BenchBench-Cloning: Evaluating Molecular Cloning Design and Protocol Development

Abstract

Molecular cloning is one of the most routine wet-lab workflows, yet existing evaluations of language models in biology mostly test knowledge recall or isolated steps rather than end-to-end experimental planning. We introduce BenchBench-Cloning, a benchmark for large language models comprising 65 molecular cloning tasks grounded in sequence records, laboratory notebooks, and published experimental studies. Planning a molecular cloning experiment requires defining a set of constructs needed for a scientific objective and a construction route to produce them. BenchBench-Cloning contains 50 protocol-development tasks, in which agents produce an executable protocol for a specified construct, and 15 construct-design tasks, in which agents determine the constructs a scientific objective calls for. Protocol-development tasks are evaluated by execution in a cloning simulator; construct-design tasks are evaluated with task-specific deterministic checks and, where needed, rubric-based LLM-as-a-judge evaluation. Across eight systems with repeated attempts per task, GPT-6 Astra scores highest at 30.6%, with the others between 8.6% and 22.2%, and the benchmark remains unsaturated under best-of-ten sampling. As integrating individual cloning decisions into complete, valid plans remains challenging even for frontier models, we expect BenchBench-Cloning to serve as a useful benchmark for tracking progress in experimental planning.