The Crispr Quandary

Jennifer Kahn in The New York Times:

One day in March 2011, Emmanuelle Charpentier, a geneticist who was studying flesh-eating bacteria, approached Jennifer Doudna, an award-winning scientist, at a microbiology conference in Puerto Rico. Charpentier, a more junior researcher, hoped to persuade Doudna, the head of a formidably large lab at the University of California, Berkeley, to collaborate. While walking the cobblestone streets of Old San Juan, the two women fell to talking. Charpentier had recently grown interested in a particular gene, known as Crispr, that seemed to help flesh-eating bacteria fight off invasive viruses. By understanding that gene, as well as the protein that enabled it, called Cas9, Charpentier hoped to find a way to cure patients infected with the bacteria by stripping it of its protective immune system.Among scientists, Doudna is known for her painstaking attention to detail, which she often harnesses to solve problems that other researchers have dismissed as intractable.

…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.

…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. Even more surprising was how easy the system was to use. To edit a gene, a scientist simply had to take a strand of guide RNA and include an ‘‘address’’: a short string of letters corresponding to a particular location on the gene. The process was so straightforward, one scientist told me, that a grad student could master it in an hour, and produce an edited gene within a couple of days.

More here.