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2011 Genetics Prize

Ronald Davis

Biochemist and geneticist Ronald W. Davis grew up in the small city of Charleston, Illinois, which is located about 160 miles south of Chicago. He was fascinated from a young age with machines that flew, first airplanes and then rockets. By middle school, he was building his own model rockets, firing them off from a vacant field near his home.

“I read a lot about rocket fuels, but I soon exhausted the textbooks at my high school,” he recalls. “So I started to break into the local college library at night. I’d sit in the stacks and read the chemistry journals. I couldn’t get access any other way.”

To acquire the chemicals he wanted for ever-more-sophisticated fuels, he created a fake company with letterhead—and ordered the fuels through the mail.

“I got pretty exotic with my rocket fuels, but I still have all my fingers—a testimonial to the fact that I’m a good chemist,” he says with a laugh.

Despite this precociousness, Davis struggled in school. “I had some learning disabilities that weren’t understood at the time. I’m dyslexic,” he says. Because of those struggles, Davis was told by his high school counselor that he wasn’t college material, and his dad, a carpenter who had dropped out of school in seventh grade, concurred. But after much discussion, Davis and his father made a pact: Davis would find a way to pay the tuition at nearby Eastern Illinois University, and his parents would give him free room and board at home.

Davis’ undergraduate years were hectic. He worked three part-time jobs and took extra math and science courses each semester “to counter my other grades and ensure that my grade point would stay high,” he recalls. When he graduated in 1964, his official major was chemistry, but he also had enough credits for unofficial majors in physics, mathematics, and botany.

With strong recommendations from his professors—and excellent scores on the advanced chemistry GRE—Davis was accepted into graduate school at the California Institute of Technology (Caltech). “It was a miracle for me,” he recalls. “I was scared to death, but I loved it. It was where I always wanted to be. I kept asking everybody questions all the time. I was sure I wasn’t going to make it there, so I decided I was going to enjoy myself and learn as much as I could until they ‘discovered’ me and kicked me out.”

But they didn’t kick him out. Indeed, he thrived. Davis says he was fortunate that his thesis advisor at Caltech was the molecular biologist Norman Davidson—“a wonderful man who was unbelievably smart and not very arrogant.” Davis chose his thesis topic rather unorthodoxly, however. “It was hot and smoggy that first summer,” he recalls, “and I don’t like hot weather. The electron microscope was in the basement where it was cool. I had to come up with a project, so I decided it would be something I could do down there for.”

That project involved developing one of the first mapping methods for DNA, a groundbreaking achievement. For almost a decade after it was published, Davis’ thesis remained one of the top 10 most-cited papers in molecular biology. While at Caltech, Davis also developed heteroduplex technology, with which he created the first image of the pairing of two genomes.

For his postdoctoral work, Davis went to Harvard University, where he worked with molecular biologist Mark Ptashne and geneticist James Watson. “I thought I should learn something different—proteins and enzymes and stuff,” he recalls. In 1972, Davis returned to California to become an assistant professor in the Department of Biochemistry at Stanford University. He’s been at that institution ever since. Today, he is a professor of both biochemistry and genetics, and has served as director of the Stanford Genome Technology Center since 1994.

Although primarily a biochemist by training, Davis has used his deep understanding of biochemical and physical chemical principles to address problems of fundamental importance to genetics. His contributions to the field are numerous and profound. He created, for example, some of the earliest phage lambda-based cloning vectors (DNA molecules that carry foreign DNA into a host cell, where the foreign DNA can then be replicated.) Working on the genome and biology of the Saccaharomyces cerevisiae (baker’s yeast), his lab developed the first artificially constructed chromosomes, which are now routinely used to clone large genes and to map complex genomes. In 1977, Davis co-authored a landmark paper that described the very first case of what is now known as genome editing, the ability to replace any nucleotide in the yeast genome with any other nucleotide.

In 1980, in another landmark paper—one of the most highly cited in the field of human genetics—Davis and his team described how sequence variants in the genomes of humans and other species could provide genetic markers for making a genetic and physical map of the human genome. That paper helped launch the field of genomics. A few years later, Davis’ lab showed how DNA libraries could be searched with protein-finding antibodies, a technique that has made it possible for scientists to identify genes for important proteins, including in humans.

During the 1990s, Davis contributed to the development of the very first microarrays, tools that enable scientists to analyze the gene expression of thousands of genes simultaneously. He then went on to help standardize this technology, paving the way for other scientists to use it for clinical applications. In recent years, his lab has produced sequences of several yeast chromosomes: part of the Escherichia coli genome, part of the Arabidopsis thalialiana genome (Arabidopsis is a plant widely used in the study of genetics), part of the human genome, and part of the genome of Plasmodium falciparum (a parasite that causes malaria in humans). Davis also continues to develop new biotechnologies; DNA nanotechnology is a particular current focus of his lab.

“I really enjoy working on problems that others think are unsolvable,” says Davis. “And I’ve been finding, to my surprise, that the older I get, the easier it is to take on those problems.”

Davis has been an inspiration to many other biochemists and geneticists throughout his career. In addition to mentoring graduate students and postdoctoral fellows, he taught a course in Bacterial Genetics at Cold Spring Harbor from 1976 to 1981, and wrote the first manual on genetic engineering techniques (published by the Cold Spring Harbor press). He has also served on the National Institutes of Health (NIH) Genome Research Review Committee, the NIH Center for Biomedical Ethics Steering Committee, The World Health Organization Immunology of Tuberculosis Steering Committee, and as chairman of the WHO Strategic Research Steering Committee.

Davis has been the recipient of many professional honors, including memberships in the National Academy of Sciences, the American Academy of Microbiology, and the Human Genome Organization. Other honors include the Dickson Prize in Medicine from the University of Pittsburgh (2005), the Lifetime Achievement Award from the Genetics Society of America (2004), the Chiron Corporation Biotechnology Research Award (1998), the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research (1992), the Eli Lilly Award in Microbiology and Immunology (1976), and the United States Steel Award presented by the National Academy of Sciences (1981).

When not in his lab, Davis enjoys backpacking and the study of traditional Native American spirituality. He and his wife, clinical psychologist Janet Dafoe, have a sweat lodge in their backyard. They have two children, Whitney, a photographer, and Ashley, an undergraduate student.