Update: CRISPR

Summary

Radiolab – Update: CRISPR

Date: February 24, 2017
Hosts: Jad Abumrad, Robert Krulwich
Key Contributors: Carl Zimmer, Jennifer Doudna, Beth Shapiro, Kevin Esvelt, Soren Wheeler, Molly Webster

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Episode Overview

This episode of Radiolab revisits one of the most transformative discoveries in modern biology: CRISPR, a gene-editing technology with the potential to reshape life itself. The hosts reflect on the explosion of CRISPR news and research since their first episode, discuss ethical quandaries, recent landmark experiments, and the astonishing promise—as well as dangers—of tools that could let humanity rewrite evolution.

The program is part catch-up, part philosophical debate, and part news update, featuring discussions with scientists and science writers at the cutting edge of CRISPR research.

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Key Discussion Points and Insights

1. Origin and Mechanism of CRISPR

[02:13]–[18:19]

• Discovery:
  • Scientists noticed repeated DNA sequences of unknown purpose in E. coli in 1987.
  • Carl Zimmer and Jennifer Doudna explain how researchers eventually realized these "blurp repeats" (CRISPRs) were part of a bacterial defense mechanism, storing viral DNA snippets as "mugshots" to recognize and destroy future viral invaders.
    • Jennifer Doudna: “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.” [17:50]
• Gene Editing Tool:
  • CRISPR/Cas9 system allows for highly precise, cheap, and universally applicable genetic engineering.
  • Past genetic editing tools were expensive, imprecise, and slow—now, costs have dropped from ~$5,000 to ~$75.

2. Potential and Hype

[20:12]–[21:59]

• Hosts and guests imagine extreme possibilities:
  • Reviving extinct species (e.g., “turn a chicken into a dinosaur” [20:28], “CRISPR out… elephant and put in woolly mammoth” [20:53]).
  • “Designer” animals and humans (e.g., making taller children, stronger muscles [21:08]).
• Carl Zimmer grounds expectations: making “winged pigs” is evolutionarily implausible, but real changes in existing species are possible.

3. Ethical Concerns and Social Implications

[22:17]–[27:15]

• The debate over “designer babies” and germline editing:
  • Editing embryos would create permanent, heritable genetic changes.
    • Jennifer Doudna: “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.” [25:54]
  • The issue of consent: making genetic decisions for the unborn and future generations.
    • Jad Abumrad: “Consent becomes a real issue.” [26:05]
• Notable Moment: Chinese researchers edited non-viable human embryos using CRISPR, sparking international debate.

4. What Happens When Technology Leaps Ahead?

[27:27]–[32:24]

• The China embryo experiment revealed the CRISPR process is still error-prone (success in only 28 out of 86 embryos [29:09]), but this is expected to change as the technology improves.
• Comparison to IVF: initial controversy, now normalized; raises concern that germline gene editing could follow a similar path to social acceptance.
  • Carl Zimmer: “If we really are concerned about what we’re doing to the human gene pool, you know, it’s already here.” [30:14]

5. CRISPR Goes Mainstream and Scientific Landmarks

[33:00]–[38:00]

• CRISPR is now being used in crops, medicine, basic research, and livestock.
  • Notable anecdote: Even Jennifer Lopez is starring in a CRISPR-based TV drama! [33:04]
• Medical advances:
  • Early success in using CRISPR to treat muscular dystrophy in mice, resulting in dramatic muscle strength improvements. [34:44]
  • Human clinical trials are now beginning—e.g., in cancers, using CRISPR-edited immune cells to fight tumors [35:56].
  • Massive patent battles between teams led by Jennifer Doudna (UC Berkeley) and the Broad Institute (MIT/Harvard) over who owns the rights to CRISPR’s use. [36:42]

6. Alternative Applications and the “Gene Drive” Concept

[37:58]–[45:11]

• Antibiotic Alternative:
  • CRISPR could act as a targeted bacterial assassin, killing deadly pathogens without affecting others.
  • Soren Wheeler: “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.” [38:17]
• Gene Drive—the Scariest and Wildest Application:
  • Kevin Esvelt describes a way to engineer not just individuals but entire species, by passing CRISPR and its edit “instructions” down through generations (gene drive).
  • Could eradicate malaria by altering mosquito populations, but carries profound risks to ecosystems if something goes awry.
  • Kevin Esvelt: “What if we could encode CRISPR in the genome? … Program the genome to do genome editing on its own?” [40:13]
  • Esvelt: “This gene is going to spread like wildfire through the entire wild population. See, you don’t change just one mosquito… You change all of those insects, probably everywhere in the world.” [43:42]

7. Escalating Ethical Stakes and the Problem of Consent

[45:47]–[48:22]

• Editing an embryo is already contentious because it’s done without that individual’s consent; gene drive could make irreversible changes to entire populations, including untold future generations, without their knowledge or permission.
  • Jad Abumrad: “Now you’re doing it without the consent of that unborn thing and all future generations of that unborn thing. And so the consent issues just become like...unfathomable.” [48:08]
  • Robert Krulwich: “...with this gene drive, in the act of choosing it for yourself… you choose it for an uncountable number of others who do not have the choice.” [48:22]

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Notable Quotes & Memorable Moments

• Carl Zimmer:

  • “These attackers, do we know what one of them looks like?”
    – Jennifer Doudna: “It actually looks, I would describe it a little bit like a clamshell, sort of imagine Pac-Man, but kind of misshapen and rough.” [12:09]
  • On CRISPR’s universality: “You can use the same CRISPR system on anything.” [17:20]

• Jennifer Doudna:

  • “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… it cuts DNA wherever I want.” [17:50]

• Kevin Esvelt:

  • “Let me tell you, there is nothing like the sheer elation of discovery… This is the end of malaria… And then I started thinking, but, but, but, but…what if something goes wrong?” [00:19 & 45:15]
  • “What if we could encode CRISPR in the genome? … Program the genome to do genome editing on its own?” [40:13]
  • “Without any human assistance, CRISPR will cut the original version and copy over the change.” [42:44]
  • “One person [could] decide to change the local or possibly the global environment. And that’s… ethically problematic, right?” [46:42]

• Robert Krulwich (on ethics):

  • “I don’t know where the sacred begins and ends anymore on that particular turf… There's an angelic side to being human and there's a very, very dark side… That future will include the imaginations, both light and dark, of humans. And that will be new in the world.” [23:08–24:22]

• Jad Abumrad:

  • “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.” [31:51]
  • “Now you’re doing it without the consent... of all future generations... The consent issues just become, like, unfathomable.” [48:08]

---

Timeline of Key Segments

• 00:19–18:19: The mechanism and discovery of CRISPR; explanation by Carl Zimmer and Jennifer Doudna.
• 20:12–21:59: The science fiction possibilities and the line between excitement and caution.
• 22:17–27:15: The “designer baby” debate, China’s controversial embryo experiment, and the problem of heritable change.
• 27:27–32:24: Discussion of precaution, humanity already crossing lines (IVF precedent), and personal/cultural acceptance.
• 33:00–38:00: CRISPR in pop culture, medicine (cancer, muscular dystrophy), agriculture, and massive patent fights.
• 37:58–41:41: CRISPR as a new kind of antibiotic; introduction to gene drive.
• 41:46–45:11: Gene drives’ mechanism and the possibility (and risk) of editing entire species.
• 45:47–48:22: The ultimate ethical challenge: gene drive, consent, and changes at the species level.
• 49:11+: Episode wrap-up and credits.

---

Summary

“Update: CRISPR” is a whirlwind tour through one of the most consequential stories in biology. The episode clearly outlines not just how CRISPR works and its rapidly expanding applications, but also the ethical, social, and philosophical questions it forces us all to confront. With its lively, sometimes humorous tone, Radiolab makes complex molecular biology and bioethics accessible, memorable, and urgent. The episode closes with the realization that CRISPR’s potential is limited only by our collective imagination and restraint—and now, as the technology races ahead, humanity must decide how (or whether) to steer it.

Transcript

[Jad Abumrad]

Oh, wait, you're listening.

[Robert Krulwich]

Okay.

[Jad Abumrad]

All right. Okay.

[Alex Honl]

All right. You're listening to Radiolab Radio Lab from wny.

[Carl Zimmer]

See?

[Jad Abumrad]

Yep.

[Kevin Esvelt]

Let me tell you, there is nothing like the sheer elation of discovery. And I was thinking, you know, this. This is the end of malaria. This is the end of everything else. Mosquitoes spread, which. Wait a minute, you know, ticks spread Lyme disease. We can probably get rid of that, too.

[Alex Honl]

I thought so. In the morning, you were like.

[Soren Wheeler]

You were singing to the turtles in the park and.

[Kevin Esvelt]

Pretty much. And I gave myself a full day of being who. 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, which is a technology.

[Robert Krulwich]

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.

[Alex Honl]

Yeah. And we called it Antibodies, Part one.

[Jad Abumrad]

I do remember that.

[Alex Honl]

As if there was gonna be a part two.

[Soren Wheeler]

Name that. It's like telling someone you got them a birthday present, but you haven't yet.

[Robert Krulwich]

Yeah, it's true.

[Alex Honl]

Maybe we should just own up. Radiolab listeners. We did not get you a birthday present.

[Jad Abumrad]

Let's just. Let's just. That seems mean. No, we meant to. We meant to have a part two, but, you know, we were doing a story, it fell apart.

[Robert Krulwich]

Life doesn't always work out.

[Jad Abumrad]

The tape sucked, frankly. And we thought it was gonna be a story. It just didn't turn out to be a story.

[Robert Krulwich]

But now we have. What we're 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]

Has happened. Really?

[Jad Abumrad]

Yeah. Like, every day in the science section, which I know we all read religiously, there is a CRISPR thing.

[Robert Krulwich]

Yeah.

[Jad Abumrad]

So just to get us started, we're gonna play you the original piece, for those of you who never heard it, just to sort of set the baseline, and then we're gonna come back and tell you all the stuff that has happened since.

[Robert Krulwich]

Yeah. Yes.

[Jad Abumrad]

All right, so let me explain to you how I got. Got started with this.

[Robert Krulwich]

You were some kind of an affair.

[Jad Abumrad]

Yeah. So 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. There are panel discussions of various things. And 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, so everybody was, like, drunk on an empty stomach. So I was standing there with some biologists.

[Robert Krulwich]

Well, they're the fun ones, the junk biologists.

[Jad Abumrad]

Yes, as my people, apparently. And they. They started to lose their shit, like, genuinely lose their shit about this thing called crispr. And, like, I have never seen scientists this excited about anything. So I was like, what is this thing? What is crispr? And they were trying to explain it to me, but they couldn't slow down enough for me to get it. I gathered it had something to do with genetics. And then at one point, one of the biologists turned to me and he was like, I'll tell you what it is. I can use CRISPR to take a little dog and poof. Make it into a big dog. Give me a Chihuahua. I could turn it into the size of a Great Dane. And I was like, no, you can't. He's like, yes, I can. I could do it with crispr. I was like, what the hell is this thing?

[Carl Zimmer]

You want me to sit here as usual? Yeah, if you sit here, I will get out.

[Jad Abumrad]

Didn't mean to imply in any way.

[Carl Zimmer]

No, no, no, no. We'd be 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, this is a Carl thing. I gotta talk to Carl. So 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]

So you can actually find, like, the first reference to CRISPR. In a 1987 paper from some Japanese scientists, they basically described something weird in E. Coli. And they said, we don't know what this is.

[Jad Abumrad]

E Coli are bacteria inside humans. And like all living things, E. Coli is made up of DNA A's and T's and C's and G's. And what happened was that these scientists were reading a chunk of that genetic.

[Carl Zimmer]

Code when they found this really strange stretch of DNA.

[Jad Abumrad]

Strange how?

[Carl Zimmer]

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.

[Jad Abumrad]

These Little blurps would be like.

[Carl Zimmer]

And they looked at this and they're 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, you know, there must be a purpose for these. Among those purpose seekers, Jennifer Doudna, University of California, Berkeley.

[Jad Abumrad]

She's a cell biologist. Yeah. 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 start seeing these little repeat blurp repeats everywhere.

[Carl Zimmer]

Yes.

[Jad Abumrad]

Or at least some bacteria.

[Carl Zimmer]

Lots and lots and lots of species of bacteria, they say. Hm. Okay, wait a minute.

[Jennifer Doudna]

That's kind of cool.

[Carl Zimmer]

They're finding it so often that they decided they had to give it a name.

[Jad Abumrad]

Is this where the name CRISPR comes from?

[Jennifer Doudna]

Yes.

[Carl Zimmer]

The full official name is clustered regularly.

[Jennifer Doudna]

Interspaced short palindromic repeats.

[Jad Abumrad]

Oh, my God.

[Carl Zimmer]

I don't know why they called it crispr. It's kind of a crispr.

[Jad Abumrad]

It's like a furniture manufacturer or something.

[Carl Zimmer]

It sounds like an app.

[Jad Abumrad]

Yeah, yeah.

[Carl Zimmer]

Crispr. Crispr.

[Jad Abumrad]

But now scientists had this puzzle.

[Robert Krulwich]

If nature at this level preserves something intact here and here and here and here and here and here. And some of these heres are. Are creatures that have been around for hundreds of millions of years. You figure, well, whatever this is, it's doing something. It's doing something.

[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. So some scientists think, well, let's do a search. Let's see if these repeating patterns we keep finding match anything else that's out there in the world.

[Carl Zimmer]

And these scientists are using computers to just line up these stretches of DNA with thousands upon thousands of different species. And then click, all of a sudden.

[Jad Abumrad]

They discover that those bits of DNA between the repeats, the stuff in the.

[Carl Zimmer]

Middle, those blurps, these are matching virus DNA. Like you can find viruses with genes where these little, you know, these little.

[Jad Abumrad]

So the bacteria had virus inside of them?

[Carl Zimmer]

Yep.

[Robert Krulwich]

Does that mean that a virus brought it into these cells? Does it 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, which is a.

[Jad Abumrad]

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.

[Robert Krulwich]

How do we interpret this?

[Carl Zimmer]

Well, actually, there was one scientist, his name is Eugene Koonin, who looked at these results and just said, okay, I get it. It's a defense system.

[Jad Abumrad]

What?

[Robert Krulwich]

Why would he 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 just like a bit of human.

[Carl Zimmer]

Right. Well, you see, that metaphor might sort of betray your lack of skill in microbiology. I'm just saying, like, this is not a dump, all right?

[Alex Honl]

This is.

[Carl Zimmer]

Bacteria are not gonna just let virus DNA get into their genes willy nilly. Okay? Remember, viruses are the big enemy, right? If you're bacteria, viruses make your life a nightmare. Think about 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? Yeah. And we know that they have defenses. What Eugene Koonin said was, okay, I'm gonna 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 the those viruses if they come in later.

[Robert Krulwich]

It's like little Polaroid shots of the enemy, right? Know thy enemy.

[Carl Zimmer]

Yeah, like a Most Wanted poster. What you call the mugshot.

[Jad Abumrad]

This is Eugene Koonin, leader of the.

[Carl Zimmer]

Evolutionary Genomics Group at the national center for Biotechnology Information.

[Jad Abumrad]

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.

[Carl Zimmer]

But really, if I would credit myself with anything here, it was not so much guessing this, because, you know, when you see these identical sequences, that gets pretty obvious. It is figuring out how the mechanism was likely to work.

[Jad Abumrad]

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

[Carl Zimmer]

All right. What happens is, you know, when a virus comes in to a cell, it just kind of explodes and just kind of releases naked genes.

[Jad Abumrad]

Basically, if you're this bacteria, these things might take over your cell. So you've got to respond.

[Carl Zimmer]

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.

[Carl Zimmer]

And they fight really hard, 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 the virus takes over, the bacteria dies.

[Carl Zimmer]

But there is some non zero probability that you actually survive 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, and then.

[Carl Zimmer]

Cut the enemy DNA into suitable 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 right there and nowhere else.

[Robert Krulwich]

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

[Carl Zimmer]

Yes, if you will, you use it as a memory device, because here's what.

[Jad Abumrad]

Happens next time that virus shows up, sprays its genes everywhere. 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 these special molecular assassins, and it'll give those assassins a copy of that little bit of virus DNA it has in storage, basically saying, here, take this mugshot. If you see anything that matches this pattern, kill it.

[Robert Krulwich]

Ew. And these attackers, do we know what 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, sort.

[Jad Abumrad]

Of imagine Pac man, but kind of misshapen and rough. And each one of these guys, what.

[Carl Zimmer]

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.

[Jad Abumrad]

Pac man bumps into some virus DNA.

[Carl Zimmer]

It pulls apart the DNA, unzips it reads it.

[Jad Abumrad]

If it's not the right one, it goes on. Nope.

[Robert Krulwich]

Mm.

[Jad Abumrad]

Mm.

[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, cutting its head with a mighty blow.

[Robert Krulwich]

Yeah.

[Alex Honl]

Wow.

[Robert Krulwich]

So this is smart scissors.

[Jad Abumrad]

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.

[Carl Zimmer]

All right, now we're gonna kill.

[Jad Abumrad]

Oh, I see.

[Carl Zimmer]

And it has to be exact. It has to be an exact match.

[Jad Abumrad]

When scientists first discovered this whole system, they were fascinated.

[Carl Zimmer]

They were like. They were working it out. They were like, oh, okay. Then this happens. And this happens. This happens. Cool.

[Jad Abumrad]

But then in walks the dude. Jennifer Doudna with A crazy idea. Well, I don't know if it's crazy, but radical.

[Jennifer Doudna]

This could be an amazing technology.

[Carl Zimmer]

This is a tool.

[Jad Abumrad]

This is a tool.

[Jennifer Doudna]

Yeah, Right?

[Carl Zimmer]

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

[Jad Abumrad]

Her basic thought was, why don't we turn this defense into offense? Because these things, they seem to be really good at cutting, and yet they only seem to cut the things that are on their mugshot. So maybe I could just replace what's on their mugshot. So instead of them going after viruses, maybe they could go after a gene that causes Huntington's disease or hemophilia, for example. And this is actually something that's been done. Say you 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 mug shot for the bad gene, then you stick the surgeon with the new mug shot in a mouse, then you set it loose, and just like it's programmed 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 gene's gone. Now the question is, how do you put in the good gene? Right.

[Robert Krulwich]

Right.

[Jad Abumrad]

It turns out, actually, according to Jennifer Dowd, now, 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 gene used to be, just in the general vicinity.

[Jennifer Doudna]

You don't have to get super precise. I mean, it turns out that, you know, there are repair enzymes that are probably continually surveying and checking for breaks.

[Jad Abumrad]

She says what'll happen is that inside the cell, these repair crews, they'll 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.

[Robert Krulwich]

Put the pretty guy into space.

[Kevin Esvelt]

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've gone from killing to ref. Fashioning.

[Robert Krulwich]

Although haven't we been designing genes, doing genetic. A form of genetic engineering for, I don't know, like, 30 years?

[Jad Abumrad]

Yes, but not like this.

[Soren Wheeler]

Genome editing technologies have been around for a long time, but none of them have been as powerful as crispr.

[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.

[Soren Wheeler]

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

[Jad Abumrad]

I don't remember either.

[Robert Krulwich]

Must have been quite an evening to have the setting be so vague.

[Jad Abumrad]

Anyhow, here's how she put it to us back in the day. This was just like two years ago. You would have these gene editor things. You would take one, put it in.

[Soren Wheeler]

A cell, and what happened before was you would give it some instructions about where to go, and it might go there, but it might go to somewhere that's kind of related to where that was.

[Jad Abumrad]

So it's like, take a right at Staten island, but it takes a left.

[Soren Wheeler]

And not only would it take a left at Staten island and not find there, but it would have cost you a fortune and taken up six months of your time to get that thing. And now, you know, it's really easy.

[Jad Abumrad]

You just give it that mugshot and.

[Soren Wheeler]

It goes, I'm going to find that guy. Exactly.

[Jad Abumrad]

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. Crisper, 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 to certain pests, you can do it in corn, do.

[Carl Zimmer]

It in corn, do it in anything. I have not. I'm waiting for someone to say crispr doesn't work in species X, and I have not heard of that.

[Jad Abumrad]

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.

[Jennifer Doudna]

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 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 over there.

[Jad Abumrad]

Do you see?

[Robert Krulwich]

I see it's getting sort of dark over there, but we'll be right back.

[Jad Abumrad]

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.

[Carl Zimmer]

More information About [e-mail].

[Alex Honl]

Radiolab is supported.

[Jad Abumrad]

By Planet Visionaries, the podcast created in partnership with the Rolex Perpetual Planet Initiative. Stay tuned for a trailer and subscribe.

[Alex Honl]

Wherever you get your podcasts. I'm Alex Honl, professional rock climber and.

[Carl Zimmer]

Founder of the Honl Foundation. I wanted to let you know about a brand new season of the Planet Visionaries podcast in partnership with the Rolex Perpetual Planet Initiative.

[Alex Honl]

This is the podcast exploring bold ideas.

[Carl Zimmer]

And big solutions from the people leading the way in conservation.

[Alex Honl]

Join me in conversation with the likes of climate champion Mark Ruffalo, biologist and.

[Carl Zimmer]

Photographer Christina Mittermeier, and one of the.

[Alex Honl]

Most successful conservationists of our time, Chris Tompkins.

[Carl Zimmer]

Join us on Planet Visionaries.

[Alex Honl]

Wherever you get your podcasts, you should.

[Jad Abumrad]

Tell the people who we are and.

[Carl Zimmer]

What our new show is.

[Kevin Esvelt]

I'm Robert Smith and this is Jacob.

[Robert Krulwich]

Goldstein and we used to host a show called Planet Money and now we're.

[Carl Zimmer]

Back making this new podcast about the.

[Kevin Esvelt]

Best ideas and people and businesses in.

[Robert Krulwich]

History and some, some of the worst people, horrible ideas and destructive companies in.

[Carl Zimmer]

The history of business.

[Robert Krulwich]

We struggled to come up with a name, decided to call it business history.

[Kevin Esvelt]

You know why?

[Robert Krulwich]

Why?

[Jad Abumrad]

Because it's a show about the history.

[Kevin Esvelt]

Of business, available everywhere you get your podcasts.

[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? Like 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.

[Soren Wheeler]

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 CRISPRs to turn a chicken into that thing.

[Jad Abumrad]

Or what if you could take an elephant and snip, snip, snip, gradually turn it into its long lost relative, the woolly mammoth? No, because they're related. But if you're.

[Robert Krulwich]

But the woolly mammoth is over, well, right?

[Jad Abumrad]

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, then obviously I think you can go the other way too, right? 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, 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, 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.

[Carl Zimmer]

There's no winged pig lab. You know, the best you're going to hope for right now is a woolly mammoth lab. And that's down the hall from where the. 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. It hasn't been built yet. It may be 20 years from now, but that's where what you're looking at.

[Carl Zimmer]

Well, I think. But the thing is that.

[Robert Krulwich]

What's wrong with this, though? Why shouldn't anyone realize that that's really what we're talking about here?

[Carl Zimmer]

Well, because you can't make winged pigs just because of sort of evolutionary barriers. Okay, well, there's no real reason for.

[Robert Krulwich]

Pigs to fly except for the joke.

[Carl Zimmer]

Calm down, calm down.

[Jad Abumrad]

I'm just joking.

[Carl Zimmer]

I mean, okay, I don't think that we need a federal department of homeland pig with wing security. I think we're okay there. All right, well, we do need. Is like, we do need to figure out what are we gonna do about CRISPR in humans? I mean, they're gonna be using CRISPR for cancer. Okay. They're gonna take people's immune cells out of their body and they're gonna use CRISPR to basically allow them to make proteins. They're gonna be able to grab onto cancer cells and attack their own cancer.

[Robert Krulwich]

Yeah, you have to be for that. I mean, you have to be.

[Jad Abumrad]

Well, I don't know. I mean, are you. For that is.

[Carl Zimmer]

You are tinkering with someone's own body. You are altering their own cells. You know, dude, where do I.

[Robert Krulwich]

It's just. I tell you, this is me. I don't know if it's a religious thought or just the thought of a conservative person, but, I mean, I grew up in the test tube baby era. I now know many wonderful adult, formerly test tube babies. And I. 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 scientist human beings, all human beings, that there's a darkness and a light. There's an angelic side to being human, and there's a very, very dark side. Difficult set. 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, someone like Francis Bacon would say explicitly, like, science is going to be both about learning about how the world works and using that knowledge to control it. You know, this has been discovered. This has been published. Everybody knows it exists. If you're going to say, like, okay, now we're going to all. We're going to outlaw this.

[Robert Krulwich]

I'm not suggesting that.

[Carl Zimmer]

Well, what are you suggesting then?

[Robert Krulwich]

I think we should cringe a little as opposed to just have a big party.

[Carl Zimmer]

All right, let's all cringe. Ready? One, two, three.

[Jad Abumrad]

Don't make fun of it.

[Robert Krulwich]

No, no, that's not fair.

[Jad Abumrad]

Now what?

[Carl Zimmer]

We've cringed and 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.

[Robert Krulwich]

No, you cringed. You cringed meanly and you cringed. You cringe with attitude. I'm cringing with.

[Jad Abumrad]

I would like to.

[Carl Zimmer]

Because you're afraid of, like, dragons, you're saying.

[Jad Abumrad]

You're saying.

[Carl Zimmer]

Oh, my God.

[Robert Krulwich]

Yes, I'm afraid of dragons now.

[Jad Abumrad]

Okay, so that conversation with Carl was four months ago. And a lot has happened in that time because to the question that you asked, like, where does the sacred begin and end? Well, one of the lines that had been drawn by Jennifer 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.

[Jad Abumrad]

Children 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, you know, 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.

[Soren Wheeler]

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

[Jad Abumrad]

Just two months ago, it was announced that a Chinese team from Sun Yatsen.

[Soren Wheeler]

University used a technique called CRISPR to.

[Robert Krulwich]

Edit DNA in human embryos. It's a way of hacking evolution itself.

[Jad Abumrad]

Well, this is hugely controversial. Now, these embryos the Chinese teacher 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 could figure it out with those embryos, what's to stop any of us from going further? Biologists and bioethicists are sounding an alarm.

[Robert Krulwich]

The scientists face accusations that they crossed.

[Jad Abumrad]

An ethical line, that this sort of.

[Carl Zimmer]

Thing could be sort of a slippery.

[Jad Abumrad]

Slope towards designer babies, essentially genetically engineering the human race.

[Carl Zimmer]

I'm gonna use it as a chance to kind of test your levels.

[Alex Honl]

Okay.

[Jad Abumrad]

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

[Robert Krulwich]

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. Remember the Alamo. It's like, remember, remember China. And you have to. So you should just begin anytime you want, like getting on your knees and saying how sorry you are. And we can start from there.

[Carl Zimmer]

I'm sorry. So are we actually surrounded by an army of clones with superpowers?

[Robert Krulwich]

Not yet. 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, I think he wrote. Maybe it was last week. He's been writing for National Geographical for. 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 there's really no scientific surprise here.

[Jad Abumrad]

He says people have been doing all these CRISPR experiments on 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 Naturist said that four other Chinese labs are doing this kind of work as we speak. But Carl also told us, which he said was unsurprising, too. But I actually find it kind of surprising that the CRISPR work this Chinese team did didn't work very well.

[Carl Zimmer]

It worked kind of. I mean, in only a few of the cases did they really get exactly what they wanted.

[Jad Abumrad]

They tried using CRISPR in about 86 embryos, and they only got to work right in maybe 28. And in a lot of them, CRISPR's made the wrong cuts and screwed up the cells.

[Jennifer Doudna]

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]

Oh, 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. In 10 or 20 years, you know, CRISPR will be so sophisticated that people will be able to say, I can get you the change you want, and I can do it safely. I can guarantee you that you will have human embryos that have the alteration in the particular gene you want. So then what?

[Jad Abumrad]

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.

[Carl Zimmer]

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.

[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 was unnatural. I don't see people who are unable to sleep at night because of the existence of ivf.

[Kevin Esvelt]

Yeah.

[Carl Zimmer]

You know, now I'm going to sound like I'm on Robert's side of this. I mean. Okay, so. So it won't hurt.

[Robert Krulwich]

It won't. It won't. It will.

[Carl Zimmer]

Okay. All right, here we go. So okay. So breath. So you guys know about all the stuff going on in Iceland where they're looking at people's DNA and, you know, they're looking for disease genes and so on. And when they were looking at these Icelandic people, they found that some people had a gene that protects them against Alzheimer's. It reduces their odds of getting Alzheimer's. Let's imagine your doctor said, now, if you'd like, for an extra thousand dollars, we will take these IVF embryos and we will use CRISPR to give them the Alzheimer protecting variant. Would you like that? Do you want to add that to your. 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]

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 gonna say no to that? Who's gonna say no to that?

[Robert Krulwich]

That's what he just was demonstrating. Yeah.

[Jad Abumrad]

Yeah, 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 Jed's cocktail party couldn't have been more prescient. When you think about it.

[Jad Abumrad]

You know, this is one of those. This is strange cases where, like, you do a story usually, like, we just kind of leave it behind. We move on to other things. But in the last almost two years, so much has happened. Unbelievable that we figured we need to update this thing. 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, you know, what's been going on.

[Alex Honl]

Well, for one. Molly, do you want to give them the. The big news?

[Soren Wheeler]

Jennifer Lopez is gonna do a television show based on crispr.

[Jad Abumrad]

No.

[Soren Wheeler]

You mean it's like it takes an active role in the fictional narrative of the show.

[Robert Krulwich]

Oh, okay.

[Jad Abumrad]

Oh, like she's a cop or something?

[Soren Wheeler]

Yeah, she's like some sort, I don't know, medical something. And CRISPR is involved.

[Jad Abumrad]

Really?

[Soren Wheeler]

Yeah. Let me show you that got big headlines.

[Robert Krulwich]

Let me show you these scissors. Wow.

[Jad Abumrad]

It's crossed over to that extent.

[Soren Wheeler]

That's. The thing is, like, it's.

[Carl Zimmer]

It's.

[Jad Abumrad]

Yeah, I like.

[Soren Wheeler]

I Was like, jennifer Lopez knows about crispr. And she was like, this such a hot button issue. We're doing a show.

[Jad Abumrad]

That's amazing. Okay, so putting J. Lo aside.

[Robert Krulwich]

Yeah. Let's do some science developments. There've gotta have been quite a few of those. We know there have been a few of those, right?

[Jad Abumrad]

Yeah. What are the. Run us through those.

[Soren Wheeler]

I mean, I guess I would just say that it's being used everywhere now. So it's being used in crops, it's being used in medicine, it's being used in basic research. It's being used humans in.

[Jad Abumrad]

Humans in cows, really.

[Soren Wheeler]

It's being used in eyeballs.

[Jad Abumrad]

And Eyeballs.

[Soren Wheeler]

Yeah. They want to start a clinical trial where they're actually injecting a syringe full of crystals carrying viruses into your eyeball to overcome a genetic condition that leads to blindness.

[Jad Abumrad]

So this would be like the viruses injecting the CRISPR that then goes and cuts out the bad genes.

[Soren Wheeler]

Yeah, exactly.

[Carl Zimmer]

Just take, you know, a big syringe full of viruses and just stick it in people's eyes.

[Alex Honl]

Da, da, da, da.

[Carl Zimmer]

Yeah.

[Soren Wheeler]

So, of course, when we did the update, Soren and I called Carl Zimmer.

[Carl Zimmer]

Yeah, it's. Things are moving very fast and.

[Alex Honl]

What kinds of things?

[Carl Zimmer]

So they are doing things that look like curing diseases.

[Soren Wheeler]

So 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.

[Alex Honl]

Wow. Well, then mice don't become normal mice, but they get much, much stronger than they would have been.

[Soren Wheeler]

Yeah. So in your body, you have a gene that makes a protein that gives your muscles strength. But with muscular dystrophy, there's like a typo in that gene, a 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.

[Soren Wheeler]

So you have no power.

[Carl Zimmer]

Yeah.

[Jad Abumrad]

Okay.

[Carl Zimmer]

So your diaphragm gets weaker and weaker, your heart gets weaker.

[Soren Wheeler]

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 get 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?

[Alex Honl]

Pretty first. Pretty first steppy at this point.

[Carl Zimmer]

But yeah, this is literally like, one of the first experiments to show that this approach could work in muscular dystrophy.

[Jad Abumrad]

But, I mean, that's not a disease with a cure, is it?

[Alex Honl]

Not until potentially in mice now.

[Soren Wheeler]

Yeah.

[Jad Abumrad]

Wow.

[Soren Wheeler]

Yeah.

[Carl Zimmer]

And there are some human trials that have either started or are probably gonna start soon treating cancer, for example.

[Soren Wheeler]

People are talking about one in lung cancer.

[Robert Krulwich]

They think they can, what, cure lung cancer?

[Soren Wheeler]

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 brake 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. So the folks who invented this, then must stand to earn a fortune. I mean, I think if.

[Soren Wheeler]

Oh, billions. There's actually a big patent dispute that's happening right now. So one of the.

[Robert Krulwich]

Right now.

[Jad Abumrad]

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

[Soren Wheeler]

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.

[Robert Krulwich]

Oh, the one we just heard from?

[Soren Wheeler]

Yeah, 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.

[Jad Abumrad]

Okay.

[Soren Wheeler]

So there was sort of this, like, 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.

[Soren Wheeler]

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]

So in the Civil War over CRISPR patents, there has been a Gettysburg, but the war is not won.

[Soren Wheeler]

But there are many more battles. I think that will happen.

[Jad Abumrad]

Gotcha.

[Soren Wheeler]

Yeah.

[Jad Abumrad]

Is there anything else on the list of, like, what's happening now? Exciting stuff happening now?

[Alex Honl]

Oh, yeah.

[Soren Wheeler]

Can I. Oh, can I. Can we do favorite? Soren, can I do my favorite?

[Alex Honl]

You can do your favorite.

[Soren Wheeler]

You can do your favorite. So my favorite came from Carl.

[Carl Zimmer]

Yeah.

[Robert Krulwich]

Yeah.

[Carl Zimmer]

They're actually trying to use it as an alternative to antibiotics.

[Soren Wheeler]

Wait, how did I understand what that means?

[Jad Abumrad]

What are you saying?

[Soren Wheeler]

I was like, an antibiotic, to me, is a picture pill that I take. So what would crispr. How would CRISPR replace that?

[Carl Zimmer]

Well, your pill would have CRISPR in it.

[Robert Krulwich]

How would it work?

[Soren Wheeler]

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]

So you could pick out some super essential gene that it has and chop it, and that will kill the bacteria.

[Jad Abumrad]

So it would have. You would turn the assassins on the bacteria.

[Soren Wheeler]

Exactly.

[Carl Zimmer]

So there you go.

[Robert Krulwich]

Wow.

[Soren Wheeler]

Yeah. The antibiotic thing seems huge, right? Because everyone's at this moment where they're like, what happens with the next superbug? If you could actually just go in there and kamikaze the DNA of, like, staph or whatever, you'd be solving a lot of illnesses.

[Jad Abumrad]

Yeah. Well, what's. What's. Okay.

[Soren Wheeler]

Soaring. Your favorite.

[Jad Abumrad]

Yeah. What's your soaring? What's your fave?

[Alex Honl]

So the coolest thing, I guess, for me.

[Jad Abumrad]

Hello.

[Alex Honl]

Maybe the scariest, too. Hi, Kevin.

[Kevin Esvelt]

Hey, Zoe.

[Soren Wheeler]

How are you?

[Kevin Esvelt]

I'm doing great. How are you?

[Alex Honl]

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

[Kevin Esvelt]

I'm Kevin Esvelt.

[Soren Wheeler]

Esvelt.

[Alex Honl]

He's very svelte.

[Kevin Esvelt]

I'm at the MIT Media lab.

[Alex Honl]

He was sort of on the early edge of thinking about crispr.

[Kevin Esvelt]

I mean, I think of myself as.

[Alex Honl]

An evolutionary engineer before anything else got into biology. Because when he was a kid, he went to the Galapagos.

[Robert Krulwich]

Yeah.

[Kevin Esvelt]

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.

[Soren Wheeler]

You actually thought, I want to make organisms as beautiful as that?

[Kevin Esvelt]

Yeah. But then that's like the childhood vision. And then it's so hard. Right. It wasn't possible, and so you sort of forget it. But now with crispr, like, almost, like, all things become possible.

[Alex Honl]

So anyway, to get to the crazy part, Kevin, a couple years back, he's working at the Harvard Medical School, and one day he's walking to work through this park, this park called the Emerald Necklace in Boston.

[Kevin Esvelt]

It's beautiful, and there's a small river flowing through it, and you have these ponds.

[Alex Honl]

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

[Kevin Esvelt]

This thought, 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 he. What is he saying?

[Kevin Esvelt]

Well, the first gene drive system here.

[Alex Honl]

Maybe this is a way to think about it. Let's say that you want to tweak a mosquito and make it so that the little Parasite that carries malaria. Terrible, awful. Malaria either can't get into the mosquito or can't live in it. And so that mosquito will no longer carry malaria.

[Robert Krulwich]

That would be great.

[Alex Honl]

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. 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. Of having your special trait.

[Jad Abumrad]

Oh. Because only one of those two genes.

[Alex Honl]

Gets expressed right 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.

[Jad Abumrad]

So you're exponentially losing CRISPR powers.

[Alex Honl]

Your chances 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.

[Alex Honl]

Until Kevin is walking to work through the park and has his idea, which is to use CRISPR to create something called gene drive. Gene drive?

[Carl Zimmer]

Gene.

[Jad Abumrad]

Gene drive.

[Alex Honl]

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.

[Alex Honl]

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.

[Alex Honl]

Yeah. And here's how that plays out. Your first mosquito has this gene with the new change, and it also has the scissors.

[Jad Abumrad]

Yeah.

[Alex Honl]

And then it meets a normal mosquito which has the normal gene. The two end up side by side in the baby. And now the new mosquito gene makes the little scissors, which go over to the normal gene, snip it and turn it into itself. So now there's two copies of the.

[Kevin Esvelt]

New gene in the offspring. Without any human assistance, CRISPR will cut the original version and copy over the change.

[Alex Honl]

That gene does the work that I used to do in the Lab on its own, inside the baby.

[Jad Abumrad]

Oh, interesting. So, okay, so the.

[Alex Honl]

It's like I set it on autopilot.

[Jad Abumrad]

So you're basically allowing the mosquito parent to pass the scissors to the baby, which then snip, snip, snip, and then that baby passes the scissors to the next baby. Snip, snip, snip. And it is literally like a chain reaction. Yeah.

[Alex Honl]

And so, you know, from baby to grandbaby to great grandbaby. Now, instead of letting that gene disappear, you're driving it into the next generation.

[Jad Abumrad]

And then that just keeps going down the line. Down the line, down the line.

[Soren Wheeler]

Yes.

[Kevin Esvelt]

This is something that spreads indefinitely.

[Alex Honl]

This gene is going to spread like wildfire through the entire wild population. See, you don't change just one. One mosquito.

[Kevin Esvelt]

You change all of those insects, probably everywhere in the world.

[Alex Honl]

According to Kevin, this is the kind of change that could, given enough time, spread across an entire species.

[Jad Abumrad]

Huh. So this, this idea of the mosquitoes and watching it rampage through a population, have they done this?

[Kevin Esvelt]

After we had first published the idea, we tried it in yeast. Worked on the first try.

[Alex Honl]

You know, they just plopped a little yeast loaded with the gene drive into a population to see if it would take over. And one week later, yup. Kevin told us there are probably now, I think it's 10 different groups who are working on gene drive systems.

[Soren Wheeler]

Yes. They are doing it in mosquitoes and in parasitic worms and in rodents. It's all happening in the lab.

[Alex Honl]

But still they are trying out, you know, this, this method for spreading genes through a population.

[Soren Wheeler]

Yeah, I just think that sounds terrifying. Like, honestly, I just keep thinking of, it's like, oh, we've just hit over a domino and then walked away and aren't watching where the rest of them are falling.

[Kevin Esvelt]

I'm very glad you think that. It took me one full day to reach that point. Initially, I was elated. Let me tell you, there is nothing like the sheer elation of discovery. And I was thinking, you know, you know, this is the end of malaria. This is the end of everything else. Mosquitoes spread. Wait a minute. You know, ticks spread Lyme disease. We can probably get rid of that, too.

[Alex Honl]

So in the morning, you were like.

[Soren Wheeler]

You were singing to the turtles in the, in the park, and pretty much.

[Kevin Esvelt]

I gave 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?

[Alex Honl]

You know, it could be that all the frogs or the fish or whatever start to die off, and then that makes something else die off and something else die off.

[Kevin Esvelt]

And that's an incredible, incredibly complex system, and you just. You just don't know.

[Alex Honl]

Or it could be that making a mosquito malaria resistant also somehow makes it do better in some environment, and then the mosquito population blows up, and then it turns out that it somehow makes it easier to carry some other disease.

[Kevin Esvelt]

So.

[Soren Wheeler]

And you're sort of.

[Kevin Esvelt]

Is anything likely to go wrong?

[Soren Wheeler]

Yeah. And you're.

[Alex Honl]

No.

[Kevin Esvelt]

But how do you know?

[Soren Wheeler]

We should say at this point that Kevin is really thinking about all this stuff. He brought together a group of scientists to come up with some safeguards for this type of research so it doesn't escape out of the lab. And.

[Alex Honl]

And his team is only working with this version of gene drive that they. 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 reckon with is that now it's at least theoretically, and again, we don't know for sure, but it's theoretically possible for one person to decide to change the local or possibly the global environment. And that's. That's ethically problematic, right?

[Soren Wheeler]

Yeah.

[Carl Zimmer]

I mean, you know, if. If and when somebody uses CRISPR on an embryo and that embryo grows up into a person, that will be a momentous thing. But if you were to gene drive somebody, think about that, you know, gene drive, like, say a few people and not tell them and, you know, they have kids and so on. Like, and 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, and I'm thinking about the thing that Jennifer Doudna said. I think it was her in our first piece about, like, if you make a change and say, an embryo, like, okay, let me give this. Let me snip, snip, snip, Give this future child, make it taller, whatever. Like, you're doing that without the consent of that unborn child thing.

[Soren Wheeler]

Yes.

[Jad Abumrad]

But if. If you. If you now do what you guys are talking about using this gene drive thing. Well, now you're doing it without the consent of that unborn thing and all future generations of that unborn thing. And so the consent issues just become like. Yeah, unfathomable.

[Robert Krulwich]

Exactly. You know, I guess we're all for taller, but we're not all for taller. So in the end, it has something to do with democracy itself. Like, you sit there with a tool of change in your hand and you choose it, but in the act, with this gene drive, in the act of choosing it for yourself. This way, you choose it for an uncountable number of others who do not have the choice.

[Jad Abumrad]

Thank you to Soren Wheeler and Molly Webster for the update. And so I guess all the people we thanked the first time because those things still stand.

[Robert Krulwich]

Still stand.

[Jad Abumrad]

Many thanks to science writer Carl Zimmer, who's written many books. You can check them [e-mail] [e-mail] this piece was produced by Molly Webster. We had original music this hour by Eric Kowalski, otherwise known as Casino versus Japan.

[Robert Krulwich]

Special thanks to Ana Rasquet, Paz, Lee.

[Jad Abumrad]

Maguire, Dr. Blake Wiedenhalf, Dr. Luciano Maraffini, Dr. Sean Burgess and Dr. Junwei Shi. I'm Jad Abumrad.

[Robert Krulwich]

I am 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 at 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. So you might want to check that out at the Smoke.

[Soren Wheeler]

To hear the message again. Press 2 to delete it. Start of message.

[Carl Zimmer]

Hello, this is Carl Zimmer.

[Soren Wheeler]

Hi, this is Beth Shapiro. Hello, this is Jennifer Doudna. Radiolab is produced by dad Abumrad.

[Carl Zimmer]

Our staff includes Brenna Farrell, Ellen Horn.

[Soren Wheeler]

Dylan Keefe, Matt Kelty, Lynn Levy, Andy Knowles, Latif Nasser, Melissa o', Donnell, Kelsey Padgett, Arianne Wack, Molly Webster, Sean Wheeler and Jamie York.

[Carl Zimmer]

I think I said wa.

[Soren Wheeler]

Let me try it again. With help from Danny Lewis, Kelly prime and Damiano Marchetti. Our fact checkers are Eva Dasher and Michelle Harris. Awesome. Thank you. Much later. End of message.