The Philosophical Approach: An Interview with Ford Doolittle

For years, the whiteboard in my office brimmed with ideas for potential interviewees. Names were erased when an interview was completed, and new names added when a particular topic piqued my interest. Some were arranged in a kind of Venn diagram by their fields, and one such cluster—concerning the origins of early life forms—included three deep thinkers: Lynn Margulis, whose 1967 paper articulated the endosymbiotic origin of mitochondria and chloroplasts; Carl Woese, whose attempts to classify prokaryotes based on ribosomal RNA cataloging led to his championing the new kingdom of Archaea in 1977; and Ford Doolittle (Fig 1), who provided evidence for Margulis’s hypothesis using Woese’s methods. Though Woese and Margulis are now deceased, Doolittle, I can attest, is very much alive and, dare I say, “kicking!” Over time, Doolittle has cogitated on a variety of intriguing evolutionary questions, including the origin of introns, the role of lateral gene transfer in speciation, and the meaning of “function.”He is always worth listening to. Doolittle grew up in Champaign-Urbana, Illinois, the son of an art professor and now holding a BFA in photography himself. As a high-school friend of the late Sol Spiegelman’s son, he worked with Spiegelman in the summers. Following undergraduate studies at Harvard and graduate work with Charles Yanofsky at Stanford, he returned to Spiegelman’s lab for postdoctoral work and then joined Norman Pace when Spiegelman moved to New York. Since then, Doolittle has spent his career in Halifax, Nova Scotia, at Dalhousie University. Last year he was awarded Canada’s highest scientific prize, the Gerhard Herzberg Gold Medal in Science and Engineering, and plans to pursue philosophical and biological questions with its largess. I was able to learn a lot more about these pursuits one warm morning in autumn when he was visiting the Bay Area. Gitschier: Let’s start with Urbana and the atmosphere with Sol Spiegelman and Carl Woese. Doolittle: Sol Spiegelman was a major figure who should have gotten the Nobel Prize, I think. For example, he was among the first to prove the existence and nature of messenger RNA. Woese was in Urbana when I did my first postdoc with Sol. Carl was a big influence on Sol’s students, because Sol was a remote figure in some ways—very inspirational, but very intimidating. But Carl was a drinking companion of Sol’s graduate students and postdocs. That’s how I got to know him and was primed to think about evolutionary problems. Gitschier: And what were you all working on back then? Doolittle: Sol was working on RNA tumor viruses and Q-beta RNA phage at that time. One of the things that got me interested in evolution was that Sol did these famous experiments on the Q-beta “mini-monsters.” You’re selecting for more rapidly replicating RNAs, so you get