In the target article “How molecules became signs” I offer a molecular “thought experiment” that provides a paradigm for resolving the major incompatibilities between biosemiotic and natural science accounts of living processes. To resolve these apparent incompatibilities I outline a plausible empirically testable model system that exemplifies the emergence of chemical processes exhibiting semiotic causal properties from basic nonliving chemical processes. This model system is described as an autogenic virus because of its virus-like form, but its nonparasitic self-repair and reproductive (...) dynamics. The 16 commentaries responding to this proposal recognize its material plausibility but are divided on its value in resolving this basic biosemiotic challenge. In response, I have addressed some of the most serious criticisms raised and have attempted to diagnose the major sources of incompatible assumptions that distinguish the autogenic paradigm from other major paradigms. In particular, I focus on four main issues: the significance of the shift from a cellular to a viral perspective, the relevance of intrinsic versus extrinsic initiation and channeling of interpretive work, the insufficiency of molecular replication as a basis for grounding biological semiosis, and a (universal?) three step scaffolding logic that enables referential displacement of sign vehicle properties without loss of referential continuity (as exemplified by DNA-protein relations). Although I can’t conclude that this is the only way that biosemiotic properties can emerge from physical-chemical relations that otherwise lack these properties, I contend that this approach offers a biologically plausible demonstration that it is possible. (shrink)