Abstract
This evidence synthesis examines orthogonal optical control in genetically encoded perturbation of protein function in living biological systems. It argues that the appropriate object of evaluation is the chain from molecular representation and chemical mechanism through synthesis, assay, optical control, and biological interpretation, not a model score in isolation. The review brings together the assigned studies with established work on uncertainty, robustness, provenance, and governance. Across these literatures, a common problem emerges: valid structures or bright signals can be mistaken for useful molecules or specific biological mechanisms without independent controls. The proposed framework separates evidence quality, model behavior, decision policy, and operational monitoring, then asks how each layer changes under distribution shift, adversarial pressure, or incomplete information. It recommends evaluation by slices and repeated trials, explicit reject and escalation policies, preservation of data and reasoning lineage, and prospective monitoring tied to defined actions. The result is a research agenda for systems that are efficient enough to use but also bounded enough to audit. No new experiment is claimed; the article develops a comparative conceptual model and identifies tests that would make future empirical claims more credible.
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