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Brain Balls

Jan 09, 202641 minEp. 675
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Summary

This episode explores the accidental discovery of "cerebral organoids" by Madeline Lancaster, miniature 3D human brain models that have transformed neuroscience. From revealing secrets about early brain development and enabling breakthroughs in disorders like Timothy Syndrome, these "brain balls" are now used in personalized cancer treatments and linked to biocomputers playing Pong. The narrative delves into the ethical dilemmas surrounding their potential for consciousness, their implantation into animal brains, and how they challenge our very definitions of life, humanity, and intelligence.

Episode description

When neuroscientist Madeline Lancaster was a brand new postdoc, she accidentally used an expired protein gel in a lab experiment and noticed something weird. The stem cells she was trying to grow in a dish were self-assembling. The result? Madeline was the first person ever to grow what she called a “cerebral organoid,” a tiny, 3D version of a human brain the size of a peppercorn.

In about a decade, these mini human brain balls were everywhere. They were revealing bombshell secrets about how our brains develop in the womb, helping treat advanced cancer patients, being implanted into animals, even playing the video game Pong. But what are they? Are these brain balls capable of sensing, feeling, learning, being? Are they tiny, trapped humans? And if they were, how would we know?

Special thanks to Lynn Levy, Jason Yamada-Hanff, David Fajgenbaum, Andrew Verstein, Anne Hamilton, Christopher Mason, Madeline Mason-Moriarty, the team at the Boston Museum of Science, and Howard Fine, Stefano Cirigliano, and the team at Weill-Cornell. 

EPISODE CREDITS: 
Reported by - Latif Nasser
with help from - Mona Madgavkar
Produced by - Annie McEwen, Mona Madgavkar, and Pat Walters
with mixing help from - Jeremy Bloom
Fact-checking by - Natalie Middleton and Rebecca Rand
and Edited by  - Alex Neason and Pat Walters

EPISODE CITATIONS:

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Articles -


Books - 
Carl Zimmer Life’s Edge: The Search for What it Means to be Alive (https://carlzimmer.com/books/lifes-edge/)



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Transcript

Intro / Opening

Oh y wait, you're listening. Listening to Radio Lab Lab Radio Lab from WNYS. Okay, Lulu. Yeah. We're gonna start today. Mm-hmm.

The Accidental Discovery of Brain Organoids

Back in 2010 in a lab in Vienna. Oh, jumping right in. Yeah. Just picture sort of a lab with microscopes, computers, experiments. And off in one corner. Hello. Hi, how's it going? Okay. Wearing glasses and a white lab coat is this scientist named Dr. Madeline Lancaster. Call me Madeline. Okay. Madeline is just

So still sort of making friends. Still trying to make a good impression. Getting to know people, you know. And one of the first things her boss asked her to do was something called a screen. Just basically looking for specific genes in mouse neural stem cells. So that's like baby brain cells of mice? Yeah. Now she hadn't done exactly this kind of gene screen before. And that's probably why I didn't really kn you know, I was kind of naive about it all. Hm. Um But she got to work.

Cut. Preparing the baby mouse cells. The cells all become loose and apart from each other. Uh that part she'd actually done before, so you know, easy enough. Yeah. But Then something she hadn't done before, she needed to get those cells to stick flat to the glass bottom of her dish so that she could do that screen.

And to do that, she needed to use special organic proteins as a glue. And I hadn't they hadn't come in yet. I'd ordered them but they hadn't come in yet. And instead of just, you know, waiting for them to arrive. I don't know. I was So anxious to do the experiment, she decided to improvise. And so I just kind of like rummaged through the freezer. Found a random tube of glue-like proteins. I don't know how old they were.

And anyway, and I used those. Squirted it on the dishes, pipetted in the cells, popped them in the incubator, and went home for the night. Next morning took a look in her petri dishes, hoping to see a new. Yeah. But instead everything in there was really cloudy. Hm. Shouldn't be cloudy. Cloudy means those cells are floating freely around in there. Which means that those tubes of protein glue she used. You know, we're now good.

And the cells hadn't stuck. And if the cells aren't stuck in the protein, that means they're probably dead. Yeah. All the cells are dead. I'll just throw it away. And I don't know why I did this, but right before she tossed it, she thought, you know, but I'll check it. I'll just take a peek. Why not? So she slides these cloudy dishes under the microscope, peers into the eyepiece, and in the circle of light she sees these weird The cells weren't dead.

They were alive and healthy and plumped into three or four blobs. I mean, they're like a sort of beige color, like an off white tiny about the size of a grain of sand. Or these floating balls of cells. And she's like, huh. Weird. So she zeroes in on one of these blobs, turns the dial on the microscope to zoom in until she's looking basically inside the blob. And that's when she sees a tube. A tupe.

So she's like looking down into like one end of the tube. So it looks almost like a doughnut shape. W whi had you ever seen anything like that before? No. No. Huh. Yeah. I mean as far as she knew, if the cells weren't in that protein stuff stuck, you know, flat to the bottom, they should sort of die and fall apart and make a big random mess. But these ones seem to be coming together to make this shape.

She gets up from the microscope and starts sort of going around the lab a little bit subtly at first, kind of just like, Hey, has anybody Ever like C and cells do funny things, you know? Like clump up together. And everybody was just sort of like, Oh, well if if they're they're supposed to be laying flat. If they're not laying flat, you j you screwed it up. Like they they just weren't that interested. No. So I just kind of like put it in formaldehyde.

Put it away in the fridge for a little while and was like, okay, let's try this gene screen again. But this time, no floaty clumps, gonna get those cells. Flat on the bottom. And eventually she decides to try something new. This thing that I had read about called Matra gel. Basically cellular crazy glue. Like she's not taking any chance.

I'm just gonna put a whole bunch in my dish. So she squirts a lot of it on there. Okay. She puts her cells on top and again pops them in the incubator, crosses her fingers, and goes home for the night. She comes back in the morning. You know, same thing. You go to the incubator, you take it out of the incubator, you look at it, and I was like, Okay, this is weird. Once again, there's a bunch of Stuff floating in there. Huh.

I was like, okay, well the matra gel didn't work like it was supposed to. Again, it seemed like the cells had started clumping together. And that's when I then took them, put them on the tissue culture microscope. Looked down the eyepiece and again there they were. Funny shaped Balls. These ones were also beige ish. Off white kind of color. But they were bigger. And they sort of have like f bulges coming off of them. And this time when she looked inside, she saw full on architecture.

But also a little circle, sort of oblong shaped thing. And a fat layer of tightly packed cells. All lined up around a space in the middle. They were making structures, they were making things. Kinda like what cells do as an embryo is developing, which to Madeline didn't make any sense. Everybody had always taught me that

need things coming from other tissues in the body, you know, of the embryo that are necessary for building that embryo. And here was a situation where nothing was telling them what to do because they'd been completely taken out of the embryo. Hmm. And they were like forming Structures with no instructions. She's like, oh my god, like this is like there are things developing here. But toward what? Well to Madeline, it kinda looked like they were building a brain.

So these are these are neural stem cells, which inside a developing mouse starts out as a sheet of cells and then they fold up and close and form a tube. And then the neural tube elongates and that becomes the spinal cord. One end of it balloons out and that becomes the brain. And that's what it looked like the cells in Madeline's dish were doing. It it seemed like these cells on their own were starting to try to make themselves into a mouse brain. At the time, yeah, at the time I was

I was just kind of confused. So she showed some other people around the lab what she'd seen. I showed some of these structures. Tubes, the circles, the lines. But several people in the lab were just kind of I think they were just totally bored. They were like, I don't know, sometimes things just grow weird. You probably just did the gel wrong.

And the director of the lab, her boss, was like, I thought you were gonna do a screen. You know, make a flat dish of cells to screen for genes. What are you doing? And I was like, Don't worry, I'm working on it. And so over the next few months, Madeline focused on getting a nice flat layer of mouse neural stem cells on the bottom of her petri dishes so she could do those screens. And so that was like mostly what I was talking about with people in the lab. Yeah.

But at the same time, off by yourself. In her little corner, when no one was paying attention. I was always still playing around with Matra gel, growing these weird balls of cells. Tweaking the recipe. Trying to make sure I could get it to happen reproducibly. And then one day,

Growing Human Brains in a Dish

Cells that come from skin or blood that you can reprogram to an embryonic state. Where do you get those from? I think these were actually made. Um discarded human foreskin. Wow. So specific. Okay. Thank you for that. Because it's just bit of tissue that's thrown away. Yeah, right. Of course. Of course. Literally thrown away. All right. Okay. So uh wow. Yeah.

So she got these human stem cells, she put them in the matra gel, swirled them around in this nutrient-rich fluid so they could kind of eat. And she would win. Watch as these formerly foreskin cells started forming into clumpy parts of a human brain. God. And then she kept tweaking when and how much of the matri gel she would add, and she would just watch these.

Blob shapes over time get bigger. I mean they can get as big as like a pencil eraser. Side note, at the time, she was pregnant. Yeah, my oldest, I was pregnant with her. She said she had this extra maternal instinct and she was like just really nurturing these little brain balls. And then one day, couple months after the other. She's been tweaking her ball recipe. And I looked under the microscope. Inside. Yeah.

On this beige lump she could see a perfect ring of black pigment. And that was just I looked at that, I was like, that's a developing eye. Shut up and it was growing on a developing human brain. You're li no, what? Yeah. No, you what? And then then That was then when she went to her weekly lab meeting. I presented this data, I showed this picture of the beginning of an eye and I remember hearing audible gas.

And then she showed them pictures of the cells forming tubes and lobes and ventricles like an actual brain. Everybody in the lab started to get it. They were like, hey, wait a second, it's like you have a version of an early human brain in this dish. You can actually walk True though, do we not know anything about early human brain development? I just think You get all these little Like when you're pregnant you get a scan here, a scan there. Maybe we know something from animal models

But this was literally the first time anyone in human history had ever watched the early brain develop right from the beginning like this. Yeah. Which is especially important. when something in the brain has gone wrong. Now we can actually watch this process instead of just looking at the end when the person is already severely suffering. We can try to understand how it got there.

So Madeline and her boss, Jurgen Knoblik, who's on board with the whole project now, in 2013, they team up with a bunch of other researchers and publish a paper in the journal Nature. In that paper, they describe how this disorder microcephaly develops And they were like, oh, and to see all of this, we use these tiny 3D brain balls which we have discovered.

Cerebral organoids. That's when like everything changed. If you were studying human brain development, it was like someone just invented the microscope. You can see things that were invisible before.

Organoids for Neurological Disorder Research

I I don't know. So this is Carl Zimmer, science journalist, New York Times columnist, book writer. Ah, you got Zimmer. Yeah. As soon as I heard about this stuff, of course he's my first phone call and he was all over it. Sort of like humanoid, organoid, very sci-fi. And the first thing that he pointed out is that there are So many neurological disorders where the key moments are during development. It's like the key the key plot points are happening when we can't watch the movie. Right.

Totally off limits. But 2013 Madeline and Jurgen published their paper, and boom, we could watch human progenitor brain cells give rise. To parts of the brain. What what would you do with that? Like what would you see? So one example is a there's a scientist at Stanford named Sergio Posca, and he studied A very rare disease called Timothy syndrome. It's caused by a genetic mutation that causes severe neurodevelopmental problems.

And he basically created an organoid with that mutation so that he could see how a brain with Timothy syndrome develops, like from the beginning. Yeah. Now you can actually see what Timothy syndrome is about. So what and what did he see? So there are certain kinds of cells called interneurons and they make very important connections between uh different parts of the brain. And with kids with Timothy syndrome, they just don't.

They just fail to get where they need to go. And now that he knew what was going wrong. He started testing out. Some drugs to see if he could fix that. Yeah. And he and his colleagues actually ended up finding a a small drug that actually did help these uh neurons to find their way in an organ. Well, so he cu he cured it in an organoid. Right. Huh. And they are on track to actually start uh clinical trials with that drug uh next year. Wow. And you could imagine that's one disorder. That's right.

Uh a lot of other conditions. Epilepsy, schizophrenia, fetal alcohol syndrome. Any of these brain conditions that have an issue starting in development or where we might even suspect they might start that early, but aren't sure yet. Now you can see it. You know, a lot of people in the field said, Whoa, I gotta try this. This whole field of neural organoids has just totally exploded. There's I think there's thousands of labs actually using these tools now.

The study of the brain is It's fundamentally different now. That's what we are doing on Radio Lab today. We are just Lulu, we're gonna jump in. ball pit of brain balls. Okay. In which there are tons of new opportunities, but also confounding questions. Are there Thoughts in there? Is there thinking in there? How brainy are these balls? We are gonna get there after the break.

Personalized Cancer Treatment Breakthroughs

Alright, here we are. I'm in the 72nd Street subway station and I am walking to go see a fridge full of brains. Hey, I'm Latv Nasser. I'm Lulu Miller. This is Radio Lab. More specifically, a fridge full of brain organoids. Just before the break, we learned from Madeline that now thousands of labs around the world are growing these brain organoids. And it turns out that one of them

Happens to be just up the street from our studio in New York City. Only when you're recording are you truly conscious of like how much you breathe. So we sent our producer, Mona McGauker. Ooh. laboratory, caution, hazardous materials. To check them out. Where are we entering? So we're entering so we have special rooms called cell culture rooms where we grow oops, we grow um the organoids

This is Dr. Howard Fine. I'm a medical and neuro oncologist. And this is his lab at the Wild Cornell Medical Center where he studies brain cancer. A very bad kind. Probably now the most lethal of all human cancers, the average survival is about fifteen or sixteen months. And Dr. Fine says around fifteen years ago or so he hit a wall in his research. He'd been studying glioblastoma, mostly of course in mice, right?

And he admits he actually calls this at the time it was the dirty little secret of oncology that for all this research they were basically getting nowhere. Whoa. But then he came across Madeline's work on organoids. I read in Nature and it's like like a li literally not many times in you know at least my thirty seven career did I truly have a light bulb moment and I I read that paper and said, This is what we're looking for.

And even though And that's when he pivoted away from mice and started making brain organoids. Can I can we see it? Okay, so He's opening the incubator and he's pulling out So these are the Stem cells. And they looked just like Madeline described. Little beige balls floating in liquid in a dish. And under the microscope. You can see structure. Yes. But the difference between these organoids and Madeline's organoids Was that these ones had cancer.

And so the idea is we're going to make a mini brain From an individual patient. And then Oh, these are the glioma cells. Wow. Excels. looks like sugar that hasn't dissolved in tea. And then we retroengineer the patient's own glioma stem cells into the mini brain. Basically they can put a version of your brain tumor on your version of your brain. On a version of your brain

And they can basically make a bunch of those hundreds or thousands of drugs and then try a bunch of medicines on them. To look for the drugs or combination of drugs that might be most effective. So you're saying that like you can try every chemotherapy that's out there and decide like which one? Everything uh only li limited by resources. Oh my god. That is um that is beautiful. I mean that just thinking about a a a way of like a kind of bespoke medical future exploration

Ah. Right? Way better than just using mice. Oh my gosh. Leapfrog, one of the biggest reasons on average, ninety percent of clinical trials for neurological drugs. Fail. And for brain cancer, by the way, that number is even higher, 95%. They're failing because they're not predicting whether the drug actually works.

on the disease. And this is something that Madeline told me too. You might have a drug that works really well for treating mouse spinal cord injury. Like it's like, okay, great. This is not going to kill you. Because you've got the animal work to show you that it's safe. But it also doesn't make them better after their spinal cord injury. But now, sure, they can do a month trial for safety, but they can also test that drug to see if it works.

on a spinal cord organoid, which is, you know, just a tiny version of an actual human spinal cord.

The Diverse World of Organoids and Assembloids

Wait, what? I thought we were talking brain organoids. She are there are there spinal cord organoids? Spinal cordor spinal cord organoids? Yeah. Okay. So as Madeline was developing her brain organoids.

independently, around the same time, other scientists all over the world Are growing intestinal organoids, lung organoids, liver organoids, muscle organoids, skin organoids, anchorous organoids, stomach organoids, heart organoids, kidney organoids, uh breast tissue organoids that actually produce milk.

Ah. They ha they can have a breast tissue organoid that can make milk? Yes. Weird. Has anyone tasted that milk? Uh I certainly haven't. I've only read about it. I don't know. I don't know. That's a good question. Anyway. That's science writer Carl Zimmer again. And he says now you can make an organoid of basically any part of the body. And then you can connect them. What? You can like you can Does that work? You can do that? Oh yeah. They call them assembloids. Assembloids.

Yeah. No. Like you can Mr. Potato Head assemble Correct. But then do they attach to each other? They attach to each other. And do they communicate with each other? They communicate with each other, yeah. Okay. And then what uh do what with your charm bracelet human body? So here's an example. So Sergio Pasca neuroscientist at Stanford University and his colleagues thought, can we use an assembloid to study pain? The pathway of pain.

So they started with The Finger. A finger organoid? No, no, no, no, sorry, just a a nerve in the finger. Oh, okay. sensory organoid, connect that like with some other cells in the dish. Another organoid. The spinal cord. Yeah, it's a little teeny piece of spinal cord. Now we're gonna connect that to a brain organoid that is specifically the thalamus, which is the central hub in the brain that direct

signals in all sorts of different ways. And finally, we're gonna connect that one to one more brain organoid. Cortex orenoid. Whoa. This is I mean it's like Legos It's like Legos with the human body. Correct. So then they took Capsaicin, that's the molecule in like spicy food, is that the other thing? Very it can be very painful uh to the to the skin. Okay. And they said, Okay, let's let's hit it with Capsasa and see what happens.

Uh-huh. Boom. Immediately the that sensory organoid goes and starts sending really strong signals. And those signals, Carl says, zoom right up through this assembloid. To the spinal cord, the Just like it would in your own body. And they can see some kind of registering? Correct. And when they watch the way the signal travels, which is something that's normally hidden inside a body. They've discovered all sorts of things about what happens when we feel pain.

That they didn't know about before. Like, for example, signals from different parts of the assembled began firing together in these synchronized waves of signals. And the more you know about how those signals work or move, the better chance you have at stopping them. You could, for example, say, okay, can I put a molecule into this assembloid that will stop the pain?

Do Organoids Feel? Defining Consciousness

Oh wow. But um So if they're using these things to study pain Is it feeling pain? No, probably not. These organoids Our Just little bits of human tissue in order to feel pain the way we feel pain. There are other parts of the brain that come into play. The assembloid is just this super basic circuit that you send a signal through. So like this pain it Seems to be superficially registering it. And like what is the it, I think. No, no, no. I'm the f the I'm

The first thing it it's like it is this little ball, but is it a thing? Like Is it? Well, they crackle with electricity. They they form connections called synapses. They d replicate parts of the human brain with astonishing accuracy. But Carl says they're not brains. They're not brains. That's right. Okay, so if there's like a slider and on one end is brains. And then on the other end is just like some neurons in a dish. Where is this on the slider? And and how do you yeah? I would say that it's

closer still for the time being to the neuron end of the slider simply based on numbers. Our brain has something like eighty billion neurons. And the biggest human brain organoids contain About two million cells. So that's zero point zero zero two five percent. Well under one percent. Yeah. And you know, these things don't have blood vessels, so that is a

A very important key limiting factor to how big and complex it can get. Yeah. And they're not in a body. So they can't interact with the world in like a meaningful way. Okay.

Human Brain Cells in Rat Brains

Well but when I was talking to Carl about this. So um he said that a lot of that might no longer be true. Some scientists have, you know, taken organoids from human cells and have put them into the brains of rats. What So basically what they did is they basically took a rat and they like carved out a chunk of its brain. But they left some of it. They left most of it. Okay. And it's almost like it's like think about it like it's almost like they gave a rat a a little human tumor or something. Um

Brain. Human brain. It's human brain. Oh my god. And these human organoids are pretty happy in there. It sort of wired in. They connect up. With the rat neurons, they get supplied by the rat blood system. So they have In a real sense, like a new kind of being. Yeah, yeah, yeah. That did not exist before this. Correct. Um

feels like there should have been a bigger press release, but okay, do the do the do the rats act any differently? Are they suddenly like into podcasts and coffee? When you do studies on these rats. Behavioral tests, memory tests, all sorts of things. They're just rats. There seems to be nothing humane-y about them. Okay. But one thing they did notice, when you tickle its whiskers.

Yeah. You can actually measure signals from the human brain organoid neurons. The human part of the brain lights up. Yeah. So it's registering the feeling? They are receiving signals th from the rat's senses. I mean, uh strictly speaking, they are receiving signals from the rat's senses. Are they feeling it? Fi a feeling i it gets hard'cause it's kind of the pain question again.

But yeah, but now they're in a body. I mean they're in a being. Yes, but they're not the like driving force of that being. They're like a they're like a house guest in the attic. Okay, Latif, would you put make a brain ball brain organoid of your brain cell and put it in a rat. Um...

If I'm being honest with you, probably not. Okay. Okay. Okay. So I don't know, but I just think you're more on my side that this is a little scary than you in your little with your reporter's wand are letting on to, because yes. Uh there's exciting research, but it just feels like every time you try to comfort me with what we know about these things, you then end up not comforting me and then the scientists take it one step further anyway.

Um okay. Well it's it's as if you have seen the future and what the next chapter holds.

Biocomputers: Brain Cells Play Pong

Uh because that exact thing is gonna happen. Uh it's gonna get weirder and creepier and stranger and that's all after the break. Stick with us. Lutif. Lulu Radio Lab. We are back talking about brain balls, you know, bitty brains, boba brains, the brain-ish in a dish. Yes, ha ha, with all your clever wordplay. Uh, but you're about to send us into the next existential tailspin. About how people are using these things? It is possible.

So the final thing I was told to do is push record. Record, yes. That's an important button. Now tell me who you are. So I'm I'm Brett. This is Brett Kagan. He's a neuroscientist. I'm the chief scientific officer here at Cortical Labs. Cortical Labs. We're a small tech startup here in Delphine, Australia.

Did you start it? Did someone else start it? No, well it was founded by uh there was a few of us and I was contacted by doctor Han Weng Chong and Andy Kitchen and they were looking for a neuroscience. Brett had been an academic obsessed with this particular question. How do you get intelligence out of brain cells that are in a dish? And this company was like

Why don't you leave academia and help us find out? The question they had was, can brain cells in a dish do anything at all that we might want them to do? Hmm. Like, do what? What better to pick than Pong? The like seventies computer games? Yeah, the game with the paddles and the little ball. Why that? Everybody knows Pong. It was one of the first computer games. It was the first thing that machine learning, which people now like to call AI, really was trained on as a big breakout success.

And he figured out The brain runs on electricity. Then it's also a shared language of silicon computing. So why wouldn't we be able to get neurons to do something a computer could do? That exactly. Like play a simple video game. We used some hardware that allowed us to record the activity of the cells. process that and then deliver small electrical pulses back into the cultures. And they did it. Scientists just put pieces of human and mice brain on a plate and a few.

and wired it to a computer to play Pong. They learned to track the ball and control a paddle. Seriously, this is one of the craziest things I've ever covered. So here's what's going on. What? No. Yeah. And this wasn't even an organoid. This was just a flat sheet of neurons in a dish. I mean, how could it possibly be doing that? Like I mean, d can can really dumb things do that? Could like a could like a tree do that?

Trees don't have neurons, so I I I don't think a tree could do that. Okay, so so but well what what does this mean? Like are are they learning? Well, Brett says yes. I called it learning and I think learning was incredibly fair Definition because what would an improvement over time in a way that would suit a goal be called other than learning? But other people, including Madeline Lancaster I actually remain to be convinced anybody has really shown that. Say no. Because

It's really hard to interpret the signals coming from the neurons. She says when you teach brain cells to play pong, they're, you know, connected to a computer. So what what people do is they use algorithms to sort of decode that message and then send a signal back to neurons. And so you kind of have like two black boxes that you've just hooked up. It's sort of a collaboration between the brain cells and the computer. And you don't really know what either of them are doing.

Anyway, whatever is happening here, what Brett and his team took away from this is if neurons can do something a computer does. Why don't we use neurons as computers? What? Yeah. Literally a couple months ago, they released their first computer called the C L One, and it is They don't call it this, but it's it's effectively a biocomputer. It has neurons in it. Ew. Brain

Sticky real human brain matter in it? Yeah. It's got like little brain organoids in it. It has eight hundred thousand neurons interfaced with a silicon chip you can use it to do computer stuff with. Uh okay. Uh I mean I can get behind the the brain balls being used for neurological disorder research. Great. You know what? Bespoke cancer treatments? Cool. But why are we hooking up human brain cells to computers to like

That to me feels like not worth the risk. Like well, think about the problems we are having right now. with all of these data centers chugging all this energy, right? Yes. Absolutely wrecking the planet. Right? So our brains are So impressively efficient. Energy-wise, we have like a dim light bulb like screwed into our heads, right? That's the amount of energy that we need to do all the complex things that we do. If AI or if some supercomputer was doing the equivalent

It would need millions of times more power. Like the difference between a single light bulb and a large town. It's so flattering. The other thing is that like think about these AIs. You need to train it on the whole internet. Right? A human brain is much quicker to learn. If you could harness that energy efficiency, if you could harness that kind of like a knowledge efficiency in a computer, you could move mountains. Okay.

Ethical Future of Brain Organoid Research

But I guess my authentic question at this point is like, okay, you have shown us all this stuff. At this point it seems pretty clear that they can definitely register input, right? Like they've uh there's the tickle, the pain, the signal they're getting from Pong. Mm-hmm. Okay. And then this Pong example at least shows us they are then able, based on that input.

to produce some kind of output. Yeah. Okay. So let's say it is. Yeah. Okay. So my question is, if they can do those things, wouldn't they have to have some thrumming level of consciousness? Uh no, actually. No, they really don't. Like like like just like a bunch of the things you just talked about, AI can do those. Is AI conscious? Even going further than that, like

A Roomba can do. Like navigate a room. A room. Is a Roomba conscious? That's that's a signal in and out. Yeah, right. A Roomba's going, Oh, there's an edge, let me go this way. That's a signal in and out. When we talk about human consciousness, we meet self consciousness. Like you are aware of yourself. You have a past. You have a future that you're concerned about. This is Dr. Insu Hyun. I'm the director of the Center for Life Sciences at the Museum of Science in Boston.

He's a bioethicist and he's worked on a bunch of teams with scientists who are studying brain organoids. We try to identify what are the emerging scientific and ethical issues. You're like kinda like their conscience? Is that sort of the thing? And he says at this point he is not worried about brain organoids having anything like human consciousness. The brain organoids in the dish don't have that continuity.

They don't have all the regis. They don't have the interaction with the outside world. But when he thinks about the future that Brett and others are trying to create. Where maybe people start connecting more and more complicated and even more and more structured clumps of human brain cells to computers. Maybe you get it might not even be human consciousness, but some kind of consciousness could emerge. Just to the world. Okay, so what what about this, Latif?

I I would if I may, I I would like to just issue a commandment that all the smart people who are like excited by brain organoids, they all take one year to stop making organoids and use their Smarts and their technologies and their labs to like Try to understand the consciousness of the organoids that have already been made. You know, like ideally they they could all be in a dark room and just have candles and quietly, meditatively watch for any flickers.

to understand what's going on. And then and then we have a grand assembly where everyone reports back and we all collectively decide what to do. I know that like some of these scientists have this fire inside them to be like, how many cures am I not gonna find in that year? Like how many people am I not gonna help in that year? Like the glioblastoma, like those people don't have a year. And those people are telling me to just shut up because this is a

piece of discarded foreskin. That's right. If if we have a tool that we don't use Madeline Lanecaster again. And there are millions of actually conscious human beings out there that don't have treatment. But we decide, no, we're gonna put the value of organoids higher than those people, that would be unethical.

It's funny, like at the beginning, like you asked me, like, would you make a brain ball of yourself? And I said no. And then at some point, like my thinking switched where I'm like, oh, no, unless. It would save someone's life. Well that's noble and now I feel even worse saying I don't know that I would. I just I mean, yeah, okay. If it's my own kid, sure, I don't care if I'm like a little enslaved human consciousness if it saves my kid, but

As you have shown us, the scientists are gonna do more. They're gonna try new things. They're gonna build bigger brains and like There is a line and we will cross it and we won't know that we've crossed it. You know? Right. And well, and the thing about these organisms is that they're already crossing all kinds of lines. You disrupt categories that we thought were so neat and tidy and distinguishable. Life non-life. Non-human, human computer.

Those are pretty clean categories, but this research is kind of upsetting the very foundations of what we think separates these categories apart. Like a a new category of thing that is maybe alive. It is alive. We have created a new category of thing that is alive. That is w that. It's hard. It's hard to actually put it into a category that already Actual brains. That we can say absolutely certain. We almost don't really even have the Yeah. I think it's kind of A new thing.

Lot of N Mm. It was edited by Alex Neeson and Pat Walters with fact checking by Natalie Middleton and Rebecca Rand, special facts. Anne Hamilton, Christopher Mason, Madeline Mason Mariarty, plus the other. His whole team at Wild Cornell for hosting us. And if you're looking for more musings on the nature of life and what it means to be alive, Carl Zimmer has a terrific book out all about this. The search for what it means to be alive. at your local bookstore.

That's it for us from our Brain Balls T. Okay, start now. We're recording now. Hi, I'm Ellie Collins and I'm from Louisville, Kentucky, and here are the staff credits. And she's Molly's niece. Yeah. Radio Lab is hosted by Lulu Miller in Latif Nasser. Sorrin Wheeler is our executive editor. Sarah Sandback is our executive director. Our managing editor is Pat Walters.

Keefe is our director of sound design. Our staff includes Jeremy Bloom, W. Harry Fortuna, David Gable, Maria Paz Gutierrez, Sin Dune. Matt Kilti, Mona Mad Gavkar, Annie McEwen, Sara Kari. Arian Whack, Molly Webster, and Jessica Young. With help from Rebecca Rand, our fact checkers are Diane Kelly, Emily Krieger, and Natalie Middleton. I love your gickle.

Leadership support for Radiolab Science Programming is provided by the Simons Foundation and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation.

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