WEBVTT - Ep141 "What do brains and weather systems have in common?" with Nicole Rust 0:00:05.240 --> 0:00:09.640 Does brain science need a new grand plan? Is the 0:00:09.680 --> 0:00:13.360 brain less like an assembly line and more like a 0:00:13.400 --> 0:00:16.239 weather system? And if so, what does this mean for 0:00:16.320 --> 0:00:19.960 how we might go about understanding how to think about it, 0:00:20.280 --> 0:00:23.640 and how might AI help us in the near future? 0:00:24.000 --> 0:00:25.520 And what does this have to do with how the 0:00:25.600 --> 0:00:28.240 drug riddle In got its name. Today we'll speak with 0:00:28.320 --> 0:00:31.840 scientists Nicole Rust who's been thinking about these issues. So 0:00:32.000 --> 0:00:37.560 get ready for a great brain stretch. Welcome to Inner 0:00:37.560 --> 0:00:40.879 Cosmos with me David Eagleman. I'm a neuroscientist and an 0:00:40.880 --> 0:00:44.479 author at Stanford, and in these episodes we sailed deeply 0:00:44.520 --> 0:00:48.400 into our three pound universe to understand how we see 0:00:48.440 --> 0:00:51.800 the world and for that matter, how we should view 0:00:52.040 --> 0:01:08.080 the brain. For a very long time now, neuroscience has 0:01:08.120 --> 0:01:10.160 been driven by the hope that if we could just 0:01:10.680 --> 0:01:13.959 zoom in far enough, the brain would finally give up 0:01:14.080 --> 0:01:17.600 its secrets, if we could just do one more electron 0:01:17.640 --> 0:01:22.040 microscope upgrade, or nail one more molecular pathway, or get 0:01:22.080 --> 0:01:26.680 one more brain network labeled and circled in a textbook. Now, 0:01:26.680 --> 0:01:29.880 the approach so far of gathering tons of data has 0:01:30.000 --> 0:01:35.040 delivered real triumphs. We've learned an enormous amount about how 0:01:35.080 --> 0:01:40.040 neurons fire, how circuits form, how chemicals are released and sensed, 0:01:40.560 --> 0:01:44.880 And when you flip open any modern neuroscience textbook, it 0:01:45.080 --> 0:01:50.120 really is a marvel. It's densely packed with discoveries that 0:01:50.440 --> 0:01:55.160 would have been unimaginable a generation ago. But there's an 0:01:55.240 --> 0:01:59.760 uncomfortable question hovering in the background. If we understand so 0:01:59.840 --> 0:02:02.600 much much more than we used to, why do so 0:02:02.760 --> 0:02:09.959 many neuroscience problems remain so stubbornly unsolved? Why do entire 0:02:10.160 --> 0:02:16.560 classes of brain disorders like psychiatric illness or neuroggeneration, or 0:02:16.639 --> 0:02:20.760 disorders of mood and thought continue to resist our best 0:02:20.800 --> 0:02:25.640 efforts And it feels like that's been happening decade after decade. 0:02:25.840 --> 0:02:29.640 Why does it feel sometimes like knowledge is accelerating, but 0:02:30.240 --> 0:02:35.880 meaningful clinical breakthroughs lag behind. These questions force us to 0:02:35.960 --> 0:02:39.760 ask whether the challenge lies in the way we're framing 0:02:39.800 --> 0:02:43.840 the problem. That is, maybe we should be asking whether 0:02:43.919 --> 0:02:47.840 the brain is a different kind of system than the 0:02:47.880 --> 0:02:52.920 metaphors we've relied on. We should be asking whether reductionism, 0:02:53.120 --> 0:02:56.200 which is figuring out all the pieces and parts, can 0:02:56.280 --> 0:03:00.760 ever by itself, fully explain something that evolved to be 0:03:01.320 --> 0:03:05.000 adaptive and live wired, and where you have eighty six 0:03:05.160 --> 0:03:09.880 billion neurons that are like live little creatures, moving and 0:03:09.919 --> 0:03:14.320 adjusting every moment of your life. Every scientific field eventually 0:03:14.440 --> 0:03:19.600 reaches moments like this, moments where success at one scale 0:03:20.080 --> 0:03:24.280 reveals blind spots in another. Fields reach a point where 0:03:24.320 --> 0:03:29.320 accumulating facts is no longer sufficient and what's needed instead 0:03:29.760 --> 0:03:34.760 is a rethinking of first principles. That's the moment neuroscience 0:03:34.840 --> 0:03:38.040 may be in now, and it's why I want to 0:03:38.080 --> 0:03:42.160 talk with today's guest. Nicole Rust is a neuroscientist at 0:03:42.160 --> 0:03:46.280 the University of Pennsylvania, and she has spent years thinking 0:03:46.320 --> 0:03:49.839 deeply about her experiments and data, but also, in more 0:03:49.880 --> 0:03:54.280 recent years thinking about the trajectory of the field itself, 0:03:54.720 --> 0:03:59.360 about how we got here and what assumptions we've inherited, 0:03:59.640 --> 0:04:02.440 and what kinds of questions we might have to ask 0:04:02.840 --> 0:04:05.720 if we want to move forward in a meaningful way. 0:04:06.080 --> 0:04:09.480 She's written a great book about this, called Elusive Cures. 0:04:10.120 --> 0:04:12.960 Nicole is part of a growing group of scientists who 0:04:13.000 --> 0:04:16.640 are stepping back from the daily grind of incremental results 0:04:16.839 --> 0:04:20.919 to ask a simple and hard question, what kind of 0:04:21.000 --> 0:04:24.560 thing is the brain? Really? What would it mean to 0:04:24.720 --> 0:04:28.360 study it on its own terms. So today Nicole and 0:04:28.440 --> 0:04:32.520 I sat down to talk about neuroscience at a crossroads, 0:04:32.800 --> 0:04:37.159 about complexity, what counts as an explanation, and the challenge 0:04:37.160 --> 0:04:47.719 of understanding the most intricate system we've ever encountered. Okay, So, Nicole, 0:04:47.760 --> 0:04:51.599 a few years ago you started working on this idea 0:04:51.680 --> 0:04:55.480 that we need a new grand plan in neuroscience. What 0:04:55.600 --> 0:04:56.800 led you to that conclusion? 0:04:57.240 --> 0:05:03.360 I was hearing concerns from the heads of funding agencies 0:05:04.000 --> 0:05:07.840 and elsewhere that while researchers had been discovering a lot 0:05:07.880 --> 0:05:11.240 of things about the brain, those discoveries hadn't been moving 0:05:11.320 --> 0:05:16.039 the needle in helping individuals with certain classes of disorders. 0:05:17.240 --> 0:05:20.360 So you know, one of the textbooks in our field 0:05:20.480 --> 0:05:23.279 is Principles of Neuroscience. That it just keeps getting fatter 0:05:23.320 --> 0:05:26.960 over the years, absolutely, and it always has struck us 0:05:27.040 --> 0:05:30.599 that if it really were principles, it should be getting thinner. 0:05:31.120 --> 0:05:33.680 But what we just keep doing is a dated dump 0:05:34.160 --> 0:05:36.440 of all the information we're getting. But your point is 0:05:36.760 --> 0:05:40.040 we're not seeing, Ah, here's the clear pathway to solving 0:05:40.040 --> 0:05:42.120 certain problems exactly. 0:05:41.839 --> 0:05:43.039 For certain conditions. 0:05:43.480 --> 0:05:46.839 So for some conditions we have been moving the needle 0:05:47.000 --> 0:05:50.960 quite effectively. And so those include things like new drugs 0:05:50.960 --> 0:05:55.320 from ingrained headache or insomnia, epilepsy and pain. But there 0:05:55.320 --> 0:05:58.400 are other classes of conditions that we've been more frustrated with. 0:05:58.480 --> 0:05:59.799 And so yeah, that's the big question. 0:06:00.040 --> 0:06:01.640 So one of the arguments you make in your new 0:06:01.680 --> 0:06:05.599 book is that many of the pharmaceutical treatments that we have, 0:06:05.680 --> 0:06:10.559 for example, were discovered by accidents, So things like pain 0:06:11.240 --> 0:06:14.359 or ADHD or in some cases depression. So tell us 0:06:14.400 --> 0:06:15.680 about that. What's the story there? 0:06:15.800 --> 0:06:21.320 Yes, absolutely, so those stories are wonderful, the serendipitous discoveries 0:06:21.320 --> 0:06:23.320 that happened long ago before we knew much about the 0:06:23.320 --> 0:06:27.120 brain at all. One example is the first antidepressant, which 0:06:27.279 --> 0:06:32.600 was discovered during clinical trials for the lung infecting bacteria tuberculosis. 0:06:33.000 --> 0:06:35.720 So their clinical trials for the drug for TB and 0:06:35.760 --> 0:06:38.360 what they found was the patients were joyous. There's even 0:06:38.400 --> 0:06:41.000 a picture of light in Life magazine of them dancing around. 0:06:41.000 --> 0:06:43.599 They were so happy. So they realized this chemical probably 0:06:43.600 --> 0:06:45.920 has a different purpose. They put it through clinical trials 0:06:46.160 --> 0:06:48.640 and it became our first antidepressant. 0:06:48.839 --> 0:06:50.400 And what was the name of that drug. 0:06:50.240 --> 0:06:50.960 Ipronia is it? 0:06:51.360 --> 0:06:53.400 And so that was totally an accident. 0:06:53.520 --> 0:06:54.599 It was totally an accident. 0:06:54.720 --> 0:06:57.760 And interestingly, you know the history of medical science is 0:06:57.760 --> 0:07:01.080 shot through with these sorts of accidents, really is Yeah, 0:07:01.120 --> 0:07:03.839 tell us about pain medications. 0:07:03.920 --> 0:07:08.160 Pain medications? So are opioid drugs? Those come from ancient 0:07:08.279 --> 0:07:13.400 Mesopotamia where the Mesopotamians were harvesting opium from the poppy plants. 0:07:14.040 --> 0:07:17.160 And our drugs today, like oxycodone, are just a slow 0:07:17.240 --> 0:07:21.080 release form of that drug that we harvested from opium 0:07:21.120 --> 0:07:22.360 in the early nineteen hundreds. 0:07:22.360 --> 0:07:23.760 How do they end up ingesting that? 0:07:24.000 --> 0:07:25.720 I don't know. That's a great question. 0:07:25.920 --> 0:07:26.600 That's a great question. 0:07:26.720 --> 0:07:27.840 How did they figure it out? 0:07:27.920 --> 0:07:32.160 Yeah? Yeah, yeah, okay. So and adhd M. 0:07:32.240 --> 0:07:33.760 That's another great one. Riddlin. 0:07:34.480 --> 0:07:37.560 So, Ridlin was developed in the nineteen forties by a 0:07:37.680 --> 0:07:41.440 chemist who was Swiss, and he was using a technique 0:07:41.480 --> 0:07:44.080 that we call try it and see what happens. We 0:07:44.120 --> 0:07:47.119 don't do that much anymore. But so he synthesized the drug. 0:07:47.560 --> 0:07:48.200 He liked it. 0:07:48.520 --> 0:07:52.160 He gave some to his wife. She liked it too, because. 0:07:51.920 --> 0:07:54.600 It improved her tennis game, and so he named it 0:07:54.640 --> 0:07:56.720 after her. Her name was Rita, and that's why we 0:07:56.800 --> 0:08:00.400 call it Rita Lynn. So another great story of as 0:08:00.480 --> 0:08:03.160 a drug that happened long before we understood much about 0:08:03.160 --> 0:08:05.200 the brain at all and certainly wasn't based on some 0:08:05.280 --> 0:08:07.600 big discovery about the brain that led to a new breakthrough. 0:08:07.760 --> 0:08:09.200 So there are a lot of discoveries like these. 0:08:09.280 --> 0:08:09.760 Yeah. 0:08:09.800 --> 0:08:13.080 Great. So your argument is that several of the drugs 0:08:13.120 --> 0:08:17.040 that we have were totally accidental. And when it comes 0:08:17.080 --> 0:08:21.520 to things that involve science as we typically do it, 0:08:21.520 --> 0:08:23.720 where we say hey, look here's the gene, here's the 0:08:23.760 --> 0:08:28.880 chemical involved, and so on, it's an enormous undertaking. So 0:08:29.000 --> 0:08:32.440 give us a sense of let's say, for insomnia. 0:08:32.559 --> 0:08:36.440 Yes, yes, you're right, when a new discovery leads to 0:08:36.480 --> 0:08:40.680 a new drug, those discovery stories are absolutely epic. So 0:08:40.760 --> 0:08:44.280 one example of that. A drug for insomnia is subarexcent, 0:08:45.000 --> 0:08:49.000 so superreccent. The way it works is it blocks chemicals 0:08:49.000 --> 0:08:52.720 in our brain that actually keep us awake. And so 0:08:53.000 --> 0:08:56.480 the discovery of superreccent dates back to nineteen ninety eight 0:08:56.559 --> 0:09:00.120 when brain researchers discovered these chemicals in our brain the 0:09:00.160 --> 0:09:04.840 first time. They were then linked later to insomnia via 0:09:05.240 --> 0:09:09.240 studying some dogs that had genetically inherited narcolepsy. So these 0:09:09.240 --> 0:09:11.400 dogs fall asleep spontaneously during. 0:09:11.240 --> 0:09:13.800 The day, and this was the chemical erectionin. 0:09:13.520 --> 0:09:15.160 These chemical ereccin exactly. 0:09:15.480 --> 0:09:18.280 And yeah, so they figured out this was a problem 0:09:18.320 --> 0:09:20.679 in the erecxin pathway in the brain. It was then 0:09:20.760 --> 0:09:25.120 linked to human narcilepsy. And once researchers discovered that there 0:09:25.120 --> 0:09:27.160 are these chemicals in our brain that exists to keep 0:09:27.240 --> 0:09:28.959 us awake, the assumption was that at least some of 0:09:29.080 --> 0:09:32.280 us have insomnia because these chemicals are too active. So 0:09:32.320 --> 0:09:36.000 the pharmaceutical industry went wild trying to find chemicals to 0:09:36.160 --> 0:09:39.880 block the effectiveness of these keep you awake, the erecxins 0:09:39.880 --> 0:09:42.880 in the brain. And so Mark then went through to 0:09:42.920 --> 0:09:47.280 try to find such a chemical. They screened two million 0:09:47.320 --> 0:09:49.840 different chemicals to find the right one, and once they 0:09:49.840 --> 0:09:53.080 found a chemical it was effective, they improved it even 0:09:53.160 --> 0:09:56.920 further to increase its efficacy reduce its side effects. So 0:09:57.080 --> 0:10:01.040 Whurexcin then went through clinical trials and merged in twenty 0:10:01.120 --> 0:10:04.400 fourteen as a new drug. So altogether there was a 0:10:04.480 --> 0:10:07.480 sixteen year process from the big discovery about the brain 0:10:07.920 --> 0:10:12.119 the erecsans to this new drug to block their activity. 0:10:12.400 --> 0:10:13.880 And what kind of money is involved in that? 0:10:13.960 --> 0:10:15.559 It was about a billion dollars. 0:10:15.720 --> 0:10:18.920 Yeah, and that's about as quick as has ever happened 0:10:19.040 --> 0:10:21.240 from a big discovery to a new therapy. 0:10:21.480 --> 0:10:22.760 Yeah. So it's absolutely epic. 0:10:22.960 --> 0:10:26.200 Got it. So many discoveries are accidental. Ones that aren't 0:10:26.240 --> 0:10:29.480 accidental are epic in terms of the amount of time 0:10:29.520 --> 0:10:32.000 and money they take. So where does that put us 0:10:32.240 --> 0:10:36.640 in modern neuroscience research. Let's jump to nineteen ninety eight 0:10:36.840 --> 0:10:40.920 when Eric Candell wrote a paper suggesting, look, here's the 0:10:41.000 --> 0:10:43.079 framework by which we should think about these things. 0:10:43.440 --> 0:10:43.720 Yeah. 0:10:43.960 --> 0:10:46.280 So in Eric Kendall's nineteen ninety eight paper, he was 0:10:46.280 --> 0:10:49.160 really channeling the ethos of an era of brain research 0:10:49.280 --> 0:10:53.240 that followed on excitement around two big new technologies, our 0:10:53.280 --> 0:10:57.320 ability to sequence genes and image the human brain non 0:10:57.360 --> 0:11:01.280 invasively with techniques such as functional nandecoresonance imaging. 0:11:02.080 --> 0:11:04.320 And Yeah, he laid out. 0:11:04.120 --> 0:11:09.280 A proposal of the new intellectual framework, as he called it. So, 0:11:09.480 --> 0:11:12.640 in Kendell's framework, it all begins with genes. Our genes 0:11:12.640 --> 0:11:15.079 are the code that is used to make our brain cells, 0:11:15.280 --> 0:11:18.160 which are wired into these circuits, and it's the activation 0:11:18.240 --> 0:11:20.520 of those circuits that give rise to all of mental 0:11:20.520 --> 0:11:24.520 function and in term behavior, Kendell suggested that there's one 0:11:24.600 --> 0:11:28.000 big feedback loop, so our behavior, our interactions with the 0:11:28.040 --> 0:11:30.480 world feedback to shape how our brains are wired up. 0:11:30.480 --> 0:11:31.120 That's learning. 0:11:32.120 --> 0:11:36.080 And Kendell focused on this big arrow from how the 0:11:36.080 --> 0:11:38.920 brain gives rise to the mind as the great challenge 0:11:39.240 --> 0:11:43.000 for psychologists and biologists to delineate the relationship between those 0:11:43.040 --> 0:11:43.520 two things. 0:11:43.559 --> 0:11:47.120 And the arrow is pointing from genes, two circuits exsolately, Yes, 0:11:47.120 --> 0:11:48.240 experience and behavior. 0:11:48.280 --> 0:11:51.000 Okay, so yeah, to summarize this idea about the brain 0:11:51.040 --> 0:11:52.640 and the type of thing it is, it's really set 0:11:52.720 --> 0:11:55.040 up as a big chain of causes that lead to effects. 0:11:55.880 --> 0:12:00.000 And the notion then is that when the brain becomes dysfunctional, 0:12:00.040 --> 0:12:02.559 when you have some type of disorder, it's a broken. 0:12:02.280 --> 0:12:03.000 Link in the chain. 0:12:03.160 --> 0:12:05.480 It might be a mutated gene that leads to a 0:12:05.520 --> 0:12:07.640 disorder that you might want to target with a drug, 0:12:08.000 --> 0:12:09.800 or it might be a part of the brain has 0:12:09.840 --> 0:12:12.959 aberrant activity which you could then target with stimulation. 0:12:13.640 --> 0:12:15.480 So this era of brain research I. 0:12:15.480 --> 0:12:17.959 Like to call find the broken link in the chain 0:12:18.080 --> 0:12:19.839 so we can go in and target it for a fix. 0:12:20.360 --> 0:12:23.079 And that example that we just talked about super excent 0:12:23.120 --> 0:12:25.200 it was very much of that type of find the 0:12:25.240 --> 0:12:27.199 broken link in the chain target it for a fixed 0:12:27.240 --> 0:12:44.400 type of approach that led to that big discovery. 0:12:44.600 --> 0:12:47.320 Right, So sometimes that works, and that probably felt like 0:12:47.400 --> 0:12:51.160 real progress. I'm sure when Eric Candell no Bel laureate 0:12:51.320 --> 0:12:53.760 wrote this paper in ninety eight, he felt like, Hey, 0:12:54.080 --> 0:12:58.280 we're really simplifying this and getting this straight how one 0:12:58.280 --> 0:13:01.079 thing leads to another. But when you take a look 0:13:01.160 --> 0:13:03.439 at what's going on in the field, you think that's 0:13:03.480 --> 0:13:05.079 somehow not sufficient. 0:13:05.360 --> 0:13:08.320 Absolutely so, there are certain classes of disorders that have 0:13:08.520 --> 0:13:12.760 really proven to be somewhat impenetrable using that type of 0:13:12.840 --> 0:13:16.079 find the broken link in a chain approach. What's then example, 0:13:16.280 --> 0:13:20.079 So they include our psychiatric conditions like depression and anxiety 0:13:20.200 --> 0:13:23.520 and schizophrenia. So those are all cases in which we 0:13:23.559 --> 0:13:26.560 do have therapies, but they don't work for everyone. And 0:13:26.600 --> 0:13:29.679 many of those therapies date to pre date our understanding 0:13:29.720 --> 0:13:32.960 of the brain, so they were discovered serendipitously. Also our 0:13:33.000 --> 0:13:38.040 neurodegenerative conditions like Alzheimer's and Parkinson's and als, where we 0:13:38.120 --> 0:13:41.920 do have some treatments in some cases, for example Parkinson's, 0:13:42.000 --> 0:13:44.800 but we don't have ways to slow down the degeneration 0:13:44.880 --> 0:13:47.560 that's happening in the brain that's leading to the decline. 0:13:47.720 --> 0:13:49.839 In other words, when we look at all these disorders, 0:13:49.880 --> 0:13:53.679 we think, wow, this is really somehow more complicated. And 0:13:53.720 --> 0:13:56.280 why because when we look for, let's say, a gene 0:13:56.320 --> 0:13:58.199 for schizophrenia, what do we find. 0:13:58.480 --> 0:14:03.920 Absolutely so, in the case of schizophrenia, it's very rare 0:14:04.000 --> 0:14:09.079 to have a single gene variation or mutation that leads 0:14:09.120 --> 0:14:12.800 to the disorder. More likely, well, now that we've sequenced 0:14:12.840 --> 0:14:16.280 lots of genes, we know that it's variation in hundreds 0:14:16.320 --> 0:14:19.680 of genes that are tied to the condition. So if 0:14:19.680 --> 0:14:23.000 one identical twin has schizophrenia, the chances of the other 0:14:23.080 --> 0:14:26.600 identical twin having schizophrenia they're fifty percent. It's not one 0:14:26.640 --> 0:14:29.600 hundred percent, it's fifty percent. So there is a big 0:14:29.680 --> 0:14:32.440 genetic component to all of this, but there are also 0:14:32.560 --> 0:14:36.040 environmental effects and other issues at. 0:14:35.920 --> 0:14:39.640 Play, and these intertwine in ways that are super complex. 0:14:39.880 --> 0:14:42.880 As a side note, you know, the first gene pulled 0:14:42.880 --> 0:14:45.840 for a major disease was for hunting tins and it 0:14:45.880 --> 0:14:47.840 was a gene and if you have that gene, you're 0:14:47.840 --> 0:14:49.560 going to die of hunting tins unless you dive something 0:14:49.560 --> 0:14:52.280 else first, Yes, and everyone thought this is great, We're 0:14:52.280 --> 0:14:54.440 going to figure out the gene that goes with every disease, 0:14:54.480 --> 0:14:56.640 and it turned out to be much more complicated. 0:14:56.800 --> 0:14:59.440 Yeah, And even now, thirty years later, we still don't 0:14:59.440 --> 0:15:03.240 have an effect of treatment for Huntingtons, although fingers crossed, 0:15:03.240 --> 0:15:04.640 it looks like maybe there might be one on the 0:15:04.640 --> 0:15:07.600 way in clinical trials, but it's taken over thirty years 0:15:08.120 --> 0:15:10.720 to get there, even when we knew exactly what the problem. 0:15:10.480 --> 0:15:14.800 Was, right, Okay, So but for something like schizphrenia or 0:15:14.840 --> 0:15:18.360 major depressive disorder, we're looking at something that's much more complicated. 0:15:18.360 --> 0:15:21.160 We can't even find a single gene for it. As 0:15:21.200 --> 0:15:23.600 you said, we find hundreds of genes. So where does 0:15:23.640 --> 0:15:24.280 that put us? 0:15:24.640 --> 0:15:28.400 Yeah, so I think researchers are definitely waking up to 0:15:28.440 --> 0:15:32.440 the idea that this idea about the brain as a big, 0:15:32.440 --> 0:15:35.840 long chain is probably oversimplified. The human brain is often 0:15:35.880 --> 0:15:38.680 held up as the most complex thing in the entire universe, 0:15:39.200 --> 0:15:42.440 and this chain of causes the lead to effects, it's 0:15:42.480 --> 0:15:45.920 not very complicated. So we might ask ourselves, well, what's 0:15:45.920 --> 0:15:49.840 so complicated about the brain and what are we missing 0:15:50.080 --> 0:15:50.760 in this chain? 0:15:50.880 --> 0:15:51.400 Like idea. 0:15:52.000 --> 0:15:54.280 And by the way, it still might be causes leading 0:15:54.280 --> 0:15:57.400 to effects, right, but it's the feedback loops at every 0:15:57.480 --> 0:15:58.680 stage exactly. 0:15:58.920 --> 0:16:02.640 That's the complexity that we're beginning to embrace. So causes 0:16:02.680 --> 0:16:06.200 that lead to effects that feed back on themselves as causes. 0:16:06.600 --> 0:16:08.520 The brain is not like a chain in this type 0:16:08.520 --> 0:16:10.400 of idea. It's a whole different type of thing. 0:16:10.760 --> 0:16:13.600 Right. So your analogy that you make in the book, 0:16:13.600 --> 0:16:17.440 which is wonderful, is like a weather system, right, So 0:16:17.840 --> 0:16:18.880 unpack that for us. 0:16:19.240 --> 0:16:22.200 Yes, so you can think about these complex systems that 0:16:22.240 --> 0:16:25.960 have many interdependent parts, and the weather is a terrific 0:16:26.080 --> 0:16:29.560 example of that, and you can think about when a 0:16:29.720 --> 0:16:33.160 complex system goes awry, it's a lot like a weather 0:16:33.280 --> 0:16:35.240 breaking out into a storm. 0:16:35.920 --> 0:16:36.360 Yeah. 0:16:36.760 --> 0:16:38.760 We know a lot about systems like these because we've 0:16:38.760 --> 0:16:41.640 studied them quite extensively. And one thing we know about 0:16:41.640 --> 0:16:45.520 them is they're very, very hard to perturb in ways 0:16:45.560 --> 0:16:49.760 that you would want to shift them out of their storms, 0:16:49.800 --> 0:16:51.880 which in the case of the brain, would be shifting 0:16:51.920 --> 0:16:54.240 the brain from a less healthy to a more healthy state. 0:16:54.600 --> 0:16:57.040 And one second tangent in your book, you tell us 0:16:57.040 --> 0:16:59.680 a wonderful story about Johnny von Neuman and weather I 0:16:59.800 --> 0:17:01.320 had no idea tell us then. 0:17:01.480 --> 0:17:01.920 Yeah. 0:17:02.000 --> 0:17:05.840 So in the nineteen forties, the end goal of weather 0:17:05.880 --> 0:17:09.840 research really was to control the weather. Researchers wanted to 0:17:09.880 --> 0:17:12.800 not just dissipate hurricanes, which is a worthy goal in 0:17:12.840 --> 0:17:15.160 and of itself, but they also even wanted to weaponize 0:17:15.160 --> 0:17:15.600 the weathers. 0:17:15.960 --> 0:17:17.600 This was the US government that, This was. 0:17:17.520 --> 0:17:18.240 The US government. 0:17:18.280 --> 0:17:21.200 Yeah, so they were very interested in funding weather research 0:17:21.240 --> 0:17:25.399 with that end goal. Part of von Neumann's development of 0:17:25.640 --> 0:17:30.320 the first computers was explicitly in the end goal, first 0:17:30.400 --> 0:17:32.600 predict the weather, then learn how to control it. 0:17:34.640 --> 0:17:38.720 And so researchers tried that out and it didn't work out. 0:17:38.560 --> 0:17:40.119 So well, and it still hasn't worked out. 0:17:40.240 --> 0:17:41.120 It still hasn't worked out. 0:17:41.200 --> 0:17:43.440 And why it's because the weather's so complicated. 0:17:43.520 --> 0:17:46.480 It's so complicated, and it is a system because you 0:17:46.520 --> 0:17:49.760 have these big feedback loops, right, any type of intervention 0:17:49.880 --> 0:17:53.000 you try to do will reverberate in unexpected ways, and 0:17:53.040 --> 0:17:56.160 so that's what makes these systems really really difficult to control. 0:17:56.400 --> 0:17:58.920 So when we look at something like major depressive disorder, 0:17:59.280 --> 0:18:01.520 the temptation to say, look, if we could just find 0:18:01.720 --> 0:18:04.040 the gene. There is no theugen, but if we could 0:18:04.160 --> 0:18:06.719 just do this pharmaceutical here there, we can solve this, 0:18:06.840 --> 0:18:11.320 and that has proved to be ineffective precisely because of 0:18:11.400 --> 0:18:13.520 the complexity of the system here. 0:18:13.800 --> 0:18:15.359 Yes, absolutely, and so. 0:18:15.280 --> 0:18:17.280 One example that you talked about in the book was 0:18:17.560 --> 0:18:22.480 emotions research and the one hundred years' war that's happened there. 0:18:22.520 --> 0:18:23.719 So explain to us what that is. 0:18:24.720 --> 0:18:27.880 Yes, So, our ability to understand what's happening in many 0:18:27.880 --> 0:18:31.000 of the psychiatric conditions comes down to wanting to be 0:18:31.040 --> 0:18:34.359 able to measure an emotion, say, in the brain, and 0:18:34.400 --> 0:18:36.720 that's proven to be very difficult to try to do. 0:18:37.760 --> 0:18:37.840 So. 0:18:38.000 --> 0:18:41.760 Researchers for over one hundred years have been arguing about 0:18:42.160 --> 0:18:44.919 what types of things are emotions in the brain and 0:18:44.920 --> 0:18:48.240 how are they organized. It might be that different emotions 0:18:48.320 --> 0:18:52.720 like fear and disgust and happiness, they might be organized 0:18:52.760 --> 0:18:54.720 in kind of their own little compartments in the brain, 0:18:54.840 --> 0:18:56.719 kind of like our sensory systems where we have one 0:18:56.720 --> 0:18:58.919 part of our brain for vision and another part for hearing, 0:18:59.720 --> 0:19:03.359 Or might be that they're much more intermingled in the 0:19:03.400 --> 0:19:06.800 brain such that and a lot like color vision. Right, 0:19:06.840 --> 0:19:09.680 So color vision, we have one visual system and there's 0:19:09.720 --> 0:19:13.000 a continuous space in our brain upon which we put 0:19:13.080 --> 0:19:16.960 labels like cyan and red and magenta. We don't really 0:19:17.000 --> 0:19:19.800 know how emotions are organized in our brain, whether they're 0:19:19.840 --> 0:19:24.040 more like these compartments or more continuously, but understanding that 0:19:24.160 --> 0:19:26.560 is one of the keys to trying to measure an 0:19:26.560 --> 0:19:28.320 emotion in the brain. You have to figure out where 0:19:28.359 --> 0:19:29.520 is it that you want to look and how is 0:19:29.560 --> 0:19:30.600 it going to be reflected there? 0:19:31.400 --> 0:19:34.200 Yeah, and so that's led to this one hundred years 0:19:34.240 --> 0:19:36.399 war because there are people on both sides of this argument. 0:19:36.440 --> 0:19:38.600 It's either separate or it's spectral. 0:19:38.760 --> 0:19:39.520 Absolutely, yeah. 0:19:39.560 --> 0:19:41.399 And so we're looking at things like emotions and we 0:19:41.440 --> 0:19:44.399 all want an explanation for it. But the question is 0:19:44.440 --> 0:19:46.359 what will it take for us to be able to 0:19:46.520 --> 0:19:47.560 answer something like that. 0:19:47.920 --> 0:19:52.040 It will take an appreciation that the way that emotions 0:19:52.080 --> 0:19:54.200 manifest in the brain is not going to be simple 0:19:54.240 --> 0:19:56.840 and straightforward. It's not going to be an individual neuron 0:19:57.000 --> 0:20:00.960 that's activated when we feel aggression or sadness. 0:20:01.040 --> 0:20:01.920 It's going to take. 0:20:02.320 --> 0:20:05.800 Embracing these ideas that in the brain, if brain area 0:20:05.880 --> 0:20:08.639 a sense information to b be send information back to 0:20:08.680 --> 0:20:11.680 A again, and so we expect emotions to be reflected 0:20:11.920 --> 0:20:14.919 in ways that kind of reverberate and dynamically evolve in 0:20:14.960 --> 0:20:17.240 the brain as opposed to snapshots. 0:20:16.640 --> 0:20:17.639 That you could take a picture of. 0:20:17.920 --> 0:20:20.280 That's a really simple way, and in fact, it might 0:20:20.320 --> 0:20:22.879 not even be that we can talk about in let's 0:20:22.960 --> 0:20:24.560 cut two one hundred years from now, that we can 0:20:24.560 --> 0:20:28.600 talk about area A and area B, right, because in 0:20:28.640 --> 0:20:32.480 a sense, the whole brain is spectral in the sense 0:20:32.560 --> 0:20:35.240 of you've got eighty six billion neurons that are all 0:20:35.240 --> 0:20:38.359 doing their things, but they don't have border walls between them. 0:20:38.720 --> 0:20:41.160 So what we do as neuroscientists as we say, oh, 0:20:41.200 --> 0:20:44.240 this area seems to be involved in blah, but boy, 0:20:44.359 --> 0:20:46.760 these things are spread out. 0:20:46.880 --> 0:20:47.800 How do you think about that? 0:20:47.840 --> 0:20:49.960 When you think about the brain in terms of how 0:20:50.200 --> 0:20:54.120 compartmentalized is it? How much is everything everywhere all at once? 0:20:54.680 --> 0:20:56.320 What's your take on that? You've thought a lot about it? 0:20:56.359 --> 0:20:59.159 I know, I mean, you know, so starting with the 0:20:59.200 --> 0:21:03.240 experiments of Carl Lashly whatever last century, as you all know, 0:21:04.119 --> 0:21:07.080 Lashley was trying to figure out where is a memory stored? 0:21:07.119 --> 0:21:10.040 So he trained little mice to run a maze and 0:21:10.080 --> 0:21:14.639 then he would cut parts of the brain to see, Okay, 0:21:14.680 --> 0:21:17.480 where is that memory stored? So if I take all 0:21:17.480 --> 0:21:19.399 these rats and I cut different parts. Where can I 0:21:19.400 --> 0:21:21.560 find the memory store? And what he found is that 0:21:21.920 --> 0:21:26.399 none of the experiments yielded anything because the memory is 0:21:26.400 --> 0:21:29.200 somehow stored in a distributed manner. It's more like cloud 0:21:29.240 --> 0:21:31.879 computing rather than here's my hard drive and you've just 0:21:31.920 --> 0:21:35.040 broken the hard drive. And so that was one of 0:21:35.119 --> 0:21:37.720 the first examples of Wow, we're looking at a big 0:21:37.720 --> 0:21:41.520