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At the time, bacteria were thought to have only a rudimentary immune system, which simply attacked anything unfamiliar on sight. But researchers speculated that Crispr, which stored fragments of virus DNA in serial compartments, might actually be part of a human-style immune system: one that keeps records of past diseases in order to repel them when they reappear. ‘‘That was what was so intriguing,’’ Doudna says. ‘‘What if bacteria have a way to keep track of previous infections, like people do? It was this radical idea.’’

The other thing that made Crispr-Cas9 tantalizing was its ability to direct its protein, Cas9, to precisely snip out a piece of DNA at any point within the genome and then neatly stitch the ends back together. Such effortless editing had a deep appeal: In the lab, the process remained cumbersome. At the time, though, Doudna didn’t think much about Crispr’s potential as a gene-editing tool. Researchers had stumbled on such systems in the past, but struggled to harness them. Nonetheless, she says: ‘‘I had this feeling. You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, ‘Oh, this is going to be good’? It was like that.’’
Doudna arranged for a postdoctoral researcher, Martin Jinek, to collaborate with Charpentier’s team. After months of experimentation, they determined that Crispr relied on two separate kinds of RNA: a guide, which targeted the Cas9 protein to a particular location, and a tracer, which enabled the protein to cut the DNA. But even then, it wasn’t clear whether Crispr was anything more than a curiosity. Unlike most living things — people, animals, plants — the cells of bacteria have no nucleus, and their RNA and DNA interact in a different way. Because of that, Jinek says, it was hard to say ‘‘whether the system would be portable’’ — whether it would work in anything except bacteria. Going over the problem in Doudna’s office, Jinek began sketching the two RNA molecules on the whiteboard. In their natural form, the two are separate, but Doudna and Jinek believed that it would be possible to combine them into a single tool — one that was more likely to work in a wide range of organisms. ‘‘That was the moment the project went from being ‘This is cool, this is wonky’ to ‘Whoa, this could be transformative,’ ’’ Doudna says.

The tool Doudna ultimately created with her collaborators paired Crispr’s programmable guide RNA with a shortened tracer RNA. Used in combination, the system allowed researchers to target and excise any gene they wanted — or even edit out a single base pair within a gene. (When researchers want to add a gene, they can use Crispr to stitch it between the two cut ends.) Some researchers have compared Crispr to a word processor, capable of effortlessly editing a gene down to the level of a single letter.