WEBVTT - Optogenetics: Controlling Your Genes with Light

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<v Speaker 1>Welcome to Stuff You should know, a production of I

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<v Speaker 1>Heart Radios How Stuff Works. Hey, and welcome to the podcast.

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<v Speaker 1>I'm Josh Clark. There's Charles W. Chuck Bryant, and there's

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<v Speaker 1>guest producer Josh T over there, Josh T Josh Tizzy.

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<v Speaker 1>That's his new nickname. Okay, Josh nodding, goodhead, Yep, he knows,

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<v Speaker 1>he knows the score. How you doing, man? Oh, I've

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<v Speaker 1>had better days and weeks. But you know, if only

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<v Speaker 1>there was a la ed light, someone could blink in

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<v Speaker 1>my eyeballs and hits everything. I know. I that's actually

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<v Speaker 1>that was a question of mine, like earlier about you know,

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<v Speaker 1>could you just shine a light in somebody's eyeballs and

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<v Speaker 1>make this work? And I that's probably the future, but

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<v Speaker 1>who knows. It's not the it's not the present. Should

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<v Speaker 1>fortunately know? So um soon enough, Chuck though, soon enough.

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<v Speaker 1>Just hang on another fifty years. Okay. So we're talking

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<v Speaker 1>today about opti genetics. And if that word doesn't sound

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<v Speaker 1>at all familiar, don't worry. It's only been around for

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<v Speaker 1>honestly fifteen years. It's like the cutting edge in um

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<v Speaker 1>manipulating the function of brain cells to make them do

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<v Speaker 1>what you want to do or to study brain pathways

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<v Speaker 1>to see which ones are responsible for what. And it's

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<v Speaker 1>really really difficult to get across in the details. But

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<v Speaker 1>it's one of those really interesting science tech things that

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<v Speaker 1>the broad Strokes are like really understandable, you know. Yeah,

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<v Speaker 1>I mean you're literally one day, hopefully well I don't

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<v Speaker 1>know about hopefully, but possibly going to be able to

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<v Speaker 1>turn on and turn off uh neural cells. Yeah, after

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<v Speaker 1>we have modified them, right, so we can control them. Yeah,

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<v Speaker 1>and modify them genetically. That's a big, big key here, yes,

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<v Speaker 1>So but this is really important. Ed put this together

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<v Speaker 1>for us, and he makes a really good point like

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<v Speaker 1>if you read you know, kind of um cutting edge

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<v Speaker 1>side tech articles about this stuff, it sounds like we're

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<v Speaker 1>right there, like we're about to start, you know, flipping

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<v Speaker 1>on and off neural neural circuits and humans any day.

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<v Speaker 1>We're not. We are way far away from that. We're

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<v Speaker 1>still figuring out like the ethical and legal implications of

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<v Speaker 1>even beginning to try that. Yeah. I think the writers

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<v Speaker 1>like that get they get really excitable about stuff. They're

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<v Speaker 1>like fruit flies are so boring, and they're like we

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<v Speaker 1>could do this, and just think we could do this

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<v Speaker 1>and this, and it's like maybe one day, many many

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<v Speaker 1>years from now, but maybe not even yeah, because of

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<v Speaker 1>that whole moral and legal and ethical implications of it.

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<v Speaker 1>But I think, um, I think there are probably plenty

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<v Speaker 1>of people out there who are, like, my depression is

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<v Speaker 1>severe enough that I'm fine with the moral and ethical

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<v Speaker 1>implications of this. I just want this to to fix

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<v Speaker 1>things for me, because it could conceivably someday. But we

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<v Speaker 1>say that just to say, like, what we're talking about

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<v Speaker 1>is on the front tier of science. Although some of

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<v Speaker 1>the research that's been conducted has been successful, but it's

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<v Speaker 1>just been conducted in things like mice and fish and

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<v Speaker 1>fruit flies. Poor little well, we'll put a pin in

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<v Speaker 1>that one, not literally, but well maybe yeah, poor little

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<v Speaker 1>fruit flies done some things to fruit flies. So here's

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<v Speaker 1>the thing, right, the human brain is pretty complex as

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<v Speaker 1>far as organs go. You compared to your spleen, your

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<v Speaker 1>spleen is just gonna slink away and be like, there's

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<v Speaker 1>no comparison here. I just produced bile, you know. So

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<v Speaker 1>the brain is far more complicated than the spleen, which everybody,

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<v Speaker 1>everybody knows. And the reason it's so complicated because there's

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<v Speaker 1>so many specialized cells inside that brain. Neurons, right, Neurons

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<v Speaker 1>are just one tie put brains out. Yeah, and you know,

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<v Speaker 1>we've talked about the brain a lot over the years

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<v Speaker 1>on this show, and we always kind of come back

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<v Speaker 1>to the same thing, which is as much as we've learned,

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<v Speaker 1>which has been a ton, there's still a lot of

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<v Speaker 1>shrugging in the room. Yeah for sure. Jeez, I don't know.

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<v Speaker 1>I mean, but when you look at the hundred billion

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<v Speaker 1>neurons and the quadrillion synapsies, yeah, thousand trillion, that's you know,

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<v Speaker 1>give it, I'm giving humans a break here that we

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<v Speaker 1>haven't figured all of this out at this point. We haven't.

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<v Speaker 1>And then you look at the brain it's just I mean,

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<v Speaker 1>you look AT's just a big, gross, lumpy, gray mess. Yeah,

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<v Speaker 1>it's like it's like a spleen on steroids. I know, Like,

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<v Speaker 1>who even wants to get in that thing to begin with?

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<v Speaker 1>People who like making squishy sounds at their finger. It

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<v Speaker 1>should be shiny and sparkly, and god, you gotta stop

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<v Speaker 1>doing that. It is a little sparkly though, if you

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<v Speaker 1>think about it, like it's shiny because it's got it's

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<v Speaker 1>coated and it's bathed in cerebro spinal fluid. Remember, Yeah,

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<v Speaker 1>I guess I've never seen a picture of the brain

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<v Speaker 1>when it's really donuts thing. I didn't know it's so

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<v Speaker 1>exciting looking, so so okay, So the brain is extremely complex,

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<v Speaker 1>and we figured out some stuff about it. Um. Mainly

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<v Speaker 1>what we figured out starting back in the nineteenth century

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<v Speaker 1>that all of these connections, these thousand trillions and napses

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<v Speaker 1>UM that that allow neurons to communicate with one another

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<v Speaker 1>and carry like an impulse through the brain. All that

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<v Speaker 1>is based on electricity chemical electricity right to where there's

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<v Speaker 1>a difference in the concentration of different types of ion,

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<v Speaker 1>say like calcium in potassium in the cell, so that

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<v Speaker 1>when it reaches a certain concentration, it actually generates an

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<v Speaker 1>electrical impulse, and then that impulse can be translated or

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<v Speaker 1>transferred to another neuron, and then that neuron may send

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<v Speaker 1>that electrical impulse on and on and on until it

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<v Speaker 1>finally reaches its destination where suddenly you're you're flooded in

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<v Speaker 1>dopamine and you're feeling pretty good because you just try

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<v Speaker 1>to crispy cream that was fresh and hot right off

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<v Speaker 1>of the line. Yeah, So like when you hear people say,

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<v Speaker 1>or us say, like when your neurons are firing, that's

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<v Speaker 1>literally what's going on. They are tiny little electrical charges. Uh,

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<v Speaker 1>we can call them action potentials, and they measure them

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<v Speaker 1>in tiny little Miller volts. It's adorable, it is. They

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<v Speaker 1>have little bow ties on and short pants. Yeah, but

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<v Speaker 1>there's little tiny electrical triggers that go off constantly, right, right, so,

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<v Speaker 1>or they don't go off, which which also has um

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<v Speaker 1>in effect as well. Right, So, like you can have

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<v Speaker 1>something firing firing and firing and that stops firing and

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<v Speaker 1>you're suddenly not feeling pain any longer, which is great.

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<v Speaker 1>So you want to have them on and off. But

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<v Speaker 1>it all is based on electricity. And we figured this

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<v Speaker 1>out thanks to a guy named Chuck. Are you talking

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<v Speaker 1>about Luis gi Galvani? Ye, yes i am. And you

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<v Speaker 1>know that famous experiment with frog legs where you can

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<v Speaker 1>take dismembered frog legs and sprinkled salt on them and

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<v Speaker 1>they'll start twitching or whatever. Those are always creepy. Well,

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<v Speaker 1>this same guy figured out that you could introduce electricity

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<v Speaker 1>into the brains of frogs and you can make the

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<v Speaker 1>frog legs kind of twitch and hop in the in

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<v Speaker 1>the brain of a dead frog. So it shows pretty

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<v Speaker 1>clearly that electricity is what move makes the brain move,

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<v Speaker 1>and that the brain is what makes the legs move. Right.

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<v Speaker 1>And then later on there was a guy named m

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<v Speaker 1>Robert's Bartholow. Boy, this guy, did you look up this experiment?

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<v Speaker 1>I did pretty pretty pretty bad. Yeah. So there was

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<v Speaker 1>a woman named Mary Rafferty who had an ulcer on

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<v Speaker 1>her brain, which ended up resulting in a literal hole

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<v Speaker 1>in her skull. So her brain was exposed, and Robert's Bartholow,

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<v Speaker 1>I guess, was like, well, well, perfect, this is just

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<v Speaker 1>what I've been waiting for, is access to a human brain.

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<v Speaker 1>So let me see if I can stimulate these neurons

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<v Speaker 1>by looking at with needles her brain, and see what

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<v Speaker 1>happens when I stimulate that with electricity. And he kept

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<v Speaker 1>it super low voltage at first and noticed some things

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<v Speaker 1>like wow, when I poke here, her arm moves right.

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<v Speaker 1>He's like, does anyone have a question, But he ramped

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<v Speaker 1>that electricity up at higher voltage, looking for what he

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<v Speaker 1>called a more decided reaction, and he well, he argued

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<v Speaker 1>afterwards that he did not cause her death, but she

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<v Speaker 1>had a seizure. She went into a coma and she died. Right,

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<v Speaker 1>So the kind of the sticking point here is and

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<v Speaker 1>he was censured by the A M A. But nothing

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<v Speaker 1>really happened was that he was experimenting on a human being,

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<v Speaker 1>but not with the aim of curing anything that was

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<v Speaker 1>wrong with her. No. He even said in the study

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<v Speaker 1>that he produced that anyone who tried to replicate this

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<v Speaker 1>would be would be UM conducting like a criminal experiment.

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<v Speaker 1>It may be criminal. Redo it. Yeah, I'm good, right,

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<v Speaker 1>I'm all good, but just don't do this again. But

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<v Speaker 1>what's what was interesting to me is like it wasn't

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<v Speaker 1>until six that we started to um, like the scientific

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<v Speaker 1>community started to enforce informed consent after the Nazi atrocities

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<v Speaker 1>of World War two. UM, And this guy was was

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<v Speaker 1>carrying this experiment and I think in eighteen seventy four.

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<v Speaker 1>But even at the time, so in his defense, people

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<v Speaker 1>weren't about informed consent, and there were like the ethics

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<v Speaker 1>of scientific experiments weren't nearly as pronounced and structured as

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<v Speaker 1>they are today. And yet his experiment was still denounced,

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<v Speaker 1>like everybody could see that on some level that hadn't

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<v Speaker 1>been like elucidated, yet he had violated something which is

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<v Speaker 1>actually like the life of a person, like something's bothering me,

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<v Speaker 1>but I can't quite put my finger on it. Oh well,

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<v Speaker 1>now he's hit me with the electric needles in my fingers,

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<v Speaker 1>going exactly where he wanted to. Oh boy, the am

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<v Speaker 1>A actually banned human experimentation if it was not for

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<v Speaker 1>the purposes of saving a human life after this very

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<v Speaker 1>good stuff. So what we figured out though from Galvani

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<v Speaker 1>and um barth Bartho, Yeah, he's got a tough one,

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<v Speaker 1>a tough last thing, Um and others who showed that

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<v Speaker 1>electricity is the currency that moves messages around the brain.

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<v Speaker 1>Um that you can actually stimulate the brain with electricity

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<v Speaker 1>to go around its internal drives and externally make it

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<v Speaker 1>do things right. But the problem is is like if

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<v Speaker 1>you're using the society of the brain, it's really clumsy.

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<v Speaker 1>It really like an electrical impulse is really tough to

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<v Speaker 1>keep localized. So if you're trying to just kind of

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<v Speaker 1>see what one particular type of neuron does, well, t

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<v Speaker 1>s for you because you're electrically going to stimulate a

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<v Speaker 1>whole bunch of neurons in the neighborhood and it's not

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<v Speaker 1>a very um a fine tuned way of studying how

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<v Speaker 1>the brain works. And again, it's really important that we

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<v Speaker 1>understand what regions of the brain are responsible for what.

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<v Speaker 1>So if we're just kind of trying to see what

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<v Speaker 1>regions are responsible for raising your arm, we might hit

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<v Speaker 1>those neurons with electric needles, but we might also like

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<v Speaker 1>kick the leg out too. That just kind of it's

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<v Speaker 1>not as precise as it needs to be. Do you

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<v Speaker 1>want to uh use this repeated metaphor? It was a

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<v Speaker 1>fine metaphor, but it was a mixed metaphor, and the

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<v Speaker 1>first one really didn't work. Yeah, let's just go ahead

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<v Speaker 1>and say it, because it does get a little bit

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<v Speaker 1>more credible as the metaphor develops. But I agree this

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<v Speaker 1>first one was a little rough. But just just take

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<v Speaker 1>this metaphor, put in your pocket, everybody, and smoke it

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<v Speaker 1>with some salt. I don't even know what that means.

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<v Speaker 1>So imagine a neighborhood or a city, if you will,

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<v Speaker 1>with all the people, let's say New York City and

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<v Speaker 1>people everywhere moving around. These are your neural uh, this

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<v Speaker 1>is your neural network. Everyone's going places. They're taking subways

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<v Speaker 1>to run busses or driving cards, are walking. Some of

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<v Speaker 1>them have that have no conscience or in a horse

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<v Speaker 1>and buggy in Central Park and it's not trade to

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<v Speaker 1>the giant. He just stole it. And Uh, electrical stimulation,

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<v Speaker 1>which is something that deep brain stimulation we've talked about

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<v Speaker 1>on the show, with something we currently are doing and

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<v Speaker 1>are able to do just very imprecisely. So, Uh, that

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<v Speaker 1>electrical stimulation is like trying to learn about people only

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<v Speaker 1>driving Ferraris through New York City by setting a city

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<v Speaker 1>block on fire. That's where it loses me because it

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<v Speaker 1>doesn't make any sense. I just said, shocking entire city block. Sure,

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<v Speaker 1>I guess so, Yeah, that would have made more sense, right. Yeah.

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<v Speaker 1>I saw another analogy on you know how we always

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<v Speaker 1>say when you can't understand something, go to like the

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<v Speaker 1>kids science website. Sure, I found one called Frontiers for

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<v Speaker 1>Young Minds, and they were explaining up to Janet's and

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<v Speaker 1>they basically put it similarly saying, if you wanted to

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<v Speaker 1>study the movement of track Affrick in the city, Um,

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<v Speaker 1>but you wanted to see like like you were saying,

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<v Speaker 1>how ferrari Um car drivers drive. Um, you want to

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<v Speaker 1>be able to tell everybody when to drive. But the

0:13:11.240 --> 0:13:14.199
<v Speaker 1>problem is if you're using an electrical stimulation that doesn't

0:13:14.240 --> 0:13:16.840
<v Speaker 1>just tell Ferrari drivers when to drive and tells everybody

0:13:16.960 --> 0:13:19.040
<v Speaker 1>in the city you want to start to start driving,

0:13:19.080 --> 0:13:21.720
<v Speaker 1>and everyone starts driving, So it doesn't tell you anything

0:13:21.760 --> 0:13:25.600
<v Speaker 1>about just the Ferrari drivers. Yeah, that makes sense. And

0:13:25.640 --> 0:13:29.120
<v Speaker 1>by the way, Ferrari, you chucking me in Ferrari each

0:13:29.240 --> 0:13:32.560
<v Speaker 1>for all this buzz Ferrari marketing. Ferrari, I would just

0:13:32.640 --> 0:13:35.400
<v Speaker 1>like to drive one once. That'd be fun. Don't don't

0:13:35.240 --> 0:13:38.079
<v Speaker 1>set your slights higher than that, chuck. See if we

0:13:38.120 --> 0:13:40.320
<v Speaker 1>can get a free one Ferrari, just stress me out.

0:13:40.440 --> 0:13:43.480
<v Speaker 1>We'll sell it on Craigslist. I'm gonna park a Ferrari

0:13:43.600 --> 0:13:50.160
<v Speaker 1>in my driveway backwards. You back it in? Oh goodness.

0:13:50.440 --> 0:13:52.840
<v Speaker 1>Uh so should we take a break now that we

0:13:52.880 --> 0:13:55.240
<v Speaker 1>have a nice little set up in hand. Sure, all right,

0:13:55.320 --> 0:13:57.960
<v Speaker 1>let's take a break, and we're gonna talk about potassium

0:13:57.960 --> 0:14:20.760
<v Speaker 1>and calcium and color dye right for this shock. Alright.

0:14:20.800 --> 0:14:24.160
<v Speaker 1>So people figured out pretty quickly that yes, electrical impulses

0:14:24.200 --> 0:14:26.280
<v Speaker 1>will make parts of the brain work, but it's not

0:14:26.400 --> 0:14:28.720
<v Speaker 1>very precise. We need a more precise way to study

0:14:29.200 --> 0:14:31.440
<v Speaker 1>the different parts of the brain to see what's going

0:14:31.520 --> 0:14:34.960
<v Speaker 1>on where at any given time. That's right, and enter

0:14:35.200 --> 0:14:39.520
<v Speaker 1>Lawrence Cohen in the nineteen seventies, Leonard Cohen's brother. No

0:14:40.240 --> 0:14:44.560
<v Speaker 1>it could be uh no, No, I was so disappointed.

0:14:45.080 --> 0:14:49.400
<v Speaker 1>I thought, wow, that's amazing. All the genius in one family. Yeah,

0:14:49.440 --> 0:14:51.800
<v Speaker 1>it's a lot of genius. Uh And in nineteen eighty

0:14:51.840 --> 0:14:55.800
<v Speaker 1>it was further developed by man named Roger CN, Leonard

0:14:55.840 --> 0:14:59.320
<v Speaker 1>Cohen's one time stage manager. Okay, it was waiting on

0:14:59.400 --> 0:15:02.800
<v Speaker 1>that is it c N? Is it c N d N?

0:15:03.320 --> 0:15:07.040
<v Speaker 1>I don't know? T S I E N anytime your

0:15:07.120 --> 0:15:08.920
<v Speaker 1>name starts with T S I seen one of those

0:15:09.000 --> 0:15:11.960
<v Speaker 1>is silent. Yeah, but I think they together make a

0:15:12.040 --> 0:15:17.920
<v Speaker 1>D sound. Oh really, I think so? In what language? Chinese, Mandarin,

0:15:18.000 --> 0:15:20.880
<v Speaker 1>maybe Cantonese, one of those two. Okay, oh god, I

0:15:20.880 --> 0:15:26.560
<v Speaker 1>feel like I'm drowning. It's okay, grab hold of me, thanks.

0:15:26.680 --> 0:15:32.200
<v Speaker 1>Uh So what they did was they worked on um

0:15:32.360 --> 0:15:36.040
<v Speaker 1>this synthetic die UM, like I said, coming in the seventies,

0:15:36.400 --> 0:15:41.840
<v Speaker 1>refined in the eighties by Roger T and Roger you

0:15:41.920 --> 0:15:45.480
<v Speaker 1>already yeah, you already talked about in the intro about

0:15:45.640 --> 0:15:49.400
<v Speaker 1>the action potential in a neuron that's created that little

0:15:49.560 --> 0:15:52.800
<v Speaker 1>electrical charges. It's not like it's plugged into something. It's

0:15:52.840 --> 0:15:58.920
<v Speaker 1>created by concentrations of potassium and calcium shifting around right right.

0:15:59.000 --> 0:16:02.920
<v Speaker 1>So what they figured out, what Um, Lawrence and Roger

0:16:03.000 --> 0:16:06.040
<v Speaker 1>figured out is that you can actually introduce the synthetic

0:16:06.120 --> 0:16:09.960
<v Speaker 1>die so that the dye is produced or triggered or

0:16:10.520 --> 0:16:15.960
<v Speaker 1>it becomes a parent once calcium ion concentration reaches a

0:16:16.000 --> 0:16:18.680
<v Speaker 1>certain point. And if you know that a calcium ion

0:16:19.440 --> 0:16:23.760
<v Speaker 1>concentration will trigger this action potential, this electrical impulse in

0:16:23.800 --> 0:16:27.320
<v Speaker 1>the neuron, if the neuron suddenly is glowing or has

0:16:27.400 --> 0:16:31.240
<v Speaker 1>this dye colored dye that's showing up under a microscope,

0:16:31.520 --> 0:16:34.000
<v Speaker 1>you know that that neuron is just fired because the

0:16:34.040 --> 0:16:38.320
<v Speaker 1>calcium concentration changed enough for that die to become a parent. Yeah,

0:16:38.360 --> 0:16:40.720
<v Speaker 1>it's like the very easy way to say this is

0:16:40.760 --> 0:16:46.040
<v Speaker 1>scientists basically said, you know when someone uh metaphorically turns

0:16:46.040 --> 0:16:48.040
<v Speaker 1>on a light and that neuron that'd be great an

0:16:48.080 --> 0:16:50.960
<v Speaker 1>actual light turned on. Yeah, this is very similar to

0:16:51.000 --> 0:16:54.280
<v Speaker 1>that for sure, And it's still was a little it's

0:16:54.280 --> 0:16:58.680
<v Speaker 1>a little clunky, um because well, I'm not fully under

0:16:58.840 --> 0:17:01.000
<v Speaker 1>I don't fully understand why it's a little clink. I

0:17:01.000 --> 0:17:04.399
<v Speaker 1>think it's that maybe you can't control it. It's just

0:17:04.600 --> 0:17:09.040
<v Speaker 1>you can witness it. I think is the issue with it. Well,

0:17:09.160 --> 0:17:12.679
<v Speaker 1>if we're going to further that metaphor, it's really giant

0:17:12.760 --> 0:17:15.840
<v Speaker 1>to escate fast to this point, but go ahead. The

0:17:15.920 --> 0:17:18.280
<v Speaker 1>next step would be, uh, you want to learn about

0:17:18.320 --> 0:17:20.520
<v Speaker 1>these Ferrari drivers in New York City, So you just

0:17:20.600 --> 0:17:23.159
<v Speaker 1>paint and inside and the entire city block instead of

0:17:23.840 --> 0:17:27.320
<v Speaker 1>shocking it with electricity or setting it on fire. But

0:17:27.600 --> 0:17:30.400
<v Speaker 1>any car that's driving on that city plot city block

0:17:30.520 --> 0:17:34.040
<v Speaker 1>is gonna it's gonna glow or it's gonna move through

0:17:34.040 --> 0:17:37.200
<v Speaker 1>the paint. So you're gonna get car track. Sure, you're

0:17:37.200 --> 0:17:39.960
<v Speaker 1>gonna get glow paint all over every car. You still

0:17:40.000 --> 0:17:45.840
<v Speaker 1>are not just targeting the Ferrari. But it's better the metaphor. Sure,

0:17:46.359 --> 0:17:50.040
<v Speaker 1>that's right, much better, but it's still not precise enough.

0:17:50.040 --> 0:17:53.800
<v Speaker 1>And I think where it's lacking is that you, yes,

0:17:53.880 --> 0:17:56.640
<v Speaker 1>you can see now what neuron has just gone off,

0:17:57.320 --> 0:18:00.880
<v Speaker 1>but you can't make the neuron go off. But but um,

0:18:01.000 --> 0:18:05.359
<v Speaker 1>Lawrence and Roger gave future researchers an idea. They're like,

0:18:05.359 --> 0:18:08.120
<v Speaker 1>wait a minute, we're onto something here, like being able

0:18:08.200 --> 0:18:11.400
<v Speaker 1>to to to see when a neuron has gone off.

0:18:11.480 --> 0:18:13.560
<v Speaker 1>That is a great idea. Let's figure out how to

0:18:13.640 --> 0:18:17.199
<v Speaker 1>do that but also make neurons go off. And to

0:18:17.240 --> 0:18:21.000
<v Speaker 1>do this they turn to our friends in the sea

0:18:21.320 --> 0:18:24.119
<v Speaker 1>for help. Yeah, this is really interesting, and this is

0:18:24.160 --> 0:18:28.760
<v Speaker 1>where um genetics come into play, because it is it

0:18:28.840 --> 0:18:33.640
<v Speaker 1>is important to point out that neurons are basically the same. Uh.

0:18:33.680 --> 0:18:38.200
<v Speaker 1>They all contain basically the same genetic information even but

0:18:38.920 --> 0:18:43.119
<v Speaker 1>it's that mystery of the differences switching these genes on

0:18:43.240 --> 0:18:45.920
<v Speaker 1>and off, and why would one be switched on when

0:18:45.960 --> 0:18:48.800
<v Speaker 1>another switched off. That's sort of like what makes them

0:18:48.880 --> 0:18:52.800
<v Speaker 1>unique among each other, right, right, So, like if you

0:18:52.840 --> 0:18:55.680
<v Speaker 1>have a human cell, especially like say a stem cell

0:18:55.760 --> 0:18:57.720
<v Speaker 1>or whatever, but any cell has all of the your

0:18:57.760 --> 0:19:00.960
<v Speaker 1>genetic blueprint, and it's just depending on what genes are

0:19:01.000 --> 0:19:04.040
<v Speaker 1>on or off that determines what kind of cell it

0:19:04.119 --> 0:19:06.639
<v Speaker 1>is and what it's responsible for doing. You know. So

0:19:06.680 --> 0:19:08.880
<v Speaker 1>maybe it's like a retinal cell and it detects light,

0:19:09.000 --> 0:19:11.600
<v Speaker 1>or maybe it's a cardiac cell and it it makes

0:19:11.680 --> 0:19:15.800
<v Speaker 1>up heart muscle. All of them have the same DNA,

0:19:16.119 --> 0:19:18.480
<v Speaker 1>the same genetic blueprint, but some of those genes are

0:19:18.480 --> 0:19:20.480
<v Speaker 1>gonna be turned off, some are gonna be turned on.

0:19:20.800 --> 0:19:23.080
<v Speaker 1>And the same is true for neural cells. To right,

0:19:23.400 --> 0:19:26.760
<v Speaker 1>you have neural cells that are responsible for releasing dopamine.

0:19:26.920 --> 0:19:31.200
<v Speaker 1>You have neural cells that are responsible for sensing temperature. Um.

0:19:31.440 --> 0:19:33.600
<v Speaker 1>You have all these different neural cells, and all of

0:19:33.640 --> 0:19:36.479
<v Speaker 1>them are roughly the same kind of cell, but they

0:19:36.520 --> 0:19:39.600
<v Speaker 1>have different genes turned on and off. And once you

0:19:39.640 --> 0:19:42.760
<v Speaker 1>know that, and once you can differentiate between one gene

0:19:42.760 --> 0:19:46.200
<v Speaker 1>and another, you've just taken your first step towards genetically

0:19:46.200 --> 0:19:51.040
<v Speaker 1>manipulating these different genes, you know, and understanding Ferrari drivers exactly.

0:19:51.440 --> 0:19:53.960
<v Speaker 1>So you brought us to the sea, and I jumped

0:19:53.960 --> 0:19:55.720
<v Speaker 1>it right back out again, and now we are back

0:19:55.760 --> 0:20:01.280
<v Speaker 1>at the sea like the manatee. That's right. But here

0:20:01.359 --> 0:20:04.040
<v Speaker 1>this is where it gets super super cool. Uh. And

0:20:04.320 --> 0:20:06.440
<v Speaker 1>it sounds like it's confusing, but it's really not. It's

0:20:06.480 --> 0:20:10.440
<v Speaker 1>really pretty simple still. Um. There are genes in mother

0:20:10.560 --> 0:20:13.760
<v Speaker 1>nature that respond to light, and then there are proteins

0:20:13.880 --> 0:20:18.080
<v Speaker 1>that emit light when they're triggered by something. Flores Yeah,

0:20:18.160 --> 0:20:20.280
<v Speaker 1>I like to say glow. In fact, if you'll look here,

0:20:20.359 --> 0:20:24.520
<v Speaker 1>I scratched out fluoresce every single time as you did glow.

0:20:24.760 --> 0:20:26.439
<v Speaker 1>That's a lot of work you put into those, just

0:20:26.520 --> 0:20:28.560
<v Speaker 1>a lot easier to say glow. I think people get

0:20:28.560 --> 0:20:31.359
<v Speaker 1>it a lot better than Fluoresce. I watched Coming to

0:20:31.400 --> 0:20:34.720
<v Speaker 1>America the other day of Man Soul. Glow is so hilarious.

0:20:34.960 --> 0:20:37.560
<v Speaker 1>It still holds up. That movie is even better than

0:20:37.600 --> 0:20:40.159
<v Speaker 1>I remember. Actually it's great. Yeah, it's when we go

0:20:40.240 --> 0:20:42.600
<v Speaker 1>back to a lot. Like I knew Eddie Murphy was

0:20:42.720 --> 0:20:48.840
<v Speaker 1>a charmer, but dude, that guy is one charming human being. Yeah,

0:20:49.160 --> 0:20:51.520
<v Speaker 1>all the all the barbershop stuff is just so classic.

0:20:51.600 --> 0:20:53.480
<v Speaker 1>It's great, but all of it like it really, it's

0:20:53.520 --> 0:20:56.280
<v Speaker 1>just a great, great movie. You know, they're sequeling that thing.

0:20:57.040 --> 0:21:01.240
<v Speaker 1>They've been shooting it in Atlanta. Sequeling or rebooting sequel

0:21:01.520 --> 0:21:04.639
<v Speaker 1>Oh good? So uh. I mean, I think the the

0:21:04.680 --> 0:21:07.400
<v Speaker 1>easiest way to go about a sequel is what they're doing,

0:21:07.440 --> 0:21:10.919
<v Speaker 1>which is now King of Zamunda. Eddie Murphy has a

0:21:11.000 --> 0:21:13.600
<v Speaker 1>son who wants to find his love. Yeah, but I

0:21:13.600 --> 0:21:18.560
<v Speaker 1>think everyone's back, like our Cineo's back. Sure they Oh,

0:21:18.640 --> 0:21:21.480
<v Speaker 1>I'm not gonna be mean good. They found him in

0:21:21.520 --> 0:21:24.200
<v Speaker 1>great spirits and he was eager to work. He said, yeah,

0:21:24.240 --> 0:21:26.520
<v Speaker 1>that's a great idea. I can fit it into my skin.

0:21:26.720 --> 0:21:29.440
<v Speaker 1>Then he went, whoo, who did you see the Grammy's

0:21:29.480 --> 0:21:32.560
<v Speaker 1>the other day. I don't usually watch those either, but

0:21:32.640 --> 0:21:36.320
<v Speaker 1>I happened to see the entire thing, and um, I

0:21:36.320 --> 0:21:39.560
<v Speaker 1>didn't know that you were kidnapped and it was it

0:21:39.680 --> 0:21:45.840
<v Speaker 1>was like um mel Gibson and um oh conspiracy theory.

0:21:45.920 --> 0:21:48.160
<v Speaker 1>I was tied to a wheelchair and my eyes were

0:21:48.200 --> 0:21:51.200
<v Speaker 1>taped open. So you watched all of it? Huh? Yeah,

0:21:51.200 --> 0:21:52.800
<v Speaker 1>But I haven't watched all the Grammy since I was

0:21:52.800 --> 0:21:55.280
<v Speaker 1>like thirteen, Bro, I haven't either. It was really something.

0:21:55.480 --> 0:21:59.080
<v Speaker 1>It's like a marathon or an ultrathon really, but um,

0:21:59.080 --> 0:22:01.480
<v Speaker 1>Tyler the Cree eat or did like a live thing

0:22:01.600 --> 0:22:04.480
<v Speaker 1>and it was amazing. Dude. I've never heard a single

0:22:04.560 --> 0:22:07.000
<v Speaker 1>second of any of his songs or really him perform

0:22:07.119 --> 0:22:09.600
<v Speaker 1>or anything, but um, I like that guy. Now, Yeah,

0:22:09.600 --> 0:22:11.879
<v Speaker 1>he's great. And you know I listened to that early.

0:22:12.880 --> 0:22:16.159
<v Speaker 1>I can't even remember the acronym, but his sort of

0:22:16.880 --> 0:22:20.280
<v Speaker 1>hip hop collective band that they all started out of that,

0:22:20.320 --> 0:22:22.480
<v Speaker 1>like Frank Ocean came out of that. Tyler the Creator

0:22:22.560 --> 0:22:24.880
<v Speaker 1>and a bunch of other guys whoa what's it called?

0:22:25.560 --> 0:22:29.760
<v Speaker 1>Oh what was it? Do you know? Odd Future? And

0:22:29.800 --> 0:22:32.400
<v Speaker 1>then it had another like five or six words after

0:22:32.440 --> 0:22:37.120
<v Speaker 1>that Odd Future was the shortened version. Good stuff, very

0:22:37.119 --> 0:22:39.960
<v Speaker 1>good stuff. Thanks to Josh T for swooping in and

0:22:40.000 --> 0:22:43.960
<v Speaker 1>that uh that the first Frank Ocean album was is amazing.

0:22:44.720 --> 0:22:46.640
<v Speaker 1>I've not heard that either. Oh man, it's so good

0:22:46.720 --> 0:22:50.360
<v Speaker 1>Channel Orange. I think I'm always confused by rappers who

0:22:50.520 --> 0:22:55.320
<v Speaker 1>who just have normal names. Uh Frank Ocean. Yeah, he's

0:22:55.400 --> 0:22:57.840
<v Speaker 1>kind of a singer, crooner type. I mean he does Okay,

0:22:57.880 --> 0:23:00.679
<v Speaker 1>all right, now that makes sense. Yeah, he's he's awesome.

0:23:01.560 --> 0:23:05.600
<v Speaker 1>So cheeze. That's how it happens. We're in the sea.

0:23:06.840 --> 0:23:09.840
<v Speaker 1>We're in the ocean. The Grammys are over right. We

0:23:09.880 --> 0:23:13.960
<v Speaker 1>have found genes that respond uh to light and also

0:23:14.040 --> 0:23:18.360
<v Speaker 1>proteins and other organisms that emit light when triggered. I'll

0:23:18.440 --> 0:23:21.200
<v Speaker 1>let you walk people through what those two things are.

0:23:21.320 --> 0:23:24.000
<v Speaker 1>But the point is they said, we've got the two

0:23:24.080 --> 0:23:28.360
<v Speaker 1>components to make this happen. We can build we can

0:23:28.400 --> 0:23:31.760
<v Speaker 1>control jenes turning on a light, and we can also

0:23:32.720 --> 0:23:34.960
<v Speaker 1>see what happens when something responds to the light. We

0:23:35.040 --> 0:23:37.880
<v Speaker 1>just need to be able to get these two things

0:23:37.880 --> 0:23:40.080
<v Speaker 1>from two different organisms into one thing that we can

0:23:40.080 --> 0:23:45.440
<v Speaker 1>control exactly exactly, And that's the entire basis of optogenetics. Um.

0:23:45.480 --> 0:23:47.560
<v Speaker 1>I think you did a fine job of explaining it. Well,

0:23:47.600 --> 0:23:49.200
<v Speaker 1>I didn't know if you want to talk literally about

0:23:49.240 --> 0:23:53.480
<v Speaker 1>the jellyfish, and well sure so if you don't mind, no,

0:23:53.560 --> 0:23:56.639
<v Speaker 1>it's great. So the algae, like green algae, has something

0:23:56.640 --> 0:23:59.520
<v Speaker 1>called an eye so it's like a single cell organism, right, yeah,

0:24:00.160 --> 0:24:03.800
<v Speaker 1>And it has an eyehole which is light sensitive. It's

0:24:03.800 --> 0:24:07.359
<v Speaker 1>a light sensitive area on the cell. And when sunlight

0:24:07.960 --> 0:24:11.400
<v Speaker 1>hits that eyehole, it triggers the tail of the algae

0:24:11.400 --> 0:24:13.920
<v Speaker 1>to start moving towards the sunlight so that that single

0:24:13.960 --> 0:24:17.800
<v Speaker 1>cell algae can can maximize its exposure to sunlight as

0:24:17.880 --> 0:24:19.800
<v Speaker 1>much as possible. All right, So that's one half. You

0:24:19.880 --> 0:24:22.840
<v Speaker 1>got the thing that sees light and reacts to it, right,

0:24:23.080 --> 0:24:26.360
<v Speaker 1>And again, all this stuff has to do with ion channels.

0:24:26.520 --> 0:24:29.000
<v Speaker 1>That has to do with the concentration of minerals inside

0:24:29.000 --> 0:24:32.320
<v Speaker 1>and outside of these the cell in these channels, right,

0:24:32.720 --> 0:24:35.119
<v Speaker 1>and that's what triggers this movement. That's what triggers the

0:24:35.160 --> 0:24:39.640
<v Speaker 1>electrical impulse. That's the basis of all life apparently, are

0:24:39.680 --> 0:24:43.120
<v Speaker 1>the movement of minerals inside and outside of cell membranes

0:24:43.160 --> 0:24:48.840
<v Speaker 1>triggering electrical impulses. That's life in that bizarre So then

0:24:48.840 --> 0:24:51.439
<v Speaker 1>with jellyfish they have a similar thing too. We're not

0:24:51.520 --> 0:24:55.960
<v Speaker 1>exactly sure why they fluoresce, but say like a predator

0:24:56.040 --> 0:24:58.560
<v Speaker 1>comes up and they sense like a predator's coming, it

0:24:58.680 --> 0:25:01.640
<v Speaker 1>might trigger a chain inge in their eye on concentration,

0:25:01.760 --> 0:25:05.240
<v Speaker 1>which triggers a protein that fluoresces to be produced. So

0:25:05.280 --> 0:25:09.320
<v Speaker 1>the jellyfish starts to glow. And these are two separate things,

0:25:09.520 --> 0:25:11.800
<v Speaker 1>but like you were saying, at some point, I think

0:25:11.800 --> 0:25:14.480
<v Speaker 1>in two thousand five, a team led by Carl dis

0:25:14.640 --> 0:25:18.800
<v Speaker 1>roth Um published a paper that said, hey, man, we

0:25:18.840 --> 0:25:23.480
<v Speaker 1>could take this algae light sensitive gene, and we can

0:25:23.520 --> 0:25:29.119
<v Speaker 1>take this jellyfish fluorescent gene and put them together, and

0:25:29.160 --> 0:25:31.919
<v Speaker 1>then take that so that one triggers the other, and

0:25:31.920 --> 0:25:34.000
<v Speaker 1>like kind of this rubics QB way, so that if

0:25:34.040 --> 0:25:37.240
<v Speaker 1>you shine light on this one gene, it will trigger

0:25:37.320 --> 0:25:40.520
<v Speaker 1>the production of this fluorescence. And we can if we

0:25:40.560 --> 0:25:42.960
<v Speaker 1>can just figure out how to take that gene combination

0:25:43.200 --> 0:25:45.680
<v Speaker 1>and put it into another organism that doesn't have either,

0:25:46.200 --> 0:25:48.680
<v Speaker 1>then we could shine a light on the organism and

0:25:48.720 --> 0:25:53.520
<v Speaker 1>make the cells in that organism glow. And now finally, finally,

0:25:54.080 --> 0:25:57.440
<v Speaker 1>just the ferraris would start to move when we signaled

0:25:57.480 --> 0:25:59.399
<v Speaker 1>for them to move. We don't have to set a

0:25:59.480 --> 0:26:01.840
<v Speaker 1>city block on fire. We don't have to code everything

0:26:01.880 --> 0:26:05.080
<v Speaker 1>and glowing paint. We can just signal to the ferraris.

0:26:05.520 --> 0:26:09.280
<v Speaker 1>Can you believe this? It's it's astounding that that they

0:26:09.400 --> 0:26:12.399
<v Speaker 1>figured out not only like in theory, how to do this,

0:26:12.440 --> 0:26:15.080
<v Speaker 1>but they have actually, over the last fifteen years, been

0:26:15.119 --> 0:26:17.600
<v Speaker 1>successful in doing it. It seems like something that if

0:26:17.640 --> 0:26:20.560
<v Speaker 1>someone was describing, they would just be laughed out of

0:26:20.560 --> 0:26:23.879
<v Speaker 1>a room and say, yeah, that's great. Take this jellyfish

0:26:23.920 --> 0:26:27.399
<v Speaker 1>things alogy thing, put him together, shove it in a

0:26:27.440 --> 0:26:30.960
<v Speaker 1>fruit fly, up at fruit flies, but and then shine

0:26:31.000 --> 0:26:32.800
<v Speaker 1>a light on his face and make him rob a bank.

0:26:33.200 --> 0:26:37.040
<v Speaker 1>I think that's I think that's how that's the ultimate goal. Really,

0:26:37.960 --> 0:26:40.680
<v Speaker 1>it's unbelievable. It really is chuck, all right. So the

0:26:40.720 --> 0:26:45.120
<v Speaker 1>fruit fly is a great little candidate because we've been

0:26:45.160 --> 0:26:47.800
<v Speaker 1>working with fruit flies for a long long time. When

0:26:47.800 --> 0:26:51.840
<v Speaker 1>it comes to genetics, they also um we share like

0:26:52.040 --> 0:26:55.679
<v Speaker 1>jeans in gene sequences that are so closely matched that

0:26:55.720 --> 0:26:59.040
<v Speaker 1>when we find a like a novel gene in a

0:26:59.080 --> 0:27:01.480
<v Speaker 1>fruit fly, we go look at the human genome and

0:27:01.520 --> 0:27:03.760
<v Speaker 1>just try to find its match, and it usually matches.

0:27:04.000 --> 0:27:08.080
<v Speaker 1>That's how closely related we are of human genetic diseases

0:27:08.080 --> 0:27:10.679
<v Speaker 1>are also found in fruit flies. This all seems made up,

0:27:11.520 --> 0:27:16.040
<v Speaker 1>am I being? Maybe this is gonna come out April first? Maybe?

0:27:16.600 --> 0:27:20.359
<v Speaker 1>Oh uh, So the fruit fly is a great little

0:27:20.359 --> 0:27:23.280
<v Speaker 1>candidate for all those reasons, and for one other reason

0:27:23.960 --> 0:27:27.080
<v Speaker 1>is we can actually, uh, we don't need to cut

0:27:27.080 --> 0:27:29.119
<v Speaker 1>a fruit fly's head open to see its brain. We

0:27:29.119 --> 0:27:32.320
<v Speaker 1>can see that little guy's brain through a microscope. That's

0:27:32.359 --> 0:27:34.440
<v Speaker 1>pretty great, Which is a pretty good way to analyze

0:27:34.440 --> 0:27:37.280
<v Speaker 1>something just by letting it do its do its thing,

0:27:37.320 --> 0:27:39.960
<v Speaker 1>you know, especially as far as the fruit flies concerned.

0:27:40.080 --> 0:27:42.080
<v Speaker 1>Oh sure, it's like, yeah, just just hold me down,

0:27:42.080 --> 0:27:43.760
<v Speaker 1>that's fine, Just don't cut my head off. Yeah, but

0:27:43.800 --> 0:27:45.520
<v Speaker 1>you're setting people up to think it's all of mine

0:27:45.520 --> 0:27:48.720
<v Speaker 1>and roses. Yeah, it gets pretty bad. That's when you

0:27:48.760 --> 0:27:51.480
<v Speaker 1>pull a ruck out from under him. Shock. So what's

0:27:51.520 --> 0:27:53.480
<v Speaker 1>happening though, is they're putting that stuff in the fruit fly.

0:27:53.680 --> 0:27:55.960
<v Speaker 1>And then what you do is you have to breed

0:27:56.040 --> 0:27:57.800
<v Speaker 1>like the next generation. I think I don't think it

0:27:57.840 --> 0:28:01.560
<v Speaker 1>would work on that one, would it? Um? No, But

0:28:01.560 --> 0:28:04.560
<v Speaker 1>but you can very easily cultivate like a fruit fly

0:28:05.240 --> 0:28:09.000
<v Speaker 1>colony that is now genetically modified. Just throw some throwing

0:28:09.000 --> 0:28:12.560
<v Speaker 1>in a cage with some martinis and a little bit

0:28:12.560 --> 0:28:17.280
<v Speaker 1>of Sinatra classics. So this is what they did, and

0:28:17.320 --> 0:28:21.040
<v Speaker 1>it was successful. And so this gave them the ability

0:28:21.520 --> 0:28:25.000
<v Speaker 1>to do two things to map out where all these

0:28:25.040 --> 0:28:28.000
<v Speaker 1>neurons are, which was the first kind of big part

0:28:28.000 --> 0:28:30.560
<v Speaker 1>of this problem. And the second thing they could do

0:28:30.720 --> 0:28:36.320
<v Speaker 1>is actually activate these neurons with light. Right, So, now,

0:28:36.680 --> 0:28:39.160
<v Speaker 1>like one of the first things they experimented on, are

0:28:39.200 --> 0:28:41.760
<v Speaker 1>you ready to pull the rug out from people? Sure?

0:28:42.160 --> 0:28:45.440
<v Speaker 1>One of the first fruit fly experiments that they conducted,

0:28:45.520 --> 0:28:47.160
<v Speaker 1>and I shouldn't say one of the first, but one

0:28:47.200 --> 0:28:51.960
<v Speaker 1>of the big ones was that, um, they they genetically

0:28:52.040 --> 0:28:57.160
<v Speaker 1>modified fruit flies whose neurons responsible for their escape reflex,

0:28:57.800 --> 0:29:00.320
<v Speaker 1>which is when their legs tense up and their wings

0:29:00.360 --> 0:29:03.160
<v Speaker 1>tents up and they just fly away when they sense danger.

0:29:03.800 --> 0:29:08.000
<v Speaker 1>These were now genetically modified with an algae and jellyfish combination,

0:29:08.560 --> 0:29:13.840
<v Speaker 1>uh gene sequence, that's right. So they shine a light

0:29:13.880 --> 0:29:17.440
<v Speaker 1>on the fruit flies, and the fruit flies sprung away,

0:29:17.720 --> 0:29:20.440
<v Speaker 1>and they said, that's pretty great, but makes sense. It's

0:29:20.600 --> 0:29:23.240
<v Speaker 1>entirely possible that we just scared him with the light.

0:29:24.160 --> 0:29:27.680
<v Speaker 1>How could we possibly figure out if the actual neurons

0:29:27.680 --> 0:29:31.560
<v Speaker 1>are being activated optogenetically. Right. And in the movie scene,

0:29:32.240 --> 0:29:33.840
<v Speaker 1>you just hear a voice on the other side of

0:29:33.840 --> 0:29:37.560
<v Speaker 1>a desk of some scientists eating Chinese food out of

0:29:37.560 --> 0:29:40.520
<v Speaker 1>a box. He goes, no, you cut their heads off

0:29:40.560 --> 0:29:43.360
<v Speaker 1>and they still live for a little while. That's funny.

0:29:43.400 --> 0:29:47.240
<v Speaker 1>You should do that, I imagine instead um, Robert what's

0:29:47.280 --> 0:29:52.480
<v Speaker 1>his name like scratching the chalkboards slowly with yeah, with

0:29:52.600 --> 0:29:55.840
<v Speaker 1>his idea about cutting their heads off. They could probably

0:29:55.920 --> 0:29:59.000
<v Speaker 1>cheat it both ways because just like Mike the headless chicken,

0:29:59.200 --> 0:30:01.640
<v Speaker 1>had a lot of brain left when they cut his

0:30:01.680 --> 0:30:04.480
<v Speaker 1>head off, so too with the fruit fly. There are

0:30:04.640 --> 0:30:08.480
<v Speaker 1>genes um or neurons i should say, associated with the

0:30:08.600 --> 0:30:12.320
<v Speaker 1>escape reflects that are not just located in the fruit

0:30:12.320 --> 0:30:16.160
<v Speaker 1>fly's head. So they cut the fruit flies heads off because,

0:30:16.200 --> 0:30:18.400
<v Speaker 1>like you said, or like the guy who eating Chinese

0:30:18.400 --> 0:30:21.760
<v Speaker 1>food said, um, the fruit fly will still be able

0:30:21.760 --> 0:30:24.040
<v Speaker 1>to fly around and move around for a little while

0:30:24.080 --> 0:30:27.080
<v Speaker 1>without a head. So they cut the heads off, and

0:30:27.080 --> 0:30:29.320
<v Speaker 1>then they shine the light into the thorax where some

0:30:29.400 --> 0:30:32.920
<v Speaker 1>of these neurons are, and sure enough the fruit flies

0:30:33.360 --> 0:30:37.240
<v Speaker 1>sprung away and flew into the air headless, zombie like.

0:30:37.880 --> 0:30:41.920
<v Speaker 1>But they did it specifically because those neurons were reacting

0:30:41.960 --> 0:30:45.080
<v Speaker 1>to light. So they successfully showed that you can control

0:30:45.120 --> 0:30:49.400
<v Speaker 1>the behavior of a once living organism by shining a

0:30:49.480 --> 0:30:53.000
<v Speaker 1>light on it, once you genetically modified it's it's neurons

0:30:53.040 --> 0:30:55.960
<v Speaker 1>with these proteins. Yeah, I wanted to know a little

0:30:56.000 --> 0:31:00.520
<v Speaker 1>bit more about that second part. I'm sure I did

0:31:00.560 --> 0:31:03.640
<v Speaker 1>a lot of other controls, but my first instinct was

0:31:04.520 --> 0:31:07.320
<v Speaker 1>how close was this light? Did it feel like the

0:31:07.440 --> 0:31:09.360
<v Speaker 1>air move when they put it in front of it,

0:31:09.480 --> 0:31:13.200
<v Speaker 1>or was it you know, distance. But you know, they're scientists,

0:31:13.200 --> 0:31:17.040
<v Speaker 1>I'm sure Rodney and his Chinese food, I'm sure a

0:31:17.080 --> 0:31:20.920
<v Speaker 1>lot of other great suggestions for everybody. Right. The other

0:31:21.000 --> 0:31:23.600
<v Speaker 1>questions are did they mash the heads with their thumbs

0:31:23.640 --> 0:31:25.640
<v Speaker 1>to make sure there was no way that they were

0:31:25.640 --> 0:31:28.560
<v Speaker 1>getting any light info? Al Right, I feel like we

0:31:28.560 --> 0:31:33.400
<v Speaker 1>should take another break because what we've described as almost

0:31:33.400 --> 0:31:36.120
<v Speaker 1>a miracle, but like, what good does that do us?

0:31:36.640 --> 0:31:38.720
<v Speaker 1>Great question, and well we'll talk about what good it

0:31:38.840 --> 0:32:01.680
<v Speaker 1>could do us write after this. Okay, So the fruit

0:32:01.720 --> 0:32:04.239
<v Speaker 1>fly experiment that was that was pretty huge, and it

0:32:04.280 --> 0:32:06.440
<v Speaker 1>wasn't It didn't just end with fruit flies, like we said,

0:32:06.440 --> 0:32:12.360
<v Speaker 1>They've successfully experimented with mice, with fish, um worms, worms yep,

0:32:12.600 --> 0:32:15.760
<v Speaker 1>and all of these are they they use these UM

0:32:15.920 --> 0:32:20.200
<v Speaker 1>these types of of um ion channels or ion pumps

0:32:20.240 --> 0:32:26.240
<v Speaker 1>called dopsins or opsins, it's specifically rhodopsins. They respond to light,

0:32:26.320 --> 0:32:29.520
<v Speaker 1>they're stimulated by light. UM. But they've figured out how

0:32:29.520 --> 0:32:34.280
<v Speaker 1>to insert different ones in the different genes and UM. Eventually,

0:32:34.760 --> 0:32:37.400
<v Speaker 1>what they're thinking is that if we can figure out

0:32:37.400 --> 0:32:40.080
<v Speaker 1>how to use these in humans, we will be able

0:32:40.120 --> 0:32:42.960
<v Speaker 1>to do all manner of things, some of which we've

0:32:42.960 --> 0:32:47.280
<v Speaker 1>already successfully demonstrated on on things like mice and fruit flies,

0:32:47.440 --> 0:32:49.680
<v Speaker 1>not just to get a human to jump using our

0:32:49.800 --> 0:32:53.240
<v Speaker 1>escape reflex, but things like UM. Treating depression is a

0:32:53.240 --> 0:32:56.440
<v Speaker 1>big one. Well, yeah, that's sort of one of the

0:32:56.440 --> 0:32:59.760
<v Speaker 1>the huge potential benefits here is what if we could

0:33:00.040 --> 0:33:02.840
<v Speaker 1>really control the really release of dopamine and someone's brain

0:33:03.640 --> 0:33:06.719
<v Speaker 1>and when people suffer from depression and they're having a

0:33:06.720 --> 0:33:12.520
<v Speaker 1>hard time getting their dopamine reactions to occur naturally instead

0:33:12.560 --> 0:33:15.400
<v Speaker 1>of putting them on pills, which you know, a pill

0:33:15.440 --> 0:33:19.240
<v Speaker 1>doesn't just affect the cells uh that it needs to.

0:33:19.480 --> 0:33:21.520
<v Speaker 1>That's why they have a whole list of side effects

0:33:21.800 --> 0:33:24.840
<v Speaker 1>because they affect everything. UM. They're like, maybe we can

0:33:24.880 --> 0:33:27.880
<v Speaker 1>get so specific that we can literally turn on those

0:33:27.880 --> 0:33:31.800
<v Speaker 1>cells with light, give someone a dopamine hit that will

0:33:31.840 --> 0:33:34.560
<v Speaker 1>take seconds instead of weeks and weeks of being on

0:33:34.640 --> 0:33:36.720
<v Speaker 1>medication that may or may not work and may or

0:33:36.760 --> 0:33:39.600
<v Speaker 1>may not have devastating side effects. Yeah, and you just

0:33:39.680 --> 0:33:41.480
<v Speaker 1>hit the nail on the head that the effect will

0:33:41.480 --> 0:33:45.520
<v Speaker 1>take seconds. Um. That's one of the really big um

0:33:45.680 --> 0:33:49.719
<v Speaker 1>advantages of optogenetics is it's light controlled, and we have

0:33:49.880 --> 0:33:53.000
<v Speaker 1>really great lights that can turn on and off very

0:33:53.080 --> 0:33:56.960
<v Speaker 1>very quickly, like um lasers connected to fiber optics is

0:33:57.000 --> 0:33:59.200
<v Speaker 1>one way that they have figured out how to deliver this.

0:33:59.520 --> 0:34:03.720
<v Speaker 1>I saw it's cute, heartbreaking picture of a mouse with

0:34:03.880 --> 0:34:06.400
<v Speaker 1>like this kind of plastic helmet on the side of

0:34:06.400 --> 0:34:08.640
<v Speaker 1>its head, and coming out of it was a single

0:34:08.719 --> 0:34:11.960
<v Speaker 1>fiber optic cable. Remember those fiber optic kind of brushes

0:34:12.440 --> 0:34:14.120
<v Speaker 1>that had like a light source of the bottom, and

0:34:14.160 --> 0:34:16.920
<v Speaker 1>like the brush itself was just this beautiful, colorful thing.

0:34:18.800 --> 0:34:21.480
<v Speaker 1>I love those. I went and looked through like Google

0:34:21.520 --> 0:34:23.799
<v Speaker 1>images pictures of those and it's just like, God, these

0:34:23.800 --> 0:34:28.000
<v Speaker 1>are so pretty. So they had one of those fiber

0:34:28.040 --> 0:34:30.960
<v Speaker 1>optic little fibers coming out of the mouse's head and

0:34:31.000 --> 0:34:33.120
<v Speaker 1>the mouse is just this little dirt looking at the

0:34:33.200 --> 0:34:36.520
<v Speaker 1>camera like what um, But they can they can connect

0:34:36.600 --> 0:34:39.640
<v Speaker 1>the end of that fiber optic cable to a laser

0:34:40.200 --> 0:34:43.160
<v Speaker 1>and it will deliver that light source too inside the

0:34:43.160 --> 0:34:47.040
<v Speaker 1>mouse's brain. The problem is that there's um all sorts

0:34:47.040 --> 0:34:51.160
<v Speaker 1>of brain damage that you can create by inserting even

0:34:51.200 --> 0:34:54.040
<v Speaker 1>like a really tiny fiber optic fiber into the brain

0:34:54.080 --> 0:34:57.759
<v Speaker 1>of something. But it is one way to do it now. UM.

0:34:57.840 --> 0:34:59.839
<v Speaker 1>What they're working on also is, like I said, those

0:35:00.200 --> 0:35:03.680
<v Speaker 1>Rhodopson's UM. One of the one of the ones they're

0:35:03.680 --> 0:35:07.120
<v Speaker 1>looking at is like red shifted towards the red end

0:35:07.120 --> 0:35:09.720
<v Speaker 1>of the spectrum, which means that you can use something

0:35:09.760 --> 0:35:13.160
<v Speaker 1>like infrared light, which is absorbed more deeply into the body,

0:35:13.760 --> 0:35:15.920
<v Speaker 1>as an external light source. So you just shine like

0:35:15.960 --> 0:35:19.160
<v Speaker 1>an infrared light through the skull and then that will

0:35:19.400 --> 0:35:23.359
<v Speaker 1>um will activate the neurons in the brain too. So

0:35:23.600 --> 0:35:25.920
<v Speaker 1>I don't remember exactly how we started on this, but

0:35:26.280 --> 0:35:29.319
<v Speaker 1>there's there's stuff that we're starting to figure out from

0:35:29.400 --> 0:35:33.840
<v Speaker 1>these mouse models, UM, including things like treating depression. Oh yeah,

0:35:33.840 --> 0:35:37.279
<v Speaker 1>how precise it is, How precise the delivery of light is,

0:35:38.160 --> 0:35:41.920
<v Speaker 1>which is really really important because the timing of neurons

0:35:42.360 --> 0:35:46.360
<v Speaker 1>um and the the triggering them in the the cascade

0:35:46.360 --> 0:35:49.560
<v Speaker 1>of events that it sets off is extremely precisely time.

0:35:49.760 --> 0:35:52.080
<v Speaker 1>So you can't just use like a flashlight and expect

0:35:52.120 --> 0:35:54.360
<v Speaker 1>to treat depression. You would have to be able to

0:35:54.760 --> 0:35:56.560
<v Speaker 1>time it in the way that the brain is supposed

0:35:56.600 --> 0:35:58.759
<v Speaker 1>to be doing it in the first place. Yeah, what

0:35:58.800 --> 0:36:02.239
<v Speaker 1>I wonder is if in the future, and first of all,

0:36:02.280 --> 0:36:04.480
<v Speaker 1>you've got to get past all the ethical hurdles of

0:36:04.600 --> 0:36:09.520
<v Speaker 1>gene therapy to begin with, which are many um and complex.

0:36:10.560 --> 0:36:12.200
<v Speaker 1>So let's say we do get through all that, and

0:36:12.239 --> 0:36:15.000
<v Speaker 1>let's say we get FDA approval to start therapies like this.

0:36:16.440 --> 0:36:18.920
<v Speaker 1>What kind of what does that look like? Because if

0:36:18.920 --> 0:36:21.520
<v Speaker 1>it happens in seconds, does do you make an appointment

0:36:22.040 --> 0:36:25.040
<v Speaker 1>and go to a a a specialist who does this

0:36:25.200 --> 0:36:29.120
<v Speaker 1>light therapy or is this something that you do You

0:36:29.160 --> 0:36:31.600
<v Speaker 1>have a device that you're in control of, right, so,

0:36:31.800 --> 0:36:34.399
<v Speaker 1>like it would probably follow a model like deep brain

0:36:34.440 --> 0:36:37.960
<v Speaker 1>stimulation what you mentioned earlier, where you have electrodes and

0:36:38.040 --> 0:36:41.000
<v Speaker 1>planted in your brain that are doing basically the same thing,

0:36:41.680 --> 0:36:45.200
<v Speaker 1>but a lot less precise and a lot more clumsy.

0:36:45.239 --> 0:36:49.239
<v Speaker 1>But they're electrically stimulating neurons say that released dopamine to

0:36:49.280 --> 0:36:51.120
<v Speaker 1>treat depression. I don't know if we're doing that yet,

0:36:51.120 --> 0:36:54.120
<v Speaker 1>but there's definitely deep brain stimulation. But do you go

0:36:54.239 --> 0:36:56.160
<v Speaker 1>to a place to have that done? You have like

0:36:56.160 --> 0:37:00.160
<v Speaker 1>a pacemaker like device connected via wire from your sin,

0:37:00.239 --> 0:37:02.720
<v Speaker 1>and then the devices like under your skin in your chest,

0:37:03.280 --> 0:37:08.560
<v Speaker 1>but it's being controlled by a computer, Like you have

0:37:08.600 --> 0:37:11.120
<v Speaker 1>an onboard computer on you on you right, But what

0:37:11.160 --> 0:37:15.000
<v Speaker 1>I'm saying is you don't like carry around a button, No,

0:37:15.120 --> 0:37:18.439
<v Speaker 1>it's under your skin. So how would this work? Then?

0:37:19.000 --> 0:37:21.160
<v Speaker 1>I would guess the same way that we would figure

0:37:21.160 --> 0:37:25.640
<v Speaker 1>out exactly from studying opto genetically these neurons that glow

0:37:25.719 --> 0:37:27.840
<v Speaker 1>when when they go off, So we'll figure out the

0:37:27.880 --> 0:37:30.720
<v Speaker 1>brain pathways in the regions responsible for things like depression

0:37:30.760 --> 0:37:33.560
<v Speaker 1>and all that. We would figure out what this standard

0:37:34.520 --> 0:37:38.520
<v Speaker 1>normal pattern is and then to recreate it and then

0:37:38.520 --> 0:37:41.480
<v Speaker 1>the computer would regulate it when needed in the brain.

0:37:41.880 --> 0:37:43.480
<v Speaker 1>Well that makes a little more sense, But I mean

0:37:43.560 --> 0:37:47.280
<v Speaker 1>just that kind of stuff, like just that alone shows

0:37:47.320 --> 0:37:50.280
<v Speaker 1>you how far we are from actually doing this in humans,

0:37:50.280 --> 0:37:53.960
<v Speaker 1>Like we have no idea what the normal pattern in

0:37:54.000 --> 0:37:57.920
<v Speaker 1>the brain is for like um, the like normal serotonin

0:37:58.040 --> 0:38:01.200
<v Speaker 1>release for you know, a normal mood. But it also

0:38:01.280 --> 0:38:04.480
<v Speaker 1>raises these other questions to Chuck where it's like, Okay,

0:38:04.520 --> 0:38:06.799
<v Speaker 1>if we figure that out and we figure out how

0:38:06.880 --> 0:38:10.680
<v Speaker 1>to um, how to how to replicate that, why stop there?

0:38:10.680 --> 0:38:14.640
<v Speaker 1>Like why not just make everybody happier than we are normally? Yeah,

0:38:14.680 --> 0:38:18.080
<v Speaker 1>which brings in the whole free will debate which has

0:38:18.160 --> 0:38:20.960
<v Speaker 1>been around since the dawn of time, And it also

0:38:21.239 --> 0:38:23.000
<v Speaker 1>UM and ED does a great job of kind of

0:38:23.000 --> 0:38:25.279
<v Speaker 1>wrapping it up and pointing out that kind of makes

0:38:25.280 --> 0:38:28.840
<v Speaker 1>you think about things like if we are we just

0:38:28.920 --> 0:38:32.799
<v Speaker 1>a bag of cells that can be uh manipulated by

0:38:32.800 --> 0:38:36.399
<v Speaker 1>a flashing light? Like, uh, is that where you're saying

0:38:36.480 --> 0:38:40.239
<v Speaker 1>is yes, we are? Like is that what happiness is? Like?

0:38:40.360 --> 0:38:43.200
<v Speaker 1>You think happiness is seeing your dog when you get

0:38:43.200 --> 0:38:46.040
<v Speaker 1>home from work and getting those licks. But if those

0:38:46.040 --> 0:38:49.120
<v Speaker 1>are just synapsies firing, that's a very I mean, that's

0:38:49.200 --> 0:38:51.360
<v Speaker 1>scientifically what's going on, but it is a very cold

0:38:51.600 --> 0:38:54.080
<v Speaker 1>and humane way to look at things. I think I

0:38:54.760 --> 0:38:56.799
<v Speaker 1>disagree with that. I think it's just a that's a

0:38:56.840 --> 0:38:59.040
<v Speaker 1>better understanding of what's going on, But I don't think

0:38:59.040 --> 0:39:03.040
<v Speaker 1>it undermines the happiness you're experiencing. I think for a

0:39:03.040 --> 0:39:05.719
<v Speaker 1>lot of people it might well, yeah, I mean I

0:39:05.760 --> 0:39:07.600
<v Speaker 1>it's not like I can't see how it wouldn't. But

0:39:07.680 --> 0:39:10.880
<v Speaker 1>to me, it's like, no, I mean, you're still experiencing happiness.

0:39:11.080 --> 0:39:13.960
<v Speaker 1>The happiness is still important to you. Happiness is still

0:39:14.000 --> 0:39:17.160
<v Speaker 1>the point of life. This is just understanding the mechanism

0:39:17.239 --> 0:39:20.200
<v Speaker 1>that we experience happiness by. That's true. And I have

0:39:20.280 --> 0:39:23.160
<v Speaker 1>seen you around dogs and you constantly are just saying,

0:39:23.760 --> 0:39:26.839
<v Speaker 1>I'm a bag of neurons firing at once. It's like

0:39:27.200 --> 0:39:30.160
<v Speaker 1>Francis Crick, the guy who co discovered DNA. He had

0:39:30.400 --> 0:39:33.680
<v Speaker 1>a book in the seventies called The Astonishing Hypothesis. I

0:39:33.680 --> 0:39:35.200
<v Speaker 1>know we've talked about it before, but he had this

0:39:35.239 --> 0:39:37.960
<v Speaker 1>famous quote where he said, you're nothing but a pack

0:39:38.000 --> 0:39:41.919
<v Speaker 1>of neurons. And I mean, like, to me, it's that's

0:39:41.920 --> 0:39:46.120
<v Speaker 1>a really good way of maintaining a positive outlook on things.

0:39:46.120 --> 0:39:48.560
<v Speaker 1>It's like, no matter how bad things get, it's just

0:39:48.760 --> 0:39:52.759
<v Speaker 1>neurotransmitters in your head that are going haywire or that

0:39:52.800 --> 0:39:56.840
<v Speaker 1>are doing right. Well, that's that's when. That's that's the

0:39:56.920 --> 0:39:59.839
<v Speaker 1>reason to do all this is to regain control over

0:39:59.840 --> 0:40:03.319
<v Speaker 1>it and it's not functioning correctly, and then making things

0:40:03.320 --> 0:40:06.680
<v Speaker 1>even better than they are normally Naturally, there's no written

0:40:06.800 --> 0:40:09.799
<v Speaker 1>law that says if we figure out how to make

0:40:09.840 --> 0:40:13.919
<v Speaker 1>ourselves happier, that we shouldn't do that. As a matter

0:40:13.920 --> 0:40:16.600
<v Speaker 1>of fact, basically every moral code there is says we

0:40:16.640 --> 0:40:21.080
<v Speaker 1>should do that. If we can be happier, let's figure

0:40:21.080 --> 0:40:23.680
<v Speaker 1>out how to be happier. Yeah. I think the other

0:40:23.719 --> 0:40:28.640
<v Speaker 1>thing it makes me think about, slippery slope wise, is, um,

0:40:28.920 --> 0:40:33.239
<v Speaker 1>will people cease to do the things that they do

0:40:33.360 --> 0:40:36.759
<v Speaker 1>to make them happy if they can simply touch a

0:40:36.800 --> 0:40:39.600
<v Speaker 1>button to do so? Yeah, that's called wire heading. And

0:40:39.640 --> 0:40:43.000
<v Speaker 1>that's actually a big problem with artificial intelligence is um

0:40:43.040 --> 0:40:45.840
<v Speaker 1>they're saying, like, Okay, if we train artificial intelligence to

0:40:45.840 --> 0:40:48.840
<v Speaker 1>do something based on a reward, the artificial intelligence just

0:40:48.880 --> 0:40:51.040
<v Speaker 1>gonna go figure out how to go right to the reward.

0:40:51.120 --> 0:40:53.680
<v Speaker 1>But it's not. It's going to circumvent that um. And

0:40:53.719 --> 0:40:56.080
<v Speaker 1>that's that's a great question too, where if we start

0:40:56.160 --> 0:40:59.560
<v Speaker 1>to become like digital consciousness right where we migrate online

0:40:59.600 --> 0:41:02.080
<v Speaker 1>and we should at our bodies and our consciousness just

0:41:02.160 --> 0:41:04.799
<v Speaker 1>exists in digital form, then all that stuff will be

0:41:04.840 --> 0:41:08.040
<v Speaker 1>available to us. And it does make you think like, okay,

0:41:08.080 --> 0:41:11.880
<v Speaker 1>if if our existence is just digital, there's no purpose

0:41:11.920 --> 0:41:14.680
<v Speaker 1>to it except to experience pleasure. Is there anything wrong

0:41:14.719 --> 0:41:17.239
<v Speaker 1>with just sitting around experiencing pleasure all the time? Or

0:41:17.239 --> 0:41:19.520
<v Speaker 1>do we need more than that? I don't know. That's

0:41:19.520 --> 0:41:23.359
<v Speaker 1>a that's a next next level question if you ask me. Yeah,

0:41:23.400 --> 0:41:24.839
<v Speaker 1>I mean it kind of do you ever see wall

0:41:24.960 --> 0:41:28.680
<v Speaker 1>e yes? Sort of like that there could be the future,

0:41:28.760 --> 0:41:30.400
<v Speaker 1>Like why go out and take a walk if you're

0:41:30.400 --> 0:41:34.000
<v Speaker 1>feeling down to get some sunshine on your face? If

0:41:34.040 --> 0:41:37.439
<v Speaker 1>you can just press a button to do the same thing. Yeah,

0:41:37.480 --> 0:41:40.279
<v Speaker 1>And like in that movie, it's it's like there's well,

0:41:40.320 --> 0:41:43.759
<v Speaker 1>there's something inherently wrong with that. But I don't know, man,

0:41:43.880 --> 0:41:45.400
<v Speaker 1>because like if you think about it, when you go

0:41:45.440 --> 0:41:47.759
<v Speaker 1>outside and you get a walk, you feel better, you

0:41:47.960 --> 0:41:51.000
<v Speaker 1>feel like more positive if you can get that without

0:41:51.080 --> 0:41:53.440
<v Speaker 1>doing the walk. To you, if you can get everything

0:41:53.560 --> 0:41:56.440
<v Speaker 1>from a walk without having to go on a walk,

0:41:56.600 --> 0:41:58.640
<v Speaker 1>do you still need to go on a walk? Will

0:41:58.719 --> 0:42:01.520
<v Speaker 1>including like the benefits to your health and body? Yes?

0:42:01.680 --> 0:42:04.239
<v Speaker 1>If you could get every single scrap of benefit that

0:42:04.280 --> 0:42:07.360
<v Speaker 1>you can get from a walk digitally or somehow without

0:42:07.400 --> 0:42:10.319
<v Speaker 1>actually going on a walk, do you need to go

0:42:10.360 --> 0:42:12.640
<v Speaker 1>on a walk? I say yes, but you and I

0:42:12.680 --> 0:42:14.960
<v Speaker 1>are different. No, No, I'm with you. I still say

0:42:15.040 --> 0:42:18.319
<v Speaker 1>yes as well, but I can't. I can't explain why. Okay, yeah, yeah,

0:42:18.320 --> 0:42:21.360
<v Speaker 1>I'm not just like this full transhumanist guy. I definitely

0:42:21.400 --> 0:42:23.279
<v Speaker 1>have questions about the whole thing too. I think you

0:42:23.360 --> 0:42:26.799
<v Speaker 1>just built some bond water on the carpet that's never

0:42:26.840 --> 0:42:29.000
<v Speaker 1>gonna come out. I'm gonna stop it up with a

0:42:29.160 --> 0:42:35.160
<v Speaker 1>fa breeze dryer sheet. Remember that, Remember when when kids?

0:42:35.239 --> 0:42:37.200
<v Speaker 1>You saw kids do that at the dorms. Yeah, I

0:42:37.440 --> 0:42:39.600
<v Speaker 1>don't know if kids had fabrize dryer sheets when I

0:42:39.640 --> 0:42:42.120
<v Speaker 1>was in college, they didn't exist yet, Okay. Or you

0:42:42.120 --> 0:42:46.200
<v Speaker 1>mean to just like the bounce sheets? Yes, oh sure, Yeah,

0:42:46.320 --> 0:42:51.919
<v Speaker 1>yeah I've seen I've seen those old tricks. It's hilarious. Okay, Well,

0:42:51.960 --> 0:42:54.200
<v Speaker 1>you got anything else about opt to genetics? No, it's

0:42:54.239 --> 0:42:58.400
<v Speaker 1>pretty pretty fascinating stuff. Yeah, we'll see where it goes, agreed. Actually,

0:42:58.480 --> 0:43:00.239
<v Speaker 1>probably won't see where it goes in our life time.

0:43:00.280 --> 0:43:03.120
<v Speaker 1>But I don't know, man. I suspect that while we're alive,

0:43:03.160 --> 0:43:05.520
<v Speaker 1>things are going to change quite a bit. We'll live

0:43:05.560 --> 0:43:07.560
<v Speaker 1>to see a lot of this stuff. I'm gonna check

0:43:07.560 --> 0:43:11.279
<v Speaker 1>in with you in in thirty five years, we'll be

0:43:11.320 --> 0:43:13.480
<v Speaker 1>sitting across the desk from me. Still, when we get

0:43:13.480 --> 0:43:17.040
<v Speaker 1>commemorated into the Podcasting Hall of Fame, you're on that,

0:43:17.080 --> 0:43:19.919
<v Speaker 1>aren't you. You're gonna stroll into that room wearing your

0:43:20.560 --> 0:43:24.919
<v Speaker 1>your VR headset, pressing your little dopamine button right talking

0:43:24.920 --> 0:43:28.239
<v Speaker 1>about how great life is, right, just wire headed to

0:43:28.280 --> 0:43:31.759
<v Speaker 1>the Guild's right. So if you want to know more

0:43:31.760 --> 0:43:35.800
<v Speaker 1>about optogenetics, well go start reading about It's pretty interesting stuff.

0:43:36.280 --> 0:43:39.359
<v Speaker 1>And since I said that it's time for listener mail,

0:43:42.000 --> 0:43:44.680
<v Speaker 1>listener mail, I think it was me who goofed up

0:43:44.719 --> 0:43:49.400
<v Speaker 1>on the postal going Postal EPP. When I think off handedly,

0:43:49.400 --> 0:43:53.680
<v Speaker 1>when they were talking about the Californo Commission about how

0:43:53.719 --> 0:43:57.600
<v Speaker 1>much money we spent, I think it's a tex stollar money. Yeah,

0:43:57.640 --> 0:44:00.760
<v Speaker 1>like a dope because we've covered the U. S. Postal

0:44:00.840 --> 0:44:04.040
<v Speaker 1>service and we know that that is not the case.

0:44:04.200 --> 0:44:07.279
<v Speaker 1>And this is from Peter among many others. Hey guys,

0:44:07.320 --> 0:44:08.759
<v Speaker 1>want to start off by saying how much I love

0:44:08.840 --> 0:44:11.000
<v Speaker 1>the show. You always do a great job researching the

0:44:11.000 --> 0:44:14.160
<v Speaker 1>subjects you talk about. However, I knew, however, I got

0:44:14.160 --> 0:44:16.680
<v Speaker 1>a small bone to pick. In your recent episode Why

0:44:16.760 --> 0:44:19.160
<v Speaker 1>Postal Employees Go Postal, you talked about how the US

0:44:19.200 --> 0:44:22.240
<v Speaker 1>Postal Service spent four million tax dollars on the Joseph

0:44:22.280 --> 0:44:26.000
<v Speaker 1>Californo Commission. While Congress does still control the USPS budget,

0:44:26.360 --> 0:44:28.839
<v Speaker 1>it receives no funding from them at all, and has

0:44:28.880 --> 0:44:32.640
<v Speaker 1>not since the early nineteen eighties. The USPS operates solely

0:44:32.680 --> 0:44:36.600
<v Speaker 1>on the money they make from stamps and packages zero

0:44:36.719 --> 0:44:40.160
<v Speaker 1>tax dollars. Anyway, thanks for the amazing content. May you

0:44:40.239 --> 0:44:42.200
<v Speaker 1>keep doing so for many years to come. That is

0:44:42.239 --> 0:44:46.160
<v Speaker 1>from Peter and many many others. And by the way,

0:44:46.200 --> 0:44:49.960
<v Speaker 1>we heard from a lot of people, uh, postal employees

0:44:50.000 --> 0:44:52.800
<v Speaker 1>or people whose family was are or were in the

0:44:52.840 --> 0:44:56.240
<v Speaker 1>Postal Service, and we got a range of things from

0:44:56.400 --> 0:44:58.520
<v Speaker 1>you guys are crazy, my post office is great, there's

0:44:58.520 --> 0:45:02.680
<v Speaker 1>no toxic environment, to people saying oh, they're absolutely is

0:45:02.719 --> 0:45:05.440
<v Speaker 1>a very toxic environment. Yeah, like it's even worse than

0:45:05.480 --> 0:45:08.240
<v Speaker 1>you guys said. Yeah, So I think for the people

0:45:08.239 --> 0:45:10.160
<v Speaker 1>that wrote in that said that was not the case,

0:45:10.239 --> 0:45:13.000
<v Speaker 1>then I am very happy that you work in a

0:45:13.080 --> 0:45:15.840
<v Speaker 1>great place that has a great environment. But it seems

0:45:15.880 --> 0:45:19.480
<v Speaker 1>like there is a range. They're right, that's the nicest

0:45:19.480 --> 0:45:23.200
<v Speaker 1>way to say it. Yeah. Uh, well that was Peter, right, Peter,

0:45:23.719 --> 0:45:25.960
<v Speaker 1>Thanks a lot, Peter. That was a very nice way

0:45:26.000 --> 0:45:27.319
<v Speaker 1>to put it. And if you want to get in

0:45:27.320 --> 0:45:30.799
<v Speaker 1>touch with us like Peter did, you can go and

0:45:31.000 --> 0:45:33.759
<v Speaker 1>send us an email. Send it off to stuff podcast

0:45:33.960 --> 0:45:39.200
<v Speaker 1>at iHeart radio dot com. Stuff you Should Know is

0:45:39.239 --> 0:45:41.839
<v Speaker 1>a production of iHeart Radios. How stuff works for more

0:45:41.880 --> 0:45:44.319
<v Speaker 1>podcasts for my heart Radio because at the iHeart Radio app,

0:45:44.400 --> 0:45:47.040
<v Speaker 1>Apple podcasts are wherever you listen to your favorite shows.