From Restoring Sight to Reimagining the Brain, with Max Hodak

0:00The brain very literally, very clearly, plainly is a computer. You can solve computational problems by arranging matter in a certain way and then like taking your hands off and pressing go. We talk about being a brain in a vat. That's what the skull is. Like the brain is connected to the environment through a small number of wires, the cranial and spinal nerves, these little cables that carry your interaction with the world. If you can get the visual signal, auditory signal, balance, motor in and out of the brain, that is an end in itself. That is the central object. The retinal prosthesis right now, I think, is a great proof of concept that we're on the right track.

0:32Nobody had previously ever been able to restore a form vision image in the mind's eye of a blind patient in this way. We need to add depth of grayscale. We think we could see a path to get at least red and green. And so there's ways that we can compound upon this path through an engineering process to make a product that's better and better.

0:55Hi listeners, welcome back to No Priors. Today I'm here with Max Hodak, the founder and CEO of Science, formerly of Neuralink. We talk about Prima, the implant that helps people who have gone blind see again, which just got regulatory approval in Europe. Their quest to sustain the human experience and substrate independence for the brain. We also talk about alignable representations between AI models and the future of neuroscience. Welcome, Max. Max, thanks so much for doing this. Thanks for having me. So for anyone who is not familiar with science, can you just describe a little bit about why you start the company, leaving Neuralink, what the mission is?

1:36Fundamentally, we're a medical device company. But I think if the mission of lowercase s science is to use a differentiated understanding of the universe to improve the human condition. I mean, that's the mission of uppercase science. That's what we do. We use specifically an understanding of how to work with the brain to get big effect sizes that you don't get in medicine often. Our main product is a retinal prosthesis. You can think of it like a cochlear implant for the eye. Cochlear implants are some of the biggest impacts in all of medicine. I mean, if you've ever seen a video of a newborn turning it on for the first time, it's striking.

2:12And our goal is to build things like that, including our primoretinal prosthesis. And for people who are not familiar with that, it's a chip that is inserted with glasses. So it's a tiny chip that's implanted under the retina in the back of the eye for patients that have gone blind due to loss of the light sensitive cells in the eye. So specifically, this is diseases like macular degeneration, which our clinical trial was done in. We're about to do studies in retinitis pigmentosa and Stargardt and a couple of their diseases. So it is a chip that It sits under the retina and then converts it. The patient wears glasses that have a laser projector that projects an image onto the implant that then stimulates the retina to bypass the dead rods and cones and stimulate the retina directly to get a visual signal back into the brain.

2:53How did you go from we should have like a nick invasively in the brain to this particular form factor as the first premise? Oh, so when we started the company, we had a couple ideas. is um the one of the ideas was this was the bio hybrid neural interface um direction where instead of placing metal wires into the brain or genetically modifying the brain what we do is being grafted in living neurons that grow in and form new biological connections that's a big research project it's very exciting research but also um needed to be paired with another near term business and we asked ourselves like what was the most valuable thing we could do and we thought that we could restore vision to the blind with the resources available to us and where the state of the field was in early 2021 and if so if you want to do that you have to start from this understanding of like how does the brain get vision what is vision in the brain and you you could look at the retina which is obviously how vision gets into the brain the first place it's created the the first stop of the optic nerve into the brain is a structure called the lateral geniculate nucleus and the thalamus so that you could think oh we'll stimulate the lgn and then the connection from there is visual cortex.

4:05It's half a billion cells up at the back of the brain. If you want to restore vision, you can think, I can go into the retina, I can go in through the thalamus, or I can go in through V1. There's a bunch of scientific technical reasons that lead you to think if you have an optic nerve, you want to be in the retina. From there, you have a choice of, do you stimulate? There's two types of cells, and there's a couple of different ways you could stimulate them. We explored all variants of that early on we developed an in-house gene therapy that affected the retina in one direction we did a survey of electrical stimulators we looked at ultrasound and what we ended up doing is we developed indigenously a state-of-the-art gene therapy which is probably going to humans next year as well as we we found the state of the art out there in the world of people electrically stimulating the retina and there was a company in france called pixium that back in late 2022 had by far the state of the artwork.

5:03It was originally developed by an inventor at Stanford and then licensed to this small French company. And they were in the middle of clinical trials. And we got to know them over the course of a couple of years. And then we're in a position to acquire them when we saw something that I think kind of nobody else really saw at the time. And that, I mean, that deal has turned out to be great. Can you talk about the recent CE designation regulatory approval you got? Yeah. So it took us about two years for post acquisition to get it to the place where this was possible. But we just in July got marketing approval in Europe for Prima to start commercially selling it there.

5:39And so that's a major milestone. That means it's really commercially available. The first sales will happen in the coming weeks. That's amazing. I think most people think of anything in the BCI field as, you know, a moonshot project that may or may not pan out 10 years from now. Well, I mean, people forget that the moonshot worked like we went we left like boot prints on the moon. And so this comparison, I mean, I think that there's it has gotten used in Silicon Valley to mean these things that have extremely long odds and are unlikely to work. And therefore, we can vaporize a bunch of investor money just fine.

6:09It's like, you know, when we went to the moon, we did it. And so historically, the success rate of moonshots is higher than I think people give them credit for. One of the most important things is having a real business here. And this is the start of that. Can I ask how you, when you were exploring both different signaling pathways and form factors and just conditions to go attack, or how you thought about scope of timeline and engineering cost and risk? Were you just looking for like the, like big enough to be useful and feasible in some period of time? Or how did you think about funding the project and how long it could take?

6:46So there's three elements to our pipeline. The first is our work in vision. Second is our biohybrid neural interfaces. And the third is our work in a different area of medicine, perfusion, a program called Vessel. These three things together form kind of the minimum set of things that I think if they're successful on the timescale of 10 to 15 years could really drive, I think, a significant revolution in medicine broadly. People have spent huge amounts of time and money looking for drugs to restore vision or to restore hearing or to stop Parkinson's or to help paralyzed people move again. Understanding the biology and the molecular detail required to make a drug has been very difficult.

7:30Humanity just isn't that good at that, to be totally honest. On the other hand, the brain is a computer. And when you deal with the brain as a computer, you get these things to work. very like it's just again there you don't see demonstration you don't see things in medicine like a cochlear implant being turned on or a deep brain stimulator being turned on or i mean you can implant a quadriplegic patient motor cortex and and have them playing video games in like an hour like this just you just don't really see things like this in medicine in most drugs um and so there's this you know in small molecule random walk you know sifting in nature yeah i mean small molecules especially are super hard i mean even i mean you can do some super highly engineered patient specific car t and instead you get like an audit like giant immune overreaction it's like if i put electrodes in m1 you will probably be using a computer in an hour um and so it's just it's easier it's more amenable to biology in many ways you can do drug discovery for a decade run a clinical trial you're going to turn over a card the answer might be no and then everybody goes home.

8:33Whereas here, we have a clear sense of how to make the thing better. The retinal prosthesis right now, I think is a great proof of concept that we're on the right track. Nobody had previously ever been able to restore a form vision image in the mind's eye of a blind patient in this way. But at the same time, it's a small field of view. It's like looking through a straw. It's only black and white. We need to add depth of grayscale. we think we see a path to get at least red and green. Blue is a little bit trickier. And so there's ways that we can compound upon this path through an engineering process to make a product that's better and better.

9:09Can you talk a little bit about what you saw in the clinical trial in terms of variation between patients or what the ceiling was so far? Yeah, I mean, in the clinical trial, I mean, the main thing was just the existence proof of like that success was a possible outcome, right? Like that we had patients filling in Sudoku puzzles or crossword puzzles. there were patients that were reading books. And so I saw some of these patients, some of these videos met with one of the patients, talked to the surgeons. We, I mean, this is one of those things that seems too good to be true. How do clinicians react to all of this?

9:42Like do, would, would the people that you work with say at the beginning, like, yes, Max is right. Like the brain is a computer. This should definitely work. It should work at a higher likelihood and better rate of progression than our random walk in biological understanding. Well, if you want to make people angry you should tell the internet that the brain is a computer okay um start by doing that all right yeah yeah um that kind of starts you off in a um like a defensive place why don't people like that i don't know this is one of those things this just feels like bike shutting to me i mean to me i don't mean that metaphorically like the brain very literally very clearly plainly is a computer in my understanding of the world i also view the universe generally as a computer like we can solve like you can solve computational problems by arranging matter in a certain way and then like taking your hands off and letting impressing go.

10:31And so the fact that like that, that unfolds in time to solve some computational problem, I think of that as a computer, the brain's the same thing. And that, I don't think there's necessarily - That's a broader definition of computer than I had before. A deeper point there. Yeah. Yeah, I mean, there's nothing special about transistors. I mean, we understand computers in this idealized way as the, as like a Turing machine, that's an abstract computer. It's just, you're going from state to state in ways that are subject to laws that mean that the transformations are interesting and meaningful. But no, I think this was fairly contrarian, both in the sense that BCI has this broader interpretation than motor decoding, as well as like, is a retinal prosthesis a BCI?

11:17That's also kind of this minor definitional question. But if you think that it is, then that kind of opens up this interpretation of a lot of areas of medicine that could be accessible to it that other people weren't really thinking about. I mean, clearly there was interest in looking into this. It wasn't that contrarian. It's a different approach. And I think we come from a different culture than a lot of the conventional biotech industry. There's always been kind of an East Coast, West Coast divide in biotech, especially. And we are more of a tech company than a conventional biotech company.

11:50And our device view of a lot of historical biology problems makes us even more of a tech company by biotech standards. So we mostly raised from tech investors, not that much from biotech investors. In fact, there's only one VC that I sought out at all at the Series A that I went to go pitch, which was Bob Nelson, who's a biotech investor. When you describe different types of BCI products and missions, I think you have a really good way of explaining it that is on a spectrum. Can you talk about just the landscape of what devices and approaches people are working on in BCI today? I think BCI is a category, kind of like how pharma is a category.

12:29I think sometimes I'll talk to VCs and I go, oh, we have a BCI bet. I'm like, do you have a drug bet? You made one bet on drugs. That's how you think about the category. Right. Everything from versus thinking about it like in, you know, neurodegenerative and Parkinson's or a specific. Yeah. Or maybe even different bets within neurodegenerative. You've got a degrader and maybe you've got a gene therapy and maybe you've got something else like because they're different hypotheses. Yeah. And similarly, I think on one end of the spectrum, you've got silent speech devices that may be BCI in a greater or lesser degree.

13:01Like maybe they're recording a neural signal like EEG. maybe they're using something just like radar through the face which i know like i know is an idea out there um but these are all basically hand substitutes and on the one hand hands are great two on the two hands hands are great the they work really well you don't need to think like i'll talk to teams that say like oh well it'd be really nice if to go to your next thing you didn't have to like open the uber app and like call an uber you just like thought of it it was there like you probably want to communicate really unambiguously with the uber app it'd be pretty annoying if they just start like spontaneously getting notifications during meetings that like, oh, it thought that you were thinking about an Uber, therefore decided to summon two for you.

13:41And so you'll probably want these to be pretty explicit. And to the degree that that is a volitional intent, like you already don't need to do a lot to get your hands to do things. Now, could you have extra hands? Extra hands famously useful. And so having some easier way to communicate might be useful. That is kind of outside of the scope of things I spend a lot of time thinking about. Because if you get vision, hearing, balance, and a kilobit per second of motor control, you're halfway to the matrix. And this takes you into some really trippy reinterpretations of medicine. And that's the stuff that we work on.

14:19I think other people will do things like speech to text and AI communication. There is a distinction. So there's, let me come back to your broader question a second, but there's some point where you go from communicating with a thing to redrawing the border around your brain. And we don't have a great sense of exactly where that transition is yet, but there's a sense that there is one. The way that you use the two hemispheres of your brain as one integrated bound thing is different than the way that you talk to another person. It's not just that there's correlation, because all communication is about creating correlations between brains.

15:01When we speak, there's big correlations that are being driven between our brains. All communication is premised on that. If we didn't pre-share a language or some common education, like some sense of math, then we wouldn't be able to communicate those concepts. Because there's some thing that's lit up in my brain. I can serialize that to language. I can send that to you. That lights up the same pre-shared concept spaces. And so there's one mode where you've pre-shared some structure between the two brains, whether this is an AI model or a biological brain. And then you're communicating over that channel.

15:36The other is you've added some new structural capability. I think figuring out where that transition happens is a really compelling area of research for us. What are you most personally interested in in terms of exploring that boundary yourself? Yeah. Well, I mean, what is you is a really central question here. Like if the end of the artificial intelligence quest is - I don't really care. What if I just want my brain to be a better computer or a richer one in terms of understanding other people's experiences? I mean, I think that you still, there is an important question here. So if I just like scanned your brain into a computer and there is a software simulation of you, is that, does that count as you?

16:18Like, would that make you feel better about dying of cancer? Like if you were diagnosed with lung cancer and we said, okay, well, we'll scan you into a computer. So imagine that we did it like non-destructively. So you are still there, but then you're talking to the software replica of you. And then you're like, okay, I'm going to go to hospice, but this thing will keep doing my venture investing job. Does that make you feel better that much? Well, I think on this question, have you ever been under general anesthesia? Yeah. Yeah. And that produces a break there. And this is the type of thing that you have to explain about.

16:49Why does that feel different? Because I think it does feel different. I think that people are reticent to undergo general anesthesia, but they do it. They survive and they realize it's fine. and then there's if i could make a copy of you and you can talk to that copy and you're like okay i will go away now i just don't think that many people are going to be like this is it um and so you have to answer why it's different there's an asymmetry in the uh so you've got like some of the operators that actually change things in physics are like a creation or annihilation operator and we get these in life right you can create a new life or a new mind or a new soul and then there There are times when they can be annihilated, they can get destroyed.

17:30And then there's ways that they kind of change while intact. Do you study consciousness at science in a like a sequential way or directly explicitly today when you talk about the operators that are part of it? So your conscious moment is a you're experiencing a bunch of things in parallel. well. So you're seeing things and you're hearing things and you're feeling things and you're smelling things. And these things happened just simultaneously together, but they are, they're kind of different elements of the experience. And we want to understand how does the brain construct each of those and how does it cause them to be perceived together to the exclusion of other things?

18:10Like you have your vision and your hearing, you never get my vision and your hearing. And I think you kind of have this, like, you might think like, that sounds like really obvious, like it's in my brain, It's not in your brain, but we need some more fundamental explanation for really how that partitioning happens. OK, so you think that's a foundational component? Yeah. And so, yeah, so I'm in the camp that like continuity is greatly important. And so people will accept significant drift in their identity over time as long as they have continuity. But if you preserve the sense of identity, like you have a software simulation that answers exactly like you would now, but it's not phenomenally continuous, that is less satisfying.

18:48Yeah, that's an interesting trade. I think I would take dramatic morph, but continuous experience. Yeah. I don't know if I'd take like significantly degraded IQ. Laura Deming asked me this. Yeah. It's like life with provable characteristics is a thing we've never seen before. And it might be transient. Like you'd probably accept degraded IQ for some period of time if it then got backfilled some number of weeks later, and then you got some experience. I mean, at that point where you achieve substrate independence, you can really, you can take that almost anywhere you want, which is why that's really, really interesting.

19:16One of the big missing pieces here is connectomics. That is getting pretty close, I think, in terms of to the point where the project could be done. We're still relatively far from a human connectome, but I think we're not that far from a mouse connectome. That would be enormously useful for facilitating this research and understanding about how all this works. We need to understand even really basic questions like, what is the overall architecture of the brain, we have some answer for, but I don't know that it's like a really, really detailed one at this point. You are of the view that it makes sense that there is this increased interest, this surge of investor interest and founder and engineer interest in BCI as a field, given the progress of AI model research, because the representations actually should be shared, or they empirically seem to be.

20:09Yeah, I mean, this is this is the idea called the platonic representation hypothesis. And this is really interesting. It is controversial in the community. But I mean, from where I sit, there's clearly something real happening. So when you look inside these big models, the mathematical objects that you see look a lot like the things that you see in neuroscience. So if you look at how do how do these models represent just like represent concepts, then you look at the parts of the brain that represent concepts, you see these you see very similar geometry. that to me was one of the first clues like when i really saw that and we we use that practically like we use that constructively at science like that we know that that is that is true because we can get alignments between animal brain neural recordings and ai model internal representations that was a big clue to me that the ai ai was on the right track and this was like not a gimmick and not hitting a wall there's like something deeper deeper that's true here um there's some fact about the universe for these things as they're learning or grabbing onto some true underlying data manifold.

21:07I mean, it feels like a law of physics. Like if you apply enough compute to matter, you got this thing that looks like intelligence. Why do you think that's controversial? Or why is it in the field? There's some faction of people that kind of don't want this to be true for reasons that are not totally clear to me. It is also not clear. We don't completely, we don't really fully understand whatever phenomenon is happening here. It's unclear if the structure is global or if it's local in some sense that in like there's you can recover relational structures between ideas but it might be that this this works locally it doesn't like that where disconnected things might be placed might like this gets fairly detailed like tech technical quickly but there's a bunch of stuff that we just don't know and i think this causes um create space for people to wonder is this as giving us this fundamental of like a hint as it might seem, I think that it is.

22:03What do you think are the most fertile ways to study neuroscience today? If your set of beliefs is true? Yeah. Well, I mean, ironically, it's probably working on AI. Yeah, I have a couple of neuroscience friends at OpenAI and Anthropic who it's like, we joke like, oh, you left neuroscience. Like, no, no, no. It is just way easier to do neuroscience on the models. But the degree to which it is neuroscience is fascinating. I want to talk a little bit about the future and maybe the very short and the medium timescale for science, short of changing the boundary of who we are. So what does it look like to commercialize the first program for you?

22:44You said that there need to be$100 million run rate businesses in this field. How do you get there? Yeah. Well, I mean, becoming profitable or at least having the ability to do this forever is a super high priority. Restoring vision to the blind is a pretty good business if you can actually do that. Especially since almost everyone has the problem as an age-related problem. Yeah. So AMD, it's like one in two have some early stage by 80. It's like one in 10, 85 that actually have it. But it is definitely a major issue, and not just vision, but these topics in general affect everybody. We don't have firm pricing yet.

23:25This is a thing that we are being a little cautious about how we talk about publicly because we aren't totally sure yet. But the precedents for vision are all, I mean, I think we could say they're expensive. I mean, Second Sight 10 years ago. So there's a company about a decade ago that had a retinal prosthesis that works differently than ours does. It did not get the type of performance that Prima does, but was briefly approved because there's really nothing for these patients. There's always been a lot of enthusiasm for anything that could possibly help them. And they didn't get what we call form vision.

24:00They didn't get like a coherent face or like paragraph that your eyes could scan over. They got these flashes of light that patients could look at and kind of think about assembling into what they meant. They got paid about$150 ,000 per patient in the mid-2010s. There's a gene therapy that is only relevant in the first place for about 5 % of patients in one narrow indication. And it really doesn't work that well. It gets 0.1 lines of improvement. It kind of slows the rate of degeneration for some patients. that reimburses at almost half a million dollars per eye and so there's i mean some of this is a function of just how expensive it is to develop these therapies and how high the failure rate has been historically um and then um some of it is that there's just it is i mean vision's very dominant sense for us if you if you lose that that's totally debilitating and restoring it is is very important, even just like minimal vision.

24:58So the TAM will grow over time. For this first version, it's on the scale of like hundreds of thousands of patients in the US and Europe. So for the current version of FRIMA, it's probably hundreds of thousands of patients. And then the next version, which is going into animal studies now, will be in humans hopefully next year, should expand that to millions. You said something that surprised me as a intermediate point between vision and, you know, fully understanding consciousness. How does oncology or other, like how do other indications fit into the picture in terms of what you might work on?

25:33I mean, the thing that makes you, the only organ that you can't even in principle transplant is the brain. The heart, the pancreas, the liver, the lungs, as far as I'm concerned, they're really support characters. They're there to keep the brain activity interesting and going. And I think we're going to get to a point where, because the biology is so difficult, I mean, you've got this like alien nanotechnology that is around us that we are like completely surrounding us that we are completely dependent on that we understand still very poorly. Instead of needing to solve that, are there ways where we can accomplish the same fundamental goals, you know, like using a toolbox that humanity is much more advanced in?

26:13And so I'm going to be ultimately fairly disappointed if I'm murdered by my pancreas. And I think that's the worldview. It's that the thing that matters is the brain. The brain is the computer that gives us this. We talk about being a brain in a vat or having these upload thought experiments, but that's what the skull is. The brain is connected to the environment through a small number of wires, the cranial and spinal nerves. The optic nerve is nerve two. Vestibular cochlear nerve that carries hearing imbalance is nerve eight. you've got these these little cables that carry your interaction with the world that world is is generated by the brain and so if you can get visuals the visual signal auditory signal balance motor like somatosensory motor in and out of the brain that is that is an end in itself that is the central object okay and through a mix of the bcis that allow you to kind of change this this is the thing that it's interacting with and our perfusion medicine program.

27:15We think that there's ways to significantly improve not just lifespan, but healthspan and kind of create a better, a better quality of life for many patients in ways that I think will feel kind of like a lateral move rather than just solving many of the things that people have seen on the horizon. For people who are interested in working at or investing in science, if you are successful, what will be the change to the human experience 20 years from now besides you not worrying about your pancreas as much? Yeah, I mean, that's it.