Mark Zuckerberg & Priscilla Chan: How AI Will Help Cure Disease

As part of our summer replay series, we're revisiting one of our favorite conversations from the past year. Mark Zuckerberg and Dr. Priscilla Chan join Ben Horowitz, Vineeta Agarwala, and Erik Torenberg to discuss the Chan Zuckerberg Initiative's ambitious effort to help cure, prevent, and manage disease by the end of the century. Rather than funding individual breakthroughs, CZI is focused on building the tools and infrastructure that can accelerate scientific discovery across entire fields. The conversation explores Biohub, Cell Atlas, virtual cell models, open biological datasets, and the growing role of AI in helping researchers better understand human biology. They discuss why biology still lacks a "periodic table of elements," how AI could help scientists test hypotheses before running expensive experiments, and why pairing frontier biology with frontier AI may unlock a new era of medical discovery.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  This is a space that I mean, there's just gonna be a huge amount of leverage with AI. It still seems like there could be a lot more effort in this space around building tools. And it's kind of this crazy thing that we're, you know, here in, you know, 2025, and there's not the kind of periodic table of elements equivalent for biology. We think that this is like, probably one of the most important sets of tools that you need to build.

• 0:23Speaker 01

  When we first set out that the goal to cure and prevent disease by the end of the century, people like, honestly, most scientists couldn't look at us with a straight face.

• 0:32Ben Horowitz?

  They're like, you're crazy.

• 0:33Speaker 01

  Yes. And it was true because if you just decided to spend the money funding the next best grant for every single lab in the country, like you, there was no pathway to that being true.

• 0:45Speaker 00

  The biology folks, I think, looked at it as if it were crazy ambitious. And then the AI folks are like, well, that's kind of boring. That's just automatically gonna happen.

• 0:55Ben Horowitz?

  I know. It's like, okay, there's something in between there that needs to be bridged.

• 1:00Erik Torenberg?

  For our summer replay series, we're bringing back one of our favorite conversations from the past year. As AI continues to reshape nearly every industry, one of its most important applications may be in science itself. In this conversation, Mark Zuckerberg and Dr. Priscilla Chan discuss the Chan Zuckerberg's initiative's long-term effort to accelerate scientific discovery by building new tools for biology. Rather than focusing on individual therapies, they're investing in the infrastructure, data sets and AI systems they believe researchers will need to make faster progress against disease. We explore Cell Atlas, virtual cell models, Biohub, and the idea that the future of medicine may depend as much on better tools as on better treatments.

• 1:48Erik Torenberg?

  Mark, Priscilla, welcome to the A and Z podcast.

• 1:50Speaker 01

  Thanks for having us.

• 1:51Speaker 00

  Yeah, great to be here. Excited.

• 1:53Ben Horowitz?

  All right. Excited to have you. You're doing exciting stuff.

• 1:55Erik Torenberg?

  Yeah. To that end, almost a decade ago, you guys started the Chan Zuckerberg Initiative with the mission and intent to cure, prevent, manage all disease by the end of this century. There's a lot of missions that you guys could have poured your time and resources into. Take us behind the conversations of why you guys picked this one. Maybe, Priscilla, why don't we start with you and your side of the story?

• 2:15Speaker 01

  It always surprises people when I talk about how we work in basic science research. I trained as a pediatrician and people always think, oh, it must be about medicine. And for me, I went into medicine because I wanted to improve people's lives. I wanted to make a difference. I wanted to be able to help others. And I think training as a pediatrician at UCSF, I met a lot of patients and frankly, like little kids and families for which we just had no idea what the problem was. And they might have a specific gene that they could name if they were lucky, or they could be grouped into a bunch of other diseases and there'd be a general sort of PDF they'd print out, like this is what we know. And then it was my job as an intern or resident to try to translate

• 3:00Speaker 01

  like a few lines of information to how we were supposed to take care of the patient. And for me, that's when I really realized the power of basic science and how we need to work on basic science to advance the forefront of what's possible. I think of it as the pipeline of hope.

• 3:18Ben Horowitz?

  Yeah. And why did you think you could cure all disease? Cause that's like a very like aggressive goal.

• 3:25Speaker 01

  Do you want to answer that one?

• 3:25Speaker 00

  Yeah. Well, I mean, we're not gonna cure all diseases, to be clear. I mean, the strategy is to help scientists and the scientific community cure all diseases. So the strategy is really one of accelerating the pace of basic science. And the theory that we had was if you look at the history of science, most major breakthroughs are basically preceded by the invention of a new tool to observe phenomenon in a new way. Right? So think about things like the microscope, right? And being able to observe bacteria or other fields, the telescope or, you know, but it's, just to use an engineering example, without those kind of tools, it's kind of like your coding without being able to step through the code. And you both, right?

• 4:07Ben Horowitz?

  That's like the old days.

• 4:11Speaker 00

  So our whole approach on this is basically, let's help build tools that will accelerate the pace of the whole field. And I think that there's a niche that I think fits that because if you look at how funding works in science, the vast majority of funding comes from the government and NIH grants. It's parceled out into these relatively small grants that allow individual investigators to investigate usually pretty near-term things. And the development of these kind of new types of tools, whether it's imaging or building now a lot of AI things like virtual cell models, are longer term, oftentimes more expensive to develop. So think about like, on the order of maybe 100 million to a billion dollars over a 10 to 15 year period.

• 4:56Speaker 00

  And then you try to unlock those tools and give them to the scientific community to accelerate the pace. So that's kind of the theory.

• 5:01Ben Horowitz?

  Right. And it seems like there's also something that is you don't really get credit for the tools in a lot of ways. I mean, we have companies that use your tools and they're very happy about it. But I didn't even know that that was the case. And so.

• 5:14Speaker 00

  That's why it's philanthropy.

• 5:15Ben Horowitz?

  Yeah, well, it is, but most people do philanthropy to get credit too. I mean, that's kind of a part of it. So I guess, did you think about that? Or were you just like, no, like this is gonna work and if it works, that's all we need.

• 5:29Speaker 01

  We're super focused on like actually making every scientist better and beyond science, like startups, startup founders, because the point is we can't do this alone. And when we first set out the goal to cure and prevent disease by the end of the century, people like, honestly, most scientists couldn't look at us with a straight face.

• 5:50Ben Horowitz?

  They're like, you're crazy.

• 5:51Speaker 01

  Yes. And it was true because if you just decided to spend the money funding the next best grant for every single lab in the country, like you, there was no pathway to that being true. But if you forced people to really think about this and like, okay, what is the most credible pathway to doing this? And what are the barriers to that credible pathway? Then we sort of got somewhere, right? They were like, well, like there's no shared tools or we're not working on big projects and building the right data sets. And we're like, okay, well, then we can start doing something about that. And so that's where the idea of building shared tools, cause no one right now in the science.

• 6:30Ben Horowitz?

  That's so interesting. So basically you're like, we're gonna cure all disease. And they're like, can't be done. Why can't it be done? Well, cause we have other tools. Okay. That's a pretty, that's a pretty cool sequence.

• 6:42Speaker 00

  Yeah. I mean, there's also this funny thing where the biology folks, I think, looked at it as if it were crazy ambitious. And then the AI folks are like, well, that's kind of boring. That's just automatically gonna happen. I know. It's like, there's something in between there that needs to be bridged. And if you can like, kind of use the kind of modern AI tools in order to build the types of tools that biologists need. So that's a big part of how we think about our work is.

• 7:07Ben Horowitz?

  AI has got to be the most overestimated and underestimated technology ever, like simultaneously.

• 7:12Speaker 00

  I mean, yeah, well, probably like the internet early on. But, but we kind of think about ourselves and the work that we're doing at the Biohub as frontier biology paired with frontier AI. Right? So there are labs that do frontier AI that basically, you know, are building the most advanced models. And then there are lots of biological research organizations that effectively do very leading edge research to build, to either discover new data sets or looking to certain challenges. But so far, there hasn't been anyone who's tried to do both of those at once. And when you look at, I mean, even something like AlphaFold, which is amazing, right? It was built off of this data set that was a public data set that had been produced decades ago.

• 7:56Speaker 00

  Right? And what I think you have the opportunity to do if you do both of those together is produce specific data sets for the purpose of training AI models to build virtual cells that can do specific things. So I think that that's like a pretty interesting zone to be in.

• 8:12Ben Horowitz?

  Yeah.

• 8:12Speaker 00

  And of all the things that we've worked on, you know, actually when we started CZI, we kind of actually focused on a number of areas. And what we found is just that the science research has had by far the biggest returns. We've just doubled down on it over and over and over until now we're at the point that we're 10 years in. And Biohub is really the main focus of our philanthropy at this point. But yeah, I mean, that's kind of, that's basically the focus.

• 8:34Vineeta Agarwala?

  Maybe you're not giving yourselves enough credit because you're sort of saying, well, there's bite-sized science. We don't want to do that. There's century scale science and that seemed like a long time horizon, but achievable, ambitious. But you've actually identified, which I think is really fantastic, grand scientific challenges that are right in between. They're 10 to 15 year horizons, at least per kind of the way you communicate about them and the way you energize the scientific community about them. 10 to 15 is kind of an interesting time horizon. Sort of like similar to the time horizon of a venture-backed company, similar to the time horizon on which a team can work together for that period of time. How did you get to that number? And then how are you thinking about the challenges that you take on in each 10 to 15 year wave?

• 9:17Vineeta Agarwala?

  Because that's concrete, achievable. You build a lot of credibility around it, the way that you've announced those challenges.

• 9:25Speaker 01

  Well, I'm curious how you guys think about it. But for us, when we looked at the grand challenges on the 10 to 15 year time horizon, it needs to be like, when you look at it, you're like, I see a path.

• 9:37Vineeta Agarwala?

  Right.

• 9:37Speaker 01

  Not everything needs to be solved for us to take it on. In fact, if everything's solved, then that feels like that should just go.

• 9:44Vineeta Agarwala?

  Ambitious enough.

• 9:45Speaker 01

  Yeah. Like we have some risk appetite, right? So we want things where we're like, there's a credible pathway, someone who is at the helm who can do this. And there's enough ambiguity where we feel like we could take on that risk. And if we do it, like the returns could be higher than even expected. And the way we modeled that in the Biohubs is we have three Biohubs. We have one in San Francisco, one in Chicago, one in New York. The one in New York works on cell engineering. Can we engineer cells to go in and detect signals, read it out or to take certain actions? In Chicago, we're building tissues and looking at cell communications within tissues. And then in San Francisco, we're looking at deep imaging and transcriptomics.

• 10:29Speaker 01

  And that work, the locations are not by accident. We also look at the partner universities because we have folks who come to the Biohubs to do this work, collaborative, interdisciplinary, and sort of unconstrained by the traditional lab. But we also build off of the labs at these academic institutes that support the work. And so that's how we sort of choose the grand challenge and, and the locations. And then the sort of layering and the large language models and AI coming into the picture has been so interesting because we were already building tools to measure interesting data,

• 11:13Speaker 01

  building the data sets, but we didn't really know what to do with them yet. And large language models coming onto the scene, we're like, wow, we can make sense of all of this now.

• 11:24Vineeta Agarwala?

  I'm curious what you view success as in the therapeutic realm. So, you know, we think a lot about understanding biology and sometimes we bet on startups that want to unlock completely new biological areas, diseases, where we don't know what's going wrong. And then there's another group of folks who kind of say, hey, okay, now that we understand what's going wrong, let's fix it. Let's come in with a drug, let's come in with a new type of chemistry, a new type of antibody. How do you, what do you think success for the CZ Bio Hub looks like 10, 20, 50 years from now in terms of the new medicines that you've enabled?

• 12:01Speaker 01

  We want there to be like an explosion of a community who are building these, just the new wave of what it means to be deploying precision medicine. Like, I think for rare diseases and common diseases alike, you're really talking about individual biology that we sort of lump together. And they, and we often don't know how it happens, right? We know that you have this mutation, or the worst nightmare is you have a variant of unknown significance. What does that even mean?

• 12:31Vineeta Agarwala?

  The horrible V U S.

• 12:32Speaker 01

  Yes, horrible. And you're like, you tell someone you kind of know something, but we don't know what it means. But if you look at the way we've been able to look at variants and look at single cell transcriptomics, we're starting to be able to say, okay, this variant actually impacts this set of downstream cells. And then we start looking at the proteins that get expressed and how it looks similar or different to what a healthy cell would look like. Then you can start targeting, okay, like, let's look at that as a target. And you both know the specificity of the target you want to build based on the ability to connect mutation to protein expression, as well as to be able to predict off-target effects. What are the side effects?

• 13:15Speaker 01

  Because you also know where else that drug will be able to interact with the body. And so those are rare, like, and, but I really think most diseases should be thought of as rare diseases, because each one of our biology is different. And right now, we just get lumped, right? We get lumped based on age, demographics, ancestry, if we're lucky to have that level of understanding. But truly, each one of our biology is different. And say, like, if you look at hypertension or depression, like, we kind of just go by trial and error and saying, like, let's just try that drug and see what happens. But what should really happen is being able to precisely and accurately and quickly

• 13:57Speaker 01

  treat people by looking at individuals' biology. We want to enable the basic science, and we would be thrilled if people picked up the models that we build to be able to build the diagnostics, the therapeutics that need to come.

• 14:12Vineeta Agarwala?

  You've built amazing data sets, I have to say. Like, I mean, you may not hear the feedback from the startup community and the pharma community and the R and D community, but it's there because you've committed to open source. And so people may not be, they may not all be writing papers, but they are using those tools. There's a startup in our portfolio working on idiopathic pulmonary fibrosis. The name tells you how vexing the disease is. It's idiopathic. We don't know why it happens. The IPF is named that way. And so, you know, he was telling me that he used your cell by gene atlases to look at millions of single cells in patients with disease, without disease, try to pinpoint the fibroblasts, double click on the fibroblasts and their gene expression.

• 14:56Speaker 01

  It's incredible.

• 14:56Vineeta Agarwala?

  And try to, you know, use that to inform, hey, where could I go after a new drug target in this disease that's fundamentally a strange clump of idiopathic, you know, idiopathic origin? So I think there's a huge, there's a huge group of innovators who are, who love the tools, the visualizations, the query systems, and really the software approach that you've built to making that data incredibly accessible. So.

• 15:19Speaker 01

  Cell by Gene is like almost an accident, though.

• 15:23Vineeta Agarwala?

  Tell us more.

• 15:25Speaker 01

  So do you want to share a little bit about Cell by Gene? Or do you want me to start?

• 15:28Speaker 00

  Well, I mean, I don't know which part you want to get into, but I mean, but the Cell Atlas work overall, I mean, it's kind of this crazy thing that we're, you know, here in, you know, 2025, and there's not the kind of periodic table of elements equivalent for biology, right? So that was sort of a lot of the inspiration of it was, all right, how do we both through work that we're going to do in the Bio Hub and through other grants, be able to pull together and standardize a format where you can have all this data? And when we were starting off, we didn't even necessarily have in mind that we were going to use that to build virtual cell models. I think that that sort of just come into focus as the AI work has advanced. But that's a very exciting thing. We should definitely spend a bunch of time on the virtual cell models, but I'm not sure what you wanted to get into on the Cell Atlas.

• 16:12Speaker 01

  Well, the single cells work is, was one of our first RFAs 10 years ago we started. And we were like, okay, we think this is possible. We actually funded the methodology for it to standardize how it was going to be done. So that was 10 years ago. And we then, we seeded a few labs to start building out that data set, but we were like, there are like millions or billions of different cell types and different permutations, like, how are we going to do this? And especially with like a burgeoning technique. And so we ended up seeding a few groups and they started doing work. And then they told us they had a problem. There was a, there was a bottleneck in their workflow because they couldn't annotate the

• 16:57Speaker 01

  data fast enough. And so we built, Cell by Gene was an annotation tool. That's the original source of this. So we built the annotation tool to make it easy for people who are doing single cell science to be able to annotate the data. And then we put, we put the data that we collected publicly so people could share. But because everyone started using the same annotation tool, everyone was standardized then on the same data formats. And then there started being a community around the tool, and they wanted to share back and build the atlas. So now after 10 years, there are millions of cells that have been built into this shared resource for the entire scientific community. We only funded about 75% of it. Sorry, that's wrong.

• 17:41Speaker 01

  We've only funded 25% of it. 75% came from the broader community saying, this is useful and there's an easy way for us to standardize and build this together.

• 17:52Vineeta Agarwala?

  But default, have the same metadata.

• 17:53Speaker 00

  Yeah.

• 17:53Speaker 01

  That's right.

• 17:54Speaker 00

  It's like an interesting, it's like what you'd call a network effect.

• 17:57Ben Horowitz?

  Yeah, I was gonna say, it sounds like the internet.

• 18:00Vineeta Agarwala?

  Come for the annotations, stay for the, stay for the virtual cell model.

• 18:04Speaker 00

  Well, it was very important when we were getting started with the work to have everyone who was doing it have a consistent format. So that way it could be used and portable. And then once that kind of took off as the way that it would get done, then other people just found it valuable.

• 18:17Vineeta Agarwala?

  And even relative to prior databases like GEO and whatnot, they're just simply not as standardized or QC.

• 18:23Speaker 01

  Yeah.

• 18:24Vineeta Agarwala?

  Control.

• 18:24Erik Torenberg?

  Yeah. But let's get into virtual cells, one of the great challenges, the grand challenges you would focus on. Maybe talk about what is the promise or the hope and maybe some of the challenges or where we're at with it.

• 18:34Speaker 00

  Yeah, I mean, we think that one of, this is going to be one of the most important tools at this point is basically building up the kind of hierarchy from proteins to, to just different structures within the cell to whole, to like whole, like in a virtual immune system or different levels of hierarchy. And we, this is going to end up being like a very important set of tools for people to effectively generate hypotheses for, for different science work. You know, even before you get to the point where you're really running full experiments in it, you can come up with some estimate of how that might run. It will be useful for some of the precision medicine type examples that Priscilla was talking about a few minutes ago.

• 19:19Speaker 00

  But we think that this is like, probably one of the most important sets of tools that you need to build. And it's not a single thing, right? So there's different angles to come at this from. The Cell Atlas data is helpful for understanding things on a cellular level. One of the, the kind of most important things that we're doing right now, the, the, there's this, this great company, Evolutionary Scale, who actually had a bunch of researchers who'd formerly worked at Meta on protein folding models, is joining a Bio Hub. And Alex Reeves, the leader of it, is actually going to be the, the kind of head of the whole science program, which is actually kind of interesting.

• 19:58Ben Horowitz?

  Yeah.

• 19:59Speaker 00

  When you think about it, where it's like you have AI and biology coming together, and really it's like an AI person who understands biology is running it rather than a biologist who has some understanding of AI, I think, just kind of speaks a little bit to where we think the, the relative weight of these things is. But, I mean, we basically view, you know, like Priscilla was saying with the different Bio Hubs, then New York doing cellular engineering will basically make it so that you can have cells that can record different things that are going on around the body and, and share that data, and then you can build that into models. The Chicago Bio Hub being able to record inflammation and basically study that in order to kind of help understand, like, that's a, that's a different data set.

• 20:41Speaker 00

  We have the Imaging Institute, which is, we just trained our first set of models around that, which are the first, like, spatial models around understanding, like, the way that, that kind of cells look in different states. And eventually, just like you have this analogy on the, kind of the industry side around language models where you have different capabilities, and then over time you train them into models and it gets more and more general, that's kind of the idea here. So we'll, we'll, we'll build the Bio Hubs around grand biological challenges. The Bio Hubs will build tools that will generate novel data sets. We will build models based on those and then eventually combine the models into an increasingly

• 21:21Speaker 00

  general view of a virtual cell that will be useful, both for scientists and hopefully startups and companies that are working on finding drugs, which is not our part of the whole thing, but, but I think is obviously a really important part of what needs to happen.

• 21:35Speaker 01

  Yeah. And, you know, you guys think about risk all the time in terms of when you make investments. Like, I think the promise of being able to do virtual biology using a virtual cell model is you can actually take on riskier ideas. Right now, like, grant funding can be hard to come by, and the wet lab work is expensive and slow, and it's not just, you know, money, it's also time. And so you have to choose something that you think is going to have some likelihood of success to keep your lab career going. And so it naturally lends people to take on, like, some risk, but not a lot of risk, because they need to make sure that they are hitting, like, a certain percentage of

• 22:18Speaker 01

  the time to make tenure or publish or whatever they need to do. But if you had a virtual cell model where you could simulate really high quality biology, you could actually then start testing it and tinkering on the computational side and, like, ask riskier questions, things that would have been expensive and costly in terms of time and resources to do in the lab, and actually see if there is promise doing the experiments in Silco before you make the time and money investment in the wet lab.

• 22:47Vineeta Agarwala?

  Do you think of it kind of like a model organism?

• 22:49Ben Horowitz?

  Yeah.

• 22:49Vineeta Agarwala?

  Like, it's the new fly.

• 22:53Ben Horowitz?

  I was gonna ask, given the complexity of a cell, like, how close, like, how accurate do you think you'll get the model to? I mean, just assuming, I mean, maybe you get it to like a perfectly accurate representation of a cell, but like, how accurate to be useful would the virtual cell have to be?

• 23:10Speaker 01

  I think it will obviously iterate and get better and better because right now, we, like, right now, we're still just talking about transcriptomics. We're expanding into different ways of looking at the cell. But you get more and more accuracy. But I don't think it needs to be 100% accurate to be useful because you just want to be able to de-risk the idea on the front end a little bit. And the more and more you de-risk it, the more efficient it gets, obviously. But it'll be useful if you even get directional signal. And yes, I do, we do think about it like as a model organism, but in a way that's like, has fidelity to the human body, like, you know, like, I don't want to-

• 23:51Vineeta Agarwala?

  All models are wrong, some are useful.

• 23:53Speaker 01

  Yeah.

• 23:54Ben Horowitz?

  Yeah.

• 23:54Vineeta Agarwala?

  This is hopefully has, has utility on certain acts.

• 23:57Speaker 00

  Exactly. And just like the language models, you build in specific capabilities. So it's not, so, for example, you know, one of the models that we're, we're publishing is, is variant former, right? It basically, you know, makes it so that it's trained on a bunch of effectively pairs. If you, you have a cell, you apply CRISPR to it in a place, so you see what comes out at the other side. So it's, it basically is able to make that kind of a prediction. Like, okay, if you have this edit that you're doing to, to a cell, what is likely going to happen?

• 24:29Speaker 00

  Another one of the models is, it's this diffusion model. Basically, you can describe a type of cell that you would like it to simulate. Then it will just produce a kind of synthetic model of, of, of the cell.

• 24:41Speaker 00

  Again, I mean, it's kind of interesting because to Priscilla's point before about how everyone is different and, and like, and different cells have, have kind of, you know, so you want to be able to simulate these kind of rare configurations, having at least a synthetic version of what that could look like is interesting, and then you can test against that. The cryo model, I think, is interesting because it's spatial. So it kind of gives you a sense of there are all these different models that you can have that allow you to basically look at different kinds of things, and then you just train them in to be increasingly general over time.

• 25:15Ben Horowitz?

  Very interesting. And is the, is the modeling technology basically LLMs? Or like, like, is there, is there a reasoning model? Is it like a just-

• 25:23Speaker 00

  Oh, that's actually, yeah, no, that's a fascinating one, too. Because one of the new models, I think this one is very early, but it's, it's, it's basically the first reasoning model over biology. So the, the idea is that, yeah, you, you effectively have these models that, that kind of simulate world models in different ways, and then you want it to be able to not just,

• 25:46Speaker 00

  be able to spit out correlations, right? In terms of like what it's found, but actually be able to kind of reason through how things would, would evolve and why things would happen.

• 25:57Speaker 00

  I know it's quite early, but it's, but it is interesting conceptually as what I think is clearly going to be an important direction in terms of how these models evolve.

• 26:08Ben Horowitz?

  Yeah, no, because that's what I was thinking, you know, that if it doesn't work, the next question you have is why?

• 26:15Speaker 00

  Yeah. You know, like- But I think what you find in reasoning, the analogy to-

• 26:19Ben Horowitz?

  Because sometimes you're married to your hypothesis.

• 26:22Speaker 00

  Sure, sure. Yeah, I mean, the, the, yeah, I thought, I thought you were saying if, if the reasoning model doesn't work, why? I mean, I think the-

• 26:30Ben Horowitz?

  You're way in the making.

• 26:32Speaker 00

  I mean, the language model analogy for that would be you need better kind of world models or, or better pre-trained models in order to get the reasoning to be good. But it's, yeah, you just, you build more, you build more capabilities into it. And I think that there's probably an order to. So the work that Alex and the evolutionary scale folks worked on is, a lot of it is protein, which is interesting because that's at a kind of smaller resolution, obviously, than the cellular data and the cell, cell atlas. But part of the hypothesis is that you can look at all these different cells and you can kind of simulate how they might behave, but you're gonna have a somewhat shallow understanding unless you actually

• 27:11Speaker 00

  have this hierarchical understanding of what, how the subcomponents of the cells are going to interact. So our view is that you basically want to build up a state-of-the-art protein model, and then have that be a part of the state-of-the-art cellular model. And then, once you have that, you build things like the virtual immune system, which allows you to simulate much more complicated systems. But it's sort of this like hierarchical approach to building up these, these virtual models.

• 27:40Ben Horowitz?

  That makes a lot of sense because also, as you get into personalization, you've got like common proteins combining into a unique cell. So that makes it like from a systems standpoint, that makes it like much more manageable. That, that makes a lot of sense. Interesting.

• 27:57Speaker 00

  Yeah. Yeah, no, it's, it's, it's very fascinating stuff.

• 28:00Ben Horowitz?

  Yeah.

• 28:01Vineeta Agarwala?

  So you guys are announcing some big news this week. Do you want to give us a sneak preview?

• 28:06Speaker 01

  Well, the big news is thinking about how we are going to be coming together as one team. And, you know, in the past, we have done, we've run BioHubs and we've done, built software. We've done some AI research, but all that has been really thinking about, has been a little bit decentralized. But now, under Alex's leadership, we are going to come together as the Biohub, a, an, an operating philanthropy where we are doing the science in service of a singular goal together. And how do we actually advance the state of biology and research at the intersection of AI and biology?

• 28:47Vineeta Agarwala?

  Amazing. Alex is amazing.

• 28:49Speaker 00

  Yeah, no, he's great. And then, and then the other thing is that the piece that, that I've mentioned earlier, which is just, yeah, I mean, CCI has focused on a number of different things. We've really just found over time that we, we feel like we've been able to make the biggest difference in science, so we've just kept on doubling down on it. And we're gonna continue doing work in education. We're gonna continue supporting local communities and, and those different pieces. But going forward, the Biohub is really going to be the main thrust of our philanthropy. And we're very excited about that because I think that this is, there, there has been, you know, when we started the mission to see if we could help the scientific community cure and prevent diseases by the end of the century. I do think with the advances in AI, that should be possible to do significantly sooner.

• 29:30Speaker 00

  And that is a very worthy and important and very exciting goal that we think we kind of have a unique place in the ecosystem that we can help empower others to make fast progress on that.

• 29:41Ben Horowitz?

  So there, there's obviously like plenty of advantages to decentralization from a management, communication overhead and so forth. And so like, what are you trying to add by adding this kind of new layer slash unification on top? Like, what, what are the outputs? And then I guess what are the complexities to that? Because that's, I'm sorry to ask a CEO question.

• 30:04Speaker 00

  No, no, I mean, I'm like obsessed with this stuff. We think about this.

• 30:08Ben Horowitz?

  You wanna go for it? Then I can jump in.

• 30:09Speaker 01

  Yeah, so they're obviously amazing groups doing frontier AI and a lot of groups doing great frontier biology. And where we think we can do uniquely is actually tie these two together. And we are, we've funded data sets, we've built data sets. We're like building the instrumentation now to be able to look at the cell, whether it's, you know, for, at the tissue cell, cell communication, our cryo EM, where we can look at the cell at nearly atomic level. So we have the ability to not only build the data sets, but actually shape and form them the way we want, based on what we see as necessary to complement the existing body of knowledge.

• 30:53Speaker 01

  And so we have amazing teams doing that work and we're building these AI models. And so what, the reason to do it together is then we can actually complete the flywheel. Like, you know, the model is looking like it has some gaps and blind spots in this area. Okay, who do we talk to? How do we build the next data set? And, you know, we're seeing this in the lab, like, the metadata is going to be so rich that we can feed back into the way that we do this modeling.

• 31:23Ben Horowitz?

  Yeah.

• 31:23Speaker 01

  And so if we can close that loop, which is our goal, in bringing everyone together, it's, I think it's gonna be incredibly powerful. And it's, it's more than, it, it's more than just like, you know, writing down a spec and saying like, please deliver this. Like, these people need to be sort of working shoulder to shoulder and shaping each other's work for this to actually be the, a more and more accurate model of how the human cell works.

• 31:49Ben Horowitz?

  Well, yeah, that's so interesting because that is exactly, like, that's been the biggest surprise in the industry for us in AI world, like, forget biology for one second, is that the domain-specific models have been like super interesting. Like, the, the original cases, well, like, there's just, some AIs are getting so smart, they're gonna be smarter than everybody at everything. But like on video models, like, every video model is best at something, but not everything. And so knowing what problem you're solving actually turns out to be sort of ironically very important in AI because you can actually get to a way better result-

• 32:30Speaker 01

  Yes.

• 32:31Ben Horowitz?

  -if you put the two together. Like, yeah, we're, we're seeing that over and over, over again, in a way that, that is- I would say very counterintuitive to the whole narrative kind of going into it.

• 32:42Vineeta Agarwala?

  In biology, it used to be the, or at least, you know, one assumption was all the data sets aren't on the internet. So part of the reason you need a domain-specific model is that the data sets are not public. You guys are kind of bucking that trend, too, by creating a lot of open source access to the data. And then even then, it sounds like you're betting, you know, on the trend that we're seeing in other industries. But still, there will be nuance in how you annotate that data, curate that data.

• 33:06Ben Horowitz?

  Well, and how you talk to a scientist, right? Like, so, because you have to not only know the data and the model and so forth, but like, the conversation is what we keep finding out ends up being very, very important, right?

• 33:16Speaker 01

  So rich and so important in how you actually.

• 33:18Ben Horowitz?

  A scientist isn't going to talk to it like, you know, I talked to ChatGPT or whatever.

• 33:22Vineeta Agarwala?

  Well, this is the first fly you can talk to.

• 33:24Ben Horowitz?

  Yeah, that's really, that's super exciting.

• 33:28Speaker 01

  And I think user interface is actually really important. You talked about, you guys have a founder who's using Cell by Gene. That user interface was intentionally designed to not need to have a computational, or really a very deep biological background to be able to use. Because you want people coming from different fields to look at the problem. It's like, look here, help us solve problems here. And so, building that user interface in a way where it's not a very high barrier to entry, to be able to poke around and learn something and bring knowledge back to your work, that's intentional. And we're really hoping when we build these virtual models, that we get to a place where

• 34:08Speaker 01

  we can allow a lower and lower barrier entry for people to say like, you know, like, I have some knowledge about this, maybe I can contribute. A very pertinent example is, turns out, I think immunology has a ton to do with neurodegeneration, right?

• 34:23Vineeta Agarwala?

  Seems like immunology is behind all this.

• 34:25Speaker 01

  Everything.

• 34:25Vineeta Agarwala?

  So might be part of your century vision.

• 34:28Speaker 01

  So you need to be able to allow the immunologists to come in and understand neurodegeneration and understand how their world fits in. And so, the more you lower the barrier to entry allows people to actually think in a sort of truly collaborative and interdisciplinary way.

• 34:45Vineeta Agarwala?

  So will the Biohub grow as a team? Like, will you employ more people at the Biohub proper? Or are you moving towards more of a network model with more sites, more labs, more community-driven data sets? Like, which, which is the thrust, or maybe it's both?

• 35:01Speaker 00

  Probably a little of both. And we've added new Biohubs over time. And then, we're also building up more of this, like, central AI team.

• 35:11Vineeta Agarwala?

  Cool.

• 35:12Speaker 00

  So, but I don't, I think that these organizational questions of how do you set this up are fascinating. And a lot of our approach is sort of informed by what the rest of the field is doing. Because you kind of think about science as, it's this portfolio, right? Society has a portfolio of stuff that it's trying to do. And as, in terms of philanthropy, you want to be the most additive that you can be by trying to figure out what else is underrepresented. So, science by default is very decentralized, right? It's like, kind of the, the way that granting has worked, the way that I think scientists by default want to work. So I think a lot of what we've found is that figuring out ways to encourage collaboration

• 35:56Speaker 00

  in ways that otherwise seem very simple, but weren't happening before, can unlock a lot of value. So the very first Biohub, what we did, there were two kind of interesting things. One was, it was this collaboration between UCSF, Stanford, and Berkeley. And there are all these really smart people at all these different places who previously, I guess in theory, they could have figured out a way to work together, but there was not really a formal construct for them to do that. And this just allowed a lot more collaboration. The other one is cross-discipline, basically having biologists sit next to engineers. And this view that like, these two disciplines are things that need to, and I don't know, I mean, I'm sure, you know, you've seen this in a lot of, in a lot of the companies, but

• 36:40Speaker 00

  like, it's, there's so many interesting.

• 36:43Ben Horowitz?

  And the companies, they always set them apart.

• 36:44Speaker 00

  Well, it's interesting, no, it's interesting how many organizational questions or problems you can fix just by having two teams sit together, right? It's like, it doesn't matter what the org chart is, or like, whatever. It's like, you guys need to sit next to each other and, until you get this thing to work. And that's something I really believe in, so.

• 37:02Vineeta Agarwala?

  And you have time.

• 37:02Ben Horowitz?

  Yeah.

• 37:02Vineeta Agarwala?

  You have time to 15 years.

• 37:03Ben Horowitz?

  Well, no, it's all like, communication is such an underrated problem in general.

• 37:08Speaker 00

  Yeah.

• 37:08Ben Horowitz?

  In, in all kinds of, in building anything, or solving anything. So, that's a, that's pretty neat.

• 37:15Speaker 00

  Yeah, and it's, it's just really kind of simple stuff, but, but I think it's, it's sort of novel as a model. And one of the things that's, so we've now copied this from the first Biohub to the Biohub network and expanded it to other models. But it's also just been neat to see other folks who are working in the field also adopt similar models, because it's a pretty intuitive thing. But, you know, at some point, you'll reach the point where, you know, actually, it's really good to have decentralized work, too, right? So it shouldn't be that like, we're not saying that this is like, the way that all science should work. We're just saying that there's a space for this that can unlock a lot of value because it, for whatever reason, hasn't been the default.

• 37:53Speaker 01

  Yeah. And we still rely on, like.

• 37:56Ben Horowitz?

  Yeah, there's famous like, stories in the MIT lab about that. That's how they invented lasers and so forth, is they put a bunch of people from different departments in the same space.

• 38:06Speaker 01

  Well, actually, physics is where we got a lot of the inspiration. Like, physics has just historically been, like, labs have just rallied around big projects and big shared resources.

• 38:18Speaker 01

  And we will, you know, we are relatively centralized, but we still depend on a lot of labs who are doing sort of exact frontier work, or complementary work to come together to support this, there's that. But, one more thought on your expansion question is like, and maybe this is like, the modern AI lab, we are not expanding, like, a lot of square footage, per se, but we're expanding our compute.

• 38:43Speaker 00

  The researchers, they don't want employees working for them, they don't want space. Yeah, they just want GPUs.

• 38:47Speaker 01

  So, it's just like, in a sense, that's new lab space. It's much more expensive than what lab space.

• 38:55Vineeta Agarwala?

  And you guys have always been creative on that, even in the last few years. You've created ways to share access to compute, you've enabled academic labs to, you know, I forgot the name of your program.

• 39:07Speaker 01

  Yeah, um, scientists and residents, or something like that.

• 39:10Speaker 00

  Yeah.

• 39:12Vineeta Agarwala?

  Rental kind of hoteling.

• 39:13Speaker 01

  The core of it is, you know, if you look at individual labs, they'll have like, like, a large lab would have tens of GPUs. And we were the first to really build a large-scale compute cluster. A thousand, now we're, we have plans to move to the 10,000 range. And that, one, requires a different type of project, obviously. You're, you're able to ask different types of questions. And it's a resource that we use, but also, we've invited scientists to apply and say like, what question do you have that could use this amount of resource and be able to stem, sort of seed collaborations that way?

• 39:57Vineeta Agarwala?

  And so, if a scientist is out there listening, like, who's not employed by the Biohub, or working at the Biohub, but wants to collaborate with the Biohub.

• 40:05Speaker 01

  Yeah.

• 40:05Vineeta Agarwala?

  That you're going to create.

• 40:07Speaker 01

  Come talk to us.

• 40:07Vineeta Agarwala?

  Really interesting, interesting doors to utilize their resources. That's awesome.

• 40:12Speaker 00

  Yeah, I mean, the GPUs are somewhat zero sum, right? So, the data isn't, so, yeah.

• 40:18Speaker 01

  Yeah, fair enough, fair enough.

• 40:20Erik Torenberg?

  So you're about to celebrate 10 years doing this. As, as you look out in the years to come, what else can you tell us about either things that you're thinking about for the future, or maybe even principles, or a north star that's going to guide how you guys grow and evolve going forward?

• 40:36Speaker 01

  You know, it's been really interesting in the past 10 years, because I actually spent the first few years completely envious of people working for for-profit companies. Because there's so much clarity, like, the market will tell you, whether or not it's private or public, will tell you if you're doing a good job.

• 40:54Speaker 00

  If they think you're doing it.

• 40:55Speaker 01

  If they think you're doing it.

• 40:57Ben Horowitz?

  They're not always right.

• 40:58Speaker 01

  They're not always right.

• 40:59Erik Torenberg?

  I know, it's a big difference.

• 41:01Speaker 01

  But I was still envious, because that was, I was like, I craved that feedback, like, am I doing a good job? And, you know, 10 years in, you know, the reason why we're doubling down on biology is like, not only did we achieve what we said we were going to do, and when we set out to, set out on these projects, it actually delivered more than we thought we were going to. And I was like, okay, that's a signal I can latch on to. And like, that's a signal, like, we can really continue doubling down and doing more of that. And so, I think it's continuing to tolerate the early ambiguity, when you're like, okay, I'm going to do more of this. And, and being patient, but, being willing to have a long time horizon, but be impatient

• 41:46Speaker 01

  at the same time. Because it's all those iterations along the way that have sort of allowed us to get to this place, where, you know, to get lucky, ready, having built data, data sets, to take advantage of AI and large language models, that's because of all the work that we have been doing. And so, being able to continue moving forward in this ambiguity, and sometimes lack of signal, on a big goal, like, I think we sort of set the DNA for that.

• 42:12Vineeta Agarwala?

  Amazing.

• 42:12Speaker 01

  Oh, no pun intended.

• 42:14Speaker 00

  Yeah. But we get to see how many people use the tools and the feedback. Yeah, yeah, yeah.

• 42:19Ben Horowitz?

  Yeah, you have customers, which is pretty cool.

• 42:21Speaker 00

  Yeah.

• 42:21Speaker 01

  Yeah.

• 42:21Ben Horowitz?

  For philanthropy, like, that's awesome.

• 42:23Speaker 00

  Yeah, no, it's, it's one of the fun things about building tools. It's like, you kind of get to see, how valuable do people find the tools? Do people use the tools in order to publish important work?

• 42:34Ben Horowitz?

  Right, right, right, right. Yeah, and I mean, our feedback is, they're awesome.

• 42:41Ben Horowitz?

  And completely unique, by the way. So like, the, the other thing is, like, what would you use if you didn't have this? It's like, there's nothing.

• 42:49Speaker 00

  No, yeah, it's a real, it's a real kind of void. I mean, there's this whole pipeline that, that needs to exist, from accelerating basic science, to funding a lot of people to use it, to then, you can get into the biotechs that basically can start to work on, on, on basically coming up with novel therapies, and then you get the pharma companies that do them at scale. And then there's a space for philanthropy on the other side of public health, of basically taking the, the therapies and, and kind of bringing them out to everyone in the world. But this is a, a space that, I mean, that there's just going to be a huge amount of leverage with AI. And it is, yeah, it, it still seems like there could be a lot more effort in this space around building tools and just accelerate the whole thing a lot better.

• 43:33Ben Horowitz?

  Yeah, and I do think it is the place where you are completely unique, right? The other things, there are other people who can do that, but there's nobody doing what you're doing.

• 43:43Speaker 00

  It's got good, good founder market.

• 43:44Ben Horowitz?

  Yes, founder market, if we didn't exist, would it be a problem? Yes, like, those questions really land.

• 43:53Speaker 00

  It's like, one of us is an engineer, the other one, scientist, doctor.

• 43:57Ben Horowitz?

  Yeah, very happy in this direction.

• 43:59Speaker 00

  Yeah.

• 44:00Ben Horowitz?

  We thank you very much, not only for our companies, but for us as humans, for working on this work. It's amazing work.

• 44:07Speaker 00

  Oh, thank you.

• 44:08Speaker 01

  Thank you.

• 44:09Erik Torenberg?

  Thank you, guys.

• 44:09Speaker 01

  Thank you guys.

• 44:10Vineeta Agarwala?

  Much.

• 44:12Erik Torenberg?

  Thanks for listening to this episode of the A16Z Podcast. If you liked this episode, be sure to like, comment, subscribe, leave us a rating or review, and share it with your friends and family. For more episodes, go to YouTube, Apple Podcasts, and Spotify. Follow us on X, A16Z, and subscribe to our Substack at A16Z.substack.com. Thanks again for listening, and I'll see you in the next episode. As a reminder, the content here is for informational purposes only, should not be taken as legal, business, tax, or investment advice, or be used to evaluate any investment or security, and is not directed at any investors or potential investors in any A16Z fund. Please note that A16Z and its affiliates may also maintain investments in the companies discussed in this podcast.

• 44:56Erik Torenberg?

  For more details, including a link to our investments, please see A16Z.com/disclosures.