Transcript
00:00:00 The following is a conversation with Paola Arlotta.
00:00:03 She’s a professor of stem cell and regenerative biology
00:00:06 at Harvard University and is interested in understanding
00:00:09 the molecular laws that govern the birth, differentiation,
00:00:13 and assembly of the human brain’s cerebral cortex.
00:00:16 She explores the complexity of the brain
00:00:18 by studying and engineering elements
00:00:21 of how the brain develops.
00:00:22 This was a fascinating conversation to me.
00:00:25 It’s part of the Artificial Intelligence podcast.
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00:00:39 And I’d like to give a special thank you to Amy Jeffress
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00:00:52 Your support means a lot and inspires me
00:00:55 to keep the series going.
00:00:57 And now here’s my conversation with Paola Arlotta.
00:01:03 You studied the development of the human brain
00:01:05 for many years.
00:01:06 So let me ask you an out of the box question first.
00:01:11 How likely is it that there’s intelligent life out there
00:01:14 in the universe outside of earth
00:01:17 with something like the human brain?
00:01:19 So I can put it another way.
00:01:20 How unlikely is the human brain?
00:01:24 How difficult is it to build a thing
00:01:28 through the evolutionary process?
00:01:30 Well, it has happened here, right?
00:01:32 On this planet.
00:01:33 Once, yes.
00:01:34 Once.
00:01:36 So that simply tells you that it could, of course,
00:01:39 happen again other places.
00:01:42 It’s only a matter of probability.
00:01:44 What the probability that you would get a brain
00:01:46 like the ones that we have, like the human brain.
00:01:51 So how difficult is it to make the human brain?
00:01:53 It’s pretty difficult, but most importantly,
00:01:59 I guess we know very little
00:02:00 about how this process really happens.
00:02:04 And there is a reason for that,
00:02:06 actually multiple reasons for that.
00:02:09 Most of what we know about how the mammalian brain,
00:02:13 so the brain of mammals develop comes from studying
00:02:17 in labs other brains, not our own brain,
00:02:20 the brain of mice, for example.
00:02:22 But if I showed you a picture of a mouse brain,
00:02:25 and then you put it next to a picture of a human brain,
00:02:28 they don’t look at all like each other.
00:02:31 So they’re very different.
00:02:32 And therefore there is a limit to what you can learn
00:02:36 about how the human brain is made
00:02:37 by studying the mouse brain.
00:02:41 There is a huge value in studying the mouse brain.
00:02:43 There are many things that we have learned,
00:02:45 but it’s not the same thing.
00:02:46 So in having studied the human brain,
00:02:49 or through the mouse and through other methodologies
00:02:51 that we’ll talk about, do you have a sense?
00:02:54 I mean, you’re one of the experts in the world.
00:02:57 How much do you feel you know about the brain
00:03:01 and how often do you find yourself
00:03:05 in awe of this mysterious thing?
00:03:07 Yeah, you pretty much find yourself in awe all the time.
00:03:12 It’s an amazing process.
00:03:15 It’s a process by which,
00:03:17 by means that we don’t fully understand,
00:03:20 at the very beginning of embryogenesis,
00:03:23 the structure called the neural tube,
00:03:26 literally self assembles.
00:03:28 And it happens in an embryo
00:03:30 and it can happen also from stem cells in a dish.
00:03:33 Okay.
00:03:34 And then from there,
00:03:36 these stem cells that are present within the neural tube
00:03:39 give rise to all of the thousands and thousands
00:03:42 of different cell types that are present in the brain
00:03:45 through time, right?
00:03:46 With the interesting, very intriguing, interesting
00:03:50 observation is that the time that it takes
00:03:54 for the human brain to be made, it’s human time.
00:03:58 Meaning that for me and you,
00:04:02 it took almost nine months of gestation to build the brain
00:04:05 and then another 20 years of learning postnatally
00:04:08 to get the brain that we have today
00:04:09 that allows us to this conversation.
00:04:12 A mouse takes 20 days or so for an embryo to be born.
00:04:19 And so the brain is built in a much shorter period of time.
00:04:23 And the beauty of it is that if you take mouse stem cells
00:04:27 and you put them in a culture dish,
00:04:29 the brain organoid that you get from a mouse
00:04:33 is formed faster than if you took human stem cells
00:04:37 and put them in the dish
00:04:39 and let them make a human brain organoid.
00:04:41 So the very developmental process is…
00:04:45 Controlled by the speed of the species.
00:04:49 Which means it’s on purpose, it’s not accidental
00:04:54 or there is something in that temporal…
00:04:58 It’s very, exactly, that is very important
00:05:01 for us to get the brain we have.
00:05:04 And we can speculate for why that is.
00:05:08 You know, it takes us a long time as human beings
00:05:11 after we’re born to learn all the things
00:05:14 that we have to learn to have the adult brain.
00:05:17 It’s actually 20 years, think about it.
00:05:20 From when a baby is born to when a teenager
00:05:23 goes through puberty to adults, it’s a long time.
00:05:27 Do you think you can maybe talk through
00:05:30 the first few months and then on to the first 20 years
00:05:35 and then for the rest of their lives?
00:05:37 What is the development of the human brain look like?
00:05:41 What are the different stages?
00:05:42 Yeah, at the beginning, you have to build a brain, right?
00:05:46 And the brain is made of cells.
00:05:48 What’s the very beginning?
00:05:49 Which beginning are we talking about?
00:05:52 In the embryo, as the embryo is developing in the womb,
00:05:56 in addition to making all of the other tissues
00:05:58 of the embryo, the muscle, the heart, the blood,
00:06:02 the embryo is also building the brain.
00:06:04 And it builds from a very simple structure
00:06:08 called the neural tube, which is basically nothing
00:06:11 but a tube of cells that spans sort of the length
00:06:14 of the embryo from the head all the way to the tail,
00:06:18 let’s say, of the embryo.
00:06:20 And then over in human beings, over many months of gestation
00:06:25 from that neural tube, which contains stem cell
00:06:30 like cells of the brain, you will make many, many
00:06:35 other building blocks of the brain.
00:06:36 So all of the other cell types, because there are many,
00:06:40 many different types of cells in the brain
00:06:43 that will form specific structures of the brain.
00:06:46 So you can think about embryonic development of the brain
00:06:49 as just the time in which you are making
00:06:51 the building blocks, the cells.
00:06:54 Are the stem cells relatively homogeneous, like uniform,
00:06:57 or are they all different types?
00:06:59 It’s a very good question.
00:07:00 It’s exactly how it works.
00:07:01 You start with a more homogeneous,
00:07:04 perhaps more multipotent type of stem cell.
00:07:09 With multipotent.
00:07:10 With multipotent it means that it has the potential
00:07:13 to make many, many different types of other cells.
00:07:17 And then with time, these progenitors become
00:07:20 more heterogeneous, which means more diverse.
00:07:22 There are gonna be many different types of the stem cells.
00:07:26 And also they will give rise to progeny to other cells
00:07:30 that are not stem cells, that are specific cells
00:07:32 of the brain that are very different
00:07:34 from the mother stem cell.
00:07:35 And now you think about this process of making cells
00:07:38 from the stem cells over many, many months
00:07:41 of development for humans.
00:07:43 And what you’re doing, you’re building the cells
00:07:46 that physically make the brain,
00:07:48 and then you arrange them in specific structures
00:07:52 that are present in the final brain.
00:07:55 So you can think about the embryonic development
00:07:58 of the brain as the time where you’re building the bricks,
00:08:02 you’re putting the bricks together to form buildings,
00:08:05 structures, regions of the brain.
00:08:08 And where you make the connections
00:08:10 between these many different type of cells,
00:08:13 especially nerve cells, neurons, right?
00:08:15 That transmit action potentials and electricity.
00:08:19 I’ve heard you also say somewhere, I think,
00:08:21 correct me if I’m wrong,
00:08:22 that the order of the way this builds matters.
00:08:25 Oh yes.
00:08:26 If you are an engineer and you think about development,
00:08:29 you can think of it as, well, I could also take all the cells
00:08:35 and bring them all together into a brain in the end.
00:08:38 But development is much more than that.
00:08:40 So the cells are made in a very specific order
00:08:43 that subserve the final product that you need to get.
00:08:47 And so, for example, all of the nerve cells,
00:08:49 the neurons are made first,
00:08:52 and all of the supportive cells of the neurons,
00:08:54 like the glia, is made later.
00:08:56 And there is a reason for that
00:08:58 because they have to assemble together in specific ways.
00:09:02 But you also may say, well,
00:09:03 why don’t we just put them all together in the end?
00:09:05 It’s because as they develop next to each other,
00:09:09 they influence their own development.
00:09:11 So it’s a different thing for a glia
00:09:13 to be made alone in a dish,
00:09:15 than a glia cell be made in a developing embryo
00:09:19 with all these other cells around it
00:09:21 that produce all these other signals.
00:09:23 First of all, that’s mind blowing,
00:09:25 this development process.
00:09:27 From my perspective in artificial intelligence,
00:09:29 you often think of how incredible the final product is,
00:09:33 the final product, the brain.
00:09:35 But you’re making me realize that the final product
00:09:38 is just, the beautiful thing
00:09:42 is the actual development process.
00:09:44 Do we know the code that drives that development?
00:09:51 Yeah.
00:09:52 Do we have any sense?
00:09:53 First of all, thank you for saying
00:09:55 that it’s really the formation of the brain.
00:09:59 It’s really its development.
00:10:00 It is this incredibly choreographed dance
00:10:05 that happens the same way every time
00:10:07 each one of us builds the brain, right?
00:10:10 And that builds an organ that allows us
00:10:12 to do what we’re doing today, right?
00:10:14 That is mind blowing.
00:10:16 And this is why developmental neurobiologists
00:10:18 never get tired of studying that.
00:10:21 Now you’re asking about the code.
00:10:23 What drives this?
00:10:24 How is this done?
00:10:26 Well, it’s millions of years of evolution
00:10:29 of really fine tuning gene expression programs
00:10:33 that allow certain cells to be made at a certain time
00:10:37 and to become a certain cell type,
00:10:41 but also mechanical forces of pressure bending.
00:10:47 This embryo is not just, it will not stay a tube,
00:10:50 this brain for very long.
00:10:52 At some point, this tube in the front of the embryo
00:10:54 will expand to make the primordium of the brain, right?
00:10:58 Now the forces that control that the cells feel,
00:11:02 and this is another beautiful thing,
00:11:04 the very force that they feel,
00:11:06 which is different from a week before, a week ago,
00:11:10 will tell the cell, oh, you’re being squished
00:11:12 in a certain way, begin to produce these new genes
00:11:16 because now you are at the corner
00:11:18 or you are in a stretch of cells
00:11:21 or whatever it is, and that,
00:11:23 so that mechanical physical force
00:11:26 shapes the fate of the cell as well.
00:11:29 So it’s not only chemical, it’s also mechanical.
00:11:32 So from my perspective,
00:11:34 biology is this incredibly complex mess, gooey mess.
00:11:40 So you’re saying mechanical forces.
00:11:43 How different is like a computer
00:11:47 or any kind of mechanical machine that we humans build
00:11:52 and the biological systems?
00:11:54 Have you been,
00:11:54 because you’ve worked a lot with biological systems.
00:11:57 Are they as much of a mess as it seems
00:12:00 from a perspective of an engineer, a mechanical engineer?
00:12:03 Yeah, they are much more prone
00:12:08 to taking alternative routes, right?
00:12:11 So if you, we go back to printing a brain
00:12:16 versus developing a brain,
00:12:18 of course, if you print a brain,
00:12:20 given that you start with the same building blocks,
00:12:23 the same cells,
00:12:23 you could potentially print it the same way every time,
00:12:28 but that final brain may not work the same way
00:12:32 as a brain built during development does
00:12:34 because the very same building blocks that you’re using
00:12:38 developed in a completely different environment, right?
00:12:41 It was not the environment of the brain.
00:12:43 Therefore, they’re gonna be different just by definition.
00:12:46 So if you instead use development to build,
00:12:50 let’s say a brain organoid,
00:12:52 which maybe we will be talking about in a few minutes.
00:12:55 Those things are fascinating.
00:12:56 Yes, so if you use processes of development,
00:13:01 then when you watch it,
00:13:03 you can see that sometimes things can go wrong
00:13:06 in some organoids and by wrong,
00:13:08 I mean different one organoid from the next.
00:13:10 While if you think about that embryo, it always goes right.
00:13:14 So this development, it’s for as complex as it is.
00:13:18 Every time a baby is born has, with very few exceptions,
00:13:23 so the brain is like the next baby,
00:13:26 but it’s not the same if you develop it in a dish.
00:13:31 And first of all, we don’t even develop a brain,
00:13:33 you develop something much simpler in the dish,
00:13:36 but there are more options for building things differently,
00:13:39 which really tells you that evolution
00:13:42 has played a really tight game here
00:13:48 for how in the end the brain is built in vivo.
00:13:53 So just a quick, maybe dumb question,
00:13:55 but it seems like this is not,
00:13:58 the building process is not a dictatorship.
00:14:01 It seems like there’s not a centralized,
00:14:04 like high level mechanism that says,
00:14:07 okay, this cell built itself the wrong way,
00:14:10 I’m gonna kill it.
00:14:11 It seems like there’s a really strong distributed mechanism.
00:14:15 Is that in your sense for what you mean?
00:14:18 There are a lot of possibilities, right?
00:14:20 And if you think about, for example,
00:14:23 different species building their brain,
00:14:26 each brain is a little bit different.
00:14:28 So the brain of a lizard is very different
00:14:31 from that of a chicken, from that of one of us
00:14:35 and so on and so forth and still is a brain,
00:14:38 but it was built differently starting from stem cells
00:14:43 that pretty much had the same potential,
00:14:45 but in the end, evolution builds different brains
00:14:49 in different species because that serves in a way
00:14:52 the purpose of that species
00:14:53 and the wellbeing of that organism.
00:14:56 And so there are many possibilities,
00:15:00 but then there is a way and you were talking about a code.
00:15:04 Nobody knows what the entire code of development is.
00:15:07 Of course we don’t.
00:15:08 We know bits and pieces of very specific aspects
00:15:13 of development of the brain,
00:15:14 what genes are involved to make a certain cell types,
00:15:17 how those two cells interact to make the next level structure
00:15:20 that we might know, but the entirety of it,
00:15:22 how it’s so well controlled, it’s really mind blowing.
00:15:26 So in the first two months in the embryo or whatever,
00:15:29 the first few weeks, months,
00:15:32 so yeah, the building blocks are constructed.
00:15:37 The actual, the different regions of the brain,
00:15:40 I guess in the nervous system.
00:15:42 Well, this continues way longer
00:15:44 than just the first few months.
00:15:46 So over the very first few months,
00:15:50 you build a lot of the cells,
00:15:52 but then there is continuous building of new cell types
00:15:56 all the way through birth.
00:15:58 And then even postnatally,
00:16:00 I don’t know if you’ve ever heard of myelin.
00:16:03 Myelin is this sort of insulation
00:16:06 that is built around the cables of the neurons
00:16:09 so that the electricity can go really fast from.
00:16:12 The axons, I guess they’re called.
00:16:13 The axons, they’re called axons, exactly.
00:16:15 And so as human beings,
00:16:19 we myelinate our cells postnatally.
00:16:24 A kid, a six year old kid has barely started
00:16:28 the process of making the mature oligodendrocytes,
00:16:31 which are the cells that then eventually
00:16:33 will wrap the axons into myelin.
00:16:36 And this will continue, believe it or not,
00:16:38 until we are about 25, 30 years old.
00:16:42 So there is a continuous process of maturation
00:16:45 and tweaking and additions,
00:16:47 and also in response to what we do.
00:16:51 I remember taking AP Biology in high school,
00:16:53 and in the textbook, it said that,
00:16:57 I’m going by memory here,
00:16:58 that scientists disagree on the purpose
00:17:01 of myelin in the brain.
00:17:04 Is that totally wrong?
00:17:06 So like, I guess it speeds up the,
00:17:12 okay, I might be wrong here,
00:17:13 but I guess it speeds up the electricity
00:17:14 traveling down the axon or something.
00:17:17 Yeah, so that’s the most sort of canonical,
00:17:20 and definitely that’s the case.
00:17:21 So you have to imagine an axon,
00:17:24 and you can think about it as a cable of some type
00:17:27 with electricity going through.
00:17:29 And what myelin does, by insulating the outside,
00:17:34 I should say there are tracts of myelin
00:17:36 and pieces of axons that are naked without myelin.
00:17:39 And so by having the insulation,
00:17:41 the electricity, instead of going straight
00:17:43 through the cable, it will jump
00:17:45 over a piece of myelin, right,
00:17:47 to the next naked little piece and jump again.
00:17:49 And therefore, that’s the idea that you go faster.
00:17:52 And it was always thought that in order to build
00:17:57 a big brain, a big nervous system,
00:18:00 in order to have a nervous system
00:18:03 that can do very complex type of things,
00:18:05 then you need a lot of myelin
00:18:06 because you wanna go fast with this information
00:18:09 from point A to point B.
00:18:12 Well, a few years ago, maybe five years ago or so,
00:18:16 we discovered that some of the most evolved,
00:18:19 which means the newest type of neurons that we have
00:18:23 as nonhuman primates, as human beings
00:18:25 in the top of our cerebral cortex,
00:18:28 which should be the neurons that do some
00:18:29 of the most complex things that we do,
00:18:32 well, those have axons that have very little myelin.
00:18:36 Wow.
00:18:36 And they have very interesting ways
00:18:41 in which they put this myelin on their axons.
00:18:43 You know, a little piece here,
00:18:44 then a long track with no myelin, another chunk there.
00:18:47 And some don’t have myelin at all.
00:18:49 So now, you have to explain
00:18:52 where we’re going with evolution.
00:18:57 And if you think about it,
00:18:58 perhaps as an electrical engineer,
00:19:01 when I looked at it, I initially thought,
00:19:05 and I’m a developmental neurobiologist,
00:19:06 I thought maybe this is what we see now,
00:19:10 but if we give evolution another few million years,
00:19:13 we’ll see a lot of myelin on these neurons too.
00:19:15 But I actually think now that that’s instead the future
00:19:19 of the brain.
00:19:20 Less myelin.
00:19:21 Less myelin might allow for more flexibility
00:19:24 on what you do with your axons,
00:19:26 and therefore more complicated
00:19:28 and unpredictable type of functions,
00:19:31 which is also a bit mind blowing.
00:19:33 So it seems like it’s controlling the timing of the signal.
00:19:37 So they’re in the timing, you can encode a lot of information.
00:19:42 Yeah.
00:19:43 And so the brain.
00:19:44 The timing, the chemistry of that little piece of axon,
00:19:48 perhaps it’s a dynamic process where the myelin can move.
00:19:52 Now you see how many layers of variability you can add,
00:19:57 and that’s actually really good
00:19:58 if you’re trying to come up with a new function
00:20:02 or a new capability or something unpredictable in a way.
00:20:06 So we’re gonna jump around a little bit,
00:20:08 but the old question of how much is nature
00:20:12 and how much is nurture?
00:20:14 In terms of this incredible thing
00:20:17 after the development is over,
00:20:20 we seem to be kind of somewhat smart, intelligent,
00:20:26 cognition, consciousness,
00:20:27 all of these things are just incredible,
00:20:29 ability to reason and so on emerge.
00:20:31 In your sense, how much is in the hardware,
00:20:34 in the nature and how much is in the nurture
00:20:39 is learned through with our parents
00:20:40 through interacting with the environment and so on.
00:20:42 It’s really both, right?
00:20:43 If you think about it.
00:20:45 So we are born with a brain as babies
00:20:48 that has most of its cells and most of its structures.
00:20:53 And that will take a few years to grow,
00:20:57 to add more, to be better.
00:21:00 But really then we have this 20 years
00:21:04 of interacting with the environment around us.
00:21:07 And so what that brain that was so perfectly built
00:21:10 or imperfectly built due to our genetic cues
00:21:16 will then be used to incorporate the environment
00:21:20 in its further maturation and development.
00:21:22 And so your experiences do shape your brain.
00:21:26 I mean, we know that like if you and I
00:21:29 may have had a different childhood or a different,
00:21:32 we have been going to different schools,
00:21:35 we have been learning different things
00:21:36 and our brain is a little bit different because of that.
00:21:38 We behave differently because of that.
00:21:41 And so especially postnatally
00:21:44 experience is extremely important.
00:21:46 We are born with a plastic brain.
00:21:48 What that means is a brain that is able to change
00:21:51 in response to stimuli that can be sensory.
00:21:56 So perhaps some of the most illuminating studies
00:22:01 that were done were studies in which
00:22:03 the sensory organs were not working, right?
00:22:06 Like if you are born with eyes that don’t work,
00:22:09 then your very brain, that piece of the brain
00:22:12 that normally would process vision, the visual cortex,
00:22:17 develops postnatally differently
00:22:19 and it might be used to do something different, right?
00:22:23 So that’s the most extreme.
00:22:25 The plasticity of the brain, I guess,
00:22:27 is the magic hardware that it,
00:22:29 and then it’s flexibility in all forms
00:22:32 is what enables the learning postnatally.
00:22:36 Can you talk about organoids?
00:22:39 What are they?
00:22:40 And how can you use them to help us understand the brain
00:22:44 and the development of the brain?
00:22:45 This is very, very important.
00:22:47 So the first thing I’d like to say,
00:22:49 please skip this in the video.
00:22:52 The first thing I’d like to say is that an organoid,
00:22:56 a brain organoid is not the same as a brain.
00:23:00 Okay?
00:23:01 It’s a fundamental distinction.
00:23:03 It’s a system, a cellular system
00:23:08 that one can develop in the culture dish,
00:23:12 starting from stem cells that will mimic some aspects
00:23:17 of the development of the brain, but not all of it.
00:23:21 They are very small, maximum,
00:23:23 they become about four to five millimeters in diameters.
00:23:27 They are much simpler than our brain, of course,
00:23:32 but yet they are the only system
00:23:35 where we can literally watch a process
00:23:39 of human brain development unfold.
00:23:42 And by watch, I mean, study it.
00:23:44 Remember when I told you that we can’t understand
00:23:47 everything about development in our own brain
00:23:49 by studying a mouse?
00:23:51 Well, we can’t study the actual process
00:23:53 of development of the human brain
00:23:54 because it all happens in utero.
00:23:55 So we will never have access to that process ever.
00:23:58 And therefore, this is our next best thing.
00:24:02 Like a bunch of stem cells that can be coaxed
00:24:06 into starting a process of neural tube formation.
00:24:10 Remember that tube that is made by the embryo early on.
00:24:13 And from there, a lot of the cell types
00:24:15 that are present within the brain,
00:24:19 and you can simply watch it and study,
00:24:23 but you can also think about diseases
00:24:27 where development of the brain
00:24:29 does not proceed normally, right, properly.
00:24:33 Think about neurodevelopmental diseases.
00:24:34 There are many, many different types.
00:24:37 Think about autism spectrum disorders.
00:24:39 There are also many different types of autism.
00:24:41 So there you could take a stem cell,
00:24:44 which really means either a sample of blood
00:24:46 or a sample of skin from the patient,
00:24:50 make a stem cell, and then with that stem cell,
00:24:53 watch a process of formation of a brain organ
00:24:56 or a brain organoid of that person with that genetics,
00:25:00 with that genetic code in it.
00:25:02 And you can ask, what is this genetic code doing
00:25:05 to some aspects of development of the brain?
00:25:08 And for the first time, you may come to solutions
00:25:12 like what cells are involved in autism, right?
00:25:16 So many questions around this.
00:25:17 So if you take this human stem cell
00:25:20 for that particular person with that genetic code,
00:25:23 how, and you try to build an organoid,
00:25:26 how often will it look similar?
00:25:28 What’s the, yeah, so.
00:25:31 The reproducibility?
00:25:33 Yes, or how much variability is the flip side of that?
00:25:36 Yeah, so there is much more variability
00:25:40 in building organoids than there is in building brain.
00:25:44 It’s really true that the majority of us,
00:25:47 when we are born as babies,
00:25:49 our brains look a lot like each other.
00:25:52 This is the magic that the embryo does,
00:25:54 where it builds a brain in the context of a body
00:25:57 and there is very little variability there.
00:26:01 There is disease, of course,
00:26:02 but in general, a little variability.
00:26:03 When you build an organoid,
00:26:07 we don’t have the full code for how this is done.
00:26:09 And so in part, the organoid somewhat builds itself
00:26:13 because there are some structures of the brain
00:26:15 that the cells know how to make.
00:26:18 And another part comes from the investigator,
00:26:21 the scientist adding to the media factors
00:26:26 that we know in the mouse, for example,
00:26:27 would foster a certain step of development,
00:26:30 but it’s very limited.
00:26:33 And so as a result,
00:26:36 the kind of product you get in the end
00:26:38 is much more reductionist,
00:26:39 is much more simple than what you get in vivo.
00:26:42 It mimics early events of development as of today,
00:26:46 and it doesn’t build very complex type of anatomy
00:26:49 and structure does not as of today,
00:26:52 which happens instead in vivo.
00:26:54 And also the variability that you see,
00:26:59 one organ to the next tends to be higher
00:27:02 than when you compare an embryo to the next.
00:27:05 So, okay, then the next question is,
00:27:07 how hard and maybe another flip side of that expensive
00:27:11 is it to go from one stem cell to an organoid?
00:27:14 How many can you build in like,
00:27:16 because it sounds very complicated.
00:27:18 It’s work definitely, and it’s money definitely,
00:27:23 but you can really grow a very high number
00:27:28 of these organoids, can go perhaps,
00:27:31 I told you the maximum,
00:27:32 they become about five millimeters in diameter.
00:27:35 So this is about the size of a tiny, tiny raisin,
00:27:40 or perhaps the seed of an apple.
00:27:43 And so you can grow 50 to 100 of those
00:27:47 inside one big bioreactors, which are these flasks
00:27:51 where the media provides nutrients for the organoids.
00:27:55 So the problem is not to grow more or less of them.
00:28:01 It’s really to figure out how to grow them in a way
00:28:06 that they are more and more reproducible,
00:28:08 for example, organoid to organoid,
00:28:09 so they can be used to study a biological process.
00:28:13 Because if you have too much variability,
00:28:15 then you never know if what you see
00:28:17 is just an exception or really the rule.
00:28:19 So what does an organoid look like?
00:28:22 Are there different neurons already emerging?
00:28:25 Is there, well, first, can you tell me
00:28:28 what kind of neurons are there?
00:28:29 Yes.
00:28:30 Are they sort of all the same?
00:28:35 Are they not all the same?
00:28:38 How much do we understand?
00:28:39 And how much of that variance, if any,
00:28:43 can exist in organoids?
00:28:45 Yes.
00:28:47 So you could grow,
00:28:49 I told you that the brain has different parts.
00:28:52 So the cerebral cortex is on the top part of the brain,
00:28:55 but there is another region called the striatum
00:28:57 that is below the cortex and so on and so forth.
00:28:59 All of these regions have different types of cells
00:29:03 in the actual brain, okay?
00:29:05 And so scientists have been able to grow organoids
00:29:08 that may mimic some aspects of development
00:29:11 of these different regions of the brain.
00:29:13 And so we are very interested in the cerebral cortex.
00:29:16 That’s the coolest part, right?
00:29:17 Very cool.
00:29:18 I agree with you.
00:29:20 We wouldn’t be here talking
00:29:22 if we didn’t have a cerebral cortex.
00:29:23 It’s also, I like to think, the part of the brain
00:29:26 that really truly makes us human,
00:29:27 the most evolved in recent evolution.
00:29:30 And so in the attempt to make the cerebral cortex
00:29:33 and by figuring out a way to have these organoids
00:29:37 continue to grow and develop for extended periods of times,
00:29:40 much like it happens in the real embryo,
00:29:42 months and months in culture,
00:29:44 then you can see that many different types of neurons
00:29:48 of the cortex appear.
00:29:50 And at some point, also the astrocytes,
00:29:52 so the glia cells of the cerebral cortex also appear.
00:29:57 What are these astrocytes?
00:30:00 The astrocytes are not neurons, so they’re not nerve cells,
00:30:03 but they play very important roles.
00:30:06 One important role is to support the neuron.
00:30:08 But of course, they have much more active type of roles.
00:30:11 They’re very important, for example, to make the synapses,
00:30:14 which are the point of contact and communication
00:30:17 between two neurons.
00:30:21 So all that chemistry fun happens in the synapses,
00:30:25 happens because of these cells?
00:30:28 Are they the medium in which?
00:30:29 It happens because of the interactions,
00:30:31 happens because you are making the cells
00:30:34 and they have certain properties,
00:30:36 including the ability to make neurotransmitters,
00:30:40 which are the chemicals that are secreted to the synapses,
00:30:43 including the ability of making these axons grow
00:30:46 with their growth cones and so on and so forth.
00:30:49 And then you have other cells around it
00:30:51 that release chemicals or touch the neurons
00:30:55 or interact with them in different ways
00:30:57 to really foster this perfect process,
00:30:59 in this case of synaptogenesis.
00:31:02 And this does happen within organoids.
00:31:05 So the mechanical and the chemical stuff happens.
00:31:09 The connectivity between neurons,
00:31:11 this in a way is not surprising
00:31:13 because scientists have been culturing neurons forever.
00:31:18 And when you take a neuron, even a very young one,
00:31:20 and you culture it, eventually finds another cell
00:31:23 or another neuron to talk to, it will form a synapse.
00:31:26 Are we talking about mice neurons?
00:31:28 Are we talking about human neurons?
00:31:29 It doesn’t matter, both.
00:31:30 So you can culture a neuron, like a single neuron
00:31:33 and give it a little friend and it starts interacting?
00:31:37 Yes, so neurons are able to, it sounds,
00:31:41 it’s more simple than what it may sound to you.
00:31:44 Neurons have molecular properties and structural properties
00:31:48 that allow them to really communicate with other cells.
00:31:50 And so if you put not one neuron,
00:31:53 but if you put several neurons together,
00:31:55 chances are that they will form synapses with each other.
00:32:00 Okay, great.
00:32:01 So an organoid is not a brain.
00:32:03 No.
00:32:04 But there’s some, it’s able to,
00:32:09 especially what you’re talking about,
00:32:10 mimics some properties of the cerebral cortex, for example.
00:32:15 So what can you understand about the brain
00:32:17 by studying an organoid of a cerebral cortex?
00:32:21 I can literally study all this incredible diversity
00:32:25 of cell type, all these many, many different classes
00:32:28 of cells, how are they made?
00:32:30 How do they look like?
00:32:32 What do they need to be made properly?
00:32:34 And what goes wrong if now the genetics of that stem cell
00:32:39 that I used to make the organoid came from a patient
00:32:42 with a neurodevelopmental disease?
00:32:44 Can I actually watch for the very first time
00:32:47 what may have gone wrong years before in this kid
00:32:51 when its own brain was being made?
00:32:53 Think about that loop.
00:32:54 In a way, it’s a little tiny rudimentary window
00:32:59 into the past, into the time when that brain
00:33:04 in a kid that had this neurodevelopmental disease
00:33:07 was being made.
00:33:10 And I think that’s unbelievably powerful
00:33:12 because today we have no idea of what cell types,
00:33:16 we barely know what brain regions
00:33:18 are affected in these diseases.
00:33:20 Now we have an experimental system
00:33:23 that we can study in the lab.
00:33:25 And we can ask, what are the cells affected?
00:33:28 When during development things went wrong?
00:33:31 What are the molecules among the many, many
00:33:34 different molecules that control brain development?
00:33:36 Which ones are the ones that really messed up here
00:33:39 and we want perhaps to fix?
00:33:42 And what is really the final product?
00:33:44 Is it a less strong kind of circuit and brain?
00:33:48 Is it a brain that lacks a cell type?
00:33:51 What is it?
00:33:52 Because then we can think about treatment
00:33:54 and care for these patients that is informed
00:33:59 rather than just based on current diagnostics.
00:34:02 So how hard is it to detect
00:34:04 through the developmental process?
00:34:06 It’s a super exciting tool
00:34:10 to see how different conditions develop.
00:34:15 How hard is it to detect that, wait a minute,
00:34:17 this is abnormal development.
00:34:20 Yeah.
00:34:21 How much signal is there?
00:34:24 How much of it is it a mess?
00:34:26 Because things can go wrong at multiple levels, right?
00:34:29 You could have a cell that is born and built
00:34:34 but then doesn’t work properly
00:34:36 or a cell that is not even born
00:34:38 or a cell that doesn’t interact with other cells differently
00:34:40 and so on and so forth.
00:34:42 So today we have technology
00:34:44 that we did not have even five years ago
00:34:47 that allows us to look for example
00:34:49 at the molecular picture of a cell,
00:34:52 of a single cell in a sea of cells with high precision.
00:34:56 And so that molecular information
00:34:58 where you compare many, many single cells
00:35:01 for the genes that they produce
00:35:03 between a control individual
00:35:06 and an individual with a neurodevelopmental disease,
00:35:10 that may tell you what is different molecularly.
00:35:13 Or you could see that some cells are not even made,
00:35:18 for example, or that the process of maturation
00:35:20 of the cells may be wrong.
00:35:22 There are many different levels here
00:35:25 and we can study the cells at the molecular level
00:35:29 but also we can use the organoids to ask questions
00:35:33 about the properties of the neurons,
00:35:35 the functional properties,
00:35:37 how they communicate with each other,
00:35:38 how they respond to a stimulus and so on and so forth.
00:35:41 And we may get an abnormalities there, right?
00:35:46 Detect those.
00:35:47 So how early is this work in the,
00:35:51 maybe in the history of science?
00:35:54 So, I mean like, so if you were to,
00:35:59 if you and I time travel a thousand years into the future,
00:36:05 organoids seem to be, maybe I’m romanticizing the notion
00:36:09 but you’re building not a brain
00:36:12 but something that has properties of a brain.
00:36:15 So it feels like you might be getting close to,
00:36:18 in the building process, to build this to understand.
00:36:23 So how far are we in this understanding
00:36:29 process of development?
00:36:31 A thousand years from now, it’s a long time from now.
00:36:34 So if this planet is still gonna be here
00:36:36 a thousand years from now.
00:36:38 So, I mean, if, you know, like they write a book,
00:36:41 obviously there’ll be a chapter about you.
00:36:43 That’s right, that science fiction book, today.
00:36:47 Yeah, today, about, I mean, I guess where
00:36:49 we really understood very little about the brain
00:36:52 a century ago, I was a big fan in high school
00:36:55 of reading Freud and so on, still am of psychiatry.
00:36:59 I would say we still understand very little
00:37:01 about the functional aspect of just,
00:37:04 but how in the history of understanding
00:37:07 the biology of the brain, the development,
00:37:09 how far are we along?
00:37:11 It’s a very good question.
00:37:12 And so this is just, of course, my opinion.
00:37:15 I think that we did not have technology
00:37:19 even 10 years ago or certainly not 20 years ago
00:37:23 to even think about experimentally investigating
00:37:27 the development of the human brain.
00:37:30 So we’ve done a lot of work in science
00:37:32 to study the brain or many other organisms.
00:37:35 Now we have some technologies which I’ll spell out
00:37:39 that allow us to actually look at the real thing
00:37:43 and look at the brain, at the human brain.
00:37:45 So what are these technologies?
00:37:46 There has been huge progress in stem cell biology.
00:37:50 The moment someone figured out how to turn a skin cell
00:37:54 into an embryonic stem cell, basically,
00:37:57 and that how that embryonic stem cell
00:38:00 could begin a process of development again
00:38:02 to, for example, make a brain,
00:38:04 there was a huge advance,
00:38:06 and in fact, there was a Nobel Prize for that.
00:38:08 That started the field, really,
00:38:10 of using stem cells to build organs.
00:38:14 Now we can build on all the knowledge of development
00:38:17 that we build over the many, many, many years
00:38:18 to say, how do we make the stem cells
00:38:20 now make more and more complex aspects
00:38:22 of development of the human brain?
00:38:25 So this field is young, the field of brain organoids,
00:38:28 but it’s moving faster.
00:38:30 And it’s moving fast in a very serious way
00:38:32 that is rooted in labs with the right ethical framework
00:38:35 and really building on solid science
00:38:40 for what reality is and what is not.
00:38:44 But it will go faster and it will be more and more powerful.
00:38:49 We also have technology that allows us
00:38:51 to basically study the properties of single cells
00:38:54 across many, many millions of single cells,
00:38:59 which we didn’t have perhaps five years ago.
00:39:02 So now with that, even an organoid
00:39:04 that has millions of cells can be profiled in a way,
00:39:08 looked at with very, very high resolution,
00:39:11 the single cell level to really understand
00:39:13 what is going on.
00:39:14 And you could do it in multiple stages of development
00:39:17 and you can build your hypothesis and so on and so forth.
00:39:20 So it’s not gonna be a thousand years.
00:39:22 It’s gonna be a shorter amount of time.
00:39:25 And I see this as sort of an exponential growth
00:39:29 of this field enabled by these technologies
00:39:33 that we didn’t have before.
00:39:34 And so we’re gonna see something transformative
00:39:36 that we didn’t see at all in the prior thousand years.
00:39:41 So I apologize for the crazy sci fi questions,
00:39:44 but the developmental process is fascinating
00:39:48 to watch and study, but how far are we away from
00:39:53 and maybe how difficult is it to build
00:39:57 not just an organoid, but a human brain from a stem cell?
00:40:02 Yeah, first of all, that’s not the goal
00:40:05 for the majority of the serious scientists
00:40:07 that work on this because you don’t have to build
00:40:12 the whole human brain to make this model useful
00:40:16 for understanding how the brain develops
00:40:17 or understanding disease.
00:40:20 You don’t have to build the whole thing.
00:40:22 So let me just comment on this, fascinating.
00:40:25 It shows to me the difference between you and I
00:40:29 as you’re actually trying to understand
00:40:31 the beauty of the human brain and to use it
00:40:34 to really help thousands or millions of people
00:40:36 with disease and so on, right?
00:40:38 From an artificial intelligence perspective,
00:40:41 we’re trying to build systems that we can put in robots
00:40:45 and try to create systems that have echoes
00:40:49 of the intelligence about reasoning about the world,
00:40:52 navigating the world.
00:40:53 It’s different objectives, I think.
00:40:56 Yeah, that’s very much science fiction.
00:40:57 Science fiction, but we operate in science fiction a little bit.
00:41:00 So on that point of building a brain,
00:41:03 even though that is not the focus or interest, perhaps,
00:41:06 of the community, how difficult is it?
00:41:08 Is it truly science fiction at this point?
00:41:11 I think the field will progress, like I said,
00:41:13 and that the system will be more and more complex
00:41:17 in a way, right?
00:41:18 But there are properties that emerge from the human brain
00:41:23 that have to do with the mind,
00:41:25 that may have to do with consciousness,
00:41:26 that may have to do with intelligence or whatever
00:41:29 that we really don’t understand
00:41:31 even how they can emerge from an actual, real brain.
00:41:35 And therefore, we can now measure or study in an organoid.
00:41:39 So I think that this field, many, many years from now,
00:41:43 may lead to the building of better neural circuits
00:41:48 that really are built out of understanding
00:41:50 of how this process really works.
00:41:52 And it’s hard to predict how complex this really will be.
00:41:57 I really don’t think we’re so far from,
00:42:00 it makes me laugh, really.
00:42:01 It’s really that far from building the human brain.
00:42:05 But you’re gonna be building something
00:42:07 that is always a bad version of it,
00:42:11 but that may have really powerful properties
00:42:14 and might be able to respond to stimuli
00:42:18 or be used in certain context.
00:42:21 And this is why I really think
00:42:23 that there is no other way to do this science,
00:42:25 but within the right ethical framework,
00:42:28 because where you’re going with this is also,
00:42:31 we can talk about science fiction and write that book,
00:42:34 and we could today,
00:42:36 but this work happens in a specific ethical framework
00:42:41 that we don’t decide just as scientists,
00:42:43 but also as a society.
00:42:44 So the ethical framework here is a fascinating one,
00:42:48 is a complicated one.
00:42:49 Yes.
00:42:51 Do you have a sense, a grasp
00:42:53 of how we think about ethically of building organoids
00:43:00 from human stem cells to understand the brain?
00:43:04 It seems like a tool
00:43:06 for helping potentially millions of people cure diseases
00:43:11 or at least start the cure by understanding it.
00:43:14 But is there more, is there gray areas
00:43:17 that we have to think about ethically?
00:43:22 Absolutely.
00:43:23 We must think about that.
00:43:25 Every discussion about the ethics of this
00:43:29 needs to be based on actual data
00:43:32 from the models that we have today
00:43:34 and from the ones that we will have tomorrow.
00:43:36 So it’s a continuous conversation.
00:43:37 It’s not something that you decide now.
00:43:39 Today, there is no issue really.
00:43:42 Very simple models that clearly can help you in many ways
00:43:47 without much think about,
00:43:49 but tomorrow we need to have another conversation
00:43:52 and so on and so forth.
00:43:53 And so the way we do this
00:43:54 is to actually really bring together constantly
00:43:57 a group of people that are not only scientists,
00:44:00 but also bioethicists, the lawyers, philosophers,
00:44:03 psychiatrists and so on,
00:44:04 psychologists and so on and so forth
00:44:06 to decide as a society really what we should
00:44:13 and what we should not do.
00:44:15 So that’s the way to think about the ethics.
00:44:17 Now, I also think though, that as a scientist,
00:44:21 I have a moral responsibility.
00:44:23 So if you think about how transformative it could be
00:44:29 for understanding and curing a neuropsychiatric disease,
00:44:34 to be able to actually watch and study
00:44:37 and treat with drugs the very brain
00:44:40 of the patient that you are trying to study.
00:44:43 How transformative at this moment in time this could be.
00:44:47 We couldn’t do it five years ago,
00:44:48 we could do it now, right?
00:44:50 If we didn’t do it.
00:44:51 Taking a stem cell of a particular patient.
00:44:52 Patient and make an organoid for a simple
00:44:56 and different from the human brain,
00:44:58 it still is his process of brain development
00:45:02 with his or her genetics.
00:45:04 And we could understand perhaps what is going wrong.
00:45:08 Perhaps we could use as a platform,
00:45:09 as a cellular platform to screen for drugs,
00:45:12 to fix a process and so on and so forth, right?
00:45:15 So we could do it now, we couldn’t do it five years ago.
00:45:18 Should we not do it?
00:45:20 What is the downside of doing it?
00:45:24 I don’t see a downside at this very moment.
00:45:27 If we invited a lot of people,
00:45:30 I’m sure there would be somebody who would argue against it.
00:45:33 What would be the devil’s advocate argument?
00:45:37 Yeah, yeah.
00:45:39 So it’s exactly perhaps what you alluded at
00:45:42 with your question,
00:45:44 that you are enabling some process of formation of the brain
00:45:51 that could be misused at some point,
00:45:54 or that could be showing properties
00:45:59 that ethically we don’t wanna see in a tissue.
00:46:03 So today, I repeat, today, this is not an issue.
00:46:07 And so you just gain dramatically from the science without,
00:46:11 because the system is so simple and so different
00:46:15 in a way from the actual brain.
00:46:17 But because it is the brain,
00:46:19 we have an obligation to really consider all of this, right?
00:46:23 And again, it’s a balanced conversation
00:46:27 where we should put disease and betterment of humanity
00:46:30 also on that plate.
00:46:32 What do you think, at least historically,
00:46:35 there was some politicization,
00:46:37 politicization of embryonic stem cells,
00:46:44 a stem cell research.
00:46:46 Do you still see that out there?
00:46:49 Is that still a force that we have to think about,
00:46:53 especially in this larger discourse
00:46:55 that we’re having about the role of science
00:46:57 in at least American society?
00:47:00 Yeah, this is a very good question.
00:47:03 It’s very, very important.
00:47:04 I see a very central role for scientists
00:47:08 to inform decisions about what we should
00:47:12 or should not do in society.
00:47:14 And this is because the scientists
00:47:16 have the firsthand look and understanding
00:47:20 of really the work that they are doing.
00:47:23 And again, this varies depending on
00:47:26 what we’re talking about here.
00:47:27 So now we’re talking about brain organoids.
00:47:31 I think that the scientists need to be part
00:47:33 of that conversation about what is,
00:47:36 will be allowed in the future
00:47:37 or not allowed in the future to do with the system.
00:47:40 And I think that is very, very important
00:47:43 because they bring the reality of data to the conversation.
00:47:48 And so they should have a voice.
00:47:51 So data should have a voice.
00:47:53 Data needs to have a voice.
00:47:55 Because in not only data,
00:47:57 we should also be good at communicating
00:48:01 with non scientists, the data.
00:48:04 So there has been often time,
00:48:06 there is a lot of discussion and, you know,
00:48:11 excitement and fights about certain topics
00:48:16 just because of the way they are described.
00:48:19 I’ll give you an example.
00:48:20 If I called the same cellular system
00:48:23 we just talked about a brain organoid,
00:48:27 or if I called it a human mini brain,
00:48:30 your reaction is gonna be very different to this.
00:48:34 And so the way the systems are described,
00:48:37 I mean, we and journalists alike need to be a bit careful
00:48:42 that this debate is a real debate and informed by real data.
00:48:46 That’s all I’m asking.
00:48:47 And yeah, the language matters here.
00:48:49 So I work on autonomous vehicles
00:48:51 and there the use of language
00:48:53 could drastically change the interpretation
00:48:56 and the way people feel about
00:48:58 what is the right way to proceed forward.
00:49:01 You are, as I’ve seen from a presentation, you’re a parent.
00:49:06 I saw you show a couple of pictures of your son.
00:49:09 Is it just the one?
00:49:11 Two.
00:49:12 Two.
00:49:13 Son and a daughter.
00:49:13 Son and a daughter.
00:49:14 So what have you learned from the human brain
00:49:17 by raising two of them?
00:49:20 More than I could ever learn in the lab.
00:49:24 What have I learned?
00:49:25 I’ve learned that children really have
00:49:27 these amazing plastic minds, right?
00:49:30 That we have a responsibility to, you know,
00:49:34 foster their growth in good, healthy ways.
00:49:38 That keep them curious, that keeps them adventurous,
00:49:41 that doesn’t raise them in fear of things.
00:49:45 But also respecting who they are,
00:49:47 which is in part, you know,
00:49:49 coming from the genetics we talked about.
00:49:51 My children are very different from each other
00:49:53 despite the fact that they’re the product of
00:49:55 the same two parents.
00:49:58 I also learned that what you do for them comes back to you.
00:50:03 Like, you know, if you’re a good parent,
00:50:05 you’re gonna, most of the time,
00:50:08 have, you know, perhaps a decent kids at the end.
00:50:11 So what do you think, just a quick comment,
00:50:12 what do you think is the source of that difference?
00:50:16 That’s often the surprising thing for parents.
00:50:20 Is that they can’t believe that our kids,
00:50:23 oh, they’re so different,
00:50:26 yet they came from the same parents.
00:50:28 Well, they are genetically different.
00:50:29 Even they came from the same two parents
00:50:31 because the mixing of gametes,
00:50:33 you know, we know this genetics,
00:50:35 creates every time a genetically different individual,
00:50:39 which will have a specific mix of genes
00:50:43 that is a different mix every time from the two parents.
00:50:46 And so they’re not twins.
00:50:50 They are genetically different.
00:50:52 Even just that little bit of variation,
00:50:55 because you said really from a biological perspective,
00:50:58 the brains look pretty similar.
00:51:00 Well, so let me clarify that.
00:51:02 So the genetics you have, the genes that you have,
00:51:05 that play that beautiful orchestrated symphony
00:51:08 of development, different genes
00:51:12 will play it slightly differently.
00:51:13 It’s like playing the same piece of music,
00:51:16 but with a different orchestra and a different director.
00:51:20 The music will not come out.
00:51:21 It will be still a piece by the same author,
00:51:25 but it will come out differently
00:51:27 if it’s played by the high school orchestra
00:51:28 instead of the Scala in Milan.
00:51:34 And so you are born superficially with the same brain.
00:51:39 It has the same cell types,
00:51:41 similar patterns of connectivity,
00:51:43 but the properties of the cells
00:51:45 and how the cells will then react to the environment
00:51:47 as you experience your world will be also shaped
00:51:51 by who genetically you are.
00:51:53 Speaking just as a parent,
00:51:55 this is not something that comes from my work.
00:51:56 I think you can tell at birth that these kids are different,
00:52:01 that they have a different personality in a way, right?
00:52:05 So both is needed, the genetics,
00:52:08 as well as the nurturing afterwards.
00:52:11 So you are one human with a brain,
00:52:15 sort of living through the whole mess of it,
00:52:17 the human condition, full of love, maybe fear,
00:52:21 ultimately mortal.
00:52:24 How has studying the brain changed the way you see yourself?
00:52:27 When you look in the mirror, when you think about your life,
00:52:30 the fears, the love, when you see your own life,
00:52:33 your own mortality.
00:52:34 Yeah, that’s a very good question.
00:52:38 It’s almost impossible to dissociate some time for me.
00:52:43 Some of the things we do or some of the things
00:52:46 that other people do from,
00:52:48 oh, that’s because that part of the brain
00:52:52 is working in a certain way.
00:52:54 Or thinking about a teenager,
00:52:59 going through teenage years and being at time funny
00:53:02 in the way they think.
00:53:03 And impossible for me not to think it’s because
00:53:07 they’re going through this period of time
00:53:09 called critical periods of plasticity
00:53:13 where their synapses are being eliminated here and there,
00:53:16 and they’re just confused.
00:53:17 And so from that comes perhaps a different take
00:53:22 on that behavior, or maybe I can justify it scientifically
00:53:27 in some sort of way.
00:53:29 I also look at humanity in general,
00:53:32 and I am amazed by what we can do
00:53:36 and the kind of ideas that we can come up with.
00:53:39 And I cannot stop thinking about how the brain
00:53:43 is continuing to evolve.
00:53:46 I don’t know if you do this,
00:53:47 but I think about the next brain sometimes.
00:53:49 Where are we going with this?
00:53:50 Like, what are the features of this brain
00:53:53 that evolution is really playing with
00:53:57 to get us in the future, the new brain?
00:54:02 It’s not over, right?
00:54:04 It’s a work in progress.
00:54:06 So let me just a quick comment on that.
00:54:09 Do you think there’s a lot of fascination
00:54:14 and hope for artificial intelligence
00:54:15 of creating artificial brains?
00:54:17 You said the next brain.
00:54:20 When you imagine over a period of a thousand years,
00:54:23 the evolution of the human brain,
00:54:25 do you sometimes envisioning that future
00:54:28 see an artificial one, artificial intelligence,
00:54:32 as it is hoped by many, not hoped,
00:54:34 thought by many people would be actually
00:54:37 the next evolutionary step in the development of humans?
00:54:40 Yeah, I think in a way that will happen, right?
00:54:45 It’s almost like a part of the way we evolve.
00:54:48 We evolve in the world that we created,
00:54:51 that we interact with, that shape us as we grow up
00:54:55 and so on and so forth.
00:54:58 Sometime I think about something that may sound silly,
00:55:00 but think about the use of cell phones.
00:55:04 Part of me thinks that somehow in their brain,
00:55:07 there will be a region of the cortex
00:55:09 that is attuned to that tool.
00:55:13 And this comes from a lot of studies
00:55:16 in modern organisms where really the cortex,
00:55:20 especially adapts to the kind of things you have to do.
00:55:24 So if we need to move our fingers in a very specific way,
00:55:28 we have a part of our cortex that allows us
00:55:30 to do this kind of very precise movement.
00:55:34 An owl that has to see very, very far away
00:55:36 with big eyes, the visual cortex, very big.
00:55:39 The brain attunes to your environment.
00:55:43 So the brain will attune to the technologies
00:55:47 that we will have and will be shaped by it.
00:55:51 So the cortex very well may be.
00:55:52 Will be shaped by it.
00:55:54 In artificial intelligence, it may merge with it,
00:55:57 it may get, envelop it and adjust.
00:56:01 Even if it’s not a merge of the kind of,
00:56:04 oh, let’s have a synthetic element together
00:56:06 with a biological one.
00:56:08 The very space around us, the fact, for example,
00:56:11 think about we put on some goggles of virtual reality
00:56:15 and we physically are surfing the ocean, right?
00:56:18 Like I’ve done it.
00:56:19 And you have all these emotions that come to you.
00:56:22 Your brain placed you in that reality.
00:56:27 And it was able to do it like that
00:56:29 just by putting the goggles on.
00:56:31 It didn’t take thousands of years of adapting to this.
00:56:35 The brain is plastic.
00:56:37 So adapts to new technology.
00:56:39 So you could do it from the outside
00:56:41 by simply hijacking some sensory capacities that we have.
00:56:47 So clearly over recent evolution,
00:56:51 the cerebral cortex has been a part of the brain
00:56:53 that has known the most evolution.
00:56:55 So we have put a lot of chips
00:56:58 on evolving this specific part of the brain.
00:57:02 And the evolution of cortex is plasticity.
00:57:05 It’s this ability to change in response to things.
00:57:10 So yes, they will integrate.
00:57:12 That we want it or not.
00:57:14 Well, there’s no better way to end it, Paola.
00:57:18 Thank you so much for talking today.
00:57:19 You’re very welcome.
00:57:20 This is very exciting.