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CRISPR-Cas9 has transformed biology by providing a new tool for genome editing. This key experiment reveals how Doudna, Charpentier and colleagues discovered how to repurpose a molecular machine, which normally protects bacteria against viruses, into a programmable tool that can be used to edit the nucleotide sequence of a genome. The key experiment, which sparked the genome editing revolution, is a simple but nonobvious test-tube reaction that could be performed in an afternoon.

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