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.