Evaluating calibrated refusal and safe usefulness in dual-use biology settings

Frontier large language models are increasingly deployed as orchestration backbones for biological research workflows, yet no shared evidence base exists for comparing their refusal behaviour on legitimate research prompts. RefusalBench, introduced here, is a matched-triple benchmark of 141 prompts in 47 bundles that holds task framing constant while varying only biological risk tier (benign, borderline, dual-use), enabling tier-conditioned comparisons robust to subdomain confounding. A 15-prompt should-refuse positive-control module establishes per-model calibration floors; three models fail to refuse even these prompts. Across 19 frontier models in the May 2026 snapshot, strict refusal rates span 0.1% to 94.6% on identical prompts. Jurisdiction does not predict refusal in this snapshot (Mann-Whitney U, p = 0.393; EU n = 1, US bimodal); provider identity does, with Anthropic's API stack predicting refusal at OR = 21.03 (95% CI: 14.58-30.34 prompt-clustered; 5.70-77.55 under model-clustered GEE). This effect is best read as access-path-level rather than model-weight-level: 99.8% of Anthropic's strict refusals carry the same safety_policy adjudicated reason code, consistent with a small set of canonical refusal templates rather than case-by-case model reasoning. Strict refusal rate misranks safety calibration: Grok 4.20 achieves the highest tier discrimination (Youden's J = 0.787) while ranking only seventh by overall refusal rate, and Claude Opus 4.7's J dropped 65% from prior versions with no improvement in dual-use detection. Nine of 18 frontier models exhibit a hedge-but-help partial-compliance pattern at dual-use tier that binary refusal metrics cannot detect.

Large language models (LLMs) are rapidly acquiring capabilities relevant to biological research, from literature synthesis to interpretation of experimental data. Increasingly, LLM agents can also perform in silico biology tasks that previously required experienced human biologists. These emerging AI capabilities offer new opportunities for scientific discovery and biomedical advances, but they also shift the landscape of biosecurity risks. To address this, we introduce the Agentic Bio-Capabilities Benchmark (ABC-Bench), a suite of tasks to measure agentic biosecurity-relevant capabilities. ABC-Bench evaluates LLM agents on both benign and dual-use biology tasks: writing code to operate liquid handling robots, designing DNA fragments for in vitro assembly, and evading DNA synthesis screening. These tasks require a combination of biology and software expertise. All tested LLM agents outperformed the median expert human baseliner on all three tasks. Agents performed highly on tasks drawing on published knowledge and well-documented protocols, and more weakly on a task requiring novel bioinformatics reasoning. In three wet-lab validation experiments, we found that OpenAI's o4-mini-high produced scripts that, when run on an OpenTrons liquid handling robot, successfully assembled DNA with expected sequences.

This paper addresses a rapidly emerging policy challenge: how to generate and interpret credible evidence about the biological capabilities and risks of AI scientists, or agentic AI systems capable of autonomously or collaboratively performing multi-step scientific tasks. As these systems enter real research workflows, decision-makers increasingly face evaluation results whose meaning depends on underlying design choices that are often implicit or under-documented. We synthesize current evidence on AI-enabled biological risks and introduce biological agentic evaluations as a promising, but interpretation-sensitive, tool for assessing these systems. Our central contribution is a set of practical, experience-grounded considerations -- drawing from our own evaluations -- that show how choices around defining, designing, running, scoring, and documenting evaluations materially shape what results do and do not imply about risk. The analysis is intended to help policymakers interpret biological evaluation outputs with appropriate caution; guide public and private funders toward high-leverage investments in AI-biology evaluation research; and support biosecurity practitioners assessing emerging AI systems. A secondary audience includes researchers designing or conducting agentic evaluations within frontier AI labs, AI providers, scientific institutions, and third-party evaluation organizations.