Stuff You Should Know - How Gene Editing Works

Episode Date: June 2, 2016

With the discovery of a surprising immune response in E coli bacteria, we are facing a new era of freedom from genetic mutations that lead to disease by simply and precisely editing our genes. But there is also a potential dark side to gene editing. Learn more about your ad-choices at https://www.iheartpodcastnetwork.comSee omnystudio.com/listener for privacy information.

On the podcast, Hey Dude, the 90s called, David Lasher and Christine Taylor, stars of the cult classic show, Hey Dude, bring you back to the days of slip dresses and choker necklaces. We're gonna use Hey Dude as our jumping off point, but we are going to unpack and dive back into the decade of the 90s.

We lived it, and now we're calling on all of our friends to come back and relive it. Listen to Hey Dude, the 90s called on the iHeart radio app, Apple Podcasts, or wherever you get your podcasts. Hey, I'm Lance Bass, host of the new iHeart podcast, Frosted Tips with Lance Bass. Do you ever think to yourself, what advice would Lance Bass

and my favorite boy bands give me in this situation? If you do, you've come to the right place because I'm here to help. And a different hot, sexy teen crush boy bander each week to guide you through life. Tell everybody, ya everybody, about my new podcast and make sure to listen so we'll never, ever have to say. Bye, bye, bye.

Listen to Frosted Tips with Lance Bass on the iHeart radio app, Apple Podcasts, or wherever you listen to podcasts. This episode of Stuff You Should Know is brought to you by Squarespace. Whether you need a landing page, a beautiful gallery, a professional blog, or an online store, it's all possible with a Squarespace website.

And right now, listeners to Stuff You Should Know can start a free trial today. Just go to squarespace.com and enter the offer code STUFF, and you'll get 10% off your first purchase. Squarespace, set your website apart. Welcome to Stuff You Should Know, from HowStuffWorks.com. Hey, and welcome to the podcast. I'm Josh Clark with Charles W. Chuck Bryant,

and there's Jerry. Did you see that Squirrel W. Chuck Bryant picture? Yeah, it's pretty great, huh? Big thanks to Sally Ridge Illustrator, Drawer of Things, who made us one of, we used to get a lot of fan art. You notice we don't get that much anymore? Yeah, everybody takes this for granted.

Well, maybe. No, we get jingles now. Yeah, we get all kinds of cool stuff, but we just used to get a ton of fan art, and this is one of the more delightful pieces of fan art we've ever gotten. We posted it on our Instagram, actually. Yeah, and Facebook, so thank you, Sally, for that.

You can go to SallyRidge.net to see her work. I'm a little squirrel. I'm a weasel, which I don't know what to make of. I'm just going with it. It's cute. I first saw that, too, and I was like, huh. You're right. It was like, if it was a weasel and a skunk,

it'd be like, I'd really have to think it through. But as a squirrel, you have a little beard, even, too. It's pretty cute. It is very cute. So, Chuck, we say all that to say, have you ever seen a gene? A grown gene naked? Can you keep up with genes and DNA and all that,

nucleotides, do you remember this stuff? A little bit. I had to go back and brush up on a little. If you have a primer, feel free, because. I have a bit of a primer. I'll probably screw it up royally. Well, I was going to say an alternate title for this show could be called,

how the CRISPR gene editing works, AKA, what's Chuck going to mess up? Yeah, it's kind of, I mean. It's sort of simple, but it also is a little mind-bending. It's simple if you are a geneticist. Right. It's almost like laughably, scarily simple. But to people like us, it's like, oh.

Sure. All right, well, let's go back. Let's talk a little bit about genes first, right? It's a little weasel in a squirrel. So, if you go into one of those squirrel cells and you go into the nucleus of the cell, you're going to find a pair of chromosomes, right? And these chromosomes are made up of DNA.

And the DNA itself is made up of nucleotide pairs. What is it? G-A to T-C, is that right? Ad9 goes to, oh, who is it? Yeah, ad9 goes to thymine and guanine goes to cytosine, right? Okay. So you got gattica. Yes.

And when you put these amino acids together, you have what are called nucleotide-based pairs and they make up DNA. Yeah. Now, if you take a strand of DNA, this thing from, it's like a Stanford site for dummies. So it really spoke to me. But it said that if you could stretch out your DNA,

it would be like six feet long. Did you know that? That's all. In the nucleus of a cell. I thought you were about to say it would be the exact height that you are. That'd be pretty neat. Yeah, my mind would have been blown.

Yeah, that'd be something else. Sure. Wow, maybe it is, because I'm about six feet. Because supposedly your wingspan is a fingertip to fingertip is the same as your height. I've heard that before. That's not true though, because some people have larger wingspans than others, than their height.

Like proportionally. I got you. Anyway, go ahead. So it's just a dirty lie? I think so. Well, if you take this DNA and you look at it, you can see that there's different sequences. And along this very long six foot strand of DNA,

these sequences are broken down into what are called genes. And so a gene is really just a string of nucleotide base pairs that create or lead to the production of a specific protein. And you say, OK, well, great, protein. We eat that. It's steak. Done.

No, proteins do way more than that. They're involved in just about every part of your body, from the building blocks of cells to chewing, to blinking, to thinking. Like proteins are very, very important. And your proteins are expressed through your genes. OK? Yeah.

I think I got that fairly right. Every once in a while, this code, especially when a cell divides and the DNA that was in the original cell is copied to the new cell, that translation can go a little bit wrong. And so all of a sudden, along these billions of base pairs, there was a mistranslation. And what you have then is a mutation.

For the most part, mutations are not problems. As a matter of fact, any one of us has something like an estimated 5 to 10 mutations, deadly mutations, in our genes right now. Crazy. But we only have one copy. And there are very few diseases that you only need one copy of a genetic defect for.

Right. So we're basically fine. If you get two pairs of mutated problematic genes, then you can have a disease. And there's a lot of diseases that are genetic in origin. Everything from cystic fibrosis to cancer is the result of a gene that's mutated and gone haywire. The whole point of everything I just said

is that we, from dawn of humanity, even before then, ever since we were little amoeba, have been subject to the whims and vagaries of genetic mutations. Sometimes they help us, sometimes they do nothing, sometimes they create disease. But as of 2012, we are technically leaving the thumb of genetic mutations tyranny.

Potentially, yeah. Through CRISPR gene editing. Yeah, it's pretty remarkable. It really is. It's very tough. I know I say this a lot. I think I said it's tough to underestimate the craze of super balls or something stupid like that.

It's really tough to overstate how much the CRISPR gene editing technique could change humanity, the world. If everything goes well, hopefully within the next decade, we'll see real human trials for some of these applications. That's the hope. And it may happen because this is one of the most heavily funded arms of scientific health medicinal research out there right now.

It's also one of the newest, too. And it's already one of the most heavily funded because it's showing that much promise. Like everybody keeps looking into it more and more and more. And they're like, every time they look at it more, they're like, we just unlocked a secret of life. We just figured it out. Yeah, and we can make so much money on it.

So let's start a company and invest a lot of money in its research. All right, so CRISPR, C-R-I-S-P-R, all capitalized, stands for Clustered Regularly Interspaced Short Palindromic Repeats, which is why they called it CRISPR. Because that is a mouthful. And unless you're a geneticist, like you said, that probably those string of words together probably

just make your head spin. Right. But if you take them and separate them, I watch this video. I can't remember who did it. But I'll post it on the podcast page. Was it a TED Talk? No, it wasn't a TED Talk.

It was by a dude. Oh, what's Bozeman Science? It was a Bozeman Science video. It was really good. Bozeman Montana? It was just Bozeman Science. So now there's a Bozeman Montana and a Bozeman Science. But anyway, the guy on the video said,

just kind of take it separately. And it's actually two parts. You've got the short palindromic repeats are the thing. And the clustered, regularly interspaced thing kind of describes what that thing is, right? Yeah. So the short palindromic repeats is what you need to focus on to start.

Sure. But let's back up a little bit. OK. Let's talk a little bit about genetically modifying things. We've been doing this for a while. Everyone knows about Dolly the sheep and cloning and genetically modified fruits and vegetables. Even selective breeding is a type of genetic modification.

Sure. So it's nothing new. It's been going on for a while. But in the early 2000s, there was a discovery of an enzyme. Well, not a discovery of the enzyme, but a discovery of how to use an enzyme called a zinc finger nuclease. And what that would do is replace,

it would delete and replace very specific bad genes that would make you get a disease, let's say. Right. And it was a huge finding, but really expensive. Yeah, they were about $5,000 a piece, and they didn't work every time, for sure. No. And they were just difficult to manufacture,

difficult to understand, difficult to implement. But they did do something pretty amazing, which was they went in, removed a gene from a strip of DNA, and could replace it with another gene that you wanted. The thing is, it was just tough to use, basically. So it was a big breakthrough, but it wasn't a sweeping breakthrough because it was fragile and difficult and expensive.

That's right. Fast forward to, well, I guess, go back in time, rather, to 1987, sophomore in high school. George Brett was the man. Yeah, sure he was. John Cusack started to say anything. In 87? Well, maybe something around there.

I think that was 89-ish. No. Singles was like 89-90. No, Singles was definitely in the 90s because I was in college. But I think it was like 90. I'm going to go with 91. Please continue. All right, while you look that up.

So 1987 is when the word CRISPR first appears in a journal article because the scientists said, you know what, we found this thing in E. coli. These short repeats, what year was it? 89. These short repeats in the E. coli bacteria of DNA. And that's weird. There should not be repeats of DNA in this bacteria.

So it was noteworthy. Yeah, it's like, what is that? Right, it's a little weird. So they took note. And I guess just saying he came out and they decided to watch Cameron Crow movies for the next decade. As of 1992.

So they got bad. They started watching Singles. And in 2012 is when CRISPR, and this is just a few short years ago, is when CRISPR really came on the scene. And that's when all this money started pouring into the research. And it's like advanced light years in the last four years. Right, and the big difference between what happened in 1987 and what happened in 2012 is that they figured out

what these short palindromic repeats were, right? So you had these little strips of DNA in E. coli. And then they found out later on, you could find it in most bacteria, if not all. These short little strips seem to be separating out these what seem to be like random strings of DNA. But they separated them out in a regular interspersed manner. So they looked at the little bits of random DNA.

And they realized that it matched viral DNA. Which is totally weird. Yeah, because they're like, well, wait, this is a bacteria. What is viral DNA doing in here? And someone, I'm not exactly sure who. Scientist Eugene Coonan. Coonan was a paradigm-changing giant who is the unsung hero in this.

Coonan said, you know what I think is going on? I think what we're seeing here is essentially a database that a bacteria houses in its own DNA, where when it's invaded by a virus, it captures that virus's DNA or RNA, snips up some of it, and stores it in this genetic database so that when it sees that again, it will recognize the virus and can attack it.

Yeah, it's a genetic adaptation present. And it is not all bacteria, but in many bacteria cells to help it survive. Because a bacteria has a few minutes once it starts to get attacked by a virus to live. Right, OK. So it's part of its immune system, right? This database of what's called CRISPR.

Yeah. Then there's another thing that they figured out about bacteria that's associated with the CRISPR database and any given bacteria and a bacteria that has it. It's called Cas9. Yeah. It's CRISPR-associated enzymes, I think. Yeah, CAS9, it's a protein.

It's an RNA-guided enzyme and protein. Right, and it has this really neat function. It goes to a virus or viral DNA or viral RNA, and it captures it. It unzips it, which is not everything can do that. No. And then it also precisely snips it and then delivers that snip to the bacteria's CRISPR database

for storage. Yeah, so what you have is it's an edit as opposed to, like we've been working with genetic addition and transfer for years, like treating people with transferring into bone marrow, let's say. But this is an actual edit. Like, they liken it in this article, even though our own article never mentioned Cas9, which

is, like, I can't even believe. Yeah, you can't really have one without the other pretty much. No, it was weird. But this Cas9 is literally, they liken it to an assassin like that comes in very surgically with a pair of scissors very specifically removes, ideally, just that part. Yeah, the bad part. So we'll talk a little more about this.

We've got to take a break, though, everybody. We're getting a little work done. Run it, go, run it, go, go, run it, go, go, go, go, go! On the podcast, HeyDude, the 90s, called David Lasher and Christine Taylor, stars of the cult classic show, HeyDude, bring you back to the days of slipdress.