§14 · feasibility map

Disease promoters are R19 switches; the corrective sign is mechanism-forced, orthogonal to γ

The map extends to disease: 25 cancer and neurodegeneration promoters (SNCA shallowest, HTT deepest) are each R19 switches, flip-drive ordered by measured γ. The corrective drive's sign is forced by mechanism (gain-of-function → −, loss → +), orthogonal to γ. A reversible Lever-B drive reaches every switch; coding lesions need Lever-A. Cross-package γ reproduces with no tuning. [F]/[V]/[O].

DM1 maps 25 disease promoters (16 oncology, 9 neurodegeneration; shallowest SNCA γ 1.2490, deepest HTT γ 1.6142). DM2: the mechanism-forced corrective sign corrects every gene and is orthogonal to γ (point-biserial -0.0148). DM4: the cross-package γ for four shared loci reproduces against reference with no tuning.

Cancer and neurodegeneration promoters are the same R19 switches

The disease panel spans 25 promoters — 16 oncogenes/suppressors and 9 neurodegeneration loci. Every one is an R19 bistable switch and the absolute flip-drive is monotone in measured γ, from the shallowest (SNCA, γ 1.2490) to the deepest (HTT, γ 1.6142).

The corrective sign is forced by mechanism, not by γ

Difficulty (γ) says how hard a switch is to move; it does not say which way to push. The corrective direction is forced by the disease mechanism — a gain-of-function lesion is corrected by a negative (silencing) drive, a loss-of-function lesion by a positive (activating) drive — and this forced sign corrects every gene in the panel, while the opposite sign does not. The sign is orthogonal to γ: its point-biserial correlation with the γ order is -0.0148, and the γ ranges of the plus-sign and minus-sign genes overlap. Operationally this is a two-lever decision: a reversible Lever-B expression drive reaches every switch (required drive growing with γ, with HTT nearest a tolerable cap), whereas a broken coding sequence is reserved for the irreversible Lever-A edit that the promoter γ does not read.

Cross-package reproduction: the same γ with no tuning

The honesty gate is the same as for RNA — a self-contained “corrected” verdict is a Δh-replay, not evidence. What the package can verify is that its measured γ is anchor-determined, not fitted: four loci shared with the other packages reproduce the same γ to four decimals, computed independently and with no tuning.

The reachability, ordering, and corrective sign are read or forced; the absolute dose, the tolerable cap, and the coding-lesion magnitude remain [O], and clinical care is handed to clinicians.