In the Tradition of Science: An Interview with Victor Ambros

I was on shaky footing with RNA interference (RNAi) and microRNAs (miRNAs), and I knew I had to do something about it. As the number of miRNAs in humans escalated and I tried to sort through the twists and turns of the compelling story of their discovery, I turned to a colleague for insight. ‘‘Interview Victor Ambros,’’ he said, and I took his advice. For those of you who might also benefit from a little primer on the topic, RNAi is a well-established phenomenon of using double-stranding RNA to effect gene silencing, and it flourished as an investigative tool years before its connection to the tiny endogenous miRNAs was made. RNAi had been first recognized in plants as a response to infections, and the cellular machinery, such as Argonaut and Dicer, to effect RNAi had also emerged. But these advances had been made without appreciating the cellular fleet of stealth molecules—miRNAs—that had piloted under our radar, scanning and tempering our genome. I asked Victor Ambros to fill me in on some of these discoveries, moments he shared with his wife Rosalind and his longterm scientific collaborator and friend, Gary Ruvkun. After I had to abort plans to visit Victor in Massachusetts, we eventually settled on a Skype interview, and I persuaded him to shoot his own photo on his computer’s photo booth (Image 1). We had a grainy connection but a lot of fun. Victor grew up on a small farm in Vermont, his father and mother having made the commitment to a rural life, where they set about raising a family of eight children. He went to MIT for undergrad, grad, and post-doctoral work, ventured down Massachusetts Avenue to Harvard for his first job, and managed to slip out of state to Dartmouth for his second. He then returned to the Boston area where he has now settled in at the University of Massachusetts, Worcester. Gitschier: What do you think funneled you into a career in science? Ambros: I’m not sure. My earliest recollection was that I dreamed of being a baseball player. But that was until about age 8 or 9. After that, I can’t recall not wanting to be a scientist, and I must trace it to reading books that were lying around the house. I just got intrigued by the tradition of doing science. I read a book about famous inventors and books about astronomers, and decided I wanted to be an astronomer. These were plans and dreams that just sort of came together without any kind of authentic, realistic experience. Just a child reading books and deciding that’s what he wanted to do. It seemed like it was a wonderful tradition to be part of—that tradition of scientists and inventors. Somebody got me a toy telescope when I was young, and I became an amateur astronomer when I was 11 or 12. I built a telescope out of a book. My father encouraged me an awful lot. He was excited that I was interested in science and he would help me with building projects. Gitschier: He was a hands-on kind of a guy. Ambros: Yeah, my dad is exceedingly clever. I’d say he is a brilliant man who, because he was born at the wrong time in Europe—in Poland—was caught up in World War II. He went to high school only for a year or so because the schools closed down at the onset of the war. He became essentially a fugitive from the Russians and Germans in Poland. He was captured by the Germans and spent the rest of the War as a forced laborer. He spent from the age of 15 to 19 having no education at all. When he was liberated by the American army, he worked for the army as an aide to some army officers, and he was exposed to a lot of books in the mansions of the exGerman rich folk, which were being used by the American army as headquarters. That’s how he began to teach himself English. By the time I was born, in 1953, I came to know my dad as someone who was very, very clever, could build almost anything, and was very well-read. It was fun to listen to him talk about books that he had read, and even today we recommend books to each other and discuss them. He speaks four or five languages. My dad is someone whom I admire enormously, especially because I felt that he was someone who had missed an opportunity to be a formally educated person, but he still made a great life for himself and his family. I remember from a very young age being very conscious of pleasing my dad because of the contrast between what I felt I had, which were all sorts of opportunities, and the opportunities that he missed. So that would help keep me on track—