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You're listening to Radiolab.

Radiolab. From WNYC.

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.

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 Lancaster.

Call me Madeline.

Madeline has just finished her PhD and moved to Austria, just joined the lab to start her postdoc research.

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, you know, I was kind of naive about it all.

Hmm.

But she got to work.

You put this enzyme on, it just cuts those proteins.

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.

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.

Came in.

Took a look in her Petri dishes, hoping to see a nice, clean, clear layer of cells.

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.

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.. blobs.

The cells weren't dead.

They were...

Alive and healthy and...

Plumped into three or four blobs.

Huh.

Yeah, can you as vividly as you can describe them?

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 tube.

Yeah.

So she's like looking down into like one end of the tube.

So it looks almost like a donut shape.

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.

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 like seen cells do funny things, you know?

clump up together.

100

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.

101

Like, they just weren't that interested.

102

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.

103

Let's try this gene screen again.

104

But this time, no floaty clumps, gonna get those cells to stick flat on the bottle.

105

And eventually she decides to try something new.

106

This thing that I had read about called Matrigel.

107

Basically, cellular crazy glue.

108

Like, she's not taking any chances.

109

I'm just going to put a whole bunch in my dish.

110

So she squirts a lot of it on there.

111

Okay.

112

She puts her cells on top. And again.

113

Pops them in the incubator, crosses her fingers, and goes home for the night.

114

She comes back in the morning.

115

Yeah, same thing.

116

You go to the incubator, you take it out of the incubator, you look at it, and I was like, okay, this is weird.

117

Once again.

118

There's a bunch of stuff floating in there.

119

Huh.

120

I was like, okay, well, the Matrigel didn't work like it was supposed to.

121

Again, it seemed like the cells had started clumping together.

122

And that's when I then took them, put them on the tissue culture microscope, looked down the eyepiece, and again...

123

There they were.

124

Funny-shaped balls.

125

These ones were also beige-ish.

126

Off-white kind of color.

127

But they were bigger.

128

And they sort of have, like, bulges coming off of them.

129

And this time, when she looked inside, she saw full-on...

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Architecture.

131

There was a tube, but also...

132

A little circle, sort of oblong-shaped thing.

133

And a fat layer of tightly packed cells...

134

All lined up around a space in the middle.

135

They were making structures, they were making things.

136

Kind of like what cells do as an embryo is developing, which to Madeline didn't make any sense.

137

Everybody had always taught me that cells need things coming from other tissues in the body,

138

you know, of the embryo that are necessary for building that embryo.

139

And here was a situation where nothing was telling them what to do because they'd been completely taken out of the embryo.

140

And they were like forming structures with no instructions.

141

She's like, oh my God, like this is like there are things developing here. But toward what?

142

Well, to Madeline, it kind of looked like...

143

They were building a brain.

144

So these are neural stem cells, which inside a developing mouse...

145

Starts out as a sheet of cells, and then they fold up and close and form a tube.

146

And then the neural tube elongates, and that becomes the spinal cord.

147

One end of it balloons out, and that becomes the brain.

148

And that's what it looked like the cells in Madeline's dish were doing.

149

It seemed like these cells on their own were starting to try to make themselves into a mouse brain.

150

At the time, yeah, at the time, I was just kind of confused.

151

So she showed some other people around the lab what she'd seen.

152

I showed some of these structures.

153

The tubes, the circles, the lines, but...

154

Several people in the lab were just kind of, I think they were just totally bored.

155

They were like, I don't know, sometimes things just grow weird.

156

You probably just did the gel wrong.

157

And the director of the lab, her boss, was like, I thought you were going to do a screen.

158

You know, make a flat dish of cells to screen for genes.

159

What are you doing?

160

And I was like, don't worry, I'm working on it.

161

And so over the next few months,

162

Madeline focused on getting a nice flat layer of mouse neural stem cells on the bottom of her Petri dishes

163

so she could do those screens.

164

And so that was like mostly what I was talking about with people in the lab.

165

But at the same time...

166

Off by herself, in her little corner, no one was paying attention.

167

I was always still playing around with Matrigel, growing these weird balls of cells.

168

Tweaking the recipe.

169

Trying to make sure I could get it to happen reproducibly.

170

And then one day, she gets her hands on some human stem cells.

171

Cells that come from skin or blood that you can reprogram to an embryonic state.

172

Where do you get those from?

173

I think these were actually made from discarded human foreskin.

174

Wow. So specific.

175

Okay.

176

What a detail.

177

All right.

178

Thank you for that.

179

Because it's just a bit of tissue that's thrown away.

180

Yeah.

181

Right. Of course. Of course.

182

Literally thrown away.

183

All right.

184

Okay. So, wow.

185

Yeah.

186

So anyway, so then...

187

So she got these human stem cells.

188

She put them in the matrigel, swirled them around in this nutrient-rich fluid so they could kind of eat.

189

and she would watch as these formerly foreskin cells started forming into clumpy parts of a human brain.

190

Oh my God.

191

And then she kept tweaking when and how much of the matrigel she would add

192

and she would just watch these blob shapes over time get bigger.

193

I mean, they can get as big as like a pencil eraser.

194

Side note, at the time she was pregnant.

195

Yeah, my oldest, I was pregnant with her.

196

So she said she had this extra maternal instinct and she was like just really nurturing these little brain balls.

197

Yeah.

198

And then one day, a couple months after, she's been tweaking her ball recipe.

199

And I looked under the microscope.

200

Inside.

201

Yeah.

202

On this beige lump, she could see a perfect ring of black pigment.

203

And that was just, I looked at that.

204

I was like, that's a developing eye.

205

Shut up.

206

And it was growing on a developing human brain.

207

You're like, no, what?

208

Yeah.

209

No, you, what?

210

And then, then.

211

That was then when she went to her weekly lab meeting.

212

I presented this data.

213

I showed this picture of this beginning of an eye.

214

And I remember hearing audible gasps.

215

And then she showed them pictures of the cells forming tubes and lobes and...

216

Ventricles, like an actual brain.

217

Everybody in the lab started to get it.

218

They were like, hey, wait a second.

219

It's like you have a version of an early human brain in this dish,

220

and you can actually watch the earliest stages of this process of development.

221

That we know almost nothing about. Is that true, though?

222

Do we not know anything about early human brain development?

223

I just think you get all these little...

224

Like when you're pregnant, you get a scan here, a scan there.

225

Maybe we know something from animal models.

226

But this was literally the first time anyone in human history

227

had ever watched the early brain develop right from the beginning like this.

228

Yeah.

229

Which is especially important when something in the brain has gone wrong.

230

Now we can actually watch this process instead of just looking at the end when the person is already severely suffering.

231

We can try to understand how it got there.

232

So Madeline and her boss, Jurgen Knoblik, who's on board with the whole project now,

233

in 2013, they team up with a bunch of other researchers and publish a paper in the journal Nature.

234

In that paper, they describe how this disorder microcephaly develops in a fetal brain.

235

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.

236

That's when, like, everything changed.

237

If you were studying human brain development, it was like someone just invented the microscope.

238

Yes.

239

You can see things that were invisible before.

240

So this is Carl Zimmer, science journalist, New York Times columnist, book writer.

241

Ah, you got Zimmer.

242

Yeah, as soon as I heard about this stuff, of course, he's my first phone call.

243

And he was all over it.

244

Sort of like humanoid, organoid, very sci-fi.

245

And the first thing that he pointed out is that there are so many neurological disorders where...

246

The key moments are during development.

247

It's like the key plot points are happening when we can't watch the movie.

248

Right.

249

Totally off limits. But 2013...

250

Madeline and Juergen published their paper and boom.

251

We could watch human progenitor brain cells give rise to parts of the brain.

252

What would you do with that?

253

Like, what would you see?

254

So one example is a, there's a scientist at Stanford, Sergio Pasca, and he studied a very rare disease called Timothy syndrome.

255

It's caused by a genetic mutation that causes severe neurodevelopmental problems.

256

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.

257

Yeah.

258

Now you can actually see what

259

Timothy syndrome is about.

260

So when, what did he see?

261

So there are certain kinds of cells called interneurons, and they make very important connections between different parts of the brain.

262

And with kids with Timothy syndrome, they just don't.

263

They just fail to get where they need to go.

264

And now that he knew what was going wrong...

265

He started testing out some drugs to see if he could fix that.

266

Yeah.

267

And he and his colleagues actually ended up finding a small drug that actually did help these neurons to find their way.

268

Ah.

269

In an organoid.

270

So he cured it in an organoid.

271

Right.

272

Huh.

273

And they are on track to actually start clinical trials with that drug next year.

274

Wow.

275

And you could imagine that's one disorder.

276

That's right.

277

A lot of other conditions.

278

Epilepsy, schizophrenia.

279

Fetal alcohol syndrome.

280

Any of these brain conditions that have an issue starting in development

281

or where we might even suspect they might start that early but aren't sure yet, now you can see it.

282

A lot of people in the field said, whoa, I got to try this.

283

This whole field of neural organoids has just totally exploded.

284

I think there's thousands of labs actually using these tools now.

285

The study of the brain is fundamentally different now.

286

That's what we are doing on Radiolab today.

287

We are just, Lulu, we're gonna jump into the ball pit of brain balls.

288

Okay.

289

In which there are tons of new opportunities, but also confounding questions.

290

Are there thoughts in there?

291

Is there thinking in there?

292

How brainy are these balls?

293

We are gonna get there after the break.

294

All right, here we are.

295

I'm in the 72nd

296

Street subway station, and I am walking to go see a fridge full of brains.

297

Hey, I'm Latif Nasser.

298

I'm Lulu Miller.

299

This is Radiolab.

300

More specifically, a fridge full of brain organoids.

301

Just before the break, we learned from Madeline that now thousands of labs around the world are growing these brain organoids.

302

And it turns out that one of them happens to be just up the street from our studio in New York City.

303

Only when you're recording are you truly conscious of, like, how much you breathe.

304

So we sent our producer, Mona McGaulker.

305

Laboratory, caution, hazardous materials.

306

To check them out.

307

Where are we entering?

308

So we're entering, so we have special rooms called cell culture rooms where we grow, oops, we grow the organoids.

309

This is Dr. Howard Fine.

310

I'm a medical and neuro-oncologist.

311

And this is his lab at the Weill Cornell Medical Center where he studies brain cancer.

312

The type of brain tumor known as a glioblastoma.

313

A very bad kind.

314

Probably now the most lethal of all human cancers.

315

The average survival is about 15 or 16 months.

316

And Dr. Fine says around 15 years ago or so, he hit a wall in his research.

317

We've probably made the least amount of progress with.

318

So he'd been studying glioblastoma, mostly, of course, in mice, right?

319

And he admits he actually calls this at the time it was the dirty little secret of oncology

320

that for all this research, they were basically getting nowhere.

321

Whoa.

322

But then, you know, he came across Madeline's work on organoids.

323

And it was Lancaster's paper.

324

I read in Nature, and it's like, literally, not many times in my 37 career, did I truly have a light bulb moment?

325

And I read that paper and said, this is what we're looking for.

326

And that's when he pivoted away from mice and started making brain organoids.

327

Can we see them?

328

We can take a look.

329

Okay, so he's opening the incubator and he's pulling out.

330

These are the stem cells.

331

And they looked just like Madeline described.

332

They're kind of like a beige color.

333

They look like a kidney bean or like a nerd candy.

334

Little beige balls floating in liquid in a dish.

335

It feels surrounded by a major child.

336

And under the microscope.

337

I see like a dark shape and then I see these little bubbles off the side, almost like little popcorn-y shapes.

338

You can see structure.

339

Dr. Vint, these are from specific patients, like your patients?

340

Yes.

341

But the difference between these organoids and Madeline's organoids was that these ones had cancer.

342

So the idea is we're going to make a mini brain from an individual patient. And then...

343

Oh, these are the glioma cells.

344

Wow.

345

They take cells from that patient's brain tumor.

346

Almost just looks like sugar that hasn't dissolved in tea.

347

And then we retroengineer the patient's own glioma stem cells into the mini brain.

348

Basically, they can put a version of your brain tumor on your...

349

A version of your brain on a version of your brain, and they can basically make a bunch of those.

350

We can test hundreds or thousands of drugs.

351

And then try a bunch of medicines on them.

352

To look for the drugs or combination of drugs that might be most effective.

353

So you're saying that, like, you can try every chemotherapy that's out there and decide, like, which one?

354

Everything, only limited by resources, as you could imagine.

355

Oh, my God.

356

That is beautiful.

357

I mean, that just thinking about a way of like a kind of bespoke medical future exploration.

358

Right.

359

Way better than just using mice.

360

Oh, my gosh.

361

Partly

362

because it also could help us leapfrog one of the biggest

363

reasons on average 90 percent of clinical trials for neurological drugs fail.

364

And for brain cancer, by the way, that number is even higher, 95 percent.

365

They're failing because they're not predicting whether the drug actually works on the disease.

366

And this is something that Madeline told me, too.

367

You might have a drug that works really well for treating mouse spinal cord injury.

368

Like it's like, OK, great.

369

This is not going to kill you.

370

Because you've got the animal work to show you that it's safe.

371

But it also doesn't make them better after the spinal cord injury.

372

But now, sure, they can do a mouse trial for safety.

373

But they can also test that drug to see if it works on a spinal cord organoid,

374

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

375

Wait, what?

376

I thought we were talking brain organoids.

377

Are there are there spinal cord organoids?

378

Spinal cord organoids?

379

Yeah.

380

Okay.

381

So as Madeline was developing her brain organoids, independently, around the same time,

382

other scientists all over the world are growing intestinal organoids, lung organoids, liver organoids, muscle organoids,

383

skin organoids, ancreas organoids, stomach organoids, heart organoids, kidney organoids, breast tissue organoids that actually produce milk.

384

Ah, they can have a breast tissue organoid that can make milk?

385

Yes.

386

Weird.

387

Has anyone tasted that milk?

388

I certainly haven't.

389

I've only read about it.

390

I don't know.

391

I don't know.

392

That's a good question.

393

Anyway.

394

That's science writer

395

Carl Zimmer again.

396

And he says now you can make an organoid of basically any part of the body.

397

And then you can connect them.

398

What?

399

You can, like, you can...

400

Does that work?

401

You can do that?

402

Oh, yeah.

403

They call them assembloids.

404

Assembloids.

405

Yeah.

406

No, like you can Mr. Potato Head assemble.

407

Correct.

408

But then do they attach to each other?

409

They attach to each other, yeah.

410

And do they communicate with each other?

411

They communicate with each other, yeah.

412

Okay, and then what? Do what?

413

With your charm bracelet human body?

414

So here's an example.

415

So Sergio Pasca...

416

Neuroscientist at Stanford University and his colleagues thought, can we use an assembloid to study pain?

417

The pathway of pain.

418

So they started with the finger.

419

A finger organoid?

420

No, no, no, sorry.

421

Just a nerve in the finger.

422

Oh, okay.

423

The sensory organoid.

424

Connect that.

425

Like with some other cells in the dish.

426

Another organoid, the spinal cord.

427

Yeah, it's the little teeny piece of spinal cord.

428

Now we're going to connect that.

429

To a brain organoid that is specifically the thalamus, which is the central hub in the brain that directs signals in all sorts of different ways.

430

And finally, we're going to connect that one to one more brain organoid, a cortex organoid.

431

Whoa, this is so weird.

432

I mean, it's like Legos.

433

It's like Legos.

434

With the human body.

435

Correct.

436

So then they took capsaicin.

437

That's the molecule in...

438

In like spicy food, is that right?

439

In spicy food, in chili peppers, yeah.

440

It can be very painful to the skin.

441

Okay.

442

And they said, okay, let's hit it with capsaicin and see what happens.

443

Uh-huh.

444

Boom.

445

Immediately, that sensory organoid goes...

446

Right.

447

And starts sending really strong signals.

448

And those signals, Carl says, zoom right up through this assembloid.

449

To the spinal cord, the thalamus, to the cortex.

450

Just like it would in your own body.

451

And they can see some kind of registering?

452

Correct.

453

And when they watch the way the signal travels, which is something that's normally hidden inside a body...

454

They discovered all sorts of things about what happens when we feel pain that they didn't know about before.

455

Like, for example, signals from different parts of the assembloid began firing together in these synchronized waves of signals.

456

Okay.

457

And the more you know about how those signals work or move, the better chance you have at stopping them.

458

You could, for example, say, okay, can I put a molecule into this assembloid that will stop the pain?

459

Oh, wow.

460

But, um, So if they're using these things to study pain, is it feeling pain?

461

No, probably not.

462

These organoids are just little bits of human tissue.

463

In order to feel pain the way we feel pain, there are other parts of the brain that come into play.

464

The assembloid is just this super basic circuit that you send a signal through.

465

So like this pain, it seems to be superficially registering it.

466

And like what is it, I think?

467

The capsaicin in that case.

468

No, no, no. I'm the first it.

469

It's like it is this little ball, but is the it a thing?

470

Like, what is it?

471

Well, they crackle with electricity.

472

They form connections called synapses.

473

They replicate parts of the human brain with astonishing accuracy.

474

But, Carl says...

475

They're not brains.

476

They're not brains.

477

That's right.

478

So if there's like a slider and on one end is brains

479

and then on the other hand is just like some neurons in a dish, where is this on the slider and how do you?

480

Yeah, I would say

481

that it's closer still for the time being to the neuron end of the slider simply based on numbers.

482

Our brain has something like 80 billion neurons neurons.

483

And the biggest human brain organoids contain about 2 million cells.

484

That's 0.0025%.

485

Well under 1%.

486

Yeah.

487

And you know, these things don't have blood vessels.

488

So that is a very important limiting factor to how big and complex it can get.

489

Yeah.

490

And they're not in a body.

491

So they can't interact with the world in like a meaningful way.

492

Okay.

493

Well, but when I was talking to Carl about this. So, um...

494

He said that a lot of that might no longer be true.

495

Some scientists have, you know, taken organoids from human cells and put them into the brains of rats.

496

What?

497

So basically what they did is they basically took a rat and they, like, carved out a chunk of its brain.

498

But they left some of it?

499

They left most of it.

500

And it's almost like, think about it, it's almost like they gave a rat a little human tumor something.

501

I mean, it doesn't...

502

But the tumor is like just brain, human brain.

503

It's human brain.

504

It's human brain.

505

And these human organides are pretty happy in there.

506

It's sort of wired in.

507

They connect up with the rat neurons.

508

They get supplied by the rat blood system.

509

So they have made, in a real sense, like a new kind of being.

510

Yeah, yeah, yeah.

511

That did not exist before this.

512

Correct.

513

Okay.

514

It feels like there should have been a bigger press release, but okay, do the rats act any differently?

515

Are they suddenly like into podcasts and coffee?

516

When you do studies on these rats, behavioral tests, memory tests, all sorts of things, they're just rats.

517

There seems to be nothing human-y about them.

518

Okay.

519

But one thing they did notice, when you tickle its whiskers...

520

Yeah.

521

You can actually measure signals from the human brain organoid neurons.

522

The human part of the brain lights up.

523

What?

524

Yeah.

525

So it's registering the feeling?

526

They are receiving signals from the rat's senses.

527

I mean, strictly speaking, they are receiving signals from the rat's senses.

528

Are they feeling it?

529

feeling it gets hard because it's kind of the pain question again.

530

But yeah, but now they're in a body.

531

I mean, they're in a being.

532

Yes, but they're not the like driving force of that being.

533

They're like a house guest in the attic.

534

Okay, Latif, would you put, make a brain ball, brain organoid of your brain cell and put in a rat?

535

If I'm being honest, probably not.

536

Probably not.

537

Okay.

538

So I don't know, but I just think you're more on my side

539

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,

540

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.

541

And then the scientists take it one step further anyway.

542

Um, okay.

543

Well, it's as if you have seen the future and what the next chapter holds, because that exact thing is going to happen.

544

It's going to get weirder and creepier and stranger, and that's all after the break.

545

Stick with us.

546

Latif.

547

Lulu, Radiolab.

548

We are back talking about brain balls, you know, bitty brains, boba brains, the brain-ish in a dish.

549

Yes, ha ha, with all your clever wordplay.

550

But you are about to send us into the next existential tailspin about how people are using these things.

551

It is possible.

552

So the final thing I was told to do is push record.

553

Record, yes.

554

That's an important button.

555

Now, tell me who you are.

556

So I'm Brett.

557

This is Brett Kagan.

558

He's a neuroscientist.

559

I'm the chief scientific officer here at Cortical Labs.

560

Cortical Labs.

561

We're a small tech startup here in Melbourne, Australia.

562

Did you start it?

563

Did someone else start it?

564

No, well, it was founded by, there was a few of us, and I was contacted by Dr. Hon Weng Chong and Andy Kitchen,

565

and they were looking for a neuroscientist.

566

Brett had been an academic, obsessed with this particular question.

567

How do you get intelligence out of brain cells that are in a dish?

568

And this company was like, why don't you leave academia and help us find out?

569

The question they had was, can brain cells in a dish do anything at all that we might want them to do?

570

Hmm.

571

Like, do what?

572

What better to pick than Pong?

573

Pong?

574

The, like, 70s computer game?

575

Yeah, the game with the paddles and the little ball.

576

Why that?

577

Everybody knows Pong.

578

It was one of the first computer games.

579

It was the first thing that machine learning, which people now like to call AI, really was trained on as a big breakout success.

580

And he figured the brain runs on electricity.

581

And it's also a shared language as silicon computing.

582

So why wouldn't we be able to get neurons to do something a computer could do? That exactly.

583

Like play a simple video game.

584

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.

585

And they did it.

586

Scientists just put pieces of human and mice brain on a plate and wired it to a computer to play pong.

587

They learned to track the ball and control a paddle.

588

Seriously, this is one of the craziest things I've ever covered.

589

So here's what's going on.

590

What?

591

No. Yeah.

592

And this wasn't even an organoid.

593

This was just a flat sheet of neurons in a dish.

594

I mean, how could it possibly be doing that?

595

Like, I mean, can really dumb things do that?

596

Could like a tree do that?

597

Trees don't have neurons.

598

I don't think a tree could do that.

599

Okay, so, but well, what does this mean?

600

Like, are they learning?

601

Well, Brett says yes.

602

I called it learning.

603

And I think learning was an incredibly fair definition

604

because what would an improvement over time in a way that would suit a goal be called other than learning?

605

But other people, including Madeline Lancaster...

606

I actually remain to be convinced anybody has really shown that.

607

Say no. because it's really hard to interpret the signals coming from the neurons.

608

She says when you teach brain cells to play Pong, they're, you know, connected to a computer.

609

So what people do is they use algorithms to sort of decode that message and then send a signal back to neurons.

610

And so you kind of have like two black boxes that you've just hooked up.

611

It's sort of a collaboration between the brain cells and the computer.

612

And you don't really know what either of them are doing.

613

Anyway, whatever is happening here, what Brett and his team took away from this is if neurons can do something a computer does,

614

why don't we use neurons as computers?

615

What?

616

Yeah.

617

Literally a couple months ago, they released their first computer called the CL1.

618

And it is, they don't call it this, but it's effectively a biocomputer.

619

It has neurons in it.

620

Ew.

621

Brain, sticky, real human brain matter in it?

622

Yeah.

623

It's got like little brain organoids in it.

624

It has 800,000 neurons interfaced with a silicon chip you can use it to do computer stuff with.

625

Okay.

626

I mean, I can get behind the brain balls being used for neurological disorder research.

627

Great.

628

You know what?

629

Bespoke cancer treatments?

630

Cool.

631

But why are we hooking up human brain cells to computers to, like, make money?

632

That, to me, feels like not worth the risk.

633

Well, think about the problems we are having right now with all of these data centers chugging all this energy, right?

634

Absolutely wrecking the planet.

635

Right.

636

So our brains are so impressively efficient.

637

Energy wise, we have like a dim light bulb like screwed into our heads.

638

Right.

639

That's the amount of energy that we need to do all the complex things that we do.

640

If AI or if some supercomputer was doing the equivalent, it would need millions of times more power.

641

Like the difference between a single light bulb and a large town. So flattering.

642

The other thing is that, like, think about these AIs.

643

You need to train it on the whole Internet, right?

644

A human brain is much quicker to learn.

645

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.

646

OK, but I guess my authentic question at this point is like, OK, you have shown us all this stuff.

647

At this point, it seems pretty clear that they can definitely register input, right?

648

Like there's the tickle, the pain, the signal they're getting from Pong.

649

Okay.

650

And then this Pong example at least shows us they are then able, based on that input, to produce some kind of output.

651

Yeah.

652

Okay.

653

So let's say it is.

654

Yeah.

655

Okay.

656

So my question is, if they can do those things, wouldn't they have to have some thrumming level of consciousness?

657

No, actually.

658

No, they really don't.

659

Like a bunch of the things you just talked about, AI can do those.

660

Is AI conscious?

661

Even going further than that, like a Roomba can do, like navigate a room.

662

Is a Roomba conscious?

663

That's a signal in and out.

664

Yeah, right.

665

A Roomba's going, oh, there's an edge.

666

Let me go this way.

667

That's a signal in and out.

668

When we talk about human consciousness, we mean self-consciousness.

669

Like you are aware of yourself.

670

You have a past.

671

You have a future that you're concerned about.

672

There's like that continuity of experience.

673

This is Dr. In-Soo Hyun.

674

I'm the director of the Center for Life Sciences at the Museum of Science in Boston.

675

He's a bioethicist, and he's worked on a bunch of teams with scientists who are studying brain organoids.

676

We try to identify what are the emerging scientific and ethical issues.

677

You're like kind of like their conscience?

678

Is that sort of the thing?

679

You know what?

680

Sometimes I feel like a priest in secular clothes.

681

And he says at this point, he is not worried about brain organoids having anything like human consciousness.

682

The brain organoids in the dish don't have that continuity.

683

They don't have all the regions.

684

They don't have the interaction with the outside world.

685

But when he thinks about the future that

686

Brett and others are trying to create,

687

where maybe people start connecting more and more complicated and even more and more structured clumps of human brain cells to computers.

688

Maybe you get, it might not even human consciousness, but some kind of consciousness could emerge.

689

he's hooked up to the world

690

yeah okay so what about this Latif

691

I would if I may I would like to just issue a commandment that all the smart people who are like

692

excited by brain organoids.

693

They all take one year to stop making organoids

694

and use their smarts and their technologies

695

and their labs to like try to understand the consciousness of the organoids that have already been made.

696

You know, like ideally they could all be in a dark room and just have candles and quietly,

697

meditatively watch for any flickers to understand what's going on.

698

And then And then we have a grand assembly where everyone reports back and we all collectively decide what to do.

699

But I know that like some of these scientists have this fire inside them to be like,

700

how many cures am I not going to find in that year?

701

Like how many people am I not going to help in that year?

702

Like the glioblastoma, like those people don't have a year.

703

And those people are telling me to just shut up because this is a piece of discarded foreskin.

704

That's right.

705

If we have a tool that we don't use.

706

Madeline Lancaster again.

707

And there are millions of actually conscious human beings out there that don't have treatments.

708

But we decide, no, we're going to put the value of organoids higher than those people. That would be unethical.

709

It's funny, like at the beginning, like you asked me, like, would you make a brain ball of yourself?

710

And I said no. And then at some point, like my thinking switch where I'm like,

711

oh, no, unless it would save someone's life.

712

Well, that's noble.

713

And now I feel even worse saying I don't know that I would.

714

I just I mean, yeah.

715

OK, if it's my own kid, sure.

716

I don't care if I'm like a little enslaved human consciousness, if it saves my kid.

717

But as you have shown us, the scientists are going to do more.

718

They're going to try new things.

719

They're going to build bigger brains.

720

And like, there is a line and we will cross it and we won't know that we've crossed it, you know?

721

Right.

722

And the thing about these organoids is that they're already crossing all kinds of lines.

723

You disrupt categories that we thought were so neat and tidy and distinguishable.

724

Life, non-life.

725

Human, non-human.

726

Human, computer.

727

We thought those were pretty clean categories.

728

But this research is kind of upsetting the very foundations of what we think separates these categories apart.

729

It does feel like it's like, oh, we've created a new category of thing, like a new category of thing that is maybe alive.

730

It is alive.

731

We have created a new category of thing that is alive.

732

That is weird.

733

Oh, yeah.

734

It's hard.

735

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.

736

But they're also not just a few neurons in a dish either.

737

We almost don't really even have the words for it.

738

I think it's kind of a new thing.

739

Latif Nasser.

740

This episode was produced by Annie McKeown, Mona Madgaukar, and Pat Walters.

741

It was edited by Alex Neeson and Pat Walters with fact-checking by Natalie Middleton and Rebecca Rand.

742

Special thank-you shout-outs to Lynn Levy, Jason Yamada-Hanf, David Fagenbaum, Andrew Verstein, Anne Hamilton, Christopher Mason, Madeline Mason-Mariarty,

743

plus Howard Fine and his whole team at Weill Cornell for hosting us.

744

And if you're looking for more musings on the nature of life and what it means to be alive,

745

Carl Zimmer has a terrific book out all about this stuff.

746

It's called Life's Edge, the search for what it means to be alive.

747

Get it at your local bookstore.

748

That's it for us from our brain balls to yours.

749

See you next week.

750

Okay, start now.

751

I almost practiced.

752

No, you don't need to.

753

You don't need to practice anymore.

754

Shh.

755

We're recording now.

756

Hi, I'm Ellie Columns, and I'm from Louisville, Kentucky, and here are the staff credits.

757

And she's Molly's niece.

758

Yeah.

759

Radio Lab is hosted by Lulu Miller and Latif Nasser.

760

Sorin Wheeler is our executive editor.

761

Sarah Sandback is our executive director.

762

Our managing editor is Pat Walters.

763

Dylan Keefe is our director of sound design.

764

Our staff includes Jeremy Bloom, W.

765

Harry Fortuna, David Gable, Maria Paz Gutierrez, Sindhu Nana Sambandan

766

Matt Kilty Mona Madgavkar Annie McEwan Alex Neeson Sarah Kari

767

Anissa Vietes Arian Wack

768

Molly Webster and Jessica Young With help from Rebecca Rand Our fact checkers are Diane Kelly Emily Krieger

769

and Natalie Middleton I love your giggle

770

leadership support for radio lab science programming is provided by the simons foundation

771

and the john templeton foundation foundational support for radio lab was provided by the alfred p sloan foundation

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音标练习掌握每个音

词汇学习建立你的词库

词汇游戏边玩边学

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FOR YOU

本课的词汇与口语要点

视频中反复出现的词有：brain, organoid, cell。这段视频共有 771 个句子、6651 个单词可供跟读。讲话部分时长为 41:20。说话人语速自然，每分钟约 161 个词，接近日常对话。只有 81% 的单词属于英语最常用的 3,000 词，词汇难度较高。

视频中的重点词汇

视频中 15 个值得学习的单词，附发音和释义：

单词	发音	释义
dish 名词	/dɪʃ/	碟子, 盤子 /盘子
mouse 名词	/maʊs/	лочў, 鳥鼠 /鸟鼠
tube 名词	/tuːb/	筒
cord 名词	/ˈkoɹd/	繩 /绳, 繩子 /绳子
spinal 形容词	/spaɪ.nəl/	脊的
consciousness 名词	/ˈkɑnʃəsnəs/	意識 /意识
microscope 名词	/ˈmaɪ.kɹəˌskoʊp/	顯微鏡 /显微镜
connect 动词	/kəˈnɛkt/	連接 /连接
tissue 名词	/ˈtɪʃ.(j)u/	纸巾
syndrome 名词	/ˈsɪndɹoʊm/	綜合徵 /综合征, 症候群
tumor 名词	/tuː.məɹ/	腫瘤 /肿瘤, 瘤子
gene 名词	/d͡ʒiːn/	基因
disorder 名词	/dɪsˈɔɹdɚ/	混亂 /混乱, 紊亂 /紊乱
rat 名词	/ɹæt/	лочў, 鳥鼠 /鸟鼠
float 动词	/fləʊt/	浮, 漂浮

视频中出现的短语动词

单词	发音	释义
end up 动词		到达
shut up	/ʃʌt ʌp/	閉嘴 /闭嘴, 住口
throw away 动词		棄置 /弃置, 扔
find out 动词		找出, 查明
point out 动词		指, 指出
turn out 动词		原來 /原来

值得反复跟读的句子

视频中简短而完整的句子，可以直接用在日常对话里：

Had you ever seen anything like that before?
Where do you get those from?
You're like, no, what?
What would you do with that?
You're like kind of like their conscience?

视频中的语法

说话人最常用的结构，并附上视频中的原话：

结构	视频中的用法
条件句 if + 从句，will/would + 动词 — 条件及其结果	if they can do those things, wouldn't they · if I may I would like
现在完成时 have/has + 过去分词 — 过去发生但与现在仍有关联的事	has just finished · has gone · have decided
被动语态 be + 过去分词 — 强调发生了什么，而不是谁做的	were actually made · was told · was founded
定语从句 who / which + 从句 — 补充说明人或事物	there, which means · thalamus, which is · travels, which is

需要注意的发音

说话人用了 131 次缩略和弱读形式，例如 don't, they're, I'm。请按听到的简短形式来说。

“th” 音: breathe /bɹiːð/, thalamus /ˈθæləməs/
“sh” 和 “zh” 音: dish /dɪʃ/, consciousness /ˈkɑnʃəsnəs/, tissue /ˈtɪʃ.(j)u/, conscious /ˈkɑn.ʃəs/, sheet /ʃit/
长单词——注意重音位置: neurological /nɝəˈlɑd͡ʒɪkəl/, electricity /ɪˌlɛkˈtɹɪsɪti/, efficiency /ɪˈfɪʃ.ən.si/, experiment /ɪkˈspɛɹ.ə.mənt/, communicate /kəˈmjuːnɪkeɪt/

中文母语者容易读错的音：

/v/ — 不要读成 /w/，上齿轻触下唇: arrive /əˈɹaɪv/, survival /sɚˈvaɪ.vəl/, vessel /ˈvɛsəl/, convince /kənˈvɪns/, clever /ˈklɛv.ɚ/
词尾辅音 — 要读清楚，后面不要加元音: dish /dɪʃ/, mouse /maʊs/, tube /tuːb/, cord /ˈkoɹd/, consciousness /ˈkɑnʃəsnəs/
/r/ 和 /l/ 的区别: neural /ˈnʊɹəl/, electricity /ɪˌlɛkˈtɹɪsɪti/, electrical /ɪˈlɛktɹɪkəl/, incredibly /ɪŋˈkɹɛdɪbli/, laboratory /ˈlæb(ə)ɹəˌtɔɹi/

如何用这段视频练习

先完整听一遍视频，不要开口，记下不认识的单词。
先用 0.75 倍速逐句跟读，熟练之后再回到正常速度。
录下自己的声音并与原声对比，特别注意 dish, mouse, tube 这类单词。

什么是跟读法？

跟读法 (Shadowing) 是一种有科学依据的语言学习技巧，最初开发用于专业口译员的培训，并由多语言者Alexander Arguelles博士普及。这个方法简单而强大：您在听英语母语原声的同时立即大声重复——就像是一个延迟1-2秒紧跟说话者的影子。与被动听力或语法练习不同，跟读法强迫您的大脑和口腔肌肉同时处理并模仿真实的讲话模式。研究表明它能显着提高发音准确性，语调，节奏，连读，听力理解和口语流利度——使其成为雅思口语备考和真实英语交流最有效的方法之一。

影子跟读法: 阅读完整分步指南 →

跟读练习: Brain Balls | Radiolab Podcast - 通过视频学习英语口语

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本课的词汇与口语要点

视频中的重点词汇

视频中出现的短语动词

值得反复跟读的句子

视频中的语法

需要注意的发音

如何用这段视频练习

什么是跟读法？