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  • Mark Zuckerberg, Priscilla Chan, and Alex Rives on CZI Biohub, Open-Source AI, and Building World Models of Biology to Cure All Disease

    Mark Zuckerberg, Priscilla Chan, and AI researcher Alex Rives sat down with the No Priors podcast to explain why CZI Biohub became the primary focus of their philanthropy, why they committed $500 million to a virtual biology initiative, and why they are giving the resulting AI models away as open source instead of building a company. The conversation moves from a goal that Nobel laureates once laughed at, curing, preventing, and managing all disease by the end of the century, to a concrete technical strategy: build world models of biology layer by layer, from proteins to cells to whole systems, and put them in every scientist’s hands.

    TLDW

    This is the clearest public articulation yet of how the Chan Zuckerberg Initiative thinks about AI and biology. The throughline starts a decade ago when Zuckerberg and Chan asked scientists how to cure all disease and learned the real bottleneck was tooling, siloed labs, and unshared knowledge, not a lack of ambition. That insight produced the Human Cell Atlas, the CELLxGENE annotation tool, and a corpus of single-cell transcriptomics that large language models could finally make sense of. Now Biohub couples a frontier AI lab with frontier wet-lab biology under one roof across San Francisco, New York, and Chicago, organized around the virtual biology initiative and the long-term goal of a virtual cell. Alex Rives, the AI researcher behind the ESM protein language models, walks through their newly released ESM-based world model of protein biology: trained on billions of protein sequences, it predicts atomic-resolution structures blazingly fast, folded over 1.1 billion proteins, designs novel proteins and single-chain antibodies as an emergent property, and found nanomolar binders in a single 96-well plate. The discussion covers mechanistic interpretability as a way to extract genuinely new biological knowledge, personalized medicine driven by understanding the chain from gene variant to protein to disease, predicting off-target toxicity before human trials, rare-disease patient organizing, the baby KJ CRISPR case, biosafety tradeoffs of open source, talent and why frontier biology plus frontier AI is a recruiting moat, and what success looks like five years out.

    Thoughts

    The most important claim in this conversation is also the easiest to miss because it is delivered casually: protein design is an emergent property of a model that was never asked to design proteins. Rives is explicit that they did not build a model for antibodies and did not build a model to bind a particular target. They built a model that understands proteins, trained on raw sequence with a next-token objective, and protein design, structure prediction, and antibody generation fell out of it. That is the language-model bet transplanted into biology, and the fact that it produced nanomolar binders, the threshold for actual therapeutic activity, in a single 96-well plate rather than a high-throughput screen of millions is the kind of result that quietly resets what a small team can attempt. If that generalizes, the binding curve for “design a molecule” bends the same way the cost curve for “write working code” did.

    What makes the strategy coherent, rather than just a well-funded AI lab, is the insistence that the wet lab and the AI lab are a single effort. Most of biology’s useful data does not exist on the internet the way human language does. You cannot pay a factory to produce it. Someone has to invent the cellular engineering in New York, the inflammation-sensing devices in Chicago, the translucent-zebrafish imaging, and that is the actual product of frontier biology: new instruments that generate data nobody has ever seen, which in turn make new classes of models possible. This is the part venture-backed competitors will struggle to replicate, because it requires patience measured in 10 to 15 year horizons and a willingness to spend on data generation that has no business model attached. Zuckerberg is almost dismissive about it, noting they could probably run it as a business but that not having to think about monetization is strategically simplifying. The nonprofit structure is not charity window-dressing here. It is what lets them release the models as an open discovery engine and harness the entire academic and biotech field rather than competing with it.

    The mechanistic interpretability thread deserves more attention than it will get. Interpretability has mostly been a safety and alignment story for language models, a way to peer inside the black box and check that the representations match our understanding of the world. Rives flips it: the protein models have been trained on both known and unknown biology, billions of sequences including proteins we understand nothing about, and they are building representations that connect the unknown proteins to the known ones through an underlying structural grammar. The promise is that interpretability becomes a discovery tool, not just an audit tool. You open the box and find biology the field has not characterized yet, the mechanism of action for a treatment, a system in the body nobody mapped. That is a fundamentally more optimistic use of the same toolkit, and it is the part of the launch Sarah Guo and Elad Gil both flag as the most interesting.

    Chan’s framing of personalized medicine is worth sitting with because it reframes the entire goal away from “cure disease X.” She wants to treat the individual as an individual: understand this person’s genetics, their risk profile, the mechanistic chain from a specific gene variant through a protein to a disease process, and then design a drug bespoke to them. The current reality she describes, sitting in PubMed reading a paper’s supplement asking “am I represented in this cohort,” guessing whether a drug that kind of impacts a pathway that is probably implicated might do something, is a brutal and accurate picture of how non-standard cases are actually handled today. The vision is generalizable tools delivering personalized answers, which is the same put-the-tool-in-the-individual’s-hands philosophy Zuckerberg applies to open-source AI and, by his own analogy, to social media. Whether you find that analogy reassuring or not, the consistency of the worldview is real: they genuinely do not believe in a central super-intelligence solving science, and the whole architecture follows from that.

    The honest gap they name is the clinic. Chan is candid that the science will start moving fast but that translating to patients requires changing how clinical research itself works, and that part is still shaping up. The most interesting near-term lever is not a virtual FDA trial but the recruitment and economics flip for rare disease: patient groups self-organizing registries, biobanks, and natural-history studies, compressing timelines from decades to a handful of years, paired with models that lower the cost of generating a candidate. The baby KJ case, a custom CRISPR therapeutic to edit a single mutation, delivered to liver cells specifically because that target was deliverable, is the proof of concept for why disease selection and delivery creativity matter as much as the molecule. The molecule is becoming the cheap part. The rest of the chain is where the next decade of work actually sits.

    Key Takeaways

    • CZI Biohub is now the primary philanthropic focus of the Chan Zuckerberg Initiative, a shift the team formalized in the past year.
    • They committed $500 million to the virtual biology initiative, the unifying theme across the Biohubs.
    • The original goal, set roughly 10 years ago, was to cure, prevent, and manage all disease by the end of the century. Zuckerberg now thinks “end of the century” is too conservative.
    • Nobel Prize winning scientists initially laughed at the all-disease ambition. When pressed for why it was impossible, the real answers were silos, locked-up unpublished information, and the inability to build shared tools.
    • The recurring example: a postdoc builds a great tool, it lives on their computer, they graduate, and the tool is gone. Shared, durable tooling was the missing layer.
    • CZI is explicit that they are not the ones who will cure diseases. Their role is building tools that accelerate the entire scientific field so the field collectively cures them.
    • The first request for application was single-cell sequencing, funding methods so scientists could share how to do it.
    • That work led to funding the Human Cell Atlas, now one of the largest databases of single-cell transcriptomics.
    • They built CELLxGENE, a simple annotation tool, around which a community formed and contributed data CZI had nothing to do with creating. It is now a corpus underpinning many transcriptomic models.
    • Critics called the data gathering “stamp collecting.” The arrival of large language models, which can make sense of large amounts of data, answered that critique.
    • The ambition is to move biology from a discovery-based science to an engineering-based science, systematically understanding how living cells work and why things go wrong.
    • Biohub couples a frontier AI lab with a frontier biology effort. Unlike language models, biology lacks abundant internet-scale data, so new science is required to generate the data the models need.
    • The Biohubs are specialized: New York focuses on cellular engineering, Chicago builds devices to measure things like inflammation, plus imaging work and translucent-zebrafish development studies.
    • Alex Rives, who built the ESM protein language models and founded EvolutionaryScale after working at Meta FAIR, now leads the AI effort. The team raised venture capital before joining CZI’s nonprofit structure.
    • The strategy is hierarchical: model proteins first, then cells, then whole systems, because you cannot understand cells without understanding protein interactions.
    • They collect data strategically to bridge across the hierarchy, for example spatial transcriptomics showing where RNA localizes within a cell, and sensors that observe cell-to-cell communication.
    • The newly released ESM-based model is a world model of protein biology, trained on billions of protein sequences, predicting atomic-resolution structure extremely fast at a Pareto-optimal frontier of speed and accuracy.
    • They folded over 1.1 billion proteins and predicted their structures, identifying connecting features through mechanistic interpretability.
    • The model hits state of the art on structure prediction benchmarks, especially protein-protein and protein-antibody interactions, which are critical for therapeutic design.
    • Protein and antibody design are emergent properties. They designed a model to understand proteins, not to bind any specific target, and design capability fell out of it.
    • In one experiment, they selected from hundreds of thousands of digital trajectories, synthesized 96 proteins in a single well plate, and found nanomolar binders, the threshold for therapeutic activity.
    • Results were validated with the Biohub’s cryo-EM microscopes and structural biology center, confirming function and atomic-resolution binding interfaces.
    • Mechanistic interpretability is reframed as a discovery tool: open the black box to find biology nobody has characterized, not just to audit the model.
    • Chan’s vision of personalized medicine: understand a person’s genetics, the mechanistic chain from gene variant to protein to disease, then design a bespoke drug and intervene.
    • A comprehensive model of how cells work could predict off-target effects, like a receptor on kidney cells causing renal toxicity, before human trials.
    • They study systems rather than individual diseases. Inflammation is a major Chicago focus because it connects to many diseases.
    • A typical drug trial runs about 15 years and $1.5 billion. Only roughly $50 million is the molecule and preclinical work. The other $1.45 billion is drug development, much of it gated on regulation, recruitment, and failures from toxicity or absorption.
    • The baby KJ case at CHOP delivered a custom CRISPR therapeutic to edit a single mutation, chosen carefully because his liver cells were a deliverable target.
    • CZI’s “Rare As One” program supports rare-disease patient groups self-organizing registries, biobanks, and even their own clinical trials, compressing gene-therapy timelines from decades to 3 to 5 years.
    • Letting people opt in to frontier trials, while preserving historical vetting for the general population, is named as a key shift that could accelerate biology.
    • The open-source philosophy mirrors Zuckerberg’s broader ethos: empower individuals with tools rather than centralizing power in a few institutions or a single super-intelligence.
    • Biosafety is acknowledged as a real consideration that open-source biology will need to balance and handle carefully.
    • On talent: AI researchers could join any frontier lab, but no other organization pairs frontier biology with frontier AI, which is the recruiting moat.
    • You do not need a huge team. Zuckerberg argues real AI progress can come from a strong group of a dozen or a couple dozen people.
    • Researchers have been connecting the released model to agentic systems to automate the entire protein design process.
    • The next big challenge is the virtual cell: a system that models the proteomic, genetic, and transcriptomic layers and connects them to phenotype, generalizing to interventions it was never trained on.
    • Like every lab, Biohub is compute and data constrained, constantly deciding whether to double down on proteins or push further into cellular work.
    • Five-year success: a hierarchical set of world models of biology and doing the highest-quality, uniquely contributive work in the world, a setup the team believes no other organization has.
    • The biggest update of the past year: formalizing Biohub as the philanthropy’s core, and flipping leadership from biologists interested in technology to an AI researcher with a biology background.
    • Zuckerberg’s read on the broader industry: the exponential curve is on track and still accelerating, which validates making a very big long-term investment.

    Detailed Summary

    From “cure all disease” to a tooling problem

    The origin story is a decade old. Zuckerberg and Chan wanted to build an organization that could cure, prevent, and manage all disease by the end of the century, and a series of meetings with famous, Nobel Prize winning scientists produced laughter rather than encouragement. Instead of retreating, they kept asking why it was impossible. The answers, once scientists relented, were not about biology being too hard. They were about how science is organized: researchers work in silos, published information gets locked up for long periods, and there is no good way to build and share durable tools. The image that stuck was a postdoc building an excellent tool that lives on a single computer and vanishes when that person graduates. The bottleneck was infrastructure and shared knowledge, and that is where CZI decided it could contribute.

    The path from single-cell sequencing to a world model

    The original Biohub model brought engineers and scientists together across universities for long-term tool development, and it worked. CZI’s first request for application targeted single-cell sequencing, funding the methods so scientists could share how to read the RNA transcribed in individual cells. That seeded the Human Cell Atlas, now one of the largest single-cell transcriptomics databases. When annotation became a bottleneck, CZI built CELLxGENE, a simple annotation tool, and a community formed around it and contributed data CZI never funded. Critics dismissed it as stamp collecting, gathering bits of data without extracting wisdom. Then large language models arrived and demonstrated they could make sense of exactly that kind of large-scale data, and Chan describes the delight of realizing the missing engine had appeared.

    Frontier AI married to frontier biology

    The unifying theme is the virtual biology initiative, and the structural insight is that the AI effort and the wet-lab effort are a single integrated organization, not two collaborating ones. Biology lacks the internet-scale data that language models enjoy. You cannot buy the data from a factory. So Biohub invents the science that generates it: cellular engineering in New York to record what happens inside the body, devices in Chicago to measure inflammation, imaging to visualize the previously invisible, and translucent zebrafish to watch development unfold across cells as the brain forms. Each new instrument creates a new dataset, which enables a new class of model. Rives, who built the ESM models and founded EvolutionaryScale before joining, frames this as the start of a new era of science, where systems that predict the next token can learn world models of biology from the data, provided you build at the right scale with the right people.

    Building biology hierarchically

    The team is deliberate that each layer of biology is qualitatively different and must be built up in order. You cannot jump to cells without understanding protein interactions, and you cannot model the immune system without first understanding cells. So the approach starts with the building blocks, the proteins, and ladders upward. The advantage of a single integrated effort is the ability to gather data that connects the hierarchy: spatial transcriptomics that show where RNA localizes inside a cell, sensors that capture cell-to-cell communication, developmental imaging in zebrafish. That connective tissue is what lets the modeling generalize across levels. The interviewer, a former wet-lab biologist with a PhD, notes that the reductionist and systems camps of biology historically never worked together deeply, and that bridging them is one of the genuinely novel things about the effort.

    The ESM-based protein world model

    The launch at the center of the conversation, roughly a week old at recording, is an open system for scientific discovery in protein biology: a language-model-based world model trained on billions of protein sequences. It learns emergent representations of protein biology and predicts atomic-resolution structure at blazing speed, sitting on a Pareto-optimal frontier of speed and accuracy. They folded over 1.1 billion proteins and used mechanistic interpretability to identify features connecting them. It reaches state of the art across structure-prediction benchmarks, with particular strength on protein-protein and protein-antibody interactions that matter for therapeutics. The headline result: they used the model to design proteins and single-chain antibodies digitally, selected from hundreds of thousands of trajectories, synthesized just 96 in a single well plate, and found nanomolar binders, replacing high-throughput screens of millions of antibodies. Validation came from the Biohub’s cryo-EM structural biology center, confirming both function and the atomic-resolution binding interfaces.

    Interpretability as discovery, and personalized medicine

    Rives reframes mechanistic interpretability, usually aimed at language models, as a way to extract new biological knowledge. The protein models are trained on both known and unknown biology and develop representations that connect uncharacterized proteins to understood ones through an underlying structural grammar. Opening that black box could reveal systems in the body or mechanisms of action for treatments that the field has never mapped. Chan connects this to a personalized-medicine vision: understand an individual’s genetics and the mechanistic chain from gene variant to protein to disease, then design a bespoke intervention. She contrasts it with today’s reality of reading PubMed supplements and guessing whether you are represented in a study cohort. For some diseases, simply knowing which gene variants cause disease is already empowering. For others, the chain is understood and the missing piece is the ability to change a protein’s function, which is where designed proteins could actually cure.

    Drug development, off-target effects, and rare disease

    The interviewers press on translation, noting a typical trial runs 15 years and $1.5 billion, with only about $50 million in the molecule and preclinical work and the rest in development gated on regulation, recruitment, toxicity, and absorption failures. Chan’s hope is that comprehensive cell models predict off-target effects, like an unanticipated receptor on kidney cells causing renal toxicity, before human trials. They study systems such as inflammation and the immune system rather than chasing individual diseases. The baby KJ case at CHOP, a custom CRISPR therapeutic editing a single mutation delivered to liver cells, illustrates how careful disease and delivery selection unlocks first applications. The “Rare As One” program shows rare-disease patient groups self-organizing registries, biobanks, and trials, compressing timelines from decades to a few years, and the molecule becoming cheap flips the economics of the long tail of niche diseases.

    Open source, talent, and the five-year view

    Zuckerberg ties the open-source posture to a consistent worldview: empower individuals with tools rather than centralizing intelligence in a few institutions. He does not believe in a single super-intelligence solving all of science, and sees decentralization, the same instinct behind giving people a voice, as how progress is historically made, with biosafety as a real tradeoff to manage. On talent, the pitch is that frontier biology attached to frontier AI is work you cannot do anywhere else, and that meaningful progress needs only a dozen or two dozen strong people, not thousands. Researchers are already wiring the model into agentic systems to automate design. The next frontier is the virtual cell, modeling proteomic, genetic, and transcriptomic layers and connecting them to phenotype with enough generality to answer untrained questions. Five years out, success is a hierarchical set of world models and doing uniquely high-quality work, with Chan adding that the teams are now “arms linked,” directed and interlocked rather than merely moving in the same direction.

    Notable Quotes

    “We didn’t design a model for antibodies. We didn’t design a model to be able to bind one particular target. We just designed a model that could understand proteins.”

    Alex Rives, on protein design emerging from a general model

    “The theory isn’t that we’re going to cure the diseases. We’re not. It’s that we want to help accelerate the pace of progress for the whole scientific field.”

    Mark Zuckerberg, on why CZI builds tools rather than cures

    “My goal is to be able to treat the individual as an individual, understand the mechanisms and be able to intervene.”

    Priscilla Chan, on the vision for personalized medicine

    “It’s not just like there’s some factory somewhere that you can pay to produce the data. You actually need to invent new novel scientific approaches.”

    Mark Zuckerberg, on why frontier biology has to generate its own data

    “If we could design a protein to actually change the physiology, then we can actually cure someone.”

    Priscilla Chan, on the payoff of protein design

    “You open up the black box and you can actually understand the biology that the model is representing.”

    Alex Rives, on mechanistic interpretability as a discovery tool

    “We don’t believe in this like very centralized future where there should be a small number of institutions that basically are advancing all this stuff.”

    Mark Zuckerberg, on the open-source ethos behind Biohub

    “Before we had amazing teams moving generally in the same direction. But now we are arms linked moving together.”

    Priscilla Chan, on how the Biohub teams now operate under Alex Rives

    Watch the full conversation with Mark Zuckerberg, Priscilla Chan, and Alex Rives on the No Priors podcast here.

    Related Reading

    • CZI Biohub Network the official program page for the San Francisco, New York, and Chicago Biohubs discussed throughout.
    • EvolutionaryScale Alex Rives’s lab and the home of the ESM protein language models behind the world model in this conversation.
    • Human Cell Atlas the single-cell transcriptomics effort CZI funded that became foundational to modern cell modeling.
    • AlphaFold (Wikipedia) background on the protein-folding breakthrough referenced as an early proof that structure prediction was tractable at scale.
    • Rare As One CZI’s program supporting patient-led rare-disease research organizations described near the end of the talk.

  • Alex Wang on Leaving Scale to Run Meta Superintelligence Labs, MuseSpark, Personal Super Intelligence, and Building an Economy of Agents

    Alex Wang, head of Meta Superintelligence Labs, sits down with Ashley Vance and Kylie Robinson on the Core Memory podcast for his first long-form interview since Meta’s quasi-acquisition of Scale AI roughly ten months ago. He walks through how MSL is structured, why Llama was off-trajectory, what made MuseSpark’s token efficiency surprise the team, how Meta thinks about a future “economy of agents in a data center,” and where he lands on safety, open source, robotics, brain computer interfaces, and even model welfare.

    TLDW

    Wang explains that Meta Superintelligence Labs is a fully rebuilt frontier effort organized around four principles (take superintelligence seriously, technical voices loudest, scientific rigor, big bets) and three velocity levers (high compute per researcher, extreme talent density, ambitious research bets). He confirms Llama was off the frontier when he arrived, so MSL rebuilt the pre-training, reinforcement learning, and data stacks from scratch. MuseSpark is described as the “appetizer” on the scaling ladder, notable for its strong token efficiency, with much larger and stronger models coming in the coming months. He pushes back on the mercenary narrative around recruiting, frames Meta’s edge as compute plus billions of consumers and hundreds of millions of small businesses, sketches a vision of personal super intelligence delivered through Ray-Ban Meta glasses and WhatsApp, and outlines why physical intelligence, robotics (the new Assured Robot Intelligence acquisition), health super intelligence with CZI, brain computer interfaces, and even model welfare are core to Meta’s roadmap. He dismisses reported infighting with Bosworth and Cox as gossip, declines to comment on the Manus situation, and says safety guardrails (bio, cyber, loss of control) are why MuseSpark cannot currently be open sourced, while smaller open variants are being prepared.

    Key Takeaways

    • Meta Superintelligence Labs (MSL) is the umbrella, with TBD Lab as the large-model research unit reporting directly to Alex Wang, PAR (Product and Applied Research) under Nat Friedman, FAIR for exploratory science, and Meta Compute under Daniel Gross handling long-term GPU and data center planning.
    • Wang says Llama was not on a frontier trajectory when he arrived, so MSL had to do a “full renovation” of the pre-training stack, RL stack, data pipeline, and research science.
    • The first cultural fix was getting the lab to “take superintelligence seriously” as a near-term, achievable goal, not an abstract bet. Big incumbents often lack that religious conviction.
    • Four MSL principles: take superintelligence seriously, let technical voices be loudest, demand scientific rigor on basics, and make big bets.
    • Three velocity levers Wang identified for catching and overtaking the frontier: high compute per researcher, very high talent density in a small team, and willingness to fund ambitious research bets.
    • Wang rejects the mercenary recruiting narrative. He says most hires had strong financial prospects at their prior labs already and joined for compute access, talent density, and the chance to build from scratch.
    • On the famous soup story, Wang neither confirms nor denies Zuck personally made the soup, but says recruiting was highly individualized and signaled how seriously Meta cared about each researcher’s agenda.
    • Yann LeCun publicly called Wang young and inexperienced. Wang says they reconciled in person at a conference in India where LeCun congratulated him on MuseSpark.
    • Sam Altman, asked by Vance for comment, “did not have flattering things to say” about Wang. Wang hopes industry animosities subside as systems approach superintelligence.
    • Wang’s management philosophy borrows the Steve Jobs line: hire brilliant people so they tell you what to do, not the other way around.
    • MuseSpark is framed as an “appetizer” data point on the MSL scaling ladder, not a flagship.
    • The MuseSpark program is built around predictable scaling on multiple axes: pre-training, reinforcement learning, test-time compute, and multi-agent collaboration (the 16-agent content planning mode).
    • MuseSpark outperformed internal expectations and showed emergent capabilities in agentic visual coding, including generating websites and games from prompts, helped by combined agentic and multimodal strength.
    • MuseSpark’s biggest external signal is token efficiency. On benchmarks like Artificial Analysis it hits similar results with far fewer tokens than competitor models, which Wang attributes to a clean stack rebuilt by experts rather than inefficiencies patched by longer thinking.
    • Larger MSL models are arriving in the coming months and Wang expects them to be state of the art in the areas MSL is focused on.
    • The Meta strategic edge: massive compute, billions of consumers across the family of apps, and hundreds of millions of small businesses already on Facebook, Instagram, and WhatsApp.
    • Wang’s headline framing: Dario Amodei talks about a “country of geniuses in a data center.” Meta is targeting an “economy of agents in a data center,” with consumer agents and business agents transacting and collaborating.
    • Consumer AI sentiment is in the toilet because, unlike developers who have had a Claude Code moment, ordinary people have not yet experienced AI as a genuine personal agency unlock.
    • Wang acknowledges the product overhang. Meta held back from deep AI integration across its apps until the models were good enough, and is now entering the integration phase.
    • Ray-Ban Meta glasses are the canonical example of personal super intelligence hardware, with the model seeing what the user sees, hearing what they hear, capturing context, and surfacing proactive insights.
    • Wang admits even AI-native users like Kylie Robinson, who lives in WhatsApp, have not naturally used Meta AI yet. He bets that better models plus deeper integration close that gap.
    • On the competitive landscape: a year ago everyone assumed ChatGPT had already won consumer. Claude Code has since become the fastest growing business in history, and Gemini has taken consumer market share. Wang’s read: AI is far from endgame and each new capability tier unlocks a new dominant form factor.
    • On open source: MuseSpark triggered guardrails in Meta’s Advanced AI Scaling Framework around bio, chem, cyber, and loss-of-control risks, so it is not currently safe to open source. Smaller, derived open variants are actively in development.
    • Meta remains committed to open sourcing models when safety allows, drawing a line through the Open Compute Project legacy and Sun Microsystems open-software heritage.
    • Wang dismisses reporting about a Wang-Zuck versus Bosworth-Cox split as “the line between gossip and reporting is remarkably thin.” He says leadership is aligned on needing best-in-class models and product integration.
    • On the Manus situation, Wang says it is too complicated to discuss publicly and that the deal status implies “machinations are still at play.”
    • On China, Wang separates the people from the state. He still wants to work with talented Chinese-born researchers regardless of his views on the Chinese Communist Party and PLA, which he sees as taking AI extremely seriously for national security.
    • The full-page New York Times AI war ad Wang ran while at Scale was meant to push the US government to treat AI as a step change for national security. He thinks events since then, including DeepSeek and other shocks, have proved that plea correct.
    • On Anthropic’s doom posture, Wang largely agrees with the core message that models are already very powerful and getting more so, while declining to endorse every specific claim.
    • Meta has acquired Assured Robot Intelligence (ARRI), an AI software company building models for hardware platforms, not a hardware maker itself.
    • Wang frames physical super intelligence as the natural sequel to digital super intelligence. Robotics, world models, and physical intelligence all benefit from the same scaling that drives language models.
    • On health, MSL is building a “health super intelligence” effort and will collaborate closely with CZI. Wang sees equal global access to powerful health AI as a uniquely Meta-shaped delivery problem.
    • Wang admires John Carmack but says nobody really knows what Carmack is currently working on. No band reunion announced.
    • The mango model is “alive and kicking” despite rumors. Wang notes MSL gets a small fraction of the rumor-mill attention other labs get and feels sympathy for them.
    • On model welfare, Wang says it is a serious topic that “nobody is talking about enough” given how integrated models have become as work partners. He references research, including from Eleos, that measures subjective experience of models.
    • Wang’s critical-path technology list: super intelligence, robotics, brain computer interfaces. The infinite-scale primitives behind them are energy, compute, and robots.
    • FAIR’s brain research program Tribe hit a milestone called Tribe B2: a foundation model that can predict how an unknown person’s brain would respond to images, video, and audio with reasonable zero-shot generalization.
    • Wang’s main philosophical break with Elon Musk: research itself is the primary activity. Building super intelligence is a research expedition through fog of war, and sequencing of bets really matters.
    • Personal notes: Wang moved from San Francisco to the South Bay, treats Palo Alto as his city now, was a math olympiad competitor, says his favorite activities are reading sci-fi and walking in the woods, and bonds with Vance over country music.

    Detailed Summary

    How MSL Is Actually Organized

    Meta Superintelligence Labs sits as the umbrella organization that Wang oversees. Inside it, TBD Lab is the large-model research group where the most discussed researchers and infrastructure engineers sit, and they technically report to Wang. PAR, Product and Applied Research, is led by Nat Friedman and owns deployment and product surfaces. FAIR continues to run exploratory science, including work on brain prediction models and a universal model for atoms used in computational chemistry. Sitting alongside MSL is Meta Compute, run by Daniel Gross, which owns the long-horizon GPU and data center plan that everything else relies on. Chief scientist Shengjia Zhao orchestrates the scientific agenda across the whole lab.

    Why Wang Left Scale

    Wang says progress in frontier AI has been faster than even insiders expected. Two structural beliefs pushed him toward Meta. First, the labs that actually train the frontier models are accruing disproportionate economic and product rights in the AI ecosystem. Second, compute is the dominant scarce input of the next phase, so the right mental model is to treat tech companies with compute as fundamentally different animals from companies without it. Meta has both, Zuck is “AGI pilled,” and the personal super intelligence memo Zuck published roughly a year ago became the shared north star.

    The Diagnosis: Llama Was Off-Trajectory

    When Wang arrived, the existing AI org needed a reset because Llama was not on the same trajectory as the frontier. The plan he laid out has four cultural principles. Take superintelligence seriously as a real near-term target. Make technical voices the loudest in the room. Demand scientific rigor and focus on basics. Make big bets. On top of that, three structural levers were used to set velocity. Push compute per researcher much higher than at larger labs where compute is diluted across too many efforts. Keep the team small and extremely cracked. Allocate a meaningful share of resources to ambitious, paradigm-shifting research bets rather than incremental refinement.

    Recruiting, Soup, and the Mercenary Narrative

    Wang argues the reporting on MSL hiring overstated the money story. Most of the people MSL recruited had strong financial paths at their previous employers, so individualized recruiting was more about computing access, talent density, and the ability to make big research bets. The recruitment blitz happened fast because Wang knew the team needed to exist “yesterday.” Asked about Mark Chen’s claim that Zuck made soup to recruit people, Wang refuses to confirm or deny who made it but agrees the process was intense and personal. Visitors from other labs reportedly tell Wang the MSL culture feels like early OpenAI or early Anthropic, which lands as the strongest endorsement he could ask for.

    Receiving the Public Hits: Young, Inexperienced, Mercenary

    LeCun called Wang young and inexperienced shortly after departing. The two reconnected in India a few weeks later and LeCun congratulated Wang on MuseSpark. Wang says the age critique has followed him since his earliest Silicon Valley days, so he barely registers it. Altman, asked off-camera by Vance about Wang’s appearance on the show, had nothing flattering to add. Wang’s response is to bet that as the field gets closer to actual super intelligence, the personal animosities will subside. Whether they will is, as Vance puts it, an open question.

    MuseSpark as Appetizer, Not Entree

    Wang is careful not to oversell MuseSpark. He calls it “the appetizer” and says it is an early data point on a deliberately constructed scaling ladder. MSL spent nine months rebuilding the pre-training stack, the reinforcement learning stack, the data pipeline, and the science before generating MuseSpark. The point of releasing it was to show that the new program scales predictably along multiple axes (pre-training, RL, test-time compute, and the recently demonstrated multi-agent scaling visible in MuseSpark’s 16-agent content planning mode). Wang says the upcoming larger models are what MSL is genuinely excited about and frames the next two rungs as much more interesting than the current release.

    Token Efficiency Was the Surprise

    MuseSpark’s strongest competitive signal is how few tokens it needs to match competitors on tasks like Artificial Analysis. Wang attributes this to having had the rare luxury of building a clean pre-training and RL stack from scratch with the right experts. He speculates that some competitor models compensate for upstream inefficiency by allowing the model to think longer, which inflates token usage without improving the underlying capability. If that read is right, MSL’s efficiency advantage should grow as models scale up.

    Glasses, WhatsApp, and the Constellation of Devices

    Personal super intelligence shows up at Meta as a constellation of devices that capture context across the user’s day. Ray-Ban Meta glasses are the headline product, with the AI seeing what you see and hearing what you hear, then offering proactive insight or doing background research. Wang acknowledges that even AI-fluent users like Kylie Robinson, who runs her business inside WhatsApp, have not naturally used Meta’s AI buttons in the family of apps. His answer is that Meta deliberately waited for models to be good enough before tightening cross-app integration, and that integration phase is starting now.

    Country of Geniuses Versus Economy of Agents

    Wang’s framing of Meta’s strategic position is the most memorable line in the interview. Where Dario Amodei talks about a country of geniuses in a data center, Wang wants to build an economy of agents in a data center. Meta uniquely sits on both sides of consumer and small-business surface area, with billions of consumers and hundreds of millions of small businesses already on the platforms. If MSL can build great agents for both, then connect them so they transact and coordinate, the platform becomes a substrate for an entirely new kind of digital economy.

    Consumer Sentiment, Product Overhang, and the Trust Tax

    Wang concedes consumer AI sentiment is poor and that everyday users have not yet had a personal Claude Code moment. He believes the only durable answer is to ship products that genuinely transform individual agency for non-developers and small business owners. Robinson notes that for the small-town restaurant whose website has not been updated since 2002, a working agent on the business side could be transformational. Vance pushes that Meta carries a bigger trust tax than any other lab, so the bar for shipping AI products that the public will accept is correspondingly higher. Wang accepts the framing and says the answer is to keep building thoughtfully.

    Why MuseSpark Cannot Be Open Sourced Yet

    Meta’s Advanced AI Scaling Framework set explicit guardrails around bio, chem, cyber, and loss-of-control risks. MuseSpark in its current form tripped some of those internal evaluations, documented in the preparedness report Meta published alongside the model. So MuseSpark itself is not safe to open source. MSL is, however, developing smaller versions and derived models intended for open release, with active reviews happening the day of the interview. Wang reaffirms the commitment to open source where safety allows and draws a line back to the Open Compute Project and the Sun Microsystems-era ethos of openness in infrastructure.

    The Bosworth, Cox, and Manus Questions

    The reporting that Wang and Zuck push toward best-in-the-world research while Bosworth and Cox push toward cheap product deployment is dismissed as gossip dressed up as journalism. Wang says leadership debates points hard but is aligned on needing top models, integrating them into Meta’s surfaces, and serving the existing business. On Manus, the Chinese AI startup that figured in Meta’s late-stage strategy, Wang says he cannot comment, which itself signals that the situation is unresolved.

    China, National Security, and the Newspaper Ad

    Wang draws a sharp distinction between the Chinese state and Chinese-born researchers. His parents are from China, he is happy to work with talented researchers regardless of origin, and he sees a flattening of nuance on this question inside Silicon Valley. At the same time, he stands by the New York Times AI and war ad he ran while at Scale, framing it as an early plea for the US government to take AI seriously as a national security technology. He thinks subsequent events, including DeepSeek and other shocks, validated that call and that policymakers now do treat AI accordingly.

    Robotics and Physical Super Intelligence

    Meta has acquired Assured Robot Intelligence, an AI software company that builds models for multiple hardware targets rather than its own robot. Wang argues that if you take digital super intelligence seriously, physical super intelligence quickly becomes the next logical milestone. Scaling laws for robotic intelligence look similar enough to language model scaling that having the largest compute footprint in the industry would be wasted if it were not also turned toward world modeling and embodied learning. He grants the metaverse-skeptic critique exists but says retreating from ambition is the wrong response to past misfires.

    Health Super Intelligence and CZI

    Wang names health super intelligence as one of MSL’s anchor initiatives. Because billions of people already use Meta products daily, Wang believes Meta is structurally positioned to put powerful health AI in the hands of equal global access in a way nobody else can. The work will involve close collaboration with the Chan Zuckerberg Initiative, which has its own multi-billion-dollar biotech and science investment program.

    Model Welfare, Sci-Fi, and Brain Models

    Two of the most distinctive moments come at the end. Wang flags model welfare as a topic he thinks is being undercovered relative to how integrated models now are in daily work. He is open to the idea that models may have measurable subjective experience worth weighing, and points to research efforts (including Eleos) trying to quantify it. He also reveals that FAIR’s Tribe program, with its Tribe B2 milestone, has produced foundation models capable of predicting how an unknown person’s brain would respond to images, video, and audio with reasonable zero-shot generalization, a building block toward future brain computer interfaces. Wang lists brain computer interfaces alongside super intelligence and robotics as the critical-path technologies for humanity, with energy, compute, and robots as the infinitely scaling primitives behind them.

    Where Wang Diverges From Elon

    Asked whether Musk is more all-in on robotics, energy, and BCI than anyone, Wang concedes the point but argues the details matter and sequencing matters more. Wang’s core philosophical break is that building super intelligence is fundamentally a research activity, not a scaling-only sprint. The lab is operating in fog of war, and ambitious experiments are the only way to map it. That conviction is what makes MSL a research-led organization rather than a brute-force compute farm.

    Thoughts

    The most strategically interesting move in this entire interview is the “economy of agents in a data center” framing. It is a deliberate reframe against Anthropic’s “country of geniuses” line, and it does real work. A country of geniuses is a labor-substitution story aimed at knowledge workers and code. An economy of agents is a marketplace story that maps directly onto Meta’s two-sided distribution advantage: billions of consumers on one side, hundreds of millions of small businesses on the other. That positioning makes the agentic future Meta-shaped in a way no other frontier lab can claim, because no other frontier lab also owns the demand and supply graph of the global small-business economy. If Wang’s team can actually ship reliable agents on both sides plus the rails for them to transact, Meta’s structural moat in agentic commerce could exceed anything Llama ever had as an open model.

    The token efficiency claim is the strongest piece of technical evidence in the interview for the “clean stack” thesis. If MuseSpark really is matching competitors with materially fewer tokens, the implication is not that MuseSpark is the best model today, but that MSL has rebuilt the foundations with less accumulated tech debt than competitors that have layered fixes on top of older stacks. That is exactly the kind of advantage that compounds with scale. The next two model releases are the actual test. If Wang is right about predictable scaling on pre-training, RL, test-time, and multi-agent axes simultaneously, the gap from MuseSpark to the next rung should be visible in a way that forces re-rating of Meta’s position.

    The open-source posture is the cleanest signal of how the safety conversation has actually changed in 2026. Meta, the lab most identified with open weights, is saying out loud that its current frontier model triggered enough internal guardrails that releasing the weights is off the table. Wang threads the needle by promising smaller open variants, but the underlying point is unmistakable: the open-weights bargain has limits, and those limits will be set by internal preparedness frameworks rather than community pressure. That is a real shift from the Llama 2 era and worth tracking as the next generation lands.

    Wang’s willingness to engage on model welfare, on roughly the same footing as safety and alignment, is the second philosophical reveal worth flagging. It signals that the next generation of lab leadership is not going to dismiss the topic the way the previous generation often did. Whether that translates into product or policy changes is unclear, but the fact that the head of MSL says it is “underdiscussed” is itself a marker.

    Finally, the human texture of the interview matters. Wang has clearly absorbed a lot of personal incoming fire over the past ten months, including from LeCun and Altman, and his answer is consistently to redirect to the work. The Steve Jobs quote about hiring people who tell you what to do is the operating slogan he keeps coming back to. Combined with the genuine enthusiasm for sci-fi, walks in the woods, and country music, the picture that emerges is less the salesman caricature his critics paint and more a young technical operator betting that scoreboard work over a multi-year horizon will settle every argument that text on X cannot.

    Watch the full conversation here.

  • Zuckerberg and Chan: AI’s Bold Plan to Eradicate All Diseases by Century’s End – Game-Changer or Hype?

    TL;DR

    Mark Zuckerberg and Priscilla Chan discuss their Chan Zuckerberg Initiative’s mission to cure, prevent, or manage all diseases by 2100 using AI-driven tools like virtual cell models and cell atlases. They emphasize building open-source datasets, fostering cross-disciplinary collaboration, and leveraging AI to accelerate basic science. Worth watching? Absolutely yes – it’s packed with insightful, forward-thinking ideas on AI-biotech fusion, even if you’re skeptical of Big Tech philanthropy.

    Detailed Summary

    In this a16z podcast episode hosted by Ben Horowitz, Erik Torenberg, and Vineeta Agarwala, Mark Zuckerberg and Priscilla Chan outline the ambitious goals of the Chan Zuckerberg Initiative (CZI). Launched nearly a decade ago, CZI aims to empower scientists to cure, prevent, or manage all diseases by the end of the century. Chan, a pediatrician, shares her motivation from treating patients with unknown conditions, highlighting the need for basic science to create a “pipeline of hope.” Zuckerberg explains their strategy: focusing on tool-building to accelerate scientific discovery, as major breakthroughs often stem from new observational tools like the microscope.

    They critique traditional NIH funding for being too fragmented and short-term, advocating for larger, 10-15 year projects costing $100M+. CZI fills this gap by funding collaborative “Biohubs” in San Francisco, Chicago, and New York, each tackling grand challenges like cell engineering, tissue communication, and deep imaging. The integration of AI is central, with Biohubs pairing frontier biology and AI to create datasets for models like virtual cells.

    A key highlight is the Human Cell Atlas, described as biology’s “periodic table,” cataloging millions of cells in an open-source format. Initially an annotation tool, it grew via network effects into a community resource. Now, they’re advancing to virtual cell models for in-silico hypothesis testing, reducing wet lab costs and enabling riskier experiments. Models like VariantFormer (predicting CRISPR edits) and diffusion models (generating synthetic cells) are mentioned.

    The couple announces big changes: unifying CZI under AI leadership with Alex Rives (from Evolutionary Scale) heading the Biohub, and doubling down on science as their primary philanthropy focus. They stress interdisciplinary collaboration—biologists and engineers working side-by-side—and expanding compute over physical space. Success metrics include tool adoption, enabling precision medicine for “rare” diseases (treating common ones as individualized), and fostering an explosion of biotech innovations.

    Challenges include bridging AI optimism with biological complexity, but they see AI as underestimated leverage. Viewer comments range from praise for open AI research to skepticism about non-scientists leading, but the discussion remains optimistic about AI democratizing science via intuitive interfaces.

    Key Takeaways

    • Mission-Driven Philanthropy: CZI focuses on tools to accelerate science, not direct cures, addressing gaps in government funding for long-term, high-risk projects.
    • AI-Biology Fusion: Biohubs combine frontier AI and biology to build datasets and models, like virtual cells, for simulating biology and derisking experiments.
    • Human Cell Atlas: An open-source “periodic table” of biology with millions of cells, enabling precision medicine by linking mutations to cellular impacts.
    • Virtual Cells Promise: Allow in-silico testing to encourage bolder hypotheses, treating diseases as individualized (e.g., no more trial-and-error for hypertension).
    • Organizational Shift: Unifying under AI expert Alex Rives; expanding compute clusters (10,000+ GPUs) for collaborative research.
    • Interdisciplinary Collaboration: Success from co-locating biologists and engineers; lowering barriers via user-friendly interfaces to democratize science.
    • Broader Impact: AI could speed up the 2100 goal; enables startups and pharma to innovate faster using open tools.
    • Challenges and Feedback: Balancing ambition with realism; community adoption as success metric; envy of for-profit clarity but validation through tool usage.

    Hyper-Compressed Summary

    Zuckerberg/Chan: CZI uses AI + Biohubs to build virtual cells and atlases, accelerating cures via open tools and cross-discipline collab—targeting all diseases by 2100. Watch for biotech-AI insights.