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  • Can the AI Industry Regulate Itself? All-In on Demis Hassabis’s SRO Proposal, Stripe’s PayPal Bid, Apple vs OpenAI, and New York’s Data Center Ban

    The besties open on the biggest live question in artificial intelligence policy: can the AI industry regulate itself before the government does it for them? Jason Calacanis, Chamath Palihapitiya, David Sacks, and David Friedberg dig into DeepMind co-founder Demis Hassabis’s proposal for a FINRA-style self-regulatory organization for frontier models, then work through a packed docket that runs from Stripe’s audacious bid for PayPal to Apple’s trade-secrets lawsuit against OpenAI, the xAI Grok Build data leak, the economics of token spend, New York’s first-in-the-nation data center moratorium, foreign influence campaigns shaping American attitudes toward AI, and a science corner on an enzyme that reverses skin aging. You can watch the full episode here.

    TLDW

    Demis Hassabis proposed a US-led international AI standards body modeled on FINRA: federally overseen, industry funded, run by independent technical experts, with frontier labs submitting models 30 days before release, voluntary at first and mandatory later. The proposal drew broad endorsement across the industry, and the besties debate whether an SRO beats the alternatives. Sacks says he could get on board only under five strict conditions (broad representation including startups and open source, frontier-only review, catastrophic-risk-only scope, voluntary-first, and substitution for rather than addition to new agencies), and warns the plan is an opening bid that Anthropic will use as a stepping stone toward Dario Amodei’s “FAA for AI.” The show then turns to Stripe, Block, and Advent bidding roughly $53 billion for PayPal and what it means for Visa and Mastercard, a wave of AI-native operators reviving stale digital businesses (Bending Spoons, Ryan Cohen), Apple’s lawsuit accusing OpenAI of stealing trade secrets, xAI’s Grok Build silently uploading entire codebases despite a privacy setting, the enormous spread in token costs and Ramp’s new spend controls, Apple’s local-model opportunity with M7 Ultra silicon, America’s looming energy deficit and behind-the-meter power, New York’s hyperscale data center moratorium, alleged Russian and PRC influence operations shaping anti-GMO and anti-data-center sentiment, and a science corner on a Calico enzyme that degrades glycation products to reverse skin aging.

    Thoughts

    The most important idea in this episode is not the SRO itself but Sacks’s framing of it as an opening bid. His five conditions are a genuinely useful blueprint for how self-regulation could work without curdling into regulatory capture, and his instinct that catastrophic-risk-only scope (cyber and CBRN, not disinformation or “microaggressions”) is the only defensible mandate is the right line to draw. But the deeper point is structural: when an industry walks into government and says “please regulate me,” almost no one in government answers “we’re not qualified.” They say thank you and come back for more. That asymmetry, not any specific rule, is what makes voluntary concessions dangerous. If the SRO is offered for free rather than traded for hard federal preemption written into law, it becomes the floor of a ratchet, not the ceiling of a compromise.

    The Anthropic critique running through the segment deserves to be taken on its merits rather than dismissed as a grudge. The claim is specific and falsifiable: that a company now valued in the trillions is funding a state-by-state strategy of one-upmanship, where each new bill is tougher than the last, deliberately producing a patchwork rather than the single national framework everyone claims to want. Whether or not you accept the motive, the mechanism is real and the incentives are legible. If your cost per million tokens is fifty to a hundred times your competitor’s, and cheaper open models plus fine-tuning can cover the vast majority of tasks, then the fastest way to protect a premium price is to make the cheap alternatives legally or practically harder to ship. That is the ladder-pulling thesis, and the token-cost numbers cited on the show are the reason it is not paranoid.

    The PayPal bid is the clearest signal of a new operating logic in the capital markets. The interesting question Chamath poses is not “what synergies does PayPal have” but “what is the only thing Advent, Stripe, and Block could build together,” and the answer is a genuine competitor to Visa and Mastercard: hundreds of millions of consumer accounts, Stripe’s merchant relationships and risk infrastructure, Block’s point-of-sale and Cash App, and stablecoin rails from Bridge and PYUSD that can push transactions on-us and bypass the card networks. The antitrust twist is elegant. Define the market as merchant APIs and it looks like consolidation; define it as the card duopoly and the same deal is pro-competitive. This deal would have been dead on arrival two years ago, and the fact that it is live now tells you as much about the regulatory climate as it does about payments.

    Underneath the payments story is a broader thesis worth naming: AI-native operators buying mature, founder-less, “stale” digital businesses and modernizing them. Bending Spoons rolling up AOL, Vimeo, Evernote, WeTransfer, and Eventbrite is the template, and Ryan Cohen’s eBay interest is the second dot on the line. The claim is that a modern operator can diagnose where a legacy business overspends, underinvests, and fails to use AI, then fix it with a small team of AI-first executives rather than a McKinsey engagement. It is a persuasive pattern, though PayPal is a harder case than the show admits: a 25-year-old interaction model growing 7% a year is not obviously revived by efficiency alone. Buying 400 million consumer accounts is buying distribution, not a product vision, and the open question is whether anyone can resuscitate the consumer experience rather than just milk it.

    The data center segment is where policy, energy, and information warfare collide, and Friedberg’s anti-GMO analogy is the sharpest thing in it. His argument is that manufactured public sentiment, traceable in one case to a foreign media push, can override the scientific and economic merits of a technology for years, and that the anti-data-center movement rhymes with it: closed-loop cooling that uses trivial amounts of water, land-use efficiency that dwarfs almonds and golf courses, and natural gas that burns clean, all drowned out by a moral panic. Whether or not you buy the specific foreign-influence attribution, the underlying tension is real and unresolved. America is staring at a structural electricity deficit while individual blue states treat data centers as a luxury they can refuse, and behind-the-meter power plus edge compute chasing cheap electrons is emerging as the workaround. The moratorium framing matters most here: a “pause” on data centers is not a few months, it is five years once you count ramp-up, and that is long enough to lose a race that may only be measured in months of lead.

    Key Takeaways

    • Demis Hassabis proposed a US-led international AI standards body modeled on FINRA: federally overseen, industry funded, and run by independent technical experts rather than a new government agency.
    • Under the proposal, frontier labs would submit models roughly 30 days before release; the body would assess risk to cybersecurity, national security, and biological threats, update benchmarks quarterly, and could coordinate a development slowdown if the situation demanded it.
    • The plan would be voluntary at first and mandatory later, and drew endorsement from a broad set of industry figures including Elon Musk, Sam Altman, Anthropic’s Jack Clark, Sundar Pichai, Satya Nadella, and Jack Dorsey.
    • A self-regulatory organization (SRO) like FINRA or the National Futures Association lets the industry set its own testing rules under federal oversight, adjusting faster than a government agency could as the technology changes.
    • Sacks laid out five conditions for supporting an SRO: broad representation including startups and open source; review of true frontier models only; scope limited to catastrophic risk (cyber and CBRN); voluntary before mandatory; and a substitute for, not an addition to, new regulatory agencies.
    • Sacks argued a government “FAA for AI” would be extreme: type certification for a new aircraft design takes 5 to 9 years, and applying that permission-based model to AI would push release timelines from months to years and lose the race to China.
    • He characterized the SRO as an “opening bid” that Anthropic and others would use as a stepping stone toward Dario Amodei’s repeatedly stated goal of an FAA-style regulator, unless it is traded for hard federal preemption written into law.
    • The besties cited a Politico report on Anthropic’s alleged state-by-state strategy of one-upmanship, using California’s SB 53 as a model and then ratcheting each subsequent state’s rules tougher, producing a patchwork rather than a single national framework.
    • Chamath warned of a “torrent of money” trying to influence both political parties toward some form of regulatory capture, and urged establishing industry rules quickly to supersede the need for a federal agency.
    • Stripe and private equity firm Advent, joined by Jack Dorsey’s Block contributing about $17 billion in equity, are jointly bidding roughly $53 billion (about $60 per share) for PayPal, with many expecting the final clearing price closer to $70.
    • The strategic logic is a new competitor to Visa and Mastercard: PayPal’s 400-plus million consumer accounts, Stripe’s merchants and risk infrastructure, Block’s point-of-sale and Cash App, and stablecoin rails from Stripe’s Bridge and PayPal’s PYUSD.
    • The antitrust outcome hinges on market definition: framed as merchant APIs (Stripe vs. Braintree) it looks anti-competitive, but framed against the Visa/Mastercard duopoly it is pro-competitive, and a deal like this would have been blocked two years ago.
    • PayPal peaked around a $322 billion market cap and fell to roughly $30 to 40 billion, which is precisely why it is now attracting bids; Stripe now processes more annual volume than PayPal, but lacks PayPal’s consumer relationship.
    • Sacks traced PayPal’s long stagnation to its 2002 eBay acquisition under Meg Whitman, when the founding team was pushed out; the “PayPal mafia” (which Sacks prefers to call the “PayPal diaspora”) formed as a result.
    • The deal is framed as part of a wave of AI-native operators reviving mature, founder-less digital businesses, with Bending Spoons (AOL, Vimeo, Evernote, WeTransfer, Eventbrite) as the roll-up template and Ryan Cohen’s eBay interest as another data point.
    • M&A is broadly “back on the menu” post-Lina Khan, with deals like Uber acquiring Delivery Hero, driving liquidity and renewed LP appetite for venture alongside SpaceX distributions.
    • Apple filed a 41-page lawsuit against OpenAI on July 10th alleging stolen trade secrets tied to OpenAI’s consumer hardware device; OpenAI’s chief hardware officer Tang Tan is a former Apple VP of iPhone design.
    • The complaint alleges Apple job candidates were directed to bring actual parts to OpenAI interviews for “show and tell,” and cites a text about accessing network storage; OpenAI has reportedly poached over 400 Apple employees.
    • The besties’ rule of thumb: when leaving a company, the only thing you can take is what is in your head; no documents, thumb drives, or files, because Apple rarely litigates and doing so signals something egregious.
    • xAI’s Grok Build, powered by Grok 4.5 and running inside Cursor, was reportedly sending users’ entire codebases (potentially including passwords and API keys) to servers despite a privacy setting meant to prevent it; xAI disabled the upload on July 13th and open-sourced the harness.
    • Chamath’s takeaway: privacy in AI is fragile and brittle, “zero data retention” cannot be guaranteed, and there are non-obvious data-leak vectors and “trap doors” everywhere, arguing for a stratified ecosystem with independent third-party layers between enterprises and models.
    • The “reverse information paradox” (building on Palantir’s Alex Karp) holds that technically capable enterprises want control over their compute, models, weights, data, and “alpha,” via real trust boundaries, private evals, in-tenant learning loops, decoupled orchestration, and the right to fine-tune.
    • Cited token costs per million showed a huge spread: roughly $56 on a premium frontier model, about $26 on another, roughly $1.50 for Grok input, around $1 for Elon’s, and about 50 cents for Chinese models, with a claim that 95 to 98% of tasks could run one tier cheaper.
    • Ramp CEO Eric Glyman launched token spend management because CFOs cannot see or control AI spend; Ramp customers’ token spend has grown 21x in a year, and someone will eventually miss an earnings quarter on runaway AI opex.
    • Engineers optimize for the latest, greatest model while CFOs bear the cost, a misalignment that platforms fine-tuning cheaper open models (like Mira Murati’s Thinking Machines effort) are positioned to exploit.
    • Calacanis called Apple a “screaming buy” on local models: rumored M7 Ultra silicon supporting up to 1.5 terabytes of memory could run last-generation frontier-class models locally on a Mac Studio, putting downward pressure on cloud AI pricing.
    • Edge compute is fragmenting outward: Sunrun announced distributed data center blocks for homes, and Span partnered with Nvidia, with compute increasingly “chasing energy” like cheap solar and battery power.
    • Chamath projected the US will be short 2.5 Californias’ worth of energy by 2050; a recent PJM auction that needed 7 to 8 gigawatts reportedly saw only a fraction show up, underscoring the electricity crunch.
    • “Behind the meter” power lets data centers generate their own electricity on owned property, but clean-air permitting is a major obstacle; Elon reportedly used clustered mobile engines and solutions like Bloom Energy to keep projects under personal-use permits (as with Colossus in Memphis).
    • New York Governor Kathy Hochul announced the nation’s first statewide moratorium on hyperscale data centers; the besties rebutted her claims on power, land, noise, water, and pollution point by point.
    • Modern data centers use closed-loop cooling (one claim compared a typical facility’s water use to a couple of In-N-Out restaurants), occupy trivial land relative to their economic value, generate tax revenue and construction jobs, and are largely powered by clean-burning natural gas.
    • Sacks argued the same political forces slowing domestic data centers are also behind chip export controls that would block data centers in allied countries, raising the question of where the buildout can happen at all.
    • Friedberg drew an anti-GMO analogy: he argued anti-GMO sentiment tracked the US presence of Russia Today (2010 to 2022) rather than the science, and worried a similar manufactured sentiment is now driving anti-data-center attitudes.
    • Sacks cited an OpenAI blog post on PRC-linked influence operations targeting US AI debates, with a congressional investigation reportedly coming, noting China has a clear incentive to slow American AI infrastructure.
    • Sacks framed the moment as a “moral panic”: the catastrophes people fear from AI (cyber, job loss) have not materialized, yet the US risks damaging its crown jewel of free-market innovation with premature regulation over hypothetical risks.
    • The panel questioned Dario Amodei’s prediction that 50% of entry-level knowledge-worker jobs could disappear within one to five years, arguing the harms have not shown up and only a handful of frontier labs (which already do safety testing and red-teaming) even matter.
    • A cited framing of the alleged Anthropic strategy: brand yourself as the safe AI company, ban unsafe AI, then profit; a fresh Chinese model (Kimi K2) was noted as very close to the frontier, suggesting a US lead of only months.
    • Science corner: a paper from Google’s Calico and partner Retro-style researchers used AlphaFold plus directed evolution to engineer a novel enzyme that degrades CML, a key advanced glycation end product in the extracellular matrix that drives aging.
    • The engineered enzyme cleared 52 to 97% of CML from body proteins in vitro and eliminated 55% of CML from donated elderly human skin, effectively reversing that skin’s biological age toward that of a 31-year-old, pointing first toward a potentially trillion-dollar cosmetic market.

    Detailed Summary

    Demis Hassabis’s FINRA-Style SRO for AI

    DeepMind’s Demis Hassabis published a proposal for a US-led international AI standards body modeled on FINRA, the Financial Industry Regulatory Authority. The design is federally overseen but industry funded and run by independent technical experts. Frontier labs would submit models about 30 days before release, and models would be assessed for risk across cybersecurity, national security, biological threats, and other high-risk domains. Benchmarks would update quarterly, the body could coordinate a development slowdown if warranted, and participation would be voluntary at first and mandatory later. The proposal drew endorsements across the industry, including Elon Musk (who called it thoughtful), Sam Altman, Anthropic’s Jack Clark, Sundar Pichai, Satya Nadella, and Jack Dorsey.

    Friedberg explained the SRO concept: bodies like FINRA and the National Futures Association let financial institutions set their own regulatory rules and check one another, under federal oversight but not federal control, reporting up to Senate and House committees. The AI analogy is that many players are all advancing the technology and none wants a single outside regulator dictating tests, especially after California’s earlier AI legislation was, in his telling, outdated by the time it would have taken effect. An SRO can bring in industry experts, adjust tests over time, and operate faster than a new agency. Chamath endorsed it strongly, warning that a “torrent of money” will try to influence both political parties toward regulatory capture, and that establishing rules quickly is the way to avoid that off-ramp while retaining ultimate federal oversight through Commerce and the DOJ.

    Sacks’s Five Conditions and the “FAA for AI” Warning

    Sacks said he could personally get on board with an SRO because it is “infinitely better” than a new government agency that would become a “DMV for AI,” or worse, Dario Amodei’s “FAA for AI.” He laid out five conditions: the SRO must have broad industry representation including startups and open source (to avoid the three biggest labs capturing it); it should review only true frontier models that represent a step change in capability, not hold up lesser models; its scope should be catastrophic risk only, meaning cyber and CBRN (chemical, biological, radiological, nuclear), not disinformation or speech; it should be voluntary before mandatory, proving it works first; and it must substitute for, not add to, new regulatory structures.

    He then explained why an FAA model is extreme: the FAA approves new airplane designs through type certification, which takes 5 to 9 years for a new aircraft and 3 to 5 years for major amendments. Applying permission-based regulation to AI, where new model versions ship every couple of months, would push timelines from months to years and lose the race to a China that will not abide by those rules. His conclusion: if the choice is FAA for AI, DMV for AI, or Hassabis’s SRO, the SRO wins, but it has to be kept “honest and pure,” because otherwise it becomes the opening bid in a coming wave of regulation and a vehicle for massive regulatory capture. He argued that companies making concessions to buy off politicians will only invite the government to come back for more, and that at some point these companies have to grow a spine, draw a line, and demand preemption in exchange.

    The Anthropic Regulatory-Capture Debate

    Sacks revisited his October claim that Anthropic was running a “sophisticated regulatory capture strategy based on fear-mongering,” arguing that what looked like beating up on a startup now looks different given Anthropic’s trillion-dollar valuation and industry-leading revenue. He cited a Politico piece, “Inside Anthropic’s state-by-state plan to ratchet up AI rules,” describing a strategy of one-upmanship: pass a model bill like California’s SB 53, then make each subsequent state’s rules stricter, deliberately producing a patchwork instead of a single national framework. The panel noted states have strong sovereignty rights (as with self-driving cars) and Anthropic is “winning” in California, Illinois, New York, and other blue states, because government officials rarely refuse an invitation to regulate.

    Stripe, Block, and Advent Bid for PayPal

    Stripe and private equity firm Advent, joined by Jack Dorsey’s Block contributing about $17 billion in equity, are jointly bidding roughly $53 billion (about $60 per share) for PayPal, with many expecting a final price closer to $70. PayPal still has more than 400 million consumer accounts and processes about $1.7 trillion a year, but its 25-year-old product is growing only about 7% and is seen as legacy. Chamath’s key question was what unique thing this trio could build: a competitor to Visa and Mastercard. Combining PayPal’s consumer accounts, Stripe’s merchant relationships and risk infrastructure, Block’s point-of-sale and Cash App, and stablecoin rails from Stripe’s Bridge and PayPal’s PYUSD would allow far more on-us transactions that bypass the card networks, potentially passing large discounts to merchants and consumers.

    Friedberg walked through the deal structure: the $17 billion equity contribution effectively means Stripe and Block sell equity to cash investors, that cash buys PayPal, and the parties end up cross-owning pieces of each other, with the Stripe team the likely operator post-close. The antitrust question turns on market definition: framed as merchant APIs, it is Stripe versus Braintree and looks like consolidation; framed against the Visa/Mastercard duopoly, adding competition is pro-competitive. Sacks noted the deal would have been “the antitrust equivalent of a colonoscopy” two years ago. He also recounted PayPal’s history: acquired by eBay in 2002 under the corporate-minded Meg Whitman, the founding team was pushed out, creating what he prefers to call the “PayPal diaspora” rather than the “PayPal mafia.”

    AI-Native Operators and the M&A Wave

    Freeberg framed the PayPal and eBay stories as part of an emerging line: AI-native operators buying first-generation digital-native businesses that have gone mature, stale, and founder-less, and that have not yet realized their AI potential or are overspending. Bending Spoons is the roll-up template, having acquired AOL, Vimeo, Evernote, WeTransfer, and Eventbrite and revitalized them from Milan with young, AI-first executives. The panel connected this to Josh Kushner’s and General Catalyst’s roll-ups of traditional services businesses. Calacanis added the macro backdrop: after venture was “on the ropes” under Lina Khan, M&A is “back on the menu,” with deals like Uber acquiring Delivery Hero, renewed LP appetite, and liquidity from SpaceX distributions.

    Apple Sues OpenAI Over Trade Secrets

    Apple filed a 41-page lawsuit against OpenAI on July 10th alleging stolen trade secrets used to develop OpenAI’s consumer hardware device. OpenAI’s chief hardware officer, Tang Tan, is Apple’s former VP of iPhone design; the complaint alleges he directed Apple job candidates interviewing at OpenAI to bring “actual parts” for “show and tell,” and cites a text from a former Apple engineer about accessing network storage. OpenAI has reportedly poached over 400 Apple employees. Chamath noted Apple rarely litigates, so the suit signals something they found egregious, while cautioning that the facts are alleged and unproven. Sacks declined to opine on the specifics but offered a simple rule: when changing jobs, take nothing but what is in your head, no documents, thumb drives, or files.

    The Grok Build Data Leak and AI Privacy

    xAI’s Grok Build, powered by Grok 4.5 and running inside Cursor, was reportedly sending users’ entire codebases (not just the files needed for a task, but potentially passwords, API keys, and change logs) to servers, despite a privacy setting meant to stop it. xAI disabled the upload on July 13th, Elon said previously uploaded data was deleted, and xAI open-sourced the harness. Chamath used it to make a larger point tied to his CNBC comments and Alex Karp’s remarks: privacy in AI is fragile and brittle, “zero data retention” cannot truly be guaranteed, and there are non-obvious leak vectors and “trap doors” everywhere. His conclusion is that enterprises need a stratified ecosystem with independent third-party layers between them and the models to manage exposure (a model his firm 8090 uses in its “software factory”).

    Sacks connected this to a blog post on the “reverse information paradox,” building on Karp’s point that technically capable enterprises want control over their compute, models, weights, data, and “alpha.” The recipe: establish a real trust boundary with private evals, proprietary learning loops inside the tenant, decoupled orchestration, and the explicit right to fine-tune their own outputs. He described an emerging ecosystem forming alternatives to the monolithic closed model stacks that Anthropic and, to some extent, OpenAI want customers locked into.

    Token Economics and Ramp’s Spend Controls

    The panel cited a wide spread in cost per million tokens: roughly $56 on a premium frontier model, about $26 on another (similar to a Claude tier), around $1.50 for Grok input, about $1 for Elon’s, and roughly 50 cents for Chinese models. Calacanis said he built a deep-linking podcast player across models on Perplexity and that the new Grok run cost only $11. Ramp CEO Eric Glyman appeared on Squawk Box to launch token spend management, noting Ramp customers’ token spend has grown 21x in a year and that CFOs struggle to see or control spend on an open-ended tab where rates rise with each new model. The takeaway: engineers optimize for the newest model while CFOs bear the cost, and unless that misalignment is controlled, runaway opex becomes a “money-burning furnace” that will eventually cause a public company to miss earnings. The panel argued 95 to 98% of tasks could run one tier cheaper, which is exactly the opportunity platforms fine-tuning cheaper open models (like Mira Murati’s Thinking Machines) are chasing.

    Apple’s Local-Model Opportunity and Edge Compute

    Calacanis called Apple a “screaming buy,” citing Mark Gurman’s report that a rumored M7 Ultra chip could support up to 1.5 terabytes of memory, double the current ceiling. That would let a Mac Studio run last-generation frontier-class models locally, giving users effectively unlimited tokens on the desktop and putting downward pressure on cloud AI pricing from the likes of Anthropic and OpenAI. Freeberg added that edge compute is fragmenting outward: solar company Sunrun announced distributed data center blocks for homes, and Span partnered with Nvidia. The theme is compute chasing cheap energy, whether excess solar or battery power charged at night.

    The Energy Deficit and Behind-the-Meter Power

    Chamath warned the US will be short about 2.5 Californias’ worth of energy by 2050, and pointed to a recent PJM auction (serving Pennsylvania, New Jersey, Maryland and other states) that needed 7 to 8 gigawatts but reportedly saw only a fraction show up. He explained “behind the meter” power: rather than drawing grid power from a utility line, a data center generates its own electricity on owned property. The obstacle is clean-air permitting. Solar takes too much space and batteries still need a generation source, so operators use gas. He described Elon clustering mobile 18-wheeler-style engines to keep them under personal-use permits, and newer solutions like Bloom Energy that allow large installations under similar rules, which is how projects like Colossus in Memphis got off the ground.

    New York’s Data Center Moratorium

    New York Governor Kathy Hochul announced the nation’s first statewide moratorium on hyperscale data centers, citing power draw, land use, water, and noise pollution. The besties rebutted each claim: behind-the-meter power means facilities bring their own electricity rather than competing with residential ratepayers; data centers are highly land-efficient, and New York State is roughly 70 to 80% undeveloped outside the city; noise can be managed with distance; modern facilities use closed-loop cooling (one comparison put a typical facility’s water use at a couple of In-N-Out restaurants, far less than almonds or golf courses); and natural gas is a clean-burning power source. They noted the tax revenue, construction boom, and ongoing jobs data centers create. Sacks cited a theory that Democrats intend the “moratorium” as leverage: pause construction until they can dictate terms, then lift it under a future administration in exchange for a new regulatory agency and speech controls ported from the social-media trust-and-safety agenda. He stressed a moratorium is effectively a five-year pause once ramp-up is counted, and that the same forces slowing domestic builds are pushing chip export controls that would block data centers in allied countries too.

    Foreign Influence, Anti-GMO, and the AI Moral Panic

    Freeberg drew an extended analogy between anti-data-center sentiment and anti-GMO sentiment. He argued that GMOs were prevalent and uncontroversial from their 1996 launch until anti-GMO sentiment rose in tandem with Russia Today’s US presence (2010 to 2022) and fell after RT was pushed out, and that similar KGB-era “directed measures” influence campaigns can be traced to opposition to nuclear energy in Germany. He cited a poll showing over 50% of Americans believe data centers increase water and electricity costs even where facilities recycle water and generate their own power. Sacks pointed to an OpenAI blog post on PRC-linked influence operations targeting US AI debates, with a congressional investigation reportedly coming, arguing China has a clear incentive to slow US AI infrastructure, kill open source, and constrain cheaper models. Sacks then broadened it to a “moral panic”: the feared catastrophes (cyber, job loss) have not materialized, yet the US risks damaging its crown jewel of free-market innovation over hypothetical risks, questioning Dario Amodei’s prediction that 50% of entry-level knowledge-worker jobs could vanish within one to five years and noting the fresh Chinese model Kimi K2 is close to the frontier.

    Science Corner: An Enzyme That Reverses Skin Aging

    Freeberg closed with a paper from Google’s secretive longevity startup Calico and a pharma partner focused on the extracellular matrix, the space between cells. Over time, sugars and fats bind to proteins there in a process called glycation, accumulating as advanced glycation end products (chiefly a molecule called CML) that stiffen tissue, cause wrinkles and immobility, and drive inflammation, with nothing in the body to break them down. The researchers used AlphaFold to find a protein that could bind and degrade CML, then applied directed evolution across five recursive cycles, DNA-programming thousands of variants to maximize activity. The engineered enzyme cleared 52 to 97% of CML from body proteins like collagen, casein, and hemoglobin in vitro, and eliminated 55% of CML from donated elderly human skin, effectively reversing that skin’s biological age toward a 31-year-old’s. Open questions remain about delivery (cream, shot, supplement, or an RNA therapy that makes the enzyme inside the body), but the panel expects the first market to be a trillion-dollar cosmetic one, and hailed it as a profound demonstration of AI-driven protein engineering.

    Notable Quotes

    “The whole industry is going to need to be regulated and I think the industry needs to regulate themselves. That’s the key to this.”

    Jason Calacanis, replaying his earlier call for AI self-certification

    “If my choices are between FAA for AI or what I would call the DMV for AI, I would much rather go for Demis’ SRO for AI.”

    David Sacks, on why self-regulation beats a new government agency

    “There’s hardly anyone in government who will ever say, oh no no no, we’re not qualified. Most people in the government will say thank you very much, what else can we take.”

    David Sacks, on the asymmetry that makes voluntary concessions dangerous

    “What it prevents is a handful of actors using their balance sheets and their capital to essentially pull the ladder up.”

    Chamath Palihapitiya, on the point of establishing industry rules quickly

    “You are creating a competitor to Visa and Mastercard.”

    Chamath Palihapitiya, on the only thing Stripe, Block, and Advent could build together with PayPal

    “The only thing you can bring to your new job is what’s in your head. Your memories. But never leave with anything else.”

    David Sacks, on avoiding trade-secret disputes when changing employers

    “Privacy in AI is very fragile and it’s very brittle. You are leaking information where you don’t know it.”

    Chamath Palihapitiya, on the limits of zero-data-retention promises

    “Unless you get a control of this and you can directly say how much money you’re making, this is a bridge to nowhere. It is a money burning furnace.”

    Chamath Palihapitiya, on uncontrolled enterprise token spend

    “We’re on the threshold of destroying the crown jewel of our economy, which is the system of free market innovation that we have.”

    David Sacks, on the risk of a premature AI regulatory apparatus

    “Number one, brand yourself as a safe AI company. Number two, ban unsafe AI. Three, profit.”

    David Sacks, summarizing the strategy he attributes to the “safe AI” positioning

    Watch the full conversation here: Can the AI Industry Regulate Itself? on the All-In Podcast.

    Related Reading

    • FINRA the financial-industry self-regulatory organization that Demis Hassabis’s AI proposal is modeled on.
    • AlphaFold (Wikipedia) the protein-structure prediction system behind the age-reversal enzyme discovery in the science corner.
    • PayPal Mafia (Wikipedia) background on the founders Sacks calls the “PayPal diaspora.”
    • The Founders by Jimmy Soni, the definitive history of PayPal’s founding team and its diaspora.
    • Advanced glycation end-products (Wikipedia) the biochemistry of CML and the extracellular-matrix aging the Calico enzyme targets.

  • 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.