Brett Lindenbach: Deconstructing and reconstructing hepatitis C

H epatitis C virus (HCV), discovered almost 20 years ago, was resistant to being researched. Despite multiple attempts, researchers simply could not get this human pathogen to grow in culture. Lindenbach, as a young and enthusiastic graduate student had grand ideas about studying HCV, but fearing a dead-end project for a PhD student, his supervisor advised Lindenbach to work on the more willing yellow fever virus. The advice was wise; Linden-bach passed his PhD, after making yellow fever yield the secret of how a secreted protein could control viral replication inside the cell (1, 2). Lured by the success, Lindenbach started a post-doc studying other research-friendly viruses. But his satisfaction was shallow, and the puzzle of how to grow HCV was continually on his mind. In 2005, Lindenbach cracked the puzzle. He built a new, artifi cial HCV (3) that could not only replicate in culture, but could also infect animals (4), proving that it was just like the real thing, only now researchable. When did you get interested in science? I was interested in science at an early age, but both my parents were artists, so I didn't have a lot of exposure to science. My dad encouraged my interest, because he thought it was diffi cult to make a living as an artist—I don't think he realized that science is just as hard! But also, I think it was a way for him to live the scientifi c life vicariously—he had technical leanings. I actually became interested in viruses in middle school. I thought they were really cool. I remember reading a book that described the fi rst genome ever sequenced. It was a small bacteriophage and its entire genome was written on half a page in the book. I thought to myself, " I can't believe that this is everything that little virus needs. " It blew my mind. Where did you go to college? I went to the University of Illinois and majored in general biology. I was not sure what to do after college, but then I had a really great experience working as a tech in the laboratory of Ralph Wolfe. He studied archaebacteria, in particular methano-gens, and I became fascinated. Not with methanogenesis per se, but with working in the laboratory. I decided I would go to graduate school and enrolled at Washing-ton University in St. Louis. I studied for a PhD with …