PDB

🔬Causal Models Need Causal Data - Xaira’s X-Cell model (Bo Wang & Ci Chu)

Jul 21, 2026 · 1:29:47

Bo Wang and Ci Chu from Xaira Therapeutics present X-Cell, a 4.9-billion-parameter diffusion language model trained on the largest genome-wide CRISPRi Perturb-seq dataset (25.6 million single cells, 16 biological contexts) that predicts cellular responses to genetic perturbations and generalizes from immortalized cell lines to primary T cells from real donors. They explain why observational atlases describe biology but can't predict interventions, why they abandoned autoregression for a diffusion 'editing' approach, and how a model trained on immortalized cells predicted perturbation responses in primary T cells. They highlight a counterintuitive scaling result: X-Cell scales like an LLM on training loss, but generalization is bottlenecked by data diversity, not compute. The episode also covers Xaira's three-platform strategy (protein design, virtual cell, patient representation) and the central thesis that for causal models, the hard part isn't the model, it's the data.

🔬 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.