Does reflective LLM feedback survive a wet-lab-scale label budget?

Abstract

Can reflective language-model feedback improve a biological predictor when each cycle buys only one plate of labels? We separate three possible sources of benefit: proposing model edits, choosing measurements, and revising decisions through repeated feedback. We replay $36$ ProteinGym assays, starting with $96$ labels and acquiring $96$ per round for six rounds, with a sealed test set and a shared edit schema. The pre-specified comparison of full LLM control against random edits detects no advantage in test rank correlation ($Δz=-0.008$, $95\%$ CI $[-0.034,+0.018]$); equivalence is also unestablished. Exploratory ablations nevertheless identify useful model editing. With random acquisition fixed, LLM edits improve Fisher-transformed test Spearman by $0.043$ over no edits; with acquisition fixed to upper confidence bound, they improve normalized top-variant recovery by $0.023$. LLM acquisition alone does not detectably outperform fixed adaptive rules, and repeated feedback does not detectably outperform one initial recommendation under full control. Thus, the observed gains support constrained specialist editing, while the incremental value of recursive reflection remains unestablished at this label budget.