Speaker 1: Welcome to Stuff You should know, a production of I
Speaker 1: Heart Radios How Stuff Works. Hey, and welcome to the podcast.
Speaker 1: I'm Josh Clark. There's Charles W. Chuck Bryant, and there's
Speaker 1: guest producer Josh T over there, Josh T Josh Tizzy.
Speaker 1: That's his new nickname. Okay, Josh nodding, goodhead, Yep, he knows,
Speaker 1: he knows the score. How you doing, man? Oh, I've
Speaker 1: had better days and weeks. But you know, if only
Speaker 1: there was a la ed light, someone could blink in
Speaker 1: my eyeballs and hits everything. I know. I that's actually
Speaker 1: that was a question of mine, like earlier about you know,
Speaker 1: could you just shine a light in somebody's eyeballs and
Speaker 1: make this work? And I that's probably the future, but
Speaker 1: who knows. It's not the it's not the present. Should
Speaker 1: fortunately know? So um soon enough, Chuck though, soon enough.
Speaker 1: Just hang on another fifty years. Okay. So we're talking
Speaker 1: today about opti genetics. And if that word doesn't sound
Speaker 1: at all familiar, don't worry. It's only been around for
Speaker 1: honestly fifteen years. It's like the cutting edge in um
Speaker 1: manipulating the function of brain cells to make them do
Speaker 1: what you want to do or to study brain pathways
Speaker 1: to see which ones are responsible for what. And it's
Speaker 1: really really difficult to get across in the details. But
Speaker 1: it's one of those really interesting science tech things that
Speaker 1: the broad Strokes are like really understandable, you know. Yeah,
Speaker 1: I mean you're literally one day, hopefully well I don't
Speaker 1: know about hopefully, but possibly going to be able to
Speaker 1: turn on and turn off uh neural cells. Yeah, after
Speaker 1: we have modified them, right, so we can control them. Yeah,
Speaker 1: and modify them genetically. That's a big, big key here, yes,
Speaker 1: So but this is really important. Ed put this together
Speaker 1: for us, and he makes a really good point like
Speaker 1: if you read you know, kind of um cutting edge
Speaker 1: side tech articles about this stuff, it sounds like we're
Speaker 1: right there, like we're about to start, you know, flipping
Speaker 1: on and off neural neural circuits and humans any day.
Speaker 1: We're not. We are way far away from that. We're
Speaker 1: still figuring out like the ethical and legal implications of
Speaker 1: even beginning to try that. Yeah. I think the writers
Speaker 1: like that get they get really excitable about stuff. They're
Speaker 1: like fruit flies are so boring, and they're like we
Speaker 1: could do this, and just think we could do this
Speaker 1: and this, and it's like maybe one day, many many
Speaker 1: years from now, but maybe not even yeah, because of
Speaker 1: that whole moral and legal and ethical implications of it.
Speaker 1: But I think, um, I think there are probably plenty
Speaker 1: of people out there who are, like, my depression is
Speaker 1: severe enough that I'm fine with the moral and ethical
Speaker 1: implications of this. I just want this to to fix
Speaker 1: things for me, because it could conceivably someday. But we
Speaker 1: say that just to say, like, what we're talking about
Speaker 1: is on the front tier of science. Although some of
Speaker 1: the research that's been conducted has been successful, but it's
Speaker 1: just been conducted in things like mice and fish and
Speaker 1: fruit flies. Poor little well, we'll put a pin in
Speaker 1: that one, not literally, but well maybe yeah, poor little
Speaker 1: fruit flies done some things to fruit flies. So here's
Speaker 1: the thing, right, the human brain is pretty complex as
Speaker 1: far as organs go. You compared to your spleen, your
Speaker 1: spleen is just gonna slink away and be like, there's
Speaker 1: no comparison here. I just produced bile, you know. So
Speaker 1: the brain is far more complicated than the spleen, which everybody,
Speaker 1: everybody knows. And the reason it's so complicated because there's
Speaker 1: so many specialized cells inside that brain. Neurons, right, Neurons
Speaker 1: are just one tie put brains out. Yeah, and you know,
Speaker 1: we've talked about the brain a lot over the years
Speaker 1: on this show, and we always kind of come back
Speaker 1: to the same thing, which is as much as we've learned,
Speaker 1: which has been a ton, there's still a lot of
Speaker 1: shrugging in the room. Yeah for sure. Jeez, I don't know.
Speaker 1: I mean, but when you look at the hundred billion
Speaker 1: neurons and the quadrillion synapsies, yeah, thousand trillion, that's you know,
Speaker 1: give it, I'm giving humans a break here that we
Speaker 1: haven't figured all of this out at this point. We haven't.
Speaker 1: And then you look at the brain it's just I mean,
Speaker 1: you look AT's just a big, gross, lumpy, gray mess. Yeah,
Speaker 1: it's like it's like a spleen on steroids. I know, Like,
Speaker 1: who even wants to get in that thing to begin with?
Speaker 1: People who like making squishy sounds at their finger. It
Speaker 1: should be shiny and sparkly, and god, you gotta stop
Speaker 1: doing that. It is a little sparkly though, if you
Speaker 1: think about it, like it's shiny because it's got it's
Speaker 1: coated and it's bathed in cerebro spinal fluid. Remember, Yeah,
Speaker 1: I guess I've never seen a picture of the brain
Speaker 1: when it's really donuts thing. I didn't know it's so
Speaker 1: exciting looking, so so okay, So the brain is extremely complex,
Speaker 1: and we figured out some stuff about it. Um. Mainly
Speaker 1: what we figured out starting back in the nineteenth century
Speaker 1: that all of these connections, these thousand trillions and napses
Speaker 1: UM that that allow neurons to communicate with one another
Speaker 1: and carry like an impulse through the brain. All that
Speaker 1: is based on electricity chemical electricity right to where there's
Speaker 1: a difference in the concentration of different types of ion,
Speaker 1: say like calcium in potassium in the cell, so that
Speaker 1: when it reaches a certain concentration, it actually generates an
Speaker 1: electrical impulse, and then that impulse can be translated or
Speaker 1: transferred to another neuron, and then that neuron may send
Speaker 1: that electrical impulse on and on and on until it
Speaker 1: finally reaches its destination where suddenly you're you're flooded in
Speaker 1: dopamine and you're feeling pretty good because you just try
Speaker 1: to crispy cream that was fresh and hot right off
Speaker 1: of the line. Yeah, So like when you hear people say,
Speaker 1: or us say, like when your neurons are firing, that's
Speaker 1: literally what's going on. They are tiny little electrical charges. Uh,
Speaker 1: we can call them action potentials, and they measure them
Speaker 1: in tiny little Miller volts. It's adorable, it is. They
Speaker 1: have little bow ties on and short pants. Yeah, but
Speaker 1: there's little tiny electrical triggers that go off constantly, right, right, so,
Speaker 1: or they don't go off, which which also has um
Speaker 1: in effect as well. Right, So, like you can have
Speaker 1: something firing firing and firing and that stops firing and
Speaker 1: you're suddenly not feeling pain any longer, which is great.
Speaker 1: So you want to have them on and off. But
Speaker 1: it all is based on electricity. And we figured this
Speaker 1: out thanks to a guy named Chuck. Are you talking
Speaker 1: about Luis gi Galvani? Ye, yes i am. And you
Speaker 1: know that famous experiment with frog legs where you can
Speaker 1: take dismembered frog legs and sprinkled salt on them and
Speaker 1: they'll start twitching or whatever. Those are always creepy. Well,
Speaker 1: this same guy figured out that you could introduce electricity
Speaker 1: into the brains of frogs and you can make the
Speaker 1: frog legs kind of twitch and hop in the in
Speaker 1: the brain of a dead frog. So it shows pretty
Speaker 1: clearly that electricity is what move makes the brain move,
Speaker 1: and that the brain is what makes the legs move. Right.
Speaker 1: And then later on there was a guy named m
Speaker 1: Robert's Bartholow. Boy, this guy, did you look up this experiment?
Speaker 1: I did pretty pretty pretty bad. Yeah. So there was
Speaker 1: a woman named Mary Rafferty who had an ulcer on
Speaker 1: her brain, which ended up resulting in a literal hole
Speaker 1: in her skull. So her brain was exposed, and Robert's Bartholow,
Speaker 1: I guess, was like, well, well, perfect, this is just
Speaker 1: what I've been waiting for, is access to a human brain.
Speaker 1: So let me see if I can stimulate these neurons
Speaker 1: by looking at with needles her brain, and see what
Speaker 1: happens when I stimulate that with electricity. And he kept
Speaker 1: it super low voltage at first and noticed some things
Speaker 1: like wow, when I poke here, her arm moves right.
Speaker 1: He's like, does anyone have a question, But he ramped
Speaker 1: that electricity up at higher voltage, looking for what he
Speaker 1: called a more decided reaction, and he well, he argued
Speaker 1: afterwards that he did not cause her death, but she
Speaker 1: had a seizure. She went into a coma and she died. Right,
Speaker 1: So the kind of the sticking point here is and
Speaker 1: he was censured by the A M A. But nothing
Speaker 1: really happened was that he was experimenting on a human being,
Speaker 1: but not with the aim of curing anything that was
Speaker 1: wrong with her. No. He even said in the study
Speaker 1: that he produced that anyone who tried to replicate this
Speaker 1: would be would be UM conducting like a criminal experiment.
Speaker 1: It may be criminal. Redo it. Yeah, I'm good, right,
Speaker 1: I'm all good, but just don't do this again. But
Speaker 1: what's what was interesting to me is like it wasn't
Speaker 1: until six that we started to um, like the scientific
Speaker 1: community started to enforce informed consent after the Nazi atrocities
Speaker 1: of World War two. UM, And this guy was was
Speaker 1: carrying this experiment and I think in eighteen seventy four.
Speaker 1: But even at the time, so in his defense, people
Speaker 1: weren't about informed consent, and there were like the ethics
Speaker 1: of scientific experiments weren't nearly as pronounced and structured as
Speaker 1: they are today. And yet his experiment was still denounced,
Speaker 1: like everybody could see that on some level that hadn't
Speaker 1: been like elucidated, yet he had violated something which is
Speaker 1: actually like the life of a person, like something's bothering me,
Speaker 1: but I can't quite put my finger on it. Oh well,
Speaker 1: now he's hit me with the electric needles in my fingers,
Speaker 1: going exactly where he wanted to. Oh boy, the am
Speaker 1: A actually banned human experimentation if it was not for
Speaker 1: the purposes of saving a human life after this very
Speaker 1: good stuff. So what we figured out though from Galvani
Speaker 1: and um barth Bartho, Yeah, he's got a tough one,
Speaker 1: a tough last thing, Um and others who showed that
Speaker 1: electricity is the currency that moves messages around the brain.
Speaker 1: Um that you can actually stimulate the brain with electricity
Speaker 1: to go around its internal drives and externally make it
Speaker 1: do things right. But the problem is is like if
Speaker 1: you're using the society of the brain, it's really clumsy.
Speaker 1: It really like an electrical impulse is really tough to
Speaker 1: keep localized. So if you're trying to just kind of
Speaker 1: see what one particular type of neuron does, well, t
Speaker 1: s for you because you're electrically going to stimulate a
Speaker 1: whole bunch of neurons in the neighborhood and it's not
Speaker 1: a very um a fine tuned way of studying how
Speaker 1: the brain works. And again, it's really important that we
Speaker 1: understand what regions of the brain are responsible for what.
Speaker 1: So if we're just kind of trying to see what
Speaker 1: regions are responsible for raising your arm, we might hit
Speaker 1: those neurons with electric needles, but we might also like
Speaker 1: kick the leg out too. That just kind of it's
Speaker 1: not as precise as it needs to be. Do you
Speaker 1: want to uh use this repeated metaphor? It was a
Speaker 1: fine metaphor, but it was a mixed metaphor, and the
Speaker 1: first one really didn't work. Yeah, let's just go ahead
Speaker 1: and say it, because it does get a little bit
Speaker 1: more credible as the metaphor develops. But I agree this
Speaker 1: first one was a little rough. But just just take
Speaker 1: this metaphor, put in your pocket, everybody, and smoke it
Speaker 1: with some salt. I don't even know what that means.
Speaker 1: So imagine a neighborhood or a city, if you will,
Speaker 1: with all the people, let's say New York City and
Speaker 1: people everywhere moving around. These are your neural uh, this
Speaker 1: is your neural network. Everyone's going places. They're taking subways
Speaker 1: to run busses or driving cards, are walking. Some of
Speaker 1: them have that have no conscience or in a horse
Speaker 1: and buggy in Central Park and it's not trade to
Speaker 1: the giant. He just stole it. And Uh, electrical stimulation,
Speaker 1: which is something that deep brain stimulation we've talked about
Speaker 1: on the show, with something we currently are doing and
Speaker 1: are able to do just very imprecisely. So, Uh, that
Speaker 1: electrical stimulation is like trying to learn about people only
Speaker 1: driving Ferraris through New York City by setting a city
Speaker 1: block on fire. That's where it loses me because it
Speaker 1: doesn't make any sense. I just said, shocking entire city block. Sure,
Speaker 1: I guess so, Yeah, that would have made more sense, right. Yeah.
Speaker 1: I saw another analogy on you know how we always
Speaker 1: say when you can't understand something, go to like the
Speaker 1: kids science website. Sure, I found one called Frontiers for
Speaker 1: Young Minds, and they were explaining up to Janet's and
Speaker 1: they basically put it similarly saying, if you wanted to
Speaker 1: study the movement of track Affrick in the city, Um,
Speaker 1: but you wanted to see like like you were saying,
Speaker 1: how ferrari Um car drivers drive. Um, you want to
Speaker 1: be able to tell everybody when to drive. But the
Speaker 1: problem is if you're using an electrical stimulation that doesn't
Speaker 1: just tell Ferrari drivers when to drive and tells everybody
Speaker 1: in the city you want to start to start driving,
Speaker 1: and everyone starts driving, So it doesn't tell you anything
Speaker 1: about just the Ferrari drivers. Yeah, that makes sense. And
Speaker 1: by the way, Ferrari, you chucking me in Ferrari each
Speaker 1: for all this buzz Ferrari marketing. Ferrari, I would just
Speaker 1: like to drive one once. That'd be fun. Don't don't
Speaker 1: set your slights higher than that, chuck. See if we
Speaker 1: can get a free one Ferrari, just stress me out.
Speaker 1: We'll sell it on Craigslist. I'm gonna park a Ferrari
Speaker 1: in my driveway backwards. You back it in? Oh goodness.
Speaker 1: Uh so should we take a break now that we
Speaker 1: have a nice little set up in hand. Sure, all right,
Speaker 1: let's take a break, and we're gonna talk about potassium
Speaker 1: and calcium and color dye right for this shock. Alright.
Speaker 1: So people figured out pretty quickly that yes, electrical impulses
Speaker 1: will make parts of the brain work, but it's not
Speaker 1: very precise. We need a more precise way to study
Speaker 1: the different parts of the brain to see what's going
Speaker 1: on where at any given time. That's right, and enter
Speaker 1: Lawrence Cohen in the nineteen seventies, Leonard Cohen's brother. No
Speaker 1: it could be uh no, No, I was so disappointed.
Speaker 1: I thought, wow, that's amazing. All the genius in one family. Yeah,
Speaker 1: it's a lot of genius. Uh And in nineteen eighty
Speaker 1: it was further developed by man named Roger CN, Leonard
Speaker 1: Cohen's one time stage manager. Okay, it was waiting on
Speaker 1: that is it c N? Is it c N d N?
Speaker 1: I don't know? T S I E N anytime your
Speaker 1: name starts with T S I seen one of those
Speaker 1: is silent. Yeah, but I think they together make a
Speaker 1: D sound. Oh really, I think so? In what language? Chinese, Mandarin,
Speaker 1: maybe Cantonese, one of those two. Okay, oh god, I
Speaker 1: feel like I'm drowning. It's okay, grab hold of me, thanks.
Speaker 1: Uh So what they did was they worked on um
Speaker 1: this synthetic die UM, like I said, coming in the seventies,
Speaker 1: refined in the eighties by Roger T and Roger you
Speaker 1: already yeah, you already talked about in the intro about
Speaker 1: the action potential in a neuron that's created that little
Speaker 1: electrical charges. It's not like it's plugged into something. It's
Speaker 1: created by concentrations of potassium and calcium shifting around right right.
Speaker 1: So what they figured out, what Um, Lawrence and Roger
Speaker 1: figured out is that you can actually introduce the synthetic
Speaker 1: die so that the dye is produced or triggered or
Speaker 1: it becomes a parent once calcium ion concentration reaches a
Speaker 1: certain point. And if you know that a calcium ion
Speaker 1: concentration will trigger this action potential, this electrical impulse in
Speaker 1: the neuron, if the neuron suddenly is glowing or has
Speaker 1: this dye colored dye that's showing up under a microscope,
Speaker 1: you know that that neuron is just fired because the
Speaker 1: calcium concentration changed enough for that die to become a parent. Yeah,
Speaker 1: it's like the very easy way to say this is
Speaker 1: scientists basically said, you know when someone uh metaphorically turns
Speaker 1: on a light and that neuron that'd be great an
Speaker 1: actual light turned on. Yeah, this is very similar to
Speaker 1: that for sure, And it's still was a little it's
Speaker 1: a little clunky, um because well, I'm not fully under
Speaker 1: I don't fully understand why it's a little clink. I
Speaker 1: think it's that maybe you can't control it. It's just
Speaker 1: you can witness it. I think is the issue with it. Well,
Speaker 1: if we're going to further that metaphor, it's really giant
Speaker 1: to escate fast to this point, but go ahead. The
Speaker 1: next step would be, uh, you want to learn about
Speaker 1: these Ferrari drivers in New York City, So you just
Speaker 1: paint and inside and the entire city block instead of
Speaker 1: shocking it with electricity or setting it on fire. But
Speaker 1: any car that's driving on that city plot city block
Speaker 1: is gonna it's gonna glow or it's gonna move through
Speaker 1: the paint. So you're gonna get car track. Sure, you're
Speaker 1: gonna get glow paint all over every car. You still
Speaker 1: are not just targeting the Ferrari. But it's better the metaphor. Sure,
Speaker 1: that's right, much better, but it's still not precise enough.
Speaker 1: And I think where it's lacking is that you, yes,
Speaker 1: you can see now what neuron has just gone off,
Speaker 1: but you can't make the neuron go off. But but um,
Speaker 1: Lawrence and Roger gave future researchers an idea. They're like,
Speaker 1: wait a minute, we're onto something here, like being able
Speaker 1: to to to see when a neuron has gone off.
Speaker 1: That is a great idea. Let's figure out how to
Speaker 1: do that but also make neurons go off. And to
Speaker 1: do this they turn to our friends in the sea
Speaker 1: for help. Yeah, this is really interesting, and this is
Speaker 1: where um genetics come into play, because it is it
Speaker 1: is important to point out that neurons are basically the same. Uh.
Speaker 1: They all contain basically the same genetic information even but
Speaker 1: it's that mystery of the differences switching these genes on
Speaker 1: and off, and why would one be switched on when
Speaker 1: another switched off. That's sort of like what makes them
Speaker 1: unique among each other, right, right, So, like if you
Speaker 1: have a human cell, especially like say a stem cell
Speaker 1: or whatever, but any cell has all of the your
Speaker 1: genetic blueprint, and it's just depending on what genes are
Speaker 1: on or off that determines what kind of cell it
Speaker 1: is and what it's responsible for doing. You know. So
Speaker 1: maybe it's like a retinal cell and it detects light,
Speaker 1: or maybe it's a cardiac cell and it it makes
Speaker 1: up heart muscle. All of them have the same DNA,
Speaker 1: the same genetic blueprint, but some of those genes are
Speaker 1: gonna be turned off, some are gonna be turned on.
Speaker 1: And the same is true for neural cells. To right,
Speaker 1: you have neural cells that are responsible for releasing dopamine.
Speaker 1: You have neural cells that are responsible for sensing temperature. Um.
Speaker 1: You have all these different neural cells, and all of
Speaker 1: them are roughly the same kind of cell, but they
Speaker 1: have different genes turned on and off. And once you
Speaker 1: know that, and once you can differentiate between one gene
Speaker 1: and another, you've just taken your first step towards genetically
Speaker 1: manipulating these different genes, you know, and understanding Ferrari drivers exactly.
Speaker 1: So you brought us to the sea, and I jumped
Speaker 1: it right back out again, and now we are back
Speaker 1: at the sea like the manatee. That's right. But here
Speaker 1: this is where it gets super super cool. Uh. And
Speaker 1: it sounds like it's confusing, but it's really not. It's
Speaker 1: really pretty simple still. Um. There are genes in mother
Speaker 1: nature that respond to light, and then there are proteins
Speaker 1: that emit light when they're triggered by something. Flores Yeah,
Speaker 1: I like to say glow. In fact, if you'll look here,
Speaker 1: I scratched out fluoresce every single time as you did glow.
Speaker 1: That's a lot of work you put into those, just
Speaker 1: a lot easier to say glow. I think people get
Speaker 1: it a lot better than Fluoresce. I watched Coming to
Speaker 1: America the other day of Man Soul. Glow is so hilarious.
Speaker 1: It still holds up. That movie is even better than
Speaker 1: I remember. Actually it's great. Yeah, it's when we go
Speaker 1: back to a lot. Like I knew Eddie Murphy was
Speaker 1: a charmer, but dude, that guy is one charming human being. Yeah,
Speaker 1: all the all the barbershop stuff is just so classic.
Speaker 1: It's great, but all of it like it really, it's
Speaker 1: just a great, great movie. You know, they're sequeling that thing.
Speaker 1: They've been shooting it in Atlanta. Sequeling or rebooting sequel
Speaker 1: Oh good? So uh. I mean, I think the the
Speaker 1: easiest way to go about a sequel is what they're doing,
Speaker 1: which is now King of Zamunda. Eddie Murphy has a
Speaker 1: son who wants to find his love. Yeah, but I
Speaker 1: think everyone's back, like our Cineo's back. Sure they Oh,
Speaker 1: I'm not gonna be mean good. They found him in
Speaker 1: great spirits and he was eager to work. He said, yeah,
Speaker 1: that's a great idea. I can fit it into my skin.
Speaker 1: Then he went, whoo, who did you see the Grammy's
Speaker 1: the other day. I don't usually watch those either, but
Speaker 1: I happened to see the entire thing, and um, I
Speaker 1: didn't know that you were kidnapped and it was it
Speaker 1: was like um mel Gibson and um oh conspiracy theory.
Speaker 1: I was tied to a wheelchair and my eyes were
Speaker 1: taped open. So you watched all of it? Huh? Yeah,
Speaker 1: But I haven't watched all the Grammy since I was
Speaker 1: like thirteen, Bro, I haven't either. It was really something.
Speaker 1: It's like a marathon or an ultrathon really, but um,
Speaker 1: Tyler the Cree eat or did like a live thing
Speaker 1: and it was amazing. Dude. I've never heard a single
Speaker 1: second of any of his songs or really him perform
Speaker 1: or anything, but um, I like that guy. Now, Yeah,
Speaker 1: he's great. And you know I listened to that early.
Speaker 1: I can't even remember the acronym, but his sort of
Speaker 1: hip hop collective band that they all started out of that,
Speaker 1: like Frank Ocean came out of that. Tyler the Creator
Speaker 1: and a bunch of other guys whoa what's it called?
Speaker 1: Oh what was it? Do you know? Odd Future? And
Speaker 1: then it had another like five or six words after
Speaker 1: that Odd Future was the shortened version. Good stuff, very
Speaker 1: good stuff. Thanks to Josh T for swooping in and
Speaker 1: that uh that the first Frank Ocean album was is amazing.
Speaker 1: I've not heard that either. Oh man, it's so good
Speaker 1: Channel Orange. I think I'm always confused by rappers who
Speaker 1: who just have normal names. Uh Frank Ocean. Yeah, he's
Speaker 1: kind of a singer, crooner type. I mean he does Okay,
Speaker 1: all right, now that makes sense. Yeah, he's he's awesome.
Speaker 1: So cheeze. That's how it happens. We're in the sea.
Speaker 1: We're in the ocean. The Grammys are over right. We
Speaker 1: have found genes that respond uh to light and also
Speaker 1: proteins and other organisms that emit light when triggered. I'll
Speaker 1: let you walk people through what those two things are.
Speaker 1: But the point is they said, we've got the two
Speaker 1: components to make this happen. We can build we can
Speaker 1: control jenes turning on a light, and we can also
Speaker 1: see what happens when something responds to the light. We
Speaker 1: just need to be able to get these two things
Speaker 1: from two different organisms into one thing that we can
Speaker 1: control exactly exactly, And that's the entire basis of optogenetics. Um.
Speaker 1: I think you did a fine job of explaining it. Well,
Speaker 1: I didn't know if you want to talk literally about
Speaker 1: the jellyfish, and well sure so if you don't mind, no,
Speaker 1: it's great. So the algae, like green algae, has something
Speaker 1: called an eye so it's like a single cell organism, right, yeah,
Speaker 1: And it has an eyehole which is light sensitive. It's
Speaker 1: a light sensitive area on the cell. And when sunlight
Speaker 1: hits that eyehole, it triggers the tail of the algae
Speaker 1: to start moving towards the sunlight so that that single
Speaker 1: cell algae can can maximize its exposure to sunlight as
Speaker 1: much as possible. All right, So that's one half. You
Speaker 1: got the thing that sees light and reacts to it, right,
Speaker 1: And again, all this stuff has to do with ion channels.
Speaker 1: That has to do with the concentration of minerals inside
Speaker 1: and outside of these the cell in these channels, right,
Speaker 1: and that's what triggers this movement. That's what triggers the
Speaker 1: electrical impulse. That's the basis of all life apparently, are
Speaker 1: the movement of minerals inside and outside of cell membranes
Speaker 1: triggering electrical impulses. That's life in that bizarre So then
Speaker 1: with jellyfish they have a similar thing too. We're not
Speaker 1: exactly sure why they fluoresce, but say like a predator
Speaker 1: comes up and they sense like a predator's coming, it
Speaker 1: might trigger a chain inge in their eye on concentration,
Speaker 1: which triggers a protein that fluoresces to be produced. So
Speaker 1: the jellyfish starts to glow. And these are two separate things,
Speaker 1: but like you were saying, at some point, I think
Speaker 1: in two thousand five, a team led by Carl dis
Speaker 1: roth Um published a paper that said, hey, man, we
Speaker 1: could take this algae light sensitive gene, and we can
Speaker 1: take this jellyfish fluorescent gene and put them together, and
Speaker 1: then take that so that one triggers the other, and
Speaker 1: like kind of this rubics QB way, so that if
Speaker 1: you shine light on this one gene, it will trigger
Speaker 1: the production of this fluorescence. And we can if we
Speaker 1: can just figure out how to take that gene combination
Speaker 1: and put it into another organism that doesn't have either,
Speaker 1: then we could shine a light on the organism and
Speaker 1: make the cells in that organism glow. And now finally, finally,
Speaker 1: just the ferraris would start to move when we signaled
Speaker 1: for them to move. We don't have to set a
Speaker 1: city block on fire. We don't have to code everything
Speaker 1: and glowing paint. We can just signal to the ferraris.
Speaker 1: Can you believe this? It's it's astounding that that they
Speaker 1: figured out not only like in theory, how to do this,
Speaker 1: but they have actually, over the last fifteen years, been
Speaker 1: successful in doing it. It seems like something that if
Speaker 1: someone was describing, they would just be laughed out of
Speaker 1: a room and say, yeah, that's great. Take this jellyfish
Speaker 1: things alogy thing, put him together, shove it in a
Speaker 1: fruit fly, up at fruit flies, but and then shine
Speaker 1: a light on his face and make him rob a bank.
Speaker 1: I think that's I think that's how that's the ultimate goal. Really,
Speaker 1: it's unbelievable. It really is chuck, all right. So the
Speaker 1: fruit fly is a great little candidate because we've been
Speaker 1: working with fruit flies for a long long time. When
Speaker 1: it comes to genetics, they also um we share like
Speaker 1: jeans in gene sequences that are so closely matched that
Speaker 1: when we find a like a novel gene in a
Speaker 1: fruit fly, we go look at the human genome and
Speaker 1: just try to find its match, and it usually matches.
Speaker 1: That's how closely related we are of human genetic diseases
Speaker 1: are also found in fruit flies. This all seems made up,
Speaker 1: am I being? Maybe this is gonna come out April first? Maybe?
Speaker 1: Oh uh, So the fruit fly is a great little
Speaker 1: candidate for all those reasons, and for one other reason
Speaker 1: is we can actually, uh, we don't need to cut
Speaker 1: a fruit fly's head open to see its brain. We
Speaker 1: can see that little guy's brain through a microscope. That's
Speaker 1: pretty great, Which is a pretty good way to analyze
Speaker 1: something just by letting it do its do its thing,
Speaker 1: you know, especially as far as the fruit flies concerned.
Speaker 1: Oh sure, it's like, yeah, just just hold me down,
Speaker 1: that's fine, Just don't cut my head off. Yeah, but
Speaker 1: you're setting people up to think it's all of mine
Speaker 1: and roses. Yeah, it gets pretty bad. That's when you
Speaker 1: pull a ruck out from under him. Shock. So what's
Speaker 1: happening though, is they're putting that stuff in the fruit fly.
Speaker 1: And then what you do is you have to breed
Speaker 1: like the next generation. I think I don't think it
Speaker 1: would work on that one, would it? Um? No, But
Speaker 1: but you can very easily cultivate like a fruit fly
Speaker 1: colony that is now genetically modified. Just throw some throwing
Speaker 1: in a cage with some martinis and a little bit
Speaker 1: of Sinatra classics. So this is what they did, and
Speaker 1: it was successful. And so this gave them the ability
Speaker 1: to do two things to map out where all these
Speaker 1: neurons are, which was the first kind of big part
Speaker 1: of this problem. And the second thing they could do
Speaker 1: is actually activate these neurons with light. Right, So, now,
Speaker 1: like one of the first things they experimented on, are
Speaker 1: you ready to pull the rug out from people? Sure?
Speaker 1: One of the first fruit fly experiments that they conducted,
Speaker 1: and I shouldn't say one of the first, but one
Speaker 1: of the big ones was that, um, they they genetically
Speaker 1: modified fruit flies whose neurons responsible for their escape reflex,
Speaker 1: which is when their legs tense up and their wings
Speaker 1: tents up and they just fly away when they sense danger.
Speaker 1: These were now genetically modified with an algae and jellyfish combination,
Speaker 1: uh gene sequence, that's right. So they shine a light
Speaker 1: on the fruit flies, and the fruit flies sprung away,
Speaker 1: and they said, that's pretty great, but makes sense. It's
Speaker 1: entirely possible that we just scared him with the light.
Speaker 1: How could we possibly figure out if the actual neurons
Speaker 1: are being activated optogenetically. Right. And in the movie scene,
Speaker 1: you just hear a voice on the other side of
Speaker 1: a desk of some scientists eating Chinese food out of
Speaker 1: a box. He goes, no, you cut their heads off
Speaker 1: and they still live for a little while. That's funny.
Speaker 1: You should do that, I imagine instead um, Robert what's
Speaker 1: his name like scratching the chalkboards slowly with yeah, with
Speaker 1: his idea about cutting their heads off. They could probably
Speaker 1: cheat it both ways because just like Mike the headless chicken,
Speaker 1: had a lot of brain left when they cut his
Speaker 1: head off, so too with the fruit fly. There are
Speaker 1: genes um or neurons i should say, associated with the
Speaker 1: escape reflects that are not just located in the fruit
Speaker 1: fly's head. So they cut the fruit flies heads off because,
Speaker 1: like you said, or like the guy who eating Chinese
Speaker 1: food said, um, the fruit fly will still be able
Speaker 1: to fly around and move around for a little while
Speaker 1: without a head. So they cut the heads off, and
Speaker 1: then they shine the light into the thorax where some
Speaker 1: of these neurons are, and sure enough the fruit flies
Speaker 1: sprung away and flew into the air headless, zombie like.
Speaker 1: But they did it specifically because those neurons were reacting
Speaker 1: to light. So they successfully showed that you can control
Speaker 1: the behavior of a once living organism by shining a
Speaker 1: light on it, once you genetically modified it's it's neurons
Speaker 1: with these proteins. Yeah, I wanted to know a little
Speaker 1: bit more about that second part. I'm sure I did
Speaker 1: a lot of other controls, but my first instinct was
Speaker 1: how close was this light? Did it feel like the
Speaker 1: air move when they put it in front of it,
Speaker 1: or was it you know, distance. But you know, they're scientists,
Speaker 1: I'm sure Rodney and his Chinese food, I'm sure a
Speaker 1: lot of other great suggestions for everybody. Right. The other
Speaker 1: questions are did they mash the heads with their thumbs
Speaker 1: to make sure there was no way that they were
Speaker 1: getting any light info? Al Right, I feel like we
Speaker 1: should take another break because what we've described as almost
Speaker 1: a miracle, but like, what good does that do us?
Speaker 1: Great question, and well we'll talk about what good it
Speaker 1: could do us write after this. Okay, So the fruit
Speaker 1: fly experiment that was that was pretty huge, and it
Speaker 1: wasn't It didn't just end with fruit flies, like we said,
Speaker 1: They've successfully experimented with mice, with fish, um worms, worms yep,
Speaker 1: and all of these are they they use these UM
Speaker 1: these types of of um ion channels or ion pumps
Speaker 1: called dopsins or opsins, it's specifically rhodopsins. They respond to light,
Speaker 1: they're stimulated by light. UM. But they've figured out how
Speaker 1: to insert different ones in the different genes and UM. Eventually,
Speaker 1: what they're thinking is that if we can figure out
Speaker 1: how to use these in humans, we will be able
Speaker 1: to do all manner of things, some of which we've
Speaker 1: already successfully demonstrated on on things like mice and fruit flies,
Speaker 1: not just to get a human to jump using our
Speaker 1: escape reflex, but things like UM. Treating depression is a
Speaker 1: big one. Well, yeah, that's sort of one of the
Speaker 1: the huge potential benefits here is what if we could
Speaker 1: really control the really release of dopamine and someone's brain
Speaker 1: and when people suffer from depression and they're having a
Speaker 1: hard time getting their dopamine reactions to occur naturally instead
Speaker 1: of putting them on pills, which you know, a pill
Speaker 1: doesn't just affect the cells uh that it needs to.
Speaker 1: That's why they have a whole list of side effects
Speaker 1: because they affect everything. UM. They're like, maybe we can
Speaker 1: get so specific that we can literally turn on those
Speaker 1: cells with light, give someone a dopamine hit that will
Speaker 1: take seconds instead of weeks and weeks of being on
Speaker 1: medication that may or may not work and may or
Speaker 1: may not have devastating side effects. Yeah, and you just
Speaker 1: hit the nail on the head that the effect will
Speaker 1: take seconds. Um. That's one of the really big um
Speaker 1: advantages of optogenetics is it's light controlled, and we have
Speaker 1: really great lights that can turn on and off very
Speaker 1: very quickly, like um lasers connected to fiber optics is
Speaker 1: one way that they have figured out how to deliver this.
Speaker 1: I saw it's cute, heartbreaking picture of a mouse with
Speaker 1: like this kind of plastic helmet on the side of
Speaker 1: its head, and coming out of it was a single
Speaker 1: fiber optic cable. Remember those fiber optic kind of brushes
Speaker 1: that had like a light source of the bottom, and
Speaker 1: like the brush itself was just this beautiful, colorful thing.
Speaker 1: I love those. I went and looked through like Google
Speaker 1: images pictures of those and it's just like, God, these
Speaker 1: are so pretty. So they had one of those fiber
Speaker 1: optic little fibers coming out of the mouse's head and
Speaker 1: the mouse is just this little dirt looking at the
Speaker 1: camera like what um, But they can they can connect
Speaker 1: the end of that fiber optic cable to a laser
Speaker 1: and it will deliver that light source too inside the
Speaker 1: mouse's brain. The problem is that there's um all sorts
Speaker 1: of brain damage that you can create by inserting even
Speaker 1: like a really tiny fiber optic fiber into the brain
Speaker 1: of something. But it is one way to do it now. UM.
Speaker 1: What they're working on also is, like I said, those
Speaker 1: Rhodopson's UM. One of the one of the ones they're
Speaker 1: looking at is like red shifted towards the red end
Speaker 1: of the spectrum, which means that you can use something
Speaker 1: like infrared light, which is absorbed more deeply into the body,
Speaker 1: as an external light source. So you just shine like
Speaker 1: an infrared light through the skull and then that will
Speaker 1: um will activate the neurons in the brain too. So
Speaker 1: I don't remember exactly how we started on this, but
Speaker 1: there's there's stuff that we're starting to figure out from
Speaker 1: these mouse models, UM, including things like treating depression. Oh yeah,
Speaker 1: how precise it is, How precise the delivery of light is,
Speaker 1: which is really really important because the timing of neurons
Speaker 1: um and the the triggering them in the the cascade
Speaker 1: of events that it sets off is extremely precisely time.
Speaker 1: So you can't just use like a flashlight and expect
Speaker 1: to treat depression. You would have to be able to
Speaker 1: time it in the way that the brain is supposed
Speaker 1: to be doing it in the first place. Yeah, what
Speaker 1: I wonder is if in the future, and first of all,
Speaker 1: you've got to get past all the ethical hurdles of
Speaker 1: gene therapy to begin with, which are many um and complex.
Speaker 1: So let's say we do get through all that, and
Speaker 1: let's say we get FDA approval to start therapies like this.
Speaker 1: What kind of what does that look like? Because if
Speaker 1: it happens in seconds, does do you make an appointment
Speaker 1: and go to a a a specialist who does this
Speaker 1: light therapy or is this something that you do You
Speaker 1: have a device that you're in control of, right, so,
Speaker 1: like it would probably follow a model like deep brain
Speaker 1: stimulation what you mentioned earlier, where you have electrodes and
Speaker 1: planted in your brain that are doing basically the same thing,
Speaker 1: but a lot less precise and a lot more clumsy.
Speaker 1: But they're electrically stimulating neurons say that released dopamine to
Speaker 1: treat depression. I don't know if we're doing that yet,
Speaker 1: but there's definitely deep brain stimulation. But do you go
Speaker 1: to a place to have that done? You have like
Speaker 1: a pacemaker like device connected via wire from your sin,
Speaker 1: and then the devices like under your skin in your chest,
Speaker 1: but it's being controlled by a computer, Like you have
Speaker 1: an onboard computer on you on you right, But what
Speaker 1: I'm saying is you don't like carry around a button, No,
Speaker 1: it's under your skin. So how would this work? Then?
Speaker 1: I would guess the same way that we would figure
Speaker 1: out exactly from studying opto genetically these neurons that glow
Speaker 1: when when they go off, So we'll figure out the
Speaker 1: brain pathways in the regions responsible for things like depression
Speaker 1: and all that. We would figure out what this standard
Speaker 1: normal pattern is and then to recreate it and then
Speaker 1: the computer would regulate it when needed in the brain.
Speaker 1: Well that makes a little more sense, But I mean
Speaker 1: just that kind of stuff, like just that alone shows
Speaker 1: you how far we are from actually doing this in humans,
Speaker 1: Like we have no idea what the normal pattern in
Speaker 1: the brain is for like um, the like normal serotonin
Speaker 1: release for you know, a normal mood. But it also
Speaker 1: raises these other questions to Chuck where it's like, Okay,
Speaker 1: if we figure that out and we figure out how
Speaker 1: to um, how to how to replicate that, why stop there?
Speaker 1: Like why not just make everybody happier than we are normally? Yeah,
Speaker 1: which brings in the whole free will debate which has
Speaker 1: been around since the dawn of time, And it also
Speaker 1: UM and ED does a great job of kind of
Speaker 1: wrapping it up and pointing out that kind of makes
Speaker 1: you think about things like if we are we just
Speaker 1: a bag of cells that can be uh manipulated by
Speaker 1: a flashing light? Like, uh, is that where you're saying
Speaker 1: is yes, we are? Like is that what happiness is? Like?
Speaker 1: You think happiness is seeing your dog when you get
Speaker 1: home from work and getting those licks. But if those
Speaker 1: are just synapsies firing, that's a very I mean, that's
Speaker 1: scientifically what's going on, but it is a very cold
Speaker 1: and humane way to look at things. I think I
Speaker 1: disagree with that. I think it's just a that's a
Speaker 1: better understanding of what's going on, But I don't think
Speaker 1: it undermines the happiness you're experiencing. I think for a
Speaker 1: lot of people it might well, yeah, I mean I
Speaker 1: it's not like I can't see how it wouldn't. But
Speaker 1: to me, it's like, no, I mean, you're still experiencing happiness.
Speaker 1: The happiness is still important to you. Happiness is still
Speaker 1: the point of life. This is just understanding the mechanism
Speaker 1: that we experience happiness by. That's true. And I have
Speaker 1: seen you around dogs and you constantly are just saying,
Speaker 1: I'm a bag of neurons firing at once. It's like
Speaker 1: Francis Crick, the guy who co discovered DNA. He had
Speaker 1: a book in the seventies called The Astonishing Hypothesis. I
Speaker 1: know we've talked about it before, but he had this
Speaker 1: famous quote where he said, you're nothing but a pack
Speaker 1: of neurons. And I mean, like, to me, it's that's
Speaker 1: a really good way of maintaining a positive outlook on things.
Speaker 1: It's like, no matter how bad things get, it's just
Speaker 1: neurotransmitters in your head that are going haywire or that
Speaker 1: are doing right. Well, that's that's when. That's that's the
Speaker 1: reason to do all this is to regain control over
Speaker 1: it and it's not functioning correctly, and then making things
Speaker 1: even better than they are normally Naturally, there's no written
Speaker 1: law that says if we figure out how to make
Speaker 1: ourselves happier, that we shouldn't do that. As a matter
Speaker 1: of fact, basically every moral code there is says we
Speaker 1: should do that. If we can be happier, let's figure
Speaker 1: out how to be happier. Yeah. I think the other
Speaker 1: thing it makes me think about, slippery slope wise, is, um,
Speaker 1: will people cease to do the things that they do
Speaker 1: to make them happy if they can simply touch a
Speaker 1: button to do so? Yeah, that's called wire heading. And
Speaker 1: that's actually a big problem with artificial intelligence is um
Speaker 1: they're saying, like, Okay, if we train artificial intelligence to
Speaker 1: do something based on a reward, the artificial intelligence just
Speaker 1: gonna go figure out how to go right to the reward.
Speaker 1: But it's not. It's going to circumvent that um. And
Speaker 1: that's that's a great question too, where if we start
Speaker 1: to become like digital consciousness right where we migrate online
Speaker 1: and we should at our bodies and our consciousness just
Speaker 1: exists in digital form, then all that stuff will be
Speaker 1: available to us. And it does make you think like, okay,
Speaker 1: if if our existence is just digital, there's no purpose
Speaker 1: to it except to experience pleasure. Is there anything wrong
Speaker 1: with just sitting around experiencing pleasure all the time? Or
Speaker 1: do we need more than that? I don't know. That's
Speaker 1: a that's a next next level question if you ask me. Yeah,
Speaker 1: I mean it kind of do you ever see wall
Speaker 1: e yes? Sort of like that there could be the future,
Speaker 1: Like why go out and take a walk if you're
Speaker 1: feeling down to get some sunshine on your face? If
Speaker 1: you can just press a button to do the same thing. Yeah,
Speaker 1: And like in that movie, it's it's like there's well,
Speaker 1: there's something inherently wrong with that. But I don't know, man,
Speaker 1: because like if you think about it, when you go
Speaker 1: outside and you get a walk, you feel better, you
Speaker 1: feel like more positive if you can get that without
Speaker 1: doing the walk. To you, if you can get everything
Speaker 1: from a walk without having to go on a walk,
Speaker 1: do you still need to go on a walk? Will
Speaker 1: including like the benefits to your health and body? Yes?
Speaker 1: If you could get every single scrap of benefit that
Speaker 1: you can get from a walk digitally or somehow without
Speaker 1: actually going on a walk, do you need to go
Speaker 1: on a walk? I say yes, but you and I
Speaker 1: are different. No, No, I'm with you. I still say
Speaker 1: yes as well, but I can't. I can't explain why. Okay, yeah, yeah,
Speaker 1: I'm not just like this full transhumanist guy. I definitely
Speaker 1: have questions about the whole thing too. I think you
Speaker 1: just built some bond water on the carpet that's never
Speaker 1: gonna come out. I'm gonna stop it up with a
Speaker 1: fa breeze dryer sheet. Remember that, Remember when when kids?
Speaker 1: You saw kids do that at the dorms. Yeah, I
Speaker 1: don't know if kids had fabrize dryer sheets when I
Speaker 1: was in college, they didn't exist yet, Okay. Or you
Speaker 1: mean to just like the bounce sheets? Yes, oh sure, Yeah,
Speaker 1: yeah I've seen I've seen those old tricks. It's hilarious. Okay, Well,
Speaker 1: you got anything else about opt to genetics? No, it's
Speaker 1: pretty pretty fascinating stuff. Yeah, we'll see where it goes, agreed. Actually,
Speaker 1: probably won't see where it goes in our life time.
Speaker 1: But I don't know, man. I suspect that while we're alive,
Speaker 1: things are going to change quite a bit. We'll live
Speaker 1: to see a lot of this stuff. I'm gonna check
Speaker 1: in with you in in thirty five years, we'll be
Speaker 1: sitting across the desk from me. Still, when we get
Speaker 1: commemorated into the Podcasting Hall of Fame, you're on that,
Speaker 1: aren't you. You're gonna stroll into that room wearing your
Speaker 1: your VR headset, pressing your little dopamine button right talking
Speaker 1: about how great life is, right, just wire headed to
Speaker 1: the Guild's right. So if you want to know more
Speaker 1: about optogenetics, well go start reading about It's pretty interesting stuff.
Speaker 1: And since I said that it's time for listener mail,
Speaker 1: listener mail, I think it was me who goofed up
Speaker 1: on the postal going Postal EPP. When I think off handedly,
Speaker 1: when they were talking about the Californo Commission about how
Speaker 1: much money we spent, I think it's a tex stollar money. Yeah,
Speaker 1: like a dope because we've covered the U. S. Postal
Speaker 1: service and we know that that is not the case.
Speaker 1: And this is from Peter among many others. Hey guys,
Speaker 1: want to start off by saying how much I love
Speaker 1: the show. You always do a great job researching the
Speaker 1: subjects you talk about. However, I knew, however, I got
Speaker 1: a small bone to pick. In your recent episode Why
Speaker 1: Postal Employees Go Postal, you talked about how the US
Speaker 1: Postal Service spent four million tax dollars on the Joseph
Speaker 1: Californo Commission. While Congress does still control the USPS budget,
Speaker 1: it receives no funding from them at all, and has
Speaker 1: not since the early nineteen eighties. The USPS operates solely
Speaker 1: on the money they make from stamps and packages zero
Speaker 1: tax dollars. Anyway, thanks for the amazing content. May you
Speaker 1: keep doing so for many years to come. That is
Speaker 1: from Peter and many many others. And by the way,
Speaker 1: we heard from a lot of people, uh, postal employees
Speaker 1: or people whose family was are or were in the
Speaker 1: Postal Service, and we got a range of things from
Speaker 1: you guys are crazy, my post office is great, there's
Speaker 1: no toxic environment, to people saying oh, they're absolutely is
Speaker 1: a very toxic environment. Yeah, like it's even worse than
Speaker 1: you guys said. Yeah, So I think for the people
Speaker 1: that wrote in that said that was not the case,
Speaker 1: then I am very happy that you work in a
Speaker 1: great place that has a great environment. But it seems
Speaker 1: like there is a range. They're right, that's the nicest
Speaker 1: way to say it. Yeah. Uh, well that was Peter, right, Peter,
Speaker 1: Thanks a lot, Peter. That was a very nice way
Speaker 1: to put it. And if you want to get in
Speaker 1: touch with us like Peter did, you can go and
Speaker 1: send us an email. Send it off to stuff podcast
Speaker 1: at iHeart radio dot com. Stuff you Should Know is
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