Andrew Fire (Carnegie Institution) and Craig Mello (University of Massachusetts Medical School) published in 1998 'Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans', describing a previously unknown cellular mechanism: when injecting double-stranded RNA (dsRNA) into the worm C. elegans, they observed that it silenced specific genes far more potently than the single-stranded RNA used previously in similar experiments — an observation that contradicted the prevailing intuition in molecular biology. The mechanism, called RNA interference (RNAi), turns out to be an evolutionarily ancient cellular defense system conserved in plants, animals, and humans, which destroys specific messenger RNA via the RISC protein complex guided by small RNA fragments (siRNA). The discovery simultaneously resolves previously unexplained phenomena in plants ('co-suppression', observed since 1990) and opens a completely new avenue for selectively silencing any gene for research or therapeutic purposes. RNAi becomes a standard laboratory tool in subsequent years and a therapeutic platform — the first siRNA-based drugs (patisiran, 2018) receive FDA approval twenty years after the original paper. The discovery is also conceptually prior to CRISPR: both are natural gene regulation/defense systems redirected by humans toward targeted gene editing and silencing.