Bill Pak's Vision: The Neurogenetics of Phototransduction

We have created a special issue of the Journal of Neurogenetics to honor Bill Pak in the year of his 80th birthday. His research program has been in place at Purdue University since 1965. The research efforts from his laboratory tell a remarkable story of focus and steady progress towards the understanding of the process of phototransduction: How does a photoreceptor cell convert a photon of light into a physiological response that is communicated to the nervous system? There is no question that there has been great progress in the understanding of phototransduction. Bill Pak ’ s research efforts span a time frame in which little was known about the molecular workings of the light response. The story now is much different. We now have a very solid understanding of the molecular machinery and biochemical processes responsible for the phototransduction response. We also know that there are two major classes of photoreceptors, microvillar and ciliary photoreceptors, and two different signaling pathways in each of these classes. Although historically these two classes were viewed as distinct invertebrate and vertebrate forms of a photoreceptor, we now know that both types of photoreceptors can be found in a single species, and that both are represented in most major divisions of the animal kingdom. Bill ’ s PhD training was in physics, initially specializing in characterizing the properties of high-energy cosmic rays. He transitioned to biology research while working as a postdoctoral at University of Chicago. In 1965, Bill started as an assistant professor at Purdue University. He brought with him research expertise in electrophysiology on the vertebrate retina, in particular the very rapid lightevoked response called the early receptor potential. His initial research at Purdue continued to use electrophysiology to study vertebrate photoreceptors. It was during this time that he made a profound and infl uential decision to bring a genetic approach to the study of vision. The approach has provided a wealth of valuable experimental tools and created a fi eld that both dominated his research career and provided inspiration, insights, and opportunities for his trainees and other scientists to develop their own scientifi c careers. His decision was to use Drosophila as a model organism, and approach the problem of phototransduction using the genetic analysis of vision-defective mutants (Alawi et al., 1972; Pak et al., 1969, 1970; Pak & Pinto, 1976). Of course, in hindsight, this looks to be an easy decision, given the success of the endeavor, and of course the myriad profound advances in developmental biology, cell biology, and physiology made possible by this experimental system. However, Bill will be among the fi rst to tell you of the skepticism he heard in the 1960s, such as might be phrased as “ Phototransduction is too fast a process to involve biochemical steps controlled by the enzymes directly under genetic control, ” “ The process of vision in Drosophila seems to be so specialized that it won ’ t apply to other animals, ” and “ Vision and other nervous system functions are so closely connected that most visual defi cits having a genetic basis will also cause lethality. ” For these and other reasons, a commitment to using a genetic approach in Drosophila required some resolve. To be fair, there was also a sense that a genetic approach was needed to understand processes such as vision. About this same time, others would also successfully use systematic searches for Drosophila mutations affecting complex processes in higher organisms. Closest to Bill ’ s efforts were those of Seymour Benzer and Martin Heisenberg, as these two researchers capitalized on the phototactic (Benzer, 1967; Hotta & Benzer, 1969) and optomotor (Heisenberg, 1971) visual behaviors of Drosophila . All three scientists have played major roles in generating the momentum for using Drosophila as a model organism for neurobiological studies. Bill ’ s efforts are distinguished by a focus and long-term commitment to the study of process of phototransduction. Bill ’ s major contributions are well documented within the scientifi c literature. His group has isolated vision-impaired Drosophila mutants that identify more than 60 different complementation groups (Pak, 1995). Ching Kung gave a humorous perspective on the effort in a presentation in 2002 (see Figure 1). At least 20 of these genes have been subjected to extensive molecular characterization (Hardie, 2012; Montell, 2012; Pak, 2010). One result is that Drosophila is now the premier research