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🔬Causal Models Need Causal Data - Xaira’s X-Cell model for Drug Discovery (Bo Wang & Ci Chu, Chief Discovery Officer & Chief AI Scientist) Jul 21, 2026

Show notes

Bet on information

If test loss flatlines after 1.5B parameters while training loss continues to drop as you scale, that tells you that your model is limited by the amount of information in your data.

Training on a single, smallish data set exposed an information gap: the 3.1B model falls off the scaling trend. Neither parameters nor compute will improve performance past this wall. For predicting changes to gene expression, you need more information rich data.

This is what Chu and Bo’s teams have done, and here is what ~30x the information buys you:

Now we can scale with parameters and training compute! We don’t know how much this effort costed, but we can guess that data collection experiments and infrastructure was a few tens of millions, and compute + headcount + research was a few million. The budget looks like a RL rollout budget, rather than a data rich pre-training one.

We were lucky enough to have the two central figures in this story on our podcast. Taking the lead from Ci Chu and Bo Wang, Xaira Therapeutics is betting that information rich data is the key to AI-driven drug development. Chu was recently promoted to Chief Discovery Officer and Bo to Chief AI Scientist, underscoring just how strategic Xaira considers this bet.

Reverse engineering the human cell

If you had to figure out how a human cell works, what would you do? A good place to start might be by documenting what genes are expressed (e.g. what RNA is floating around) in different kinds of cells, in different circumstances.

That is CELLxGENE, a database of 168M cells built by Chan Zuckerberg Institute that maps each cell to a count of how many times 20K-30K genes were detected in that cell, plus detailed metadata about every cell. A ~4 trillion-entry matrix.

If the Protein Data Bank (PDB) unlocked structural biology models (Boltz Episode, ESM/BioHub Episode), CELLxGENE has done the same thing for Virtual Cell models. Like PDB, CELLxGENE has inspired a zoo of AI models of RNA expression; so much so that RNA expression models have become synonymous with Virtual Cell models. Bo Wang built one of the most influential, scGPT, that became the starting point for Xaira’s new model.

RNA expression ≠ Virtual Cell

Models trained on CELLxGENE describe the relationship between cell types and cell states, but they are not good at predicting what will happen if we make changes to RNA expression. Changes in gene expression are highly correlated, and its is difficult (impossible) to figure out what causes what in most cases.

If you could “turn the dial down” on one gene at a time, however, then you would be able to observe what is upstream and downstream of a given gene. You could tell if A → B & C or B → A & C or B → A, C → B → … If you did this for all of the genes, then maybe you could train a model that could predict what would happen to a cell if you change a gene (e.g. with a drug or a gene edit). Or maybe you could figure out the least invasive way to change a particular gene’s expression.

X-Atlas → X-Cell

This is exactly what Chu and Bo’s teams have done. The data set is called X-Atlas and the model is called X-Cell.

In this episode, we discuss:

* Why the team abandoned autoregression for diffusion

* The CRISPR-based experiments that run millions of tests in parallel, and generate the raw data for X-Atlas and X-cell

* Generalization to real lab experiments in real human cells

* Beating the linear baseline that has outperformed previous models

* Justifying a kitchen-sink of priors, and how that stacks up vs. data and architecture

Bo also shared with us some of the (major) advantages he has as an academic vs. industry leader, and how his labs keep up with the breakneck pace of AI innovation.

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🔬 The Lab of the Future Should Feel Like a Data Center — Andy Beam & Rafa Gómez-Bombarelli, Lila Sciences Jul 16, 2026

Show notes

Imagine a dark warehouse. Racks and racks of devices with wires, tubes, and electronics sticking out. The next AI data center? No. This is Lila Sciences‘ dream for the future of science. A dark warehouse full of AI-guided robotics and lab equipment, cranking out new experiments 24/7, building toward a scientific superintelligence.

Their automated lab is almost hypnotizing to watch. They have floating plates zipping around on Wall-E-esque tracks, used vision-language models to control Windows 95 boxes, and created the world’s largest collection of voided warranties. In the process they’ve built a massive library of scientific reasoning tokens. Over 10 trillion of them, all experimentally validated.

No warranties were voided in the making of this video

To say Lila is ambitious is an understatement. Their goal is a scientific superintelligence wired directly into the wet lab. They are all in on the bitter lesson, and the thesis follows from it: a lab is an infinite token generator. Produce data at scale, and the synergies give you a general reasoner that can tackle any scientific problem. They are committing hard. Biology, chemistry, drug discovery, and materials science, all at the same time. Time will tell if it works, but it is an exciting hypothesis.

In our latest episode we sat down with Lila’s very own Andy Beam (CTO) and Rafa Gómez-Bombarelli (CSO, physical sciences) and went on a journey through the possibilities of AI-run science, almost as wide-ranging as Lila’s goals.

Did we mention they do both materials science and biology? In the same AI science factory? Same time, same lab, same AI. Finally a guest who can settle a long-running debate we’ve had amongst ourselves: is biology or materials science harder?

Watch to find out!

We discuss:

* The internet is spent, science is next. Why Lila thinks the scientific method is the last untapped internet-scale dataset, and why they treat RL as a data generation mechanism with nature as the verifier.

* The lab as a data center. Instruments as nodes on a graph, a magnetically levitating “PCI bus” transport layer between them, orchestration as a slurm queue. Andy is not short on analogies.

* Why Lila insists it is not an automation company. They optimize for flexibility and generalizability over raw throughput, which means humans stay below the API line wherever automating does not pay.

* Your experiment has a runtime. We put Escalante Bio’s question to Andy: if science is the token generator, what is the runtime of your data collection? His answer, in short, is that you cannot make the ribosome go faster. Why Lila bets on fast round-over-round iteration rather than big noisy multiplexed screens, and how Rafa’s team rebuilt a gas sorption measurement to run roughly 2,500x faster.

* What is actually in 10 trillion scientific tokens. Not sequences. Experimentally verified reasoning traces, a kind of data that Andy argues exists on the internet in quantities that round to zero.

* Breadth as a path to depth. Small molecule chemistry priors transferring to metal organic frameworks for carbon capture, and the claim that the general model beats domain-specific models sample for sample.

* If you have the data, what do you need the model for? Sri Kosuri’s koan about the ML-for-drug-discovery business model, and Andy’s answer: the coding model got better because it also read Shakespeare and carnitas recipes.

* The serendipity they want to automate. Emily Whitehead survived the first pediatric CAR-T cure only because the doctor treating her happened to know, from pediatric arthritis, which antibody would blunt her IL-6 response. Roll that dice again and you probably lose her. Breadth is how you stop depending on luck.

* Move 37 for catalysts. Model suggestions for platinum-group-free electrocatalysts that went from boring, to what a 40-paper expert called stupid, to the best performers they have made.

* Six months to in vivo CAR-T data in non-human primates, and the zero-FTE virtual startup commercial model that fell out of it. For context on why that number is startling, AbbVie paid $2.1B for Capstan on the strength of preclinical in vivo CAR-T data.

* You cannot have scientific superintelligence if you are just a good test taker. Ken Stanley, who wrote Why Greatness Cannot Be Planned, runs open-endedness at Lila. RL at scale gives you a ruthlessly Vulcan problem solver. Machine creativity is a different thing, and it is the part nobody has solved.

* The chain of thought is an unreliable narrator. The model reasons in latent space and only emits tokens. Sometimes it skips the experiment entirely and is still right. So how much do you trust the reasoning versus the verifier?

* Reward hacking when the rollout is physical. Chains of thought that collapse into repetition, and a model that got annoyed and swore at the scientist who kept asking it to redo a plate map. What happens when a pathological loop has a wet lab inside it?

* The bittersweet lesson. Rafa’s inversion of the bitter lesson: in AI, scaling is a roadmap. In materials, scaling is a filter, because only the things that scale end up mattering.

* Not your typical Flagship company. Why a famously single-asset biotech incubator spun out a platform bet, and Andy’s line that if Lila called itself a biopharma it would have a top-three GPU cluster.

* Bottlenecks they would remove by fiat. Sim-to-real for physics-based simulation, and the fact that RL training runs at roughly 5% mean FLOP utilization.

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Why AI Infrastructure must evolve for Agent Experience — Akshat Bubna, Modal CTO Jul 08, 2026

Show notes

We’ve been running a bit of an Agent Cloud series surveying all the top inference/compute/cloud providers, from Databricks to Daytona to Railway and, even further back, E2B, but we’re excited to conclude this series returning to Modal, which has just raised a monster $355M Series C.The cloud was built for developers. But agents are now changing that.The old infra stack was designed for a human who could read docs, reason through YAML, and understand dashboards to figure out what they need when something broke. While this was painful for developers, it worked since they could fill in missing context in their heads.However, agents don’t have that luxury. Now in this new era of agents, everything has to be tighter.They need a place to write code, run it, inspect the output, change the environment, debug failures, and try again. Fast iteration and feedback loops with all the necessary context are crucial for agents to operate properly. Furthermore, sandboxes are a clear representation of this shift as agents can easily spin up isolated environments. This programmatic infra even extends to research:Two years ago, we were one of the first to cover Modal with CEO Erik Bernhardsson and Alessio designed our favorite LS thumbnail of all time:At the time, Modal was just a teeny little company with a $17M Series A.Today, fresh off their $355M Series C, Modal is one of the clearest examples of the agent cloud future being built in real time: a cloud platform moving past traditional web app assumptions toward the workloads AI actually creates such as elastic inference, sandboxes, GPU burst, post-training, background agents, and infrastructure that agents themselves can operate.In this episode, Modal CTO Akshat Bubna joins swyx and Vibhu to unpack why AI applications don’t fit traditional cloud assumptions, why Kubernetes was never designed for bursty compute-heavy workloads, and why Modal is now shifting from developer experience to agent experience.We go deep on Modal’s AI infra stack: serverless functions, decorator-based infrastructure, elastic inference for custom models, GPU snapshotting, DeFlash, speculative decoding, Auto Endpoints, sandboxes, persistent storage, networked containers, private IPv6, RDMA, multi-node training, and Modal’s capacity pool across 17 cloud providers. Akshat also explains why RL rollouts can require 100,000 sandboxes, why production agents need hard guardrails, why observability may matter more than reading code, and why AI has made infrastructure exciting again.We discuss:* Why Kubernetes wasn’t built for bursty AI workloads* How Modal started as a better runtime before becoming an AI cloud* Why Modal added GPUs before ChatGPT* The shift from developer experience to agent experience* Why observability matters when agents are writing the code* Elastic inference for custom models across audio, video, robotics, and comp bio* GPU snapshotting, cold starts, and why inference workloads are so bursty* Why RL rollouts can require 100,000 sandboxes* DeFlash, speculative decoding, and frontier-level inference performance* Auto Endpoints and making optimized inference easier to deploy* What Modal adds beyond vLLM, SGLang, and raw GPU rental* Modal’s 17-cloud capacity pool and supercloud strategy* Networked sandboxes, sidecars, private IPv6, and RDMA* Serverless multi-node training for post-training and research workloads* Auto-research, model-guided sweeps, and agents launching GPU experiments* Compute strategy, capacity planning, and batch tiers* Why production agents need specialized sandboxes and hard guardrails* Modal’s take on managed agents, CI, Gitpod/Ona, Python, TypeScript, and Modal BenchAkshat Bubna* LinkedIn: https://www.linkedin.com/in/akshat-bubna-188885103* X: https://x.com/akshat_bModal* Website: https://modal.comTimestamps00:00:00 Introduction00:00:39 Modal’s origin and why Kubernetes wasn’t enough00:04:32 Developer Experience → Agent Experience00:06:21 Modal’s AI cloud primitives00:09:14 Sandboxes, agent loops, and proto-Cognition00:12:12 Elastic inference, GPU snapshotting, and 100,000 sandboxes00:15:24 DeFlash, speculative decoding, and Auto Endpoints00:19:59 Production-grade inference beyond raw GPUs00:22:00 Background agents, Ramp Inspect, and the agent lifecycle00:24:08 Modal’s 17-cloud supercloud strategy00:26:40 Networked sandboxes, private IPv6, and RDMA00:32:48 Multi-node training, post-training, and auto research00:37:36 Compute strategy, capacity planning, and batch tiers00:40:55 Open models, real-time AI, and production agent infra00:43:06 Hard guardrails, managed agents, and specialized sandboxes00:46:06 Why AI made infrastructure exciting again00:48:30 Model APIs, differentiated products, and agentic video00:51:50 CI, coding-agent infra, SDKs, and Modal Bench00:57:28 Closing ThoughtsTranscriptIntroduction: Modal, Series C, and the Art PartySwyx [00:00:00]: We’re here with Akshat, CTO of Modal, together with Vibhu. Congrats on your Series C.Akshat [00:00:10]: Thank you.Swyx [00:00:11]: Your party yesterday was amazing.Akshat [00:00:15]: Yeah.Swyx [00:00:15]: From all the photos and all the swag.Akshat [00:00:17]: We had a bunch of art installations, which was fun, seeing, like, our products on pedestals next to, like, Rodin.Swyx [00:00:25]: Very nice. Very nice. When you started, it was not the GPU inference company. Maybe it was in your mind. Take us back to the origin story.Modal’s Origin: A New Runtime Beyond KubernetesAkshat [00:00:39]: I first met Eric, who’s the CEO, through an investor. Back then Eric was already thinking about building, a new runtime, and he got there thinking through why are workflow orchestration products so hard to use. It’s because you have to run them on Kubernetes. Kubernetes is hard to manage. It’s not built for burstiness and, custom images,Swyx [00:01:03]: YeahAkshat [00:01:03]: It has a terrible developer experience.Swyx [00:01:05]: And I’ll, I’ll interjectAkshat [00:01:06]: YeahSwyx [00:01:07]: For listeners, who are new, we interviewed Eric two years ago, and there’s a bit more of the story there from Spotify and all those things.Swyx [00:01:14]: And I came across Eric through Data Council because he did that talk on the serverless container stack that you guys did, which was like, that was my first like, “Okay, I need to take Modal very seriously” moment.Akshat [00:01:26]: Yeah.Swyx [00:01:26]: But it was still very unclear, like, do I need all this for just my data pipelines?Akshat [00:01:33]: Yeah. initially what we were thinking about was if we build a better runtime, it’s a very useful primitive in itself. It’s There’s a lot of things that, get solved by serverless functions, like you can do, ETL stuff, you can do job queues, you can do all this, like, bursty processing, which it turns out every company had needs for. but then we also were thinking about this as like, this is a primitive that we can build a whole collection of products on, which are very verticalized. So perhaps data engineering would’ve been the first one, but we were thinking about inference. Back then it was more classical inference, like computer vision stuff and running XGBoosts and whatnot. But we added GPUs to the product a year before ChatGPT came out.From Serverless Containers to GPU WorkloadsSwyx [00:02:19]: Nice.Akshat [00:02:19]: We just didn’t think it would be that big of a deal.Swyx [00:02:22]: Yeah, just like add A100.Vibhu [00:02:23]: Was there any, like, early key problem that really sparked off why you built it?Akshat [00:02:28]: Yeah. Primarily it’s just, none of the tooling that was out there was built for, one, a really great developer experience, and also there’s a general trend of, a lot of the workloads that we were seeing were very. I wish there was a better word for it, but compute-heavy. Like, they need, one, like, need a lot more resources, so you need to burst up and down a lot, versus like Kubernetes designed for, like, slow scaling and, more for, like, web server use cases. And also there’s just a lot more specialization in, like, what kinds of environments these workloads run in. Like, we had sometimes they need accelerators, sometimes they need different kinds of images, and this is just like a consistent thing that we saw across a lot of companies. That would be the next step.Software-Defined Infrastructure and Decorator-Based DXSwyx [00:03:13]: Yeah. Yeah. Be nice. I don’t know how much this factored into the early story, but I wrote a post when I was at Temporal about infrastructure, software-defined infrastructure or something like that.Akshat [00:03:22]: Yeah, the self-provisioningSwyx [00:03:23]: Self-provisioning.Akshat [00:03:24]: Yeah.Swyx [00:03:24]: Yeah. I can’t even remember my own post.Swyx [00:03:26]: And then you put me on the landing page.Akshat [00:03:28]: Yeah. We really like, the term and so we stole it.Swyx [00:03:32]: Because you had the insight that everything can just be in decorators co-located with the code, right?Akshat [00:03:37]: Yeah.Swyx [00:03:37]: Was that a big part of the originalAkshat [00:03:39]: YesSwyx [00:03:39]: Story or it was just like a DX layer?Akshat [00:03:41]: That was, really important because we really didn’t want people to spend, so much time, writing YAML, and it seemed like you could really condense the surface area of what you’re doing, put it in code so you can operate on it just like you operate on other code, and like build stuff that’s more expressive and dynamic. and so yeah, that was always a very important part.Swyx [00:04:04]: Then the pushback is this is a DSL.Akshat [00:04:07]: Yeah.Swyx [00:04:07]: It’s you’re closed source. I am locked into Modal.Akshat [00:04:11]: Yeah. We never really got pushback for that because the nice thing about Modal is you can bring whatever code you have, and sure, the DSL is at the configuration layer for, what hardware you’re using, how you’re scaling things up, but you still own the code.Akshat [00:04:27]: And that’s, that’s been an important, part of our story, even as we do inference now.Swyx [00:04:32]: Yeah.Vibhu [00:04:32]: How much of do you think still stays the same today? Like if you were to build something today, DevX very important, but I feel like, a lot of this has been changed with just hook it up to an agent, have Claude Code, have Codex implement a tool. there’s very agent native primitives that are different than if I’m doing this myself, right?Developer Experience → Agent ExperienceAkshat [00:04:54]: We’ve changed our SDK team to think about agent experience instead of, developer experience and we think that the same benefits that apply for DX also apply for AX, which is why would you have an agent read through hundreds of Kubernetes files and like write YAML that’s not even typed when it can make a couple of changes in a decorator and it gets this self-provisioning runtime of, being able to see its changes live in action? yeah, it just seems from the customers we talk to, they find Modal is much faster for agents to use versus operating on a different substrate.Swyx [00:05:34]: Yeah, because like you, again, you co-locate the infrastructure requirements to the code that runs it.Akshat [00:05:38]: Yeah.Swyx [00:05:38]: Well, the negative thesis now is that nobody’s looking at their code anymore, so there’s no point.Akshat [00:05:44]: Yeah, people aren’t looking at code. one thing we still see is really important is observability.Swyx [00:05:51]: Yeah.Akshat [00:05:51]: Like how good is your dashboard? And of course, like we have, we push a lot of it to the CLI so the agents can do their own investigation, but you still need humans to go interpret what’s going on and, make judgment calls and whatnot. and that’s I feel like, Maybe more important now than looking at the code itself.Swyx [00:06:11]: Yes, because like, you can try to treat the code as a black box and then use, see the observable action that comes out of it, and then just prompt a change.What Modal Is For: AI Cloud PrimitivesAkshat [00:06:21]: Yeah.Swyx [00:06:22]: So I think it takes a bit of restraint to not specialize, to say, “I want to ship a new primitive,” and then just be general purpose.Swyx [00:06:31]: People ask you, “What are you for?” You’re like, “ I don’t know. We can do this, we can do that.”Vibhu [00:06:36]: Well, I’d be curious to see, like, okay, if we were to ask you, like, what is Modal for even at a high level? There’s a lot you guys do, sandboxes, GPUs, everything. How do you answer?Akshat [00:06:46]: Modal is a cloud platform that’s built for, where we’ve built the primitives from scratch for AI applications. and right now it covers, inference, training, batch processing, and sandbox workloads.Akshat [00:07:00]: But we’re building a lot moreSwyx [00:07:02]: I noticed you didn’t say web server, so there is still a role for, like, the always-on large-scale Kubernetes type things.Akshat [00:07:09]: Yeah, absolutely. We’re, we’re not trying to compete with the renders of the world, because yeah, we think the differentiator for us is the, are the workloads that need specialized compute, need to scale up and down a lot. yeah, they’re, they’re, they’re just shaped differently.Working Alongside Frontier StartupsVibhu [00:07:26]: I think you’re building a lot of it alongside the startups, right? They’re innovating quite a bit, even in your, like, latest blog post. Like, even in the series C, the customers that you mention here, the cognitions, technical ones, ramps and whatnot, they’re, they’re innovating with you, right? And that’s not something AWS is doing directly with.Akshat [00:07:45]: Yeah, absolutely. I think, this is again classic. We’re a small team. We can move really fast. our engineers are working with our customers and figuring it out. Yeah.Swyx [00:07:54]: So my first week at Cognition, I walked in, there was someone wearing a Modal shirt. I was like, “What are you doing here?” They’re like, “Yeah, I just. I am embedded inside of Cog.”Akshat [00:08:05]: Yeah, I think that was Peyton. We sent him overSwyx [00:08:07]: Yeah.Akshat [00:08:07]: Because, the latency of communication was too high otherwise.Swyx [00:08:12]: Yeah, distributed node, you have to - you have to place one and collocate.Vibhu [00:08:16]: Yeah.Swyx [00:08:16]: So I had a, I had direct personal experience, right? So I worked on smol developer three years ago. it was inspired by Claude 1. I think you onboarded me at some point, like, just before, and I was like, “Oh, like, I need some bursty compute. Like, I was just gonna try using Modal.” And it was a, it was a pretty pleasant experience. apparently, I showed up in the board meeting, like the analytics.smol developer, Sandboxes, and Proto-CognitionAkshat [00:08:39]: Yeah, you blew up on Hacker News and,Swyx [00:08:41]: YeahAkshat [00:08:41]: We got a big traffic spike. I. I think the way you used smol developer was Modal functions for running stuff, which was. Like, the, that was a good use case. but then, yeah.Swyx [00:08:53]: Yeah. That - So to me, that was proto-cognition.Akshat [00:08:55]: Right.Swyx [00:08:56]: If only I had, like, stuck to it.Swyx [00:08:58]: Like, that was like, if - did you say draw the tech treeAkshat [00:09:00]: AbsolutelySwyx [00:09:00]: You’re just like, “Yeah, like, probably this will happen.”Akshat [00:09:02]: Yeah. Like, he was so close. You were just rebuilding upon usSwyx [00:09:04]: I just didn’t realize.Akshat [00:09:05]: But the funny story there is at the same time, we were talking to a bunch of customers who needed something like sandboxing.Swyx [00:09:14]: Yeah.Akshat [00:09:14]: This is like twenty-three.Swyx [00:09:15]: Yeah.Akshat [00:09:16]: So we builtSwyx [00:09:17]: You introduced a new API right after that.Akshat [00:09:18]: Yeah.Swyx [00:09:19]: Yes.Akshat [00:09:19]: Like, we built sandboxes in May of twenty-three before anyone was even knew this was gonna be a thing. And the first example we published was, we took smol developerSwyx [00:09:…

Full show notes at the publisher

🔬 The Coolest Diffusion Research Isn't in LLMs — Evan Feinberg & Sergey Edunov, Genesis Molecular AI Jul 01, 2026

Show notes

This episode has a fun personal twist: There’s a counterfactual world where I was employee #1 at Genesis Molecular AI, the company behind today’s episode. A certain introduction happened a few weeks too late and I had already happily signed at Atomwise, another ML-for-drug-discovery startup. Same problem, different company. I was certain ML was going to transform small molecule drug discovery. Early results were underwhelming. Useful at times, but nowhere near revolutionary. In the last year I’ve seen signs that ML is finally ready to deliver on my convictions from a decade ago. Genesis is one of the places that might have finally cracked this problem. I was super excited to come full circle and catch up with co-founder Evan Feinberg and CTO Sergey Edunov.

If you are at all interested in small molecule drug discovery, we think you will find this fascinating!

In our nearly two hour chat we cover:

* What is small molecule drug discovery, and why is it hard

* Structure prediction as a hotbed of innovation in AI algorithms

* How advances in AI elsewhere have enabled stepwise improvements in predictive power

* How the community benchmarks are essentially calling AI slop good enough

* The Genesis flagship model (PEARL) can routinely hit a threshold that is necessary for real-world applications

* New agentic workflows enabled by these highly accurate models

Read on for more, and also some personal thoughts on the future at the end.

The coolest diffusion research is happening at Genesis

Sergey Edunov came to Genesis from Meta where he led Llama 2 training and Llama 3 pretraining. Sergey was a former physicist who thought he was done with physics after many years of training LLMs. Then, he discovered Genesis, and was blown away with all the novel architecture work they’ve been developing.

It probably surprises no one that modern LLM research has not resulted in fundamentally novel or exciting updates in architectures since almost the advent of the transformer — the entire field is using variants on the same idea that came out in the original “Attention is all you need” paper. Sure, some were quite useful (mixture-of-experts in particular allowed for the massive model paradigm we’re at today), but there was very little conceptually exciting.

“We sort of had to wait for the right primitive to get created, and that turned out to be diffusion… Actually, some of the most innovative diffusion research that’s happening in our field is happening in 3D structure prediction right now.” — Evan Feinberg

The field of 3D structure prediction on the other hand has been a hotbed of research. Genesis’ recent model PEARL (Place Every Atom at the Right Location) is able to understand protein flexibility, and model not just where the ligand goes, but also make small adjustments of the protein so that the two fit better than either alone. The field knew this was missing for a long time, but it was really hard to model until now.

Agentic Discovery

What makes this problem so hard? As Sergey points out, there are 10^60 possible drug-like small molecules. You’ll never be able to search them all, and trying to find the good ones is something like finding a needle in a haystack — except everything except your needle is dangerous.

“There are 10 to the 60 drug-like small molecules in the universe… it’s like finding a needle in a haystack, where everything except your needle is very, very dangerous.” — Sergey Edunov

“Or finding hay in a needle stack might be a more apt analogy.” — Evan Feinberg

Trying to solve the multi-parameter optimization problem is even worse. What makes a strong binder and a molecule with good “ADMET Properties” are oftentimes at tension with each other. For example, a good binder is likely greasy, but a greasy molecule is likely insoluble so it won’t enter the bloodstream and get to where it needs to go!

Genesis’ advances in generative AI have now pushed them beyond the threshold where they believe agentic drug discovery loops are finally possible. We all remember the early days of LLMs. They were great chatbots but terrible agents, as small errors compounded rapidly into uselessness. As LLMs got better, the usefulness of agents rapidly improved. Evan and Sergey argue that their models at Genesis recently passed a similar threshold. Their internal agentic drug-discovery system (code named SAPPHIRE) can now iterate like a chemist: look at and reason about poses, form hypotheses, read literature, use internal tools, create candidates for the next iteration. Combining this with automated lab partnerships like the one Genesis has with Incyte, we’re rapidly approaching a time of drug discovery agents running 24/7 making/testing new molecules. Exciting times!

Benchmark crisis: Everyone’s favorite benchmark is slop

One surprising point that isn’t talked enough about: the academic field of “co-folding” has settled on a benchmark value of “2 Angstrom RMSD” as a metric for a “good pose”. Evan does not mince words: this threshold is just bad. Perhaps even deceptively bad. For many strong binders, there’s a very clear pose, one that you can even directly resolve in the PDB electron density! And yet, with a 2Å RMSD threshold, you can get the pose quite wrong in ways that might even mislead a medicinal chemist. For example, flip around an aromatic ring, and everything looks reasonable, but you’re no longer modeling the right interactions.

Evan makes the strong claim that 1Å RMSD is really the threshold necessary to ensure the core of the molecule is sitting where it needs to be, and models all interactions.

“If your model is sitting at 1.8, 1.9 Angstrom RMSD, that’s slop, most likely.” — Evan Feinberg

As a simple example, he points out hydrogen bonds which are responsible for many of the most important interactions in protein-ligand systems. Hydrogen bonds only have a 0.6Å range to be valid! Clearly if you’re accurately resolving all H-bonds, you generally have to be doing much better than the 2Å threshold.

This is clearly a hard-fought lesson for Evan and Genesis. In their opinion, the community is stuck on these benchmarks because academics developing methods were not users. Evan does see signs of life, with the use of new metrics such as lDDT for co-folding. Hopefully soon the community can agree that “1.8Å RMSD is slop”, and start hill climbing on this much harder task.

For a more thorough exploration of the weaknesses in conventional benchmarks, see the PEARL technical report.

PEARL tops OpenBind

Which makes what happened next all the more striking. Near the end of the podcast, we talked about a recent “proof-is-in-the-pudding” moment for Genesis — evaluating their PEARL model on a recently released OpenBind benchmark. This benchmark featured 802 never before seen co-complexes on a target protein EV-A71. This target seems almost custom-chosen to give most classical docking methods a problem. When a ligand binds to the main binding site, the protein moves around to close off the path the ligand used to enter the binding pocket. This process, known as “induced fit” is notoriously hard for traditional methods to model. The tradeoff is easy to understand: treating the protein as a static structure, it becomes difficult to place a ligand in a binding pocket. Treat the protein as dynamic, and now you have to simulate complicated processes that take a long time to resolve.

PEARL was able to model the induced fit of the ligand without running long MD simulations. Across the different evaluation metrics, PEARL came out not just ahead, but oftentimes well ahead of any public model. A truly impressive result.

“Where PEARL was exceptionally good is figuring out how to move this loop. We are basically correct for every single pose.” — Sergey Edunov

Even more exciting, this was done without any fine-tuning, or using any data on the target or homologous targets — the template PDB was released after PEARL’s training cutoff.

Where does co-folding go now?

As someone who has followed or participated in ML techniques for protein-ligand interactions for almost a decade, I was genuinely impressed with the results that Genesis has released recently. This has been many years in development, and I’m sure Evan and the team had many sleepless nights trying to get to this point. I also think other teams are making similar progress — both Isomorphic and Deep Origin have released results that seem spiritually similar and combine computation, wetlab data, ML, to achieve genuine predictive power that seemed impossible a decade ago. Sadly, all of the above are closed source so there’s no way to honestly compare them. Looking at the results I think there might be a time in the not so distant future where we can consider protein-ligand binding “solved”.

I sincerely hope that the academic community can take inspiration from these developments. Once you know something can be done, it’s much easier to execute. Still, I believe that the key enabler in all of the above was the tight integration of ML, large-scale computation, and real-world drug discovery applications. Sadly academia is just not structured in a way that makes such a development easy.

With those parting thoughts, we hope you give the podcast a listen!

This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.latent.space/subscribe

Why the Frontier Ecosystem must be Open — Matei Zaharia and Reynold Xin, Databricks Jun 24, 2026

Show notes

We’re excited to have Databricks join us at AIEWF, among hundreds of the top companies in the AI Engineer ecosystem. LS subscribers can use their discount to get past the late bird pricing and access over $50k in sponsor offers! Everyone is still talking about Satya’s Frontier Ecosystems post, but few have actually built a (now $175 billion) frontier ecosystem and cloud like our guests today.From open-sourcing the layer above coding agents to rethinking databases for the agent era, Databricks cofounders Matei Zaharia and Reynold Xin are pushing the company beyond the lakehouse into a full data-and-AI operating system. In this episode, Matei and Reynold join swyx at the 2026 Data + AI Summit to unpack Omnigent, LTAP, Lakebase, agent security, open formats, Mosaic, and why databases may matter more than ever once AI agents start doing real work.We go deep on Omnigent: Databricks’ open-source meta-harness for combining, controlling, and sharing agents across Claude Code, Codex, Cursor, Pi, custom agents, and internal tools. Matei explains why coding agents and enterprise agents run into the same problems: portability, collaboration, session history, security, spend controls, and the need for a common API above every harness.Then Reynold walks through Databricks’ database dream: why CDC is brittle enough to joke that it means “continuous data corruption,” why HTAP has been the holy grail of database engineering, and why Databricks thinks LTAP gets most of the benefits by unifying the storage layer instead of collapsing every query engine. We also cover Databricks’ infrastructure scale, the culture behind rapid prototyping, the difference between tech and enterprise customers, Databricks vs Snowflake, whether vector databases should have ever existed, the Mosaic model strategy, Genie, AI Runtime, RL fine-tuning, and the thesis that traditional software gets rewritten once the data is in the right place and agents sit on top.Databricks began as a company for the big data era. The origination of Spark from the Berkeley AMPLab which eventually turned into the product Lakehouse convinced enterprises that they didn’t need a separate data lake, warehouse, ML platform, and governance layer. They just needed one open foundation where all of their data could live and be reasoned over.Since then a lot has changed, but data has only become more important. Data is no longer something you keep track of and analyze ad hoc, it’s the necessary context agents need in order to act. So the framing has shifted from “where do we put all of our data?” to “how do we expose the right slice of state, history, permissions, and business logic to an AI system at the exact moment it’s doing work?”If frontier model performance becomes commoditized, the durable advantage then becomes the company-specific context around them: proprietary data, governed access, operational state, transaction logs, workflows, and feedback loops. Which makes Databricks positioned perfectly.Now coming fresh off the Data + AI Summit 2026, the company is moving just as fast to keep up, announcing Genie One, Omnigent, LTAP, and many more, indicating a central mission in its newer work: Databricks is trying to become the operating system for enterprise agents.Models are getting good enough, but agents are only useful if they have the right context, permissions, memory, state, cost controls, and access to live business data. Fundamentally it appears that significantly better model performance in production is a systems problem, one that data guys like us are remarkably well prepared to solve!We discuss:* Why Databricks built Omnigent as a meta-harness above existing AI agents* Why coding agents and custom enterprise agents need the same infrastructure* The common API for agent sessions, files, streams, tool calls, and cancellation* Why persistent sessions, cloud sandboxes, sharing, search, and collaboration matter* Why Databricks open-sourced Omnigent instead of keeping it proprietary* Databricks’ internal agent usage, cloud sandboxes, and coding workflows* The scale of Databricks: 50–60 million virtual machines a day and exabytes before breakfast* Why agent security needs contextual and stateful policies* How an agent could read confidential docs, install a compromised npm package, and leak data* Why spend control matters when an agent can burn $500 reading logs* Startup opportunities around coding-agent analytics, quality, skills, and spend* LTAP, Lakebase, and why Databricks wants to rethink the database stack* OLTP vs OLAP, CDC, and why data pipelines break at 3 a.m.* Why HTAP has historically been the holy grail of database engineering* Why Databricks thinks LTAP is “HTAP done right”* How writing transactional data into column-oriented formats changes analytics* Why agents need live operational context from databases, not just telemetry* How Databricks prototypes strategic systems without endless process* Enterprise vs tech customers, governance, procurement, and DIY culture* The “second system syndrome” risk of rewriting a database engine* Building a database engine from a decade of traces and quadrillions of data points* Why vector databases should never have been a separate category* Why open formats and AI changed the race with Snowflake* The Mosaic story, DBRX, Genie, document parsing models, and specialized model training* Why model customization and RL fine-tuning may become mainstream* Why “get the data there, slap some agent on top” may rewrite traditional softwareMatei Zaharia* LinkedIn: https://www.linkedin.com/in/mateizaharia* X: https://x.com/matei_zahariaReynold Xin* LinkedIn: https://www.linkedin.com/in/rxin* X: https://x.com/rxinDatabricks* Website: https://www.databricks.com* X: https://x.com/databricksTimestamps00:00:00 Introduction00:02:22 Omnigent and the Agent Infrastructure Layer00:08:39 Agent Clouds, Common APIs, and Open Source00:16:52 Databricks Scale and Internal AI Workflows00:18:03 Agent Security, Governance, and Spend Controls00:27:34 LTAP and the Database Dream00:30:30 CDC, HTAP, and Why Data Pipelines Break00:34:05 Lakebase, Parquet, and Live Data for Agents00:36:47 Databricks’ Culture of Fast Prototyping00:43:40 The Dream Engine and Rewriting the Database Stack00:51:02 Vector Databases, Query Engines, and LTAP00:52:36 Databricks vs Snowflake00:57:48 Mosaic, DBRX, Genie, and Specialized Models01:03:11 Context, AI Runtime, and RL Fine-Tuning01:06:15 Why Data + Agents May Rewrite Software01:07:09 Closing ThoughtsTranscriptIntroduction: Databricks, Data + AI Summit, and Founder DynamicsSwyx [00:00:00]: Matei and Reynold from Databricks, welcome to Latent Space.Reynold Xin [00:00:06]: Hey, thanks for having us.Swyx [00:00:07]: Yeah.Matei Zaharia [00:00:08]: Yeah, thanks so much.Swyx [00:00:09]: thanks for taking time out. You have your Databricks, Data AI Summit going on. You were just telling me how the first summit that you guys ran was just 50 peopleReynold Xin [00:00:17]: Yeah, it wasSwyx [00:00:17]: in BerkeleyReynold Xin [00:00:18]: little meetup at Berkeley, I thinkMatei Zaharia [00:00:19]: YeahReynold Xin [00:00:19]: put togetherMatei Zaharia [00:00:20]: We were doing these tutorials and, yeah, just teach people Spark.Swyx [00:00:23]: Yeah. obviously now it’s like, I think like the headline number’s like 100,000 people around the world, 30,000 in person.Swyx [00:00:30]: it’s a crazyMatei Zaharia [00:00:31]: AmazingSwyx [00:00:31]: community. Well, I just saw the keynote.Swyx [00:00:35]: Ali’s just. Did was it obvious or that back when that Ali would be, like, such a great, like, CEO? LikeReynold Xin [00:00:42]: OhSwyx [00:00:42]: such a great presenter?Reynold Xin [00:00:43]: What do you think?Matei Zaharia [00:00:44]: I think among our group of founders it was clear that, I think he’d be the best at this.Swyx [00:00:50]: Yeah.Matei Zaharia [00:00:50]: And yeah, it turned out great. And he’s, he’s ramped up on so many topics growing a company. He would just go in and, like, study it and, be talk to all the experts. Like, even if he can’t hire the person, learn enough about, like, finance and sales and whatever it was, and, and go from there. Yeah.Swyx [00:01:09]: Yeah.Reynold Xin [00:01:10]: he’s obviously very high IQ and a very high EQ, but it wasn’t. Like, Ali today is quite different from Ali from, like 10 years ago. I think there’s a lot of work that he put in to, get to this point.Swyx [00:01:20]: Yeah. no, to me the most appealing thing about him is that he’s funny. And like, it, it’s, it’Matei Zaharia [00:01:26]: It’s true, yeahSwyx [00:01:26]: it’s hard to make jokes about, data warehousesReynold Xin [00:01:30]: About serious topicsSwyx [00:01:31]: securityMatei Zaharia [00:01:32]: YeahSwyx [00:01:32]: what have you.Matei Zaharia [00:01:33]: Oh, yeah. That’s for sure.Swyx [00:01:34]: Yeah. So you guys launched a whole bunch of things. I’ll, I’ll just name check briefly, the stuff because we’re not gonna cover everything. Omnigentt, your baby. LTAP, your baby, your dream engine.Swyx [00:01:47]: we’re also gonna cover Genie, cover CustomerLake, you acquired PantherMatei Zaharia [00:01:52]: YeahSwyx [00:01:52]: Open Sharing, and there’s Unity AI Gateway. A lot of these, I think, like, are things that you would expect a Databricks to do. It’s, it’s like part of the roadmap. Everyone in your category has similar things. But I think, probably the two of you are leading the two most unique and differentiated initiativesOmnigent and the Agent Infrastructure LayerSwyx [00:02:09]: on, in the landscape. Maybe we’ll start with, Omnigentt we’ll, we’ll, we’ll, we’ll go into it. I do think that a lot of people are exploring this meta harness concept.Matei Zaharia [00:02:21]: Yeah, totally.Swyx [00:02:21]: What led you to it?Matei Zaharia [00:02:22]: Yeah. There were a couple of, like, converging lines, which I think is a good sign that you need something new. So on the one hand, there’s all the coding agent info internally. We have really great, dev infra team. they built something called Isaac, that’s like a wrapper on Claude Code and Codex, and, lets you use them either on the web in, like, sandboxes or, just on your dev machine or on your laptop or whatever. And then, they were adding all kinds of stuff there. And we saw all the more advanced engineers like, were building their own workflows with tons of agents, and they were building their own UIs and stuff on top or even on top of that. And then the other one was, like, us building agents. We ship this, like, data science agent called Genie on the research team, which I lead. We also build a lot of internal ones for various things, and then we have all the customer ones. And all of them running into this thing of like, “Oh, I need to switch model and harness and so on,” every few months. Plus the agent is, like, completely useless if you can’t share sessions with someone and have history and have search and all this, like, layer on top of it for collaboration. I thought a bit about it from both contexts and, at first people thought it was weird. They’re like, “Why are you doing coding agents and custom agents in the same thing?” But I said it’s, it’s the same problems and, you just wanna build the stuff that lets you deliver the agent, maybe control it if you care about security, and, make it portable across things. And then we prototyped some things as experiments. We saw, yeah, we can make it work, and then we built that for real.Swyx [00:04:06]: I’m wondering if this let’s call it architectureMatei Zaharia [00:04:11]: YeahSwyx [00:04:11]: maps to anything in your careers in the past. like I always think about how a lot of things just tie back to operating systems.Swyx [00:04:18]: A lot of operatingMatei Zaharia [00:04:19]: YeahSwyx [00:04:20]: systems tie back to databases,Matei Zaharia [00:04:21]: SoSwyx [00:04:21]: or the other way aroundMatei Zaharia [00:04:22]: so the thing, I do think it ties a lot to, like, network protocols, internet protocol. we alsoSwyx [00:04:29]: Communication between entities.Matei Zaharia [00:04:30]: Yeah. We did stuff with, like, data sharing also, which is probably, most viewers probably won’t know unless they’Swyx [00:04:36]: Yeah, open protocol is the term.Matei Zaharia [00:04:37]: Yeah.Swyx [00:04:38]: Open sharing. Open sharing.Matei Zaharia [00:04:38]: Open sharing.Swyx [00:04:39]: Yes.Matei Zaharia [00:04:39]: Yeah. So it’s like you have a company, you maintain some table, like let’s say like a Walmart or something. They have like the, inventory and what’s been sold in each store. And then you also have suppliers, and they would love to produce more things and ship them, like, exactly the moment you need them. So they would love, like, real-time access to your table. So instead of like sending emails around or Excel sheets or phone calls, why can’t you share like a view of that table in real time with them? Then they query, they, join it with their data, and they decide what to send. So it’s one of these things where you, like you might ask like today since we can vibe code anything so fast, why do we even need to design like protocols or APIs or software? Why can’t you just vibe code things on demand? But for this type of interoperability where multiple parties that are moving at different speeds are building stuff and you still want some layer on top to coordinate, you do wanna design it and build it. So it reminds me of that, like agents talking to each other and, users talking to agents and tools.Agent Clouds, Cloud Sandboxes, and Keeping Sessions AliveSwyx [00:05:42]: Reynold, any other comments alternative viewpoints?Reynold Xin [00:05:46]: I think, by the way, we had a debate on exactly which set of benefits would, matter a lot, and I think around the time we decided to do this thing I was telling Matei, “Hey,” it just happened to be there’s a particular week that I was coding nonstopSwyx [00:06:00]: from the moment I woke up to, like, the moment I went to bed, I was, like, looking at my Claude sessions, my Codex sessions. And one of the things that was particularly annoying was having to keep my laptop open.Swyx [00:06:12]: I was driving to a doctor’s appointment, and I remember because I wanted to make sure the whole thing continues working.Matei Zaharia [00:06:18]: But by the way, it’s so comforting to hear you say that because I’m like, “I don’t know if I’m a clown and I’m doing this or like.”Swyx [00:06:25]: Yeah. Like honestly, I was driving and I was tethering my laptop to my phone.Matei Zaharia [00:06:29]: huh.Swyx [00:06:29]: Keeping it on the side. Whenever I hit a red light, I started looking at what’s going on my laptop.Matei Zaharia [00:06:35]: Yeah.Swyx [00:06:35]: And I just felt that was ridiculous.Matei Zaharia [00:06:37]: Yeah.Swyx [00:06:37]: It felt like we went back to the dark agesMatei Zaharia [00:06:39]: YeahSwyx [00:06:40]: programming. the productivity you gain from all this coding age is amazing, but, yeah.Matei Zaharia [00:06:45]: Have you heard of cloud?Swyx [00:06:47]: Yeah.Swyx [00:06:48]: It was crazy to me.Matei Zaharia [00:06:49]: Oh, the thing you were working on was the sandboxes or was this before that?Swyx [00:06:52]: It was a sandbox.Matei Zaharia [00:06:53]: Okay.Swyx [00:06:54]: I was workMatei Zaharia [00:06:54]: So you were inSwyx [00:06:55]: So I was approaching from a very different angle. I wanted to, “Hey, we’re gonna have cloud sandboxes that doesn’t shut down. You can get one very quickly,” but not just for running agentic sessions.Matei Zaharia [00:07:06]: Yeah.Swyx [00:07:06]: It’s also for running development. So I was personally building that week, and through building that, I ran into all these issues, and then I wroteMatei Zaharia [00:07:15]: YeahSwyx [00:07:15]: a document for Matei, it’s like, “Here’s my wish list of what the actual environment should do.” And I think he ended up almost implementingMatei Zaharia [00:07:22]: YeahSwyx [00:07:22]: every single one…

Full show notes at the publisher

Red-Teaming after Mythos — Zico Kolter & Matt Fredrikson, Gray Swan Jun 22, 2026

Show notes

AI Engineer World’s Fair regular bird tix will sell out ~today! Join us next week ahead of the Late Bird price hike and get >$40,000 in sponsor credits for attending!Thanks to the US Government issuing an export control directive on Mythos and Fable, the risks of jailbreaks and (industry term) indirect prompt injection are suddenly the talk of the town, though we have been covering AI security for a few years now, from Hackaprompt to the enigmatic Pliny the Elder.Zico Kolter, member of OpenAI’s board of directors on the Safety & Security Committee, and Matt Fredrikson, CMU professor and CEO of Gray Swan, co-authored the definitive paper on Indirect Prompt Injections, and Gray Swan were cited authorities on the Mythos model card, directly investigating the exact capabilities that are under scrutiny right now:We seized the opportunity to ask them the state of AI Red Teaming, and Shade, the adversarial red teaming tool that Anthropic used to evaluate the robustness of their models against prompt injection attacks in coding environments. Shade is part of their overall toolkit covering Simon Willison’s Lethal Trifecta, including Cygnal, an AI guardrails product, and the world’s largest AI Red Teaming Arena, including AIRT celebrity Wyatt Walls.All of this security tooling, and yet, we’re only staving off the inevitable.The risks of extremely smart AI increasingly feel like gray swan events: an event that everyone can see coming. In this episode, Gray Swan cofounders Zico Kolter and Matt Fredrikson join swyx to explain why AI security is not just “cybersecurity with AI,” why agents introduce a new class of vulnerabilities, and why the next major AI incident may be a gray swan: unlikely, but clearly visible before it happens.We go deep on prompt injection, automated red teaming, model robustness, agent identity, computer-use agents, enterprise guardrails, and the emerging AI insurance/compliance stack. Zico and Matt also explain why frontier models are not automatically safer as they scale, why specialized red-teaming models can now beat humans at breaking AI systems, and why the future of AI security may depend on AI systems attacking, defending, and interpreting other AI systems.We discuss:* Why AI systems need a different security mindset from traditional software* How prompt injection creates a new exploit class for agents like Codex and Claude Code* Gray Swan Arena and the rise of community red teaming* Shade: AI that can outperform humans at breaking models* Why LLMs are an alien form of intelligence that fail differently from humans* Human vs browser-agent robustness and why humans ranked fourth* Why eval awareness and capability elicitation matter* Cygnal: Gray Swan’s guardrail model for policy enforcement* Why bigger models do not automatically become more robust* The lethal trifecta: untrusted data, private data, and exfiltration* Why “just prompt it better” is not enough for enterprise AI security* OpenClaw, computer-use agents, and the agent security nightmare* Agent-native identity, permissions, and enterprise deployment* Why AI security may become part of insurance and compliance* Why the first major AI prompt-injection breach may be inevitableGray Swan* Website: https://www.grayswan.ai/Zico Kolter* X: https://x.com/zicokolter* Website: https://zicokolter.com/* LinkedIn: https://www.linkedin.com/in/zico-kolter-560382a4/Matt Fredrikson* Website: https://www.mattfredrikson.com/* LinkedIn: https://www.linkedin.com/in/matt-fredrikson-7596349/Timestamps00:00:00 Introduction00:02:31 Why AI Security Is Different00:06:38 Testing Claude, Codex, and Prompt Injection00:07:47 Gray Swan Arena and Automated Red Teaming00:11:14 AI That Breaks Models Better Than Humans00:14:00 LLMs as Alien Intelligence00:19:00 Humans vs AI Agents00:24:35 Red Teaming, Jailbreaks, and Capability Elicitation00:26:11 Cygnal: Guardrails for AI Agents00:34:04 The Lethal Trifecta00:39:31 Can AI Automate AI Research?00:45:47 OpenClaw and the Computer-Use Security Problem00:50:44 Agent Identity, Permissions, and Enterprise AI00:54:24 The Future of AI Security01:00:30 AI Insurance and Compliance01:04:32 The Gray Swan Event Everyone Sees Coming01:06:04 Closing ThoughtsTranscriptIntroduction: Gray Swan, AI Security, and CMUSwyx [00:00:00]: We’re here in the studio with Gray Swan, Matt and Zico. Welcome.Zico [00:00:08]: Great to be here.Matt [00:00:09]: Thanks for having us.Swyx [00:00:10]: You’re visiting from Pittsburgh? The home of all good computer science. I don’t know if I’m overstating things. A very strong university.Zico [00:00:18]: CMU has been the center of a lot of AI since really the dawn of the field.Swyx [00:00:22]: Especially a lot of self-driving and some language learning. Congrats on your Series A. You’re here because you’re attending Snowflake Summit, and Snowflake is one of your investors. Let’s introduce crisply at the top: what is Gray Swan, and what have you chosen as your startup domain?Matt [00:00:42]: At Gray Swan, our mission is to empower everyone to use AI safely and securely. Large language models are software, and if you want to deploy them or build applications on top of them, you need to understand the vulnerabilities and what can go wrong. That includes everyday mistakes, like an agent making the wrong tool call, but also worst-case scenarios where an attacker has an incentive to make your agent misbehave, leak data, or steal credentials. Gray Swan grew out of our research at Carnegie Mellon, where Zico and I have spent over a decade studying new vulnerabilities and attack surfaces in deep learning systems: how to test for them, understand their severity, and make inference more robust.Adversarial Examples and Why AI Security Is DifferentSwyx [00:02:05]: Honestly, a very fruitful area of study for any academic. Throwback, this is 10 years ago, which is basically the entirety of me. I got a lot of inspiration from Ian Goodfellow, a friend of the pod, and this is one of those initial adversarial settings.Matt [00:02:23]: This paper was directly inspired by Ian’s work.Swyx [00:02:29]: Zico, what about your side of the story?Zico [00:02:31]: Like Matt, I have been faculty at Carnegie Mellon for a while. Fundamentally, we believe in the transformative power of AI. It has already transformed the software ecosystem, and it will transform many other ecosystems going forward. The issue is that these systems behave very differently from the software we are used to. I do not just mean that AI can find vulnerabilities in software, though it can. I mean that AI systems have inherent vulnerabilities of their own. They can be tricked in ways people can be tricked, so you need a different security mindset.Zico [00:03:23]: This matters especially when there is the possibility of correlated failures. It is not just that there are many AI systems out there; it is that everyone is using a few models. If you find vulnerabilities in agents that everyone uses, like Codex and Claude Code, you have a new class of exploit. The labs are doing a lot of work here, but when a new platform emerges, a separate security system often emerges alongside it. That is where we are with AI: there is a need for specifically minded AI safety and security providers, and the demand is only going to grow.Treating Models as Untrusted SystemsSwyx [00:04:55]: I want to highlight right at the top that this is not a cyber episode in the traditional sense. A lot of people looking at the title might think that, but you’re actually trying to treat these models inherently as untrusted entities?Zico [00:05:11]: Exactly. This is a common conflation because AI is also good at cybersecurity problems, both solving them and causing them. But AI systems themselves introduce new vulnerabilities. Gray Swan is not about using AI to make your cyber infrastructure better; it is about understanding and mitigating the security risks you bring in when you adopt and deploy AI.Matt [00:05:49]: A big part of that is how people are using artificial intelligence. Once you build entire autonomous systems on top of models and integrate them into your larger platform or network, you have a potential cybersecurity risk. The goal is to mitigate the risk posed by the AI as it relates to your broader cybersecurity goals.Testing Claude, Codex, and Indirect Prompt InjectionZico [00:06:17]: Part of this is red teaming. One reason we reached out to you was that you were involved in the Claude Mythos preview, where you were one of the authorities on IPI, or indirect prompt injection. When you receive a model, it does not have to be Mythos, but that is the most prominent one right now: what do you do with it?Matt [00:06:38]: We do a range of things. In the Mythos case, the concern from Anthropic was how robust the model is to indirect prompt injection. If you operate a coding agent and use Mythos as the model, it will fetch untrusted content and read text you do not control. How robust will it be at staying true to its original objective and not getting hijacked? We also help frontier labs test their safeguards for issues like cyber misuse. Broadly, we provide adversarial safety and security evaluations so model builders can assess progress from one iteration to the next.Zico [00:07:37]: They also do this in-house, and Anthropic is very ideologically inclined to do it. What do they choose to outsource versus keep in-house?Gray Swan Arena and Automated Red TeamingMatt [00:07:47]: So there are two things that I think, we stand out for. One is the Gray Swan Arena. So we operate a community of red teamers. We provide, prize challenges. a lot of these come from the needs of the lab sponsors. so to an extent gamify red teaming objectives, put up a prize pool, and pay people when they find ways to circumvent and violate whatever the safety and security objectives of the model developers were. So that’s, that’s one. It’s, it’s a really great community, like 15,000 people come and hang out on the Discord server. Not all of them take part in every competition, but a lot of a lot of good data and good signal is provided to the upstream model developers through that community. The second is the automated red teaming that we do. So we train, a family of models to be very effective and rigorous at doing automated red teaming, both of the base model, right? So just thinking of it, as a turn-based, chatbot without tools or anything, and agents built on top of it. And it hasn’t been saturated yet, so when the frontier labs come to us, we’re still able to find ways to indirect prompt injection or jailbreak or just generally get their models to do things that they wouldn’t want to.Zico [00:09:11]: Did you say without tools?Matt [00:09:12]: With and without tools.Zico [00:09:13]: With and without tools.Matt [00:09:13]: So we definitely operate on On agents as well.Zico [00:09:16]: Obviously that would be more useful.Matt [00:09:17]: Yep. that’s, that’s actually a fairly recent thing. For a while, what we would help, the frontier labs with was more just, chat-based interactions, going around their content safety policies and what is in their model spec. Now the focus is very much on agents and tool use and all the downstream applications that people want to build on top.Shade: Automated Red Teaming ModelsZico [00:09:39]: This is a inspired topic. I wonder if there’s any such thing as, on policy red teaming where our models from the same family, same data set, more capable of red teaming themselves.Matt [00:09:51]: That’s an interesting question. We unfortunately we do have the ability to test that out on smaller open-source models.Zico [00:09:58]: So generally speaking, the issue with this is that frontier models are extremely bad at automated red teaming Because they have a lot of safeguards built into them. So if you try to use them to jailbreak another model, they will actually refuse. Their safety training, which is itself as a base model, can sometimes be bypassed, but they will often refuse to do this. Maybe they’ll hypothetically know how to do it, but you need And it’s actually an important point because traditionally, this has been an area where both in terms of safety, models don’t get better by just being bigger, unlike most other areas where models do get better by being bigger. Safety has not been like that traditionally. you have to train them explicitly to be safe or they won’t do that. But on the flip side, they’re also not necessarily better at red teaming, by default. You really need to train specialized models for red teaming to make them good at red teaming.Matt [00:10:56]: That’s awesome for you guys.Zico [00:10:58]: And so, and what do you need to do that? Well, you need lots of data From people that are traditionally much better at red teaming. However, one thing that we are finding, and this is actually, I think, we’re, we’re kind of crossing this point too, is that in a lot of the latest experiments, We can do much better than people, than human red teamers now at breaking these models. When I say we, our automated red teaming model. It’s a system called Shade. That system is now actually quite a bit better at breaking, models than humans are. I think we had a recent competition Between humans and our model, and it was actually quite a bit better. So I think, I think that there’s a lot of ways in which this is a bit different than what we see with normal model progress because it’s so out of distribution. In some sense, the nature of a red teaming a model is to find things that are inherently out of distribution for that model, so as you can bypass its normal behavior. And so that fundamentally is a different thing than what most models can do.Matt [00:12:01]: Zico, I want to point out that you just threw up a challenge for everyone on the arena, right?Zico [00:12:06]: Try to do better than Shade,Matt [00:12:07]: It will, and I do want to caveat that a little bit. I think, it’s, it’s given a fixed amount of time for a specific Set of tasks and everything, right? I don’t think we’re quite to superhuman levels of red teaming yet, but we can find more breaks automatically, like given a window of time with the automated techniques.Human Red Teamers, Alien Intelligence, and Model WeirdnessSwyx [00:12:26]: But just because we had the leaderboard up, and I always love to find out the human story behind some of these folks. Do you I assume some of them. Are they celebrities in their own right? what’sZico [00:12:35]: Wyatt’s a big person on Twitter. You should, you should follow him on Twitter If you’re not already. Yeah.Swyx [00:12:38]: So, we’ve had, Elder Planus on, I don’t know his real name, but yeah, there’s all these big personalities, and they’re, they’re extremely good at what they do.Matt [00:12:49]: They’re, they’re very good at what they do.Swyx [00:12:51]: Oh, he’s an Aussie.Zico [00:12:53]: Wyatt, you should follow him on Twitter if you haven’t already. He makes, he makes great He makes these really insightful posts. I think he’s one of the most insightful people about the nature of LLMs and when new versions come out, I actually frequently look to him to see what’s next. He’s a lawyer, I think, right?Matt [00:13:09]: He’s an attorney.Swyx [00:13:13]: There’s red lining, red teaming The other thing. Yep.Zico [00:13:16]: Yes. Our top, competitors are often people that, Do this a lot.Swyx [00:13:22]: What’s an example of a thing that you’ve learned from Wyatt? Oh.Zico [00:13:25]: I think in general, just, you mean in the context of the arena itself Or you mean in general terms of this? I think he just has great insights in the nature of models as a whole. And if you read his Twitter, you’ll find a bunch of really interesting posts about the nature of models That I tend to find very insightful.Swyx [00:13:42]: Riley’s like this as well, right? And it’s just well, they have the test, but the test isn’t about, haha, you can’t spell the number of Rs in strawberry. The t…

Full show notes at the publisher

The Professor of Outputmaxxing — Anjney Midha, AMP Jun 18, 2026

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Last 4 days before regular tickets sell out at AI Engineer World’s Fair - this is the single biggest gathering of AI Engineers, Founders, Leaders, and Researchers in the world. Attendees get >$5000 worth of sponsor credits and talk tracks are looking FANTASTIC. Join us!The AI scaling debate always focuses on the question of “how do we get more GPUs?” but the better question may be: how do we make the most of ones we already have.The fact that a frontier lab like xAI could be running at sub-10% MFU (Model FLOPs Utilization) is just a hint at what the real problem may be.For context, older frontier-scale training runs were already much higher than 10%. GPT-3 was around 21% MFU. Gopher was around 32%. Megatron-Turing NLG was around 30%. PaLM reached around 46%. And our guest Anjney says best-in-class MFU today is closer to 60–70%.It’s not necessarily that xAI is uniquely incompetent (it’s clear they have talented folks) but rather the priorities may be flipped in the GPU arms race.While GPU access is a bottleneck, simply increasing CapEx won’t automatically translate to better models as frontier AI is increasingly a systems problem: scheduling, utilization, networking, kernels, frameworks, data pipelines, parallelism, cluster reliability, and the thousand small decisions that determine whether your theoretical FLOPs become real training progress.From building Discord’s developer platform and backing frontier AI companies like Anthropic, Mistral, Black Forest Labs, and Periodic Labs to now building AMP’s independent compute grid, Anjney Midha has spent years close to the real bottlenecks of AI scaling. In this episode, Anjney joins swyx at Periodic Labs to unpack why the AI race is not just about buying more GPUs, why 95% utilization would have been considered an outage at Google, and why the next era of AI infrastructure has to be more aligned, more efficient, and more responsible.We go deep on AMP’s vision for a compute grid that makes FLOPs flow like megawatts, the difference between full-stack AI labs and horizontal pooling, why AI data centers need community buy-in, and how compute markets could evolve into something closer to an independent system operator. Anjney also explains why DeepMind’s unpublished research points to a market failure, why end-of-life prediction remains one of the most important AI applications he has thought about for fourteen years, and why “output maxing” may become a new discipline for frontier systems.We also discuss Anthropic’s culture, why “luck favors the prepared mind” in coding models, how Claude cracked coding, why too much capital too early can make AI labs fragile, what Periodic Labs is trying to do with science and superconductors, why great researchers can become great CEOs, and why Silicon Valley is both deeply missionary and deeply mercenary.We discuss:* Why 95% utilization was considered an outage at Google* Why AI infrastructure waste compounds at frontier-lab scale* Why “move fast and break things” does not work for AI data centers* How data center backlash, power grids, and community incentives shape AI scaling* AMP’s vision for making FLOPs flow like megawatts* Why compute needs an independent system operator* How interruptible demand and dynamic prioritization worked inside Google* Why DeepMind research hoarding creates negative externalities* AMP’s 1.2GW base-load ambition and the need for 6GW of spike capacity* Why end-of-life prediction could become one of AI’s most important healthcare applications* Frontier Systems, output maxing, and full-stack alignment* Why APIs and abstraction layers become lossy as organizations scale* Superconductors, standards, and the dream of lossless systems* SF Compute, open protocols, and the future of compute marketplaces* Why non-NVIDIA chips can still benefit from NVIDIA’s reference architecture* Trust boundaries and why chip startups need visibility into future model architectures* Why VCs often underestimate researchers as CEOs* Scientists as star athletes of the mind* Why great CEOs need to be confrontational up and down the stack* Why leading the frontier matters more than “winning”* How Anthropic cracked coding* Why culture is fragile, not a permanent moat* Why hardship was a feature, not a bug, for Anthropic* Why Anthropic’s P0 was coding from day one* Periodic Labs, physics as the constraint, and technical reality* Silicon Valley mercenaries, missionary teams, and what happens after a breakthroughAnjney Midha* LinkedIn: https://www.linkedin.com/in/anjney* X: https://x.com/AnjneyMidhaAMP PBC* Website: https://amppublic.com/* X: https://x.com/amppublicTimestamps00:00:00 Introduction00:00:09 Why AI Compute Is Being Wasted00:03:17 Responsible Infrastructure and Data Center Backlash00:06:07 AMP Grid: Making FLOPs Flow Like Megawatts00:12:41 Foundry, Frontier Labs, and Research Hoarding00:14:42 Gigawatt-Scale Compute and End-of-Life Prediction00:24:08 Frontier Systems, Output Maxing, and Alignment00:27:38 Compute Markets, SF Compute, and Non-NVIDIA Chips00:32:57 Trust Boundaries, Co-Design, and Researcher CEOs00:38:17 AI Coachella and First-Principles Thinking00:42:43 Leading vs Winning in Frontier AI00:45:54 How Anthropic Cracked Coding00:48:25 Culture, Hardship, and Anthropic’s P000:54:03 Periodic Labs, Physics, and Silicon Valley Mercenaries00:56:26 Rishi Valley, Singapore, and Money as a Measure00:58:47 Closing ThoughtsTranscriptIntroduction: Anjney Midha, AMP, and Compute WasteSwyx [00:00:00]: We’re in Periodic Labs with Anjney Midha, CEO, founder of AMP. Welcome.Compute Utilization: Node Allocation, MFU, and AlignmentAnjney [00:00:09]: Thanks for having me. At Google, there are two types of utilization usually, right? That you’re measuring in these clusters. One is node allocation, and then the other’s MFU. Node utilization is usually like what percentage of cards in the data center are just, used, and that, if it’s not at, 95%-Swyx [00:00:29]: There is no excuseAnjney [00:00:29]: There’s no excuse, right? I think 95% at Google, which is where my co-founder, Seb, came from, he built the Borg, PBorg/GQM scheduler at Google, and there I think 95% was considered an outage, so 96% node utilization is, should be standard. And most single-tenant clusters are not running at that. So that’s one. And then MFU should be, I would say the best in class today is somewhere between 60 and 70%. I think this is a leadership question, right? Fundamentally it’s an alignment question, which is are the people who are funding the cluster and then deploying the cluster actually aligned? And sometimes theoretically they are, but in practice the number of people in the chain, the supply chain between, the capital and all the way to whoever’s managing the cluster and then whoever’s measuring what the output is, are just so many, degrees of separation away that, the, The Have you ever heard the radian metaphor, which is at the beginning of an arc, if you have two arcs that are two lines that are just off by a few degrees, that-Swyx [00:01:33]: It spreads outAnjney [00:01:34]: It spreads out, right? Or at scale. And I think what’s happening is a lot of cluster implementations and infrastructure, a lot of frontier labs and other teams, that’s what’s happening, is they’re, they initialize the plan, which is kind of like North Star with a team that wants to do good, but then they’re, required to scale so fast instead of iteratively that the wastage just compounds really fast at scale. And so I think we know the answer, which is just do iterative bring ups. If you spend time with people who’ve been in the semiconductor industry or the DSN industry for a long time, this is not new, and I don’t think AI should be an excuse. Sure. Something What is new? Okay. We have a lot of new capabilities, but that doesn’t mean just abandon common sense. Common sense should always be in fashion. ? AI scaling doesn’t change the in fact, if anything, AI scaling should be putting a premium on the value of common sense and infrastructure because the margin of error now is so much lower and the costs of wastage are so much higher. And the cost of wastage, by the way, is not just economic. I’m, obviously I’m, I’m an investor, or I’m an investor by background. Over the last few years now we’re running an AI infrastructure business called, AMP. And I think that it’s okay to say this time is different on the capabilities front. We are genuinely getting capabilities at, of the, of a kind we haven’t had before. That doesn’t give you an excuse to say this time is different for everything, especially infrastructure. So look, I love the hacker mindset and the hustler mindset. Now, that’s great for the startup mindset, but you remember this moment where Zuck went from saying, “Move fast, break things” to, move-Responsible Infrastructure and Data Center BacklashSwyx [00:03:10]: Fast and stable infrastructureAnjney [00:03:11]: Move fast with stable infrastructure. I think now we need to move fast with, responsible infrastructure. People are going to ask where the impact is. There was a really In our class yesterday, Scott Nolan, who’s the founder of General Matter, came by at Stanford to speak about energy bottlenecks. And he had a phenomenal idea. He said, “if you look at the marginal unit economics of compute per hour,” he goes, “let’s call it, $4 an hour. If you’re having to bring up a new data center in a new community, why not just say we’re going to charge 4.50 an hour, and that marginal impact or that marginal increase, we just literally take that and give it to the local community as cash?” I can tell you as a customer of that compute, I would love that. I’d be happy to pay an additional 50 cents per hour at scale.Swyx [00:03:57]: Wow. Yeah.Anjney [00:03:58]: Because if that means the public benefit is so clear to the communities that the data centers are coming up in, I’m going to feel like that compute is much more reliable. Up to 20% of all data centers this year in the US, my understanding is are at risk.Swyx [00:04:13]: Of community backlash?Anjney [00:04:14]: Correct. Of not getting the community support they need to get brought up.Swyx [00:04:19]: Wow. That’s a huge number.Anjney [00:04:20]: Yeah. Now, we, I think we should dig into what that number is. I think it’s a little bit of overstated. These things can get over-reported, but it-Swyx [00:04:27]: They don’t just care about jobs. They care about all the other stuff around it, right? They care about power grid, they care about environments-Anjney [00:04:33]: Power grid, permitting, and so on. And imagine I think if you said there’s a new AI deal. If we’re bringing up a data center in your community, we’re actually going to reduce the cost of your electricity bill. Okay, now we’re talking. Right? The community’s going, “Okay. Now this is a deal. I feel like a partner in this.” Right now that’s not happening. There will be audits, there will be investigations, and when the, when the regulators come, I don’t know when it’s going to be, the folks who are moving fast and breaking things in the name of AI progress better be prepared. That’s certainly not how we’re procuring compute. Or we’re, we’re trying as much as we can to work with partners who have long-term track records. Many of whom, by the way, are not, AI providers. I think this whole idea of neoclouds being somehow this new category is a lot of marketing speak. There are really good, reliable, trusted data center providers in America who’ve been around 20 plus years. I love those folks. They know how to Sure. Are they sponsoring happy hours at NeurIPS? No. Are they legibly listed in Build? No. Are they hanging out in my, in, situational awareness parties? No. But they’re adults. I trust them.Swyx [00:05:44]: They can run LAN. They can run power.Anjney [00:05:45]: They can run LAN, power, and shell. They have credit histories. We sit down, we have a conversations. Many of them live in Silicon Valley. They’ve, they’ve had to deal with the boom and bust cycles of the internet, and I love those folks. They are stable infrastructure partners and thinkers. And I think there’s a lot of short-term thinking going on in the compute layer, and it’s going to catch up to us. It’s not going to be good.AMP Grid: Making FLOPs Flow Like MegawattsSwyx [00:06:07]: You talk about aligning incentives, and, I would think that aligning incentives means you have the full stack in one company, which is xAI and OpenAI, right? So you as a standalone infrastructure layer, why are you somehow more aligned to your portfolio companies than people who just own the whole thing?Anjney [00:06:28]: In systems design, right, there’s, there’s two regimes of, architecture, right? You have integration, and then you have pooling and utilization, right? So the Or rather, the way to increase utilization often is you can do systems integration where you collapse a lot of process into one node, or you can pull out a process from a node and share that amongst various That resource amongst several different nodes. And so we see the AMP grid, which is, the, what, the system we’re building here, which is basically a compute grid. We’re trying to do for compute what the electric grid-Swyx [00:07:02]: PowerAnjney [00:07:02]: Yeah, what the power grid did for electricity. It-- this is a pooling and utilization layer across clouds, And so we’re actually the opposite of a full stack integration like approach.Swyx [00:07:12]: Super horizontal.Anjney [00:07:13]: Where it’s much more horizontal and it’s, it’s multi-cloud, it’s multi-silicon. The goal is to try to make FLOPs flow like megawatts, and that is very hard to do today for many reasons. There’s stranded pools of compute all over the place and there’s no fungibility. And so right now we do it at the level of scheduling, and we often do it at the economic layer. But as we start to announce what we’re working on, it’s extraordinary like how many folks are coming out of the woodworks and saying, “Hey, I’m actually working on a way to make compute fungible at this part of the stack and that part of the stack.” And as a grid, we’d like all of these folks to participate on the grid. There’s, people often ask me, “Andra, are you a new cloud?” And I go, “No, actually neoclouds are suppliers.” sometimes they’ll ask, “Are you a venture capital firm?” I go, “No, actually they are, they are demand like sort of off-takers of the grid.” We see ourselves as what’s called an independent system operator. So if you study the history of the electric grid, once it became legible to a lot of factories and industrial sort of participants that, hey, actually it turns out pooling is a good idea. We should pool our generators instead of all having a generator running at half capacity in our backyard. There was a need for an independent entity who could coordinate all these parties. Transmission line, power generation, facilities, transmission lines, factories, and that neutral coordination mechanism is very critical. In order-- If you study like the history of grids, the most enduring ones were those that never owned their own assets. They were ones that had, or often started with long-term anchors who are uncorrelated sources of demand, a steel factory, a shoe mill or whatever in a particular town who weren’t competitive, where the steel factory want to spike up at night, the shoe mill wanted to spike up during the day. So then you pool and you share, right? So each of you is guaranteed some base load, but then you kind of schedule your spikes to drive a peak utilization across the town. The gold standard, so to speak, historically, has been these utility companies like PJM Interconnect in the northeast of America, where they, over many years became this what’s called an ISO, an independent system operator of the grid. So that’s how we see ourselves. Economically, that’s what we are. From a technical perspective, we started at the scheduling layer because Seb a…

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🔬 The Self-Driving Lab — Joseph Krause, Radical AI Jun 17, 2026

Show notes

On the Science pod, we’ve been covering a lot of the ground on how AI is revolutionizing STEM, but one of our favorite off the record topics since our launch is which field is harder to accelerate: math, bio, or physics? Today we’re back in Materials Science land with Radical — Unlike biological molecules that can be represented (and predicted!) by token strings, the success of materials involve many more macro complex variables like supply chains, microstructures, and manufacturing processes. If you recall the LK99 drama of 2023, while the basic ingredients were known, part of the confusion came from the lack of disclosure around manufacturing, and therefore defeated reproducibility. There is probably no "one-shot" model capable of designing a material that works perfectly at scale.

How Radical is accelerating materials discovery >10x the pace of DARPA/GE MACH

Joseph Krause is a materials scientist through and through. And after spending his career watching industries stall out waiting for better materials, he founded Radical AI to do something about it.

We recently sat down with Joseph to talk about Radical AI, materials discovery, self-driving labs, and the future of AI science. Joseph did not sugar coat anything: accelerating the materials discovery pipeline is a hard problem. But it’s one that he strongly believes we need to invest in, for the future of consumer products, aerospace, computing, and defense, and get them into every day use:

“We count it as a discovery when you pick up your phone and there’s a new material sitting inside of it.”

How does Joseph plan on accelerating the rate of discovery? To understand this, it’s important to understand why this is such a hard problem in the first place. The first thing to keep in mind is that the material that is manufactured is far more than a chemical formula going into it. The process of mixing, annealing, growing, or generating the final material can result in wildly different outcomes. The entire materials discovery process, both from early discovery to large scale manufacturing, needs to be understood and characterized.

The Self-Driving Lab

This philosophy has grown into a key insight at Radical AI: The construction of the self-driving lab. This lab is one that is not just automated, but in fact uses an “AI scientist” that combines scientific knowledge, computational techniques, and human intuition to generate and test hypotheses in an automated lab. Creating an AI scientist was key to making Radical’s self-driving labs work, since Joseph argues that no single AI model can one-shot materials.

“In materials, the ground truth is the material itself. You have to be able to test it and characterize it.”

Joseph talked at length about the self-driving labs at Radical. Joseph argues that experimental data is the true “moat” in this industry. An SDL functions as a closed-loop system where an AI scientist generates hypotheses, and automated robotics synthesize and characterize materials, running research campaigns in parallel rather than serially.

The successes here were both on the automation side and on the science side. Radical has managed to scale their alloy discovery pipeline up to producing and characterizing 1200 alloys in six months — this nearly 10x speedup over the DARPA/GE MACH program that aimed to create 500 new alloys in a year. Joseph claims they can scale this up even more and estimates they can produce a hundred new alloys tested and characterized in a day. A truly new paradigm in high-throughput alloy experimentation.

On the science side, their AI scientist proposed and tested 300 new materials, ten of which were found to have novel state-of-the-art properties that are already being further developed for commercial applications. The robustness of this first materials campaign reinforces Joseph’s claim that the moat is the lab and data.

“It’s moved into elemental families or alloy families no one has ever published on before.”

Interestingly, Radical’s AI scientist has made some novel discoveries, expanding into elements that just were not explored prior. This is fascinating from a scientific perspective, but it’s also important for helping reduce supply chain bottlenecks for vital industries!

Joseph spent a lot of time in D.C. before founding Radical, and he’s clear-eyed about the competitive threat. China’s centralized model lets it stand up manufacturing hubs and immediately scale new materials from lab to production. We can’t replicate that, and Joseph is very clear we shouldn’t try. But we do need an answer. For Joseph, that means transforming the scientific workforce, investing in self-driving lab infrastructure at the national lab level, and leaning hard into public-private partnerships.

“Now imagine every scientist in the United States doing 10 times the research output. That’s fundamental. That just changes the trajectory of discovery.”

Before we close, we’d like to give a shout out to Joseph and Radical for publishing and open sourcing much of their internal tooling pipeline. This includes:

* TorchSim (preprint, blog): an open-source PyTorch-based MD simulation framework, which has been spun off into its own non-profit.

* MATRIX/MATRIX-PT (preprint, blog): An open-source dataset for benchmarking autonomous self-driving labs (MATRIX), along with with an open source model based upon this dataset (MATRIX-PT). We could talk about this extensively, but a fun data point is that improving reasoning in the area of materials also improved reasoning for biological systems! This is a truly unexpected result.

Big shout-out to the Radical team for sharing their work!

Materials discovery has been stuck on a 20–30 year timeline for generations. Joseph thinks that’s about to change, and Radical AI is putting that thesis to the test in the lab, one sample at a time.

We had a great time talking with Joseph. We hope you give it a listen!

Timestamps

* 0:00 Introduction to the challenges of AI in material science

* 0:52 Welcome and introduction to Joseph Krause and Radical AI

* 1:38 Why Radical AI is different: The focus on experimental data and Self-Driving Labs (SDLs)

* 6:19 The process: Candidate generation, synthesis, and characterization

* 11:05 The application of exotic alloys in extreme environments (aerospace and defense)

* 13:20 Barriers to entry: The slow process of qualification and manufacturing

* 16:06 Supply chain constraints in material science

* 19:24 Human-in-the-loop: Training the AI using scientific intuition

* 20:35 The engineering challenges of automating a laboratory

* 23:17 Defining the “Self-Driving Lab”: Research campaigns vs. just automation

* 24:39 Mechanical challenges: Handling high-temperature samples

* 27:41 Future scaling plans and the “Vertical Integration” strategy

* 30:08 Validation timelines for high-tech industries (semiconductors, aerospace)

* 31:47 The active learning loop and handling “negative results”

* 35:32 AI exploring elemental families beyond human bias

* 39:13 Throughput targets and the difference between AI and human exploration

* 43:52 Why the dataset size is less critical than the quality of experimental feedback

* 46:20 Addressing the lack of an “AlphaFold” for materials

* 53:49 War stories from the lab: Building the infrastructure

* 58:12 The shift in industry sentiment toward SDLs and tool interfaces

* 1:01:14 Geopolitical considerations and the race in material science innovation

* 1:06:12 Calls to action for ML and AI engineers: Rethinking the scientific stack

* 1:09:53 The Matrix model and using VLM for scientific knowledge extraction

* 1:13:10 Why Radical AI is open-sourcing their work

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Reality: The Final Eval — Lukas Petersson and Axel Backlund of Andon Labs Jun 04, 2026

Show notes

The new AIEWF website is live! Get your tickets booked ASAP as they -will- sell out. Take the AI Engineering Survey and get >$2k in credits and free AIE WF tickets!Most industry benchmarks compress intelligence and reasoning ability into scores.SWE-Bench Pro, MMLU, Humanity’s Last Exam, etc. These metrics are useful, but don’t always represent the full extent of how a model performs in the real world. Some of the most interesting evals today look less like exams and more like operating businesses in the real world. One of which is Vending Bench.In Anthropic’s Mythos Preview System Card, Andon was the only third party eval to get their own section, observing increasingly concerning aggressive behavior:You don’t know what a model is capable of doing in the real world unless you actually give it inventory, a wallet, tools, customers, competitors, humans, & some time. More often than not, it’ll surprise you how much a model is capable of and in doing so, also reveal unexpected behavior: deception, context collapse, emergent coordination, & bizarre negotiation behavior.While an inflection point in personal agents came post-OpenClaw after full file access with bypass permissions became the norm, it is yet to come for agents in the real-world. However Andon Market, an actual in person store fully run and managed by AI, is paving the way for what is possible.Full Video PodFrom Claude trying to call the FBI over a $2/day vending machine charge to AI agents forming price cartels, hiring human employees, running physical stores, and writing existential robot musicals, Andon Labs is stress-testing what happens when frontier models stop being chatbots and start acting in the real world. In this episode, Andon Labs cofounders Lukas Petersson and Axel Backlund join swyx and Vibhu to unpack the strange, funny, and genuinely concerning edge cases that emerge when agents run businesses over long horizons.We go deep on Vending-Bench, Project Vend, Vending-Bench Arena, Bengt, Butter-Bench, Luna, and Andon’s broader mission of building realistic real-world evals for autonomous AI systems. Lukas and Axel explain why dollar-denominated evals reveal things traditional benchmarks miss, how Claude ended up reporting its vending machine fees as cybercrime, why long context windows can drive agents into meltdown loops, what happens when agents compete with each other, and why the future of AI safety may depend on testing models in messy physical environments instead of clean benchmark sandboxes.We discuss:* Why Andon Labs started with dangerous capability evals and long-running agents* Vending-Bench and why running a vending machine is a deceptively hard AI benchmark* Why money-based evals avoid the saturation problem of traditional benchmarks* How Claude tried to call the FBI over a $2/day fee* Why long-horizon agents can spiral into existential and legalistic breakdowns* Project Vend: putting an AI-run vending machine inside Anthropic* Why real humans are “out of distribution” for simulated agents* Claudius, Seymour Cash, and the chaos of AI CEOs* How a human briefly became CEO of Claudius through a manipulated election* Why multi-agent systems can converge back into “helpful assistant” behavior* Bengt, Andon’s internal office agent with email, spending, terminal, phone, camera, and internet access* How Bengt traded Amazon purchases for face-recognition training data* Claude’s aggressive behavior, lies, refund avoidance, and price-cartel behavior in Arena* Why eval awareness may become the AI version of “are we living in a simulation?”* Blueprint Bench, spatial intelligence, and why models still misunderstand physical rooms* Butter-Bench and testing LLMs as robot orchestrators* Luna, the AI-run physical store with a three-year lease and human employees* The new Andon cafe in Sweden and why real-world geography matters for agent evals* Rotten tomatoes, perishable goods, and the hidden difficulty of running a physical businessLukas Petersson* LinkedIn: https://www.linkedin.com/in/lukas-petersson-181a83172/* X: https://x.com/lukaspetAxel Backlund* LinkedIn: https://www.linkedin.com/in/axelbacklund* X: https://x.com/axelbacklundAndon Labs* Website: https://andonlabs.com* Vending-Bench: https://andonlabs.com/evals/vending-bench* Andon Vending: https://andonlabs.com/vendingTimestamps00:00:00 Introduction00:01:00 Andon Labs and the Origins of Vending-Bench00:05:21 Why Money-Based Evals Matter00:09:51 Agent Harnesses and Self-Modifying Systems00:13:36 Claude Calls the FBI00:16:33 Project Vend: Claude Runs a Real Vending Machine00:21:44 Seymour Cash, AI CEOs, and Election Chaos00:27:16 Multi-Agent Coordination and Slack Observability00:30:18 When Will Agents Run Real Businesses?00:34:56 Bengt: Andon’s Internal Office Agent00:40:06 Real-World AI Safety and Long-Horizon Traces00:44:28 Lying, Refunds, and Price Cartels in Arena00:52:42 Eval Awareness and Simulation Behavior00:56:06 Blueprint Bench, Butter-Bench, and Robotics01:04:37 Luna: The AI-Run Physical Store01:09:29 The Sweden Cafe and Real-World Expansion01:13:16 What Comes Next for Andon LabsTranscriptIntroduction: Andon Labs, Long-Running Agents, and Real-World EvalsSwyx [00:00:00]: Welcome to Lukas and Axel from Andon Labs, and I’m joined by my, favorite guest host. Anything security, safety, alignments, Vibhu., welcome.Lukas [00:00:15]: Thank you for having us.Axel [00:00:16]: Thank you.Swyx [00:00:17]: Let’s match names to voices., maybe you wanna take turns introducing yourselves.Lukas [00:00:21]: I’m Lukas.Axel [00:00:22]: And I’m Axel.Swyx [00:00:24]: Let’s introduce Andon Labs a bit. How did you guys come together?, you have different backgrounds, but you’re both Swedish., was that, a big part of it?Lukas [00:00:33]: So when I went to high school, there was this really cool guy who had a superpower. He could code. So he made like the or like the app for the, for the school and stuff, and he was super cool, and I wanted to be like him, and that was that guy.Axel [00:00:47]: I don’t know about this.Swyx [00:00:49]: But you went to different universities, right?Lukas [00:00:51]: But same high school.Swyx [00:00:52]: I see.Lukas [00:00:52]: So we always said, “Oh, once we graduate university, then we should start a company,” and that’s what we did.Swyx [00:00:58]: Wow, there you go. And about a year ago, you kinda burst onto the scene with Vending Bench, but, was there a thing before that was, kind of like the inception?From Dangerous Capability Evals to Vending BenchAxel [00:01:07]: So we did work, yeah, with, Anthropic was one of our, early customers in doing, evals. So we did, dangerous capability evals., nothing we published openly. But then we started thinking about doing some kind of, public benchmark, and one thing that we really started thinking about, was like running agents and specifically agents managing businesses., ‘cause-- and this was, early 2025., and I think the first, mentions of people will be running, person unicorns or even autonomous companies. So we thought, “Let’s make a benchmark of how well can an agent run the probably simplest business, possible,” and, that’s probably, running a vending machine. So that’s the first public one we did. And it was very, like-- there was almost no one that noticed it in the first couple of months, I think., so we released it in February last year, and then I think around Easter last year, we got, the first viral tweet about it, that someone else did.Lukas [00:02:11]: We tweeted a bunch, uh When it came out and, tried our best.Axel [00:02:15]: We tried.Vibhu [00:02:16]: It’s the one at Anthropic, right?Lukas [00:02:18]: So thisSwyx [00:02:19]: This is a classic thing we should get out of the way.Lukas [00:02:20]: Exactly. There’s two versions.Swyx [00:02:22]: Everyone does this. Yes.Lukas [00:02:23]: There’s Vending Bench, which is the simulated one, which we did, completely independently in February., and then, like Axel said, that was like-- That was the thing that didn’t get any traction in the beginning, but then some random person made a tweet about it, and thatAxel [00:02:38]: You have the paperLukas [00:02:38]: That is the paper. Correct, yeah., and then since we thought this was very fun, we thought, oh, I think this is also, one thing with Andon Labs, the way we kind of like decide what to do next and what projects to do, it’s what is like the heuristic we use is what is fun? Is What would be a fun project? And doing this in real life sounded quite fun for us, and maybe also scientifically useful. So, then we basically had this idea, and then we, like-- But then we needed a place for it and, putting it out in the public would probably not really work., would get vandalized and stuff. So we pitched it to the people we were already working with at Anthropic, and they were “Yeah, you can have space. This sounds fun.” UmSwyx [00:03:21]: It’s like a small fridge, right? It’s like a mini fridge.Axel [00:03:23]: Absolutely.Swyx [00:03:24]: People-- There’s like a stripe thing or like anVibhu [00:03:27]: Oh, okay. So it was very OG, the early daysLukas [00:03:28]: That’s the OG one. YeahVibhu [00:03:29]: IPad on this. We saw it in June, like two months after After it had been there. They upgraded a little bit. There’s a security camera for making sure you actually Venmo the thing.Swyx [00:03:40]: So, my impression, okay, we’re, we’re going straight into project Ven because it’s such a iconic thing. I do want to cover a little bit of that, the origin story even before Project Ven and even into Vending Bench. I think a lot of people are like yourselves, like smart, interested in future of AI, interested in developing evals. But how the hell do you just, walk into Anthropic’s doors and, work with them, right? What is What are they looking for? What works? And then maybe, when you launch, I always think, obviously it would be better to launch with a lab, but, sometimesVibhu [00:04:12]: It’s harder to do than it seems.Swyx [00:04:13]: Exactly. So either of those, which are more sort of newbie beginner questions, but, I think it’s meaningful advice to others.Lukas [00:04:21]: We get this question a lot, and I don’t think our experience is maybe the best., but, the way we did it was that we just built a bunch of things that we had conviction would be useful, and then we just, set up a server and sent it to them for free to use. And then after a while they were “Oh, yeah, this is actually kind of useful. We should probably pay for this.”, but that took a while. I don’t know if this is, the best path to doing it, but that’s how it went for us.Axel [00:04:47]: I think maybe generally, building-- everyone is interested in good evals, and especially evals that, don’t saturate that easily. So, if you can build an eval that, tests something novel, something useful, and you have, good separation of models, like your, the more advanced models rank higher than the worst models, and then you can, yeah, you can, publish it and, try to get some traction, sort of how Vending Bench got attention., and then probably some lab will be interested or you can at least have something to reach out with, when you’re doing that.Why Dollar-Based Evals MatterSwyx [00:05:21]: I think you are in, you’re in one of the few categories of, evals that correlate to real money. Like Suelancer was also last year, right? Where, people solve actual Upwork. Was it Upwork or other tasks?, something. Where’s the, where’s, like It’s like a dollar value, right? Forget your ELO scores. Forget yourAxel [00:05:37]: PercentilesSwyx [00:05:38]: Zero to one hundred percents. Just go straight for dollars and, that’s AGI.Lukas [00:05:43]: And there’s like-- I think the nice thing is that there’s no ceiling. You can just-- It never saturates because it could just make more and more money. Like If there’s oh, Percentage-wise, then, you can’t go above, a hundred. And I think like Even when you’re not at the hundred, I think a lot of these, evals have a lot of problems in them. So, actually it’s like if you getAxel [00:06:05]: To like 92 or something like that, many of them. It’s like then there’s like there’s no really no difference between 92 and 93 because the eval itself is problematic and has noise in it. And I think a lot of evals are saturated like that, but people like pretend that there ‘s still signal in them, but there really isn’t.Vending Bench 1, Harness Design, and SaturationSwyx [00:06:24]: Like Super bench verified., even Vending Bench 1 saturated, right? Maybe we can talk about that., may- and maybe set up Vending Bench for a lot of folks who don’t know. Actually, things that were very basic like there’s limited slots, like you have to pay rent., these are elements where like it doesn’t come across in the, in the narrative, but even being adversarial towards the agent, I think these are all like very interesting dimensions.Axel [00:06:47]: I don’t really think it’s saturated, right? Like it It was more like it was not designed in a way that was really, like true to how AI developed. Like we had an agent harness in it that wasn’t really how people used harnesses and stuff like that., so I think it wasn’t really that it saturated, it was more like it wasn’t really, the best benchmark.Vibhu [00:07:12]: This is Vending Bench one, right?Axel [00:07:14]: I think that like schematic maps sort of to Vending Bench 2 as well., butSwyx [00:07:19]: Including the email.Axel [00:07:20]: The email The emails exist still. Exactly., and then we still we simulate the purchases and it’s all, yeah, it’s this very open environment for the agent to just run its business. And then for, yeah, Vending Bench 2 we did that, like you said, to just improve the harness., a lot of like nice, like easier, improvements to make it easier for us to run as well., like when you make an eval you ideally want don’t want to change it after you made it. So, you want to make it really good and then not to rerun all the models when you make an update because that’s also really expensive with the Vending Bench when you run the frontier models. But like as an example, like one thing we didn’t have, we didn’t have prompt caching in Vending Bench 1, because when we made Vending Bench 1 it wasn’t really a thing., so that ‘s just an example of like in Vending Bench 2 like we paid a lot more to run these things because we didn’t have prompt caching. So for Vending Bench 2 that was one thing we added and there was a bunch of things like this., and that’Swyx [00:08:17]: Also the conversations are a lot longer in Vending Bench 2, right?Axel [00:08:21]: I think it’s kind of similar.Swyx [00:08:22]: Is it similar?Axel [00:08:23]: I think it’s similar. The models at the time were worse, so they crashed out earlier., and now they survive the full year all the time.Swyx [00:08:31]: Which is like thousands of turns. Hundreds of thousands of hundreds of millions of tokens output. That’s the, that’s the rough order of magnitude. I always wonder about the harness. The harness matters a lot. It’s your harness. Was there any question about like use cloud code, use something else?Axel [00:08:48]: I think our philosophy around harnesses is like we try to make something that’s quite minimalistic, like quite simple. Like we don’t wanna favor one model a lot over the other, but also don’t make like a super complex harness. So like it’s obvious like a model may be lucky and just be good in one harness., so like it is similar to a lot of the harnesses out there in like you have the, like a running loop., you have some like a bunch of tools that are like quite, descriptive for the agent, we think, and not a lot of like fancy agents or anything ‘cause we wanna really test the model, not like some specific harness.Vibhu [00:09:27]: It seems more neutral as well to test the model’s agnostic of the harness,?Axel [00:09:32]: There are arguments like you want to elicit maximum performance of the model, but it’s like a t…

Full show notes at the publisher

🔬Scaling Past Informal AI - Carina Hong, Axiom Math Jun 03, 2026

Show notes

In 2025, seven-month-old startup Axiom solved all 12 of the problems Putnam exam (scoring 8/12 in the time limit) a prestigious undergraduate math exam. The 12/12 score is better than the top undergraduates (110/120) and the closest AI system that reported a result (DeepSeek 103/120), although it is unclear what the people and other systems would have scored with more time. Nonetheless, the Putnam exam is legendary for its difficulty, with the median score typically being 0 or 1 points. Taken by itself, this seems like a minor feather in the cap of AI; one of a long series of accomplishments by AI systems in elite competitions with humans, starting with Deep Blue beating Kasparov.

Fast forward to mid-2026, and Claude Code is eating the world. In 2024 Anthropic’s bet on code and enterprise looked like a more pragmatic niche play vs. OpenAI’s better models and massive consume scale. Today, Amodei’s all in bet on acceleration via code (images and video be damned) seems prescient.

Despite Anthropic’s growing momentum, however, Axiom CEO Carina Hong sees coding ability as a necessary but not sufficient milestone on the path to AGI. Code arguably pushes the jagged frontier to the point of super intelligence in some domains outside of coding, but there are surprising gaps (link) that Carina believes will bottleneck AI progress. (Stats on math benchmarks).

The informal bottleneck

“Verified AI” sounds like eating broccoli (footnote: I actually love broccoli, but then again, I also believe strongly in Test Driven Development, so ¯\(ツ)/¯ ) and paying taxes, but to Axiom it means something very different. “Verification to me is about scaling brilliance, compounding brilliance,” Carina told us.

It actually took a while for me to understand what she means by this. It sounded like marketing-speak to me, until it clicked. Carina emphasizes an story about legendary mathematician Srinivasa Ramanujan to illustrate the point. When G.H. Hardy finally persuaded Ramanujan to formally prove theorems instead of relying on his (formidable) intuition, it reportedly improved his own capabilities. This is presumably because formally proving things forced Ramanujan to articulate the details in a way that open up new lines of thinking, etc. This is one part of “compounding.”

But formally proving things also allowed others to benefit from his intuition: the proofs are way of communicating an intuition and persuading others that the intuition is correct. This is scaling (more people use the result) and compounding (people can learn from and build on his work).

This is the analogy that Carina wants us to focus on.

Verified Generation

There are two ways that Verified AI shows up: in training and in inference.

But a quick detour: to a first approximation, “Formal Verification” means using type checkers (like for TypeScript, C++ or Rust, but more capable) to verify mathematical proofs that are meticulously specified using a language like Lean (footnote: Formal verification also includes model checking (TLA+, SPIN), SMT-based tools (Dafny, F*, Why3), and refinement-type systems (Liquid Haskell) — many of which don’t look much like “type checking a proof” from the user’s perspective even when there’s a similar logical core underneath. It also gets applied to software and hardware correctness, not only pure mathematics.). It takes a lot of work to translate an “informal” proof (albeit one that most people would not remotely call “informal”) in to a Lean proof (footnote: This is an understatement. Most theorems remain informal because formalization is so hard to do. There has been a great deal of effort to formalize the most important proofs, with mixed results)

You can imagine how this would be (very) useful during Reinforcement Learning: instead of relying on best guesses based on statistics (GRPO, RLHF, etc.), you can just verify the proof is correct using a Lean verifier. This is obviously a much stronger reward signal, akin to compiling code and testing it (which is what is typically done with RL on coding).

The catch: LLM are not (currently) very good at proving things with Lean.

Enter Axiom: While they have not officially reported benchmark numbers besides the 12/12 Putnam result, Carina reports that they have achieved a very impressive 99% (187/189) ProofGen on the Verina benchmark. This benchmark is to generate code and proof of correctness for a series of problems. For context, OpenAI o3 (the last known OpenAI run) achieved 4.9% on this benchmark.

Based on the sparse benchmarking, it’s hard to say what the frontier labs are currently doing, but Carina suggests that they still are not training to generate Lean proofs directly, rather relying on informal proofs.

Time will tell if the frontier labs’ current approaches will close this gap.

Scaling and compounding

Carina’s Ramanujan analogy is pretty direct. Better proofs → better Lean generation → better RL. A stronger signal means higher sample efficiency and higher maximum performance. Great!

Scaling is pretty clear too: once I have proved something in Lean, the quality of the output is basically (footnote: one might argue that its a bit lower because the proof is in distribution for the LLM) as high as if it came from a human, so my high quality training set has grown in a way that an informal rollout corpus cannot. I can trust my Lean proofs.

Compounding is also clear: now all of future inference and training can build upon those proofs.

On the other hand, a model trained only using statistical signals like GRPO during RL lacks the sample efficiency, maximum performance and compounding corpus that a system that uses formal verification benefits from.

All roads lead to verification

Broccoli and taxes notwithstanding, “verification” has shown up in a lot of conversations recently. In the in physical system control:

“I think [verifiability] is probably the hardest problem right now, because the as the models get better, it can be harder and harder to find the faults on the system. And so the problem of doing proper eval to find those faults, that problem also keeps getting harder as the models get better.” -

In theoretical physics:

“…now that we’re in this regime where you can just get ChatGPT to tackle thousands of questions at the same time, it will return proofs for a significant fraction of them. Now actually the onus is back on the humans to verify all the outputs. And so, yeah, as that becomes a bottleneck, I think formalizing math and automating verification will become more valuable.” -

Verification is, in fact, the key differences between AI for science and AI for computation: in science you to have to actually test (verify) your hypothesis by performing physical experiments. Lab in the loop systems like Radical AI and Lila build around exactly this premise (we have recorded episodes with both of these teams and will release them soon!)

And yes, formally verifying critical systems such as flight control, nuclear power plants and pacemakers is a growing focus as the software and hardware that run them becomes more complex.

Carina believes so strongly that AGI requires verified generation that she makes the unqualified claim that “We do not believe there is any other possible future.”

Expensive to produce, cheap to verify

Lean proofs are hard generate, but they can be easily shown to be correct or incorrect. But how do you know that the proof you created maps correctly to the problem you care about? As Carina puts it: “Anything that can be specified can be proven. Humans are bad at specifying everything we want.”

Are we now in the specification business? Check out the episode to hear Carina’s take, as well as:

* Why hardware verification is a killer app

* Details on the AXLE open API and recently released Discovery toolkit

* The Erdos debacle

* The OpenAI GPT-f diaspora

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