Interview with John Spence, Richard Snell Professor of Physics at Arizona State University. Spence discusses his dual role as a Director of Science at NSF and his focus on research at the intersection of biology and physics. He recounts his childhood in Australia and his undergraduate education at Queensland University. Spence describes his graduate research on plasmons at Melbourne and the opportunities that led to his postdoctoral appointment at Oxford, where he worked with Mike Whelan and David Cockayne on quantifying atom arrangements in solids. He describes his decision to join the faculty at Arizona State, and the nascent field of high-resolution electron microscopy, which compelled him to write a book on the topic. Spence discusses his work on the structure of defects in superconductors and his collaborations with Bell Labs, and he explains the significance of the LCLS to his research. He describes the BioXFEL project, his work as part of the broader community of crystallographers, and the intellectual origins of the book "Lightspeed". At the end of the interview, Spence credits Michael Crow for bringing ASU to the forefront of so much innovation in science, and he reflects on how physics has never failed to surprise him.