The Eureka Moment: An Interview with Sir Alec Jeffreys

In 1984, while tracking the veins of globin gene evolution and panning the human genome for hypervariable linkage markers, Sir Alec Jeffreys accidentally struck gold—he discovered a way to identify any human being by a DNA ‘‘fingerprint’’. To use Jeffreys’ words, he has been ‘‘branded’’ by DNA fingerprinting, but he delights in its application and the hook it provides for public curiosity about science. Like Jeffreys himself, I wanted to dig below the surface of this discovery as well as that of another genetic nugget—the intervening sequence—found as a post-doctoral fellow seven years earlier. On the heels of my interview with Adrian Bird (published in the October issue of PLoS Genetics), I made my way to Jeffreys through another branch of the British Rail system. When I arrived at his building on the leafy Leicester campus about 45 minutes early for our appointment, his assistant suggested I get a cup of coffee while Jeffreys finished his experiment. I certainly wouldn’t have needed one. Jeffreys (Image 1) is an animated speaker, with a resonant voice and a rapid delivery of succinct clauses strung together in run-on sentences. His story could have cut through anyone’s jet lag. Gitschier: I didn’t realize that you still work in the laboratory. Jeffreys: I certainly do! Gitschier: Tell me about the experiment you were just doing. Jeffreys: Right, well, we won’t go into the gory details. Copy number variation [CNV] in the human genome is a real hot topic at the moment. Gitschier: The kind of variations people are looking for in association with autism and psychiatric diseases. Jeffreys: That’s exactly right. It’s a common phenomenon, and we’ve actually known that for decades. What we’re doing is going back to some of the absolutely classic examples of CNV. These are in my favorite gene family— the globin genes—and that’s where I cut my scientific teeth. Gitschier: We’re going to be coming back to that! Jeffreys: Right. So, what I’ve done in my scientific career is this gigantic circle, starting off in globin genes, going all around the place in forensics, and returning back to my first love. The experiment I’m doing at the moment is looking at de novo copy number variation in the fetal cglobin genes at the single molecule level in both somatic and germline DNA.