HypoEvolve: Genetic Algorithms Enable Multi-Agent LLMs to Discover Scientific Hypotheses
HypoEvolve couples a generational genetic algorithm with specialized LLM agents to generate drug-repurposing hypotheses, beating six baselines on DepMap selectivity (0.171 vs 0.115).
HypoEvolve coordinates specialized LLM agents through a generational genetic algorithm in which scientific judgments and new proposals reshape a hypothesis population. Evaluation centers on drug repurposing, linking mechanistic explanations to target-level biological claims assessed via external measures adapted from DepMap and Open Targets. Across 34 cancer types, HypoEvolve scores highest against six baselines on both measures, with DepMap selectivity of 0.171 versus 0.115 for the strongest baseline, and gains generalize to held-out cancer types.
- Genetic algorithm coordinates specialized LLM agents over evolving hypothesis populations
- Drug repurposing ties generated hypotheses to target-level biological claims
- DepMap and Open Targets adapted as external evaluation measures
- DepMap selectivity 0.171 versus 0.115 for strongest baseline across 34 cancer types
- Gains over single-pass generation hold on held-out cancer types
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Scientific agents contribute to hypothesis discovery by synthesizing evidence, assessing proposals, and developing new explanations. Recent systems combine scientific agents with evolutionary search through critique, comparison, and revision. However, how different forms of agent collaboration affect hypothesis quality remains an open question. Answering this question requires separating the effects of agents' scientific capabilities from those of their collaboration. A framework must therefore preserve agents' scientific roles and support rules for combining, revising, and retaining hypotheses. Building on this view, we introduce HypoEvolve, which makes collaboration explicit through successive updates to a hypothesis population. Specifically, we propose a generational genetic algorithm to coordinate specialized large language model (LLM) agents that integrate mechanistic arguments, reconsider assumptions, and assess evidence and testability. Each generation specifies how scientific judgments and new proposals reshape the population, making collaboration effects on hypothesis quality directly testable. Moreover, we design our evaluation around scientifically meaningful hypotheses that explain how a proposed intervention could work. Drug repurposing links these explanations to target-level biological claims assessed against external evidence. Specifically, we adapt DepMap and Open Targets into complementary external measures grounded in experimental, genetic, and clinical evidence. Across 34 cancer types, HypoEvolve achieves the highest scores against six baselines on both measures. DepMap selectivity reaches 0.171, versus 0.115 for the strongest baseline. Gains over single-pass generation also generalize to held-out cancer types. HypoEvolve advances a vision of autonomous science in which AI research teams achieve a capacity for discovery beyond that of individual models.
Text extracted automatically; images, tables and formatting may be missing. Original: https://arxiv.org/abs/2609.15938