In this interview, William Bialek, John Archibald Wheeler/Battelle Professor Physics, and a member of the Lewis-Sigler Institute for Integrative Genomics. Bialek recounts his familys Jewish heritage in Europe and their observances of Jewish ritual during his childhood in San Francisco. He connects his natural curiosity to early interests in math and scientific theory which led to a formative high school experience learning about biophysics at UCSF. Bialek describes his undergraduate experience at UC Berkeley and he surveys the allegiances and separations between the science departments. He explains how his interests in connecting theory to biophysics led him to John Hopfield and why he decided to remain at Berkeley for graduate school under the direction of Alan Bearden. Bialek discusses his postgraduate research in the Netherlands where he found a strong tradition of biophysics research and where he developed a long term collaboration with Rob de Ruyter. He explains his decision to pursue his second postdoctoral appointment at the ITP at UC Santa Barbara, where he found a multidisciplinary research that fit his interests. Bialek explains that the opportunities that allowed him to return to Berkeley as a faculty member with joint appointments in Physics and Biophysics. He narrates the story of the threat of not getting tenure in the Physics Department and he explains his decision to leave Berkeley for a position at NEC in New Jersey. Bialek relates a reassuring conversation with David Gross that he would be connected to Princeton during his time at NEC. He narrates the origins of NEC and how his research agenda fit within it and he talks about the collaborations that led to the book Spikes. Bialek describes the eroding management culture at NEC and the opportunity that he had to join Princetons faculty and Lewis-Sigler. He talks about his interests in signal processing and information flow in neuroscience, and he reflects on the opportunities that biophysics presents for the broader integration of theory and experiment. At the end of the interview, Bialek addresses some of the deep questions posed by neural networks, he considers the notion of metaphysics, and he explains why he sees his research accomplishments not as revolutionary but as part of a foundation of future discovery.