Radiolab - Brain Balls

Episode Date: January 11, 2026

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-Mariarty, the team at the Boston Museum of Science, and Howard Fine, Stefano Cirigliano, and the team at Weill-Cornell. EPISODE CREDITS: Reported by - Latif Nasserwith help from - Mona MadgavkarProduced by - Annie McEwen, Mona Madgavkar, and Pat Walterswith mixing help from - Jeremy BloomFact-checking by - Natalie Middleton and Rebecca Randand Edited by  - Alex Neason and Pat WaltersEPISODE CITATIONS:Videos - “Growing Mini Brains to Discover What Makes Us Human,” Madeline Lancaster’s TEDxCERN Talk, Nov 2015 (https://zpr.io/6WP7xfA27auR)Brain cells playing Pong (https://zpr.io/pqgSqguJeAPK)Reuters report on CL1 computer launch in March 2025 (https://zpr.io/cdMf8Yjvayyd) Articles - Madeline Lancaster: The accidental organoid – mini-brains as models for human brain development (https://zpr.io/nnwFwUwnm2p6), MRC Laboratory of Molecular Biology What We Can Learn From Brain Organoids (https://zpr.io/frUfsg4pxKsb), by Carl Zimmer. NYT, November 6, 2025Ethical Issues Related to Brain Organoid Research (https://zpr.io/qyiATHEhdnSa), by Insoo Hyun et al, Brain Research, 2020 Brain organoids get cancer, too, opening a new frontier in personalized medicine (https://zpr.io/nqMCQ) STAT Profile of Howard Fine and his lab’s glioblastoma research at Weill Cornell Medical Center: By re-creating neural pathway in dish, Stanford Medicine research may speed pain treatment (https://zpr.io/UnegZeQZfqn2) Stanford Medicine profile of Sergiu Pasca’s research on pain in organoids A brief history of organoids (https://zpr.io/waSbUCSrL9va) by Corrò et al, American Journal of Physiology - Cell Physiology, Books - Carl Zimmer Life’s Edge: The Search for What it Means to be Alive (https://carlzimmer.com/books/lifes-edge/)Sign up for our newsletter!! It includes short essays, recommendations, and details about other ways to interact with the show. Signup (https://radiolab.org/newsletter)!Radiolab is supported by listeners like you. Support Radiolab by becoming a member of The Lab (https://members.radiolab.org/) today.Follow our show on Instagram, Twitter and Facebook @radiolab, and share your thoughts with us by emailing radiolab@wnyc.org.Leadership support for Radiolab’s 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.

Transcript
Discussion (0)
Starting point is 00:00:01 Wait, you're listening. Okay. All right. You're listening to Radio Lab. Radio Lab. From. W. N. Y. C.
Starting point is 00:00:14 See? Yeah. Okay, Lulu. Yeah. We're going to start today. Mm-hmm. Back in 2010 in a lab in Vienna. Oh, jumping right in.
Starting point is 00:00:27 Yeah. Just picture sort of a lab with microscopes, computers, experiments. And off in one corner. Hello. Hi, how's it going? Wearing glasses and a white lab coat is this scientist named Dr. Madeline Lincaster. Call me, Madeline. Madeline has just finished her Ph.D. and moved to Austria.
Starting point is 00:00:45 Just joined the lab to start her postdoc research. I was 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?
Starting point is 00:01:05 Yeah. Now, she hadn't done exactly this kind of gene screen before. And that's probably why I didn't really, you know, I was kind of naive about it all. But, so anyway, she got to work.
Starting point is 00:01:18 You put this enzyme on. It just cuts those. Preparing the baby mouse cells. The cells all become loose and apart from each other. That part she'd actually done before, so you know, easy enough. Yeah, but.
Starting point is 00:01:29 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.
Starting point is 00:01:43 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
Starting point is 00:01:56 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, The dishes pipetted in the cells, popped them in the incubator, and went home for the night. Next morning, came in. Took a look in her petri dishes, hoping to see a nice, clean, clear layer of cells.
Starting point is 00:02:18 Like flat on the dish. But instead, everything in there was... Really cloudy. Hmm. 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 no good, and the cells hadn't stuck.
Starting point is 00:02:33 And if the cells aren't so... stuck in the protein, that means they're probably dead. Yeah, all the cells are dead. I'll just throw it away. Hmm. And I don't know why I did this, but... Right before she tossed it, she thought... You know, but I'll check it.
Starting point is 00:02:46 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 blobs. The cells weren't dead. They were... Alive and healthy and... Plumped in...
Starting point is 00:03:03 into three or four blobs. Huh. Yeah, can you, as vividly as you can describe him? I mean, they're like a sort of beige color, like an off-white tiny. About the size of a grain of sand. Are these floating balls of cells? And she's like, huh? Weird.
Starting point is 00:03:19 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 tube. Yeah. So she's like looking down into like one end of the tube. So it looks almost like a donut shape.
Starting point is 00:03:41 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.
Starting point is 00:04:03 So 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 seen cells do funny things, you know? Huh. Clump up together. And everybody was just sort of like, oh, well, if they're supposed to be laying flat, if they're not laying flat, you screwed it up. Like, they just weren't that interested. No. So...
Starting point is 00:04:29 I just kind of like put it in formaldehyde, put it away in the fridge for a little. a little while and was like, okay. Let's try this gene screen again. But this time, no floaty clumps, going to get those cells to stick flat on the bottom. And eventually she decides to try something new. This thing that I'd read about called
Starting point is 00:04:47 matrogel. Basically, cellular crazy glue. Like, she's not taking any chances. I'm just going to 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
Starting point is 00:05:03 She comes back in the morning. Yeah, 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.
Starting point is 00:05:16 Huh. I was like, okay, well, the matri 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, look down the eyepiece. And again, there they were. funny shaped balls. These ones were also beige-ish.
Starting point is 00:05:37 Off-white kind of color. But they were bigger. And they sort of have like bulges coming off of them. And this time, when she looked inside, she saw full-on... Architecture. There was a tube, but also... A little circle sort of oblong-shaped thing. And a fat layer of tightly packed cells...
Starting point is 00:05:57 All lined up around a space in the middle. They were making structures. They were making things. Kind of like what cells do as an embryo is developing, which to Madeline didn't make any sense. Everybody had always taught me that cells 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
Starting point is 00:06:23 because they'd been completely taken out of the embryo. 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 kind of looked like. They were building a brain. So these are, these are neural stem cells, which inside a developing mouse starts out as a shade of cells and then they fold up and close and form a tube. And then the neural tube elongates and that becomes a spinal cord, one end of it balloons out,
Starting point is 00:07:06 and that becomes the brain. And that's what it looked like the cells in Madeline's dish were doing. 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 just kind of confused. So she showed some other people around the lab what she'd seen. I showed some of these structures.
Starting point is 00:07:30 The 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 going to do a screen. You know, make a flat dish of cells to screen for jeans.
Starting point is 00:07:48 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.
Starting point is 00:08:09 Off by yourself. In her little corner when no one was paying attention. I was always still playing around with matri 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, she gets her hands on some human stem cells. Cells that come from skin or blood that you can reprogram to an embryonic state.
Starting point is 00:08:32 Where do you get those from? I think these were actually made from discarded human foreskin. Wow. So specific. Okay. What a detail. All right. Thank you for that.
Starting point is 00:08:46 Because it's just a bit of tissue that's thrown away. Yeah, right. Of course. Of course. Literally thrown away. All right. Okay. So, uh, wow.
Starting point is 00:08:54 Yeah. So anyway. So then with... So she got these human stem cells. She put them in the matri gel, swirled them around in this nutrient-rich fluid so they could kind of eat, and she would watch as these formerly foreskin cells started forming into clumpy parts of a human brain.
Starting point is 00:09:12 Oh, my 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. So she said she had this ex-executive. maternal instinct and she was like just really nurturing these little brain balls.
Starting point is 00:09:36 Yeah. And then one day, a couple months after 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.
Starting point is 00:09:58 Shut up. And it was growing on a developing human brain. You're like, no, what? Yeah. No, you, what? And then, then. That was then when she went to her weekly lab meeting. I presented this data.
Starting point is 00:10:13 I showed this picture of this beginning of an eye. And I remember hearing audible gasps. 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 lot. a version of an early human brain in this dish,
Starting point is 00:10:35 and you can actually watch the earliest stages of this process of development. That we know almost nothing about. Is that 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.
Starting point is 00:11:03 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, Yergan Knoblek, 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.
Starting point is 00:11:31 In that paper, they describe how this disorder microcephaly develops in a fetal brain. And they were like, oh, and to see all of this, we use these tiny 3D brain balls, which we have decided to call cerebral organoids. That's when, like, everything changed. If you were studying human brain development, it was like someone just invented the microscope. Yes. You can see things that were invisible before. So this is Carl Zimmer.
Starting point is 00:12:01 Science journalist, New York Times columnist, bookwriter. 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.
Starting point is 00:12:21 It's like the key plot points are happening when we can't watch the movie. Right. Totally off limits. But 2013, Madeline and Yurgan published their paper and boom. We could watch human progenitor brain cells give rise to parts of the brain. What would you do with that? Like, what would you see? So one example is a, there's a scientist at Stanford, Sanford-Raeo Paska,
Starting point is 00:12:43 and he studied a very rare disease called Timothy's syndrome, which is caused by a mutation that produces autistic behavior. As well as a bunch of other things like seizures. And he basically created an organoid with that mutation so that he could see how a brain with Timothy's, Timothy syndrome develops, like from the beginning. Yeah. Now you can actually see what Timothy syndrome is about.
Starting point is 00:13:08 So what did he see? So there are certain kinds of cells called interneurons, and they make very important connections between different parts of the brain. And with kids with Timothy's 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.
Starting point is 00:13:33 And he and his colleagues actually ended up finding a small drug that actually did help these neurons to find their way. Ah. In an organoid. So he cured it in an organoid. Right. Huh. And they are on track to actually start clinical trials with that drug next year.
Starting point is 00:13:57 Wow. And you could imagine that's one disorder. That's right. A lot of other conditions. Epilepsy schizophrenia, autism. 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. A lot of people in the field said, whoa, I got to try this. This whole field of neural organoids has just totally exploded.
Starting point is 00:14:24 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 going to jump into the ball pit
Starting point is 00:14:43 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 going to get there after the break.
Starting point is 00:15:01 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 Lathiv Nasser. I'm Lou 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.
Starting point is 00:15:42 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 McGaalker. 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,
Starting point is 00:16:02 oops, we grow the organoids. This is Dr. Howard Fine. I'm a medical and neuroanologist. And this is his lab at the Wild Cornell Medical Center where he studies brain cancer. The type of brain tumor known as a glioblastoma. A very bad kind. Probably now the most lethal of all human cancers. The average survival is about 15 or 16 months.
Starting point is 00:16:24 And Dr. Fine says around 15 years ago or so, he hit a wall in his research. We've probably made the least amount of progress with when I was a... So 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, you know, he came across Madeline's work on organoids.
Starting point is 00:16:52 And it was Lancastor's paper. I read in nature and it's like literally not many times. It's my 37 career. Did I truly have a light bulb moment? And I read that paper and said, this is what we're looking for. And that's when he pivoted away from mice and started making brain organoids. Can we see him? We're going to take a look.
Starting point is 00:17:11 Okay, so he's opening the incubation. and he's pulling out. So these are the stem cells. And they looked just like Madeline described. They're kind of like a beige color. They look like a kidney bean or like a nerd candy. Little beige balls floating in liquid and it is. And under the microscope,
Starting point is 00:17:29 I see like a dark shape and then I see these little bubbles off the side, almost like little popcorny shapes. You can see structure. Dr. Vind, these are from specific patients, like your patients? Yes. But the difference between these organoids and Madeline's organoids was that these ones had cancer. So the idea is we're going to make a mini brain from an individual patient.
Starting point is 00:17:54 And then... Oh, these are the glioma cells. Wow. They take cells from that patient's brain tumor. Almost just 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.
Starting point is 00:18:14 On a version of your brain. And they can basically make a bunch of those. We can test 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, only limited by resources. As you could imagine.
Starting point is 00:18:35 Oh, my God. That is beautiful. I mean, that, just thinking about a way. of like a kind of bespoke medical future exploration. Right? Way better than just using mice. Oh my gosh. Partly because it also could help us leapfrog one of the biggest reasons on average
Starting point is 00:19:00 90% 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
Starting point is 00:19:18 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 the spinal cord injury. But now, sure, they can do a mouse trial for safety,
Starting point is 00:19:32 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. Wait, what? I thought we were talking brain organoids. Are there spinal cord organoids? Spinal cordynoids?
Starting point is 00:19:52 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. Long organoids. Liver organoids. Muscle organoids. Skin organoids. Anchorage organoids. Astemic organoids. Heart organoids. Kidney organoids. Breast tissue organoids. Breast tissue. organoids that actually produce milk. Ah. They can have a breast tissue organoid that can make milk? Yes.
Starting point is 00:20:22 Weird. Has anyone tasted that milk? I certainly haven't. I've only read about it. I don't know. I don't know. That's a good question. Anyway.
Starting point is 00:20:31 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.
Starting point is 00:20:48 Assembloids. Yeah. No, like you can Mr. Potato Head assemble. Correct. But then do they attach to each other? They attach to each other, yeah. And do they communicate with each other? They communicate with each other, yeah.
Starting point is 00:21:00 Okay. And then what, do what? With your charm bracelet, human body. So here's an example. So Sergio Paska. Neuroscientist at Stanford University. And his colleagues thought, can we use an assembloid to study pain? The pathway of pain.
Starting point is 00:21:18 So they started with... The finger. A finger organoid? No, no, no, sorry. Just a nerve in the finger. Oh, okay. The sensory organoid, connect that. Like with some other cells in the dish.
Starting point is 00:21:30 Another organoid. The spinal cord. Yeah, it's a little teeny piece of spinal cord. Now we're going to 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 going to connect that one to one more brain organoid. A cortex
Starting point is 00:21:47 organoid. Whoa. This is so weird. 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... And like spicy food, is that right? In spicy food. In chili? Right. Yeah.
Starting point is 00:22:03 It can be very painful to the skin. Okay. And they said, okay, let's hit it with capcason and see what happens. Uh-huh. Boom. Immediately, that sensory organoid goes and starts sending really strong signals. And those signals, Carl says,
Starting point is 00:22:17 zoom right up through this assembloid. To the spinal cord, the thalamus, to the cortex. 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,
Starting point is 00:22:32 they've discovered all sorts of things about what happened when we feel pain that they didn't know about before. Like, for example, signals from different parts of the assembloid began firing together in these synchronized waves of signals. Okay. And the more you know about how those signals work or move, the better chance you have it stopping them. You could, for example, say, okay, can I put a molecule into this assembloid that will stop the pain?
Starting point is 00:22:59 Oh, wow. But, um, so if they're using these things to study pain, is it feeling pain? No, probably not. These organoids are 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.
Starting point is 00:23:29 And like what is the it, I think. The capcation in that case. No, no, no, I'm the first it. It's like it is this little ball, but it is the it a thing. Like, what is it? Well, they crackle with electricity. They form connections called synapses. They replicate parts of the human brain with astonishing accuracy.
Starting point is 00:23:55 But Carl says, they're not brains. They're not brains. That's right. So if there's like a slider and on one end is brains, and then on the other hand is just like some neurons in a dish, where is this on the slider 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.
Starting point is 00:24:19 Our brain has something like 80 billion neurons. And the biggest human brain organoids contain about 2 million cells. That's 0.0025%. Well under 1%. Yeah. And, you know, these things don't have blood vessels. So that is a very important. key limiting factor to how big and complex it can get.
Starting point is 00:24:43 Yeah. And they're not in a body. So they can't interact with the world in like a meaningful way. Okay. Well. But when I was talking to Carl about this, so, he said that a lot of that might no longer be true. Some scientists have, you know,
Starting point is 00:25:02 taken organoids from human cells. Yeah. And it 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.
Starting point is 00:25:18 And it's almost like, think about it. Like, it's almost like they gave a rat a little human tumor or something. Yes. But the tumor is like just brain. Human brain. It's human brain. It's human brain. And these human organides are pretty happy in there.
Starting point is 00:25:33 It's sort of wired in. They connect up with the rat neurons. They get supplied by the. rat blood system? So they have made in a real sense, like a new kind of being? Yeah, yeah, yeah, that did not exist before this, correct. Okay, feels like there should have been a bigger press release, but okay, do the, 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.
Starting point is 00:26:09 They're just rats. There seems to be nothing human-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.
Starting point is 00:26:25 The human part of the brain lights up. What? Yeah. So it's registering the feeling? They are receiving signals from the rat's senses. I mean, strictly speaking, they are receiving signals from the rat's senses. Are they feeling it?
Starting point is 00:26:46 Feeling, it gets hard because 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 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. If I'm being honest, probably not. Probably not. Okay. Okay. Okay. So I don't know,
Starting point is 00:27:18 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, 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. Okay. Well, it's as if you have seen the future and what the next chapter holds. Because that exact thing is going to happen.
Starting point is 00:27:48 It's going to get weirder and creepier and stranger. And that's all after the break. Stick with us. Lathif. Lulu, Radio Lab. We are back talking about brain balls, you know, bitty brains, boba brains, the brainish in a dish. Yes. ha-ha, with all your clever wordplay, but you are about to send us into the next existential
Starting point is 00:28:17 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 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 Melbourne, Australia. Did you start it? Did someone I'll start it? No, well, it was founded by, there was a few of us, and I was contacted by Dr. Hon Wen Chong and Andy Kitchen, and they were looking for a neuroscientist. Brett had been an academic, obsessed with this particular question. How do you get intelligence out of brain cells that are in a dish?
Starting point is 00:28:56 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? Pong? The like 70s computer game? Yeah, the game with the paddles and a little ball. Why that?
Starting point is 00:29:16 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 the brain runs on electricity. And 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? Exactly. Like play a simple video game. We use some hardware that allowed us to record the actual.
Starting point is 00:29:39 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 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?
Starting point is 00:30:11 Like, I mean, can really dumb things do that? Could like a tree do that? Trees don't have neurons. So I don't think a tree could do that. Okay, so, but well, what does this mean? Like, are they learning? Well, Brett says yes. I called it learning, and I think learning was an incredibly fair definition,
Starting point is 00:30:30 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 Lerner, 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 people do is they use algorithms to sort of decode that message and then send a signal back to neurons.
Starting point is 00:31:00 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.
Starting point is 00:31:23 Literally, a couple months ago, they released their first computer called the CL1, and it is, they don't call it this, but 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 800,000 neurons interfaced with a silicon chip. You can use it to do computer stuff with. Okay.
Starting point is 00:31:54 I mean, I can get behind 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 make money? That to me feels like not worth the risk. Well, think about the problems we are having right now with all of these data centers chugging all this energy.
Starting point is 00:32:28 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. So flattering.
Starting point is 00:32:57 The other thing is that, like, think about these AIs. You need to train it on the. 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. But I guess my authentic question at this point is like, okay, you've shown us all this stuff. At this point, it seems pretty clear that they can definitely register input, right? Like there's the tickle, the pain, the signal they're getting from Pong.
Starting point is 00:33:31 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? No, actually. No, they really don't. Like a bunch of the things you just talked about, AI can do those. Is AI conscious?
Starting point is 00:33:58 even going further than that, like a Roomba can do, like navigate a room. A Roomba conscious? That's a signal in and out. Right. A Roomba's going, oh, there's an edge. Let me go this way.
Starting point is 00:34:10 That's a signal in and out. When we talk about human consciousness, we mean self-consciousness. Like you are aware of yourself. You have a past. You have a future that you're concerned about. There's like that continuity of experience. This is Dr. Insu-Hyung.
Starting point is 00:34:25 I'm the director of the Center for Life Sciences at the Museum of Science in Bowen. 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 kind of like their conscience? Is that sort of the thing? You know what? Sometimes I feel like a priest in secular clothes. 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 regions. They don't have the interaction with the outside world. But when he thinks
Starting point is 00:34:58 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. It's hooked up to the world. Yeah. Okay. So what about this, Latif?
Starting point is 00:35:40 I would, if I may, I would like to just issue a command. 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 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 we have a grand assembly
Starting point is 00:36:17 where everyone reports back and we all collectively decide what to do. But I know that some of these scientists have this fire inside them to be like, how many cures am I not going to find in that year? Like how many people am I not going to help in that year? Like the glioblastoma, like those people don't have a year.
Starting point is 00:36:32 And those people are telling me to just shut up because this is a piece of discarded foreskin. That's right. If we have a tool that we don't use Madeline Lancaster again. And there are millions of actually conscious human beings out there that don't have treatments. But we decide, no, we're going to put the value of organoids higher than those people. That would be unethical.
Starting point is 00:36:58 It's funny. Like at the beginning, like you asked me, like, would you make a brainball of yourself? And I said no. And then at some point, like my thinking switch where I'm like, oh, no, unless it's a brainball. it would save someone's life. Well, that's noble, and now I feel even worse, saying I don't know that I would.
Starting point is 00:37:18 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 going to do more. They're going to try new things. They're going to build bigger brains.
Starting point is 00:37:30 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 the thing about these organizations is that they're already crossing all kinds of lines. You disrupt categories that we thought were so neat and tidy and distinguishable.
Starting point is 00:37:51 Life, non-life. Human, non-human. Human, computer. We thought those were pretty clean categories, but this research is kind of upsetting the very foundations of what we think separates these categories apart. It does feel like it's like, oh, we've created a new category,
Starting point is 00:38:15 of thing, like 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 weird. Oh, yeah. It's hard. It's hard to actually put it into a category that already exists, I think, because they're not actual brains that we can say absolutely certainly.
Starting point is 00:38:41 But they're also not just a few neurons in a number. dish either. We almost don't really even have the words for it. I think it's kind of a new thing. Latif Nasser. This episode was produced by Annie McEwen, Mona Madgalker, and Pat Walters.
Starting point is 00:39:29 It was edited by Alex Neeson and Pat Walters with fact-checking by Natalie Middleton and Rebecca Rand. Special thank you shout-outs to Lynn Levy, Jason Yamada Hanf, David Faganbaum, Andrew Verstein, Anne Hamilton, Christopher Mason, Madeline Mason, Maryardi, plus Howard Fine and his whole team at Wild Cornell for hosting us.
Starting point is 00:39:48 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 stuff. It's called Life's Edge, The Search for What It Means to Be Alive. Get it at your local bookstore. That's it for us, from our brain balls to yours. See you next week. Okay, start now. I was practicing.
Starting point is 00:40:09 No, you don't need to. You don't need to practice anymore. Shh. We're recording now. Hi, I'm Ellie Colms, 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 and Latif Nasser.
Starting point is 00:40:27 Sorwin Wheeler is our executive editor. Sarah Sandback is our executive director. Our managing editor is Pat Walters. Dylan Keith is our director of sound design. Our staff includes Jeremy Bloom, W. Harry, Fortuna, David Gable, Maria Pazzo. Gutierrez, Sindu, Nana Sambandan, Matt Kilty, Mona Madgavkar, Annie McEwen, Alex Neeson, Sara Kari, Anissa Vietez, Ariane Wack, Molly Webster, and Jessica Young. With help from Rebecca Rand, our fact checkers are Diane Kelly, Emily Krieger, and Natalie Middleton.
Starting point is 00:41:07 I love your kickle. Leadership support for Radio Lab Science Programming is provided by the Simons Foundation and the John Templeton Foundation. Foundational support for Radio Lab was provided by the Alfred P. Sloan Foundation.

There aren't comments yet for this episode. Click on any sentence in the transcript to leave a comment.