The secret history of DNA: Pus, fish sperm, life as we know it : Short Wave It's been 150 years since the first article was published about the molecule key to life as we know it — DNA. With help from researcher Pravrutha Raman, Short Wave producer Berly McCoy explains how DNA is stored in our cells and why the iconic double helix shape isn't what you'd see if you peeked inside your cells right now.

Read more about the discovery of DNA: https://bit.ly/3wNe7hn

Curious about all the other biology that defines us? Email the show at shortwave@npr.org — we're all ears ... and eyes and toes and ... a lot of things. Thanks, DNA!

The secret history of DNA: Pus, fish sperm, life as we know it

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MADDIE SOFIA, BYLINE: You're listening to SHORT WAVE...

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SOFIA: ...From NPR.

MARIA GODOY, HOST:

Hi, SHORT WAVErs. Maria Godoy here with producer Berly McCoy.

BERLY MCCOY, BYLINE: Hi, Maria.

GODOY: All right, Berly, what do you have for the pod today?

MCCOY: I want to talk about the beautiful, extraordinary substance that is responsible for all of life as we know it.

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MCCOY: Nuclein.

GODOY: Say what?

MCCOY: You don't know about nuclein?

GODOY: Not so much.

MCCOY: It's got beauty. It's got mystique. And it's got a really long history.

GODOY: Really?

MCCOY: Yeah. The first article about it was published back in 1871, which was 150 years ago this year. It was found by a Swiss scientist named Friedrich Miescher in Germany. And back then, we didn't know much about cells, so he was literally just trying to figure out what was on the insides of cells.

GODOY: What did he do? How did he find this?

MCCOY: The only logical way - with pus he got from off of used surgical bandages.

GODOY: Oh, my God. Berly, that's pretty gross.

MCCOY: The things we do for science.

GODOY: Indeed.

MCCOY: And so Friedrich is doing his experiments, and he keeps getting a mysterious clump of goo that's definitely not proteins. So he eventually realizes it's a whole new thing, an undiscovered molecule.

GODOY: Ooh, that sounds exciting. And did he find it in the nucleus? Is that why it's called nuclein?

MCCOY: Yes. But these days, nuclein's got a new name. And I think if I tell you about his later experiments, you might be able to guess its new name. See, later, Miescher started experimenting with fish sperm.

GODOY: My God. First pus, now fish sperm. Are you kidding me?

MCCOY: I know, I know. So that's when he started guessing nuclein had something to do with fertilization and inheritance.

GODOY: Oh, my God. Is it DNA? Did I win? Ding, ding, ding.

MCCOY: Yeah.

GODOY: Woo.

MCCOY: Yeah - ding, ding, ding. It turns out sperm have a lot of DNA in them - right? - which makes sense since it's kind of their purpose in life, literally.

GODOY: I see what you did there. Today on the show, we're talking about the myth, the molecule, the legend - DNA.

MCCOY: And how that nice, long double helical shape you might've learned about is not what you would see if you could peek inside your cells right now.

GODOY: I'm Maria Godoy.

MCCOY: And I'm Berly McCoy.

GODOY: And you're listening to SHORT WAVE, the daily science podcast from NPR.

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GODOY: OK, Berly, so we're talking all about DNA, deoxyribonucleic acid, a frickin' mouthful to say.

MCCOY: It definitely is. And as molecules go, it's a pretty big one.

GODOY: Well, it's got a big job. It made you and me, you know?

MCCOY: It does make up you and me. DNA is the blueprint that our cells use to make all of the proteins that we need to function, from digestion enzymes to keratin proteins that make up our hair and nails. I talked to Pravrutha Raman about all this. She's a researcher at the Fred Hutchinson Cancer Research Center. And she says that even though we are really complex, our DNA is impressively simple. It's just four chemical letters.

PRAVRUTHA RAMAN: It's just different combinations of A, T, G, C. That is essentially what makes up DNA, which is kind of cool. It's just four nucleotides, and that's all it takes to make up all of the DNA.

MCCOY: So if you remember learning about DNA structure, all those nucleotides are basically like rungs on a ladder...

GODOY: Yeah.

MCCOY: ...Where the sides of the ladder are, you know, two long strands of alternating sugar and phosphate molecules. Then those two strands wrap around each other to make the iconic double helix shape.

GODOY: OK, but, Berly, just a little bit ago, you told me that if I could take the Magic School Bus and go into my cell nucleus right now, I would not see a long strand of double helixes of DNA. So what gives?

MCCOY: I know, I know. Minds are being blown. But there's a good reason for it. If you took all of the DNA from just one of your cells and stretched it out, it would be more than 6 feet tall.

GODOY: Berly, I'm only 5-foot-4 on a good day. Like, how am I getting 6 feet of DNA inside me?

MCCOY: I know. And not even just your body - in an individual cell.

GODOY: Whoa. That's a lot of DNA in an itty-bitty living space. So how are we cramming that much information, something, like, that long into a tiny individual cell?

MCCOY: Maria, very precisely, because we still need to be able to use it all the time. Packing our DNA is actually a super organized, complicated process. And it's what Pravrutha studies - how DNA is packed down into the nucleus of our cells, which is only about 10 micrometers across. That's somewhere on the order of a hundred times smaller than a grain of sand.

GODOY: And all of my 6 feet of DNA is packed into that. Like, what does that even look like?

MCCOY: I asked Pravrutha the same thing.

RAMAN: So the double helix is actually packaged much more tightly in a cell. So there are proteins that we have around which this DNA is packaged, and it was very beautifully called beads on a string. And every bead is made up of these histone proteins. And then the string that's wrapped around the beads or between the beads is the DNA double helix.

GODOY: It's been years since I've been in bio class, so remind me; these beads, these histone proteins - what are they?

MCCOY: Yeah. Essentially, their whole job is to help organize the DNA. And really, as proteins go, histones are ancient. Pravrutha told me we basically have the same histone proteins as yeast, which we parted ways with on the evolutionary tree more than a billion years ago.

GODOY: Whoa. So if evolution hasn't changed them in all this time, I'm guessing that must mean that they're really, really important, right?

MCCOY: They definitely are.

RAMAN: These proteins are absolutely essential. You can't remove them. If you lose histones, all cells are dead.

GODOY: Whoa.

MCCOY: So basically, these histone proteins serve as kind of a spool for thread, which in this case is the DNA.

GODOY: So cool.

MCCOY: And because our DNA has a negative charge and these histone proteins hold a positive charge, they attract each other, which helps compact the DNA down.

RAMAN: And those beads can then be really close to each other or further away from each other, which helps with more tight or more loose packaging.

MCCOY: And then the beaded strings have even more levels of organization that Pravrutha says scientists are still trying to understand.

GODOY: That's really kind of clever and sort of amazing that it can all fit in there.

MCCOY: Yeah.

GODOY: OK, but here's my question. If DNA is a blueprint and our cells need to read that blueprint to make us, then how do our cells read our DNA if it's all packed away like that?

MCCOY: This is where it gets really interesting, Maria. Pravrutha told me that the different kinds of packaging change how accessible the DNA is to our cells. So, like, really tightly packaged DNA isn't accessible, and that's where our star protein, the histone, comes in.

RAMAN: The parts of the DNA that are accessible or not can be changed using these histones. And essentially, every time you want to access a piece of DNA that is bound by these beads, you can either - to evict the beads or remove the beads or move the beads so that the DNA becomes more accessible.

MCCOY: So our cells are busy with a million jobs all the time, but those jobs change. Like, if a cell is about to divide, it'll need to read different parts of the DNA than if it isn't. Depending on what a cell needs, it'll send different signals, which tell the histones how tight or loose to pack the DNA, which then in turn control which sections of the DNA can be read.

GODOY: So these histone proteins that the DNA is wrapped around, they're, like, really powerful 'cause they actually control which parts of the DNA can be read, right?

MCCOY: Yeah, yeah.

GODOY: That's really cool. That's got to affect, like, a lot of what's going on in a cell.

MCCOY: Totally.

RAMAN: So if you think about sort of through development or if you look at different cells, you want to make different proteins in these different cells.

MCCOY: Your muscle cells are going to need to read a different part of the blueprints than the cells in your tongue or the cells in your lungs, and that's controlled by histone proteins. So the DNA in our nucleus is actually a mix of super tight and super loosely packed DNA, depending on what the cell needs at the time.

GODOY: OK, Berly, so I get what DNA looks like in a cell - very organized beads on a string. And I get why it's organized that way. But I have a more poetic question for you.

MCCOY: OK.

GODOY: (Imitating British accent) How doth this tiny string make something as complex as you and me, Berly?

MCCOY: (Laughter) OK, it's pretty astounding - right? - especially since the DNA code is really simple. So to describe how our DNA makes us, Pravrutha starts from the beginning

RAMAN: So we all start out as that one-cell embryo. But then you go on to make skin cells and blood cells and heart cells. And so to make each of those cells, you have to access different parts of the DNA to make the protein that you want so that the cell can then become sort of what it's finally meant to be.

MCCOY: And those cells make up tissues, and those tissues make up organs. It's a pretty amazing process

RAMAN: To start with something that's simple but to be able to make something really complex at the end of it that all functions together as one cohesive unit, that's crazy to me.

MCCOY: It's also kind of wondrous, though, if you think about it, the marvels of the human body.

GODOY: Yeah. Thank you, DNA. And thank you, Berly, for bringing us this story.

MCCOY: You're welcome.

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GODOY: This episode was produced by Eva Tesfaye, edited by Rebecca Ramirez and fact-checked by Margaret Cirino. The audio engineer was Stu Rushfield. I'm Maria Godoy. Thanks for listening to SHORT WAVE, the daily science podcast from NPR. Adios for now.

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