[ARCHIVE CLIP, instructor: Lesson number eight. How does it make the ribosome without a ribosome to make the ribosome?]

[ARCHIVE CLIP, instructor: Come si forma il ribosoma senza un ribosoma per formare il ribosoma?]

[ARCHIVE CLIP, instructor: Now you try.]

JAD ABUMRAD: Do you guys mind if in the remaining few minutes, we go on an RNA fishing exposition?

CARL ZIMMER: [laughs] Sure. Sure.

JAD: Because here's our quandary, Carl.

CARL ZIMMER: Okay, what's your situation?

JAD: We're doing a show on Trans ...

JAD: Okay. So recently, we sat down with reporter and science writer Carl Zimmer to talk about RNA, of all things. We were talking about something else, and RNA came up at the end. Because here's why: ever since we started doing this show, Robert got his—got his ...

ROBERT KRULWICH: I got a little insistent, I think.

JAD: A little insistent because you were like, "RNA! We gotta do RNA!"

ROBERT: Yes, I said that. RNA.

JAD: And I was like, "What do you wanna do?" And you were like, "I wanna do RNA." And I was like, "But is there a story?" And you're like, "No."

ROBERT: No, I didn't say that. I just said that if you understood what RNA does, you'd realize that translation is profoundly important to our existence. That's what I said.

JAD: Yeah. Well, as often happens, you wore me down. And I was like, "All right, fine. Let's just try it." So when we were talking with Carl Zimmer, we brought it up. Now unfortunately, I think this is a day when you were out of town.

ROBERT: Yes.

JAD: I think your son was getting married.

ROBERT: Yes, he was. Carl was doing tag team work for me.

JAD: [laughs]

CARL ZIMMER: Okay. All right. So the definition of 'translation' in biology is taking a sequence in DNA and using the genetic code to translate it into proteins.

JAD: Mm-hmm. Right.

CARL ZIMMER: And the discovery of this was maybe even more exciting than the discovery of the double helix structure.

JAD: Really?

CARL ZIMMER: Yeah.

JAD: It was bigger than Watson and Crick?

CARL ZIMMER: Yeah. Well, at least equivalent.

JAD: Wow!

CARL ZIMMER: So here's the quick story. So what happened was ...

JAD: Okay, so, just to set the table here, we all know that DNA is a thing, and that when you're born, you get half your DNA from your mom and half your DNA from your dad. Now Francis Crick and James Watson just figured out the structure of DNA, that basically the recipe of DNA, your recipe, is comprised of four bases and a long string: A, T, C and G. That's it. But here's the problem. See, we humans, we're more than DNA. We are these fleshy, peeing piles of muscle and bone. And all of that stuff, all the stuff-stuff of us comes from proteins.

CARL ZIMMER: Yeah. We have, like, 100,000 different proteins in our body. Different kinds of proteins.

JAD: So the question was ...

CARL ZIMMER: Like, how does all that get generated?

JAD: Like, how do those four simple bases become the amino acids that become the hundreds of thousands of proteins that make us us?

CARL ZIMMER: How do you make the translation?

JAD: Hmm.

CARL ZIMMER: People were thinking of this as just this incredibly complicated problem that might never be solved. And the first person to really think seriously about this was not a geneticist, it was a cosmologist named George Gamow.

JAD: Huh!

CARL ZIMMER: And Gamow just said, "Wait a minute, this isn't that complicated. This is just cryptography. This is a code problem."

JAD: Gamow thought, "Okay, I know that DNA contains four bases: A, T, C and G. And I know that they somehow create hundreds of thousands of proteins.

CARL ZIMMER: So I just need to think of a clever way of, you know, creating a little code machine where you put in the DNA ...

JAD: ATCACCGATCACGA.

CARL ZIMMER: ... sequence, and then out comes the protein. What simple code could I do to do that?

JAD: And just sitting there—no experiments, no nothing, just thinking—this guy Gamow decides ...

CARL ZIMMER: I think that our cells read our genes three bases at a time.

JAD: Like, instead of AT CG AC, Gamow thought maybe it's ATA, CCG, TCA, AAC, AAG, ATT. In other words, whatever it was that was reading the DNA in the cell, maybe it was reading it in triples, not pairs. Because if you have sets of three rather than two, Gamow figured, well that mathematically would give you more possibilities, and that might put you on the path to making all those hundreds of thousands of proteins.

CARL ZIMMER: Yep.

JAD: Now this was just a guess. But shortly after, the double helix duo, Watson and Crick ...

CARL ZIMMER: And a group of other scientists worked it all out. They figured out how you get from—physically get from DNA into proteins.

JAD: Here's how it works—sort of. Inside the cell, the DNA is sitting there all coiled up. A set of molecules come along, attach to it, unzip it ...

CARL ZIMMER: And make a copy of it.

JAD: This copy is now made of RNA, which is like DNA, very similar.

CARL ZIMMER: Still in a basic sort of four-letter format.

JAD: But it's now on the move because it pedals over to this big old factory in the cell called ...

CARL ZIMMER: The ribosome. It's just this crazy, floppy, convulsive collective of molecules.

JAD: And once the RNA copy is inside this big factory, another kind of RNA comes over and begins to—bzzt bzzt bzzt, bzzt bzzt bzzt—read the bases three at a time. Like ...

CARL ZIMMER: Okay. ATA. Well, that must be, oh, you know, GGC. Well, that's gonna be the chain.

JAD: And it begins to create this chain of amino acids, which are sort of the beginning of proteins. And eventually, the ribosome will take this chain and eject it out so that they can ...

CARL ZIMMER: Do their thing. You know, grab oxygen, or cut up your food.

JAD: Or make your hair, or the cartilage in your ear, your teeth or your toes, or the neurons that carry the thoughts you think.

CARL ZIMMER: Or whatever.

JAD: It does displace the quote, "author" of you. Because I mean, I remember growing up thinking, "Oh, DNA is my sort of like, manual or my blueprint or something. All of me is in there, and that's just somehow it opens and then out pops me. But you're saying that there's this thing that is reading these three-base pairs and forming any of a hundred thousand proteins? Suddenly I'm thinking that's where their game is. Not the DNA, but in the thing that's reading the DNA.

CARL ZIMMER: Well, yeah. I mean, DNA is just a totally meaningless molecule just flopping around unless there is a way of reading it.

JAD: But doesn't the reader of the DNA come from the DNA?

CARL ZIMMER: Sure.

JAD: See, that's just weird.

CARL ZIMMER: Yes. So you have genes for the parts of the ribosome.

JAD: At this point, producer Tim Howard and producer Soren Wheeler stepped in.

TIM HOWARD: It's like a book that births its own reader that will read the book.

CARL ZIMMER: Not exactly, though, because that does—you are sort of putting DNA up on that pedestal.

JAD: But sequentially it is.

CARL ZIMMER: Hmm?

JAD: Sequentially it is. It's first.

CARL ZIMMER: What is?

JAD: DNA.

CARL ZIMMER: How's DNA first?

JAD: Well, you're saying it's—in the order of events, you begin with DNA, and then after that, you get the ribosome and the RNA.

CARL ZIMMER: Events of what?

JAD: Of you.

CARL ZIMMER: Okay, but you gotta bear in mind that you—I don't know how far back you want to go with you.

JAD: [laughs]

CARL ZIMMER: No, seriously. Where do we start with you? Do you want to start Jad, the fertilized egg?

JAD: Well, sure. Yeah.

CARL ZIMMER: Okay. Jad, the fertilized egg has DNA and these ribosomes.

JAD: Oh, so the readers are already present.

CARL ZIMMER: When a cell divides, two new copies of DNA go into each new cell, but they also divide up all the ribosomes from the original cell. So they're taking the factories with them.

JAD: Oh!

CARL ZIMMER: So the DNA is never without the code.

SOREN WHEELER: I see.

TIM: Okay, so it's like Moses with the tablets together, right?

CARL ZIMMER: Uh ...

TIM: Or is it Noah?

CARL ZIMMER: Can I just say I've never thought of it that way. So I might need to think about this.

JAD: What makes the ribosomes then? Does it come from the DNA? I thought you just said that.

CARL ZIMMER: Yes.

SOREN: But how does it make the ribosome without the ribosome to help it make the ribosome?

CARL ZIMMER: What? Wait. Okay, wait.

SOREN: You need to translate the DNA codes for the ribosomes, so how do you make the ribosome without a ribosome to translate the code to make the ribosome?

CARL ZIMMER: You couldn't.

JAD: Wait a second. I'm so confused right now.

CARL ZIMMER: You've gotta take the DNA and the ribosome partnership all the way back through billions of years. These two parts of the system evolved and became dependent on each other very early in the history of life.

JAD: In fact, Carl says a lot of biologists think that life ...

CARL ZIMMER: Started out as just RNA.No DNA. And so you would basically have these little organisms that would have these little kind of proto-genes made of RNA, and eventually these RNA molecules started to connect amino acids together to make the little building blocks of proteins.

JAD: So you're saying that people generally think RNA came first?

CARL ZIMMER: That is one of a couple leading hypotheses today.

JAD: Okay. So it's possible that RNA came first, then DNA. Somehow, suddenly I'm thinking, "Oh, we should have been talking about RNA all along."

CARL ZIMMER: [laughs] Well I mean, just in general, RNA has been incredibly neglected and ignored.

SOREN: So the Bible, instead of "In the beginning was the word," should have been "In the beginning was the person reading the word."

CARL ZIMMER: Or "In the beginning was the code." Yeah.

JAD: Did you guys feel the earth shake just now? I really—no, there was some kind of vibration happening. And in my head, too, because I was thinking, "I finally get it now." Like, I get it.

CARL ZIMMER: Good.

JAD: Because DNA got sold to us as, like, this is the first step in understanding the mystery of life, right? But it somehow doesn't feel like that anymore. I'm suddenly like, "RNA. The ribosome! That's where the real mystery is."

CARL ZIMMER: I like the way you're thinking.

ROBERT: And so Jad discovers that we are all translations. That translation is the true mystery, the deep secret of life.

JAD: Who invited you in here?

ROBERT: [laughs] If I said "I told you so," you wouldn't be able to translate that. Honestly.

[ARCHIVE CLIP, instructor: Very good. And now let's say "Goodbye." Tura dishri barai. Now you try!]

[ARCHIVE CLIP, Margaret Glasby: [singing in Korean] I'm done. This one's so hard. [laughs] it doesn't make any sense because all the syllables are totally off. Okay. [singing in Korean] Yay!]

ROBERT: That heroic translation from the Korean of "Aura Lea" is by Margaret Glasby. So thank you, Margaret.

JAD: Yeah. And thanks to all our singers. Viesta, who sang "Old McDonald" in Bambara, which is a Malian language.

ROBERT: Catherine McCarthy, who did our Italian version of "Yankee Doodle Dandy."

JAD: Leah Torres, who did the German "I've Been Working On The Railroad."

ROBERT: Azza Khalil, who did the Arabic "Amazing Grace." And she's the mom of our intern.

JAD: Reem!

ROBERT: Reem, yes.

JAD: And of course our puppeteer from our Apocalyptical show. Miron Gusso, did our Russian version of "You Are My Sunshine."

ROBERT: Kiran Ahluwalia, doing the Hindi version of "Three Blind Mice."

JAD: And finally on—with the piano and musical interpretation on everything, Jon Dryden.

ROBERT: Thank you, Jon.

JAD: Thank you, Jon. Oh, and you know what? If you go to our website, Radiolab.org, you can hear a proto-version of Radiolab in Spanish, which we'd like your feedback on.

ROBERT: Yep.

JAD: I'm Jad Abumrad.

ROBERT: I'm Robert Krulwich. Varkator.

[ANSWERING MACHINE: Start of message.]

[DAVID EAGLEMAN: Hi, this is David Eagleman.]

[CARL ZIMMER: Hello, this is Carl Zimmer.]

[KYMME VAN CLEEF: This is Kymme Van Cleef.]

[DAVID EAGLEMAN: Radiolab is produced by Jad Abumrad.]

[KYMME VAN CLEEF: Our staff includes Ellen Horne, Soren Wheeler ...]

[CARL ZIMMER: Soren Wheeler, who produced this show. Whoo!]

[DAVID EAGLEMAN: Tim Howard, Brenna Ferrell ...]

[CARL ZIMMER: Molly Webster, Malissa O'Donnell, Dylan Keefe ...]

[KYMME VAN CLEEF: Jamie York ...]

[CARL ZIMMER: Andy Mills, Kelsey Padgett and Matt Kielty.]

[KYMME VAN CLEEF: With help from Adrian Rock, Reem Abdou and Clare Toeniskoetter.]

[DAVID EAGLEMAN: Special thanks to Nancy Updike, Larry Kaplow ...]

[CARL ZIMMER: Emily Condon, John Lonbergh ...]

[DAVID EAGLEMAN: Nick Nuciforo ...]

[KYMME VAN CLEEF: PJ Vogt, Alberto Ferraro ...]

[DAVID EAGLEMAN: Wallace Almeida, Suzanne Franks, and everyone at Language Line.]

[ANSWERING MACHINE: End of message.]

JAD: All right. So listen, the show's over, right?

ROBERT: It's definitely ...

JAD: Totally over.

ROBERT: We've said goodbye.

JAD: Yeah, yeah. So like, anyone ...

ROBERT: So this is like a—this is now—we're not even here, really.

JAD: No. This is—this is for—this is for the people who want to venture into some well, hideous territory, really. Awful territory.

ROBERT: Because we have—we asked listeners to send in ...

JAD: Tell us what you think of us. Tell us—you know, like, do you like us? And here's what we got.

[listeners swearing in other languages]

 

-30-

 

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