vtt/episode_032_small.vtt

WEBVTT

00:00.000 --> 00:03.360
 The following is a conversation with Paola Arlada.

00:03.360 --> 00:06.400
 She is a professor of stem cell and regenerative biology

00:06.400 --> 00:09.760
 at Harvard University and is interested in understanding

00:09.760 --> 00:13.160
 the molecular laws that govern the birth, differentiation,

00:13.160 --> 00:16.600
 and assembly of the human brain's cerebral cortex.

00:16.600 --> 00:18.400
 She explores the complexity of the brain

00:18.400 --> 00:21.000
 by studying and engineering elements

00:21.000 --> 00:22.880
 of how the brain develops.

00:22.880 --> 00:25.640
 This was a fascinating conversation to me.

00:25.640 --> 00:28.560
 It's part of the Artificial Intelligence podcast.

00:28.560 --> 00:30.600
 If you enjoy it, subscribe on YouTube,

00:30.600 --> 00:32.360
 give it five stars on iTunes.

00:32.360 --> 00:35.760
 Support on Patreon or simply connect with me on Twitter

00:35.760 --> 00:39.960
 at Lex Freedman, spelled F R I D M A N.

00:39.960 --> 00:43.120
 And I'd like to give a special thank you to Amy Jeffers

00:43.120 --> 00:45.560
 for her support of the podcast on Patreon.

00:45.560 --> 00:47.680
 She's an artist and you should definitely check out

00:47.680 --> 00:52.680
 her Instagram at LoveTruthGood, three beautiful words.

00:52.720 --> 00:55.640
 Your support means a lot and inspires me

00:55.640 --> 00:57.720
 to keep the series going.

00:57.720 --> 01:01.720
 And now here's my conversation with Paola Arlada.

01:03.120 --> 01:05.320
 You studied the development of the human brain

01:05.320 --> 01:06.680
 for many years.

01:06.680 --> 01:10.520
 So let me ask you an out of the box question first.

01:11.480 --> 01:14.600
 How likely is it that there's intelligent life out there

01:14.600 --> 01:17.160
 in the universe outside of earth

01:17.160 --> 01:19.320
 with something like the human brain?

01:19.320 --> 01:20.760
 So I can put it another way.

01:20.760 --> 01:24.320
 How unlikely is the human brain?

01:24.320 --> 01:28.360
 How difficult is it to build a thing

01:28.360 --> 01:30.400
 through the evolutionary process?

01:30.400 --> 01:32.520
 Well, it has happened here, right?

01:32.520 --> 01:33.360
 On this planet.

01:33.360 --> 01:34.200
 Once, yes.

01:34.200 --> 01:35.040
 Once.

01:35.040 --> 01:39.960
 So that simply tells you that it could, of course,

01:39.960 --> 01:44.120
 happen again, other places is only a matter of probability.

01:44.120 --> 01:46.600
 What the probability that you would get a brain

01:46.600 --> 01:51.200
 like the ones that we have, like the human brain.

01:51.200 --> 01:54.000
 So how difficult is it to make the human brain?

01:54.000 --> 01:55.400
 It's pretty difficult.

01:56.480 --> 02:00.960
 But most importantly, I guess we know very little

02:00.960 --> 02:04.440
 about how this process really happens.

02:04.440 --> 02:06.320
 And there is a reason for that,

02:06.320 --> 02:09.160
 actually multiple reasons for that.

02:09.160 --> 02:13.400
 Most of what we know about how the mammalian brains

02:13.400 --> 02:15.680
 or the brain of mammals develop,

02:15.680 --> 02:18.960
 comes from studying in labs other brains,

02:18.960 --> 02:22.560
 not our own brain, the brain of mice, for example.

02:22.560 --> 02:25.400
 But if I showed you a picture of a mouse brain

02:25.400 --> 02:28.400
 and then you put it next to a picture of a human brain,

02:28.400 --> 02:31.160
 they don't look at all like each other.

02:31.160 --> 02:33.040
 So they're very different.

02:33.040 --> 02:36.240
 And therefore, there is a limit to what you can learn

02:36.240 --> 02:40.560
 about how the human brain is made by studying the mouse brain.

02:40.560 --> 02:43.320
 There is a huge value in studying the mouse brain.

02:43.320 --> 02:45.080
 There are many things that we have learned,

02:45.080 --> 02:46.600
 but it's not the same thing.

02:46.600 --> 02:49.200
 So in having studied the human brain

02:49.200 --> 02:51.440
 or through the mouse and through other methodologies

02:51.440 --> 02:54.760
 that we'll talk about, do you have a sense?

02:54.760 --> 02:57.560
 I mean, you're one of the experts in the world.

02:57.560 --> 03:01.160
 How much do you feel you know about the brain?

03:01.160 --> 03:05.920
 And how often do you find yourself in awe

03:05.920 --> 03:07.840
 of this mysterious thing?

03:07.840 --> 03:12.200
 Yeah, you pretty much find yourself in awe all the time.

03:12.200 --> 03:15.360
 It's an amazing process.

03:15.360 --> 03:17.960
 It's a process by which,

03:17.960 --> 03:20.720
 by means that we don't fully understand

03:20.720 --> 03:23.640
 at the very beginning of embryogenesis,

03:23.640 --> 03:28.800
 the structure called the neural tube literally self assembles.

03:28.800 --> 03:30.440
 And it happens in an embryo

03:30.440 --> 03:33.720
 and it can happen also from stem cells in a dish.

03:33.720 --> 03:34.960
 Okay.

03:34.960 --> 03:38.720
 And then from there, these stem cells that are present

03:38.720 --> 03:41.640
 within the neural tube give rise to all of the thousands

03:41.640 --> 03:43.440
 and thousands of different cell types

03:43.440 --> 03:46.560
 that are present in the brain through time, right?

03:46.560 --> 03:51.760
 With the interesting, very intriguing, interesting observation

03:51.760 --> 03:56.280
 is that the time that it takes for the human brain to be made,

03:56.280 --> 04:01.480
 it's human time, meaning that for me and you,

04:01.480 --> 04:04.560
 it took almost nine months of gestation to build the brain

04:04.560 --> 04:08.080
 and then another 20 years of learning postnatally

04:08.080 --> 04:09.360
 to get the brain that we have today

04:09.360 --> 04:11.360
 that allows us to this conversation.

04:11.360 --> 04:14.960
 A mouse takes 20 days or so

04:14.960 --> 04:22.200
 for an embryo to be born and so the brain is built

04:22.200 --> 04:24.840
 in a much shorter period of time and the beauty of it

04:24.840 --> 04:27.160
 is that if you take mouse stem cells

04:27.160 --> 04:29.880
 and you put them in a cultured dish,

04:29.880 --> 04:34.840
 the brain organoid that you get from a mouse is formed faster

04:34.840 --> 04:39.120
 that if you took human stem cells and put them in the dish

04:39.120 --> 04:42.120
 and let them make a human brain organoid.

04:42.120 --> 04:45.560
 So the very developmental process is...

04:45.560 --> 04:49.000
 Controlled by the speed of the species.

04:49.000 --> 04:54.080
 Which means it's by its own purpose, it's not accidental

04:54.080 --> 04:59.800
 or there is something in that temporal dynamic to that development.

04:59.800 --> 05:04.000
 Exactly, that is very important for us to get the brain we have

05:04.000 --> 05:08.120
 and we can speculate for why that is.

05:08.120 --> 05:13.000
 It takes us a long time as human beings after we're born

05:13.000 --> 05:16.040
 to learn all the things that we have to learn

05:16.040 --> 05:17.920
 to have the adult brain.

05:17.920 --> 05:20.160
 It's actually 20 years, think about it.

05:20.160 --> 05:23.440
 From when a baby is born to when a teenager

05:23.440 --> 05:27.160
 goes through puberty to adults, it's a long time.

05:27.160 --> 05:32.320
 Do you think you can maybe talk through the first few months

05:32.320 --> 05:35.080
 and then on to the first 20 years

05:35.080 --> 05:37.640
 and then for the rest of their lives?

05:37.640 --> 05:41.080
 What does the development of the human brain look like?

05:41.080 --> 05:43.360
 What are the different stages?

05:43.360 --> 05:46.720
 At the beginning you have to build a brain, right?

05:46.720 --> 05:48.840
 And the brain is made of cells.

05:48.840 --> 05:51.960
 What's the very beginning? Which beginning are we talking about?

05:51.960 --> 05:53.280
 In the embryo.

05:53.280 --> 05:56.000
 As the embryo is developing in the womb,

05:56.000 --> 05:59.680
 in addition to making all of the other tissues of the embryo,

05:59.680 --> 06:02.040
 the muscle, the heart, the blood,

06:02.040 --> 06:04.960
 the embryo is also building the brain.

06:04.960 --> 06:08.480
 And it builds from a very simple structure

06:08.480 --> 06:10.000
 called the neural tube,

06:10.000 --> 06:13.160
 which is basically nothing but a tube of cells

06:13.160 --> 06:15.800
 that spans sort of the length of the embryo

06:15.800 --> 06:20.840
 from the head all the way to the tail, let's say, of the embryo.

06:20.840 --> 06:23.360
 And then over in human beings,

06:23.360 --> 06:25.520
 over many months of gestation,

06:25.520 --> 06:28.240
 from that neural tube,

06:28.240 --> 06:32.480
 which contains a stem cell like cells of the brain,

06:32.480 --> 06:37.000
 you will make many, many other building blocks of the brain.

06:37.000 --> 06:39.600
 So all of the other cell types,

06:39.600 --> 06:43.080
 because there are many, many different types of cells in the brain,

06:43.080 --> 06:46.640
 that will form specific structures of the brain.

06:46.640 --> 06:49.800
 So you can think about embryonic development of the brain

06:49.800 --> 06:54.440
 as just the time in which you are making the building blocks, the cells.

06:54.440 --> 06:56.840
 Are the stem cells relatively homogeneous,

06:56.840 --> 06:59.240
 like uniform, or are they all different types?

06:59.240 --> 07:01.280
 It's a very good question. It's exactly how it works.

07:01.280 --> 07:05.200
 You start with a more homogeneous,

07:05.200 --> 07:09.120
 perhaps more multipotent type of stem cell.

07:09.120 --> 07:13.520
 That multipotent means that it has the potential

07:13.520 --> 07:17.360
 to make many, many different types of other cells.

07:17.360 --> 07:21.440
 And then with time, these progenitors become more heterogeneous,

07:21.440 --> 07:22.840
 which means more diverse.

07:22.840 --> 07:26.200
 There are going to be many different types of these stem cells.

07:26.200 --> 07:28.760
 And also they will give rise to progeny,

07:28.760 --> 07:31.760
 to other cells that are not stem cells,

07:31.760 --> 07:33.320
 that are specific cells of the brain,

07:33.320 --> 07:36.080
 that are very different from the mother stem cell.

07:36.080 --> 07:40.360
 And now you think about this process of making cells from the stem cells

07:40.360 --> 07:43.760
 over many, many months of development for humans.

07:43.760 --> 07:48.200
 And what you're doing here, building the cells that physically make the brain,

07:48.200 --> 07:52.400
 and then you arrange them in specific structures

07:52.400 --> 07:55.440
 that are present in the final brain.

07:55.440 --> 07:59.280
 So you can think about the embryonic development of the brain

07:59.280 --> 08:02.120
 as the time where you're building the bricks.

08:02.120 --> 08:05.520
 You're putting the bricks together to form buildings,

08:05.520 --> 08:08.120
 structures, regions of the brain,

08:08.120 --> 08:13.040
 and where you make the connections between these many different types of cells,

08:13.040 --> 08:15.200
 especially nerve cells, neurons, right,

08:15.200 --> 08:19.240
 that transmit action potentials and electricity.

08:19.240 --> 08:22.280
 I've heard you also say somewhere, I think, correct me if I'm wrong,

08:22.280 --> 08:25.080
 that the order of the way this builds matters.

08:25.080 --> 08:26.040
 Oh, yes.

08:26.040 --> 08:29.880
 If you are an engineer and you think about development,

08:29.880 --> 08:34.960
 you can think of it as, well, I could also take all the cells

08:34.960 --> 08:37.960
 and bring them all together into a brain in the end.

08:37.960 --> 08:40.320
 But development is much more than that.

08:40.320 --> 08:43.880
 So the cells are made in a very specific order

08:43.880 --> 08:47.400
 that subserve the final product that you need to get.

08:47.400 --> 08:52.200
 And so, for example, all of the nerve cells, the neurons, are made first.

08:52.200 --> 08:56.760
 And all of the supportive cells of the neurons, like the glia, is made later.

08:56.760 --> 09:02.080
 And there is a reason for that because they have to assemble together in specific ways.

09:02.080 --> 09:05.720
 But you also may say, well, why don't we just put them all together in the end?

09:05.720 --> 09:08.920
 It's because as they develop next to each other,

09:08.920 --> 09:11.280
 they influence their own development.

09:11.280 --> 09:15.400
 So it's a different thing for a glia to be made alone in a dish

09:15.400 --> 09:19.360
 than a glia cell be made in a developing embryo

09:19.360 --> 09:23.680
 with all these other cells around it that produce all these other signals.

09:23.680 --> 09:27.840
 First of all, that's mind blowing, that this development process.

09:27.840 --> 09:29.760
 From my perspective in artificial intelligence,

09:29.760 --> 09:33.480
 you often think of how incredible the final product is,

09:33.480 --> 09:35.200
 the final product, the brain.

09:35.200 --> 09:40.400
 But you just, you're making me realize that the final product is just,

09:40.400 --> 09:44.480
 is the beautiful thing is the actual development process.

09:44.480 --> 09:51.640
 Do we know the code that drives that development?

09:51.640 --> 09:53.640
 Do we have any sense?

09:53.640 --> 09:59.320
 First of all, thank you for saying that it's really the formation of the brain.

09:59.320 --> 10:05.120
 It's really its development, this incredibly choreographed dance

10:05.120 --> 10:10.560
 that happens the same way every time each one of us builds the brain, right?

10:10.560 --> 10:14.880
 And that builds an organ that allows us to do what we're doing today, right?

10:14.880 --> 10:16.360
 That is mind blowing.

10:16.360 --> 10:21.880
 And this is why developmental neurobiologists never get tired of studying that.

10:21.880 --> 10:23.800
 Now, you're asking about the code.

10:23.800 --> 10:26.520
 What drives this? How is this done?

10:26.520 --> 10:29.720
 Well, it's millions of years of evolution

10:29.720 --> 10:33.120
 of really fine tuning gene expression programs

10:33.120 --> 10:37.480
 that allow certain cells to be made at a certain time

10:37.480 --> 10:41.680
 and to become a certain cell type,

10:41.680 --> 10:47.360
 but also mechanical forces of pressure bending.

10:47.360 --> 10:50.280
 This embryo is not just, it will not stay a tube,

10:50.280 --> 10:52.000
 this brain for very long.

10:52.000 --> 10:55.720
 At some point, this tube in the front of the embryo will expand

10:55.720 --> 10:58.160
 to make the primordium of the brain, right?

10:58.160 --> 11:02.880
 Now, the forces that control the cells feel,

11:02.880 --> 11:04.840
 and this is another beautiful thing,

11:04.840 --> 11:09.240
 the very force that they feel, which is different from a week before,

11:09.240 --> 11:11.080
 a week ago, will tell the cell,

11:11.080 --> 11:13.640
 oh, you're being squished in a certain way,

11:13.640 --> 11:16.560
 begin to produce these new genes,

11:16.560 --> 11:18.400
 because now you are at the corner,

11:18.400 --> 11:23.160
 or you are in a stretch of cells or whatever it is.

11:23.160 --> 11:26.000
 And so that mechanical physical force

11:26.000 --> 11:29.440
 shapes the fate of the cell as well.

11:29.440 --> 11:31.880
 So it's not only chemical, it's also mechanical.

11:31.880 --> 11:38.360
 So from my perspective, biology is this incredibly complex mess,

11:38.360 --> 11:40.160
 gooey mess.

11:40.160 --> 11:43.440
 So you're seeing mechanical forces.

11:43.440 --> 11:50.000
 How different is a computer or any kind of mechanical machine

11:50.000 --> 11:53.840
 that humans build and the biological systems?

11:53.840 --> 11:57.000
 Have you been, because you've worked a lot with biological systems,

11:57.000 --> 11:59.960
 are they as much of a mess as it seems

11:59.960 --> 12:03.520
 from a perspective of an engineer, a mechanical engineer?

12:03.520 --> 12:11.680
 Yeah, they are much more prone to taking alternative routes, right?

12:11.680 --> 12:18.160
 So if you, we go back to printing a brain versus developing a brain,

12:18.160 --> 12:20.440
 of course, if you print a brain,

12:20.440 --> 12:23.960
 given that you start with the same building blocks, the same cells,

12:23.960 --> 12:28.600
 you could potentially print it the same way every time.

12:28.600 --> 12:32.520
 But that final brain may not work the same way

12:32.520 --> 12:34.440
 as a brain built during development does,

12:34.440 --> 12:38.680
 because the very same building blocks that you're using

12:38.680 --> 12:41.440
 developed in a completely different environment, right?

12:41.440 --> 12:43.000
 That was not the environment of the brain.

12:43.000 --> 12:47.120
 Therefore, they're going to be different just by definition.

12:47.120 --> 12:51.840
 So if you instead use development to build, let's say, a brain

12:51.840 --> 12:55.840
 organoid, which maybe we will be talking about in a few minutes.

12:55.840 --> 12:57.000
 Those things are fascinating.

12:57.000 --> 13:01.960
 Yes, so if you use processes of development,

13:01.960 --> 13:06.480
 then when you watch it, you can see that sometimes things can go wrong

13:06.480 --> 13:07.520
 in some organoids.

13:07.520 --> 13:10.880
 And by wrong, I mean different one organoid from the next.

13:10.880 --> 13:14.840
 While if you think about that embryo, it always goes right.

13:14.840 --> 13:18.960
 So it's this development, it's for as complex as it is.

13:18.960 --> 13:23.680
 Every time a baby is born has, you know, with very few exceptions,

13:23.680 --> 13:26.200
 the brain is like the next baby.

13:26.200 --> 13:31.320
 But it's not the same if you develop it in a dish.

13:31.320 --> 13:33.840
 And first of all, we don't even develop a brain.

13:33.840 --> 13:36.080
 You develop something much simpler in the dish.

13:36.080 --> 13:39.680
 But there are more options for building things differently,

13:39.680 --> 13:46.080
 which really tells you that evolution has played a really

13:46.080 --> 13:53.280
 tight game here for how in the end the brain is built in vivo.

13:53.280 --> 13:55.360
 So just a quick maybe dumb question,

13:55.360 --> 14:01.120
 but it seems like the building process is not a dictatorship.

14:01.120 --> 14:06.680
 It seems like there's not a centralized high level mechanism

14:06.680 --> 14:10.320
 that says, OK, this cell built itself the wrong way.

14:10.320 --> 14:11.560
 I'm going to kill it.

14:11.560 --> 14:15.480
 It seems like there's a really strong distributed mechanism.

14:15.480 --> 14:18.440
 Is that in your sense for what you have?

14:18.440 --> 14:20.920
 There are a lot of possibilities, right?

14:20.920 --> 14:25.080
 And if you think about, for example, different species,

14:25.080 --> 14:28.920
 building their brain, each brain is a little bit different.

14:28.920 --> 14:31.360
 So the brain of a lizard is very different from that

14:31.360 --> 14:36.560
 of a chicken, from that of one of us, and so on and so forth.

14:36.560 --> 14:40.960
 And still is a brain, but it was built differently.

14:40.960 --> 14:44.120
 Starting from stem cells, they pretty much

14:44.120 --> 14:46.040
 had the same potential.

14:46.040 --> 14:49.400
 But in the end, evolution builds different brains

14:49.400 --> 14:51.520
 in different species, because that

14:51.520 --> 14:54.040
 serves in a way the purpose of that species

14:54.040 --> 14:56.680
 and the well being of that organism.

14:56.680 --> 15:00.720
 And so there are many possibilities,

15:00.720 --> 15:04.880
 but then there is a way, and you were talking about a code.

15:04.880 --> 15:07.560
 Nobody knows what the entire code of development is.

15:07.560 --> 15:08.680
 Of course, we don't.

15:08.680 --> 15:13.400
 We know bits and pieces of very specific aspects

15:13.400 --> 15:15.680
 of development of the brain, what genes are involved

15:15.680 --> 15:18.520
 to make a certain cell types, how those two cells interact

15:18.520 --> 15:21.480
 to make the next level structure that we might know,

15:21.480 --> 15:24.560
 but the entirety of it, how it's so well controlled.

15:24.560 --> 15:26.160
 It's really mind blowing.

15:26.160 --> 15:29.120
 So in the first two months in the embryo,

15:29.120 --> 15:32.720
 or whatever, the first few weeks, few months.

15:32.720 --> 15:37.120
 So yeah, the building blocks are constructed,

15:37.120 --> 15:40.040
 the actual, the different regions of the brain,

15:40.040 --> 15:42.760
 I guess, in the nervous system.

15:42.760 --> 15:46.520
 Well, this continues way longer than just the first few months.

15:46.520 --> 15:50.480
 So over the very first few months,

15:50.480 --> 15:52.080
 you build a lot of these cells,

15:52.080 --> 15:56.800
 but then there is continuous building of new cell types

15:56.800 --> 15:58.480
 all the way through birth.

15:58.480 --> 16:00.400
 And then even postnatally,

16:01.520 --> 16:04.000
 I don't know if you've ever heard of myelin.

16:04.000 --> 16:06.720
 Myelin is this sort of insulation

16:06.720 --> 16:09.800
 that is built around the cables of the neurons

16:09.800 --> 16:12.200
 so that the electricity can go really fast from.

16:12.200 --> 16:13.520
 The axons, I guess they're called.

16:13.520 --> 16:15.720
 The axons are called axons, exactly.

16:15.720 --> 16:20.720
 And so as human beings, we myelinate ourselves

16:22.920 --> 16:27.000
 postnatally, a kid, a six year old kid,

16:27.000 --> 16:29.720
 as barely started the process of making

16:29.720 --> 16:31.640
 the mature oligodendrocytes,

16:31.640 --> 16:33.400
 which are the cells that then eventually

16:33.400 --> 16:36.360
 will wrap the axons into myelin.

16:36.360 --> 16:38.720
 And this will continue, believe it or not,

16:38.720 --> 16:42.200
 until we are about 25, 30 years old.

16:42.200 --> 16:45.080
 So there is a continuous process of maturation

16:45.080 --> 16:46.600
 and tweaking and additions,

16:46.600 --> 16:51.040
 and also in response to what we do.

16:51.040 --> 16:53.960
 I remember taking api biology in high school,

16:53.960 --> 16:57.040
 and in the textbook, it said that,

16:57.040 --> 16:58.560
 I'm going by memory here,

16:58.560 --> 17:02.000
 that scientists disagree on the purpose of myelin

17:03.040 --> 17:04.720
 in the brain.

17:04.720 --> 17:06.400
 Is that totally wrong?

17:06.400 --> 17:10.000
 So like, I guess it speeds up the,

17:12.000 --> 17:13.200
 okay, but I'd be wrong here,

17:13.200 --> 17:15.280
 but I guess it speeds up the electricity traveling

17:15.280 --> 17:17.680
 down the axon or something.

17:17.680 --> 17:20.160
 So that's the most sort of canonical,

17:20.160 --> 17:21.760
 and definitely that's the case.

17:21.760 --> 17:24.880
 So you have to imagine an axon,

17:24.880 --> 17:27.680
 and you can think about it as a cable or some type

17:27.680 --> 17:29.520
 with electricity going through.

17:29.520 --> 17:34.400
 And what myelin does by insulating the outside,

17:34.400 --> 17:36.360
 I should say there are tracts of myelin

17:36.360 --> 17:39.600
 and pieces of axons that are naked without myelin.

17:39.600 --> 17:41.760
 And so by having the insulation,

17:41.760 --> 17:44.040
 the electricity instead of going straight through the cable,

17:44.040 --> 17:47.240
 it will jump over a piece of myelin, right?

17:47.240 --> 17:49.960
 To the next naked little piece and jump again,

17:49.960 --> 17:52.720
 and therefore, that's the idea that you go faster.

17:53.920 --> 17:58.720
 And it was always thought that in order to build

17:58.720 --> 18:01.840
 a big brain, a big nervous system,

18:01.840 --> 18:04.160
 in order to have a nervous system

18:04.160 --> 18:06.440
 that can do very complex type of things,

18:06.440 --> 18:09.400
 then you need a lot of myelin because you wanna go fast

18:09.400 --> 18:13.320
 with this information from point A to point B.

18:13.320 --> 18:17.960
 Well, a few years ago, maybe five years ago or so,

18:17.960 --> 18:20.680
 we discovered that some of the most evolved,

18:20.680 --> 18:24.120
 which means the newest type of neurons that we have

18:24.120 --> 18:26.520
 as non human primates, as as human beings,

18:26.520 --> 18:29.120
 in the top of our cerebral cortex,

18:29.120 --> 18:30.920
 which should be the neurons that do some

18:30.920 --> 18:33.200
 of the most complex things that we do.

18:33.200 --> 18:37.080
 Well, those have axons that have very little myelin.

18:37.080 --> 18:42.080
 Wow. And they have very interesting ways

18:42.080 --> 18:44.400
 in which they put this myelin on their axons,

18:44.400 --> 18:46.400
 you know, a little piece here, then a long track

18:46.400 --> 18:48.680
 with no myelin, another chunk there,

18:48.680 --> 18:50.600
 and some don't have myelin at all.

18:50.600 --> 18:53.120
 So now you have to explain

18:54.760 --> 18:57.960
 where we're going with evolution.

18:57.960 --> 19:01.360
 And if you think about it, perhaps as an electrical engineer,

19:02.800 --> 19:06.000
 when I looked at it, I initially thought,

19:06.000 --> 19:07.560
 I'm a developmental neurobiology,

19:07.560 --> 19:10.880
 I thought maybe this is what we see now,

19:10.880 --> 19:14.160
 but if we give evolution another few million years,

19:14.160 --> 19:16.520
 we'll see a lot of myelin on these neurons too.

19:16.520 --> 19:18.840
 But I actually think now that that's instead

19:18.840 --> 19:22.000
 the future of the brain, less myelin,

19:22.000 --> 19:24.720
 and my allow for more flexibility

19:24.720 --> 19:26.720
 on what you do with your axons,

19:26.720 --> 19:28.560
 and therefore more complicated

19:28.560 --> 19:32.200
 and unpredictable type of functions,

19:32.200 --> 19:34.320
 which is also a bit mind blowing.

19:34.320 --> 19:38.480
 So it seems like it's controlling the timing of the signal.

19:38.480 --> 19:40.160
 So they're in the timing,

19:40.160 --> 19:43.320
 you can encode a lot of information.

19:43.320 --> 19:44.680
 And so the brain...

19:44.680 --> 19:48.600
 The timing, the chemistry of that little piece of axon,

19:48.600 --> 19:52.160
 perhaps it's a dynamic process where the myelin can move.

19:52.160 --> 19:57.160
 Now you see how many layers of variability you can add,

19:57.520 --> 19:58.960
 and that's actually really good.

19:58.960 --> 20:02.320
 If you're trying to come up with a new function

20:02.320 --> 20:06.600
 or a new capability or something unpredictable in a way.

20:06.600 --> 20:08.240
 So we're gonna jump right out a little bit,

20:08.240 --> 20:12.880
 but the old question of how much is nature

20:12.880 --> 20:14.560
 and how much is nurture,

20:14.560 --> 20:17.360
 in terms of this incredible thing

20:17.360 --> 20:18.920
 after the development is over,

20:20.280 --> 20:25.160
 we seem to be kind of somewhat smart, intelligent,

20:26.160 --> 20:27.600
 cognition, consciousness,

20:27.600 --> 20:30.680
 all these things are just incredible ability of reason

20:30.680 --> 20:32.080
 and so on emerge.

20:32.080 --> 20:34.960
 In your sense, how much is in the hardware,

20:34.960 --> 20:39.320
 in the nature and how much is in the nurtures

20:39.320 --> 20:41.040
 learned through with our parents

20:41.040 --> 20:42.480
 through interacting with the environment, so on.

20:42.480 --> 20:43.800
 It's really both, right?

20:43.800 --> 20:45.040
 If you think about it.

20:45.040 --> 20:48.040
 So we are born with a brain as babies

20:48.040 --> 20:53.040
 that has most of its cells and most of its structures

20:53.640 --> 20:57.920
 and that will take a few years to grow,

20:57.920 --> 21:00.640
 to add more, to be better.

21:00.640 --> 21:04.160
 But really then we have this 20 years

21:04.160 --> 21:07.080
 of interacting with the environment around us.

21:07.080 --> 21:10.800
 And so what that brain that was so perfectly built

21:10.800 --> 21:15.800
 or imperfectly built due to our genetic cues

21:16.480 --> 21:20.200
 will then be used to incorporate the environment

21:20.200 --> 21:22.760
 in its farther maturation and development.

21:22.760 --> 21:27.000
 And so your experiences do shape your brain.

21:27.000 --> 21:29.480
 I mean, we know that like if you and I

21:29.480 --> 21:33.000
 may have had a different childhood or a different,

21:33.000 --> 21:35.080
 we have been going to different schools,

21:35.080 --> 21:36.480
 we have been learning different things

21:36.480 --> 21:38.080
 and our brain is a little bit different

21:38.080 --> 21:41.200
 because of that we behave differently because of that.

21:41.200 --> 21:44.080
 And so especially postnatally,

21:44.080 --> 21:46.040
 experience is extremely important.

21:46.040 --> 21:48.800
 We are born with a plastic brain.

21:48.800 --> 21:51.480
 What that means is a brain that is able to change

21:51.480 --> 21:54.280
 in response to stimuli.

21:54.280 --> 21:56.400
 They can be sensory.

21:56.400 --> 22:01.040
 So perhaps some of the most illuminating studies

22:01.040 --> 22:03.440
 that were done were studies in which

22:03.440 --> 22:07.000
 the sensory organs were not working, right?

22:07.000 --> 22:09.520
 If you are born with eyes that don't work,

22:09.520 --> 22:12.520
 then your very brain, the piece of the brain

22:12.520 --> 22:16.000
 that normally would process vision, the visual cortex

22:17.240 --> 22:19.840
 develops postnatally differently

22:19.840 --> 22:23.520
 and it might be used to do something different, right?

22:23.520 --> 22:25.600
 So that's the most extreme.

22:25.600 --> 22:27.480
 The plasticity of the brain, I guess,

22:27.480 --> 22:29.480
 is the magic hardware that it,

22:29.480 --> 22:32.960
 and then its flexibility in all forms

22:32.960 --> 22:36.320
 is what enables the learning postnatally.

22:36.320 --> 22:39.280
 Can you talk about organoids?

22:39.280 --> 22:40.920
 What are they?

22:40.920 --> 22:43.760
 And how can you use them to help us understand

22:43.760 --> 22:45.760
 the brain and the development of the brain?

22:45.760 --> 22:47.360
 This is very, very important.

22:47.360 --> 22:49.920
 So the first thing I'd like to say,

22:49.920 --> 22:51.440
 please keep this in the video.

22:51.440 --> 22:56.040
 The first thing I'd like to say is that an organoid,

22:56.040 --> 23:01.040
 a brain organoid, is not the same as a brain, okay?

23:01.600 --> 23:03.640
 It's a fundamental distinction.

23:03.640 --> 23:08.560
 It's a system, a cellular system,

23:08.560 --> 23:12.200
 that one can develop in the culture dish

23:12.200 --> 23:17.200
 starting from stem cells that will mimic some aspects

23:17.200 --> 23:21.400
 of the development of the brain, but not all of it.

23:21.400 --> 23:23.760
 They are very small, maximum,

23:23.760 --> 23:27.920
 they become about four to five millimeters in diameters.

23:27.920 --> 23:32.920
 They are much simpler than our brain, of course,

23:33.400 --> 23:36.480
 but yet they are the only system

23:36.480 --> 23:39.520
 where we can literally watch a process

23:39.520 --> 23:42.560
 of human brain development unfold.

23:42.560 --> 23:45.080
 And by watch, I mean study it.

23:45.080 --> 23:48.000
 Remember when I told you that we can't understand

23:48.000 --> 23:50.040
 everything about development in our own brain

23:50.040 --> 23:51.560
 by studying a mouse?

23:51.560 --> 23:53.600
 Well, we can't study the actual process

23:53.600 --> 23:54.840
 of development of the human brain

23:54.840 --> 23:56.320
 because it all happens in utero.

23:56.320 --> 23:59.320
 So we will never have access to that process ever.

24:00.400 --> 24:04.320
 And therefore, this is our next best thing,

24:04.320 --> 24:08.400
 like a bunch of stem cells that can be coaxed

24:08.400 --> 24:11.720
 into starting a process of neural tube formation.

24:11.720 --> 24:14.680
 Remember that tube that is made by the embryo rion?

24:14.680 --> 24:17.160
 And from there, a lot of the cell types

24:17.160 --> 24:20.680
 that are present within the brain

24:20.680 --> 24:24.960
 and you can simply watch it and study,

24:24.960 --> 24:28.680
 but you can also think about diseases

24:28.680 --> 24:30.880
 where development of the brain

24:30.880 --> 24:34.200
 does not proceed normally, right, properly.

24:34.200 --> 24:35.920
 Think about neurodevelopmental diseases

24:35.920 --> 24:38.280
 that are many, many different types.

24:38.280 --> 24:40.200
 Think about autism spectrum disorders,

24:40.200 --> 24:42.640
 there are also many different types of autism.

24:42.640 --> 24:45.320
 So there you could take a stem cell

24:45.320 --> 24:47.520
 which really means either a sample of blood

24:47.520 --> 24:50.960
 or a sample of skin from the patient,

24:50.960 --> 24:54.360
 make a stem cell, and then with that stem cell,

24:54.360 --> 24:57.480
 watch a process of formation of a brain organoid

24:57.480 --> 25:00.640
 of that person, with that genetics,

25:00.640 --> 25:02.240
 with that genetic code in it.

25:02.240 --> 25:05.840
 And you can ask, what is this genetic code doing

25:05.840 --> 25:08.800
 to some aspects of development of the brain?

25:08.800 --> 25:12.040
 And for the first time, you may come to solutions

25:12.040 --> 25:15.440
 like, what cells are involved in autism?

25:15.440 --> 25:17.400
 So I have so many questions around this.

25:17.400 --> 25:20.560
 So if you take this human stem cell

25:20.560 --> 25:23.400
 for that particular person with that genetic code,

25:23.400 --> 25:26.560
 how, and you try to build an organoid,

25:26.560 --> 25:28.880
 how often will it look similar?

25:28.880 --> 25:31.880
 What's the, yeah, so.

25:31.880 --> 25:33.320
 Reproducibility.

25:33.320 --> 25:37.360
 Yes, or how much variability is the flip side of that, yeah.

25:37.360 --> 25:42.360
 So there is much more variability in building organoids

25:42.360 --> 25:44.560
 than there is in building brain.

25:44.560 --> 25:47.320
 It's really true that the majority of us,

25:47.320 --> 25:49.600
 when we are born as babies,

25:49.600 --> 25:52.480
 our brains look a lot like each other.

25:52.480 --> 25:54.920
 This is the magic that the embryo does,

25:54.920 --> 25:57.680
 where it builds a brain in the context of a body

25:57.680 --> 26:01.280
 and there is very little variability there.

26:01.280 --> 26:02.320
 There is disease, of course,

26:02.320 --> 26:04.000
 but in general, little variability.

26:04.000 --> 26:08.400
 When you build an organoid, we don't have the full code

26:08.400 --> 26:09.520
 for how this is done.

26:09.520 --> 26:13.440
 And so in part, the organoid somewhat builds itself

26:13.440 --> 26:15.560
 because there are some structures of the brain

26:15.560 --> 26:17.280
 that the cells know how to make.

26:18.160 --> 26:21.840
 And another part comes from the investigator,

26:21.840 --> 26:26.160
 the scientist, adding to the media factors

26:26.160 --> 26:28.040
 that we know in the mouse, for example,

26:28.040 --> 26:30.760
 would foster a certain step of development.

26:30.760 --> 26:33.240
 But it's very limited.

26:33.240 --> 26:36.160
 And so as a result,

26:36.160 --> 26:38.200
 the kind of product you get in the end

26:38.200 --> 26:39.720
 is much more reductionist.

26:39.720 --> 26:42.680
 It's much more simple than what you get in vivo.

26:42.680 --> 26:46.200
 It mimics early events of development as of today.

26:46.200 --> 26:49.080
 And it doesn't build very complex type of anatomy

26:49.080 --> 26:51.440
 and structure does not as of today,

26:52.600 --> 26:54.920
 which happens instead in vivo.

26:54.920 --> 26:59.120
 And also the variability that you see

26:59.120 --> 27:02.800
 one organoid to the next tends to be higher

27:02.800 --> 27:05.560
 than when you compare an embryo to the next.

27:05.560 --> 27:08.960
 So, okay, then the next question is how hard

27:08.960 --> 27:11.120
 and maybe another flip side of that expensive

27:11.120 --> 27:14.960
 is it to go from one stem cell to an organoid?

27:14.960 --> 27:16.760
 How many can you build in like,

27:16.760 --> 27:18.480
 because it sounds very complicated.

27:18.480 --> 27:23.480
 It's work, definitely, and it's money, definitely.

27:23.480 --> 27:28.080
 But you can really grow a very high number

27:28.080 --> 27:31.640
 of these organoids, you know, can go perhaps,

27:31.640 --> 27:33.160
 I told you the maximum they become

27:33.160 --> 27:34.800
 about five millimeters in diameter.

27:34.800 --> 27:39.800
 So this is about the size of a tiny, tiny, you know, raising

27:40.800 --> 27:43.160
 or perhaps the seed of an apple.

27:43.160 --> 27:47.560
 And so you can grow 50 to 100 of those

27:47.560 --> 27:51.360
 inside one big bioreactors, which are these flasks

27:51.360 --> 27:55.520
 where the media provides nutrients for the organoids.

27:55.520 --> 28:00.520
 So the problem is not to grow more or less of them.

28:01.760 --> 28:06.480
 It's really to figure out how to grow them in a way

28:06.480 --> 28:08.440
 that they are more and more reproducible.

28:08.440 --> 28:10.000
 For example, organoid to organoid,

28:10.000 --> 28:13.200
 so they can be used to study a biological process

28:13.200 --> 28:15.640
 because if you have too much of variability,

28:15.640 --> 28:17.160
 then you never know if what you see

28:17.160 --> 28:19.560
 is just an exception or really the rule.

28:19.560 --> 28:22.160
 So what does an organoid look like?

28:22.160 --> 28:25.120
 Are there different neurons already emerging?

28:25.120 --> 28:27.520
 Is there, you know, well, first,

28:27.520 --> 28:29.920
 can you tell me what kind of neurons are there?

28:29.920 --> 28:30.920
 Yes.

28:30.920 --> 28:35.560
 Are they sort of all the same?

28:35.560 --> 28:37.480
 Are they not all the same?

28:37.480 --> 28:39.560
 Is how much do we understand

28:39.560 --> 28:42.440
 and how much of that variance

28:42.440 --> 28:45.800
 if any can exist in organoids?

28:45.800 --> 28:49.360
 Yes, so you could grow,

28:49.360 --> 28:52.440
 I told you that the brain has different parts.

28:52.440 --> 28:56.000
 So the cerebral cortex is on the top part of the brain,

28:56.000 --> 28:57.960
 but there is another region called the striatum

28:57.960 --> 28:59.960
 that is below the cortex and so on and so forth.

28:59.960 --> 29:03.760
 All of these regions have different types of cells

29:03.760 --> 29:05.040
 in the actual brain.

29:05.040 --> 29:05.880
 Okay.

29:05.880 --> 29:08.880
 And so scientists have been able to grow organoids

29:08.880 --> 29:11.440
 that may mimic some aspects of development

29:11.440 --> 29:13.920
 of these different regions of the brain.

29:13.920 --> 29:16.480
 And so we are very interested in the cerebral cortex.

29:16.480 --> 29:17.720
 That's the coolest part, right?

29:17.720 --> 29:18.560
 Very cool.

29:18.560 --> 29:20.880
 I agree with you.

29:20.880 --> 29:23.880
 We wouldn't be here talking if we didn't have a cerebral cortex.

29:23.880 --> 29:25.200
 It's also, I like to think,

29:25.200 --> 29:27.600
 the part of the brain that really truly makes us human,

29:27.600 --> 29:30.200
 the most evolved in recent evolution.

29:30.200 --> 29:33.600
 And so in the attempt to make the cerebral cortex

29:33.600 --> 29:37.200
 and by figuring out a way to have these organoids

29:37.200 --> 29:40.240
 continue to grow and develop for extended periods of time,

29:40.240 --> 29:42.400
 much like it happens in the real embryo,

29:42.400 --> 29:44.240
 months and months in culture,

29:44.240 --> 29:47.920
 then you can see that many different types

29:47.920 --> 29:50.200
 of neurons of the cortex appear

29:50.200 --> 29:52.200
 and at some point also the astrocytes,

29:52.200 --> 29:57.200
 so the glia cells of the cerebral cortex also appear.

29:57.640 --> 29:59.000
 What are these?

29:59.000 --> 29:59.840
 Astrocytes.

29:59.840 --> 30:00.680
 Astrocytes.

30:00.680 --> 30:02.080
 The astrocytes are not neurons,

30:02.080 --> 30:03.440
 so they're not nerve cells,

30:03.440 --> 30:06.160
 but they play very important roles.

30:06.160 --> 30:09.000
 One important role is to support the neuron,

30:09.000 --> 30:11.880
 but of course they have much more active type of roles.

30:11.880 --> 30:13.280
 They're very important, for example,

30:13.280 --> 30:14.560
 to make the synapses,

30:14.560 --> 30:17.640
 which are the point of contact and communication

30:17.640 --> 30:21.480
 between two neurons, they...

30:21.480 --> 30:25.680
 So all that chemistry fun happens in the synapses

30:25.680 --> 30:28.160
 happens because of these cells?

30:28.160 --> 30:29.680
 Are they the medium in which?

30:29.680 --> 30:32.000
 Happens because of the interactions,

30:32.000 --> 30:34.760
 happens because you are making the cells

30:34.760 --> 30:36.320
 and they have certain properties,

30:36.320 --> 30:40.360
 including the ability to make neurotransmitters,

30:40.360 --> 30:43.320
 which are the chemicals that are secreted to the synapses,

30:43.320 --> 30:46.480
 including the ability of making these axons grow

30:46.480 --> 30:49.240
 with their growth cones and so on and so forth.

30:49.240 --> 30:51.400
 And then you have other cells around there

30:51.400 --> 30:55.200
 that release chemicals or touch the neurons

30:55.200 --> 30:57.200
 or interact with them in different ways

30:57.200 --> 30:59.880
 to really foster this perfect process,

30:59.880 --> 31:02.480
 in this case of synaptogenesis.

31:02.480 --> 31:05.680
 And this does happen within organoids.

31:05.680 --> 31:06.520
 Or with organoids.

31:06.520 --> 31:09.760
 So the mechanical and the chemical stuff happens.

31:09.760 --> 31:11.640
 The connectivity between neurons.

31:11.640 --> 31:13.320
 This, in a way, is not surprising

31:13.320 --> 31:18.160
 because scientists have been culturing neurons forever.

31:18.160 --> 31:20.760
 And when you take a neuron, even a very young one,

31:20.760 --> 31:23.480
 and you culture it, eventually finds another cell

31:23.480 --> 31:26.960
 or another neuron to talk to, it will form a synapse.

31:26.960 --> 31:28.520
 Are we talking about mice neurons?

31:28.520 --> 31:29.600
 Are we talking about human neurons?

31:29.600 --> 31:30.600
 It doesn't matter, both.

31:30.600 --> 31:33.280
 So you can culture a neuron like a single neuron

31:33.280 --> 31:37.920
 and give it a little friend and it starts interacting?

31:37.920 --> 31:40.240
 Yes. So neurons are able to...

31:40.240 --> 31:44.560
 It sounds... It's more simple than what it may sound to you.

31:44.560 --> 31:48.320
 Neurons have molecular properties and structural properties

31:48.320 --> 31:51.120
 that allow them to really communicate with other cells.

31:51.120 --> 31:53.160
 And so if you put not one neuron,

31:53.160 --> 31:55.120
 but if you put several neurons together,

31:55.120 --> 32:00.240
 chances are that they will form synapses with each other.

32:00.240 --> 32:01.120
 Okay, great.

32:01.120 --> 32:03.360
 So an organoid is not a brain.

32:03.360 --> 32:03.880
 No.

32:03.880 --> 32:07.600
 But there's some...

32:07.600 --> 32:10.440
 It's able to, especially what you're talking about,

32:10.440 --> 32:15.120
 mimic some properties of the cerebral cortex, for example.

32:15.120 --> 32:17.960
 So what can you understand about the brain

32:17.960 --> 32:21.040
 by studying an organoid of the cerebral cortex?

32:21.040 --> 32:26.400
 I can literally study all this incredible diversity of cell type,

32:26.400 --> 32:29.040
 all these many, many different classes of cells.

32:29.040 --> 32:30.760
 How are they made?

32:30.760 --> 32:32.520
 How do they look like?

32:32.520 --> 32:34.920
 What do they need to be made properly?

32:34.920 --> 32:36.280
 And what goes wrong?

32:36.280 --> 32:39.680
 If now the genetics of that stem cell

32:39.680 --> 32:42.800
 that I used to make the organoid came from a patient

32:42.800 --> 32:44.320
 with a neurodevelopmental disease,

32:44.320 --> 32:47.600
 can I actually watch for the very first time

32:47.600 --> 32:51.400
 what may have gone wrong years before in this kid

32:51.400 --> 32:53.480
 when its own brain was being made?

32:53.480 --> 32:54.720
 Think about that loop.

32:54.720 --> 32:59.600
 In a way, it's a little tiny rudimentary window

32:59.600 --> 33:04.240
 into the past, into the time when that brain,

33:04.240 --> 33:07.680
 in a kid that had this neurodevelopmental disease,

33:07.680 --> 33:10.120
 was being made.

33:10.120 --> 33:12.880
 And I think that's unbelievably powerful

33:12.880 --> 33:16.800
 because today we have no idea of what cell types,

33:16.800 --> 33:20.880
 we barely know what brain regions are affected in these diseases.

33:20.880 --> 33:23.720
 Now we have an experimental system

33:23.720 --> 33:25.440
 that we can study in the lab

33:25.440 --> 33:28.440
 and we can ask what are the cells affected?

33:28.440 --> 33:31.840
 When, during development, things went wrong.

33:31.840 --> 33:35.200
 What are the molecules among the many, many different molecules

33:35.200 --> 33:36.600
 that control brain development?

33:36.600 --> 33:39.720
 Which ones are the ones that really messed up here

33:39.720 --> 33:42.160
 and we want perhaps to fix?

33:42.160 --> 33:44.520
 And what is really the final product?

33:44.520 --> 33:48.560
 Is it a less strong kind of circuit and brain?

33:48.560 --> 33:50.560
 Is it a brain that lacks a cell type?

33:50.560 --> 33:52.040
 Is it a, what is it?

33:52.040 --> 33:54.920
 Because then we can think about treatment

33:54.920 --> 33:59.360
 and care for these patients that is informed

33:59.360 --> 34:02.040
 rather than just based on current diagnostics.

34:02.040 --> 34:06.240
 So how hard is it to detect through the developmental process?

34:06.240 --> 34:09.920
 It's a super exciting tool

34:09.920 --> 34:15.160
 to see how different conditions develop.

34:15.160 --> 34:17.640
 How hard is it to detect that, wait a minute,

34:17.640 --> 34:20.760
 this is abnormal development.

34:20.760 --> 34:22.080
 Yeah.

34:22.080 --> 34:24.840
 That's how hard it, how much signals there,

34:24.840 --> 34:26.520
 how much of it is it a mess?

34:26.520 --> 34:29.520
 Because things can go wrong at multiple levels, right?

34:29.520 --> 34:34.360
 You could have a cell that is born and built

34:34.360 --> 34:36.280
 but then doesn't work properly

34:36.280 --> 34:38.360
 or a cell that is not even born

34:38.360 --> 34:40.760
 or a cell that doesn't interact with other cells differently

34:40.760 --> 34:42.160
 and so on and so forth.

34:42.160 --> 34:44.440
 So today we have technology

34:44.440 --> 34:47.800
 that we did not have even five years ago

34:47.800 --> 34:49.800
 that allows us to look, for example,

34:49.800 --> 34:52.160
 at the molecular picture of a cell,

34:52.160 --> 34:56.840
 of a single cell in a sea of cells with high precision.

34:56.840 --> 34:58.920
 And so that molecular information

34:58.920 --> 35:01.840
 where you compare many, many single cells

35:01.840 --> 35:03.720
 for the genes that they produce

35:03.720 --> 35:06.240
 between a control individual

35:06.240 --> 35:10.200
 and an individual with a neurodevelopmental disease,

35:10.200 --> 35:13.880
 that may tell you what is different, molecularly.

35:13.880 --> 35:18.640
 Or you could see that some cells are not even made,

35:18.640 --> 35:20.840
 for example, or that the process of maturation

35:20.840 --> 35:22.680
 of the cells may be wrong.

35:22.680 --> 35:25.080
 There are many different levels here

35:26.040 --> 35:29.640
 and we can study the cells at the molecular level

35:29.640 --> 35:33.440
 but also we can use the organoids to ask questions

35:33.440 --> 35:35.360
 about the properties of the neurons,

35:35.360 --> 35:37.400
 the functional properties,

35:37.400 --> 35:39.000
 how they communicate with each other,

35:39.000 --> 35:41.440
 how they respond to a stimulus and so on and so forth

35:41.440 --> 35:46.440
 and we may get abnormalities there, right?

35:46.440 --> 35:51.440
 And detect those, so how early is this work in the,

35:51.920 --> 35:54.400
 maybe in the history of science?

35:54.400 --> 35:59.400
 So, so, I mean, like, so if you were to,

35:59.840 --> 36:04.840
 if you and I time travel a thousand years into the future,

36:05.280 --> 36:10.040
 organoids seem to be, maybe I'm romanticizing the notion

36:10.040 --> 36:12.880
 but you're building not a brain

36:12.880 --> 36:15.800
 but something that has properties of a brain.

36:15.800 --> 36:19.120
 So it feels like you might be getting close to,

36:19.120 --> 36:23.320
 in the building process, to build us to understand.

36:23.320 --> 36:28.320
 So how far are we in this understanding

36:29.160 --> 36:30.360
 process of development?

36:31.520 --> 36:34.320
 A thousand years from now, it's a long time from now.

36:34.320 --> 36:36.560
 So if this planet is still gonna be here,

36:36.560 --> 36:38.280
 a thousand years from now.

36:38.280 --> 36:42.080
 So I mean, if, you know, like they write a book,

36:42.080 --> 36:44.120
 obviously there'll be a chapter about you.

36:44.120 --> 36:47.320
 That's probably the science fiction book today.

36:47.320 --> 36:48.160
 Yeah, today.

36:48.160 --> 36:50.840
 But I mean, I guess where we really understood

36:50.840 --> 36:53.400
 very little about the brain a century ago,

36:53.400 --> 36:55.920
 where I was a big fan in high school,

36:55.920 --> 36:58.760
 reading Freud and so on, still am of psychiatry.

36:59.680 --> 37:01.480
 I would say we still understand very little

37:01.480 --> 37:04.720
 about the functional aspect of just,

37:04.720 --> 37:07.760
 but how in the history of understanding

37:07.760 --> 37:09.640
 the biology of the brain, the development,

37:09.640 --> 37:11.240
 how far are we along?

37:11.240 --> 37:12.960
 It's a very good question.

37:12.960 --> 37:15.520
 And so this is just, of course, my opinion.

37:15.520 --> 37:19.720
 I think that we did not have technology,

37:19.720 --> 37:23.160
 even 10 years ago or certainly not 20 years ago,

37:23.160 --> 37:27.760
 to even think about experimentally investigating

37:27.760 --> 37:30.160
 the development of the human brain.

37:30.160 --> 37:32.200
 So we've done a lot of work in science

37:32.200 --> 37:35.480
 to study the brain on many other organisms.

37:35.480 --> 37:39.600
 Now we have some technologies which I'll spell out

37:39.600 --> 37:43.120
 that allow us to actually look at the real thing

37:43.120 --> 37:45.040
 and look at the brain, at the human brain.

37:45.040 --> 37:46.840
 So what are these technologies?

37:46.840 --> 37:50.440
 There has been huge progress in stem cell biology.

37:50.440 --> 37:54.080
 The moment someone figured out how to turn a skin cell

37:54.080 --> 37:57.760
 into an embryonic stem cell, basically,

37:57.760 --> 38:00.160
 and that how that embryonic stem cell

38:00.160 --> 38:02.480
 could begin a process of development again

38:02.480 --> 38:04.000
 to, for example, make a brain,

38:04.000 --> 38:06.040
 there was a huge, you know, advance.

38:06.040 --> 38:08.200
 And in fact, there was a Nobel Prize for that.

38:08.200 --> 38:10.440
 That started the field, really,

38:10.440 --> 38:14.240
 of using stem cells to build organs.

38:14.240 --> 38:17.080
 Now we can build on all the knowledge of development

38:17.080 --> 38:18.560
 that we build over the many, many, many years

38:18.560 --> 38:20.720
 to say, how do we make these stem cells?

38:20.720 --> 38:22.680
 Now make more and more complex aspects

38:22.680 --> 38:25.280
 of development of the human brain.

38:25.280 --> 38:28.480
 So this field is young, the field of brain organoids,

38:28.480 --> 38:30.120
 but it's moving fast.

38:30.120 --> 38:32.560
 And it's moving fast in a very serious way

38:32.560 --> 38:35.960
 that is rooted in labs with the right ethical framework

38:35.960 --> 38:39.720
 and really building on, you know,

38:39.720 --> 38:43.520
 solid science for what reality is and what is not.

38:43.520 --> 38:46.120
 And, but it will go fast

38:46.120 --> 38:49.120
 and it will be more and more powerful.

38:49.120 --> 38:52.480
 We also have technology that allows us to basically study

38:52.480 --> 38:54.640
 the properties of single cells

38:54.640 --> 38:59.240
 across many, many millions of single cells,

38:59.240 --> 39:02.160
 which we didn't have perhaps five years ago.

39:02.160 --> 39:04.840
 So now with that, even an organoid

39:04.840 --> 39:08.480
 that has millions of cells can be profiled in a way,

39:08.480 --> 39:11.320
 looked at with very, very high resolution,

39:11.320 --> 39:14.960
 the single cell level to really understand what is going on.

39:14.960 --> 39:17.520
 And you could do it in multiple stages of development

39:17.520 --> 39:20.120
 and you can build your hypothesis and so on and so forth.

39:20.120 --> 39:22.600
 So it's not gonna be a thousand years.

39:22.600 --> 39:25.240
 It's gonna be a shorter amount of time.

39:25.240 --> 39:29.480
 And I see this as sort of an exponential growth

39:29.480 --> 39:33.560
 of this field enabled by these technologies

39:33.560 --> 39:35.000
 that we didn't have before.

39:35.000 --> 39:36.960
 And so we're gonna see something transformative

39:36.960 --> 39:41.880
 that we didn't see at all in the prior thousand years.

39:41.880 --> 39:44.640
 So I apologize for the crazy sci fi questions,

39:44.640 --> 39:48.840
 but the developmental process is fascinating to watch

39:48.840 --> 39:53.360
 and study, but how far are we away from

39:53.360 --> 39:57.280
 and maybe how difficult is it to build

39:57.280 --> 40:02.280
 not just an organoid, but a human brain from a stem cell?

40:02.280 --> 40:05.640
 Yeah, first of all, that's not the goal

40:05.640 --> 40:09.400
 for the majority of the serial scientists that work on this

40:09.400 --> 40:14.160
 because you don't have to build the whole human brain

40:14.160 --> 40:17.000
 to make this model useful for understanding

40:17.000 --> 40:20.440
 how the brain develops or understanding disease.

40:20.440 --> 40:22.440
 You don't have to build the whole thing.

40:22.440 --> 40:25.200
 So let me just comment on that, it's fascinating.

40:25.200 --> 40:29.200
 It shows to me the difference between you and I

40:29.200 --> 40:32.240
 is you're actually trying to understand the beauty

40:32.240 --> 40:35.520
 of the human brain and to use it to really help

40:35.520 --> 40:38.800
 thousands or millions of people with disease and so on, right?

40:38.800 --> 40:41.480
 From an artificial intelligence perspective,

40:41.480 --> 40:45.600
 we're trying to build systems that we can put in robots

40:45.600 --> 40:49.080
 and try to create systems that have echoes

40:49.080 --> 40:52.360
 of the intelligence about reasoning about the world,

40:52.360 --> 40:53.600
 navigating the world.

40:53.600 --> 40:56.040
 It's different objectives, I think.

40:56.040 --> 40:57.520
 Yeah, that's very much science fiction.

40:57.520 --> 41:00.280
 Science fiction, but we operate in science fiction a little bit.

41:00.280 --> 41:03.440
 But so on that point of building a brain,

41:03.440 --> 41:05.800
 even though that is not the focus or interest,

41:05.800 --> 41:08.520
 perhaps, of the community, how difficult is it?

41:08.520 --> 41:11.200
 Is it truly science fiction at this point?

41:11.200 --> 41:13.960
 I think the field will progress, like I said,

41:13.960 --> 41:17.960
 and that the system will be more and more complex in a way,

41:17.960 --> 41:18.720
 right?

41:18.720 --> 41:23.880
 But there are properties that emerge from the human brain

41:23.880 --> 41:26.640
 that have to do with the mind, that may have to do with consciousness,

41:26.640 --> 41:29.840
 that may have to do with intelligence or whatever.

41:29.840 --> 41:33.720
 We really don't understand even how they can emerge

41:33.720 --> 41:36.880
 from an actual real brain, and therefore, we cannot measure

41:36.880 --> 41:40.160
 or study in an organoid.

41:40.160 --> 41:43.040
 So I think that this field, many, many years from now,

41:43.040 --> 41:48.240
 may lead to the building of better neural circuits

41:48.240 --> 41:50.640
 that really are built out of understanding of how

41:50.640 --> 41:52.400
 this process really works.

41:52.400 --> 41:57.000
 And it's hard to predict how complex this really will be.

41:57.000 --> 42:01.200
 I really don't think we're so far from, it makes me laugh, really.

42:01.200 --> 42:05.120
 It's really that far from building the human brain.

42:05.120 --> 42:10.040
 But you're going to be building something that is always

42:10.040 --> 42:14.800
 a bad version of it, but that may have really powerful properties

42:14.800 --> 42:18.560
 and might be able to respond to stimuli

42:18.560 --> 42:21.880
 or be used in certain contexts.

42:21.880 --> 42:24.800
 And this is why I really think that there is no other way

42:24.800 --> 42:28.200
 to do this science, but within the right ethical framework.

42:28.200 --> 42:31.440
 Because where you're going with this is also,

42:31.440 --> 42:34.160
 we can talk about science fiction and write that book,

42:34.160 --> 42:36.600
 and we could today.

42:36.600 --> 42:41.520
 But this work happens in a specific ethical framework

42:41.520 --> 42:44.880
 that we don't decide just as scientists, but also as a society.

42:44.880 --> 42:48.560
 So the ethical framework here is a fascinating one,

42:48.560 --> 42:51.120
 is a complicated one.

42:51.120 --> 42:55.680
 Do you have a sense, a grasp of how we think about ethically,

42:55.680 --> 43:04.160
 of building organoids from human stem cells to understand the brain?

43:04.160 --> 43:09.720
 It seems like a tool for helping potentially millions of people

43:09.720 --> 43:14.960
 cure diseases, or at least start to cure by understanding it.

43:14.960 --> 43:20.560
 But is there more, is there gray areas that are ethical,

43:20.560 --> 43:22.320
 that we have to think about ethically?

43:22.320 --> 43:23.160
 Absolutely.

43:23.160 --> 43:25.520
 We must think about that.

43:25.520 --> 43:29.560
 Every discussion about the ethics of this

43:29.560 --> 43:34.480
 needs to be based on actual data from the models that we have today

43:34.480 --> 43:36.280
 and from the ones that we will have tomorrow.

43:36.280 --> 43:37.800
 So it's a continuous conversation.

43:37.800 --> 43:39.840
 It's not something that you decide now.

43:39.840 --> 43:42.000
 Today, there is no issue, really.

43:42.000 --> 43:47.240
 Very simple models that clearly can help you in many ways

43:47.240 --> 43:49.880
 without much to think about.

43:49.880 --> 43:52.200
 But tomorrow, we need to have another conversation,

43:52.200 --> 43:53.160
 and so on and so forth.

43:53.160 --> 43:57.120
 And so the way we do this is to actually really bring together

43:57.120 --> 44:00.440
 constantly a group of people that are not only scientists,

44:00.440 --> 44:04.160
 but also bioethicists, lawyers, philosophers, psychiatrists,

44:04.160 --> 44:06.680
 and psychologists, and so on and so forth,

44:06.680 --> 44:13.040
 to decide as a society, really, what we should

44:13.040 --> 44:15.320
 and what we should not do.

44:15.320 --> 44:17.600
 So that's the way to think about the ethics.

44:17.600 --> 44:21.440
 Now, I also think, though, that as a scientist,

44:21.440 --> 44:23.840
 I have a moral responsibility.

44:23.840 --> 44:28.360
 So if you think about how transformative

44:28.360 --> 44:32.640
 it could be for understanding and curing a neuropsychiatric

44:32.640 --> 44:37.320
 disease, to be able to actually watch and study

44:37.320 --> 44:41.480
 and treat with drugs the very brain of the patient

44:41.480 --> 44:44.720
 that you are trying to study, how transformative

44:44.720 --> 44:47.200
 at this moment in time this could be.

44:47.200 --> 44:47.960
 We couldn't do it.

44:47.960 --> 44:50.800
 Five years ago, we could do it now.

44:50.800 --> 44:53.440
 Taking a stem cell of a particular patient

44:53.440 --> 44:57.480
 and make an organoid for a simple and different

44:57.480 --> 45:01.160
 from the human brain, it still is his process

45:01.160 --> 45:04.720
 of brain development with his or her genetics.

45:04.720 --> 45:08.280
 And we could understand perhaps what is going wrong.

45:08.280 --> 45:10.960
 Perhaps we could use as a platform, as a cellular platform,

45:10.960 --> 45:13.720
 to screen for drugs, to fix a process,

45:13.720 --> 45:15.280
 and so on and so forth.

45:15.280 --> 45:18.840
 So we could do it now, we couldn't do it five years ago.

45:18.840 --> 45:20.480
 Should we not do it?

45:20.480 --> 45:24.760
 What is the downside of doing it?

45:24.760 --> 45:27.320
 I don't see a downside at this very moment.

45:27.320 --> 45:30.880
 If we invited a lot of people, I'm sure there would be

45:30.880 --> 45:33.440
 somebody who would argue against it,

45:33.440 --> 45:37.680
 what would be the devil's advocate argument?

45:39.680 --> 45:42.960
 So it's exactly perhaps what you alluded at

45:42.960 --> 45:47.120
 with your question, that you are making a,

45:47.120 --> 45:51.680
 enabling some process of formation of the brain

45:51.680 --> 45:54.440
 that could be misused at some point,

45:54.440 --> 45:59.080
 or that could be showing properties

45:59.080 --> 46:03.960
 that ethically we don't wanna see in a tissue.

46:03.960 --> 46:07.760
 So today, I repeat, today this is not an issue.

46:07.760 --> 46:11.280
 And so you just gain dramatically from the science

46:11.280 --> 46:13.720
 without, because the system is so simple

46:13.720 --> 46:17.840
 and so different in a way from the actual brain.

46:17.840 --> 46:20.000
 But because it is the brain,

46:20.000 --> 46:23.960
 we have an obligation to really consider all of this, right?

46:23.960 --> 46:27.160
 And again, it's a balanced conversation

46:27.160 --> 46:30.360
 where we should put disease and betterment of humanity

46:30.360 --> 46:32.440
 also on that plate.

46:32.440 --> 46:35.440
 What do you think, at least historically,

46:35.440 --> 46:37.280
 there was some politicization,

46:37.280 --> 46:42.280
 politicization of embryonic stem cells,

46:44.360 --> 46:45.960
 a stem cell research.

46:47.160 --> 46:49.160
 Do you still see that out there?

46:49.160 --> 46:53.600
 Is that still a force that we have to think about,

46:53.600 --> 46:55.600
 especially in this larger discourse

46:55.600 --> 46:57.600
 that we're having about the role of science

46:57.600 --> 47:00.640
 in at least American society?

47:00.640 --> 47:03.520
 Yeah, this is a very good question.

47:03.520 --> 47:05.040
 It's very, very important.

47:05.040 --> 47:08.480
 I see a very central role for scientists

47:08.480 --> 47:12.040
 to inform decisions about what we should

47:12.040 --> 47:14.440
 or should not do in society.

47:14.440 --> 47:16.400
 And this is because the scientists

47:16.400 --> 47:20.440
 have the firsthand look and understanding

47:20.440 --> 47:23.520
 of really the work that they are doing.

47:23.520 --> 47:26.080
 And again, this varies depending on

47:26.080 --> 47:27.480
 what we're talking about here.

47:27.480 --> 47:30.800
 So now we're talking about brain organoids.

47:30.800 --> 47:33.800
 I think that the scientists need to be part

47:33.800 --> 47:36.520
 of that conversation about what is,

47:36.520 --> 47:38.040
 will be allowed in the future

47:38.040 --> 47:40.840
 or not allowed in the future to do with the system.

47:40.840 --> 47:43.400
 And I think that is very, very important

47:43.400 --> 47:47.880
 because they bring reality of data to the conversation.

47:48.880 --> 47:51.720
 And so they should have a voice.

47:51.720 --> 47:53.400
 So data should have a voice.

47:53.400 --> 47:55.200
 Data needs to have a voice.

47:55.200 --> 47:59.360
 Because in not only data, we should also be good

47:59.360 --> 48:04.240
 at communicating with non scientists the data.

48:04.240 --> 48:06.840
 So there has been, often time,

48:06.840 --> 48:11.840
 there is a lot of discussion and excitement

48:12.280 --> 48:16.320
 and fights about certain topics

48:16.320 --> 48:19.320
 just because of the way they are described.

48:19.320 --> 48:21.000
 I'll give you an example.

48:21.000 --> 48:23.400
 If I called the same cellular system,

48:23.400 --> 48:27.080
 we just talked about a brain organoid.

48:27.080 --> 48:30.320
 Or if I called it a human mini brain,

48:30.320 --> 48:34.600
 your reaction is gonna be very different to this.

48:34.600 --> 48:37.760
 And so the way the systems are described,

48:37.760 --> 48:40.720
 I mean, we and journalists alike

48:40.720 --> 48:43.720
 need to be a bit careful that this debate

48:43.720 --> 48:46.080
 is a real debate and informed by real data.

48:46.080 --> 48:47.960
 That's all I'm asking.

48:47.960 --> 48:49.600
 And yeah, the language matters here.

48:49.600 --> 48:51.280
 So I work on autonomous vehicles

48:51.280 --> 48:54.960
 and there the use of language could drastically

48:54.960 --> 48:57.480
 change the interpretation and the way people feel

48:57.480 --> 49:01.520
 about what is the right way to proceed forward.

49:01.520 --> 49:04.720
 You are, as I've seen from a presentation,

49:04.720 --> 49:06.240
 you're a parent.

49:06.240 --> 49:09.840
 I saw you show a couple of pictures of your son.

49:09.840 --> 49:11.440
 Is it just the one?

49:11.440 --> 49:12.280
 Two.

49:12.280 --> 49:13.120
 Two.

49:13.120 --> 49:13.960
 Son and a daughter.

49:13.960 --> 49:14.800
 Son and a daughter.

49:14.800 --> 49:17.360
 So what have you learned from the human brain

49:17.360 --> 49:20.120
 by raising two of them?

49:20.120 --> 49:22.800
 More than I could ever learn in a lab.

49:22.800 --> 49:25.600
 What have I learned?

49:26.840 --> 49:28.640
 I've learned that children really have

49:28.640 --> 49:31.520
 these amazing plastic minds, right?

49:31.520 --> 49:35.880
 That we have a responsibility to, you know,

49:35.880 --> 49:38.440
 foster their growth in good, healthy ways

49:39.360 --> 49:42.320
 that keep them curious, that keep some adventures,

49:42.320 --> 49:45.920
 that doesn't raise them in fear of things.

49:46.840 --> 49:48.920
 But also respecting who they are,

49:48.920 --> 49:51.320
 which is in part, you know, coming from the genetics

49:51.320 --> 49:53.840
 we talked about, my children are very different

49:53.840 --> 49:55.240
 from each other despite the fact

49:55.240 --> 49:57.840
 that they're the product of the same two parents.

49:59.320 --> 50:03.080
 I also learned that what you do for them

50:03.080 --> 50:04.280
 comes back to you.

50:04.280 --> 50:05.840
 Like, you know, if you're a good parent,

50:05.840 --> 50:09.800
 you're gonna, most of the time have, you know,

50:09.800 --> 50:12.200
 perhaps decent kids at the end.

50:12.200 --> 50:13.760
 So what do you think, just a quick comment,

50:13.760 --> 50:17.760
 what do you think is the source of that difference?

50:17.760 --> 50:20.960
 It's often the surprising thing for parents.

50:20.960 --> 50:24.000
 I can't believe that our kids,

50:25.640 --> 50:28.080
 they're so different, yet they came from the same parents.

50:28.080 --> 50:29.640
 Well, they are genetically different.

50:29.640 --> 50:31.920
 Even they came from the same two parents

50:31.920 --> 50:33.640
 because the mixing of gametes,

50:33.640 --> 50:35.720
 so when we know these genetics,

50:35.720 --> 50:39.800
 creates every time a genetically different individual

50:39.800 --> 50:43.760
 which will have a specific mix of genes

50:43.760 --> 50:46.560
 that is a different mix every time from the two parents.

50:46.560 --> 50:50.320
 And so they're not twins.

50:50.320 --> 50:52.960
 They're genetically different.

50:52.960 --> 50:55.320
 Just that little bit of variation.

50:55.320 --> 50:58.320
 As you said, really from a biological perspective,

50:58.320 --> 51:00.600
 the brains look pretty similar.

51:00.600 --> 51:02.400
 Well, so let me clarify that.

51:02.400 --> 51:05.400
 So the genetics you have, the genes that you have,

51:05.400 --> 51:08.680
 that play that beautiful orchestrated symphony

51:08.680 --> 51:12.040
 of development, different genes

51:12.040 --> 51:13.920
 will play it slightly differently.

51:13.920 --> 51:16.120
 It's like playing the same piece of music

51:16.120 --> 51:17.960
 but with the different orchestra

51:17.960 --> 51:20.000
 and a different director, right?

51:20.000 --> 51:21.440
 The music will not come out.

51:21.440 --> 51:25.400
 It will be still a piece by the same author

51:25.400 --> 51:27.040
 but it will come out differently

51:27.040 --> 51:28.920
 if it's played by the high school orchestra

51:28.920 --> 51:33.440
 instead of the, instead of the Scala in Milan.

51:34.680 --> 51:39.160
 And so you are born superficially with the same brain.

51:39.160 --> 51:43.440
 It has the same cell types, similar patterns of connectivity

51:43.440 --> 51:45.200
 but the properties of the cells

51:45.200 --> 51:47.600
 and how the cells will then react to the environment

51:47.600 --> 51:51.320
 as you experience your world will be also shaped

51:51.320 --> 51:53.680
 by who genetically you are.

51:53.680 --> 51:55.120
 Speaking just as a parent,

51:55.120 --> 51:56.880
 this is not something that comes from my work.

51:56.880 --> 51:58.840
 I think you can tell at birth

51:58.840 --> 52:01.120
 that these kids are different

52:01.120 --> 52:04.560
 and that they have a different personality in a way, right?

52:05.560 --> 52:07.600
 So both is needed.

52:07.600 --> 52:10.800
 The genetics as well as the nurturing afterwards.

52:11.760 --> 52:14.600
 So you are one human with a brain

52:14.600 --> 52:17.200
 sort of living through the whole mess of it.

52:17.200 --> 52:21.000
 The human condition, full of love, maybe fear,

52:21.000 --> 52:22.880
 ultimately mortal.

52:23.880 --> 52:27.080
 How has studying the brain changed the way you see yourself?

52:27.080 --> 52:29.880
 When you look in the mirror, when you think about your life,

52:29.880 --> 52:31.880
 the fears, the love.

52:31.880 --> 52:34.040
 When you see your own life, your own mortality.

52:34.040 --> 52:36.840
 Yeah, that's a very good question.

52:37.960 --> 52:43.160
 It's almost impossible to dissociate some time for me.

52:43.160 --> 52:45.880
 Some of the things we do or some of the things

52:45.880 --> 52:48.200
 that other people do from,

52:48.200 --> 52:51.080
 oh, that's because that part of the brain

52:51.960 --> 52:54.080
 is working in a certain way.

52:54.080 --> 52:57.840
 Or thinking about a teenager,

52:59.080 --> 53:01.800
 going through teenage years and being a time funny

53:01.800 --> 53:03.560
 in the way they think.

53:03.560 --> 53:07.200
 And impossible for me not to think it's because

53:07.200 --> 53:10.480
 they're going through this period of time called

53:10.480 --> 53:12.640
 critical periods of plasticity.

53:12.640 --> 53:13.480
 Yeah.

53:13.480 --> 53:16.400
 Where their synapses are being eliminated here and there

53:16.400 --> 53:17.760
 and they're just confused.

53:17.760 --> 53:22.280
 And so from that comes perhaps a different take

53:22.280 --> 53:27.280
 on that behavior or maybe I can justify scientifically

53:28.080 --> 53:30.120
 in some sort of way.

53:30.120 --> 53:32.280
 I also look at humanity in general

53:32.280 --> 53:37.040
 and I am amazed by what we can do

53:37.040 --> 53:39.960
 and the kind of ideas that we can come up with.

53:39.960 --> 53:42.840
 And I cannot stop thinking about

53:42.840 --> 53:46.440
 how the brain is continuing to evolve.

53:46.440 --> 53:47.360
 I don't know if you do this,

53:47.360 --> 53:49.720
 but I think about the next brain sometimes.

53:49.720 --> 53:51.080
 Where are we going with this?

53:51.080 --> 53:53.920
 Like what are the features of this brain

53:53.920 --> 53:57.920
 that evolution is really playing with

53:57.920 --> 54:02.920
 to get us in the future, the new brain?

54:03.080 --> 54:04.280
 It's not over, right?

54:04.280 --> 54:07.200
 It's a work in progress.

54:07.200 --> 54:09.280
 So let me just a quick comment on that.

54:09.280 --> 54:14.280
 Do you see, do you think there's a lot of fascination

54:14.520 --> 54:16.240
 and hope for artificial intelligence

54:16.240 --> 54:17.960
 of creating artificial brains?

54:17.960 --> 54:20.320
 You said the next brain.

54:20.320 --> 54:23.600
 When you imagine over a period of a thousand years

54:23.600 --> 54:25.760
 the evolution of the human brain,

54:25.760 --> 54:28.920
 do you sometimes envisioning that future

54:28.920 --> 54:31.440
 see an artificial one?

54:31.440 --> 54:34.280
 Artificial intelligence as it is hoped by many,

54:34.280 --> 54:36.840
 not hoped, thought by many people

54:36.840 --> 54:39.120
 would be actually the next evolutionary step

54:39.120 --> 54:40.680
 in the development of humans.

54:40.680 --> 54:45.480
 Yeah, I think in a way that will happen, right?

54:45.480 --> 54:48.760
 It's almost like a part of the way we evolve.

54:48.760 --> 54:51.400
 We evolve in the world that we created,

54:51.400 --> 54:55.520
 that we interact with, that shape us as we grow up

54:55.520 --> 54:56.840
 and so on and so forth.

54:58.440 --> 55:01.120
 Sometime I think about something that may sound silly,

55:01.120 --> 55:04.720
 but think about the use of cell phones.

55:04.720 --> 55:07.240
 Part of me thinks that somehow in their brain

55:07.240 --> 55:09.160
 there will be a region of the cortex

55:09.160 --> 55:13.720
 that is attuned to that tool.

55:13.720 --> 55:16.600
 And this comes from a lot of studies

55:16.600 --> 55:21.000
 in model organisms where really the cortex

55:21.000 --> 55:24.280
 especially adapts to the kind of things you have to do.

55:24.280 --> 55:28.640
 So if we need to move our fingers in a very specific way,

55:28.640 --> 55:31.040
 we have a part of our cortex that allows us to do

55:31.040 --> 55:33.080
 this kind of very precise movement.

55:34.440 --> 55:37.000
 An owl that has to see very, very far away

55:37.000 --> 55:39.440
 with big eyes, the visual cortex, very big.

55:39.440 --> 55:43.280
 It's the brain attunes to your environment.

55:43.280 --> 55:47.600
 So the brain will attune to the technologies

55:47.600 --> 55:51.200
 that we will have and will be shaped by it.

55:51.200 --> 55:53.000
 So the cortex very well may be.

55:53.000 --> 55:54.640
 Will be shaped by it.

55:54.640 --> 55:57.360
 In artificial intelligence, it may merge with it,

55:57.360 --> 56:01.240
 it may get enveloped and adjusted.

56:01.240 --> 56:04.200
 Even if it's not a merge of the kind of,

56:04.200 --> 56:07.000
 oh, let's have a synthetic element together

56:07.000 --> 56:08.800
 with a biological one.

56:08.800 --> 56:11.840
 The very space around us, the fact, for example,

56:11.840 --> 56:15.280
 think about we put on some goggles of virtual reality

56:15.280 --> 56:18.840
 and we physically are surfing the ocean, right?

56:18.840 --> 56:21.800
 Like I've done it and you have all these emotions

56:21.800 --> 56:26.800
 that come to you, your brain placed you in that reality.

56:27.200 --> 56:29.720
 And it was able to do it like that

56:29.720 --> 56:31.160
 just by putting the goggles on.

56:31.160 --> 56:36.040
 I didn't take thousands of years of adapting to this.

56:36.040 --> 56:39.360
 The brain is plastic, so adapts to new technology.

56:39.360 --> 56:41.840
 So you could do it from the outside

56:41.840 --> 56:46.840
 by simply hijacking some sensory capacities that we have.

56:47.680 --> 56:51.640
 So clearly over recent evolution,

56:51.640 --> 56:54.040
 the cerebral cortex has been a part of the brain

56:54.040 --> 56:56.040
 that has known the most evolution.

56:56.040 --> 57:00.840
 So we have put a lot of chips on evolving

57:00.840 --> 57:02.640
 this specific part of the brain

57:02.640 --> 57:06.000
 and the evolution of cortex is plasticity.

57:06.000 --> 57:10.320
 It's this ability to change in response to things.

57:10.320 --> 57:13.840
 So yes, they will integrate that we want it or not.

57:15.000 --> 57:18.200
 Well, there's no better way to end it, Paola.

57:18.200 --> 57:19.520
 Thank you so much for talking to me.

57:19.520 --> 57:20.360
 You're very welcome.

57:20.360 --> 57:21.200
 That's great.

57:21.200 --> 57:31.200
 Thank you.