ESM

🔬They Thought the Model Was Broken — Matt McPartlon & Neil Patil, Chai Discovery

Aug 11, 2026 · 1:35:20

Matt McPartland and Neil Patil of Chai Discovery explain why pharma partners like Eli Lilly, Pfizer, Novartis, and argenx are buying their AI design tools, arguing that Chai-2's all-atom diffusion model crossed a usefulness threshold by designing antibodies to 50 targets with hits on half at ~20% hit rate. They trace the lineage from open-sourced Chai-1 structure prediction through Chai-2's co-design of sequence and structure, and detail how validation via cryo-EM achieved a 0.33 Å error, making them suspect data leakage. The product resembles SolidWorks or Figma, not ChatGPT, with paint-tool epitope selection and content-aware fill for binder generation, built under strict pharma IP constraints via single-tenancy. They discuss convincing skeptical scientists—one cried after seeing a binder for a target she'd spent a decade on—and argue the compute market is mispriced for this model class, with bottlenecks in validation loops and talent obscurity rather than data or compute.

🔬 The Bitter Lesson is Coming for Proteins - Alex Rives, BioHub

May 27, 2026 · 1:10:12

Alex Rives, head of science at BioHub, argues that scaling language models on protein sequences—the 'bitter lesson' for biology—yields emergent biological understanding, culminating in the open-source ESMC model and ESMFold 2. ESMC, trained on 6.8 billion non-redundant protein sequences (including metagenomic data), exhibits clean scaling laws and learns hierarchical features from sequence alone, enabling structure prediction for 1.1 billion proteins. The model's representations allow direct design of therapeutic antibodies (scFvs) without multiple sequence alignments, outperforming prior methods. Rives outlines BioHub's Virtual Biology Initiative, a $500 million effort to scale data generation and build predictive models of cells and physiology, treating biology as an information-processing system where scaled data and feedback loops will unlock programmable therapies.