Stuff You Should Know - Optogenetics: Controlling Your Genes with Light

Episode Date: February 11, 2020

What if a genetic brain disease could be turned off simply by flashing a light in your eyes? What if your depression could be cured that way? Sounds amazingly wonderful, true, but what if your behavior could be controlled that way too? 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. Welcome to Step You Should Know, a production of iHeart radios, How Stuff Works. Hey, and welcome to the podcast. I'm Josh Clark. There's Charles W. Chuck Bryant.

There's guest producer Josh T. over there. Josh T. Josh Tizzy. That's his new nickname, okay, Josh? He's nodding. Good, yep. He knows the score. How you doing, man?

Oh, I've had better days and weeks, but you know, if only there was a LED light, someone could blink in my eyeballs and fix everything. I know, that's actually, that was a question of mine like earlier about, you know, could you just shine a light in somebody's eyeballs and make this work? And that's probably the future, but who knows?

He's not the present, I should say. Unfortunately, no. So soon enough, Chuck, though, soon enough, just hang on another 50 years. Okay. So we're talking today about optogenetics. And if that word doesn't sound at all familiar, don't worry, it's only been around for honestly 15 years.

It's like the cutting edge in manipulating the function of brain cells to make them do what you wanna do, or to study brain pathways to see which ones are responsible for what. Right. And it's really, really difficult to get across in the details, but it's one of those really interesting science tech things

that the broad strokes are like really understandable, you know? Yeah, I mean, you're literally one day, hopefully, well, I don't know about hopefully, but possibly going to be able to turn on and turn off neural cells after we have modified them. Right. So we can control them.

Yeah, and modify them genetically. That's a big, big key here. Yes. So, but this is really important. And Ed put this together for us, and he makes a really good point. Like if you read, you know, kind of cutting edge side tech articles about this stuff,

it sounds like we're right there. Like we're about to start, you know, flipping on and off neural circuits in humans any day. Yeah, we're not. We are way far away from that. We're still figuring out like the ethical and legal implications of even beginning to try that. Yeah, I think the writers like that

they get really excitable about stuff. They're like, fruit flies are so boring. And they're like, we could do this and just think we could do this and this. Right. It's like maybe one day, many, many years from now, but maybe not even. Yeah, because of that whole moral and legal

and ethical implications of it. But I think there are probably plenty of people out there who are like, my depression is severe enough that I'm fine with the moral and ethical implications of this. I just want this to fix things for me because it could conceivably someday. But we say that just to say, like what we're talking about is on the frontier of science,

although some of the research that's been conducted has been successful, but it's just been conducted in things like mice and fish and fruit flies. Poor little, well, we'll put a pin in that one. Okay. Not literally, but. Well, maybe.

Yeah, poor little fruit flies. We've done some things to fruit flies. So here's the thing, right? The human brain is pretty complex as far as organs go. You compare it to your spleen. Your spleen's just gonna slink away and be like, there's no comparison here. I just produce bile.

Yeah. You know? So the brain is far more complicated than the spleen, which everybody knows. And the reason it's so complicated is because there's so many specialized cells inside that brain, neurons, right? Neurons are just one type of brain cell.

Yeah. We talked about the brain a lot over the years on the show and we always kind of come back to the same thing, which is as much as we've learned, which has been a ton, there's still a lot of shrugging going on in the room. Yeah, for sure. Geez, I don't know.

I mean, but when you look at the 100 billion neurons and the quadrillion synapses. Yeah, a thousand trillion. That's, you know, I'm giving humans a break here that we haven't figured all of this out at this point. Sure. No, we haven't. And then you look at the brain.

It's just, I mean, you look at just the big gross lumpy gray mess. Yeah, it's like a spleen on steroids. I know. Like who even wants to get in that thing to begin with? Right. People who like making squishy sounds with their finger. It should be shiny and sparkly and...

God. You gotta stop doing that. It is a little sparkly though, if you think about it. Like it's shiny because it's got, it's coated and it's bathed in cerebrospinal fluid, remember? Yeah, I guess I've never seen a picture of the brain when it's really doing its thing.

I didn't know it was so exciting looking. So, okay. So the brain is extremely complex and we figured out some stuff about it. Mainly what we figured out, starting back in the 19th century, that all of these connections, these thousand trillion synapses

that allow neurons to communicate with one another and carry like an impulse through the brain. All that is based on electricity. Chemical electricity, right? To where there's a difference in the concentration of different types of ions, say like calcium and potassium in the cell. So that when it reaches a certain concentration,

it actually generates an electrical impulse and then that impulse can be translated or transferred to another neuron. And then that neuron may send that electrical impulse on and on and on until it finally reaches its destination where suddenly you're flooded in dopamine and you're feeling pretty good because you just tried a Krispy Kreme

that was fresh and hot right off of the line. Yeah, so like when you hear people say or us say, like when your neurons are firing, that's literally what's going on. They are tiny little electrical charges. We can call them action potentials. And they measure them in tiny little millivolts. It's adorable.

It is, they have little bow ties on and short pants. Yeah, but there's little tiny electrical triggers that go off constantly. Right, right. So or they don't go off, which also has an effect as well, right? So like you can have something firing, firing, firing and then it stops firing

and you're suddenly not feeling pain any longer, which is great. So you want to have them on and off but it all is based on electricity. And we figured this out thanks to a guy named Chuck. Are you talking about Luigi Galvani? Yeah, yes, I am.

And you know that famous experiment with frog legs where you can take dismembered frog legs and sprinkle salt on them and they'll start twitching or whatever. Those are always creepy. Well, this same guy figured out that you could introduce electricity into the brains of frogs

and you can make the frog legs kind of twitch and hop in the brain of a dead frog. So it shows pretty clearly that electricity is what makes the brain move and that the brain is what makes the legs move, right? And then later on there was a guy named Roberts Barthelot. Oh boy, this guy. Did you look up this experiment?

I did. Pretty bad. Yeah, so there was a woman named Mary Rafferty who had an ulcer on her brain which ended up resulting in a literal hole in her skull. So her brain was exposed and Roberts Barthelot I guess was like, well, perfect. This is just what I've been waiting for,

is access to a human brain. So let me see if I can stimulate these neurons by poking it with needles, her brain, and see what happens when I stimulate that with electricity. And he kept it super low voltage at first and notice some things like, wow, when I poke here, her arm moves. Right, he's like, does anyone have a question?

Oh, Mary, you do? But he ramped that electricity up at higher voltage looking for what he called a more decided reaction. And he, well, he argued afterward that he did not cause her death, but she had a seizure, she went into a coma and she died. Right. So the kind of the sticking point here is,

and he was censured by the AMA, but nothing really happened was that he was experimenting on a human being, but not with the aim of curing anything that was wrong with her. No, he even said in the study that he produced that anyone who tried to replicate this would be conducting like a criminal experiment.

Yeah, but me. That it would be criminal to redo it. Yeah. I'm good. All right, I'm all good, but just don't do this again. But what was interesting to me is like, it wasn't until 1946 that we started to like the scientific community

started to enforce informed consent after the Nazi atrocities of World War II. And this guy was carrying this experiment on I think in 1874, but even at the time. So in his defense, people weren't about informed consent and there were like the ethics of scientific experiments weren't nearly as pronounced and structured as they are today.

And yet his experiment was still denounced. Like everybody could see that on some level that hadn't been like elucidated yet. He had violated something, which is actually like the life of a person. They're like, something's bothering me, but I can't quite put my finger on it. Oh, well, now he's hit me with the electric needles

and my finger is going exactly where he wants it to. Oh boy. The AMA actually banned human experimentation if it was not for the purposes of saving a human life after this. Very good stuff. So what we figured out though, from Galvani and Bartholo, yeah,

he's got a tough one, a tough last thing. And others who've showed that electricity is the currency that moves messages around the brain. That you can actually stimulate the brain with electricity to go around its internal drives and externally make it do things, right? But the problem is, is like, if you're using the site of the brain,

it's really clumsy. It really like an electrical impulse is really tough to keep localized. So if you're trying to just kind of see what one particular type of neuron does, well, TS for you because you're electrically gonna stimulate a whole bunch of neurons in the neighborhood.

And it's not a very fine-tuned way of studying how the brain works. And again, it's really important that we understand what regions of the brain are responsible for what. So if we're just kind of trying to see what regions are responsible for raising your arm, we might hit those neurons with electric needles,

but we might also like kick the leg out too. Right. That just kind of, it's not as precise as it needs to be. Do you want to use this repeated metaphor? It was a fine metaphor, but it was a mixed metaphor. And the first one really didn't work. Yeah, let's just go ahead and say it. Okay.

Because it does get a little bit more credible as the metaphor develops. But I agree, this first one was a little rough. But just take this metaphor, put it in your pocket, everybody. And smoke it with some salt. I don't even know what that means. So imagine a neighborhood or a city, if you will,

with all the people, let's say New York City, and people everywhere moving around. These are your neural network. Everyone's going places. They're taking subways, they're riding buses, they're driving cars, they're walking. Some of them that have no conscience are in a horse and buggy in Central Park.

And... It's Andre the Giant, he just stole it. And electrical stimulation, which is something that, deep brain stimulation, we talked about on the show, something we currently are doing and are able to do. Right now. Just very imprecisely.

So that electrical stimulation is like trying to learn about people only driving Ferraris through New York City by setting a city block on fire. That's where it loses me. Because it doesn't make any sense. Okay. I saw it.

She said shocking entire city block. Sure, I guess so, yeah. That would have made more sense, right? Yeah, I saw another analogy on, you know how we always say when you can't understand something go to like the kids science website? Oh, sure. I found one called Frontiers for Young Minds,

and they were explaining optogenetics, and they basically put it similarly saying, if you wanted to study the movement of traffic in the city, but you wanted to see like, like you were saying how Ferrari car drivers drive, you wanna be able to tell everybody when to drive. But the problem is if you're using an electrical stimulation, that doesn't just tell Ferrari drivers when to drive.

It tells everybody in the city when to start driving and everyone starts driving. So it doesn't tell you anything about just the Ferrari drivers. Yeah, that makes sense. And by the way, Ferrari, you owe Chuck and me a new Ferrari each for all this Buzz Ferrari marketing Ferrari. I would just like to drive one once.

That'd be fun. Don't set your sights higher than that, Chuck. I'm not a car guy. See if we can get a free one. Ferrari would just stress me out. We'll sell it on Craigslist. I'm gonna park a Ferrari in my driveway. Backwards, you back it in.

Oh goodness. So should we take a break now that we have a nice little setup in hand? Sure. Let's take a break and we're gonna talk about potassium and calcium and color dye right after this. And inside me, I should have one, Chuck.

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. It's a podcast packed with interviews, co-stars, friends, and non-stop references to the best decade ever. Do you remember going to Blockbuster? Do you remember Nintendo 64? Do you remember getting Frosted Tips?

Was that a cereal? No, it was hair. Do you remember AOL Instant Messenger and the dial-up sound like poltergeist? So leave a code on your best friend's beeper because you'll want to be there when the nostalgia starts flowing. Each episode will rival the feeling

of taking out the cartridge from your Game Boy, blowing on it and popping it back in as we take you back to the 90s. 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.

The hardest thing can be knowing who to turn to when questions arise or times get tough or you're at the end of the road. Ah, okay, I see what you're doing. 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. This, I promise you. Oh, God. Seriously, I swear. And you won't have to send an SOS because I'll be there for you. Oh, man. And so, my husband, Michael.

Um, hey, that's me. Yep, we know that, Michael. And a different hot, sexy teen crush boy bander each week to guide you through life, step by step. Oh, not another one. Kids, relationships, life in general can get messy. You may be thinking, this is the story of my life. Just stop now.

If so, tell everybody, yeah, 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. All right, so people figured out pretty quickly that, yes, electrical impulses will make parts of the brain work,

but it's not very precise. We need a more precise way to study the different parts of the brain to see what's going on where at any given time. That's right. And enter Lawrence Cohen in the 1970s. Leonard Cohen's brother. No.

It could be. Oh, oh man. You don't know. I was so disappointed. I thought, wow, that's amazing. All the genius in one family. You're right, yeah, that's a lot of genius. And in 1980, it was further developed

by a man named Roger Cien. Leonard Cohen's one-time stage manager. Okay, I was waiting on that. Is it Cien? Is it Cien? Dien. I don't know, T-S-I-E-N. Yeah.

Anytime your name starts with T-S, I send one of those as silent. Yeah, but I think they together make a D sound. Oh, really? I think so. In what language? Chinese, Mandarin maybe, Cantonese, one of those two. Okay.

Oh God, I feel like I'm drowning. It's okay. Grab hold of me. Yeah, thanks Chuck. So what they did was they worked on this synthetic dye. Like I said, Cohen in the 70s, refined in the 80s by Roger T. Roger T-S.

You already talked about in the intro about the action potential in a neuron that's created that little electrical charges. It's not like it's plugged into something, it's created by concentrations of potassium and calcium shifting around. Right. Right, so what they figured out,

what Lawrence and Roger figured out is that you can actually introduce the synthetic dye so that the dye is produced or triggered or it becomes apparent once a calcium ion concentration reaches a certain point. And if you know that a calcium ion concentration will trigger this action potential, this electrical impulse in the neuron,

if the neuron suddenly is glowing or has this dye, colored dye that's showing up under a microscope, you know that that neuron is just fired because the calcium concentration changed enough for that dye to become apparent. Yeah, it's like the very easy way to say this is scientists basically said, you know, when someone metaphorically turns on a light

in that neuron, that'd be great if an actual light turned on. Yeah, this is very similar to that for sure. And it still was a little, it's a little clunky because well, I'm not fully under, I don't fully understand why it's a little clunky. I think it's that maybe you can't control it. It's just you can witness it, I think is the issue with it. Well, if we're going to further that metaphor.

I was really trying to escape past this one, but go ahead. The next step would be, you want to learn about these Ferrari drivers in New York City. So you just paint an entire city block instead of shocking it with electricity or setting it on fire. But any car that's driving on that city block

is going to glow. Or it's going to move through the paint. So you're going to get- Glow paint, I see. Car track, sure. You're going to get glow paint all over every car. You still are not just targeting the Ferrari. But it's better.

The metaphor, sure. That's right. Much better. But it's still not precise enough. And I think where it's lacking is that, yes, you can see now what neuron has just gone off, but you can't make the neuron go off. But Lawrence and Roger gave future researchers an idea.

They're like, wait a minute, we're on to something here. Like being able to see when a neuron has gone off, that is a great idea. Let's figure out how to do that, but also make neurons go off. And to do this, they turn to our friends in the sea for help. Yeah, this is really interesting.

And this is where genetics come into play because it is important to point out that neurons are basically the same. They all contain basically the same genetic information even, but it's that mystery of the differences switching these genes on and off, and why would one be switched on when another switched off? That's sort of like what makes them unique among each other.

Right, right. So like if you have a human cell, especially like say a stem cell or whatever, but any cell has all of your genetic blueprint in it. It's just depending on what genes are on or off, that determines what kind of cell it is and what it's responsible for doing. So maybe it's like a retinal cell and it detects light,

or maybe it's a cardiac cell and it makes up a heart muscle. All of them have the same DNA, the same genetic blueprint, but some of those genes are gonna be turned off, some are gonna be turned on. And the same is true for neural cells too, right? You have neural cells that are responsible for releasing dopamine. You have neural cells that are responsible

for sensing temperature. You have all these different neural cells, and all of them are roughly the same kind of cell, but they have different genes turned on and off. And once you know that, and once you can differentiate between one gene and another, you've just taken your first step toward genetically manipulating these different genes,

you know? And understanding Ferrari drivers. Exactly. So you brought us to the sea and I jumped right back out again, and now we are back at the sea. Like the manatee. That's right.

But here, this is where it gets super, super cool. And sounds like it's confusing, but it's really not. It's really pretty simple still. There are genes in mother nature that respond to light, and then there are proteins that emit light when they're triggered by something. They fluoresce. Yeah, I like to say glow.

In fact, if you'll look here, I scratched out fluoresce every single time. Yes, you did. Wow. That's a lot of work you put into those genes. It's just a lot easier to say glow. I think people get it a lot better than fluoresce. I watched Coming to America the other day,

and man, Soul Glow is so hilarious. It still holds up. That movie's even better than I remember actually. It's great. Yeah, it's what we go back to a lot. Like I knew Eddie Murphy was a charmer, but dude, that guy is one charming human being. Yeah, all the barbershop stuff is just so classic.

It's great, but all of it, like it really, it's just a great movie. You know, they're sequeling that thing. No. They've been shooting it in Atlanta. Sequeling or rebooting? Sequeling. Oh, good.

So, I mean, I think the easiest way to go about a sequel is what they're doing, which is now King of Zamunda, Eddie Murphy, has a son who wants to find his love, but I think everyone's back, like Arsenio's back. Sure. They, oh, I'm not gonna be mean. Good.

They found him in great spirits, and he was eager to work. He said, yeah, that's a great idea. I can fit it into my sked. Then he went, woof, woof, woof. Did you see the Grammys the other day? No. I don't usually watch those either,

but I happen to see the entire thing. Oh, wow. And I- I didn't know that you were kidnapped and held against your rules. I was. It was like Mel Gibson and, oh, conspiracy theory. Okay.

I was tied to a wheelchair and my eyes were taped open. So you watched all of it, huh? Yeah, but- I watched all the Grammys since I was like 13, bro. I haven't either. It was really something. It's like a marathon or an ultrathon, really. But Tyler, the creator did like a live thing,

and it was amazing, dude. I've never heard a single second of any of his songs or see him perform or anything, but I like that guy now. Yeah, he's great. And, you know, I listened to that early. I can't even remember the acronym, but his sort of hip hop collective band

that they all started out of that like Frank Ocean came out of that. Tyler, the creator and a bunch of other guys. Whoa, what's it called? Oh, what was it? Do you know Odd Future? And then it had another like five or six words after that. Odd Future was the shortened version.

Oh, nice. Good stuff. Well, very good stuff. Thanks to Josh T for swooping in. And that the first Frank Ocean album is amazing. I've not heard that either. Oh man, it's so good. Channel Orange, I think.

I'm always confused by rappers who just have normal names. Frank Ocean, yeah, he's kind of a singer, crooner type. I mean, he does it all. All right, now that makes sense. Yeah, he's awesome. So, geez, that's how it happens. We're in the sea. Oh, right, right.

We're in the ocean. The Grammys are over. We have found genes that respond to light and also proteins in other organisms that emit light when triggered. I'll let you walk people through what those two things are. But the point is, they said, we've got the two components to make this happen.

We can build them better. Yeah, we can control genes by turning on a light. And we can also see what happens when something responds to the light. We just need to be able to get these two things from two different organisms into one thing that we can control. Exactly, exactly.

And that's the entire basis of optogenetics. I think you did a fine job of explaining it. Well, I didn't know if you want to talk literally about the jellyfish. Well, sure. So, if you don't mind. No, it's great. So, the algae, like green algae, has something called an eye.

So, it's like a single cell organism, right? Yeah. And it has an eye hole, which is light sensitive. It's a light sensitive area on the cell. And when sunlight hits that eye hole, it triggers the tail of the algae to start moving toward the sunlight so that that single cell algae can maximize its exposure

to sunlight as much as possible. All right, so that's one half. You got the thing that sees light and reacts to it. Right. And again, all this stuff has to do with ion channels that has to do with the concentration of minerals inside and outside of the cell in these channels, right? And that's what triggers this movement.

That's what triggers the electrical impulse. That's the basis of all life, apparently, are the movement of minerals inside and outside of cell membranes triggering electrical impulses. That's life. That's right. Isn't that bizarre? It is.

So then with jellyfish, they have a similar thing too. We're not exactly sure why they fluoresce, but say like a predator comes up and they sense like a predator's coming, it might trigger a change in their ion concentration, which triggers a protein that fluoresces to be produced so that jellyfish starts to glow. And these are two separate things.

But like you were saying, at some point, I think in 2005, a team led by Carl Deeseroth published a paper that said, hey man, we can take this algae light sensitive gene and we can take this jellyfish fluorescent gene and put them together and then take that so that one triggers the other in like kind of this Rubik's QB way

so that if you shine light on this one gene, it will trigger the production of this fluorescence. And we can, if we can just figure out how to take that gene combination and put it into another organism that doesn't have either, then we could shine a light on that organism and make the cells in that organism glow. And now finally, finally, just the Ferraris

would start to move when we signaled for them to move. We don't have to set a city block on fire. We don't have to coat everything in glowing paint. We can just signal to the Ferraris. Can you believe this? It's astounding that they figured out not only like in theory how to do this, but they have actually over the last 15 years

been successful in doing it. It seems like something that if someone was describing, they would just be laughed out of a room and say, yeah, that's great. Take this jellyfish thing, this algae thing, put them together, shove it in a fruit flies, up a fruit flies butt and then shine a light on his face and make him rob a bank.

I think that's the ultimate goal, really. It's unbelievable. It really is, Chuck. All right, so the fruit fly is a great little candidate because we've been working with fruit flies for a long, long time when it comes to genetics. They also, we share like genes and gene sequences that are so closely matched that when we find

like a novel gene in a fruit fly, we go look at the human genome and just try to find its match and it usually matches. That's how closely related we are. 75% of human genetic diseases are also found in fruit flies. This all seems made up. Am I being pumped?

Maybe. Is this gonna come out April 1st? Maybe. Oh, so the fruit fly is a great little candidate for all those reasons and for one other reason is we can actually, we don't need to cut a fruit fly's head open to see its brain. We can see that little guy's brain through a microscope.

That's pretty great. Which is a pretty good way to analyze something just by letting it do its thing. Especially as far as the fruit fly's concerned. Oh, sure. It's like, yeah, just hold me down, that's fine. Just don't cut my head off. Yeah, but you're setting people up

to think it's all wine and roses. Yeah. I think it's pretty bad. That's when you pull a rug out from under and chuck. So what's happening though is they're putting that stuff in a fruit fly and then what you do is you have to breed like a next generation, I think. I don't think it would work on that one, would it?

No, but you can very easily cultivate like a fruit fly colony that is now genetically modified. Yeah, just throw them in a cage with some martinis and it's all over. A little bit of Sinatra classics. So this is what they did and it was successful. And so this gave them the ability to do two things. To map out where all these neurons are.

Which was the first kind of big part of this problem. And the second thing they could do is actually activate these neurons with light. Right, so now like one of the first things they experimented on, are you ready to pull the rug out from people? Sure. One of the first fruit fly experiments

that they conducted or I shouldn't say one of the first but one of the big ones was that they genetically modified fruit flies whose neurons responsible for their escape reflex, which is when their legs tense up and their wings tense up and they just fly away when they sense danger. These were now genetically modified with an algae and jellyfish combination gene sequence.

That's right. So they shined a light on the fruit flies and the fruit flies sprung away. And they said, that's pretty great, but... Makes sense. It's entirely possible that we just scared them with the light. How could we possibly figure out

if the actual neurons are being activated optogenetically? Right, and in the movie scene, you just hear a voice on the other side of a desk of some scientist eating Chinese food out of a box. Right. He goes, you know, you can cut their heads off and they still live for a little while. That's funny.

You should do that. I imagine instead, Robert, what's his name? Like scratching the chalkboard slowly. Robert Shaw. Well, yeah, with his idea about cutting their heads off. They could probably chew it both ways. Because just like Mike, the headless chicken had a lot of his brain left when they cut his head off,

so too with the fruit fly, there are genes or neurons, I should say, associated with the escape reflex that are not just located in the fruit flies head. Right. So they cut the fruit flies heads off because like you said, or like the guy who eaten Chinese food said, the fruit fly will still be able to fly around

and move around for a little while without a head. So they cut the heads off and then they shine the light into the thorax where some of these neurons are. And sure enough, the fruit flies sprung away and flew into the air headless zombie-like, but they did it specifically because those neurons were reacting to light.

So they successfully showed that you can control the behavior of a once living organism by shining a light on it once you genetically modified its neurons with these proteins. Yeah, I wanted to know a little bit more about that second part. I'm sure they did a lot of other controls,

but my first instinct was how close was this light? Did it feel like the air move when they put it in front of it? Or was it, you know, distance? But you know, they're scientists. I'm sure Rodney and his Chinese food. I'm sure you have a lot of other great suggestions for everybody.

The other questions are, did they mash the heads with their thumbs to make sure there was no way that they were getting any light info? All right, I feel like we should take another break because what we've described is almost a miracle. Yeah. But like, what good does that do us?

Great question. And we'll talk about what good it could do us right after this. And it's like it's a shoe up on a shock. It's a podcast packed with interviews, co-stars, friends, and nonstop references to the best decade ever. Do you remember going to Blockbuster? Do you remember Nintendo 64?

Do you remember getting Frosted Tips? Was that a cereal? No, it was hair. Do you remember AOL Instant Messenger and the dial-up sound like poltergeist? So leave a code on your best friend's beeper because you'll want to be there when the nostalgia starts flowing.

Each episode will rival the feeling of taking out the cartridge from your Game Boy, blowing on it and popping it back in as we take you back to the 90s. 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. The hardest thing can be knowing who to turn to when questions arise or times get tough or you're at the end of the road. Ah, okay, I see what you're doing. 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. This, I promise you. Oh, God. Seriously, I swear. And you won't have to send an SOS because I'll be there for you. Oh, man.

And so, my husband, Michael. Um, hey, that's me. Yep, we know that, Michael. And a different hot, sexy teen crush boy bander each week to guide you through life, step by step. Oh, not another one. Kids, relationships, life in general can get messy. You may be thinking, this is the story of my life.

Oh, just stop now. If so, tell everybody, yeah, 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 Podcast, or wherever you listen to podcasts. ["Fruitfly Experiment"]

Okay, so the Fruitfly Experiment, that was a, that was pretty huge, and it wasn't, it didn't just end with fruit flies. Like we said, they've successfully experimented with mice, with fish. Worms, I think. Worms, yep. And all of these are, they use these,

these types of, of ion channels or ion pumps called dopsins or opsins. It's specifically rhodopsins. They respond to light. They're stimulated by light. But they've figured out how to insert different ones into different genes. And eventually what they're thinking

is that if we can figure out how to use these in humans, we will be able to do all manner of things. Some of which we've already successfully demonstrated on things like mice and fruit flies. Not just to get a human to jump using our escape reflex, but things like treating depression as a big one. Well, yeah, that's sort of one of the, the huge potential benefits here is what if

we could literally control the release of dopamine in someone's brain. And when people suffer from depression and they're having a hard time getting their dopamine reactions to occur naturally. Instead of putting them on pills, which, you know, a pill doesn't just affect the cells that it needs to.

That's why they have a whole list of side effects. Cause they affect everything. They're like, maybe we can get so specific that we can literally turn on those cells with light, give someone a dopamine hit that will take seconds instead of weeks and weeks of being on medication that may or may not work and may or may not have devastating side effects.

Yeah, and you just hit the nail on the head that the effect will take seconds. That's one of the really big advantages of optogenetics is it's light controlled. And we have really great lights that can turn on and off very, very quickly. Like lasers connected to fiber optics is one way that they have figured out how to deliver this.

I saw a cute heartbreaking picture of a mouse with like this kind of plastic helmet on the side of its head and coming out of it was a single fiber optic cable. You remember those fiber optic kind of brushes that had like a light source at the bottom and like the brush itself was just this beautiful colorful thing.

I used to sell those at the laser show. I love those. I went and looked through like Google images and pictures of those and was just like, God, these are so pretty. Oh man, kids went nuts for them. So they had one of those fiber optic little fibers coming out of the mouse's head.

And the mouse is just this little dirt looking at the camera like what? But they can connect the end of that fiber optic cable to a laser and it will deliver that light source to inside the mouse's brain. The problem is, is there's all sorts of brain damage that you can create by inserting even like a really tiny fiber optic fiber

into the brain of something. Sure. But it is one way to do it now. What they're working on also is like I said, those rhodopsins, one of the ones they're looking at is like red shifted toward the red end of the spectrum, which means that you can use something like infrared light which is absorbed more deeply into the body

as an external light source. So you just shine like an infrared light through the skull and then that will activate the neurons in the brain too. So I don't remember exactly how we started on this but there's stuff that we're starting to figure out from these mouse models, including things like treating depression. Oh yeah, how precise it is,

how precise the delivery of light is. Which is really, really important because the timing of neurons and the triggering them and the cascade of events that it sets off is extremely precisely timed. So you couldn't just use like a flashlight and expect to treat depression. You would have to be able to time it

in the way that the brain's supposed to be doing it in the first place. Yeah, what I wonder is if in the future, and first of all, you've got to get past all the ethical hurdles of gene therapy to begin with, which are many and complex. So let's say we do get through all that and let's say we get FDA approval

to start therapies like this. What does that look like? Because if it happens in seconds, do you make an appointment and go to a specialist who does this light therapy or is this something that you, do you have a device that you're in control of? Right, so it would probably follow a model like deep brain stimulation, which you mentioned earlier,

where you have electrodes implanted in your brain that are doing basically the same thing, but a lot less precise and a lot more clumsy, but they're electrically stimulating neurons, say that release dopamine to treat depression. I don't know if we're doing that yet, but there's definitely deep brain stimulation. But do you go to a place to have that done?

No, you have like a pacemaker like device connected via wire from your brain, and then the device is like under your skin and your chest. But it's being controlled... By a computer, like you have an onboard computer on you. Right, but what I'm saying is you don't like carry around a button. No, it's under your skin.

Okay, so how would this work then? I would guess the same way that we would figure out exactly from studying optogenetically these neurons that glow when they go off. So we'll figure out the brain pathways in the regions responsible for things like depression and all that. We would figure out what the standard normal pattern is, and then teach a computer to recreate it,

and then the computer would regulate it when needed in the brain. Okay, well that makes a little more sense. But I mean, just that kind of stuff, like just that alone shows you how far we are from actually doing this in humans. Like we have no idea what the normal pattern in the brain is for like the normal serotonin release

for a normal mood. But it also raises these other questions too, Chuck, where it's like, okay, if we figure that out and we figure out how to replicate that, why stop there? Like why not just make everybody happier than we are normally? Yeah, which brings in the whole free will debate, which has been around since the dawn of time.

And Ed does a great job of kind of wrapping it up and pointing out that kind of makes you think about things. Like if we, are we just a bag of cells that can be manipulated by a flashing light? Like, is that what you're saying? Is yes we are? Yeah, totally. Like is that what happiness is?

Like you think happiness is seeing your dog when you get home from work and getting those licks, but if those are just synapses firing, that's a very, I mean, that's scientifically what's going on, but it is a very cold and humane way to look at things, I think. I disagree with that. I think it's just a, that's a better understanding

of what's going on, but I don't think it undermines the happiness you're experiencing. I think for a lot of people it might. Well, yeah, I mean, it's not like I can't see how it wouldn't, but to me it's like, no, I mean, you're still experiencing happiness. Happiness is still important to you.

Happiness is still the point of life. This is just understanding the mechanism that we experience happiness by. That's true, and I have seen you around dogs and you constantly are just saying, I'm a bag of neurons firing at once. It's like Francis Crick, the guy who co-discovered DNA. He had a book in the 70s called The Astonishing Hypothesis.

I know we've talked about it before, but he had this famous quote where he said, you're nothing but a pack of neurons. And I mean, like to me, that's a really good way of maintaining a positive outlook on things. Like no matter how bad things get, it's just neurotransmitters in your head that are going haywire or that are doing their thing.

Right, well, that's the reason to do all this. It's a regain control over it when it's not functioning correctly. And then making things even better than they are normally, naturally. There's no written law that says if we figure out how to make ourselves happier that we shouldn't do that.

And as a matter of fact, basically every moral code there is says we should do that. If we can be happier, let's figure out how to be happier. Yeah, I think the other thing it makes me think about slippery slope wise is will people cease to do the things that they do to make them happy if they can simply touch a button to do so? Yeah, that's called wire heading.

And that's actually a big problem with artificial intelligence is they're saying like, okay, if we train artificial intelligence to do something based on a reward, the artificial intelligence is just gonna go figure out how to go right to the reward button. It's gonna circumvent that. And that's a great question too,

where if we start to become like digital consciousness, where we migrate online and we shed our bodies and our consciousness just exists in digital form, then all that stuff will be available to us. And it does make you think like, okay, if our existence is just digital, if there's no purpose to it except to experience pleasure, is there anything wrong with just sitting around

experiencing pleasure all the time, or do we need more than that? I don't know, that's a next level question, if you ask me. Yeah, I mean, do you ever see wall E? Yes, sort of like that could be the future, like why go out and take a walk if you're feeling down to get some sunshine on your face if you can just press a button to do the same thing?

Yeah, like in that movie, it's like there's, well, there's something inherently wrong with that, but I don't know, man, cause like if you think about it, when you go outside and you get a walk, you feel better, you feel like more positive. If you can get that without doing the walk, do you, if you can get everything from a walk without having to go on a walk,

do you still need to go on a walk? Well, including like the benefits to your health and body. Yes, if you could get every single scrap of benefit that you can get from a walk digitally or somehow without actually going on a walk, do you need to go on a walk? I say yes, but you and I are different. No, no, I'm with you.

I still say yes as well, but I can't explain why. Okay. Yeah, yeah, I'm not just like this full transhumanist guy. I definitely have questions about the whole thing too. I think you just spilled some bong water on the carpet too. That's never gonna come out. I'm gonna stop it up with the Febreze. Yeah, that always works.

Dryer sheet, remember that? Remember when you saw kids do that at the dorms? Yeah, I don't know if kids had Febreze dryer sheets when I was in college. They didn't exist yet. Oh, okay. Or you mean just like the bounce sheets? Yes.

Oh, sure. Yeah. Yeah, I've seen those old tricks. It's hilarious. Okay, well, you got anything else about optogenetics? No, it's pretty fascinating stuff. Yeah, we'll see where it goes. Agreed.

Actually, we probably won't see where it goes in our lifetime, but. I don't know, man. I suspect that while we're alive, things are gonna change quite a bit. We'll live to see a lot of this stuff. Yeah. I'm gonna check in with you in 35 years.

Okay, you'll be sitting across the desk from me still. When we get commemorated into the podcasting hall of fame. Well, you're on that, aren't you? You're gonna stroll into that room wearing your VR headset, pressing your little dopamine button, talking about how great life is. Right, just wire headed to the guild.

That's right. So if you want to know more about optogenetics, well, go start reading about it. It's pretty interesting stuff. And since I said that, it's time for Listener Mail. Listener Mail. I think it was me who goofed up on the postal, going postal app.

When I think I offhandedly, when they were talking about the Califano commission, about how much money was spent, I think I said, text all their money. Yeah. Like a dope. Because we've covered the US Postal Service, and we know that that is not the case.

And this is from Peter, among many others. Hey guys, I wanted to start off by saying how much I love the show. You always do a great job researching the subjects you talk about. However, I knew however. I got a small bone to pick in your recent episode,

why postal employees go postal. You talked about how the US Postal Service spent four million tax dollars on the Joseph Califano commission. While Congress does still control the USPS budget, it receives no funding from them at all, and has not since the early 1980s. The USPS operates solely on the money they make

from stamps and packages. Zero tax dollars. Anyway, thanks for the amazing content. May you keep doing so for many years to come. That is from Peter and many, many others. That was very kind, Peter. And by the way, we heard from a lot of people, postal employees or people whose family was,

or are, or were in the Postal Service. And we got a range of things from, you guys are crazy, my post office is great, there's no toxic environment to people saying, oh, they're absolutely is a very toxic environment. Yeah, like it's even worse than you guys said. Yeah, so I think for the people that wrote in that said that was not the case,

then I am very happy that you work in a great place that has a great environment. But it seems like there is a range there. Right. That's the nicest way to say it. Yeah. Well, that was Peter, right? Peter.

Thanks a lot, Peter. That was a very nice way to put it. And if you want to get in touch with us like Peter did, you can go and send us an email. Send it off to StuffPodcast at iHeartRadio.com. Stuff You Should Know is a production of iHeartRadio's How Stuff Works. For more podcasts from iHeartRadio,

visit the iHeartRadio app. Apple podcasts are wherever you listen to your favorite shows. We're going to use HeyDude 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.

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HeyH.\ HeyDude. HeyDude. HeyDude. about my new podcast and make sure to listen so we'll never ever have to say bye. Bye. Bye. Bye Listen to Frosted Tips with Lance Bass on the iHeart Radio App, Apple Podcast, or wherever you listen to podcasts.