CRISPR is widely known as a powerful and precise gene-editing technology. The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for adapting it for that purpose. What is less widely known is that the underlying system was not invented. It evolved in bacteria and archaea, probably more than two billion years ago, as an adaptive immune system.

The acronym stands for Clustered Regularly Interspaced Short Palindromic Repeats. The first hints appeared in 1987, when the Japanese researcher Yoshizumi Ishino noticed a strange pattern of repeating sequences in the DNA of E. coli. Similar patterns turned up in many bacterial genomes over the following years, and nobody could explain what they were for. They were filed in the literature as a curiosity.

The function was identified in 2007, in a paper from researchers at the Danish food company Danisco. The team, led by Rodolphe Barrangou and Philippe Horvath, was practically interested in how to keep bacterial cultures used to produce yogurt and cheese alive against attacks by bacteriophages — viruses that infect bacteria. They showed that bacteria captured fragments of attacking viral DNA and stored them inside their own CRISPR loci as a kind of immune memory. When the same virus attacked again, the cell transcribed those fragments into RNA, used the RNA as a guide, and a protein called Cas cut the matching viral DNA in half.

In 2012, Charpentier, Doudna, and others showed that one of these proteins, Cas9, could be paired with a custom guide RNA designed in a laboratory. With the right guide, Cas9 would cut any DNA target a researcher chose. The natural bacterial defense had been turned into a programmable tool.

The most precise gene-editing technology in human history had already been running quietly in pond water and yogurt cultures for at least two billion years before anyone bothered to notice.