My roots did not originate in science. I was born in Hollywood; my mother, Evelyn, was a former stage actress and my father, Eugene, a novelist and screen/television writer. I went to elementary school with Michael Jackson and many of my high school friends pursued theatrical careers. However, I was attracted to science rather than drama. My parents, neither college educated, had broad interests and were voracious readers. My mother stimulated my interest in science by taking me to science museums. In middle school, my father took me to public lectures in astrophysics. I learned that science was as creative as the arts. There were amazing mysteries of nature waiting to be solved; perhaps one day I could solve one. If you had asked me what I wanted to become when I was 8 years old, I would have said “a scientist”.
The dream of becoming a scientist became more real in high school. For my 10th grade science project at Hollywood High, I turned our basement into an experimental lab to measure circadian rhythms (the 24 hr biological clock) of the leaf movements of bean plants. Based upon this project, my high school counselor contacted Dr. Karl Hammer at UCLA, and he allowed me to continue my own experiments there. Doing science, in contrast to studying it in school, was seducing, captivating and cemented my desire to become a scientist. My high school counselor encouraged me to submit my work to the Westinghouse Science Competition and I was lucky to be selected as one of the top 40 students in the country. While I did not win a medal, I did meet other high school students who shared my interest in science, which was eye-opening and encouraging.
I attended the College of Creative Studies at the University of California Santa Barbara, which promoted independent study. I went there partially because I admired Dr Beatrice Sweeney’s work on circadian rhythms. She was a dynamo; through her, I witnessed how a passion for science could remain strong throughout a career and into older age. During the summers, I worked on hormones and growth control in C Fred Fox’s laboratory at UCLA. Fred was very generous and allowed me to work on my own project. During my senior year, I also worked for six months with Robert Lefkowitz at Duke University during the exciting time when his Nobel Prize winning work was being conducted.
After college, I entered the MD/PhD programme at Stanford University in 1980 and was a PhD student with Eric Shooter, a wonderful mentor, working on nerve growth factor receptors. I became interested in axonal transport and was fascinated by the breakthrough made by Mike Sheetz and Jim Spudich on developing an in vitro assay for muscle motility. After talking to Mike, we decided to work on the mechanism of axonal transport at the Marine Biological Laboratory, Woods Hole where we teamed up with Bruce Schnapp and Tom Reese. This great collaboration led to the development of in vitro microtubule-based motility assays and the discovery of a new microtubule motor protein, kinesin.
Given how well research was going, I decided not to finish my MD degree and instead accepted a faculty position at UCSF. UCSF was an energizing environment for a young cell biologist, and I had fantastic junior and senior colleagues. At UCSF, I continued my pursuit of motor proteins, including an early collaboration with my fellow Shaw Prize laureate and hero Ian Gibbons. In the 1990s, the mechanism by which kinesin works got filled in step-by-step like solving a jigsaw puzzle, aided by advances in single molecule assays and clues from crystal structures. This tiny machine, unknown 15 years earlier, became alive with vivid details of how it converts ATP energy into movement. In 2004, our attention turned to cytoplasmic dynein, which is ~8-fold larger than kinesin. We began a new journey to understand its mechanism, and, over the next ten years, details of how dynein works began to unfold. This exciting adventure also involved collaborations with Dr Gibbons. Our recent work extended in new directions including T cell signaling, mitosis, and RNA biology.
My love of science also nucleated an interest in science education and outreach. I feel a sense of responsibility to ignite in others the same wonderment and interest in science that I have felt since my childhood. These interests led me to co-direct a course at the MBL, promote science in India, start the iBiology.org project, found ASAPbio.org, and tackle additional projects to democratize global access to science.
Receiving the Shaw Prize is an unexpected and wonderful honour, and one for which I am very grateful. However, my biggest reward has been the opportunity to pursue my childhood dream of becoming a scientist and pursue a career devoted to curiosity and learning.
26 September 2017 Hong Kong