Do Biological Structural Guarantees Earn Their Complexity?

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.

Large language model agents increasingly plan, execute, and interpret biological analyses, yet fluent responses, successful tool calls, and benchmark performance alone do not establish scientific credibility. Existing reviews primarily organize biological agents by application, architecture, and agentic capability, but do not jointly operationalize the accountability of agent-generated workflows. We address this gap by treating the inspectable workflow trajectory, rather than architecture or final output alone, as the primary unit of analysis. We introduce the Function--Evidence--Validation (FEV) framework, which separates demonstrated workflow operations, traceable support for actions and claims, and use-case-specific validation. Using FEV, we map 109 agentic or agent-adjacent systems and 28 benchmark or evaluation resources, representing 128 unique publications across genomics, single-cell and spatial omics, protein science, drug discovery, computational pathology, and general bioinformatics automation. Across domains, planning and tool-mediated execution have advanced more rapidly than replayability, provenance, robust scientific assessment, external validation, and prospective empirical testing. We therefore argue that agentic bioinformatics should be assessed through workflow correctness rather than final-answer correctness alone. FEV provides a practical basis for comparing systems and designing transparent, auditable, and scientifically accountable bioinformatics workflows.

Reproducing and comparing deep research agents today is hard: the same backbone evaluated on the same benchmark can report different accuracies across papers because the harness and tool registry differ, and integrating a new model into a comparable evaluation surface costs weeks of model-specific engineering. These are symptoms of a broader reproducibility problem in deep research agent research. Here, we introduce BioMedArena, an open-source toolkit that addresses this reproducibility gap and provides an arena for comparing deep research agents under a shared evaluation environment. BioMedArena decouples six layers of biomedical agent evaluation -- benchmark loading, tool exposure, tool selection, harness mode, context management, and scoring -- and exposes 166 biomedical benchmarks and 75 biomedical tools across 9 functional families. Adding a new model, benchmark, or tool can be accomplished with a few-line provider adapter. Beyond evaluation infrastructure, BioMedArena ships a library of high-quality reference components: 6 agent harnesses (including our proposed Mutual-Evolve) and 6 context-management strategies, any of which can be equipped on any backbone. Equipping these components substantially improves all 12 backbones; on each of 8 representative biomedical benchmarks, the best equipped backbone surpasses prior state-of-the-art (SOTA), by 15.01 percentage points on average. The toolkit, configurations, and per-task traces are available at https://github.com/AI-in-Health/BioMedArena.