Dr. E.J. Chichilnisky: How the Brain Works, Curing Blindness & How to Navigate a Career Path

27:46That's right. And the retina is still alive. So you are in a position to shine light on it and essentially make it behave in the same way it would if it were still lining the back of a healthy alive person. That is the beauty of these experiments. So because we can keep the retina alive and happy, and because the retinal ganglion cells, the cells that are the ones that message the visual information to the brain are on the surface. We can put them right next to the electrodes and we can record their electrical activity. In other words, we record the signal that those cells would have sent to the brain if they were still in the living person.

28:24And at the same time, as you said, we can focus an image that we create on a computer display onto the retina. So we're treating the retina, if you will, as a little electronic circuit, which it almost is, honestly, delivering light to the photoreceptor cells so that they are electrically excited. And then recording the electrical activity that the retina is sending out, if you will. That allows us to study how the retina works normally. What we also do with that same electrical apparatus is turn around and pass current through those electrodes in order to see if we can activate those ganglion cells directly with no light just electrodes.

29:05Why do we do that? We do that because it allows us to design future methods of restoring vision by electrical stimulation of the retina, which we'll probably talk about in a few minutes. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens, once or usually twice a day, is that it gets to be the probiotics that I need for gut health.

29:43Our gut is very important. It's populated by gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long -term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins and minerals that make sure that all of my foundational nutritional needs are met. And it tastes great. If you'd like to try Athletic Greens, you can go to AthleticGreens .com slash Huberman. And they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road and the car on the plane, etc.

30:21And they'll give you a year supply of vitamin D3K2. Again, that's AthleticGreens .com slash Huberman to get the five free travel packs and the year supply of vitamin D3K2. Let's take this moment to talk a little bit about cell types. So you mentioned there are about 20 different types of these retinal ganglion cells, what we may refer to in brief as RGCs. So retinal ganglion cells are GCs, same thing. And as you mentioned, these cover the entire retina so that if each cell type is extracting a different set of features from the visual or motion color, specific colors, etc. That essentially no location in the world around us fails to be represented by these cells.

31:08Put differently, these cells are looking everywhere. Each cell type is looking everywhere so that if movement occurs in any region of our visual world, we are in a position to detect it. But maybe we could talk a little bit about cell types. Such an important theme in the field of neuroscience and indeed in all of biology. But it's actually not something we have talked about very much on this podcast before either in solo episodes or in guest episodes. I don't have any specific reason for that. We've talked about brain area, as prefrontal cortex, basal ganglia, anterior mentally cortex and on and on.

31:45We've talked about neural circuits. But we've never really talked about cell types. So the ganglion cells. Brother, you let me down. I'm talking about cell types. Well, but that's why you're here. That's why I'm here. That's why you're here. Tell us about cell types. How do you figure out if you have a cell type? How do you know if it's a cell type? Or, you know, is it the shape? Is it how it responds? How do you know if you have a cell type? What's this about? I want to just put in the back of this question or rather in the back of people's minds that this issue of cell types is not just an issue pertinent to the retina.

32:20This is an issue that is critical to understanding how the brain works. It's critical to understanding consciousness. I know a lot of people like what is consciousness? We're not going there just yet. But what are cell types? How do you determine if you have a cell type? And why is this so important to understanding how the brain works? Yeah. As you said, as far as we understand, every single brain circuit is full of very distinct cell types. Those cell types are distinguished by their genetic expression, their shapes and sizes, which other cells they do contact and which cells they don't contact, where they send their information to in other parts of the brain, and what they represent.

32:59And as far as we know, this is true throughout the brain. And it's true in the retina, the different ganglion cell types, retinal ganglion cell types, about 20 of them, each of which is looking at the whole visual scene, extracts different stuff. This cell type one extracts one thing, cell type two extracts something else, but they all represent the entire visual scene. But those cell types, we know from lots of beautiful work, work that you're closely connected to, and some of which you've done, those cell types have different morphology, different shapes and sizes, different patterns of gene expression, different targets in the brain.

33:34They send their outputs to different places in the brain. So really to study the retina without understanding cell types, you're kind of lost right away. You have to know what's going on with the cell types otherwise, you can't make sense of this retinal signal. The way we identify them in two ways, and they're different for different purposes. The basic way we identify the different cell types is their function, because we study their function. We study how they respond to light images, and we can clearly separate them out. And in fact, it's a simple thing to say, but it's really true. Our 512 -electrode array technology, which you've seen in our lab and stuff that we developed with collaborators about 20 years ago, was crucial for this, because with that 512 -electrode technology, we could see many cells of each type, and we could clearly parse them apart from one another.

34:23Whereas previous studies working on one cell at a time had great difficulty doing that. So with our technology, with 512 -electrode, we record hundreds of cells simultaneously. We say, oh, there's 20 of these, there are 50 of those, there are 26 of those, and here they are, and we can just set them in different bins and say, okay, this is what's present in this retina, just what the information is they're extracting. There's another purpose, again, referring forward to the neuroengineering aspect. We need to identify the cell types, not just based on what visual information they carry, but based on their electrical features, properties, electrical properties of the cells.

34:59Cells, as you know, neurons are electrical cells. They fundamentally receive and transmit electrical information, and the way that they do that has a distinctive electrical signature. That turns out to be super important for developing devices to restore vision. Could you explain how you determine what a given cell type does. It's electrical properties. Let's just draw a mental image for people. The retina is taken out of this deceased individual, put down on this bed of nails. Of electrodes, those electrodes can detect electrical signals within the ganglion cells. You are able to shine light onto the retina and see how the retinal ganglion cells respond, meaning what electrical signals they would transmit to the brain if they were still connected to a brain.

35:47They're not connected to a brain in the experiment. They're sitting there trying, but they're trying. I could imagine playing those cells a movie of, I don't know, a checkerboard going where every square on the checkerboard goes from white to black to gray. We could do that. I could play a cartoon. I could show it this year's Academy Award winner for best picture. How do you decide what to show the retina? This is a human beings retina after all. Presumably, it looked at things that are relevant to human beings until that person died. But how do you determine cell type electrical signals? If you don't know what specific things to show it, I mean, you're going to show it, I don't know, Disney movies.

36:33What do you show it?

36:38So what we show now reflects the fact that we've built up a lot of information and our work stands on the shoulders of many scientists who have studied the retina for decades to figure out what different cell types respond to. And we know that certain cell types respond primarily to increments of light. When light gets brighter than it was. So a change from a certain brightness to a higher brightness, this particular cell type fires. Another cell type fires or sends spikes to the brain when it gets darker. Some cell types respond primarily to large targets in the visual world. Other cell types respond better to small targets in the visual world.

37:21Some cell types respond to different wavelengths of light that we can identify. There are exist certain cell types that are still poorly understood that respond to movement. So we can tailor visual stimuli to types that we kind of already know about because of much preceding research. That's not actually how we do it in our experiments, for the most part. Instead, we use a very unbiased flickering checker board pattern as it turns out, which is in a really efficient unbiased way to sample many cells simultaneously. So that in a half hour of electrical recording from a retina, we can figure out what all the 512th or so cells are that we're recording and know all of their types.

38:02And the way we do that is to play essentially random garbage TV snow type image to the retina for a period of time. And determine which bits of brightening or darkening or moving or whatever in that random garbage activated this particular cell by looking at average of cross the half hour recording and saying, oh, it looks like this cell was always firing when it became bright in this region of the screen. That must be an on cell sensitive to light in this region of the screen and so on. So we have sophisticated, efficient ways of doing it, but it all comes back to these basic things about what features in the visual world tend to cause a given cell to send a signal to the brain.

38:43Yeah, that makes a lot of sense. So you take essentially what you call random garbage, um, snow, white, black and gray pixels on a screen. The retina views that and then the cells in the retina will respond every once in a while with an electrical potential. The fire as we say, spike sometimes called. And then you take sort of a forensic approach a bit later. You look back in time and you say, you know, what was the arrangement of pixels in this random garbage right before this cell fired an electrical potential? That's right. A spike. And then from that, you can reconstruct the preferred stimulus.

39:30Yeah, right. You can say, oh, this cell and cells around it seem to like motion of things going in a particular direction, for instance. And how do you know that the cell doesn't also like a bunch of other stuff that you didn't pick up on using this random garbage? Yeah, two things. Let me just say for the record, we don't record from these cells that signal motion in particular directions. They are an elusive cell type that is best understood in rodents and other creatures and not well understood in the primate, as you know, although some people are discovering potential cells of that type now have have recently discovered them.

40:12Okay. So let's say cells that respond to small spots that are red, you know, that go from dim red to bright red. Right. Yeah. So we can go through that colored TV snow and pick out the cells that responded to a transition of the kind you described from darker to lighter or from greener to redder or something like that. Cells tend to respond to transitions in the visual scene rather than static imagery. And so we can pick that stuff up. But you ask the question, well, G is the TV snow going to capture everything about what these cells are doing? That's a really important question that I want to just mention more.

40:53Quite likely not. That's a scientific instrument. It's an unbiased way to sample a whole bunch of cells, you know, first cut, look at, you know, generally speaking, what are they up to? But that doesn't mean we've really captured their role in natural visual perception because actually you don't go through the world perceiving visual snow. You go through the world perceiving objects and meals and mates and targets and all these things, right? So the study of how the retina responds to more naturalistic visual stimuli in my lab and in many other labs around the world is really getting off the ground now.

41:29And I would say we have limited understanding. I would say we know that our simple laboratory experiments with the TVs snow don't capture the whole story. There's more. There are about 20 different cell types in the retina. We have basic characterizations of seven of them, if you count a certain way. We know that there are another 15 or so lurking right behind the curtain that we've started to sample. We don't know what naturalistic targets they respond to in the visual life of the animal. That's work that's underway. Exciting, interesting work because this, we know that the retina, they got to be there for something.

42:10One one way to think of it, I'm pretty sure you think of it this way too, is that the retina is a highly evolved organ with a lot of evolutionary pressure for it to be efficient to have a small optic nerve sending to the brain. It's probably the case that there's no accidental stuff sitting around the retina that's vestigial and sending information to the brain. It's probably the case that those signals are all doing something important for our visual behavior, for our well -being, for our sleep, all sorts of stuff. And I think, and the field is still trying to figure that out. These are the big mysteries, I think, in terms of the retina.

42:46What are those signals exactly in all those different cell types? What different behaviors and aspects of our life do they control? What is the wildest cell type you've ever encountered? Like, what did it do? What did it respond to? That's what I mean when I say wildest. You know, it cells, retinal ganglion cells that respond to, you know, increasingly red portions of the visual scene or decreasingly green portions of the visual scene. Like, okay, cool. That seems cool. Like, get some, you know, around the time of Christmas that's useful. And it's useful in other days of the year as well. But, you know, given that the retina is indeed the best understood piece of the brain.

43:31And given that you have 20 cell types, 20 is in 20 million. It's, you know, it seems tractable. How it gets understanding it in its entirety or understanding them in their entirety, excuse me. One would like to know, like, what stuff is, are we paying attention to at the level of the retina? I mean, are there like spiral cells that like spiral stuff in the environment or there's cells that like emojis like what's going on in there? You spend a lot of time doing this. We do. We spend a lot of time doing this. After all, you give up two nights sleep, which is kind of incredible. I'll just do a little, take a moment here and just say, you know, for a guy that's been doing this for this long with these sleepless nights, you look pretty good.

44:12You look pretty rested. I tend to go home. I go home before the graduate students do. They stay up. They stay up. I used to stay up until my mid 40s. I was in there doing the all nighter type things. Maybe you can help me figure out my sleep patterns. But we can talk about that this episode. We talk about how to pull all nighters and still survive. We've done plenty of those. But yeah, like what's lots at stake here. There's a human retina, you know, meaning a human gave up their eyeballs to for this experiment after they died, of course. Yeah. You've got many people on this. These are these sorts of experiments are very expensive.

44:50A lot of fancy equipment, a lot of salaries to try and figure this stuff out. This is the chief mission of the National Alliance to do. There's a lot of tax dollars. Like this is in my opinion, as important as the space program, probably more important. In my opinion, you know, restoring vision to the blind. Yeah. Obviously. So what are you finding in there? Yeah. And we have the privilege of being on the front lines of that funded by the National Institute and other institutions to be out there figuring out what's going on in this human retina. I'm with you on that. So I'll tell you how we go bad at these days.

45:21There are about seven cell types that we understand pretty well what they're doing. They're, it's not, they're not complicated. They just have different properties. Color, size, this kind of thing, temporal properties, their timing of their signals. And those seven cell types, we understand pretty well. But we're trying to really nail down the details. Why? Because of neuroengineering for vision restoration. Then there's another, I'm going to say 15 or so. And we end the anatomist, the people who study the shapes and sizes of the cells have long known that there were more cell types lurking in the retinal circuitry, but their function has not been known.

45:56And because we didn't have many recordings from them, we didn't have electrical recordings in response to light that would tell us what they naturally do. We've actually had a breakthrough in the last few years, led by a senior researcher in my lab named Alexandra Kling, who has figured out that there's another 15 or so cell types lurking in those recordings that if we look more carefully, they're there. And they have crazy properties. And so the crazy properties I can tell you about have to do with the spatial region of the visual world that they respond to. The well -known cell types that you know and I know from the textbooks kind of respond to a circular spot in the visual world.

46:37If there's light in this little circular area, they'll fire a spike. If there's no light there, they don't care. Well, okay, some cells is not quite circular. Some cells respond to the light that's there and the difference from the light that's around it. So if it's brighter than the light that's nearby, then you get a big response. The new cell types are more puzzling than that. Some of them respond to three or four blobs in the visual world. That's kind of strange, unexpected, definitely unexpected based on the textbooks. And the newest ones are weirder yet. Some of them, their visual response profiles, that is the region of the visual world that they are sensitive to light in, almost has a spidery shape, almost like the dendrites of a cell, like the processes of a cell.

47:25And some of them have blobby light sensitivity. They're sensitive to light increments here and decrements there and increments here and decrements there and some blue light over here and blue light over here. We don't understand these cells. To be clear, the seven that we understand reasonably well, I'm not trying to just pin down and really nail for vision restoration, the sort of first cut at cell type specific vision restoration. Those ones don't have these weird properties. They're just working out all the details of the timing of their responses and all that. These new ones, we don't know what's going on with them.

48:01So we're doing experiments. Those seven cell types constitute maybe 70 % of all the neurons that send visual information from the eye to the brain. So we think it's a really solid target for vision restoration to work with the simple ones. And so when I say that I think that the retina is the best understood circuit in the nervous system, I'm talking about those seven cell types, which we know a lot about what they do. We really do know a lot. It's not done, but we know a lot. I'm not talking about the other 15 cell types, which are a minority of the population, but seem to be doing very strange and surprising things that are yet to be determined.

48:35So it's a mix. We know some really good stuff. And then there's really some deep mysteries out there about these other cell types. So we've been talking a lot about how to understand the signals that the retina is sending the brain. And I know your lab has done incredible work in this arena and figured out a number of the different signals as you describe some of the features that the different cell types are extracting just a moment ago. These blobs of different colors, etc. What good is this to the everyday person? Right? What in addition to wanting to understand how we see, what sorts of medical applications can this provide in terms of potentially restoring vision to the blind, but perhaps even larger theme is this notion of neuroengineering, right?

49:27Taking this information and creating devices that can help us help our nervous system function better, maybe even function at super physiological levels. I know there's a lot of interest in this these days. In part due to neural link, right? Because Elon's out there front facing very vocal about his vision of the nopun intended of chips being implanted in people's brains that would allow them to be in conversation with 100 people at the same time just by hearing those voices in the head, maybe filtering things out so it doesn't sound like a clamor of 100 different voices. Perhaps giving people super memory, I mean, you know, skies the limit.

50:07No one really knows where this is all headed. You're working in what we call a very constrained system where it has specific properties that you're trying to understand. And once you understand those, you can start to think about real applications of like what's possible. Like could you create a visual system that can extract more color features from the world that no other human can see? Can you restore pattern vision to somebody who is essentially blind, independent on a cane or a dog or, you know, God forbid, can't even leave their house because they can't see anything at all. You know, where is this headed?

50:40What is the information useful for? And perhaps we should frame that first within the medical rehabilitative context of repairing or restoring vision rather and then get into the more kind of sci -fi type neuroengineering stuff. Absolutely. Yeah, this really is my passion these days turning that corner, continuing to figure out the mysteries in the retina, but also saying wait a second, we actually know quite a lot about this. Shouldn't this be the first place that we can solve problems like restoring vision, restoring function or augmenting our function? I think it should be. The concept of how to do this is straightforward and not invented by us in any way.

51:23And that is the following. One of the major sources of blindness in the Western world is loss of the photoreceptor cells that capture light. Macular degeneration and red knight is pigmentosa are two well -known ailments that give rise to vision loss. And the vision loss is because the cells that capture light in the first place that we talked about earlier die off. So you're no longer sensitive to light and then you're blind. The concept is that you may be able to bypass those early sections of the retina that capture the light and process the signals and instead build an electronic implant that connects up directly to the retinal ganglion cells.

52:08And this electronic implant would do the following. It would capture the light using a camera, which is relatively easy. It would process the visual information in a manner similar to the way that the retina normally does as similar as possible. And then it would electrically activate the retinal ganglion cells by passing current and causing the ganglion cells to fire spikes and send those spikes to the brain. And if we do this really well, we can essentially replace those first two layers of the retina and piggy back on to the third layer and say, okay, we'll just jump and right into that third layer.

52:39We're going to force those ganglion cells to send reasonable visual signals to the brain. And then the brain is going to think that got a natural visual signal and proceed accordingly. That's the concept. This is not our idea. People have had this concept for decades and some people have even started to make it work in human patients. And what I mean by that is implanting electrodes on the retina, stimulating and causing people who have been profoundly blind for decades to see visual sensation, blobs and streaks of light in their visual world that are reproducible. So that's happening now. That's happened.

53:13People who were at once blind are able to see objects are able to see crude blobs and flashes of light in ways that allow them to navigate their world a little bit, a little bit avoid a coffee table. Maybe or at least see a bright window in a dark wall and be able to point to that bright window or the bright doorway in a dark wall, something like that. So it's a glass half full half empty story that I want to turn that I'd like to turn attention to in this conversation because I think it's very exciting. Yes, you can see stuff by artificially electrically stimulating the gang themselves and you can see stuff that actually helps you interact with your world a tiny little bit.

53:55So great. That's the glass half full. The glass half empty is it's nothing remotely resembling what we understand as naturalistic vision where we see spine spatial detail and color and objects and can navigate complex environments and all that stuff. No chance. You can't do anything remotely like that. You can see that there's a bright doorway over that way and turn toward it which is a helpful step in your human experience, but there's a long way to go. So the question is why does this existing technology fail to give us high quality vision? What's needed to give us high quality vision? And this is the piece I'm really passionate about.

54:37It turns out that the devices that have been implanted in humans so far by pioneering bioengineers who did really hard stuff were fairly simple devices. That treated the retinas if it's a camera that is just a grid of pixels and they put a grid of electrodes down there and they stimulated according to the pixels in the visual world and thought well hopefully that will cause the retina to do the right thing and send a nice visual piece of visual information to the brain initiate vision. Unfortunately they left the science on the table and this is actually what I'm dedicating the next phase of my career too.

55:16Bringing the science that we know that we talked about to the table for vision engineering and in particular the fact that there are there really are 20 or so distinct cell types and they send different types of visual information to the different targets in the brain. I like to think of them a little bit as an orchestra playing a symphony. Each different cell type has its particular score. The violins do one thing. The obos do something else. It's a very organized signal coming out of the retina presenting to the brain this complex pattern of electrical activity that the brain assembles into our visual experience.

55:52Well current retinal implants unfortunately are too crude to do anything like that. The conductor has just scattered the sheet music everywhere and people are playing whatever. It's cacophony. You can maybe recognize a tune in there a little bit sometimes. Navigate toward a doorway but you're not going to get the full richness of the experience by ignoring the different cell types. I'm so passionate about this in part for reasons that a little bit are similar to your reasons for doing this kind of work that you do which I think is great. Which is I feel we have a mission to give back as scientists.

56:30To take all this stuff we've been talking about because we find it so interesting and cool and to deliver something to the society that has allowed us to explore these fascinating areas. In our case it's in the case of my lab and what we've done. It's to turn around and say wait a second. We understand that there's these different cell types. We understand a lot about what they do. None of this information appears in current rep retinal implants. Can't we do better by using the science to restore vision in a way that respects the circuitry of the retina? That's what we're trying to do. And the mismatch is intense.

57:09I told you when we were chatting before that nothing that we have learned about the retina since the founding of the National High Institute in 1968 is incorporated into the existing retinal implants. Nothing. We've learned a ton about the retina. Your research was funded by the National Institute. My research is funded by National Institute. A fantastic organization that allows us to learn all these things. How is this showing up in the neuroengineering to restore vision to people? Well, currently it's not. And so we're trying to do that. Now doing that turns out to be hard. And maybe we'll talk about that.

57:48It's a technological feat that's really challenging. You have to build a device that you can implant in a human that can recognize the distinct cell types. See where they are. Stimulate them separately from one another and conduct this orchestra to create a musical score that reasonably closely resembles the natural one. That's what we're all about doing. And as it turns out, and maybe we'll talk about that separately, that mission of being able to restore the patterns of activity that the retina normally creates also has extremely exciting spin -offs in three directions. One of them is understanding better how the brain puts the signals together.

58:31That's research for the brain. The second one is augmenting vision, creating novel types of visual sensations that weren't possible before and maybe doing something along the Elon Musk lines of delivering more visual information than was ever possible. And third, figuring out how to interface to the brain more broadly. Because as you and I know, the structure of the retina is very much representative of the structure of many brain areas. And if we're going to figure out how to interface to the visual cortex, we darn well, but are figure out how to interface to the retina first. That's what we're all about doing in my lab these days is figuring out how to do that well.

59:09That's a mixed science and engineering effort. We've done about 15 years of basic science on that. How do we stimulate cells? How do we recognize cells? How are we going to build a device that does all this and talks to the cells in this way? And I can go into lots of gory detail about it. But that's what we've been doing the basic research on. And the last few years, we've worked at Stanford with fantastic engineers from various disciplines, electrical engineers, material scientists, others to figure out how to put together the pieces and build an implant that can do this in a living human. So is the idea to build a robotic retina, to build essentially an artificial retina that could be put into the eye of a blind person or even put into the eye of a sighted person that would fundamentally change their ability to see or in the latter case enhance their ability to extract things from the visual world that they would otherwise not be able to see, like seeing twice as far.

1:00:06Getting, you know, hawk -like resolution of the visual world. Yep. Which that would be cool. Yep. Could be distracting. Yep. I'm not sure I want to see the fine movements of a piece of paper and somebody's notebook from across a cafe as they flutter the pages. But you might want to for a moment. There might be a moment when you want to. And if you have an electronic device that you can control that you can dial in to sense different aspects of the visual world by your choice, you might be like, yeah, it's pretty cool. I want to be able to do that right now. There's an example I like to give, which I think maybe is helpful for interpreting what we're talking about when we say being able to do more things with the optic nerve.

1:00:47You gave the example of many voices and stuff. Here's an example that I like. We know that we can drive down the road and have a phone call, hands -free, and do that quite safely, pretty safely, right? And you're, why? Because you're tapping in, you've got two types of signals coming into your brain. Your visual signal of the car is on the freeway, anyone of which could kill you in an instant. So it's important. And the sound coming into your ears, which carries the voice of your girlfriend, that's telling you something that you're interested in hearing. And these are different parts of the brain processing this information.

1:01:23And so you can do both of these things at the same time, because there's no interference. One part of the brain's working, doing one thing, and the other parts doing something else, you're good. What you can't do is to read your texts and drive down the freeway at the same time. That's not good, because now that visual system of yours that needs to be detecting these fast -moving dangerous objects is being distracted by looking at the text, and you might die, and some other people might die with you. So a lot of people texting and driving. Yeah, that's why I like to point out this example. To remind people, you can't do it well.

1:01:53It's like, it's like, you can't do it well. You probably can't. Yeah, it used to be, you know, we'll just take a brief tangent here into this topic. A few years back, there were a lot of news articles, a lot of discussion about texting and driving, a lot of attention to getting people to stop texting and driving. I've seen a few people pulled over for texting and driving before, but I would say texting and driving is rampant. Reading what's on one's phone while driving is rampant. All you have to do is be on the freeway here in Los Angeles, look in the car next to you. Yeah, look where they're looking.

1:02:27And, bringing in texting while driving, presumably when they're doing that, they're just using their peripheral vision to detect any kind of motion, and no doubt this is cause the deaths of many people. Yeah, change lanes. Get away from them. That's just like that other driver. So here's the thing. And this is, I say there's a bit tongue in cheek, but it's sort of a real example. It may be that if we harness the different cell types in the retina, to deliver different visual information to different cell types, like the image of the text on your screen to a certain cell type that you know, the so -called midget cells, or the motion of the objects in the visual scene, the cars to a different cell type.

1:03:15The whole midget cells, by the way, folks, because they're very, very small. Yes. And by named by an atomist decades ago, so we carry that nomenclature forward. And the parasol cells, which are different cells, that you can potentially encode the movement of the cars in the parasol cells. And if those two systems are operating independently, which we sort of think they may be from research that you know very well from your extensive studies in vision, maybe we can do those two things safely at the same time. Not by the way, that's not my research goal to text and drive at the same time, just to be clear.

1:03:50But it's a very tangible real world of example of if we do really have parallel pathways that can be modulated and controlled independently of one another. This opens the door to streaming all kinds of visual information in parallel into our very high bandwidth visual systems that wasn't possible during evolution because we didn't have control over the cell types. So I think of that as the world of visual augmentation. And it starts to get interesting if the different cell types are behaving in an independent way when they transmit visual information to the brain. Now, how are we going to figure that out?

1:04:23Well, we need a device that can stimulate the different cells independently and then study that to see whether people can do this kind of thing, right? What's that device? The artificial right now, the same in plan I'm telling you about that can restore vision to people because it's an electronic device that can dial up and the activity in different cell types. That same device is what we can use as a research instrument to understand if the different pathways are parallel, if the signals interact with one another and explore how the brain receives that information. And then we can use that to explore can we augment vision and allow ourselves to have new or visual sensations that we don't even know what that would look like.

1:05:02We don't even understand what it would look like to us to see those sensations. But it might be able to deliver lots of information to our brain. And if we can do all those things, then we can take that same set of tools and engineering technologies into the brain to access different cell types as well. So to just summarize a little bit of the linear flow here of what you've done, you started off with the understanding that the neural retina is perhaps the best place to try and understand how the brain works because of its arrangement, the cell types, etc. You spend a number of decades doing these wild experiments on human retinas and other retinas, recording the different cell types with these high density, what I call bed of nails.

1:05:48Two and a half decades. That matters, EJ. And you have plenty of it. You figure out what the cell types are. So then you gained an understanding of how light is transformed into different types of electrical signals that encode different features in the visual scene. Then comes the challenge of developing neural engineering tools to try and stimulate the specific cell types in a way that more or less mimics their normal patterns of activation, like not activating a huge piece of retina so that the cells that like increases in redness are also being stimulated with the cells that like edges in a way that would create some shmooey like crazy representation of the outside world.

1:06:34No, you want the same precision that light stimulation of these cells in the intact human eye provides in this explanted retina, this retina on this bed of nails. But then a device that essentially can mimic what the retina does and you needed to do all that earlier work, understanding like what is the normal retina do? What is the healthy retina do in order to try and develop this prostate device to either restore vision or because it puts you in the position of being able to stimulate cells however you want. In theory, you could create a situation in a human where the cells that respond to I don't know, outlines of objects are hyperactive so that the person could effectively see objects in one's environment better than anyone else.

1:07:24Could perceive, I know motion is a tricky one, but motion better than anyone else could see detail in the visual world that no one else could detect. We're not talking about turning people into mantis shrimp, but the analogy works because mantis shrimp can see things that we can't and vice versa. And so what you're talking about here is neural augmentation through the use of engineering. Yep. And we often do talk about it as sci -fi because the sci -fi writers have been talking, they've been writing about this for decades. It's not sci -fi anymore. It's sci. It's straight up sci right now. It's really, we just need to build the instrumentation and start working with those experiments to figure out how to make it work.

1:08:04I think we have a responsibility to do this because this is the way we take this kind of information, all that's been learned about the visual system by the National Institute since 1968 and all the people that it's funded to do this research and turn the corner and make a difference for humanity with it. And I assume and think that humanity will be leveraged nervous system knowledge to build all sorts of devices that we can interface to the world with. I think, you know, I don't know Elon Musk, but I think he's right about that, that that's where we're headed. It should be done well. It's important to do it well.

1:08:45We will hopefully be more connected to truth in the world. You're able to build devices that give us better sensations, more acute understanding of what's going on out there, better abilities to make decisions and all that, let alone just see stuff. So that frontier of developing technologies to allow our brains and our visual systems initially and then other parts of our brains to do things better is unbelievably exciting. It is sci -fi, but I just want to emphasize, I think it's the responsible way to go to think about how to do that well. All technologies that we develop can be used for good or for real.

1:09:26And I'm sure some of your listeners who are a lot of very passionate thinking people out there thinking about neuroscience and the implications worry, what does this mean? We're going to be introducing electronic circuits and our brains to do stuff. Yeah, well, we will. We pretty much clear the humanity will do that. And so in any technology development, you have to think about, well, how do you do it well? How do you do it for good? There are popular movies right now about technology development such as understanding the structure of the atom. And that technology development can be used for good or for ill to blow up cities or to save civilizations.

1:10:03How's it going to go? Well, I think as scientists, we're responsible for advancing that in a thoughtful and meaningful way. I think we can do this in the retinue. It is the place to start. I'm curious what you think, actually, as a scientist, your background is in this field or a very close field to mine. I know you speak with all sorts of scientists on this podcast. But this is pretty much your field or very close, not the neural engineering part, but understanding the retinue. And I'm curious if you agree that this is the place to start doing this stuff. The first guest ever asked me a question on this podcast during a guest interview.

1:10:40I think this would be a fun place to both answer and riff on this a little bit because first of all, I think the retina is absolutely the place to start because we understand so much of what it does, what the cell types are. But maybe by comparison, a different brain region, the hippocampus, which is involved in the formation of memories and other stuff. But formation of memories about what one did the previous day, what one did many years ago, etc. is an area that I conversation about neural prosthetics or neuroengineering or neural augmentation comes up. People think it would be cool to have a little stimulating device in the hippocampus.

1:11:19And then if I want to remember a bunch of information from a page or from a lecture, I can just stimulate and then voila, all the information is batched in there. While that's an attractive idea, I think it's worth pointing out right now that sure there is a pretty decent understanding of the different cell types in terms of their shapes, some of their electrical properties of the hippocampus. But there is in no way, shape or form, the depth of understanding about the hippocampus and what the individual cell types do and what the different layers of it do that one has for the neural retina. So what we're really saying is if you stimulate the hippocampus, you'll likely get an effect, but it's unclear what the effect is and it's not clear how to stimulate.

1:12:03That's to me the best reason to focus on the retina because you know what the cell types are, thanks to the work of your laboratory, many other laboratories, you know what sorts of stimulation matter and it provides the perfect test bed for this whole business of neural augmentation, neural engineering. I think there's also a bigger discussion to just frame this in, which is so much of what we discuss on this podcast with guests and in solo episodes relates to things like dopamine, neuromodulator, serotonin. Everyone is interested in these things because they can profoundly change the way that we perceive and interact with the world, but one only has to look to the various pharmaceuticals that increase or decrease these neuromodulators and know that indeed those pharmaceuticals can be immensely beneficial to certain individuals.

1:12:47I want to be clear about that, but that whatever quote -unquote side effects one sees or lack of effect over time is because those receptors are like everywhere around the brain, so you can't just increase dopamine in the brain and expect to only get one specific desired effect. So the reason you're here today is not because we both worked on the retina, it's not because we happened to also be friends, it's because to my mind your laboratory represents the apex of precision in terms of trying to figure out what a given piece of the brain, in your case the neural retina does, parse all its different components and then use that knowledge to create a real world technology that can actually tickle and probe and stimulate that piece of the brain in a way that's meaningful, not just sending electrical activity in.

1:13:40That to me is so important, I think if we were going to think about levels of specificity from manipulating the human brain to get it an effect, you would say, okay, crudest would be drugs. Take a drug, increase the serotonin, which might bind to particular receptors, take the drug psilocybin, a lot of excitement about psilocybin. We know that can lead to increased connectivity between different brain regions at rest. There's probably there is some demonstrate clinical benefit, there's also some potential hazards, but it's very broad scale. We don't know what's happening when the person is thinking about a piece of moss expanding into an image and a memory of their childhood.

1:14:18It's like a million different things are happening there. And then at the other far extreme is the kind of experiment that you're talking about. Stimulating one known type of retinal cell, seeing what that means for visual processing or modeling what that means for visual processing, and then building a device that can do exactly that and then maybe ramp it up 20%, 50%. I think that represents the first step into, okay, how would you stimulate the hippocampus to create a super memory? Would you stimulate a particular cell type in a particular way? And to my knowledge, there's, you know, despite the immense excitement about the hippocampus and understandably.

1:14:59So there just isn't that precision and of understanding yet. So forgive the long answer, but you know, you asked me a question on this podcast. I love that. I can be your long answer. Yeah, and specificity is what you're talking about. And we need technology to do that, to modulate neural circuits in a highly specific way. We've got to start with the piece of the neural circuit we understand best and we have best access to. That's the retina. It's sitting right there on the surface. We can get right into it and install devices. We know so much about it. That's the place to start the place that we understand.

1:15:31Build electronics that is adaptive, but senses what circuit it's embedded in and responds appropriately. It's not just electronics you stick in there and it does something and that's it. No, it first figures out who it's talking to and then learns to speak the language of the nearby neural circuitry. So a smart device. Let's push on that a little bit. So put a little chip onto the retina that constimulates specific cell types. Is there a way that it can use AI, machine learning, that it can learn something about the tissue it happens to be in contact? Absolutely. And the simplest possible way the device works in three simple steps.

1:16:12Step number one, record electrical activity, which is what we do in our lab in a room full of equipment, but this is a two millimeter size chip implanted in your eye. Record the electrical activity. Just recognize what cells are there when they're firing, what electrical properties they have to identify the cells and cell types in this specific circuit in this human. That's step one. Step two, stimulate and record. So you figure out, oh, this electrode activates cell number 14 with 50 % probability. This electrode activates cell number 12 if you pass a microamp of current with this probability and so on.

1:16:46You make a big table that tells you how these electrodes talk to these cells in your circuit. That's step two, calibrate the stimulation by stimulation and recording. Then finally, when you have a visual image and you want to represent it in the pattern of activity of these cells, you say, okay, I know from decades of basic science what these cells ought to be doing with this image that's coming in. I know exactly what they ought to be doing. That's what the science has been telling us. We've been studying the neural code for decades to understand this. I know what they should do. Use my device with my calibration where I know where the cells are.

1:17:20I know how the electrodes talk to them and Bing, Bing, Bing, Bing activate them in the correct sequence. That's what I think of as a smart device, a device that records, stimulates them records and then finally stimulates. Yes, AI is part of that. Of course it is because this is a very complex transformation, if you will, from the external visual world to the patterns of activity of these cells. It's not easy to write down just a few lines of code or a few equations. It's complicated. And AI is really helpful for that. And learning by stimulating and recording and aggregating information quickly so that you can then use the device that's absolutely a part of the engineering.

1:17:56Let me be clear. The AI doesn't help us to understand. It's just an engineering tool that helps us to capture what this thing normally does and then go ahead and execute and make it do the thing it should normally do. I hope people will appreciate this example. Perhaps not, you know, not but goodness, I don't know, 40, 50 years ago, but still today, one treatment for depression is electric shock therapy. A very, you know, on the face of it, barbaric treatment, but effective in certain conditions, it's still used for a reason. But it can appear barbaric, right? You know, people are like a bite, bite device, you know, so they don't bite through their tongue or their lips.

1:18:41They're, you know, they're strapped down and they stimulate the whole environment. They're just like stimulate all neurons in the brain, essentially. There's a huge dump of neurotransmitters and neuromodulators. Like drugs, it's completely non -specific stimulation effectively. Probably even less specific than drugs. And yet, the clinical outcomes from electric shock therapy, in some cases are pretty impressive. Like people, the brain is quote unquote reset. They still remember who they are. But presumably through the release of neuromodulators like dopamine, serotonin, acetylcholine, in a very non -specific way, there has been some symptom relief in some cases.

1:19:25What you're you know, before I said pharmaceuticals that tickle a particular neuromodulator pathway would be the opposite. Extreme methane electric shock therapy is probably the most extreme. Where is this whole business of neural prostheses going outside of the visual system? Like right now, I can imagine that there are little stimulators in the spinal cord for sake of restoring movement to paralyze people. I realize this is not your field, but are you seeing impressive stuff there? Or is it still really, really early days? There's absolutely impressive stuff, particularly for example, people reading out signals from the motor cortex or the language cortex in order to help people to communicate or to move cursors on screens in order to interact with devices.

1:20:13These are paralyzed people. Yes, excuse me, paralyzed people who can't interact with technology the way that we do. But with their thoughts can send signals through an electronic device that can be used to control a mouse on a screen and have them connect to the internet. That's a huge deal to be able to have people do that. Imagine how life -changing would be to be able to communicate if you couldn't before. So there are wonderful examples of that. You know of them. So do I. The work of Krishna Shanoi and Jamie Henderson at Stanford is one beautiful example of the engineers. Eddie Chang doing stuff now.

1:20:47You know, Nurelink doing this kind of stuff, the built on the work of Shanoi and Henderson and stuff. So that's great. You know, stimulating in spinal circuits, as you said, for creating rhythmic movements. That's happening. So this is an enormous space. And in each case what you said, I think is really highly relevant. That electrophotic shock therapy, you can think of that as, let's say your computer is not behaving right. You can reboot it. It might work. Then it'll start not working again. Then you have to reboot it again. Well, how often do you want to reboot your computer? It gets a little inconvenience to be rebooting your computer every five minutes.

1:21:26Maybe you want to go in and actually diagnose this thing and put in a piece of software that fixes the thing that was going wrong. Instead of rebooting your computer every five minutes, right? And I think of electric shock therapy a little bit as a reboot. That's at that level. So we want to intervene more specifically. How do you do that? What you have to understand this software in order to do that, you have to have specificity controlling this thing in your computer. Not this, this, this, this, this, this particular thing that's going wrong. You got to interfere with that and change it and modulate it.

1:21:54Well, that's what understanding the neural circuit is about. That's what building specific hardware that can activate specific cells is about. That's in the case of the retina again. It's just so obvious. That it's right in front of us to do this stuff. And it's right in front of us to take us into augmentation to giving us better senses. A fun example I like. This is, it's an interesting topic because the National Institutes of Health that funds a lot of research that goes in this direction tends to not be interested in augmenting our senses. They kind of want to, they're, they draw a line more or less, it's saying, look, we're trying to restore what we were as humans, not create a new kind of human.

1:22:39And that's an interesting question because I don't think there is a fine, there's an actual line, a bright line between those things. I don't think there's a bright line between those two things. The, the finest example I know is that even in the very crudest visual restoration devices, you have to actively suppress the infrared sensitivity of your camera to not have infrared vision. Why? Because many cameras are sensitive to infrared light. So in other words, if you don't put an infrared filter in front of your camera, you're going to have some infrared vision. Maybe it won't help you very much, whatever, I'm just trying to say, as soon as you start building devices to restore sensations, building electronic devices, augmentation is right around the corner.

1:23:23It'll creep up on you real fast. So I think you can't even really draw a line. Throughout today's discussion, we've been thinking of the brain as kind of a, the rest of the brain, I should say, because the neural retinas, two pieces of the brain extruded out into the eye globes during development. I like to remind people of that over and over when you're looking at somebody's eyes, you are looking at two pieces of their brain. It's no debate about that.

1:23:53But most of the reason why you can tell so much about people's interstate from their eyes. Somebody who's sleep deprived, it's not just about the droopingness of their eyelids or the circles under their eyes. There's a, there's an aliveness to the eyes that the yogis talk about people that sort of show up at the level of their eyes as opposed to sunk back into their brain. You know, these are very kind of abstract concepts. And there's some very non -abstract stuff these days looking at looking through the eye at the retina, the way the ophthalmologist do. And there's a lot of diagnostic capability just in those images of the retina.

1:24:28Oh right. This is I'm glad you brought this up. There's some interesting and increasing evidence that looking at the neural retina, because it is a piece of the brain with neurons that have the potential to both thrive or degenerate, that looking at the neural retina, which one can do with these new technologies, can provide a window into whether or not there are forms of degeneration, such as Alzheimer's and other forms of neurodegeneration, a deeper within the brain that one can't image directly because of the thick opacity of the skull. So in other words, imaging the eye in order to determine if someone is developing Alzheimer's.

1:25:03Because you have a direct view into a little piece of the brain. It's a, it's a good signal. It can help you figure stuff out about what's going on in your brain, even beyond the sunken eyes. Absolutely. Amazing. So I think the rest of the brain pieces is also really interesting. And maybe here we can go like semi -nurrofilisophical. You know that there are clearly parts of the brain that are involved in essential what I call housekeeping functions, regulating respiration, keeping us breathing, keeping our heart beating, digestion, responding to threats in some sort of basic way, like through the secretion of adrenaline and giving us the potential to move.

1:25:41But a lot of the brain is capable of plasticity. And one wonders if you were to, for instance, develop a retinal prosthesis that would allow me to see with twice the level of detail that I currently can. Would my adult brain be capable of dealing with that information? We're talking about twice as much information coming in. Same brain tissue on the receiving end. But can it make sense of it? Do we have any idea if it can make sense of it? Are there other experiments that speak to that? Yeah, that's a fantastic and interesting question. It makes you think about neural development all over again, right?

1:26:21And I take some inspiration on that from the work of someone you know, Eric Newtson, who discovered that there is plasticity beyond the periods of time. He discovered many wonderful things, but there's plasticity well beyond the period of time that we thought that there was plasticity in certain animals. And in particular, that if you make gradual adjustments to the sensory world, you can exhibit plasticity that you can't see if you make an abrupt adjustment. So plasticity is there. It just has to be brought on by more subtle manipulations that take you from A to B and little incremental steps.

1:27:01And if you take those incremental steps, you can see the adult plasticity. So coming to your question, is the brain capable of receiving the kind of extra information we provided could be that if we just show up on day one, bam, try to deliver twice the visual resolution or whatever your visual your visual system, it could be that if we try to deliver twice the visual resolution on day one, it won't work. You'll see it'll you know, they won't look sensible to you. But if we gradually introduce it by the way that we're dialing up the resolution, we may be able to get there. And there are fascinating studies to be done.

1:27:41You think about spike timing dependent plasticity, a term that your viewers may not know, but is related to how neurons adjust their strength of connectivity to one another, according to the timing of the signals in those cells. Mechanisms like that tell us, wow, the brain really cares about the very precise timing of stuff. And to the degree that that influences the way that neurons do or don't strengthen their connections to one another, so fundamental and everything from memory to visual function would have you. This relates to fire together, wire together, although it highlights the together part, how closely in time do two neurons need to be active in order for them to subsequently increase their connectivity.

1:28:23And indeed, one of them needs to be active a little bit before the other one in order for it to work optimally. Right? So what I envision is that when we have full control of the neural code with an electronic implant that can talk to the cells and do all the things that I said, and we can really control the neural code coming out of the retina, we can then start to play games and dial up that neural code very slowly and teach the remaining brain how to understand these signals, not introduce some crazy thing from day one. No, just gradually teach. Isn't that how we do everything? Well, isn't that how plasticity works?

1:28:58I love the subtlety and the rationality of your example, because so much of what we see in the internet and on the news is like chips inserted into the brain to create super memory or conversations between 50 people at the same time without anyone speaking, just hearing other people's thoughts by way of neural signals being passed from one to the next. But yet another reason why you're here today is because you represent the the realistic grounded incremental approach to really parsing this whole thing of how the brain works and how one then goes about engineering devices to augment the human brain.

1:29:41And as you just point out, it's not going to be done by just sticking electrodes in and stimulating and seeing what happens. In fact, those experiments were done in the 1960s. People like Robert Heath would put electrodes into the brain during neurosurgery, stimulate and just see what the patient would do or what they reported thinking nowadays that's done still, but with a lot more precision and intention. And we've moved far beyond that. By the way, I just want to say those were important first experiments. Yeah, that's the first thing you got to do. Heath was it was it was a rather let's be honest, not not the most savory character.

1:30:11He embarked on some experiments that had a social agenda to them and was a pretty at least by my read was not the kind of person I'd want to spend time with to say the least, but but you're right. Those experiments were critical because like electric shock therapy, like the formulation of drugs that can massively increase certain neuromodulators or decrease them, they led to some level crude, but some level of understanding about how the brain works, which is what we're really talking about today. But you represent the as I said, the astronauts of this astronauts don't go into space and just kind of blast off and see where they end up.

1:30:47There's there's there's math, there's physics, there's computer science sensors cameras. That's right. Looking where are we about to land here on the moon? Is there a crater here or not? What what's around us? We should sense what's there and then make our decisions accordingly and our electronic implants in the brain. Really, we should make them smart. Why make them dumb? We're smarter than that. We can build implants that can sense what's around them and change their patterns of activity accordingly. I use a metaphor sometimes. If you go as an American who doesn't speak Chinese to China and you start yelling in English, maybe somebody will to learn which way to go on the street.

1:31:29Somebody might understand you at some point and help you out, but it's going to be a, it's going to be not very effective way to get around. It's way better if you speak the language. You talk to people and ask them where to go. That's what we need to know. We need to say, look, we have the science. We have incredible devices we can engineer. We have AI now that even helps us to do this query of the outside world and turn it into a smarter instrument. Make our instruments smart. Make them so they know how to talk to the brain. Don't expect that the brain is just going to wrap itself around your simple electronic device.

1:32:03No, make a smart device. That's what we want to make. Smart, run a lamp lamp. Maybe we could just take a couple of minutes and talk a little bit about you and some of the things that have led to your choice to go in this direction. You always know you want to be a neuroscientist from the time you started college. What was your trajectory? I should know this, but you were an undergraduate at Princeton, at Princeton, that right, studying math. You could have just done all your work with a piece of paper and a pen, but you had to try and engineer all these electrodes. That's a pen and paper pen. I took a very random route.

1:32:43I studied math as an undergrad. I spent a few years running around, playing music and traveling, and living a bohemian life. Tell me more about that. I basically just told you all I'm going to tell. Following the grateful dead. No, not quite following them, but that was an important part of the story. Was that an important part of your personal development? Yes. Very much so. Free expression, dance, music, creative, exploratory music, all that kind of stuff. Such a contrast to the EJ that comes forward when we're talking about the persistent neural stimulation in the inspecific retinal cell types.

1:33:22I think it's useful for people to hear both young and old. That one's nervous system can be partitioned into these different abilities. You're like, go and dance and travel. You weren't doing anything academic at that time. No, for a few years, I wasn't doing that programming computers to make a living. Then I started three different PhD programs at Stanford before I sampled. Not all of them? No, no, no. In sequence, I started in the math PhD program. I learned that was not really for me. I started in the economics PhD program in the business school there. I realized after less than a year, that was not for me.

1:33:58I worked in a startup company for a while. There were a lot of stuff for a few years and took some settling. But then I decided to go into neuroscience. There were a couple of formative things. One is that I had gotten a really formative experience as an undergraduate from a wonderful guy called Don Reddy who taught of introductory neuroscience course who was really inspiring mentor. Then when I was at Stanford, I met Brian Wandel, my PhD advisor, and I was inspired by him. I thought, I didn't know why he was studying what he was studying, but I just knew I wanted to learn from this man. I wanted to study with him.

1:34:37This was the person who should be my mentor. Based on something about him. Yes. Can I ask you about these three PhD programs? Because I think people here see what you're doing and probably imagine a very linear trajectory. But now I'm hearing you like, Twitter, Rounplaying Music, then you start a PhD program. No. Then another one. No. Then another one. Without getting into all the details, I mean, were there nights spent lying away thinking, what am I going to do with my life? Or did you have the sense that you knew you wanted to do something important? You just hadn't found the right fit for you.

1:35:11How much anxiety on a scale of one to 10, 10 being total panic? Did you experience the apex of your anxiety in that kind of wandering? Am I allowed to go above 10, like turning up the app to 11? Sure. I just think it's really important for people to hear whether or not they want to be scientists or not. This idea that people that are doing important things in the world, in my view, rarely, if ever understood that that's the thing that they were going to be doing. There was some wandering about that. Sure, seems like it, doesn't it? Yeah. I experienced the same when I talked to other people and it seems like that.

1:35:43For sure, for me, it just took a while of trying different things to see number one, what I was really good at and where I felt I could make a difference. And I realized I studied math and I was okay at math, but I know I have known mathematicians who are really talented gifted math mathematicians, the one who really make a difference. I wasn't going to be one of those people. Likewise, playing music, I don't have that intrinsic talent. It's fun. I can play songs in front of people and do stuff. I like it and stuff like that, but I don't have that kind of talent. In fact, I'll say something that I say to friends sometimes and you're a good friend of mine.

1:36:22If I had the talent to get a few thousand people on their feet dancing by playing music, I'd probably just do that. Really? As long as we've been friends, I knew none of this. Most of because I think we always end up talking about neuroscience or other aspects of our life. But I didn't know, I know a great many things about you and I had no idea. It's so interesting. Do you still do dance? We had air Jarvis on the podcast, by the way, Professor Rockefeller, who studies at one point as a song and birds. He's done great many other things now in genetics of vocalization. He actually danced with or was about to dance with the Alvin -Ali Dance Company.

1:37:13He had really, really talented dancer. Dance seems to be a theme that comes up on the neuroscience guest on this podcast. Do you still dance? I love to dance. I'm a free -formed dancer. I'm not a skill dancer. But I love music. I love dancing. I think it's part of the human spirit. Some day we'll understand the neuroscience by dancing. Dancing is a universal human thing in all cultures. What is this dancing thing? Why do we do this? And other creatures don't. Well Jarvis thinks that perhaps it's one of the more early forms of language and that song came before spoken language.

1:37:54It's sort of to dance as well. There's some kind of a circuitry there. We'll provide a link to that episode. I would love to hear that. I would love to hear that. I'd like to riff on it in a different way. I did spend some time wandering around as many people do. I think particularly for your young listeners and viewers who don't know, wow, could I ever be a scientist and develop new things? Like that. Yes, you can. If you're messing around your life trying this, trying that, trying the other thing, definitely stick with it. Keep looking for the thing that works for you. I really deeply believe that.

1:38:32You got to play around. You got to find what it is that works for you. Interestingly enough, at least it's interesting for me, I spend a lot of years studying the retina in a pure basic science, just curiosity -driven research way, as you and I have both done in the past.

1:38:53As it turned out, I learned all the stuff I needed to know about the retina, to develop a high fidelity, adaptive retinal implant of the type that I'm talking about in that process. The technology, the stimulation, recording, thinking about the cell types, how do you stimulate all the stuff? I learned all that stuff. I have come to a point in my life where I realize, wow, if somebody's going to do what I think needs to be done, which is to take everything we've learned about the retina and instantiate that in smart technology that can restore vision and do all the things we've been talking about.

1:39:30Who are the people in the world who have the right training and background and know how to do that stuff? I'm one of them. I know that. It's totally by chance that I picked up and learned, or it seems by chance, that I picked up and learned the things that I need to know for this. I definitely have the right to know how to do this based on all my training and the research that I've done. It feels accidental sometimes. I look back on my own history. I'm like, how did I get here? Where this is obviously the thing I need to do? Was this on purpose? It didn't seem like it was on purpose, but now I got to do this because I know what needs to be done and it's something that needs to be done.

1:40:10That's my mission for the coming decade or so. I know you had this engineer, Matthew Geeky neuroscience. I don't want to say Geeky because it may sound like I'm not right there in the same raft with you, but I didn't know about this more free -spirited move in all directions depending on what one feels in the moment. Dancing, EJ, it's very cool. Are you still an absolute level 11 coffee snob? Yes. I used to go to meetings and EJ would bring his own coffee maker and coffee to meetings. We're not talking about an espresso machine. We're talking about extreme levels of coffee snobbery. I pressed pot, the correct ground coffee.

1:40:54The correct kind of press pot. Good, good. I expect nothing less. Proof that not all circuits in the brain are neuroplastic nor should they be. That's wrong. But to bridge off of that in a more serious way, despite the free exploration aspect to yourself and that hopefully other people don't suppress, it seems like you really are good at developing, knowing your taste. It seems like the, I think it was the great Marcus Meister, a colleague of ours who has also worked on the neural retina extensively. Of course, one said that there's a coding system in the brain that leads to either the perception, the feeling of yum, yuck, or meh.

1:41:43That so much of life is being able to register that in terms of who you interact with and how and the choices or problems to work on. It seems like you have a very keen sense of yes, that. You move toward that. You've always been very goal directed since the time I've known you. You've picked such a huge problem, but going about it in such a precise way hence the analogy to the space mission. When you experience that, may I ask, does it come about as a thought? That has to be the thing or is it a whole body sensation? What a great question. I love that question. I have two things to say that. The first is that for me, it's all, it's all feeling.

1:42:30I don't make hardly any decisions out of thoughts. I think I process, I put it all into the hopper and the hopper comes out and spits out of feeling and feelings like, yeah, that's the thing to do. 100%. And I know not everybody's like me, lots of people aren't like me, and particularly lots of scientists aren't like me. But I definitely roll that way. That is absolutely how I work. There's something that's related to that that I think is philosophically in terms of personal development and spiritual development stuff. I think is quite relevant that I think you'll relate to. My favorite aphorism is know by self.

1:43:10The Oracle. I think because if you don't know yourself, you can't do anything. You don't even know where to go. You can't even orient yourself at the next thing in your life. I think it deserves to have two carolaries that go with it or addenda. Know that self, be that self, which is not easy. It's in this world. There are all sorts of things telling us to be something other than what we are. And the third one is love myself. And it's you know having gone through much exploration of yourself and your life and your values and me too and all the things we've talked about over time. That's not easy.

1:44:03Some of us are not necessarily programmed to love ourselves. And it's a skill. And I really try my best to be with those three things all the time. Know that self, be that self, love that self. Could you elaborate a little bit more on your process for the third? This is a concept that has been very challenging for me and I think for many other people. And it gets an opaque when it starts getting in conflict with self respect and etc. Like loving myself. Do you have practices? Do you meditate? Do you journal? Do you spend time trying to cultivate a love for self? Yeah. Yeah. I meditate in an informal way in the morning with my coffee.

1:44:54Every morning I make a fantastic cup of coffee and I sit with it. I believe you. For five or ten minutes and take in my world as it's coming toward me and start to as I come into the day and come into consciousness I meditate like that. And I have a ashtanga related yoga practice. Many of your viewers listeners will know about ashtanga yoga. It's a very physical, spiritual, traditional yoga practice that has a deep meditative and breath focused component. I know you've had lots of episodes in discussion about the breath and the importance of that for awareness. You know at the end of a of many Western yoga practices you end with Namaste, which is expressing your respect and for the connectedness of what is in front of you to the whole universe and what's common to all of us and everything.

1:45:49And I usually practice yoga by myself. When I say Namaste at the end of my yoga practice a part of that is to myself. Earlier when I asked you about how you guide your decisions you said it's all feel and you provide a beautiful description as to how and why that occurs for you and you're trusting that. I don't recall you saying whether or not the feeling is in your head or it's a whole body feeling. Does it have a particular signature to it that you'd be willing to share? Is it excitement that makes you want to get up and move or is it a stillness? I think I ask because we've been talking throughout today's episode about the precision of neural coding and these signals that are at the level of individual cells and yet when it comes to feeling we actually have a pretty crude map and certainly a deficit and language to explain what this feeling thing is and I know that people experience life and feelings differently but I think it's often insightful when somebody with your understanding of the nervous system and yourself can share a bit.

1:46:56What does it feel like? I love that question and it relates to something you said to me years ago. What it feels like is ease. I remember years ago when we were talking about challenging things that each of us was facing in our lives you said to me something like I wish for you some ease with all of this. It was very moving, touching as that's what a good friend does is to give that to somebody and to them they love and it sticks with me probably 10 years later.

1:47:38The feeling I feel when I'm on the path that makes sense for me is ease. It's just okay, this is it. I love that. I don't actually recall that specific conversation because we had many many conversations sitting in your yard in San Diego on those plastic chairs with my bulldog Costello hanging out. By the way folks, EJ new Costello, my bulldog massive very well and he was not a huge fan of dogs prior to meeting Costello but Costello flipped him. He became at least a Costello lover. I love Costello. I'll never forget him. Yeah, he embodied ease. He did nothing but sleep and eat. He embodied energetic efficiency.

1:48:29And everybody loves him. Everybody who gets to be in the same room with him loves him. The people I spoke to and you're set up here, your colleagues, you know, yeah, I could see why and you have a beautiful photo of him hanging there. Yeah, yeah, he's a great, great memory. Definitely embedded in my nervousness. I often choke up when I think about it but I want to be clear because I've already cried once about him on a different podcast. I don't want to do that. They're not tears of sadness. It's this crazy thing. I love him so much. I just kind of want to explode. Yeah. So damn it. Costello got me again and publicly again.

1:49:01So he's a place laughing. So I love that. And I think if I made, you know, do you think it's worth kids and adults learning to recognize those, those kind of states, those signals that tell them they're on the right path, by paying attention to, I don't know, like we said, there's sort of a deficit of language. I ease is in the body, ease is in the mind. It's the release of, I mean, you know, it's not even worth exploring verbally because it's a, it's such a whole body, whole nervous system thing. Yeah. I feel like I actually was thinking about I was giving advice to a young fellow who is applying to graduate school recently and had a Zoom call with him about stuff.

1:49:49He had received some good advice from some other people. And then I gave him some advice. And I saw him and speak and emote and with body language drop into like, oh, yeah, that makes sense. Yeah. That feeling, of course, kind of the, of course. And I think if you can teach people to do that, I don't know if the verbal communication of that is going to, like you said, is that going to do anything? But can you at least observe it in them as a teacher, as a mentor and do things? And when you know when you've done it, because you see them drop into ease, do you think you can detect ease in people by looking at them and seeing their body language and everything?

1:50:31It's got to be an amalgam of different things that the cadence of their breathing, their pupil size. It's not worth dissecting. This is an experiment I would not want to run. Yes. But I wouldn't want to bring people into a laboratory and figure out, you know, what pupils of the eye dynamics combine with certain rhythms of breathing relaxation of the shoulders. It's too beautiful for that, isn't it? It's too beautiful and it's too nuanced and it's different when we're in motion versus when we're lying down. It's like, I mean, science is capable of a great many things, but I don't think it needs to be pointed at every aspect of human experience.

1:51:04I think that some of these things are simply worth allowing to just be. Do you feel the same way about when you have a feeling about a person, you meet somebody, and their energy just captures you. It's like, wow, what a cool person. What amazing energy. Do you want to know the science behind that? I don't. No, I don't. I think the word that comes to mind when I experience somebody like that or something like a beautiful animal or I see something, the movement of something or a beautiful piece of music or something is the word just behold. I just want to stop and take in as much of it as possible.

1:51:43And here's something I know you've done, but I'm checking to make sure I really got this right, because I've done it too. Because we sometimes get human retinas for doing our experiments. The first thing that happens when we get the human retina, we bring it back to our lab. It's a moving part going on. We have to open up the eye and look into it to see what condition that's in. And it's typically on with a dissecting scope on a chair. It's open, sitting on a chair, dissecting scope, looking down, looking into the eye. It is so beautiful. It's breathtaking. Each time I've looked at the retina, I don't know how many times.

1:52:20Each time, wow, this is what's initiating all the visual experiences I've ever had in my life or that person I've ever had in their life, right? And the beauty just keeps coming. I love it. And I love it because you're talking about a behold moment that isn't just to entertain your curiosity. Sure, it's that you want to understand how the brain works. But also a behold moment that leads from that desire to understand to a deep level of understanding now after more than two decades of exploration to a mission in service to humanity, restore vision to the blind, develop neuroprostacies and other types of neuroengineering technologies that will allow the human brain to function better than it would otherwise.

1:53:12So there's a system of, it's not just about delighting in something and spending one's time there. There's a real mission there. Oh, I love it. Well, EJ, Dr. Chicholnowski. Dr. Hubern. I rarely get called that these days. When I invited you here today, I was absolutely sure that our listeners and viewers were going to get a absolutely world -class explanation of how the nervous system works and the retina and the visual system in particular, and that it would be delivered with the utmost clarity, which it was. So thank you. I know there's been so much learning in and around that. And you beautifully framed for us what that means in terms of the larger understanding of how the nervous system works and what you and other laboratories are now in a position to really do with that information and the technologies that are being built and that will be built.

1:54:15And the purpose in bringing here today was just that, but not that alone. I think we hear so much about the brain and how it works and everyone wants to have tools and protocols to function better, but it's clear that the work that you're doing is headed in a direction that's going to vastly expand the possibilities for sake of treating human disease and for expanding human experience. I'm certain of that. What I did not expect, however, was that when I wrote down one bullet point, well actually two, I wrote still a coffee snob, question mark, the answer is yes. And yoga, you know, that we would end up in territory where you would share some of your experience that I myself was not aware of about this.

1:55:04A bit of a wandering of three different PhD programs and of this cultivation of an intuitive sense of of beauty and taste and preference that the way you described it takes you out of your rational mind and into the aspects of your nervous system that just really act as a compass toward what is absolutely right for you. And we're also lucky that what's absolutely right for you turns out to also be what's absolutely right and beneficial for the world. So thank you for coming here today. Thank you for sharing your knowledge and your heart and for doing it with such an incredible degree of openness and respect.

1:55:52So thank you so much. Thank you, Andrew. It's a great pleasure. Really appreciate it. Thank you for joining me for today's discussion with Dr. E .J. Chicholmaski to learn more about the work in the Chicholmaski lab and to find links to E .J. social media handles, please see the links in the show note captions. If you're learning from Endor and enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five star review.

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