Why it is a question
Zhao, Wytock, Reynolds and Motter (LIT-854, read in full in NOTE-655) show that in an ensemble of sign-consistent Boolean rules on the 87-gene core of the E. coli regulatory network, clamping one gene and releasing it often leaves the network in a different attractor (THEORY-178). In the model the new state is permanent by construction. In cells, noise and division may make it only long-lived, as the authors expect. The one comparison with data is evolution under a permanent crp knockout, which is not a temporary disturbance. NOTE-655 lists the cell experiment as its first open question. Until 2026-10-19 it was THEORY-178’s promote_when. THEORY-178’s body disclaimed it, so the clause moved here when the title was narrowed to the model.
What would answer it
An experiment in bacteria, read first-hand, in which a gene is perturbed transiently (for example by inducible CRISPR interference, then released) with the growth environment held fixed, and other genes stay in their changed expression state for many generations after the perturbation is gone. Slow return must be excluded (THEORY-136’s standard): either by following the culture until the state has outlasted any plausible relaxation time, or by showing that unperturbed cells started from the other state hold it under the same conditions. The paper’s candidates are crp as the perturbed gene, with zraR, melR or rhaRS as responders. It would answer no for this network if well-powered transient perturbations of those genes are always followed by a return to the starting state.
What would not answer it: further simulations or rule ensembles; agreement with strains evolved under a permanent knockout; and environmentally induced bistable switches such as the lac operon, which were known before and are not perturbations of regulation alone.