Jun 6, 2015

Antibodies Part 1: CRISPR
Hidden inside some of the world’s smallest organisms is one of the most powerful tools scientists have ever stumbled across. It's a defense system that has existed in bacteria for millions of years and it may some day let us change the course of human evolution. 

Out drinking with a few biologists, Jad finds out about something called CRISPR. No, it’s not a robot or the latest dating app, it’s a method for genetic manipulation that is rewriting the way we change DNA. Scientists say they’ll someday be able to use CRISPR to fight cancer and maybe even bring animals back from the dead. Or, pretty much do whatever you want. Jad and Robert delve into how CRISPR does what it does, and consider whether we should be worried about a future full of flying pigs, or the simple fact that scientists have now used CRISPR to tweak the genes of human embryos.

As of February 24th, 2017 we've updated this story.

THE LAB sticker

Unlock member-only exclusives and support the show

Exclusive Podcast Extras
Entire Podcast Archive
Listen Ad-Free
Behind-the-Scenes Content
Video Extras
Original Music & Playlists

Jad Abumrad:                  Wait, wait... You're listening to (laughs)

Speaker 2:                          Okay.

Jad Abumrad:                  All right.

Speaker 2:                          Okay.

Jad Abumrad:                  All right. (clears throat).

Speaker 2:                          You're listening to Radiolab, lab, lab.

Speaker 2:                          Radiolab.

Speaker 2:                          From WNYC. C. C.

Speaker 2:                          C.

Speaker 2:                          Yeah.

Speaker 2:                          (laughter)

Speaker 2:                          At NPR.

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

Robert Krulwich:           I'm Robert Krulwich.

Jad Abumrad:                  Guys let me explain to you how I got, got started with this.

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

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

Robert Krulwich:           Party.

Jad Abumrad:                  Uh, it was, it was a conference where there have a lot of different people of different disciplines come together.

Robert Krulwich:           Hmm.

Jad Abumrad:                  You know one of those. Um there were panel discussions of various things. We were at one of the like functions and, uh, 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.

Robert Krulwich:           (laughs) mm-hmm (affirmative).

Jad Abumrad:                  So I was standing there with some biologists.

Robert Krulwich:           Oh they're the fun ones. The junk biologists. Yes.

Jad Abumrad:                  That's my, my people apparently, and, uh, they, uh, we were, they, they started lose their shit, like genuinely lose their shit about this thing called CRISPR. And like I have never seen scientist 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 biologist turned to me and 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."

Robert Krulwich:           (laughs)

Jad Abumrad:                  "Give me a Chihuahua I could turn it into the size of a Great Dane.", and I was like "No, you can't." He was like "Yes I can, I can do it with CRISPR." I was like "What the hell is this thing?"

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

Jad Abumrad:                  Yeah, if you sit here I will get up. I didn't mean to imply in any way.

Carl Zimmer:                    No, no, no.

Jad Abumrad:                  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 got to talk to Carl.

Carl Zimmer:                    (laughs)

Jad Abumrad:                  So I, uh, I basically asked 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, they, the... You, you can actually find like the first reference to CRISPR in a 1987 paper from some Japanese scientist.

Carl Zimmer:                    They basically describe 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 code when...

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

Jad Abumrad:                  Strange how?

Carl Zimmer:                    Well so basically what it was, um, was five identical sequences. (sequence sound) in a row, and then they were separated by very short (loud sound) sequences in between them that were (squawk sound) all different from each other.

Jad Abumrad:                  These little blurbs so it would be like (combined sounds).

Carl Zimmer:                    And they looked at this, and they're 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, you know 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 Doudna.

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

Jad Abumrad:                  (laughs)

Jennifer Doudna:          (laughs)

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

Jad Abumrad:                  Right, anyhow.

Jad Abumrad:                  As time goes on, uh, scientist are seeing these little repeat blurb repeats everywhere.

Carl Zimmer:                    Yes.

Jad Abumrad:                  Or at least in bacteria.

Carl Zimmer:                    Lots, and lots, and lots, and lots species of bacteria they say-

Jennifer Doudna:          Hmm.

Carl Zimmer:                    Okay wait a minute.

Jennifer Doudna:          That's kind of cool.

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

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

Carl Zimmer:                    Yes. The full official name is Clustered Regularly Interspaced Short Palindromic Repeats.

Jennifer Doudna:          Clustered Regularly Interspaced Short Palindromic Repeats.

Jad Abumrad:                  Oh my God.

Robert Krulwich:           Oh.

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

Jad Abumrad:                  CRISPR it's like-

Robert Krulwich:           Furniture.

Jad Abumrad:                  Furniture manufacturer or something.

Robert Krulwich:           Yeah.

Carl Zimmer:                    It sounds like an App.

Jad Abumrad:                  Yeah.

Robert Krulwich:           Yeah. CRISPR.

Jad Abumrad:                  CRISPR. But now scientist have 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 here's are, are creatures that have been around for 100s 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 scientist 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, are using computers to just line up these stretches of DNA with thousands upon thousands of different species, and then click all of a sudden they discover...

Jad Abumrad:                  That's those bits of DNA between the repeats (sounds), the stuff in the middle, those blurbs.

Carl Zimmer:                    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. [crosstalk 00:05:17]

Robert Krulwich:           Is that what that means that a, 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.

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

Robert Krulwich:           How do we interpret this?

Carl Zimmer:                    Well actually there was this 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:                  (laughs) 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-

Jad Abumrad:                  But how do you get to that?

Robert Krulwich:           If I went to a large sanitation dump.

Carl Zimmer:                    Right.

Robert Krulwich:           And I found a teeny bit of human hair.

Jad Abumrad:                  (laughs)

Robert Krulwich:           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, um, that metaphor might sort of betray your lack of skill in microbiology.

Jad Abumrad:                  (laugh)

Carl Zimmer:                    I'm just saying like this is not a dump, all right. This is, bacteria are not going to just let virus DNA get into their genes willy-nilly. Okay.

Carl Zimmer:                    Remember viruses are the big enemy.

Jad Abumrad:                  Right.

Carl Zimmer:                    If you're bacteria viruses make your life a nightmare. Think about in the ocean, okay. The, the ocean is full of viruses and, and, uh, 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.

Carl Zimmer:                    What Eugene Koonin said was, "Okay, I'm going to be 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."

Jad Abumrad:                  Oh.

Robert Krulwich:           Like little Polaroid shots of the enemy.

Carl Zimmer:                    Right.

Robert Krulwich:           Know thy enemy.

Carl Zimmer:                    Yeah, like a most wanted poster.

Eugene Koonin:              What you call the mugshot?

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 that thunk up the whole idea that maybe these bits of virus DNA inside the bacteria is the bacteria trying to defend itself.

Eugene Koonin:              What, what really if I, if I, if I could credit myself with anything here, it was not so much guessing this, because you know when you see these identical signals it gets pretty obvious. It is uh, um, figuring out how the mechanism of light to dark.

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

Eugene Koonin:              All right. What happens is-

Carl Zimmer:                    You know when a virus comes into a cell they just kind of (sound) explodes and kind of releases naked genes basically.

Jad Abumrad:                  If you're this bacteria these things might take over your cells, so 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 say's Eugene, is you send out these enzymes (sounds) to attack the viruses. They're sort of like the ground troops, and they fight really hard.

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

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

Eugene Koonin:              But, but there is some non-zero probability (horn sound) that you actually survive the attack.

Jad Abumrad:                  If you do then what the bacteria will do is send in some enzymes to basically clean up. To go out and find any stray viruses.

Eugene Koonin:              And then cut the enemy DNA into [futable 00:09:07] small pieces.

Jad Abumrad:                  And here he says is where you get to the storage part. Those enzymes will then take those little bits 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. As a, as a, as a, you use it as a memory device.

Jad Abumrad:                  'Cause here what happens. Next time that virus shows up it spreads its genes everywhere, now you are prepared, and this where the CRISPR story really gets going.

Jad Abumrad:                  Because instead of sending out the grounds troops who are probably going to get their asses beat, now you can actually send out the big guns. (music)

Jad Abumrad:                  And in fact what the cell does is it will manufacturer the special molecular assassins. And will give those assassins a copy of that little bit of virus DNA it has in storage, basically saying here take this mug shot, if you see anything that matches this pattern. Kill it.

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

Jennifer Doudna:          Yep, so we know what the protein looks like, it, it, um, it actually looks, I would describe it, um a little bit like a clam shell.

Jad Abumrad:                  Sort of imagine PAC Man but kind of misshapen and rough. In each one of these guys...

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

Jad Abumrad:                  It's got the mugshot.

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's pulls apart the DNA, unzips it.

Jad Abumrad:                  Reads it. If it's not the right one it goes on. (music)

Jad Abumrad:                  Nope. (music)

Jad Abumrad:                  Mm-mm-(negative) (music)

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 its head with a mighty blow.

Robert Krulwich:           Wow.

Jad Abumrad:                  Oh.

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 going to kill.

Jad Abumrad:                  Oh, I see. I see.

Carl Zimmer:                    Yeah, and it has to be exact, it has to be an exact match.

Jad Abumrad:                  When scientist 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, and this happens, cool."

Jad Abumrad:                  But then in walks...

Jennifer Doudna:          The dude.

Jad Abumrad:                  Jennifer Doudna... With a crazy idea. I don't know if it's crazy, but radical.

Jennifer Doudna:          This could be an amazing, uh, 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 thing that are on their mugshots. So maybe I could just replace what's one their mugshots, So instead of them going after viruses maybe they could go after a gene that causes Huntington Disease or Hemophilia.

Jad Abumrad:                  For example and this is actually something that's been done. Say you had mouse with something like Hemophilia.

Robert Krulwich:           Okay.

Jad Abumrad:                  This is a disease that caused by one bad gene. So what you do is you take these little surgeons, you give them the mugshot for the bad gene, then you stick the surgeon with the new mugshot in a mouse.

Carl Zimmer:                    Then you set it loose.

Jad Abumrad:                  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 want it to cut.

Jad Abumrad:                  So the bad gene is 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 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 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, um, you know there are repair enzymes that are probably continually surveying and checking for breaks.

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

Robert Krulwich:           Put the pretty guy in this space.

Jad Abumrad:                  Exactly.

Jennifer Doudna:          So, 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. (music)

Carl Zimmer:                    We've gone from killing to refashioning. (music)

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. (music)

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 biologist that I drunkingly talked to at that thing.

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

Jad Abumrad:                  I don't remember either.

Robert Krulwich:           It must have been quite an evening.

Beth Shapiro:                   (laughs)

Robert Krulwich:           To have the setting be so vague.

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

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 was.

Robert Krulwich:           (laughing)

Jad Abumrad:                  So it's like take a right at Staten Island, but it takes a left.

Beth Shapiro:                   And not only will 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.

Robert Krulwich:           (laughs)

Beth Shapiro:                   And now you know it's really easy.

Jad Abumrad:                  You just give it that mugshot...

Beth Shapiro:                   And 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 you set you back about five grand just to use them once, CRISPR about 75 bucks.

Jad Abumrad:                  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 corn, do it in anything. I have not, I am 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.

Jennifer Doudna:          I really, I literally had, you know the hairs on my back of neck were standing up. (music)

Jennifer Doudna:          Just processing the fact that this thing exists, you know. And that you can 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. (laughs)

Robert Krulwich:           It is amazing unless you think about it further, which we will do in just a moment.

Robert Krulwich:           I feel a cloud coming in over the horizon, over there.

Jad Abumrad:                  (laughs) Do you see?

Robert Krulwich:           I see it's getting sort of dark.

Jad Abumrad:                  Those clouds in the horizon.

Robert Krulwich:           Over there, but we'll be right back.

Laurne:                                Hi, this is Lauren from Atalanta 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.

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

Robert Krulwich:           I'm Robert Krulwich.

Jad Abumrad:                  Okay, so, uh, clearly the possibilities are there to use CRISPR to treat disease.

Robert Krulwich:           Right.

Jad Abumrad:                  Right.

Robert Krulwich:           Mm-hmm (affirmative).

Jad Abumrad:                  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.

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 into it's long lost relative the Woolly mammoth.

Robert Krulwich:           No.

Jad Abumrad:                  Because they're related, but if there, the-

Robert Krulwich:           But the, but the

Jad Abumrad:                  Genes are simple.

Robert Krulwich:           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.

Robert Krulwich:           Yeah.

Jad Abumrad:                  Then you could compare the number of difference, 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. Right, I mean...

Jad Abumrad:                  Mm-hmm (affirmative).

Robert Krulwich:           Humans are good at design, we're designing animals. So if it, 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 of this with, uh, Carl Zimmer, science writer.

Robert Krulwich:           If, 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, you might one day get sophisticated enough to do that.

Carl Zimmer:                    Well, there's no winged pig lab. You know the best you can hope for right now is a Woolly mammoth lab, and that's down the hall from where the, where the, the, the real action is, is at.

Robert Krulwich:           But now there's hall.

Carl Zimmer:                    Yes.

Robert Krulwich:           And at the end of the hall is a winged piglet. It hasn't been built yet.

Carl Zimmer:                    No, I, I. (laughs)

Robert Krulwich:           It maybe 20 years from now but that's what you're looking at. I, you-

Carl Zimmer:                    Well I think, but the thing is that then you're, no-

Robert Krulwich:           But what's wrong with this, though? Like why shouldn't anyone realize that's what really talking about here.

Carl Zimmer:                    Well because you can't make wing, winged pigs, just because of evolutionary barriers, okay.

Robert Krulwich:           Well there's no [crosstalk 00:19:24] in for pigs to fly.

Jad Abumrad:                  No, gentlemen.

Robert Krulwich:           Except for the joke, but-

Jad Abumrad:                  Calm down, calm down.

Robert Krulwich:           I'm, I'm just stoking it.

Carl Zimmer:                    No, i mean okay, I don't think that we need a federal department of Homeland pig with wings security.

Robert Krulwich:           (laughs)

Carl Zimmer:                    I think we're okay there. All right. What we do need is like, uh, we do need to like figure out what are we going to do about CRISPR in humans.

Carl Zimmer:                    I mean they're going to be using CRISPR for cancer, okay. They're going to take people's immune cells out of their body, and they are going to use CRISPR to, uh, basically allow them to make proteins. They're going to be able to grab on to cancer cells-

Robert Krulwich:           Really. Wow.

Carl Zimmer:                    And attack their own cancer. Yeah, that's-

Robert Krulwich:           Well you have to be for that. I mean you have to be.

Jad Abumrad:                  Well I don't know I mean are you for it? That is, that is

Carl Zimmer:                    Well, your, your, you are tink, you are tinkering with someone's own body. You are altering their own cells, you know.

Jad Abumrad:                  Dude.

Robert Krulwich:           Where do I? It's just I tell you the, the, this is me, I don't know if it's a religious thought or just the thought of conservative person. But I mean I've, I grew up in the, 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.

Robert Krulwich:           I guess what I'm instead on is I'm on, on, um, a Hobbesian of human beings. That there is something about human beings-

Carl Zimmer:                    Mm-hmm (affirmative).

Robert Krulwich:           Including scientist human beings, all human beings. That there's a darkness and a light, they are, they are, there's angelic side to being human, and there's a very, very difficult side of them.

Robert Krulwich:           As the human beings get more and more power to create and design and essentially create a future. That future will include the imagination's 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 Frances 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.

Robert Krulwich:           Mm-hmm (affirmative).

Carl Zimmer:                    Um, if you, if you can say like okay now we're going all, we're going to outlaw this.

Robert Krulwich:           I'm not suggesting that?

Carl Zimmer:                    But what are you suggesting then?

Robert Krulwich:           I think we should cringe a little as suppose to just have a big party.

Carl Zimmer:                    Okay, all right. Let's all cringe. Ready.

Jad Abumrad:                  (laughs)

Carl Zimmer:                    One, two, three.

Robert Krulwich:           Don't make fun of it. You-

Jad Abumrad:                  Ooh.

Carl Zimmer:                    Ooh.

Robert Krulwich:           No, no that's fair.

Carl Zimmer:                    Now what? What if we've cringed in that way? What do we do now?

Robert Krulwich:           Well, then we, I don't know.

Carl Zimmer:                    But we all cringed if that's, if that's what you're arguing for.

Robert Krulwich:           No, you cringed.

Carl Zimmer:                    We cringed too.

Robert Krulwich:           You cringed, you cringed meanly and, and, and you cringed, you cringed with attitude.

Carl Zimmer:                    No, but-

Robert Krulwich:           I'm cringing with, with-

Carl Zimmer:                    Because you're-

Jad Abumrad:                  I would like to know-

Carl Zimmer:                    Afraid of like dragons.

Robert Krulwich:           (laughs)

Carl Zimmer:                    (laughs)

Carl Zimmer:                    You're saying, you're saying oh my God.

Robert Krulwich:           Yes, I'm afraid of dragons.

Jad Abumrad:                  Okay, so that conversation with Carl was four months ago, and, uh, a lot has happened in the, in that time. Because to the question that you asked like where does this sacred begin and end. Well one of lines that had been drawn but 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, 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, um, you can't ask the, uh, 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...

reporter:                             For the first time in history researchers in China have successfully edited the human genom in an embryo.

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

reporter:                             From Sun Yat-sen University used a technique called CRISPR...

reporter:                             To edit DNA in human embryos.

Speaker 11:                       It's a way of hacking evolution itself.

reporter:                             While this is hugely controversial.

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

reporter:                             These are embryos that are, are not going to actually develop into a person, so they're, they're going to be discarded anyway.

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

reporter:                             Biologist and bioethicist are sounding an alarm.

reporter:                             The scientist face accusations that they crossed an ethical line.

Speaker 11:                       That this sort thing could be sort of a slippery slope towards-

reporter:                             Towards designer babies.

Speaker 11:                       Essentially genetically engineering the human race.

Speaker 12:                       We're going to use the little chips to kind of test your lymph nodes.

Speaker 13:                       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, 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.

Carl Zimmer:                    Mm-hmm (affirmative).

Robert Krulwich:           I feel that I should do a small little parade of the-

Jad Abumrad:                  (laughs)

Robert Krulwich:           (laughs). If I can remember the Alamo. It's like remember, remember China. And you have to, so you should begin anytime you want. Like getting on your knees and saying how sorry you are. Why don't you start from there?

Jad Abumrad:                  (laughs)

Carl Zimmer:                    Um, I'm sorry so are we actually surrounded by a, a, an army of clones with super powers.

Jad Abumrad:                  (laughs)

Robert Krulwich:           Not yet. Not yet but I think the dike has been opened. I believe I'm going to quote somebody who said, uh, maybe, uh a few weeks ago. I think you were, maybe it was last week even writing for National Geographic. I think it was. Maybe it was somebody named Carl who said that, uh, “The news from China, and that news probably the beginning of an entire new era."

Carl Zimmer:                    I think I actually it was an historical moment.

Robert Krulwich:           That's right, yes. That's right.

Carl Zimmer:                    Yes. And I, 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, I don't feel different actually, because, um, there isn't 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 was bound to happen, and in fact it may be happening more than we think. Uh, one account in the Journal of Naturist said that four other Chinese labs are doing this kind of work as we speak.

Jad Abumrad:                  But Carl also told us, which he said was unsurprising too but I actually find it kind of surprising. That the CRISPR work that this Chinese team did, didn't work very well.

Carl Zimmer:                    It worked kind of. (laughs) I mean in only a few of the cases did they really get exactly what they wanted. Um-

Jad Abumrad:                  They tried using CRISPR on about 86 embryos and they only got it to work right in maybe 28. And in a lot of them CRISPR 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 genome line. And, um, I, I agree.

Robert Krulwich:           Oh.

Carl Zimmer:                    We sort of, we still are, are in this kind of, of fortunate position where we can say “Oh well it's dangerous, so we shouldn't use it on human embryos.”

Carl Zimmer:                    I, I just don't think that we're going to be able to sort of, uh, 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 guarantee you that you will have human embryos that have the alteration in a particular gene you want.”, so then what?

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

Jad Abumrad:                  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-

Robert Krulwich:           It won't hurt, it won't, it will not hurt.

Carl Zimmer:                    Okay, all right. Here we go. So, okay, so.

Robert Krulwich:           Deep breath.

Carl Zimmer:                    (deep breath) So you guys know about, uh, 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're looking at these Icelandic people they found that some people had, uh, a gene that, uh, protects them against Alzheimer. It reduces their odds of getting Alzheimer.

Carl Zimmer:                    Let's imagine you doctor said “Now if you'd like for an extra 1,000 dollars we will take this IVF embryos and we will use CRISPR to give them the Alzheimer protecting variant. Would you like that?"

Robert Krulwich:           Hmm.

Carl Zimmer:                    "Do you want to add that to your, to your procedure?"

Jad Abumrad:                  Sure, yeah.

Carl Zimmer:                    Or would you like your child, to, to face, a, a, a future of, of Alzheimer. Your choice.

Jad Abumrad:                  See here's my, here's my thing. Here's my thing with this whole, with this whole thing.

Carl Zimmer:                    Yeah.

Jad Abumrad:                  I'm, 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, 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.

Carl Zimmer:                    You got it.

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

Carl Zimmer:                    Yeah.

Jad Abumrad:                  We've already answered the question.

Carl Zimmer:                    Yeah. We may have. (music)

Jad Abumrad:                  Many thanks to science writer Carl Zimmer, who has written many books. You can check him out at carlzimmer.com. We're at radiolab.org. 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 Anna Ruswick plus...

Jad Abumrad:                  Lee Mcquire.

Robert Krulwich:           Dr. Blake Weedenhalf.

Jad Abumrad:                  Dr. Luciano Marfini.

Robert Krulwich:           Dr. Sean Burgess.

Jad Abumrad:                  And Dr. Jin Wey Shi.

Jad Abumrad:                  I'm Jad Abumrad.

Robert Krulwich:           I'm Robert Krulwich.

Jad Abumrad:                  Thanks for listening. (music)

Ans. Machine:                 To hear the message again press two, to delete it... Start of message.

Carl Zimmer:                    Hello this is Carl Zimmer.

Beth Shapiro:                   Hi this Beth Shapiro.

Jennifer Doudna:          Hello this is Jennifer Doudna.

Beth Shapiro:                   Radiolab is produced by Jad Abumrad.

Carl Zimmer:                    Our staff includes Brenda Ferrel, Ellen Horn, Dylan Keith.

Jennifer Doudna:          Matt Kielty, Ben Levy.

Carl Zimmer:                    [inaudible 00:30:25]

Beth Shapiro:                   Latif Nassar, Malissa O'Donnell, Kelsey Pagick.

Jennifer Doudna:          Arianne Wack, Molly Webster.

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

Jennifer Doudna:          With help from Danny Luis, Kelly Prime and Domiono Marquete.

Beth Shapiro:                   Our fact checkers are Eva Dasher and Michelle Harris. Awesome. Thank you much.

Carl Zimmer:                    See you later.

Ans. Machine:                 End of message.