich: Yeah, yes.

Jad Abumrad: Let me explain to you how I got started with this.

Robert Krulwich: You were in some kind of an affair?

Jad Abumrad: Yeah. I'll tell you how ... I was at a party.

Robert Krulwich: Party.

Jad Abumrad: It was a conference where they had a lot of different people of different disciplines come together. You know, one of those. Their panel discussions, various thing. We were at one of the functions. And it was a situation where dinner hadn't yet been served. And there was a lot of booze being served. So everybody was drunk on an empty stomach. I was standing there was some biologists.

Robert Krulwich: Oh they're the fun ones, the drunk biologists, yes.

Jad Abumrad: As my people barely. They started to lose their shit, like genuinely lose their shit about this thing called CRISPR. I've never seen scientists this excited about anything. So I was like, What is this thing? What is CRISPR? And they were trying to explain 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 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?"

Carl Zimmer: You want me to sit here as usual?

Speaker 8: Yeah. If you seat here I will get up. [inaudible 00:03:47] imply in any way.

Carl Zimmer: No, no.

Speaker 8: We've been sitting here together.

Jad Abumrad: So what happened was I came back and I immediately called science writer Carl Zimmer. Because I just figured for this kind of thing. It's a Carl thing. I got to talk to Carl. I basically asked him like why all the fuss, maybe it was just the alcohol or but maybe there's something really happening here?

Carl Zimmer: Oh, there's something totally happening here. I mean, it's big.

Jad Abumrad: He started at the beginning.

Carl Zimmer: You can actually find like the first reference to CRISPR, in 1987 paper from some Japanese scientists. They basically described something weird in E. coli and they said, we don't know what this is.

Jad Abumrad: E. Coli are a 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-

Carl Zimmer: They found this really strange stretch of DNA.

Speaker 4: Strange how?

Carl Zimmer: Well, 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.

Jad Abumrad: These little blurbs, it'd be like ...

Carl Zimmer: And they looked at this and they were like, "What? This is nothing like we've seen before."

Jennifer Doudna: Repeated sequences in bacterial genomes are kind of unusual.

Carl Zimmer: Seems very strange.

Jennifer Doudna: Some biologists felt that there must be a purpose for these.

Jad Abumrad: Among those purpose seekers.

Jennifer Doudna: Jennifer Doudna, University of California, Berkeley.

Jad Abumrad: She's a cell biologist.

Jennifer Doudna: Yeah.

Jad Abumrad: So it's Doudna, not Dudna?

Jennifer Doudna: It's Doudna. I used to be called the dude, sometimes in school.

Robert Krulwich: In the movie, she will be played by Jeff Bridges.

Jad Abumrad: Right, anyhow. As time goes on, scientists are seeing these little repeats, blurb repeats everywhere.

Carl Zimmer: Yes.

Jad Abumrad: [inaudible 00:05:44] some bacteria.

Carl Zimmer: Lots and lots of, lots of species of bacteria. They say, Okay, wait a minute.

Jennifer Doudna: That's kind of cool.

Carl Zimmer: They're finding it so often that they said they had to give it a name.

Jad Abumrad: And this is where the name CRISPR comes from?

Carl Zimmer: Yes.

Jad Abumrad: The full official name is, Clustered Regularly Inter-spaced, short Palindromic Repeats.

Jennifer Doudna: Clustered Regularly Inter-spaced, short Palindromic Repeats.

Jad Abumrad: Oh, my God.

Carl Zimmer: I don't know why they called it CRISPR. It's kind of a-

Robert Krulwich: CRISPR. It's like a furniture manufacturer or something.

Carl Zimmer: It sounds like an app.

Jad Abumrad: Yeah.

Robert Krulwich: Yeah, CRISPR.

Carl Zimmer: CRISPR.

Jad Abumrad: But now, scientists had this puzzle.

Robert Krulwich: If nature at this level, preserve something intact, here, and here, and here, and here, and here, and here. And some of these heres are creatures that have been around for hundreds of millions of years, you figure, well, whatever this is-

Jad Abumrad: It's doing something.

Robert Krulwich: ... it's doing something.

Jad Abumrad: But what?

Carl Zimmer: It doesn't take very long before the first big clue comes up.

Jad Abumrad: All right, fast forward. 2005. Now scientists have these big searchable databases of DNA sequences systems. 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.

Carl Zimmer: And the scientists are using computers to just line up these stretches of DNA with thousands and thousands of different species and then click, all of a sudden, they discover-

Jad Abumrad: That those bits of DNA between the repeats, the stuff in the middle, those blurbs.

Carl Zimmer: These are matching virus DNA. Like you can find viruses with genes where these little-

Jad Abumrad: So these bacteria had virus inside of them?

Carl Zimmer: Yep.

Robert Krulwich: Does that mean that a virus brought it into this cells? Did they tell you anything about the origin of it?

Carl Zimmer: 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.

Jad Abumrad: Which is a little weird, if you think about it. I mean, these are totally different creatures. They would be inside a human finding a little bit of mosquito DNA.

Robert Krulwich: How do we interpret this?

Carl Zimmer: Well, actually, there was one scientist named Eugene Koonin, who looked at these results and just said, "Okay, I get it. It's a defensive system."

Jad Abumrad: Why would you think that?

Carl Zimmer: Because he's a brilliant man.

Robert Krulwich: 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 like a [inaudible 00:08:15].

Carl Zimmer: Well, you see, that metaphor might sort of betray your lack of skill in microbiology. I'm just saying, 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.

Robert Krulwich: Right?

Carl Zimmer: If your bacteria viruses make your life a nightmare. Think about in the ocean, okay? The ocean is full of viruses and viruses kill up to 40% of all of those bacteria every day.

Jad Abumrad: Really?

Carl Zimmer: Every day.

Robert Krulwich: Wow.

Carl Zimmer: Yeah. And we know that they have defenses. What Eugene Koonin 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."

Robert Krulwich: Like little Polaroid shots of the enemy.

Carl Zimmer: Right.

Robert Krulwich: Know the enemy?

Carl Zimmer: Yeah, like a most wanted poster.

Eugene Koonin: What we called the mug shot.

Jad Abumrad: This is Eugene Koonin.

Eugene Koonin: Leader of the evolutionary genomics group at the National Center for Biotechnology Information.

Jad Abumrad: He's the guy that Carl referenced to [inaudible 00:09:34] up the whole idea that maybe these bits of virus DNA inside the bacteria is the bacteria trying to defend itself.

Eugene Koonin: What really, if I would credit myself with anything here, it was not so much guessing this because ... then you see the identical sequence, that gets pretty obvious. It is figuring out how the mechanism are likely to work.

Jad Abumrad: So can you walk us through how the mechanism is likely to work?

Eugene Koonin: All right? What happens if-

Carl Zimmer: When a virus comes in to a cell, they just kind of explodes and kind of releases naked genes, basically.

Jad Abumrad: If you're this bacteria, these things might take over your cells, you've got to respond.

Eugene Koonin: Most of the time, you have multiple weapons of defense.

Jad Abumrad: If 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.

Eugene Koonin: But much of the time they fail and then no one will hear about you again.

Jad Abumrad: They're not terribly sophisticated fighters. So very often, virus takes over, the bacteria dies.

Eugene Koonin: But there is some non-zero probability that you actually survived the attack.

Jad Abumrad: 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.

Eugene Koonin: And then cut the enemy DNA into [futable 00:11:16] small pieces.

Jad Abumrad: 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.

Eugene Koonin: Right there and nowhere else.

Robert Krulwich: So I use those spaces in my own DNA as a storage facility?

Eugene Koonin: Yes, if you will, you use it as a memory device.

Jad Abumrad: Because here's what happens. Next time, that virus shows up, it sprays it's genes everywhere, and now you are prepared. And this is where the CRISPR story really gets going. Because instead of sending out the ground troops, who are probably going to get their asses beat. Now you can actually send out the big guns. And in fact, what the cell does is it will manufacture the special molecular assassins. And will give those assassins a copy of that little bit of virus DNA has in stores basically saying, "Here, take this mug shot. If you see anything that matches this pattern, kill it."

Robert Krulwich: Kill. And these attackers, do we know what they look like ... one of them looks like?

Jennifer Doudna: Yep. So we know what the protein looks like. It actually looks, I would describe it a little bit like a clamshell.

Jad Abumrad: Sort of, imagine Pac Man but kind of misshapen and rough. And each one of these guys-

Carl Zimmer: What it has is a copy of that virus DNA.

Jad Abumrad: It's got the mug shot.

Carl Zimmer: That it's kind of waving around. What then happens is that-

Jad Abumrad: Whenever the Pac Man bumps into some virus DNA-

Carl Zimmer: It pulls apart the DNA and zips it-

Jad Abumrad: Reads it. If it's not the right one, it goes on. Nope. Uh-uh (negative).

Carl Zimmer: And if that RNA has the same sequence, then click, click, it just locks in.

Jennifer Doudna: And if that happens, then the DNA is trapped. And molecular blades come out.

Carl Zimmer: And chop.

Eugene Koonin: Cutting it's head with the mighty blow.

Carl Zimmer: Yeah.

Robert Krulwich: So this is smart scissors.

Jad Abumrad: 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.

Carl Zimmer: All right, now we're going to kill.

Jad Abumrad: It has to be.

Carl Zimmer: And it has to be an exact match.

Jad Abumrad: When scientists first discovered this whole system. They were fascinated.

Carl Zimmer: They were working it out. They were like, "Oh, okay, then this happens. And this happens. And this happens. Cool."

Jad Abumrad: But then in walks-

Jennifer Doudna: The dude.

Jad Abumrad: Jennifer Doudna with a crazy idea. One of if it is crazy but radical.

Jennifer Doudna: This could be an amazing technology.

Carl Zimmer: This is a tool.

Jad Abumrad: This is a tool?

Carl Zimmer: Yeah.

Jennifer Doudna: Right?

Carl Zimmer: This is a tool that we can use to cut DNA where we want to cut DNA.

Jad Abumrad: The 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 mug shot. Maybe I could just replace what's on their mug shot. Instead of them going after viruses, maybe they could go after a gene that causes Huntington's disease or hemophilia. For example, this is actually something that's been done. You got a mouse with something like hemophilia. This is a diseases that's caused by one bad gene. So what you do is you take these little surgeons, you give them the mug shot for the bad gene, then you stick the surgeon with the new mug shot in a mouse.

Carl Zimmer: Then you set it loose.

Jad Abumrad: And just like its program to, it will find that gene-

Carl Zimmer: And click, click, chop. The scissors will end up cutting exactly the gene you wanted to cut.

Jad Abumrad: So the bad genes gone. Now the question is how do you put in the good gene?

Robert Krulwich: Right.

Jad Abumrad: It turns out actually, according to Jennifer Doudna that that's actually not as hard as you would think.

Robert Krulwich: Really?

Jad Abumrad: Yeah, apparently what you do is just throw this new good gene, kind of in the neighborhood of where the old genius used to be. Just in the general vicinity.

Jennifer Doudna: You don't have to get super precise. It turns out that, they're repair enzymes that are probably continually surveying and checking for breaks.

Jad Abumrad: She says what will happen is it inside the cell, these repair crews come along, they'll see the break. They'll see the good genes just sitting there next to the break. They'll be like, All right. I'll just stick it in.

Carl Zimmer: But the pretty guy in this space.

Jad Abumrad: Exactly.

Jennifer Doudna: So we take advantage of a natural repair pathway that cells have.

Jad Abumrad: They trick both the cutters and the fixers.

Carl Zimmer: Yeah, now we're not assassinating anymore. Now we're actually engineering. We're going from killing to refashioning.

Robert Krulwich: Haven't we been designing genes, doing genetic ... a form of genetic engineering for, like 30 years?

Carl Zimmer: Yes, but not like this.

Beth Shapiro: Genome editing technologies have been around for a long time, but none of them have been as powerful as CRISPR is.

Jad Abumrad: That's Beth Shapiro from UC, Santa Cruz. She was actually one of the biologists that I drunkenly talked to at that thing.

Beth Shapiro: Was it a modern art museum? I can't even really remember it.

Jad Abumrad: I don't remember either.

Robert Krulwich: Must have been quite an evening, get to have the setting be so vague.

Jad Abumrad: Anyhow. Here's how she put it to us. Back in the day. This is just like two years ago. You would have these gene editor things. You would take one, put it in a cell.

Beth Shapiro: 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.

Jad Abumrad: So it's like, "You just take a right at Staten Island. But it takes a left.

Beth Shapiro: And not only would it take a left to 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 it's really easy.

Jad Abumrad: You just give it that mug shot.

Beth Shapiro: And it goes. I'm going to find that guy exactly.

Jad Abumrad: So 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."

Carl Zimmer: You can use the same CRISPR system on anything.

Robert Krulwich: Can you like do it if corn is vulnerable-

Carl Zimmer: Do it in corn.

Robert Krulwich: ... to a certain pest? You can do it in corn?

Carl Zimmer: Do it in corn, do it in anything. I am waiting for someone to say CRISPR doesn't work in species x. And I have not heard with that.

Jad Abumrad: So basically, what you have for the first time in science is this gene editing technology that is cheap, precise, impossibly universal. And Jennifer Doudna says, "The moment the full impact of that landed on her ...

Jennifer Doudna: I really I literally had the hairs on the back of my neck, we're standing up. Just processing the fact that this thing exists, 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.

Robert Krulwich: 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.

Jad Abumrad: Do you see this cloud in the horizon?

Robert Krulwich: I see it's getting sort of dark over there. But we'll be right back.

Lauren: 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. More information about sloan at www.sloan.org.

Pat Walters: Hey, everybody, Pat Walters here. I'm a producer at Radiolab. And I'm here because I need your help. This summer, I'm hosting a series of stories on the show. And I have requests for those of you who spend a lot of time with kids. Parents, aunts and uncles, teachers. We're looking for stories about what we're calling tiny moments of childhood brilliance. Basically, I want to hear about those times when a kid you know did something that just made you lean back and say, "Well, how did they do that?" Maybe it was the moment that a kid you'd been reading to for a month started reading back to you. Or maybe the kid was at piano lessons and you suddenly noticed they were doing advanced math on the margin of their musical score. Or maybe the kid was in math class and you notice they're writing music in the margin of their geometry homework.

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Jad Abumrad: This is Radiolab, I'm Jad Abumrad

Robert Krulwich: I'm Robert Krulwich.

Jad Abumrad: 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? What if you could actually go back in time and resurrect long lost creatures? I mean, this is something that Beth Shapiro has talked about a lot.

Beth Shapiro: 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 a chicken into that thing.

Jad Abumrad: Or what if you could take an elephant and snip, snip, snip, gradually turn it in to its long lost relative, the woolly mammoth.

Robert Krulwich: No.

Jad Abumrad: Because they're related. But the gene is similar.

Robert Krulwich: But the woolly mammoth is over.

Jad Abumrad: 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?

Robert Krulwich: If you can, in effect, go backwards in time and make changes. And obviously, I think you can go the other way, too. Humans are good at design, we're designing animals. 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.

Jad Abumrad: We sort of got into all this with Carl Zimmer, the science writer.

Robert Krulwich: 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 sophisticated enough to do that.

Jad Abumrad: There's no winged pig lab. 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 at.

Robert Krulwich: But now there's a hall. And at the end of the hall is a winged pig lab.

Jad Abumrad: No.

Robert Krulwich: It hasn't been built, yeah. It may be 20 years from now, but that's what you're looking at?

Carl Zimmer: Well, but the thing is-

Robert Krulwich: What's wrong with the thought? Why shouldn't anyone realize that that's really what we're talking about?

Carl Zimmer: Well, because you can't make winged pigs. Just because of sort of evolutionary barriers. Okay?

Robert Krulwich: Well, there's no real reason for pigs to fly except for the joke?

Carl Zimmer: No, no. Gentleman calm down. Calm down. I don't think that we need a federal Department of Homeland pig with wings security. I think we're okay there, all right. Well, what we do need is, we do need to figure out what are we going to do about CRISPR in humans. They're going to be using CRISPR for cancer, okay? They're going to take people's immune cells out body, and they're going to use CRISPR to basically allow them to make proteins. They're going to be able to grab on to cancer cells and attack their own cancer.

Robert Krulwich: Really? Wow.

Carl Zimmer: Yeah.

Robert Krulwich: There has to be for that. I mean, you have to be.

Jad Abumrad: Well, I don't know. I mean, are you for ... that is your-

Robert Krulwich: You are tinkering with someone's own body. You are altering their own selves.

Jad Abumrad: Dude.

Robert Krulwich: Where do I ... it's just ... I can't even. 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. I remember being astonished that, no. 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 Hobbes·i·an view of human beings. That there is something about human beings, including scientists human beings, all human beings. 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 light and dark of humans. And that will be new in the world.

Carl Zimmer: 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, "Science is going to be both about learning about how the world works, and using that knowledge to control it." 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 outlaw this."

Robert Krulwich: I'm not suggesting that.

Carl Zimmer: What are you suggesting then?

Robert Krulwich: I think we should cringe a little as opposed to just having a big pile.

Carl Zimmer: Okay. All right. Let's all cringe. Ready, one, two, three.

Robert Krulwich: Don't make fun of me. No, no that's fair.

Carl Zimmer: Now what, we've cringed, now what? What do we do now?

Robert Krulwich: I don't know.

Jad Abumrad: We all cringed. If that's what you're arguing for, we cringed too.

Robert Krulwich: No, you cringed meanly and you cringed with attitude. I am cringing with-

Jad Abumrad: I would like to know-

Carl Zimmer: Because you're afraid of like dragons. You're saying, "Oh my God."

Robert Krulwich: Yes. I'm afraid of dragons now that-

Jad Abumrad: Okay. That conversation with Carl was four months ago. And a lot has happened in that time. Because, to the question that you asked, where does the sacred beginning and end? Well, one of the lines that had been drawn by Jennifer Doudna 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-

Jennifer Doudna: That is a permanent change, right? That is a change to the DNA that will be passed on to their children.

Jad Abumrad: And their children's children and their children's, children's children.

Jennifer Doudna: And you can't ask the person if that's okay, because you're doing it before they're born.

Jad Abumrad: Consent becomes a real issue. And if you imagine making these changes, and they cascade through generation after generation.

Jennifer Doudna: 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.

Jad Abumrad: Wow.

Jennifer Doudna: It's kind of profound. I feel it's really profound.

Jad Abumrad: Profound, but it was just an idea. That is until.

Speaker 16: For the first time in history, researchers in China have successfully edited the human genome and an embryo.

Jad Abumrad: Just two months ago, it was announced that a Chinese team-

Speaker 16: From [inaudible 00:27:39] University use a technique called CRISPR.

Speaker 17: To edit DNA in human embryos.

Speaker 18: It's a way of hacking evolution itself.

Speaker 17: Well, this is hugely controversial.

Jad Abumrad: Now, these embryos, the Chinese team had edited they were created through IVF and they were not viable.

Jennifer Doudna: These are embryos that are not going to actually develop into a person. So they're going to be discarded anyway.

Jad Abumrad: But still if they can figure it out with those embryo, what's to stop any of us from going further?

Speaker 16: Biologists and bioethicist are sounding an alarm.

Speaker 17: The scientists face accusations that they crossed an ethical line.

Robert Krulwich: That sort of thing could be sort of a slippery slope towards-

Jennifer Doudna: Towards designer babies.

Eugene Koonin: Essentially, genetically engineering the human race.

Speaker 17: [crosstalk 00:28:19]. Okay.

Jad Abumrad: Now that the cringe party had spread, and Robert didn't seem like such a loon, we call up Carl again.

Robert Krulwich: But 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 [crosstalk 00:28:43] remember the [inaudible 00:28:45] I think, remember China. And you have to ... you should just begin anytime we want, like getting on your knees and saying how sorry you are then we can start from there.

Carl Zimmer: I'm sorry. We are actually surrounded by an army of clones with superpowers?

Jad Abumrad: Not yet.

Robert Krulwich: Not yet. But I think the dike has been open. I believe I'm going to quote somebody who said maybe a few weeks ago. Maybe it was last week he's been writing for National geographic. 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.

Carl Zimmer: I think I actually said it was a historical moment.

Robert Krulwich: That's right. Yes.

Carl Zimmer: Yes. And I still stand by that.

Jad Abumrad: Do you feel differently now than the first time we talked?

Robert Krulwich: Yeah, that's really the question.

Carl Zimmer: I don't feel different, actually. Because I didn't really know, scientific superiority is here.

Jad Abumrad: He says, people who have been doing all these CRISPR experiments in all these different mammals.

Carl Zimmer: We're mammals.

Jad Abumrad: This is bound to happen. And in fact, it may be happening more than we think. One account in the journal Nature said that for 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.

Carl Zimmer: It works, kind of. In only a few of the cases did they really get exactly what they wanted.

Jad Abumrad: They tried using CRISPR and about 86 embryos, and they only got it to work right in maybe 28. And in a lot them CRISPR has made the wrong cuts and screwed up the cells.

Beth Shapiro: 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.

Carl Zimmer: We're still are in this kind of fortunate position where we can say, "Oh, well, it's dangerous." 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, 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.

Jad Abumrad: In fact, Jennifer Doudna told us that this experiment or similar experiments had 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.

Carl Zimmer: Sometimes I feel like we're sort of displacing all our ethical concerns onto something that hasn't happened yet. We really are concerned about what we're doing to the human gene pool. It's already here.

Jad Abumrad: 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.

Carl Zimmer: And when people started doing IVF, there was a huge controversy. People said this was dangerous. This is unnatural. I don't see peoples who are unable to sleep at night because of the existence of IVF. Now, I'm going to sound like I'm on Robert side of this. I mean, okay.

Robert Krulwich: It won't hurt.

Carl Zimmer: Okay. All right. Here we go.

Robert Krulwich: Deep breath.

Carl Zimmer: You guys know about all the stuff going on in Iceland, where they're looking at people's DNA, and 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 no, 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?

Jad Abumrad: Sure yeah.

Carl Zimmer: Or would you like your child to face a future of Alzheimer's? Your choice?

Jad Abumrad: 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?

Robert Krulwich: That's what he just was demonstrating. Yeah.

Jad Abumrad: We've already answered the question.

Carl Zimmer: Yeah, we may have.

Robert Krulwich: So that's how we ended our piece, which is now two years old.

Jad Abumrad: Roughly.

Robert Krulwich: Roughly. And the drunk biologists at Chad's cocktail party couldn't have been more pressured. When you think about it.

Jad Abumrad: This is one of those 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.

Robert Krulwich: Unbelievable.

Jad Abumrad: That we figured we need to update this thing.

Robert Krulwich: Yeah.

Jad Abumrad: And so what we did is we asked our producer editor Soren Wheeler and our producer, Molly Webster, to sort of just go out, ask around, make some calls and tell us, what's been going on.

Robert Krulwich: Well, for one, Molly, do you want to give them the big news?

Molly Webster: That Jennifer Lopez is going to do a Television show based on CRISPR?

Jad Abumrad: No.

Molly Webster: It takes an active role in the fictional narrative of the show.

Robert Krulwich: Okay.

Jad Abumrad: Oh, like she's a cop or something?

Molly Webster: Yes. She's like some sort of ... I don't know-

Jad Abumrad: And she's been attacked by-

Molly Webster: ... medical something and CRISPR is involved.

Jad Abumrad: Really?

Molly Webster: Yeah. That got big headlines.

Robert Krulwich: Let me show you this scissors.

Jad Abumrad: Wow. It's crossed over to that extent?

Molly Webster: 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.

Jad Abumrad: That's amazing.

Molly Webster: Yeah.

Jad Abumrad: Okay, putting J-lO aside.

Robert Krulwich: Yeah, let's do some science developments. There got to have been quite a few of them. We know there have been a few of those, right?

Jad Abumrad: Yeah, would you run us through that.

Molly Webster: I mean, I guess I would just say that it's being used everywhere now. It's being used in crops. It's being used in medicine. It's being used in basic research. It's being used-

Robert Krulwich: Humans.

Molly Webster: ... in humans.

Robert Krulwich: In cows.

Jad Abumrad: Really?

Molly Webster: It's being used in eyeball.

Jad Abumrad: In eyeball?

Molly Webster: Yeah, they want to start a clinical trial with actually injecting a syringe full of CRISPR carrying viruses into your eyeball to overcome a genetic condition, that leads to blindness.

Jad Abumrad: This would be like the virus is injecting the CRISPR that then goes and cuts out the bad genes?

Molly Webster: Yeah, exactly.

Carl Zimmer: Just take a big syringe full of viruses and just stick it in people's eyes. Yeah.

Molly Webster: Of course, when we did the update, Soren and I called Carl Zimmer.

Carl Zimmer: Yeah, things are moving very fast.

Robert Krulwich: And what kinds of things?

Carl Zimmer: They are doing things that look like curing diseases?

Molly Webster: Carl told us about one study, where it seems like they cured a certain type of muscular dystrophy in mice.

Robert Krulwich: Cured muscular dystrophy?

Jad Abumrad: They cured Muscular Dystrophy in mice? Wow.

Robert Krulwich: Well, then mice don't become normal mice, but they get much, much stronger than they would have been?

Molly Webster: 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 genome mutation and so that protein's not made.

Carl Zimmer: And the result is that your muscles start to turn into sort of a fat like substance. That's how it's been described.

Molly Webster: [inaudible 00:36:17] with no power?

Carl Zimmer: Yeah.

Molly Webster: Okay.

Carl Zimmer: Your diaphragm gets weaker and weaker, your heart gets weaker.

Molly Webster: In this case, they use CRISPR, to fix that gene. So you get the protein in these mice, and they actually saw, 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.

Robert Krulwich: Really?

Jad Abumrad: Are they going to do that in humans?

Robert Krulwich: Pretty first step at this point, but-

Carl Zimmer: Yeah, this is literally like one of the first experiments to show that this approach could work in muscular dystrophy.

Jad Abumrad: Wait, I mean that's not a disease with a cure? Is it?

Robert Krulwich: Not until potentially in mice now.

Molly Webster: Yeah.

Robert Krulwich: Wow.

Molly Webster: Yeah.

Carl Zimmer: And there are some human trials that have either started or are probably going to start soon, treating cancer.

Molly Webster: For example, people are talking about one in lung cancer.

Robert Krulwich: They think they can, what? Cure lung cancer?

Molly Webster: 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 brakes on the immune cell.

Carl Zimmer: And so you're taking your immune cell off the leash, and it can attack tumors more aggressively.

Robert Krulwich: I see. The folks who invented this then must stand to earn a fortune I think?

Molly Webster: Oh, billions. There's actually a big patent dispute, that's happening right now.

Robert Krulwich: Right now?

Jad Abumrad: Yeah. This is the one thing that I have heard about a lot.

Molly Webster: If you had been checking your CRISPR inbox you might have seen last week. There were two teams, Jennifer Doudna team out at UC Berkeley.

Robert Krulwich: The one we just heard from?

Jad Abumrad: Yeah.

Molly Webster: Sort of the West Coast team. And then on the other side, is this group of researchers at the Broad Institute, which is on the east coast. And so basically, they both filed for a CRISPR patent. There was sort of this East Coast, West Coast for the last year showdown. And just last week, the US Patent Office decided that it would indeed go to Broad.

Jad Abumrad: This is the not Doudna team?

Molly Webster: 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.

Jad Abumrad: In the Civil War of over CRISPR patents, there has been a Gettysburg, but the war is not won.

Molly Webster: There have been a battle. But there are many more battles I think that will happen.

Jad Abumrad: Okay got you.

Molly Webster: Yeah.

Jad Abumrad: Is there anything else on the list of what's happening now? Exciting stuff happening now?

Robert Krulwich: Oh, yeah.

Molly Webster: Can we do a favorite song? Can I do my favorite?

Robert Krulwich: You can do your favorite.

Molly Webster: And then you can do your favorite?

Robert Krulwich: Yeah, sure.

Molly Webster: So my favorite came from Carl?

Carl Zimmer: Yeah, yeah, they're actually trying to use it as an alternative to antibiotics.

Molly Webster: How? I don't even understand what that means.

Jad Abumrad: What are you saying?

Molly Webster: I was like an antibiotic to me as a pill that I take. What would CRISPR ... How would CRISPR replace that?

Carl Zimmer: Well, your pill would have CRISPR in it?

Robert Krulwich: How would it work?

Molly Webster: 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?

Carl Zimmer: You could pick out some super essential gene that it has, and chop it, and that will kill the bacteria.

Robert Krulwich: Oh, you would turn the assassins on the bacteria?

Molly Webster: Exactly.

Carl Zimmer: So there you go.

Robert Krulwich: Wow.

Molly Webster: Yeah, the antibiotic thing seems huge, right?

Jad Abumrad: Yeah, that's pretty amazing.

Molly Webster: Because everyone's 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 stuff or whatever? You'd be solving a lot of illnesses.

Robert Krulwich: Yeah.

Jad Abumrad: What's [crosstalk 00:40:03], your story? What's your?

Robert Krulwich: The coolest thing, I guess for me-

Speaker 21: Hello.

Robert Krulwich: Maybe the scariest too.

Jad Abumrad: Hi, Kevin.

Kevin Esvelt: Hi [inaudible 00:40:10].

Molly Webster: How are you?

Kevin Esvelt: I'm doing great. How are you?

Robert Krulwich: Came from a conversation that we had with this guy Kevin.

Kevin Esvelt: I'm Kevin Esvelt.

Molly Webster: Esvelt.

Robert Krulwich: [inaudible 00:40:15].

Kevin Esvelt: I'm at the MIT Media Lab.

Robert Krulwich: He was sort of on that early edge of thinking about CRISPR.

Kevin Esvelt: I think of myself as an evolutionary engineer before anything else.

Robert Krulwich: Got into biology, because when he was a kid, he went to the Galapagos.

Kevin Esvelt: 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.

Molly Webster: You actually thought, "I want to make organisms as beautiful as that?"

Kevin Esvelt: Yeah.

Molly Webster: What?

Kevin Esvelt: But then that's like the childhood vision. And then it's so hard, right? It was impossible. And so you sort of forget it. But now with CRISPR, almost all things become possible.

Robert Krulwich: 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.

Kevin Esvelt: 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.

Robert Krulwich: There's turtles and whatever, geese and he's thinking about CRISPR, and what it can do, and all these different animals that are around him. And he has this thought.

Kevin Esvelt: What if we could encode CRISPR in the genome? What if we program the genome to do genome editing on its own?

Jad Abumrad: Wait, what? I'm not sure I follow that, what is it? What is he saying?

Kevin Esvelt: Well, the first gene drive system-

Robert Krulwich: 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.

Kevin Esvelt: That would be great.

Robert Krulwich: 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 into the wild, and it's got to fend for itself amongst all the other mosquitoes. 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 trait.

Kevin Esvelt: Because only one of those two genes gets expressed.

Robert Krulwich: Right, in the baby. And then in the next generation, the grand baby, there's only a 25% chance and on, and on and on.

Jad Abumrad: So you're exponentially losing CRISPR powers.

Robert Krulwich: Your chance is just each generation get less and less that this gene is going to stick around.

Kevin Esvelt: That's right, because regardless of what we do natural selection wins in the end.

Robert Krulwich: Until, Kevin is walking to work through the park and has his idea, which is to use CRISPR to create something called a-

Kevin Esvelt: A gene drive.

Robert Krulwich: Gene drive.

Kevin Esvelt: Gene drive.

Robert Krulwich: Yeah.

Kevin Esvelt: 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.

Robert Krulwich: 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.

Jad Abumrad: Like you're putting a spare scissors or something?

Robert Krulwich: Yeah. And here's how that plays out. Your first mosquito has this gene with the new change. And it also has the scissors. And then it meets a normal mosquito, which has the normal gene. The to 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 snippet, and turn it into itself. Now there's two copies of the new gene.

Kevin Esvelt: 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.

Jad Abumrad: Oh, interesting.

Kevin Esvelt: Like I set it on autopilot.

Jad Abumrad: So you're basically allowing them the mosquito parent, to pass the scissors to the baby?

Kevin Esvelt: Yap.

Jad Abumrad: Which then snip, snip, snip. And then that baby passes the scissors to the next baby snip, snip, snip.

Robert Krulwich: Yap, yap.

Jad Abumrad: And it is literally like a chain reaction.

Kevin Esvelt: Yeah. And so from baby to grand baby, to great grand baby. Now, instead of letting that gene disappear, you're driving it into the next generation.

Jad Abumrad: And then that just keeps going down the line, down the line, down the line.

Molly Webster: Yes.

Kevin Esvelt: This is something that spreads indefinitely.

Robert Krulwich: This gene is going to spread like wildfire through the entire wild population. 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 the entire species.

Jad Abumrad: So this idea of the mosquitoes and watching it rampage through a population, have they've done this?

Kevin Esvelt: After we first published the idea, we tried it in Yeast. Worked on the first try.

Robert Krulwich: They just plopped a little yeast loaded with the gene drive into a population to see if it would take over and-

Kevin Esvelt: One week later. Yep.

Robert Krulwich: Kevin told us there are probably now I think it's 10 different groups, who are working on gene drive systems?

Molly Webster: Yes, they are doing it in mosquitoes and in parasitic worms and in rodents. It's all happening in the lab.

Robert Krulwich: But still they are trying out this method for spreading genes through a population.

Kevin Esvelt: Yeah.

Molly Webster: I just think that sounds terrifying. 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.

Kevin Esvelt: I'm very glad you think that way. 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 think, this is the end of malaria, this is the end of everything else mosquitoes spread. Wait a minute, tick spread Lyme disease, we can probably get rid of that too. I thought.

Robert Krulwich: So in the morning, you're like, woo hoo.

Molly Webster: You're singing to the turtles in the park.

Kevin Esvelt: Pretty much. I give myself a full day of being who. And then I started thinking, but, 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, okay, what eats those mosquitoes and what eats those things?

Robert Krulwich: 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.

Kevin Esvelt: And that's a incredibly complex system, and you just don't know.

Robert Krulwich: 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 somehow makes it easier to carry some other disease.

Kevin Esvelt: So is it even likely to go wrong? No, but how do you know.

Molly Webster: 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.

Robert Krulwich: And his team is only working with this version of gene drive that they sort of rigged it. So that it only lasts for a certain number of generations, and it sort of runs out of steam.

Kevin Esvelt: 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? Well, I think what this technology forces us to recon 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?

Molly Webster: Yeah.

Carl Zimmer: If and when somebody uses CRISPR on an embryo and that embryo goes up into a person, that will be a momentous thing but if you were to gene drive somebody, think about that. Gene drive like say a few people and not tell them and they have kids and so on. You would be driving whatever gene it is that you are engineering into more and more people. And that's different.

Jad Abumrad: God you know what I'm thinking about the thing that Jennifer Doudna said. I think it was her in our first piece about ... If you make a change in 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.

Molly Webster: Yes.

Jad Abumrad: 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 unfathomable.

Robert Krulwich: Exactly. I guess we're all for taller, but we're not all for taller. In the end it has something to do with democracy itself. 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.

Jad Abumrad: Thank you to Soren Wheeler and Molly Webster for the update. And to I guess all the people we thanked the first time, because I think it still stands.

Robert Krulwich: It still stand.

Jad Abumrad: Many thanks to science writer Carl Zimmer who has written many books. You can check them out at Carlzimmer.com or at Radiolab.org. This piece was produced by Molly Webster. We had original music this hour by Erik Kowalski otherwise known as casino versus Japan.

Robert Krulwich: Special thanks to honor [inaudible 00:50:43].

Jad Abumrad: Lee McGuire.

Robert Krulwich: Dr. Blake Wiedenheft.

Jad Abumrad: Dr. Luciano Marraffini.

Robert Krulwich: Dr. Sean Burgess.

Jad Abumrad: And Dr. Jin [inaudible 00:50:50]. I'm Jad Abumrad.

Robert Krulwich: I'm Robert Krulwich.

Jad Abumrad: Thanks for listening.

Robert Krulwich: 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 what she'd expected. You might want to check that out at the sporkful.com.

Speaker 23: To here's the message again press two, to delete it- start of message.

Carl Zimmer: Hello this is Carl Zimmer.

Beth Shapiro: Hi, this is Beth Shapiro.

Jennifer Doudna: Hello this is Jennifer Doudna.

Beth Shapiro: Radiolab is produced by Jad Abumrad.

Carl Zimmer: Our staff includes Brenna Farrell, Ellen Horne, Dylan Keefe.

Beth Shapiro: Matt Kielty, Lynn Levy,

Carl Zimmer: Andy Mills.

Beth Shapiro: Latif Nasser, Melissa O'Donnell, Kelsey Padgett,

Jennifer Doudna: Ariane Wack, Molly Webster.

Carl Zimmer: Soren Wheeler, and Jamie York. I think I said Wabster, let me try it again.

Jennifer Doudna: With help from Danny Luis, Kelly Prime and Damiano Marchesi.

Beth Shapiro: Our fact-checkers are Eva Dasher and Michelle Harris.

Jennifer Doudna: Awesome.

Beth Shapiro: Thank you much.

Carl Zimmer: Later.

Speaker 23: End of message.