Latent Space: The AI Engineer Podcast

In recent months, the open vs closed, and US vs China discussions on model ownership and sovereign/local AI have heated up to a fever pitch. So it is very very good news that Poolside AI are finally emerging with new models, like Laguna S 2.1, that are beating Thinking Machines’ recent release nearly 10 times their size.

Poolside’s recent tech report got a lot of praise due to their level of detail, and Vibhu first covered Laguna’s recent technical report on our paper club:

From spending $12 million building language models for code before the world cared to creating a Model Factory that can take a model from pre-training to release in eight weeks, Eiso Kant has spent more than a decade betting that code is the path to AGI. In this episode, the Poolside co-founder joins swyx and Vibhu to explain why ChatGPT felt like vindication, why Poolside embraced open weights and open research, and why he would rather live in a world with 100 foundation model companies than five even if Poolside were one of the five.

We go deep on Poolside’s Model Factory: the engineering systems behind 10,000–20,000 experiments per month, streaming data directly into training, reproducible experimentation, low-precision compute, and agents that increasingly write code, launch jobs, evaluate results, and modify the pipelines used to train future models. Eiso also unpacks their recent launch Laguna S, why persistence, verification, and backtracking may matter more than raw intelligence, how much capability remains inside smaller models, why reinforcement learning will move earlier into pre-training, and why next-token prediction is still extracting too little from the web.

We also discuss model-harness co-design, Poolside’s path from coding agents to AGI, why Eiso thinks MCP and traditional tool calls are “stupid,” the real economics behind frontier-model training, Poolside’s $500 million raise, open-source AI, regulation, NVIDIA and TSMC’s influence, engineering productivity in the agent era, high-agency teams, and hiring at Poolside.

We discuss:

* How Andrej Karpathy’s RNN work inspired Eiso to start building language models for code in 2015

* Why Eiso spent four years and $12 million pursuing an idea before the market cared

* Why ChatGPT felt like vindication and brought Poolside back to open source

* Why Eiso would prefer 100 foundation model companies over an oligopoly of five

* The difference between releasing open weights and publishing genuinely open research

* Why Poolside deliberately built a global research organization outside the Bay Area talent war

* Why model building is ultimately 90% engineering

* The Model Factory: Poolside’s end-to-end system for rapidly training and improving models

* How fewer than 70 researchers run roughly 10,000–20,000 experiments each month

* How Poolside moved from six-month model cycles to five- and eight-week launches

* Why streaming data directly into training unlocked faster experimentation

* How immutable data, versioned code, and reproducibility enable rigorous model research

* Why Eiso wants capable researchers to leave their labs and become Poolside’s competitors

* Why 95% of model building can be reduced to better data or compute efficiency

* Laguna S and why persistence, verification, and backtracking can outperform raw intelligence

* Why smaller models may handle far more knowledge work than previously expected

* Why reinforcement learning will move earlier into pre-training

* Why next-token prediction is still failing to extract enough knowledge from the web

* Why distillation and environments have become the AI industry’s favorite “drugs”

* Why mid-training is really an early form of

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.

Check out the full episode on YouTube, or your favorite podcasting platform!

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,

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

* C…

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 w…

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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

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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

* Wh…

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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

* W…

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…

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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 Pod

From 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 brie…

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 …

We’ve informally heard that Satya is a listener to LS for a couple years now, but it was still absolutely surreal to meet him and do a live pod at Build, together with our friends at No Priors, the leading VC AI Podcast that we also greatly admire!

We covered the MAI model technical takeaways on yesterday’s AINews, so I will focus our recap of Satya’s main messages around three elements:

* Satya’s adaptation of the Bill Gates Line for positioning Microsoft as the Frontier Intelligence Platform — customers must gain much more value from the Microsoft ecosystem than Microsoft itself, by building on multi-model harnesses like OpenClaw and Scout, drawing on the full enterprise context exposed by context layers like Work IQ (heavily dogfooded by his C-suite), and building up private evals and traces as a new form of Token IP

* AI ROI: On one hand, enterprises are having difficult conversations around Tokenmaxxing and Layoffs, and on the other hand, there are serious re-evaluations of the End of SaaS since the Build vs Buy equation has changed so much. Our previous SemiAnalysis guest had… interesting comments on Microsoft’s position on this as the ur-SaaS titan, and Satya had great answers

* Making the Impossible Possible: Kevin Scott’s inspiring framing around what the most ambitious version of applying AI and technology at large to business and social problems, like education and social impact.

Enjoy!

Full Video

Transcript

Voiceover: Welcome swyx, Sarah Guo, Elad Gil,, and Chairman and Chief Executive Officer of Microsoft, Satya Nadella

Sarah Guo: Welcome to a crossover episode of No Priors and Lane Space with Satya Nadella. Um, congratulations on an amazing build. No, thank you so much, and it’s great to be with both of you. I listen to both of you or b- both the podcasts all the time. It’s great to be on it.

Thank you so much. [00:01:00] So you’re just talking about, um, these amazing, uh, announcements from across the Microsoft estate all morning for, I think, three hours. What is the, uh, what’s the most important reflection or takeaway you have?

AI as an Ecosystem Platform

Sarah Guo: I, I’d say there are, uh, perhaps the, the biggest one for me is let’s sort of conceptualize this more as an ecosystem play as opposed to a single model or even a single platform, right?

Satya Nadella: I mean, you know, whatever I... At least for me, having grown up at Microsoft, having seen, whatever, four major platform shifts, uh, I sort of fall into that, um, uh, camp where a platform is defined by fundamentally its ability to create more value about the platform versus what’s captured in the platform. And so if you, you view what’s happening right now, I think this morning’s keynote was how can any company, whether it’s an AI native company or a traditional enterprise company, participate as a first-class participant where they can point to AI they created, [00:02:00] right?

It’s not that they don’t use other people’s AI. Of course they will. But to me, what’s the path? What’s the recipe? How do I do it? What does a stack look like? What does the tooling look like? What is valuable? How do you do that? That’s it. That’s sort of our job to do. Yeah. Ecosystem strategy is, uh, very complicated, right?

Sarah Guo: Because you end up building certain components, partnering for certain components, supporting them. You just announced this big suite of models. Like, tell us a little bit about the, uh, training strategy for Microsoft now. Yeah.

MAI Models & Training Strategy

Sarah Guo: So, so the thing that we wanted to do with the MAI models was to build, and as Mustafa talked about, first of all, a great lineage, right?

Satya Nadella: Starting with pre-training, uh, with very good data quality, uh, doing all the ablations, making sure because in, in some sense it’s becoming even harder to build a clean lineage model just because there’s so much stuff out there, uh, that you truly need to ablate out to be able to have a fantastic [00:03:00] pre-trained model.

In fact, that’s one of the challenges of a lot of the open weight models is they look great on one benchmark or two, but they’re not great on practice. So that’s why, in fact, even in the RFDEs are, they, they are pretty gone really excited about the…

I’m excited to work with Microsoft once again as the presenting sponsors of the AI Engineer World’s Fair! We’ll streaming live from MS Build today for a special crossover pod with our friends at No Priors and the one and only Satya Nadella. However we did not hold back with this interview - we asked all the burning questions about uptime and Copilot that we know you have in your minds. Lets go!

For almost two decades, GitHub has been the home of software, where both open source and closed flow, through commits, pull requests, reviews, actions, etc.

This ecosystem flourished as open-source maintainers and contributors would continue shipping code for the benefit of the community. However as coding agents began to ship mass quantities of code - growing 1400% in 2026, it marked a new era that was both extremely exciting and challenging for GitHub.

While these agents help more people ship more projects, they also significantly increase the floor of how much code is shipped, how often it is shipped, how many people commit code, and basically orders of magnitude multiples in every dimension of GitHub infrastructure:

Now GitHub inevitably experiences more pressure on their infrastructure which was originally designed around human developers moving at human speed. This has resulted in a very publicly notable uptime story:

So it begs the question of whether current systems around code can absorb what AI produces. Can CI/CD keep up when every idea becomes a build? Can open source maintainers survive floods of AI-generated slop contributions? Can GitHub preserve the human social contract of software while becoming the operating layer for agents?

Which brings us to the perfect person to answer these questions: GitHub COO Kyle Daigle. In this episode, he joins swyx to unpack what happens when AI doesn’t just autocomplete code, but starts changing how companies operate, how open source works, how pull requests get reviewed, and how GitHub itself has to scale.

We go deep on GitHub’s internal AI workflows: micro-skills, WorkIQ, MCP, Slack, Teams, email, Copilot workflows, the new Copilot desktop app, CLI, cloud agents, and how Kyle uses agents to look backwards across company context before deciding what to do next. Kyle also reflects on GitHub’s history building webhooks, APIs, Actions, npm, Dependabot, and Semmle, why the AI era is breaking GitHub in new ways, how Actions became a general-purpose compute layer, and what Copilot becomes after code completion.

Full Video Pod

We discuss:

* Kyle’s expanded role across GitHub

* How AI got Kyle coding again after years in leadership

* Why GitHub rolls out AI through existing workflows instead of forcing new tools

* WorkIQ, MCP, Slack, Teams, email, and GitHub as company context

* Why massive “mega-skills” are giving way to small, atomic micro-skills

* How AI changes summarization, communications, marketing, and analyst work

* Why former developers in leadership may have a unique advantage in the AI era

* Kyle’s “15 agents on Saturday” workflow

* How Kyle built an AI-generated executive presentation for CRO/CFO teams

* Why AI changes the chief of staff role without removing the human work

* GitHub Actions, webhooks, arbitrary code execution, and secure agent compute

* The npm acquisition, supply-chain security, 2FA, and token invalidation

* Slop forks, vendoring, and whether AI agents change dependency management

* What pull requests become when most PRs come from agents

* Prompt requests, vouching, AI review, and trust in open source

* What counts as a “developer” when AI lowers the barrier to building

* GitHub Spark, low-code, and why GitHub refuses to hide the code

* 14x commit growth, Actions load, databases, monorepos, and availability

* Copilot’s evolution from completion to CLI, desktop app, cloud agents, and SDK

* Context, memory, rules, and making GitHub “act like Kyle wants it to act”

* Ambient AI, OpenClaw, enterprise security, and the new operating system…

We’re announcing AIEWF speakers this week! Take the AI Engineering Survey!

Today’s guest Ethan first joined us for the LS Paper Club as the lead on NVIDIA Cosmos World Model, but then joined xAI and built Grok Imagine in 3 months:

He comes back on Latent Space with some nuclear hot takes: that Video Models primarily get their intelligence from LLMs, not from training on video data, and that the next frontier for truly interactive, realtime, long-horizon world models is to work on LLMs (perhaps Interaction Models as well…)

Put it this way: In the near term, the next Sora won’t be a better video model, but a video agent.

Generative Media may more closely follow the evolution of AI coding which went from focusing on one-shot output performance and cost, to multiturn reasoning and planning models for agents and systems that can plan, edit, test, debug, and submit PRs.

At a certain point, coding models got so good that the only significant next step to improve performance was handling the orchestration of these models.

Now as the performance of video models increases significantly across realism, consistency, & prompt adherence while becoming more cost efficient, the next evolution of video generation may also be systems that can plan, generate, edit, critique, and iterate across an entire creative task.

In this episode, Ethan joins swyx and Vibhu to unpack what it actually takes to build frontier image and video systems: data, VAEs, diffusion transformers, audio-video alignment, inference speedups, and the hidden cost of storing and moving massive video datasets. From building NVIDIA’s Cosmos world model to joining xAI as Grok Imagine was being built from zero to one, Ethan He has been at the center of some of the most important work in video generation, multimodal models, and real-time world models.

We go deep on Grok Imagine, how a small xAI team shipped its first multimodal video model in three months, why iteration speed matters more than almost anything in model development, and why many of the biggest gains come from fixing tiny bugs in data and training pipelines.

Flipbook: The future of Videomaxxing

Video agents are almost a sure bet to be the trend in the coming year. We end with a glance at what’s beyond video agents:

Flipbook caused a minor sensation this year when it was released, but most treat it as a fun demo. Ethan takes it very seriously — with the speed and cost of inference coming down every year, the future of custom video JIT UI is closer than you think. We talked about why videogen models may become the front end of AI, how generative UI could replace traditional HTML/CSS, why world models need to be real-time, interactive, and long-horizon, and why the future of video generation may depend more on language models and agents than on diffusion alone.

We discuss:

* Why fast iteration mattered more than meetings

* Why small training bugs can drive huge model quality gains

* Why coding models may make compute the bottleneck again

* How image and video models are trained with synthetic captions

* The role of VAEs and latent space in frontier video models

* Why image models are the foundation for video models

* The tradeoff between temporal compression and real-time interactivity

* Flipbook, Neural OS, and the future of generative UI

* Why future interfaces may go from user intent to pixels

The new AIEWF website is live! CFPs close in 2 days and we will run our first New Engineer Orientation this weekend, 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!

One of the central tensions in the agents industry is that even while there are major decacorn agent labs like Sierra, Decagon, Notion and Cursor being built up, it is also true that it has never been easier to DIY agents, with a plethora of agent frameworks like LangGraph and Pydantic and Flue, and managed agents from Anthropic and Gemini and Amazon. There has been a wave of companies building their own background agents from Shopify to Stripe to Paradigm to Razorpay, and even Cognition’s friends Ramp have built their own coding agent with other friend Modal.

You’d think Cognition might feel a bit threatened, but they’re not - even after all this, they were way oversubscribed for the $1B Series D they just announced:

Walden Yan, coiner of context engineering and Chief Product Officer/Cofounder of Cognition, invited OpenInspect’s Cole Murray to talk about why the Devin is in the Details.

Full conversation live on the pod today:

In retrospect, async agents were the most AGI pilled bet you could make in 2024 - the models weren’t good enough yet to vibecode, and people didn’t trust AI enough to let it rip, nobody (including early Cognition) was sure about the form factors.

Now it is obvious:

* The first wave of AI coding tools made the developer faster but remain heavily in the loop. Copilor and Cursor’s tab autocomplete are prime examples However, the workflow was still heavily centered around and bottlenecked by the developer’s local workflow: a developer in an IDE, watching the model, accepting or rejecting changes, and pushing code one interaction at a time.

* The second wave was local agents: Claude Code, Windsurf, Cursor’s agents pane: first one and increasingly many terminals all running concurrently.

* The current Age of Async Agents points to a different future focused more on agent orchestration which drives end-to-end development.

According to previous guest Steve Yegge, there are finer-grained

Editor’s note: In our first BioHub pod with Priscilla and Mark they discussed their acquisition of EvoScale, led by Alex Rives, who is now Head of Science at BioHub. With ESM-1 they trained language models on millions of protein sequences drawn from across life, with a simple “next token” objective: predict the amino acids that have been randomly masked out, based on the context of the rest of the sequence. But they soon found that these models also learned biological structure and function, including properties the model had never been explicitly shown AND that this ability scales predictably with compute, leading to ESM2 and ESM3.

Today, Alex announced ESMFold 2, an open scientific engine to power prediction, design, and discovery across protein biology.

Building on Cryo-EM data (discussed in the CZI pod), ESMFold2 reports state of the art performance on protein interactions, especially antibodies, a critical modality for therapeutics, and evidence that inference time scaling is also working across five targets in cancer and immunology.

In a nod to that other famous AI x protein folding project, they are also releasing an atlas of 6.8 billion proteins, and 1.1 billion predicted structures, which you can play around with on their website. We are honored to work with them for this huge release!

One of the refrains we’ve heard on the Science pod has been that protein folding, materials design, cellular biology, etc. are very different problems from Language Modeling. They definitely are. Yet Alex Rives and the ESM team at BioHub just released a preprint and model, demonstrating that vanilla BERT-like transformer models trained on sufficiently large and diverse data sets can beat specialized models like AlphaFold3 on some of the hardest protein-related problems.

Andrew White had a great segment in our first LS-Science episode that explained how mind blowing AlphaFold2 was when it was released in 2020: it suddenly solved problems on a GPU on your desktop that DESRes had built custom-ASIC supercomputer clusters to solve. John Jumper and Demmis Hassabis received the Nobel Prize in Chemistry for this work.

AlphaFold2 took advantage of an very clever observation: if multiple species co-evolve pairs of mutations, this implies that the mutations correspond to parts of the protein that are close in 3d space. This is usually shorthanded as MSAs (multi-sequence alignments), and is the key insight which makes AlphaFold2 so effective.

Like other inductive biases, however, it hurts generalization.

Scale-pilled before it was cool

If you take a look at the timeline for scaling laws for LLMs and release of structure prediction models, the ESM team notably doubled down on their MSAs-be-damned approach after AlphaFold2 released. This obviously requires a great deal of belief in the scale hypothesis.

Why the conviction?

ESM developed at a time when many of the scaling laws and the “Bitter Lesson” were proving increasingly correct. AlphaFold2’s wild success must have been both exciting and bitterly disappointing. But using MSAs mean that the model is is dependent on training data that contains MSAs in order to be accurate in a given domain. For things like antibodies that don’t have MSAs to train on, AlphaFold tends to do poorly.

ESM takes a different approach: learn the relationship between different proteins by unsupervised training on as much diversity as you can find (sound familiar?) and then correlate that back to structures know from the Protein Data Bank (PDB) and other sources.

In other words, a World Model.

World Model …

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On the product side, everyone is getting Computer - Perplexity, Manus, Cursor, and so on. Meanwhile on the research side, agentic evals like TerminalBench and GDPVal are also assuming computer (Harbor). On both ends, the consolidating LLM OS stack has become a standard toolkit, and Daytona is one of a small set of AI Infra companies that are booming because of it.

“The end of localhost” has been Ivan Burazin’s obsession for more than a decade.

Something that is all too familiar…

Long before agents became the default way people talked about software development, Ivan was already chasing the idea that development should not depend on a fragile local machine. CodeAnywhere, one of the first browser-based IDEs, was an early attempt at that future: move the development environment into the cloud, make setup reproducible, and free developers from the endless “works on my machine” tax.

The thesis was directionally right, but the market wasn’t ready yet.However, agents changed that. They do not care about a laptop, desk setup, or favorite editor. They need a computer they can access through an API: something stateful enough to keep working, fast enough to spin up instantly, flexible enough to resize, isolated enough to be safe, and composable enough to run the messy real-world workflows that real software engineering actually requires.Daytona isn’t just selling “sandboxes” in the narrow code-execution sense. It is the latest version of Ivan’s original localhost thesis.

In this episode, Daytona’s CEO joins swyx to explain why AI agents need more than code execution boxes: they need composable computers, stateful sandboxes, instant startup, dynamic resources, and infrastructure that can survive workloads going from zero to 100,000 CPUs.

We go deep on the new agent compute market: Daytona’s hard pivot from human dev environments to AI sandboxes, the New Year’s Eve MVP that customers begged for, why Daytona runs on bare metal with its own scheduler, how one customer runs almost 850,000 sandboxes a day, and why RL/eval workloads went from 0% to roughly 50% of usage in just months. Ivan also explains why agents need Windows and macOS machines, why CLI may matter more than MCP, why Kubernetes is painful for this workload, and why the future AI cloud may look more like Stripe than AWS.

We discuss:

* How Daytona grew out of CodeAnywhere, Shift, and the “end of localhost” thesis

* Why Daytona pivoted from human dev environments to AI sandboxes

* Why agents need composable computers instead of disposable code execution boxes

* The New Year’s Eve MVP that customers chased API keys for

* Why Daytona chose bare metal, stateful snapshots, and its own scheduler

* How Daytona spins up one sandbox in ~60ms and 50,000 sandboxes in ~75 seconds

* Why Daytona’s biggest customer runs ~850,000 sandboxes a day

* How RL/eval workloads create zero-to-100,000 CPU spikes

* Why RL workloads went from 0% to roughly 50% of Daytona usage

* Why customers compare Daytona against EKS/GKS and say they’re “never going back”

* Why every AI agent may need a computer, including Windows and macOS environments

* The Apple licensing constraints that make macOS sandboxes hard

* Why CLI gives agents more power than MCP

* How open source helps agents integrate Daytona

* Why agent-generated PRs may break today’s CI/CD assumptions

* Why AI SaaS companies reselling tokens may face a cold shower

* Why the AI cloud may look more like Stripe than AWS

Ivan Burazin

Take the 2026 AI Engineering Survey and get >$2k in credits and AIE WF tickets!

This was recorded before Railway suffered a major GCP outage on May 19, despite being a multi-AZ, multi-zone mesh ring, with HA fiber interconnects between their Metal <> GCP <> AWS, because workload discoverability was unintentionally still tied to GCP. All has been resolved with a post-mortem.

Railway did not start as an AI infrastructure company.

It was founded in 2020 years before agents became the default way people thought about deploying software. Jake Cooper, formerly at Bloomberg and Uber, started Railway with a simple obsession: the activation energy to ship something to production should be near zero. Push code, get a URL, iterate. No Docker files, no Kubernetes manifests, no Ansible scripts stacked on Ansible scripts.

For years, this was a slow grind. Railway spent its first 18 months hand-acquiring its first 100 users with Jake personally greeting every Discord signup on a second monitor.

Today, Railway has raised $124m and is growing very fast. A 35-person team supports 3 million users, adding roughly 100,000 signups a week. Their bare metal data centers have a 3-month payback period vs. renting in the cloud, with 70% margins funding aggressive cloud bursting when needed. The servers they own have actually appreciated in value as RAM prices have climbed basically meaning the value of their hardware now exceeds the capital they've raised.

From rebuilding Railway’s network overlay over a weekend to moving the vast majority of workloads onto its own bare metal data centers, Jake Cooper is trying to build a new cloud for an agent-native world. In this episode, Railway’s founder and “conductor” joins swyx and Alessio to unpack why the next era of software infrastructure is not just “Heroku but newer,” what agents need that humans did not, and why the old deployment loop of Git, PRs, CI/CD, and static cloud resources may be heading for a rewrite.

We go deep on Railway’s infrastructure stack: own-metal data centers, three-month cloud payback periods, cloud bursting, data center debt, Railpack, Nixpacks, Temporal, feature flags, Central Station, content-addressable filesystems, agent-safe production forks, and why the CLI may become more important than the canvas in an agent world. Jake also shares the founder journey behind Railway, how the company survived losing $500K/month, why it now serves millions of users with only 35 people, and why he believes the pull request is dying.

We discuss:

* How Railway went from a slow six-year grind to adding 100,000 users a week

* How Railway thinks about agents as the next dominant software species

* Why agents need version control, observability, compute, storage, and orchestration at 1000x scale

* The economics of Railway’s own-metal data centers and three-month payback

* How Railway uses cloud bursting while scaling its own infrastructure

* Why data center debt can be a better tool than venture debt for infra startups

* Central Station, Railway’s internal system for clustering customer feedback and incidents

* Why responsible disclosure and over-communication matter for platforms

* Why feature flags, progressive rollouts, and shadow traffic are essential for agents

* Temporal’s strengths, pain points, and why workflows matter for agents

* Railpack, Nixpacks, Nix, and lazy-loaded content-addressable filesystems

* Why “cattle, not pets” may change if you can clone the pets

* Why Railway is building a new cloud from scratch instead of copying hyperscalers

* The solo founder path, focus, writing, and how Jake thinks about company building

Railway:

* …

The future of war has been evolving before our eyes in Ukraine, yet the west still plans to fight the last war. In this special episode, guest host Noah Smith (@noahpinion) and Brandon Anderson sit down with Yaroslav Azhnyuk (@YaroslavAzhnyuk), a serial tech founder who went from building PetCube to founding The Fourth Law, one of the world’s most advanced AI-guided drone companies. Over two hours we cover the technology, tactics, and geopolitics of drone warfare, and why the modern battlefield has already left the West behind:

* Yaroslav’s personal history and the Ukraine war [00:01:04 – 00:14:01]

* The modern drone tech stack: why FPV drones are the new god of war, the future of the rifleman, fiber optic vs. AI, five levels of autonomy, and the eight dimensions of the autonomous battlefield [00:14:01 – 01:05:13]

* The geopolitics and economics of drones: China’s manufacturing advantage, the drone race, Western defense readiness, countermeasures, and why the gap is widening [01:05:13 – 01:58:57]

For those looking for Noah Smith’s commentary, it really gets going around the 00:51:31 mark.

Yaroslav Azhnyuk / The Fourth Law:

* X: https://x.com/YaroslavAzhnyuk

* LinkedIn: https://www.linkedin.com/in/yaroslavazhnyuk/

* The Fourth Law: https://thefourthlaw.ai

Noah Smith:

* Substack: Noah Smith

* X: https://x.com/noahpinion

Timestamps

00:00:00 Cold Open: China’s 4 Billion Drones and the Cameras-to-Explosives Pipeline

00:01:04 Introduction: Brandon, Noah Smith, and Yaroslav Azhnyuk

00:05:41 From Tech Entrepreneur to Defense: PetCube, Brave One, and the D3 Fund

00:10:42 The Ethics of Building Weapons: Dual-Use Technology and the Wolf at the Door

00:14:01 The Tech Stack: Cameras, Autonomy Modules, Interceptors, and a Semiconductor Fab

00:18:47 Fiber Optic vs. AI: The Radio Horizon Problem and $32/km Cable

00:25:32 FPV Drones: The New God of War — 70–80% of Frontline Casualties

00:28:28 The Five Levels of Drone Autonomy: From Terminal Guidance to Full Autonomy

00:41:37 The Eight Dimensions of the Autonomous Battlefield

00:45:32 AI Safety and the Morality of Autonomous Weapons

00:51:31 The End of the Rifleman? Noah’s 2013 Prediction vs. Battlefield Reality

01:05:13 China’s Manufacturing Advantage and Western Vulnerabilities

01:24:21 Policy Advice for Western Defense: Defense Valley and the Widening Gap

01:32:54 The Drone Race: Who’s Ahead, Category by Category

01:41:57 Countermeasures: Shotguns, Jammers, Lasers, and Fishnets

01:58:19 The Wedding and Final Takeaway: Be Prepared for War

Transcript

Cold Open: China, FPV Drones, and the New Warning Sign

Yaroslav [00:00:00]: Think about this. Last year, Ukraine produced 4 million FPV drones. Ukraine is not the most industrious nation in the world. China can produce 4 billion of these FPV drones.

Noah [00:00:10]: Would you say that right now China is now the supreme conventional military power on Earth, given its ability to manufacture and deploy drones in the quantity and quality that you just described?

Yaroslav [00:00:20]: I don’t think we have all the information to claim that but we cannot count it out, and that alone should be a big warning sign. As I say, at some point in my life I went from making cameras that fling treats to pets to cameras that fling explosives to the occupiers. So that’s the short story. And when you think about what your nation, what your patriots are going through, you realize that’s the only morally right thing to do is to fight back, and it is immoral not to fight back, and then the choice becomes very clear.

Introducti…

Special discounts up for AIE Melbourne (LS discount) and AIE World’s Fair (group discounts up to 25% - CFPs still open for Autoresearch and Vertical AI) Cya there!

Abridge did not start as an “GPT wrapper”. It was founded in 2018, years before the Cambrian explosion of AI application layer companies. OpenAI launched ChatGPT publicly on November 30, 2022 and by then, Abridge had already spent years doing the unglamorous work of building trust for one of the highest context, most important workflows in healthcare: the conversation between a patient and a clinician.

Abridge’s original wedge was clinical documentation. Listen to the visit, generate the note, reduce the clerical burden, and let clinicians spend more time with patients instead of the EHR. By focusing on how doctors actually document, how health systems actually buy, how EHR integration actually works, how clinicians verify outputs, and how missing context during a visit turns into downstream friction across billing, prior authorization, quality, and follow-up, the adoption of LLMs became a force multiplier on a workflow already optimized for sensitive context gathering.

The company has scaled fast: Abridge says it is projected to support 80M+ patient-clinician conversations this year across 250 large and complex U.S. health systems, with support for 28+ languages and 50+ specialties. It raised $300M at a $5.3B valuation in June 2025, after a $250M round earlier that year.

Today, Janie Lee and Chaitanya “Chai” Asawa of Abridge join us for another crossover pod with Redpoint’s Jacob Effron (who is on the board of Abridge) to dive into how Abridge is building the clinical intelligence layer for healthcare starting with ambient documentation, then expanding into clinical decision support, prior authorization, payer/provider/pharma workflows, and eventually real-time agents that act before, during, and after the patient conversation.

We go inside the product, data, infra, evals, workflow, privacy, and org design choices behind bringing AI into one of the highest-stakes enterprise environments from 100M+ medical conversations and specialty-specific evals to real-time alerts, EHR integration, de-identification, clinician-scientist teams, and why healthcare may solve some of the hardest AI problems first.

We discuss:

* Why Abridge started with clinical documentation, “pajama time,” and saving clinicians 10–20 hours a week

* The transition from ambient scribe to clinical intelligence layer: save time, save money, and save lives

* Why conversations between patients and clinicians may be the most important workflow in healthcare (patient visit summary feature)

* Chai’s “healthcare-coded Glean” framing: context is king, but healthcare raises the stakes on safety, evals, and rollout

* Why Abridge wants AI to feel like “air conditioning”: always in the background, but only interrupting when it truly matters

* The prior authorization example: turning a denied MRI weeks later into real-time guidance while the patient is still in the room

* Why payer policies, EHR data, medical literature, and hospital-specific guidelines make the problem hard, and also create the moat

* How Abridge thinks about ambient form factors: mobile, desktop, in-room devices, nursing workflows, multimodality, and future AR

* The multi-sided healthcare customer: CMIOs, CFOs, CIOs, clinicians, patients, payers, and pharma

* The hardest AI problem at Abridge: high-quality, low-latency, low-cost real-time …

Some people are going crazy over GPT 5.5. Some people. This is the story of the Jagged Frontier. People who use AI to write emails or even code implementation work find the lift moderate whereas people pushing the limits of the model are figuring out that the limits just moved outwards.

Alex Lupsaska has been tracking this limit for a year and a half now. “When GPT5 came out, it was able to reproduce one of my best papers (that took a very long time to come up with) in 30 minutes.”

But Alex also notes that this shift was mostly invisible.

I remember when GPT-5 came out… on Twitter, the reception was lukewarm. A lot of people were like, well, we expected a lot more, and it’s not better at writing email. And I remember thinking, well, okay, GPT-3 could write email. How much better can it get at writing email? That’s not the point. But at the science frontier, the capabilities were really taking off.

We walk through his paper and more with him in today’s Science pod! Watch here.

The “Oscar for physics”

Alex made an early splash in his career with breakthroughs in our understanding of black holes. He’s also known for Black Hole Explorer and an iPhone app that makes visualizing black holes fun and interactive to regular audiences. Alex won the 2024 New Horizons in Fundamental Physics Breakthrough Prize. Known as the “Oscar for physics” this is arguably the most prestigious prize an early stage theoretical physicist can win.

Alex first saw promise for AI in theoretical physics after he asked o3 for help on his research. In the podcast, Alex recalls asking GPT for help with a calculation that would have taken days, and getting a result in eleven minutes.

He immediately recognized how impactful AI would be for his work even as though his physicist colleagues and the larger community gave it a lukewarm or skeptical reception.

The Move 37 Moment for AI x Physics

GPT-5 had just been released, and Alex tried asking it to solve a problem in a just published paper. GPT-5 said no answer. But Mark Chen, CRO of OpenAI, pushed a bit harder, and had Alex prime the model with a textbook warmup problem, which it easily solved. After using this “priming” trick, GPT-5 was able to reproduce his full result in eleven minutes (yes, the paper was released after the model’s training cutoff).

“This changes everything.” Alex notes that we seem to be on the edge of a massive change in theoretical physics reasoning. A year prior LLMs were just starting do correct math. Now ChatGPT could reproduce his hardest paper in the time it takes to get a coffee.

Alex was on sabbatical at Vanderbilt, and he joined OpenAI to start pushing the boundary of AI’s ability to accelerate physics.

“AI solved the problem before the plane landed”

Alex began to put GPT through it’s paces, reaching out to colleagues for problems they were stuck on. His old PhD advisor (Prof. Andrew Storminger at Harvard) had an insidght about certain physical quantities known as “single-minus gluon tree amplitudes”.

In certain cases, these amplitudes may be non-zero when previously shown to always vanish. The team pushed this intuition forward, and came up with a formula for these quantities that appeared nonzero, but which was otherwise completely intractable.

Spending over a year on this problem, no real progress was made.

Prof. Storminger planned to visit OpenAI to work on the problem the week after the initial conversation started. In that one week ChatGPT fully solved the problem, as Alex recalled, before Prof. Storminger’s plane even landed.

What was interesting is not only that ChatGPT solved this problem, but how it solved it. The mod…

From building Applied Intuition from YC-era autonomy tooling into a $15B physical AI company, Qasar Younis and Peter Ludwig have spent the last decade living through the full arc of autonomy: from simulation and data infrastructure for robotaxi companies, to operating systems for safety-critical machines, to deploying AI onto cars, trucks, mining equipment, construction vehicles, agriculture, defense systems, and driverless L4 trucks running in Japan today. They join us to explain why “physical AI” is not just LLMs on wheels, why the real bottleneck is no longer model intelligence but deployment onto constrained hardware, and why the future of autonomy may look less like one-off demos and more like Android for every moving machine.

We discuss:

* Applied Intuition’s mission: building physical AI for a safer, more prosperous world, powering cars, trucks, construction and mining equipment, agriculture, defense, and other moving machines

* Why physical AI is different from screen-based AI: learned systems can make mistakes in chat or coding, but safety-critical machines like driverless trucks, autonomous vehicles, and robots need much higher reliability

* The evolution from autonomy tooling to a broad physical AI platform: starting with simulation and data infrastructure for robotaxi companies, then expanding into 30+ products across simulation, operating systems, autonomy, and AI models

* Why tooling companies came back into fashion: Qasar on why developer tooling looked unfashionable in 2016, why Applied Intuition still bet on it, and how the AI boom made workflows and tools central again

* The three core buckets of Applied Intuition’s technology: simulation and RL infrastructure, true operating systems for vehicles and machines, and fundamental AI models for autonomy and world understanding

* Why vehicles need a real AI operating system: real-time control, sensor streaming, latency, memory management, fail-safes, reliable updates, and why “bricking a car” is much worse than bricking an iPad

* Physical machines as “phones before Android and iOS”: Peter explains why today’s vehicle and machine software stack is fragmented across many operating systems, and why Applied Intuition wants to consolidate the platform layer

* Coding agents inside Applied Intuition: Cursor, Claude Code, internal adoption leaderboards, and how AI tools are changing engineering workflows even in embedded systems and safety-critical software

* Verification and validation for physical AI: why evals get harder as models improve, how end-to-end autonomy changes simulation requirements, and why neural simulation has to be fast and cheap enough to make RL practical

* From deterministic tests to statistical safety: why autonomy validation is shifting from binary pass/fail requirements toward “how many nines” of reliability and mean time between failures

* Cruise, Waymo, and public trust: Qasar and Peter discuss why autonomy failures are not just technical issues, how companies interact with regulators, and why Waymo is setting a high bar for the industry

* Simulation vs. reality: why no simulator perfectly represents the real world, how sim-to-real validation works, and why real-world testing will never disappear

* World models for physical AI: hydroplaning, construction equipment, visual cues, cause-and-effect learning, and where world models help versus where they are not enough

* Onboard vs. offboard AI: why data-center models can be huge and slow, but onboard vehicle models need millisecond-level latency, low power, small size, and distillation-like efficiency

* Why physical AI is not constrained by model intelligence alone: the hard part is deploying models onto real hardware, under safety, latency, power, cost, and reliability constraints

* Legacy autonomy vs. intelligent autonomy: RTK GPS in mining and agriculture, why hand-coded path-following worked for decades, and why modern systems need perception and dynamic intelligence

* Planning for physical systems: how “plan mode” applies to robotaxis, mining, defense, and multi-step physical tasks where actions change the state of the world

* Why robotics demos are not production: the brittle last 1%, humanoid …

Today, we check in a year after the first Unsupervised Learning x Latent Space Crossover special to discuss everything that has changed (there is a lot) in the world of AI. This episode was recorded just after AIE Europe, but before the Cursor-xAI deal.

Unsupervised Learning is a podcast that interviews the sharpest minds in AI about what’s real today, what will be real in the future and what it means for businesses and the world - helping builders, researchers and founders deconstruct and understand the biggest breakthroughs.

Thanks to Jacob and the UL production team for hosting and editing this!

Jacob Effron

* LinkedIn: https://www.linkedin.com/in/jacobeffron/

* X: https://x.com/jacobeffron

Full Episode on Their YouTube

We discuss:

* swyx’s view from the center of the AI engineering zeitgeist: OpenClaw, harness engineering, context engineering, evals, observability, GPUs, multimodality, and why conference tracks now reveal what matters most in AI

* Whether AI infrastructure has finally stabilized: why “skills” may be the minimal viable packaging format for agents, why infra companies have had to reinvent themselves every year, and why application companies have had an easier time surviving model volatility

* The vertical vs. horizontal AI startup debate: why application companies can act as the outsourced AI team for enterprises, why some horizontal companies still matter, and why sandboxes may be the clearest reinvention of classic cloud infrastructure for the AI era

* The “agent lab” playbook: starting with frontier models, specializing for your domain, then training your own models once you have enough data, workload, and user behavior to justify the cost and latency savings

* Why domain-specific model training is real, not just marketing: how companies like Cursor and Cognition can get users to choose their in-house models, and why search, domain specialization, and distillation are becoming more important

* Open models, custom chips, and alternative inference infrastructure: why swyx has turned more bullish on open source, why non-NVIDIA hardware is suddenly getting real attention, and why every 10x speedup can unlock new product experiences

* What it means to sell to agents instead of humans: why agent experience may mostly just be good developer experience by another name, why APIs and docs matter more than ever, and how pretraining-data incumbents are compounding advantages in an agent-first world

* Why memory and personalization may become the next big wedge: today’s models mostly reward frequency of mentions, but in the future, swyx expects product choice to be shaped much more by personalized memory systems

* The state of the AI coding wars: why coding has become one of the largest and fastest-growing categories in AI, how Anthropic, OpenAI, Cursor, and Cognition have all ridden the wave, and why the category may still have more room to run

* Capability exploration vs. efficiency: why the industry is still in a token-maxing, experiment-heavy phase where people are rewarded for spending more rather than less

* Claude Code vs. Codex and the strange stickiness of coding products: why first magical product experiences may matter more than expected, and why the bigger mystery may be why only a few names have emerged as real winners so far

* What the end state of the coding market might look like: two major players, a longer tail of niche products, and possible disruption if Microsoft, Mistral, xAI, or the Chinese labs push harder into coding

* Where application companies still have room against the labs: why frontier labs are trying to expand into verticals like finance and healthcare, but still leave space for focused companies that own the workflow and the last mile

* Why coding may be a preview of every other AI market: the first category to truly go parabolic, the clearest example of foundation model companies colliding with application companies, and a template for how future vertical AI markets may develop

* Why AI valuations now feel unbounded: from billion-dollar ARR products built in a year to trillion-dollar market caps, swyx and Jacob unpack how the AI market has broken tradition…

Early bird discounts for the San Francisco World’s Fair, the biggest AIE gathering of the year, end today - prices will go up by ~$500 tonight so do please lock in ASAP!

From near-universal AI tool adoption inside Shopify to internal systems for ML experimentation, auto-research, customer simulation, and ultra-low-latency search, Mikhail Parakhin joins us for a deep dive into what it actually looks like when a 20-year-old, $200B software company goes all-in on AI. We cover why Shopify has become much more vocal about its internal stack, what changed after the December model-quality inflection, and why the real bottleneck in AI coding is no longer generation, but review, CI/CD, and deployment stability.

We also go inside Tangle, Tangent, SimGym, which are three major AI initiatives that Shopify is doing to make experimentation reproducible, optimization automatic, customer behavior simulatable, and search and catalog intelligence faster and cheaper at scale. Along the way, Mikhail explains UCP, Liquid AI, and why token budgets are directionally right but often measured badly, why AI-written code can still increase bugs in production, what makes Shopify’s customer simulation defensible, and what he learned from the Sydney era at Bing.

We discuss:

* Mikhail’s path from running a major Microsoft business unit spanning Windows, Edge, Bing, and ads to becoming CTO of Shopify

* Why Shopify is talking more publicly about AI now, and why staying at the frontier has become necessary for the company

* Shopify’s internal AI adoption curve, the December inflection, and why CLI-style tools are rising faster than traditional IDE-based tools

* Why Jensen Huang is directionally right on token budgets, but raw token count is still the wrong way to evaluate engineering output

* Why the real unlock is not more agents in parallel, but better critique loops, stronger models, and spending more on review than generation

* Why AI coding can still lead to more bugs in production even if models write cleaner code on average than humans

* Why Shopify built its own PR review flow, and why Mikhail thinks most off-the-shelf review tools miss the point

* How PR volume, test failures, and deployment rollback are becoming the real bottlenecks in the agent era

* Why Git, pull requests, and CI/CD may need a new metaphor once code is written at machine speed

* What Tangle is, and how Shopify uses it to make ML and data workflows reproducible, collaborative, and production-ready from the start

* Why Tangle is different from Airflow, and why content-addressed caching creates network effects across teams

* What Tangent is, and how Shopify is using auto-research loops to optimize search, themes, prompt compression, storage, and more

* Why Tangent is becoming a democratizing tool for PMs and domain experts, not just ML engineers

* Why AutoML finally feels real in the LLM era, and where auto-research still falls short today

* Why Tangle, Tangent, and SimGym become much more powerful when combined into one system

* What SimGym is, why simulated customers only work if you have real historical behavior, and why Shopify’s data gives it a moat

* How SimGym evolved from comparing A/B variants to telling merchants what to change on a single live storefront to raise conversions

* Why customer simulation is so expensive, from multimodal models to browser farms to serving and distillation costs

* How Shopify models merchant and buyer trajectories, runs counterfactuals, and thinks about interventions like discounts, campaigns, and notifications

* Why category-level behavior is so different across commerce, and why ideas like Chinese Restaurant Processes are showing up again in practice

* Shopify’s new UCP and catalog work, including runtime product search, bulk lookups, and identity linking

* Why Shopify is using Liquid AI, and why Mikhail sees it …

Today, we explain this piece of “clickbait” from our guest!

TL;DR: 95% of cancer treatments fail to pass clinical trials, but it may be a matching problem — if we better understood what patients have which tumors which will respond to which treatments, success rates improve dramatically and millions of lives can be saved — with the treatments we ALREADY have.

See our full episode dropping today:

Why Big Pharma is licensing AI Models

Tolstoy famously wrote, ‘All healthy cells are alike; each cancer cell is unhappy in its own way.’ Or something like that. Cancer might be the most misunderstood disease out there. It’s not one disease, it’s a family of diseases. Hundreds, maybe thousands, of unique diseases each with its own underlying biology. With this lens, saying you’ll “cure cancer” is like saying you’ll solve legos.

We keep hearing AI will cure cancer, but sadly it may not be so easy. Today’s guests — Ron Alfa and Daniel Bear from Noetik — thinks they can use AI to break through a core bottleneck in the treatment development process.

GSK recently signed a $50M deal for their technology that also includes an (undisclosed) long-term licensing deals for Noetik’s models like the recently announced TARIO-2, an autoregressive transformer trained on one of the largest sets of tumor spatial transcriptomics datasets in the world. Whole-plex spatial transcriptomics is the richest way to read a tumor, and approximately ~0% of cancer patients going through standard care ever get one — and TARIO-2 can now predict an ~19,000-gene spatial map from the H&E assay every patient already has.

Most big AI plays in BioTech have focused on discovery, and usually result in an in-house development effort (meaning tools companies usually become drug companies). This deal stands out in that it is a software licensing deal, and represents a commitment to a platform rather than a drug.

With attention on other software tools for drug development (see the Boltz episode and Isomorphic for example), it is starting to look like the appetite of Pharma for biotech tools has finally started to grow. Why the sudden interest?

Cancer is hard

Biology is hard, cancer is harder. But despite this, we’ve made incredible progress. So many cancers that would have been death sentences twenty years ago are routinely survivable. It used to be our main strategy was just chemotherapy — poison you and hope the tumor dies before you do. Now, there are many treatments that actually kill a tumor and leave the rest of you intact! Immune checkpoint inhibitors like Keytruda and Opdivo target the defenses of dozens of tumor types. CAR-T therapy adds modified T-cells to your blood that can target B-cell malignancies very accurately. Antibody Drug Conjugates such as Trastuzumab combine a drug with an antibody, allowing it to target very specific (cancer) cells. We truly live in marvelous times.

With that said, we still have a long way to go. For every type of cancer with a miracle treatment, we have many more that are still death sentences. The world spends $20-30 billion a year trying to cure cancers, with hundreds of clinical trials yearly.Yet, progress is slow with a 95% failure rate in clinical trials.

The lab doesn’t translate to the clinic

Are we leaving something on the table? Enter Noetik and Ron Alfa. Ron’s core thesis is that many of these “failed” treatments actually work! But we’re not looking at the right patients with the right tumors. If only we had a way to really understand the unique types of cancer biologies and which patients will respond to which treatments, we might be able to show a much higher success rate. Millions of lives (and billions of dollars) may ride on this.

The Hard part: Blind Faith in Data Collection

Ron and Noetik had the conviction to spend almost two years just collecting data. Lots, and lots, and lots, of data. Noetik has acquired tho…

For all those who missed out on London, see you in Miami next week!

Notion, the knowledge work decacorn, has been building AI tooling since before ChatGPT, with many hits from Q&A in 2023 and unified AI in 2024 and Meeting Notes in 2025. At the end of their last Make user conference, Ryan Nystrom teased Notion 3.0’s Custom Agents - and they are finally embracing the Agent Lab playbook!

Sarah Sachs and Simon Last of Notion join us for a deep dive into how Notion built Custom Agents, why it took years and multiple rebuilds to get right, and what it means to turn a productivity tool into an agent-native system of record for enterprise work.

We go inside the product, engineering, evals, pricing, and org design decisions behind one of the most ambitious AI product efforts in software today — from early failed tool-calling experiments in 2022 to agent harnesses, progressive tool disclosure, meeting notes as data capture, and the long-term vision for software factories and agentic work.

We discuss:

* Sarah and Simon’s path to launching Notion Custom Agents, and why the feature was rebuilt four or five times before it was ready for production

* Why early agent attempts failed: no tool-calling standard, short context windows, unreliable models, and too much complexity exposed to the model

* The “Agent Lab” thesis: not just wrapping a model, but understanding how people collaborate and building the right product system around frontier capabilities

* How Notion thinks about roadmap timing: not swimming upstream against model limitations, but also building early enough that the product is ready when the models are

* Why coding agents feel like the kernel of AGI, and how Notion is thinking about “software factories” made up of agents that spec, code, test, debug, review, and maintain codebases together

* How Sarah runs AI engineering at Notion (“notes from Token Town”): objective-setting over idea ownership, low-ego teams comfortable deleting their own work, and a culture designed to swarm around fast-changing opportunities

* The “Simon Vortex,” company hackathons, and why security gets pulled in early rather than late

* How Notion organizes AI: core AI capabilities and infrastructure, product packaging teams, and a broader company mandate that every product surface must increasingly work for both humans and agents

* Why prototypes have become much easier to build internally, and how “demos over memos” changes product development inside a tool the whole company already uses every day

* Notion’s eval philosophy: regression tests, launch-quality evals, and “frontier/headroom” evals that intentionally only pass ~30% of the time so the company can see where model capabilities are going

* What a “Model Behavior Engineer” is, and why Notion treats eval writing, failure analysis, and model understanding as a distinct function rather than just software engineering

* The changing role of software engineers in the age of coding agents, and why the new job looks less like typing code and more like supervising a rigorous outer system of agents, PRs, and verification loops

* How the “software factory” should work: specs, self-verification, bug flows, subagents, and minimizing human intervention while preserving the invariants that matter

* A live walkthrough of a Notion Custom Agent handling coworking space tenant applications by triaging email, enriching applicants with web search, and writing structured data into a Notion database

* How agents compose inside Notion: shared databases …

We’re proud to release this ahead of Ryan’s keynote at AIE Europe. Hit the bell, get notified when it is live! Attendees: come prepped for Ryan’s AMA with Vibhu after.

Move over, context engineering. Now it’s time for Harness engineering and the age of the token billionaires.

Ryan Lopopolo of OpenAI is leading that charge, recently publishing a lengthy essay on Harness Eng that has become the talk of the town:

In it, Ryan peeled back the curtains on how the recently announced OpenAI Frontier team have become OpenAI’s top Codex users, running a >1m LOC codebase with 0 human written code and, crucially for the Dark Factory fans, no human REVIEWED code before merge. Ryan is admirably evangelical about this, calling it borderline “negligent” if you aren’t using >1B tokens a day (roughly $2-3k/day in token spend based on market rates and caching assumptions):

Over the past five months, they ran an extreme experiment: building and shipping an internal beta product with zero manually written code. Through the experiment, they adopted a different model of engineering work: when the agent failed, instead of prompting it better or to “try harder,” the team would look at “what capability, context, or structure is missing?”

The result was Symphony, “a ghost library” and reference Elixir implementation (by Alex Kotliarskyi) that sets up a massive system of Codex agents all extensively prompted with the specificity of a proper PRD spec, but without full implementation:

The future starts taking shape as one where coding agents stop being copilots and start becoming real teammates anyone can use and Codex is doubling down on that mission with their Superbowl messaging of “you can just build things”.

Across Codex, internal observability stacks, and the multi-agent orchestration system his team calls Symphony, Ryan has been pushing what happens when you optimize an entire codebase, workflow, and organization around agent legibility instead of human habit.

We sat down with Ryan to dig into how OpenAI’s internal teams actually use Codex, why the real bottleneck in AI-native software development is now human attention rather than tokens, how fast build loops, observability, specs, and skills let agents operate autonomously, why software increasingly needs to be written for the model as much as for the engineer, and how Frontier points toward a future where agents can safely do economically valuable work across the enterprise.

We discuss:

* Ryan’s background from Snowflake, Brex, Stripe, and Citadel to OpenAI Frontier Product Exploration, where he works on new product development for deploying agents safely at enterprise scale

* The origin of “harness engineering” and the constraint that kicked off the whole experiment: Ryan deliberately refused to write code himself so the agent had to do the job end to end

* Building an internal product over five months with zero lines of human-written code, more than a million lines in the repo, and thousands of PRs across multiple Codex model generations

* Why early Codex was painfully slow at first, and how the team learned to decompose tasks, build better primitives, a…

Fresh off raising a monster $15B, Marc Andreessen has lived through multiple computing platform shifts firsthand, from Mosaic and Netscape to cofounding A16z.

In this episode, Marc joins swyx and Alessio in a16z’s legendary Sand Hill Road office to argue that AI is not just another hype cycle, but the payoff of an “80-year overnight success”: from neural nets and expert systems to transformers, reasoning models, coding, agents, and recursive self-improvement. He lays out why he thinks this moment is different, why AI is finally escaping the old boom-bust pattern, and why the real bottleneck may be less about models than about the messy institutions, incentives, and social systems that struggle to absorb technological change.

This episode was a dream come true for us, and many thanks to Erik Torenberg for the assist in setting this up. Full episode on YouTube!

We discuss:

* Marc’s long view on AI: from the 1980s AI boom and expert systems to AlexNet, transformers, and why he sees today’s moment as the culmination of decades of compounding technical progress

* Why “this time is different”: the jump from LLMs to reasoning, coding, agents, and recursive self-improvement, and why Marc thinks these breakthroughs make AI real in a way prior cycles were not

* AI winters vs. “80-year overnight success”: why the field repeatedly swings between utopianism and doom, and why Marc thinks the underlying researchers were mostly right even when the timelines were wrong

* Scaling laws, Moore’s Law, and what to build: why he believes AI scaling laws will continue, why the outside world is messier than lab purists assume, and how startups can still create durable value on top of rapidly improving models

* The dot-com crash and AI infrastructure risk: Marc’s comparison between today’s AI capex boom and the fiber/data-center overbuild of 2000, plus why he thinks this cycle is different because the buyers are huge cash-rich incumbents and demand is already here

* Why old NVIDIA chips may be getting more valuable: the pace of software progress, chronic capacity shortages, and the idea that even current models are “sandbagged” by supply constraints

* Open source, edge inference, and the chip bottleneck: why Marc thinks local models, Apple Silicon, privacy, trust, and economics all point toward a major role for edge AI

* American vs. Chinese open source AI: DeepSeek as a “gift to the world,” why open models matter not just because they’re free but because they teach the world how things work, and how open source strategies may shift as the market consolidates

* Why Pi and OpenClaw matter so much: Marc’s claim that the combination of LLM + shell + filesystem + markdown + cron loop is one of the biggest software architecture breakthroughs in decades

* Agents as the new “Unix”: how agent state living in files allows portability across models and runtimes, and why self-modifying agents that can extend themselves may redefine what software even is

* The future of coding and programming languages: why Marc thinks software becomes abundant, why bots may translate freely across languages, and why “programming language” itself may stop being a salient concept

* Browsers, protocols, and human readability: lessons from Mosaic and the web, why text protocols and “view source” mattered, and how similar principles may shape AI-native systems

* Real-world OpenClaw use: health dashboards, sleep monitoring, smart homes, rewriting firmware on robot dogs, and why the most aggressive users are discovering both the power and danger of agents first

* Proof of human vs. proof of bot: why Marc thinks the internet’s bot problem is now unsolvable via detection alone, and why biometric + cryptographic proof of human becomes necessary

Timestamps

* 00:00 Marc on AI’s “80-Year Overnight Success”

* 00:01 A Quick Message From swyx

* 01:44 Inside a16z With Marc Andreessen

* 02:13 The Truth About a16z’s AI Pivot

* 03:29 Why This AI Boom Is Not Like 2016

* …

We’ve been on a bit of a mini World Models series over the last quarter: from introducing the topic with Yi Tay, to exploring Marble with World Labs’ Fei-Fei Li and Justin Johnson, to previewing World Models learned from massive gaming datasets with General Intuition’s Pim de Witte (who has now written down their approach to World Models with Not Boring), to discussing the Cosmos World Model with with Andrew White of Edison Scientific on our new Science pod, to writing up our own theses on Adversarial World Models. Meanwhile Nvidia, Waymo and Tesla have published their own approaches, Google has released Genie 3, and Yann LeCun has raised $1B for AMI and published LeWorldModel.

Today’s guests have a radically different approach to World Modeling to every player we just mentioned — while Genie 3 is impressive, its many flaws demonstrate the issues with their approach - terrain clipping, noninteractivity (single player, no physics/no objects other than the player move), and maximum of 60 second immersion.

Moonlake AI (inspired by the Dreamworks logo) is the diametric opposite - immediately multiplayer, incredibly interactive, indefinite lifetime, capable of MANY different kinds of world models by simulating environments, predicting outcomes, and planning over long horizons. This is enabled by bootstrapping from game engines and training custom agents:

In Towards Efficient World Models, Chris Manning and Ian Goodfellow join Fan-Yun in explaining why their approach to efficiency with structure and casuality instead of just blind scaling is sorely needed:

SOTA models still show physical or spatial understanding glitches, such as solid objects floating in mid-air or moving “inside” other solid objects.

If the goal is to plan for the next action, how often is a high-resolution pixel view necessary for modeling the world? Our bet is that there is a disproportionately large share of economically valuable tasks where such detail is not required. After all, humans with a wide variety of sensory limitations have little difficulty doing almost everything in the world. Furthermore, for a large number of purposes, describing a scene or a situation in a few words of language (“the car’s tires squealed as it cornered sharply”) is sufficient for understanding and planning.

Experiments also show that humans only partially process visual input in a top-down, task-directed way, …

Mistral has been on an absolute tear - with frequent successful model launches it is easy to forget that they raised the largest European AI round in history last year. We were long overdue for a Mistral episode, and we were very fortunate to work with Sophia and Howard to catch up with Pavan (Voxtral lead) and Guillaume (Chief Scientist, Co-founder) on the occasion of this week’s Voxtral TTS launch:

Mistral can’t directly say it, but the benchmarks do imply, that this is basically an open-weights ElevenLabs-level TTS model (Technically, it is a 4B Ministral based multilingual low-latency TTS open weights model that has a 68.4% win rate vs ElevenLabs Flash v2.5). The contributions are not just in the open weights but also in open research: We also spend a decent amount of the pod talking about their architecture that combines auto-regressive generation of semantic speech tokens with flow-matching for acoustic tokens (typically only applied in the Image Generation space, as seen in the Flow Matching NeurIPS workshop from the principal authors that we reference in the pod).

You can catch up on the paper here and the full episode is live on youtube!

Timestamps

00:00 Welcome and Guests00:22 Announcing Voxtral TTS01:41 Architecture and Codec02:53 Understanding vs Generation05:39 Flow Matching for Audio07:27 Real Time Voice Agents13:40 Efficiency and Model Strategy14:53 Voice Agents Vision17:56 Enterprise Deployment and Privacy23:39 Fine Tuning and Personalization25:22 Enterprise Voice Personalization26:09 Long-Form Speech Models26:58 Real-Time Encoder Advances27:45 Scaling Context for TTS28:53 What Makes Small Models30:37 Merging Modalities Tradeoffs33:05 Open Source Mission35:51 Lean and Formal Proofs38:40 Reasoning Transfer and Agents40:25 Next Frontiers in Training42:20 Hiring and AI for Science44:19 Forward Deployed Engineering46:22 Customer Feedback Loop48:29 Wrap Up and Thanks

Transcript

swyx: Okay, welcome to Latent Space. We’re here in the studio with our gues co-host Vibh u. Welcome. Thanks. Excited for this one as well as Guillaume and Pavan from Mistral. Welcome. Excited to be here.

Guillaume: Thank you.

swyx: Pavan, you are leading audio research at Mistral and Guillaume, you're Chief Scientist,

Announcing Voxtral TTS

swyx

Host

(00:05) Okay. (00:05) Welcome to Lean Space. (00:06) We’re here in the studio with trustee co-hosts, Vibhu. (00:09) Welcome.

Vibhu

Host

(00:11) Very excited for this one.

swyx

Host

(00:12) As well as Guillaume and Pavan from Mistral. (00:15) Welcome. (00:16) Excited to be here. (00:17) Thank you for having us.

(00:18) Pavan, you are leading audio research at Mistral and Guillaume, you’re a chief scientist. (00:23) What are we announcing today where we’re coordinating this release with you guys?

Guillaume

Guest

(00:26) Yeah, so we are releasing Voxtral TTS. So it’s our first audio model that generates speech. It’s not our first audio model. We had a couple of releases before.

(00:35) We had one in the summer that was Voxtral, our first audio model, but it was like a transcription model, ASR. Like a few months later, we released some update on top of this, supporting more languages. Also a lot of table stack features for our customers, context biasing, precision, timestamping and transcription. We also have some real-time model that can transcribe not just at the end of the level.

(00:56) You don’t need to fill your entire audio file, but that can also come in real-time. And here, this is a natural extension in the audio, so basically speech generation. So yeah, so we support nine languages, and this is a pretty small model, 3D model, so very fast, and also state of the art. Performed at the same level as the base model, but it’s much more efficient in terms of cost, and also much, in terms of cost, it’s also much cheaper, only a fraction of the cost of our competitors.

(01:22) And we are also releasing the work that this model is running.…