
Latent Space: The AI Engineer Podcast
Written by a model from the transcript; not yet reviewed.
This episode features a discussion with Eric Nguyen, CEO and co-founder of Radical Numerics, focusing on generative genomics, foundational DNA models like Evo and Omni, and the intersection of AI with biosecurity. The guest and hosts explore how genome language models are trained on raw DNA sequences rather than annotated data, unlocking capabilities such as predicting disease-causing variants in non-coding regions and designing functional biological systems from scratch. The conversation also covers advanced machine learning techniques applied to biology, including mid-training alignment, chain of thought reasoning with RNA aptomers, and mechanisms for addressing emerging biosecurity risks through dual-mandate defensive tools.
The hosts introduce themselves and set the stage for the episode, welcoming Eric Nguyen of Radical Numerics.
Eric explains what a genomic language model is, its purpose, and how it differs from natural language models.
Omni’s mid‑training and post‑training alignment strategies are described, showing how they improve performance across diverse genomics tasks.
The team explains rigorous steps taken to avoid data leakage in training and evaluation, ensuring benchmark integrity.
The concept of chain‑of‑thought prompting is adapted to DNA, enabling the model to iteratively improve sequence fitness in silico.
Eric outlines the long‑term goal of a unified model that understands all biological modalities, moving toward a virtual cell and beyond.
The discussion covers how Omni can tackle human genomic variants, viral genome design, and antimicrobial resistance through AI‑generated phages.
A novel use case is explored where Omni designs proteins for rare‑earth mineral extraction by leveraging genomic context and evolutionary signals.
The discussion shifts to the technical hurdles of scaling context for DNA sequences, highlighting the Evo2 bacteriophage design and the limitations of current models.
The conversation explores how language model architectures were adapted to generate DNA, detailing early experiments, surprising protein benchmarks, and the decision to focus on design capabilities.
The speakers explain the emerging Meccan Tarp approach, using model embeddings and activations to uncover biological motifs and disease manifolds.
The Dual Mandate for AI Labsdebate
Radical Numerics operates with a dual mandate, building both biological design capabilities and defensive security tools because the underlying models are fundamentally the same.
What is a Genome Language Model?insight
Eric Nguyen explains that genome language models are large language models trained on raw DNA sequences instead of natural language, allowing AI to both read and write the fabric of life.
Generating a Functional Genome from Scratchstory
The discussion highlights how generative DNA models like Evo successfully designed and generated a functional viral genome from scratch, marking a major turning point for synthetic biology.
Predicting Disease in Non-Coding Regionsdata
The guest explains that Omni excels at identifying disease-causing variants in non-coding regulatory regions, which make up the vast majority of the genome and were previously difficult to analyze.
Chain of Thought Reasoning in RNAstrategy
The team applied chain of thought reasoning to genomics by feeding the model progressively better RNA aptomer sequences with fitness scores to help it self-optimize.
“The design side is going to get more capable.”
“We felt this was an area that was overlooked and that if AI could read and write DNA, it could change a lot.”
“We showcased that a single DNA model, sort of the foundation of both of those, right? From DNA, you can get RNA and proteins, that you can design a single system to generate and also function in the real world.”
“I think context matters a lot in biology.”
“We want to continually push the envelope.”
“We believe and see a gap in companies being able to safeguard that technology and make sure that it's used responsibly increasingly more.”
“I think we can be helpful and move the biodefense community forward in terms of, you know, bringing AI technology and AI frontier technology to their aid without being perfect.”
“I think one message is, I think folks have had, especially into the AI research community, felt like there was a choice that they had to make sometimes to either work on the frontier of AI technology or on enterprise related apps.”
The OpenAI → Hugging Face attack has people asking “what else do we need to worry about?” and Anthropic’s filters flag two things: cyber-security and biology. The natural question is: what about bio-security, then? Clem Delangue argues that cyber-warfare defensive capabilities need to be open and to keep pace with frontier models’ attack capabilities Radical Numerics co-founder Eric Nguyen sat down with us and explained why the same models that increase biological capability can also keep defense from falling behind. Building a virus from scratch While he was at Stanford, Eric couldn’t get traction on Genomic Language Models (GLMs) for a long time. Biologists didn’t believe it would work, didn’t think they could verify the output, and didn’t see important applications beyond what they could already do. He kept pushing, eventually helping lead the development of Evo and contributing to Evo 2 at Arc Institute. Those models were later used by a separate Arc/Stanford team to generate entire bacteriophage genomes that were synthesized into functional viruses https://www.biorxiv.org/content/10.1101/2025.09.12.675911v1! Long context unlocks biological intelligence Early ChatGPT spit out poems and email, and early DNA language models like Evo and Evo-2 could build a genome from scratch. DNA is different, however, from natural language in that it has a very small alphabet (4 characters ACTG) and that its sequences are very long: * 60K for an average human gene * long being up to 2.3M * the whole human genome around 3B. Innovation in long-context models https://github.com/togethercomputer/stripedhyena made this possible about 3 years ago (footnote: striped hyena), long before the frontier labs were building 1M+ context models. Now Eric and other AI x Bio luminaries have founded Radical Numerics to build and scale GLMs to tack a wide range of biological problems, extending well beyond generating DNA. Thinking in DNA Their GLMs already do pretty well with RNA and protein because there are clear markers in the DNA sequence for genes (RNA sequences the perform many functions) and specific genes that encode proteins. This means that the models already generalize to multiple “languages,” before even attempting to train in other modalities, such as 3d protein structure, epigenetics and natural language. If a model thinks in the DNA language, maybe it understands the imprint that environment left on different genomes as well? Perhaps the model has learned the functional relationship between different sequences, and could extrapolate to new sequences based on that? And so what we wanted to showcase was that if we show the model progressively better RNAs in a series of steps with its score, right? So you have like low scores first and then you gradually move up the chain. Can the model continue that trajectory on its own? And then in the final step, does it self optimize to a point where it's like the best score it can get? That was the experiment. Can we do that? And so we took a data set, a large data set of aptamers. We held out a portion of the best performing ones and we showed it only the lower ones, but then we ranked it, right? So we showcase lower scores with the RNA aptamers and then progressively got higher, and then ask the model to just like continue with that pattern. And it turns out it was able to recapitulate some of those higher scores that we had not shown it yet. So, voila: chain-of-thought, thinking in DNA! The arms race But much as long-context inference, chain-of-though and multi-modal perception unlocked sophisticated reasoning in natural language LLMs, these capabilities in GLMs are enabling increasingly sophisticated “biological intelligence,” and along with it, greater danger. According to Eric, defense is currently losing this battle, but Radical Numerics argues to push the frontier harder! I won’t spoil the details for you. In the episode we talk in detail about: * Biosecurity as an arms race — and how defense can keep up * The genome as the imprint of the environment on DNA * Going truly multi-modal * How chain-of-though works when you “think” in the language of DNA This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.latent.space/subscribe https://www.latent.space/subscribe?utm_medium=podcast&utm_campaign=CTA_2
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