Machine learning techniques are now routinely encountered in research laboratories across the globe. Impressive progress has been made through ML and AI techniques with regards to large data set processing. This progress has increased the ability of the experimenter to digest data and make novel predictions regarding phenomena of interest. However, machine learning predictors generated from data sets taken from the natural sciences are often treated as black boxes which are used broadly and generally without detailed consideration of the causal structure of the data set of interest. Work has been attempted to bring causality into discussions of machine learning models of natural phenomena; however, a firm and unified theoretical treatment is lacking. This series of three papers explores the union of chemical theory, biological theory, probability theory and causality that will correct current causal flaws of machine learning in the natural sciences. This paper, Part 1 of the series, provides the formal framework of the foundational causal structure of phenomena in chemical biology and is extended to machine learning through the novel concept of focus, defined here as the ability of a machine learning algorithm to narrow down to a hidden underpinning mechanism in large data sets. Initial proof of these principles on a family of Akt inhibitors is also provided. The second paper containing Part 2 will provide a formal exploration of chemical similarity, and Part 3 will present extensive experimental evidence of how hidden causal structures weaken all machine learning in chemical biology. This series serves to establish for chemical biology a new kind of mathematical framework for modeling mechanisms in Nature without the need for the tools of reductionism: inferential mechanics.
Explanations are central to causal reasoning, and cognitive science has long established that the human drive to explain is itself a mechanism for learning about causality. Despite this, learning from those abductive signals is largely ignored in artificial intelligence. While explainable AI (XAI) increasingly draws on causal models to generate explanations, the converse direction about what explanations can do for causality remains largely unexplored. To fill this gap, we propose xWhyL, a formal framework connecting causality and XAI by learning causal models from explanations. We develop a mathematical theory that translates explanations into a learning signal complementary to observational data, and demonstrate how it enables overcoming the limits of observational causal discovery. As explanations can be derived from incorrect beliefs and clash with data, a tension we call the Causal Tug-of-War, we prove conditions under which our framework rejects misspecified explanations rather than absorbing them. Our practical instantiation, Causal Interactive Learning (CIL), shows how expert explanations can efficiently support causal discovery and distinguish correct from incorrect explanations.
Nicholas Tagliapietra, Florian Peter Busch, Moritz Willig +4
Bosch Center for Artificial Intelligence, Germany · Computer Science Department, Technical University of Darmstadt, Germany · Hessian Center for AI (hessian.AI), Darmstadt, Germany
We introduce CausaLab, a scalable environment for evaluating interactive causal discovery by LLM agents. Unlike prior evaluations, CausaLab evaluates both whether an agent can solve a problem using causal evidence and whether its answer is grounded in a faithful recovered causal mechanism. Each episode places an agent in a synthetic laboratory: it receives prior measurement records, intervenes on a manipulator crystal, and predicts the resonance frequency of a held-out reactor crystal governed by the same mechanism. The hidden data-generating process is a randomly sampled structural causal model (SCM), so success requires recovering both a causal graph and structural equations rather than recalling prior knowledge. Experiments show a persistent gap between prediction and mechanism recovery: in the purely observational 6-node setting, GPT-5.2-high reaches 92% task accuracy but only 0.471 all-edge F1. Mixed observation-intervention strategies improve structural fidelity, while pure intervention remains difficult even for strong agents. We identify premature stopping as a major weakness and show that consistency verification mitigates it. CausaLab therefore separates predictive success from causal understanding and exposes current LLM agents' limits as experimental causal reasoners.
Junlin Yang, Dylan Zhang, Xiangchen Song +7
Tsinghua University · University of Illinois Urbana-Champaign · Carnegie Mellon University +2
Scientific machine learning is limited less by model size than by the data it is trained on. Observational data records what happened but not why; template synthetic data has a known generating process but only for the simulator's template, not the case a user faces. We argue a third option is now operationally feasible: instrumented data, in which every datum carries the mechanistic model that produced it, an explicit uncertainty over that model, and an executable family of counterfactuals. Verification-and-validation (V&V) instrumented image-to-simulation pipelines are one realisation: a sensor observation becomes a fully specified, solver-backed simulation with explicit, editable parameters and a propagated aleatoric/epistemic uncertainty. The substrate is case-specific, mechanistically supervised, and supports causal interventions through Pearl's do-operator. Near-term consequences for validation, auditing, and surrogate training span computational biology, climate, materials, fluid mechanics, and medical imaging; a longer-term, falsifiable implication concerns foundation models for scientific reasoning.
Daniel N. Wilke
School of Mechanical, Industrial and Aeronautical Engineering, University of the Witwatersrand, Johannesburg, South Africa