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It's Unexplainable. I'm Noam Hassenfeld. And I don't know how my brain works.
To be fair, it's not just me. Nobody really does. At a basic level, scientists don't really know exactly how our brains make us who we are. Things like genius or illness or creativity or schizophrenia. We know these things have to do with the brain, but there's this big question.
Could we ever see where these qualities come from in the brain? Like, could we locate them? It's a question that could transform medicine and explain a lot about human behavior. So scientists have been wrestling with it for a very long time. But they haven't all been approaching this question in the same way.
In this week's episode, our reporters Brian Resnick and Bird Pinkerton are going to tell two very different stories of how scientists have approached the mystery of the brain. There's tools that let us physically see more of the brain in better detail, and there's metaphors that change the story scientists tell about the brain.
We'll start with Brian and the story of brain tools, how each successive invention has pushed our ability to understand the brain further, but how technology on its own might just not be enough.
Yeah, there's a really long history here going back hundreds of years. Some of the earliest tools just kind of involved physically removing people's brains after they're dead, you know, and poking around and seeing what's different about them.
In the 1880s, there's this one famous example, this guy Charles Guiteau. He was the assassin who shot President Garfield. He suffered from a lot of delusions in his life that led him to this infamous shooting. And after he died, researchers harvested his brain and they really thought they could open his brain up and see where the delusions were.
I assume they didn't find the delusions in the brain? Yeah. Coteau's brain looked pretty normal. Maybe he had syphilis or something like that, but there wasn't a lot of evidence. There wasn't anything overly obvious. And
What's wild about this kind of line of work is that it kind of kept happening in weird and illicit ways. It kept cutting out more brains. Yeah, as late as the 1950s when Albert Einstein died, a doctor actually stole his brain. He collected it against Einstein's wishes. And it was kind of the same idea here. They wanted to open up Einstein's brain and see...
where the source of the genius was. Just like a big sign on the brain that says genius here. Yeah. And honestly, like Albert Einstein's brain just pretty much looks like a brain. So tool number one here is just a knife, I guess? Just like cutting up the brain and looking at it? Yeah. Gross anatomy dissection. Yeah. And I got to ask, is this essentially not working because...
Yeah. And to be clear, sometimes you can open up a brain and see physical abnormalities. You can see tumors, you can see pieces missing, and that can explain some differences between certain people. But you're totally right. Like, the brain is...
Chemistry, it's electrical, it's living. And the thought is like, if you could just watch it work in real time, then maybe you can start to see the differences between one brain and another.
So how do you do that? How do you examine a brain alive? That's the key question. And in the next few decades, a bunch of new tools popped up. There was like injecting people with radioactive dyes that would get sucked up by the brain. And then you can watch where those dyes go in a scanner. But that was invasive. You don't want to inject too much stuff into people's brains. Sure don't. And then starting in the 70s and 80s, this new tool comes along. It's called the MRI.
The Food and Drug Administration today approved a new kind of diagnostic machine that takes detailed pictures inside the body. Now, doctors will have to learn to look at the body in a completely new way. Right, MRI. So that's like the big, loud kind of
X-ray thing. What is an MRI exactly? Yeah, so MRI, magnetic resonance imaging, it's a machine that can take pictures of the soft tissues of your body. So like your gut, your kidneys, you know, as opposed to an X-ray, which is more suited to the hard tissues like bone. The scanner takes pictures by using radio waves and a powerful magnetic field, which lets doctors see right into the body's organ.
And the way that MRI works, it involves a giant magnet. And the basic story here is that the soft tissues of your body can be made to interact with a magnetic field. The machine picks up on those interactions and generates images of these soft tissues inside your body.
So that was the atmosphere. MRI as a method became hugely popular. So I spoke to Peter Banatini. He's kind of like this big deal MRI guy at the NIH, the National Institutes of Health. Actually, one of their website pages refers to him as Mr. MRI. Mr. MRI. Pretty much. Pretty much. But back in the early 90s, he was just a grad student.
I remember looking at old pictures where I'm like, wow, there's like, those clothes are like two sizes too large. At this time, Peter was also seeing, you know, what MRI can do, looking at pictures of the brain from MRI and just thinking, well, this still is kind of limited.
Right then, you know, if you looked at a scan, you wouldn't be able to tell the subject was dead or alive. It was just the anatomy. Peter and his advisor, basically, they wanted to take these still images that you get out of an MRI and make them into a movie. How would that work? What would you be taping, exactly? When your brain does any type of thinking, it needs energy. And when it needs energy, it calls out for blood. Blood has oxygen. Oxygen makes this whole thing work.
So they thought, like, you could just tweak the MRI to pick up on where the blood is flowing in your brain and take lots of pictures of that, one after the other. Making movies of the blood flow increase that occurs in the part of the brain that
That's active. You can see which areas of the brain are thinking at certain points of time, and you can pair that with like, okay, this part of the brain is thinking when someone is doing something. And so this would be functional MRI or fMRI, looking at the function of the brain. It's kind of like looking at a heart beating instead of like looking at just the anatomical heart. And I guess this fMRI movie would give doctors a lot more useful information about the brain?
Yeah, so the idea is if you can put different people in these scanners, you could then begin to map how their brains work. You can map their function. And again, the thought is here, once you develop this tool, functional MRI, maybe then you can start to see the differences in brains. Yeah, things like Alzheimer's disease.
schizophrenia, neurologic deficits like multiple sclerosis or even other psychiatric disorders like depression. Okay, so Peter had this dream of an fMRI, this sort of real-time MRI movie. Yeah. And he figured that it could answer this ultimate question, but there's no machine yet for it, right? How do you make...
a machine to take a movie of a brain. So back in the early 90s, Peter and his advisor Eric, they were one of a bunch of groups trying to make this exact thing happen. And they start off with just messing around with an MRI machine that was in their college's hospital. It was a clinical scanner, so we only had access to it in the evening. So we'd go down there at like midnight and
or night at night and work till six in the morning. And it was just us in this empty hospital. - This whole thing was like a Victorian science story. - The moon's rising. We've no time to lose. - You know, scientists working in the middle of the night on a strange new contraption to peer into like one of the darkest regions of the human soul. - The brain is useless.
We must find another brain. It was very raw. You know, we had this piece of equipment and we were doing something really weird with the scanner that most people had no idea what the heck we were doing. Fifteen minutes, the storm should be at its height. Then we'll be ready.
They had to jerry-rig this whole contraption, this wire headpiece, to get the MRI to focus on the brain, to take these images of the blood in the brain. We were building special coils out of, like, sewer pipe and wire and epoxy and sticking them on the scanner to make them perform better. And I was the first volunteer. Peter goes into the machine. He puts on this headpiece that they created.
And they turn it on. They wanted to see where the blood is flowing in his brain when he's moving his body. Eric would yell through the intercom, "Go and stop." That would be tapping my fingers. Tap him for 20 seconds, stop. And after we processed the data, we looked at it, and there it was.
It's thrilling. It was completely overwhelming and this was actually totally not evasive, using no radio tracer to eyes. You just put a person in there, have them do things and you see the brain activation. And it has always been a magical sort of thing. You look at a person's brain, it's like that's them. That's their essence.
And you see a map of what's going on in the brain, you actually are seeing a window into who they are. They're also genuinely excited because they think this is the key, or this could be the key to unlocking, you know, the great mystery, like what makes one brain different from another. They thought this could really be the tool. And there were neuroscientists who worked in the clinic who thought, oh, you know, now...
We can put individuals in the scanner and see if they have schizophrenia or really understand their disease much better at an individual subject level. Like, you know, put a person in, diagnose them.
So I feel like I know the answer to this, but did he do it? Could this new Frankenstein machine just kind of look at a brain and diagnose someone? I mean, Peter didn't solve the whole two brains problem, did he? The two brain question remains. Dang. It turns out to be much more difficult than we anticipated. But...
At the same time, it's not like the fMRI has been a complete wash. It has yielded so many insights. In the last 30 years since its debut, scientists really have been able to map the brain. They've mapped where we feel emotions, where we experience pain. An fMRI can even be trained to figure out what someone's dreaming about. It's like mind reading.
And there has even been some progress made on this two-brain question. Like, it turns out if you take, like, 100 brains with schizophrenia and kind of average them together, you can start to see which brain regions are implicated. You can start to see, like, you know, what brain networks are important for depression. You just can't necessarily see it still in an individual's brain. You can't diagnose it. So...
I mean, obviously, this is like a difficult problem. It's the question of the episode. But why is it so hard to figure this out in a single person's brain? Yeah. So once you start digging in the brain, you kind of realize how densely and possibly complex it is. And you start to realize like,
how much more epic the answer to the question has to be. Like, it's not a real simple, you know, you just put someone in a scanner and you see it. You put a person in a scanner who, let's say, has schizophrenia,
their brain might vary in a very subtle way and in a different way than maybe if you put another person who has schizophrenia in. There are some possibilities here for why you just can't see it in the scanner. And one is that the MRI just isn't precise enough. It is sensitive, but it's not...
quite sensitive, as we hoped, for pulling out these subtle differences. It's making movies of blood flow. It's not making movies of, like, how all the neurons in your brain are connected and trading information. Every little bit of blood here potentially can cover up the work of thousands of neurons.
It's kind of like when you're flying over a city in an airplane. You can see where the lights are on, but you don't know what people are doing in their houses. Yeah, I mean, it can tell you something, right? It can tell you where the people are or whether they're awake and using electricity, but it doesn't exactly tell you whether they're online or watching TV or anything else. Yeah, there's more detail in there that we just can't see. So maybe we just need to...
another piece of tech that can show us what every neuron is doing.
Yeah, that could be a way forward. Maybe this is the story we're in of inventing new tools, and we still don't know what the perfect tool is to peer into the human brain and spot all the differences. And we're still heading in the right direction, and we're not there yet, and we need that next leap forward. But it's also possible that fMRI could be the kind of final tool in this story, or it still has a bigger role to play than...
even what's happened in the last 30 years. Maybe it's already generated all the information we need, and perhaps we're just not interpreting that data right.
You can have the best data, but unless you have a model of how to make sense of the data, it doesn't mean anything. You know, this is how science progresses as well. I mean, you have, you know, people observe the stars with telescopes, but then it took somebody to actually make a model of the solar system to have insight about the solar system using these telescopes. Same thing with the brain. We have these tools,
And I think we're still catching up to really figure out what are the principles of brain function. So ultimately, it could be more than tools. It could be one further level of we need to know how to use the tools. Yes, exactly. Exactly.
After the break, it's not just tools that changed over time. It's the way scientists have thought about the problem of the brain. The stories they've told about it. The stories that have pushed us forward and sometimes held us back. Support for Unexplainable comes from Greenlight. People with kids tell me time moves a lot faster. Before you know it, your kid is all grown up. They've got their own credit card.
and they have no idea how to use it. But you can help. If you want your kids to get some financial literacy early on, you might want to try Greenlight. Greenlight is a debit card and money app that's made for families. Parents can send money to their kids, they can keep an eye on kids' spending and saving, and kids and teens can build money confidence and lifelong financial literacy skills.
Oda Sham is my colleague here at Vox, and she got a chance to try out Greenline. There are videos you can watch on how to invest money. So we took a portion of his savings to put into investing where I told him, watch the videos so that he can start learning how to invest money as well.
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The Walt Disney Company is a sprawling business. It's got movie studios, theme parks, cable networks, a streaming service. It's a lot. So it can be hard to find just the right person to lead it all. When you have a leader with the singularly creative mind and leadership that Walt Disney had, it like goes away and disappears. I mean, you can expect what will happen. The problem is Disney CEOs have trouble letting go.
After 15 years, Bob Iger finally handed off the reins in 2020. His retirement did not last long. He now has a big black mark on his legacy because after pushing back his retirement over and over again, when he finally did choose a successor, it didn't go well for anybody involved.
And of course, now there's a sort of a bake-off going on. Everybody watching, who could it be? I don't think there's anyone where it's like the obvious no-brainer. That's not the case. I'm Joe Adalian. Vulture and the Vox Media Podcast Network present Land of the Giants, The Disney Dilemma. Follow wherever you listen to hear new episodes every Wednesday. The Human Brain.
A pulpy mass of cells and fibers is the center of the network of fibers that make up... Unexplainable.
Unexplainable, we're back. In the first half of the show, Brian was talking about all the tools scientists have developed to study the brain. So scientists have gone from cutting it open and looking at it to a static image from an MRI to a movie from an fMRI. But every time they invent a new tool, they find that the goal of being able to find genius or illness somewhere specifically in the brain is
it remains persistently out of reach.
But our reporter Bird Pinkerton has a story about a totally different approach to thinking about the brain. Yeah. Hello, Noam. Hello. So as you mentioned, I read this book called The Idea of the Brain. It's by a guy named Matthew Cobb. And he points out that almost every time that researchers have made a big leap forward in sort of their understanding of the brain, it hasn't just been because the
They've gotten new tools to sort of study the brain or like some new way to collect data. It's often been because they got a new metaphor for how to think about the brain. What do you mean a new metaphor? So it's often been some sort of like new technology floating around cloud.
So things like clockwork back in like the 1700s or electricity or even computing, like these new technologies, they don't necessarily have anything directly to do with studying the brain. But they gave researchers new ideas of what the brain could be like. Like maybe the brain is like a clock.
Maybe it's like a power plant. And I talked with Matthew about a bunch of these different technologies. But I think that the clearest example for me of how a new technology really helped researchers come up with a metaphor for the brain was the telegraph.
So the telegraph is finally mastered in the middle of the 1830s and incredibly rapidly it spreads over whole continents. And virtually immediately, scientists, thinkers, they drew a parallel between those telegraph networks and the
the nervous system and the brain. This metaphor of communication, of wires, of a central place. And above all, there being this stuff in those wires, this information, news, facts, orders are going down from the centre to the periphery to make things happen. That changed very much how we see the brain.
So Matthew, how did sort of thinking of the brain like a telegraph and kind of sending signals out electrically from one point to another, how was that helpful to researchers? They looked, for example, at the structure of undersea cables that were carrying telegraph messages across the Atlantic.
and they could see that there was a central core of copper and then around it was insulation. And then they looked at neurons, at nerves, and they said, well, this is exactly the same. There's this outer sheath which seems to be insulating it. So even our understanding of the most very basic units of the nervous system began to be completely fused with our understanding of technology. And without that technology, we wouldn't have
either understood those structures and that organization in the same way, or we wouldn't have been able to do the experiments that led us to that point. Got it. So potentially sort of having this metaphor of an under-seas telegraph could have guided researchers or sort of helped them realize that the neuron has the structure that we now recognize, which is it sort of has this long axon that's covered in a sheath.
When did they get to a point when they realized, though, that maybe this telegraph metaphor was limited or wasn't actually sort of a perfect analogy for the brain? Well, the key problem with a telegraph system is that it's fixed and the wiring is
It's static. It doesn't change. You send a message from headquarters down to your branch office in some suburban place, and that's it. The message is then read out and things happen. But you can't decide to reroute that message to somewhere next door. It's fixed. You can't alter that. So what happened was that a new technology came along and people started to think, well, actually, the brain is much more like a telephone exchange because that was the next big development.
Is that like the switchboard operators with all the cables kind of plugging stuff in and out? A telephone exchange in the late 19th century consisted of a kind of a grid of slots with wires going into it. And if you wanted to telephone somebody, you'd pick up your receiver at home and a light would come on in the local exchange.
and one of the telephone operators, who would normally be a woman, would then plug a lead into your slot, because a little light would have come up, and she would then say, "What number do you want?" - What number do you want? - You would give the number you wanted to talk to. - Hi, I'd like to talk to Matthew at number 272, please. - And she would then connect that wire to the number you wanted to talk to. - Hello? - Hi, Brian. I have some questions about how the brain works. - So the key point here
is that messages can change their destination, that the wiring is flexible, that it alters depending on what you're doing. And this coincided with realization of the structure of the nervous system. These structures and their interconnections, they changed with time and they grew and our nervous systems aren't fixed.
And that is much more like a telephone exchange than it is like a telegraph system. So you've still got the idea of messages going down the wires, but now it can change, it can alter, and it's plastic rather than being fixed. Hello, what number would you like? Brian couldn't fully answer my question, so I'd like to talk to someone else. Could you switch me over to Matthew Cobb, please? I'll ask him about the next metaphor for the brain. Sure, that's an easy transfer. Next part of the episode is coming right up.
And what's after the telephone? Like, where are we now? Well, the dominant metaphor is that the brain is something like a computer. Sorry, I'm still processing what you said. It's carrying out some kind of calculation. I'm just not sure I have the bandwidth for this project. And that idea, which came into being in the 1940s and early 1950s, still dominates over 70 years on.
quick download about your findings. Dominates how we're thinking, not literally, but as a general kind of framework. I just need a minute to mentally recharge.
And how has that computer metaphor been helpful to modern researchers who are trying to investigate the brain? Well, I think it's in the overall framework, the idea that the brain is carrying out computations, that in some way it's doing some weird kind of calculations or computations about the real world and about what will happen if...
certain actions were to be taken. So it's the general suggestion that in some way, the outside world is represented inside our heads, and it's going to be represented in a kind of abstract, algorithmic way.
Are researchers literally saying, like, these neurons act as a computer? There aren't many scientists, I think, who would say literally the brain is literally like a computer with a central processing unit, with a graphics board. I mean, if I take out my graphics unit from my computer, it's just not going to have any image, whereas I may damage a particular part of my brain.
And if I'm lucky, there may be sufficient plasticity from the other parts of my brain to recover some aspects of those function. So a computer is dead and brains are alive. I mean, that's partly what's going on here. So there are distinct limits to this metaphor. And so if we're seeing the limits of this metaphor and given, as you mentioned, that we've been working with this metaphor for 70 years...
We actually talked in the first half of the show with a researcher who said essentially that we're gathering all sorts of data from fMRI, but we don't always know what to do with it. And I wonder, is that because the computer metaphor has sort of
outlived its usefulness? Is there a better metaphor out there? Well, if I knew that, I'd be very rich because I'd know what it was and I'd have made a fortune. So I'm not sure that simply saying, yeah, we need a new metaphor is going to help us. Because if we look at what's happened historically, it's kind of lagged behind technology. And
And over the last 40 or 50 years, people have repeatedly tried to do this, not deliberately saying, oh, we need a new metaphor, but they got excited about something.
So when I was an undergraduate, holograms were the big deal. People talked about the brain having holographic aspects. Now it doesn't, and people abandoned that. More recently, with the advent of cloud computing, people started to say, well, the brain's maybe a bit more like a cloud computing system. There's been no experiments that have emerged from the use of the metaphor. So
What I sense in reading the literature and in particular kind of despairing pieces by people who say, God, it's what an amazing time to be alive. You've got all these techniques. We've got this astonishing amount of data, but I don't know what to do with it.
So Bird. Hello, Noam. Ultimately, it seems like we've got these two histories of brain research. We've got the story of tools that showed us more and more detail of the brain. And then we've got this story of metaphor that allowed us to make some new conceptual leaps, like understanding that neurons are like telegraph wires or the brain is changeable like a phone system and an operator. But when you get to the end of both of these histories, you're like,
We hit a roadblock every time, right? We don't have the tool that answers all the questions and we don't seem to have a metaphor that's pushing our research forward in new ways right now. So where do we go from here?
I mean, I don't know that I have a better answer than Matthew Cobb, who has spent even more time than I have sort of focused on this. I think, you know, it's definitionally kind of unknown or unexplainable. But I do think that knowing both of these sort of different histories of how we reach these roadblocks is actually useful because to me, it does help us imagine kind of
A way forward that doesn't focus too much on needing any single new thing to make progress. Maybe the next leap doesn't require a new technological metaphor, for example. Like maybe the next great metaphor for understanding the brain comes from studying brains in other animals or even studying like weird alien slime mold intelligence like we kind of talked about last week and drawing a new metaphor from there. Or like
Maybe we do need a new tool, but the next new tool for studying the brain isn't like a tool that looks at the brain directly. Maybe it's AI and the AI can kind of like process all the fMRI data and see something in it that researchers couldn't.
The point here is that there's no one definitive story of how we've studied the brain. Like, technology isn't enough. Metaphors aren't enough on their own. Progress has never been sort of this one straight line. So similarly, there's also no one definitive future for where we might go next.
This episode was produced and reported by Brian Resnick and me, Bird Pinkerton. Noam Hassenfeld scored the episode and edited it along with Meredith Hodnot and Catherine Wells. Manning Nguyen checked the facts. Christian Ayala did our mixing and sound design. Liz Kelly Nelson is the VP of Vox Audio. And special thanks go to Russ Poldrack, Lauren Katz, Amina Alsadi, and Will Reed for their help and their time. If you
If you want more brain history, including stories about like old timey robots and the history of modern computing, stuff that we couldn't fit into this episode, Matthew Cobb's book is called The Idea of the Brain. And if you want to keep pondering the mysteries of intelligence more generally, last week's episode is all about weird goo that has math skills but does not have a brain.
And finally, if you have thoughts, please email them to us. We are at unexplainable at Vox.com. We'd love to hear from you. And if you felt perhaps like leaving us a nice review or like a five-star rating on Apple Podcast, I don't know. I do know that we would all really appreciate it. So Unexplainable is part of the Vox Media Podcast Network and we'll be out next week, but we'll be back the week after that.
