Lethal Mutagenesis

Lethal mutagenesis is the deliberate induction of an information catastrophe in a viral or microbial population by pushing its mutation rate above the error threshold. The strategy exploits a fundamental vulnerability of all replicating systems: if you increase their error rate enough, their encoded information collapses faster than selection can restore it. The population does not merely become sick — it loses the ability to maintain its own genomic identity and drifts into mutational meltdown.

The approach was first proposed theoretically in the context of Eigen's quasispecies model and has since been demonstrated experimentally against RNA viruses including poliovirus and influenza. Ribavirin, a mutagenic drug already in clinical use, operates in part through lethal mutagenesis by depleting the intracellular pool of correct nucleotides and forcing the viral polymerase to incorporate errors at a catastrophic rate. The therapeutic beauty of the strategy is that it targets a universal constraint rather than a virus-specific protein, making resistance evolution theoretically much more difficult.