Jennifer Doudna | Gruber Foundation

Jennifer Doudna was born in Washington, D.C., but spent most of her childhood in Hilo, Hawaii, where her father taught American literature at the University of Hawaii at Hilo and her mother lectured on history at a local community college. Doudna’s interest in science began with her explorations into the rainforests around her home. She traces her first exposure to biochemistry, however, to a copy of James Watson’s The Double Helix, which her father gave her when she was in the sixth grade. “When I picked it up, I couldn’t put it down,” she says. Later, a chemistry class in high school cemented her determination to become a scientist. Doudna chose Pomona College in California for her undergraduate education because it was small, on the West Coast, and had a strong biochemistry program. She then went to Harvard for graduate school, where she worked with future Nobel laureate Jack Szostak, who was researching ribonucleic acid (RNA), one of two types of nucleic acids (the other is DNA) found in all cells. “I just loved his creative vision about how one could understand something about the origin of life by studying the behavior of RNA molecules,” Doudna recalls. While in Szostak’s lab, Doudna helped engineer a self-replicating catalytic RNA (ribozyme). That achievement added weight to the hypothesis that RNA, not DNA, was the source of early life, for it demonstrated that RNA not only stores genetic information, but also catalyzes chemical reactions that help duplicate the information — a key attribute of life. Doudna knew that to truly understand the biochemical activities of catalytic RNA molecules, she would need to visualize their structure. So, for her postdoctoral studies, she went to the University of Colorado at Boulder to work with biochemist Tom Cech, who had just received a Nobel Prize for his discovery of the catalytic properties of RNA. Using X-ray crystallography, Doudna set out to identify the three-dimensional atomic structure of these molecules. She continued that work at Yale University, where she became an assistant professor in 1994 in the Department of Molecular Biophysics and Biochemistry. In 1996, Doudna and Cech published a landmark paper that described, for the first time, what a large-structured ribozyme (specifically, the P4-P6 domain of the Tetrahymena thermophilus group I intron ribozyme) looked like. “Seeing that structure was an exciting moment. I had chills down my spine,” recalls Doudna.  In 2002, Doudna moved to the University of California, Berkeley, where she continued to study the molecular structures and functions of RNA molecules. One of the continuing focuses of her work was to better understand how bacteria fight off viral infections using small bits of RNA. In 2005, Doudna learned about a rare type of bacteria (found in an abandoned mine) that had in its genome an unusual repeating sequence called “clustered regularly interspaced short palindromic repeats,” or CRISPR. The sequences enabled the bacterium to remember the genetic identity of a previous viral attack and then use that memory to mount a successful defense against it. Doudna was intrigued and decided to try to figure out how that process occurred, publishing a series of papers over the next few years about the molecular functions of CRISPR systems. In 2011, at a conference in Puerto Rico, Doudna met French microbiologist Emmanuelle Charpentier, who was also working with CRISPR sequences. They decided to pool their expertise —biochemistry, structural biology and microbiology — to determine how CRISPR provides bacteria with viral immunity. Along with postdoctoral researcher Martin Jinek and graduate student Krysztof Chylinski, the Doudna and Charpentier labs found that segments of the bacteria’s CRISPR RNA, generated from DNA sequences stored in the CRISPR locus from an earlier viral attack, team up with the enzyme Cas9 to seek out and cut the invading DNA in half, destroying it. “It was immediately clear that this could be a very exciting technology,” Doudna recalls. Not only could the process be used to kill viruses, it could also be used to edit DNA — and with remarkable scissor-like precision. Doudna and Charpentier published their findings in Science in August 2012. Their paper immediately and dramatically transformed the field of molecular biology and genetics. Since then, Doudna and other scientists have shown that the CRISPR/Cas9 technique works in human cells, a finding with enormous implications for preventing and treating many intractable diseases, including viral illnesses, such as HIV, and genetic conditions, such as Down syndrome and sickle cell anemia. Doudna currently holds the Li Ka Shing Chancellor’s Chair in Biomedical Sciences at the UC Berkeley. Her lab continues to study the CRISPR/Cas9 system, and is also collaborating with other labs to develop clinical applications of the technology. Doudna has received numerous honors and awards for her work, including memberships in the National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine. She lives in Berkeley with her husband, Jamie Cate, PhD, who is a professor of biochemistry at UC Berkeley, and their 12-year-old son, Andrew.