I was able to become a scientist because my father and mother made educational opportunity for my brother Paul and me their highest priority. My parents did not have the opportunity for advanced education. My father was born in the 19th century and left his family’s farm after learning everything offered in a one-room schoolhouse. My mother grew up in Oklahoma and began university at the University of Chicago but had to drop out during the worst of the Great Depression, when her father lost his job, her mother died, and her family went bankrupt. My brother and I were protected from any hardship, living north of Chicago near a very fine public high school. In high school, I learned the beauty of mathematics. From my very fine high school English teacher, I learned to treasure the English language, to value those who have used it well, and to write clearly myself. For 50 years my goal has been to teach as well as I was taught; I am still working at it. Emboldened by my math teachers, I majored in mathematics at Carleton College, even though I clearly was not strong enough to be a theoretician. But my college professors recognized my interest and suggested I consider graduate school in statistics or applied math, in particular at Berkeley. It was 1966 and I needed no more encouragement.
In my first year as a graduate student at Berkeley, I had the extraordinary good luck to wander into the genetics course taught, for the last time before his retirement, by Curt Stern. His lectures still resonate for their clarity, elegance, and whimsy. Genetics was a collection of beautiful puzzles. One could disentangle hopelessly knotty data into rational strands based on Mendelian logic, propose solutions to relationships among the strands, and test them, with flies from Strawberry Canyon offering the perfect experimental system. I couldn’t believe people were paid to do this. With the blessing and continued support of my advisors from statistics, I transferred to genetics and have never looked back.
Life as a graduate student at Berkeley was tumultuous. Becoming an experimental geneticist with no background in biology or chemistry would have been difficult in the calmest of environments and Berkeley in the 1960s was not calm. Very fortunately, my advisor Allan Wilson assured me that together we could design a project that would be within my experimental skills and perhaps even exploit my propensity to write down equations. Out of these conversations came my dissertation, the demonstration that humans and chimpanzees share 99% of our protein coding sequences, and the consequent hypothesis that our differences in morphology and behavior are due to a few critical differences in timing and regulation of genes rather than to accumulation of large numbers of mutations in primary sequences. Allan died of leukemia at age 58 in 1991, so did not see our work vindicated by the chimpanzee genome sequence. Of course, he was sure we were correct, that the experimental evidence spoke for itself.
My introduction to the problem of breast cancer came thanks to Nicholas Petrakis of UCSF, where in 1974 I took a research position that we would now call a post-doc. Nick encouraged me to follow my intuition in designing very high-risk long-term studies to test whether familial clustering of breast cancer could be due to inherited mutations in a single gene. When I moved, two years later, to a faculty position back at UC Berkeley, he urged me to take the project with me. Allan and Nick shared the understanding that proof in science takes a long time, and that the most important questions deserve whatever time it takes.
At Berkeley, our work on inherited breast cancer was carried out by a small group of postdocs and students: geneticists Jeff Hall, then Lori Friedman, Beth Ostermeyer, and Eric Lynch; epidemiologists Beth Newman and Sarah Rowell; and statistician Ming Lee. We shared curiosity, hard work, and fabulous feasts.
My move to the University of Washington in 1995 was thanks to Arno Motulsky who encouraged me to immerse myself in an environment with great strengths in both medicine and genomics, and remained my dear and critical friend until his death in 2018. I now have the great pleasure of working every day with about 20 young professors, postdocs, students and research staff. It is irresistible to be excited by every new experiment. We have many years of opportunities ahead of us.
Our breast cancer work would not have been possible without the support of both the US National Cancer Institute and private foundations. Private philanthropy is now a major force in biomedical research. I am enormously grateful.
And finally, thanks and love to my daughter Emily, whose work in Berkeley is devoted to animal welfare. She lives a life of good works, grace and style, and does so in her own way.
26 September 2018 Hong Kong
