The discovery of CRISPR in archaea and bacteria

CRISPR‐Cas are self‐/nonself‐discriminating systems found in prokaryotic cells. They represent a remarkable example of molecular memory that is hereditarily transmitted. Their discovery can be considered as one of the first fruits of the systematic exploration of prokaryotic genomes. Although this genomic feature was serendipitously discovered in molecular biology studies, it was the availability of multiple complete genomes that shed light about their role as a genetic immune system. Here we tell the story of how this discovery originated and was slowly and painstakingly advanced to the point of understating the biological role of what initially was just an odd genomic feature. Clustered, regularly interspaced short palindromic repeats (CRISPR), present in the genome of archaea and bacteria, are separated by spacer sequences derived from fragments of foreign nucleic acids. CRISPR‐RNA molecules, containing a single spacer, guide CRISPR‐associated (Cas) proteins to spacer‐complementary sequences in invader genomes to cleave a matching target, providing prokaryotes with a unique, heritable, and adaptive immune system.