INTERVIEW
Precision engineering
Biochemist and co-inventor of CRISPR gene-editing technology
Jennifer Doudna talks to Tom Ireland about one of the biggest science stories of the decade
In 2012 American biochemist Jennifer Doudna and her collaborator, Emmanuelle Charpentier, proposed that CRISPR – a group of genes and molecules used by bacteria to recognise and destroy viral DNA – could be repurposed as a powerfully simple and programmable geneediting tool.
Their work led to an explosion of interest in CRISPR and exciting new applications of gene-editing across all areas of biology. With its unprecedented efficiency and ease of use, CRISPR has not only supplanted all previous genetic engineering technologies, but has revolutionised what is possible in life science – at the same time raising profound questions about what society should and should not do with such powerful technology.
Born in Washington DC, Doudna moved to Hilo, a large town in Hawaii, aged seven. At College, after briefly considering ditching chemistry to major in French, she stuck with science, eventually gaining her PhD in biological chemistry and molecular pharmacology from Harvard in 1989.
Before CRISPR, Doudna and her laboratory (now based at the University of California, Berkeley) focused on how RNA molecules can act as chemical catalysts as well as messengers in cells. Doudna’s laboratory was the first to deduce the structure of a ribozyme – that is, a length of DNA that acts like an enzyme.
Doudna then focused on RNA interference, a process in which RNA molecules regulate gene expression or translation. It was this work that led to a meeting with Jill Banfield, a Berkeley microbiologist who at the time was trying to understand mysterious sequences of bacterial DNA known as clustered regularly interspaced short palindromic repeats – or CRISPR for short.
After years at the centre of intense media interest and patent disputes over the gene-editing technology, Doudna continues to work on the fundamental biology of CRISPR bacterial defence systems, of which there are many types, and she is a key figure in discussions on the safety and ethics of CRISPR-based technologies.
“The wave has only got bigger. So many things are happening right now on so many fronts”
So many interesting breakthroughs in science involve chance conversations, introductions and collaborations – tell me about why Jill Banfield introduced you to these weird bacterial DNA sequences called CRISPR when you were working on RNA interference in eukaryotic cells. Well, it was exactly because we were working on RNA interference that my laboratory and our research came to Jill’s attention. She was studying bacterial genomes, and particularly these DNA sequences that, at the time, were of unknown function, but had signatures that made them appear to be made up of viral DNA. Jill and just a handful of others at the time had postulated that these curious sequences, which had come to be called CRISPR, might be some kind of RNA-based adaptive immune system, although nobody at the time had any experimental evidence of that.
Crucially Jill had the insight that these systems might be controlled by RNA, and that was her purpose in reaching out to me. It sounded possible that bacteria had evolved a system for defending against viruses that was in some ways very similar to the RNA interference that goes on in eukaryotic cells.
Do you remember your first introduction to the intricacies of CRISPR, which was of course completely obscure at the time? Yes, I remember it very well. Jill and I met at a coffee bar on the Berkeley campus known as the Free Speech Movement Café – a very Berkeley sounding place! We were sitting out on the patio and Jill had a big stack of papers in front of her.
She was showing me all these examples of repetitive DNA sequences from bacteria that seemed to include sequences that came from viruses. At the time, for me, it was like drinking from a fire hose. There was a lot of data and I was struggling to understand, but Jill was clearly very excited and I really had a feeling that this was something potentially very interesting.
10 / The Biologist / Vol 66 No 5
