2016 Dickson Prize Winner
Jennifer Doudna, PhD
Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and Professor of Molecular and Cell Biology and of Chemistry, University of California, Berkeley
Investigator, Howard Hughes Medical Institute
From age 7, Jennifer Doudna lived in Hawaii, where she developed a fascination for the natural world that would eventually lead to a career in science. She earned her bachelor’s degree in biochemistry at Pomona College in California and her PhD in biological chemistry and molecular pharmacology at Harvard University in the lab of biochemist and geneticist Jack Szostak, PhD. (Szostak would go on to win a share of the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres.) During her PhD studies and a subsequent postdoctoral fellowship with Szostak, Doudna explored the function and mechanisms of catalytic and other noncoding RNAs. In 1991, she began postdoctoral studies at the University of Colorado in the lab of 1989 Nobel laureate Thomas Cech, PhD, where she began work towards solving the three-dimensional structure of RNA molecules using X-ray diffraction.
Doudna established her own lab at Yale University in 1994 and was promoted through the ranks to Henry Ford II Professor by 2000. She and her colleagues focused their initial studies on determining the first atomic-resolution structures of large RNAs. While at Yale, she was recognized with the Alan T. Waterman Award, which is given annually by the National Science Foundation to an exceptional young scientist. Doudna was credited for her innovative research leading to techniques for crystallization of RNA molecules and for determining structural features of RNA that permit greater understanding of the mechanistic basis of RNA function. In 1997, she was named an investigator of the Howard Hughes Medical Institute, and in 2002 she relocated to the University of California, Berkeley.
While investigating the control of genetic expression by RNA, Doudna became interested in a feature seen in many bacterial genomes—repeating sequences known as CRISPRs, which is short for clustered regularly interspaced short palindromic repeats. Other scientists had determined that CRISPRs are elements of a bacterial immune system. The DNA segments sandwiched between the repeated sequences are stretches of DNA taken from viruses that had previously infected the microorganism. The system functions as an identification system for invading viruses; if they are recognized, they are destroyed.
Doudna teamed up with microbiologist Emmanuelle Charpentier, PhD, to make fundamental discoveries about how CRISPR systems work. In the event that the same virus infects the bacteria again, this DNA between the repeat sequences is employed in the form of an RNA copy that, together with a second length of RNA and a protein called Cas9, can latch on to any matching strands of DNA, like those on live viruses, and destroy them. When a new virus is encountered, the CRISPR-Cas9 system is capable of inserting new snippets of viral DNA into the bacterial genome, which will then be passed on to ensuing generations to protect them from the same virus.
Doudna and Charpentier demonstrated that CRISPR-Cas9 could be used with prepared sequences of guide RNA to cut DNA at virtually any spot on the genome. Additional DNA could be deleted or added, as well. While other technologies for genome editing existed, none were as simple as CRISPR-Cas9. The paper describing these accomplishments was published in the journal Science in June 2012.
Using the CRISPR-Cas9 system, researchers have successfully corrected genetic defects in animals and altered DNA sequences in embryonic stem cells. Such technology has opened a gateway to genetic modification of human sperm and egg cells—ushering in significant ethical considerations and questions. The technology’s emerging ability to counteract congenital diseases, and even to modify nondisease traits like intelligence or physical appearance, has raised concern and calls for caution not just for researchers, but humanity. Doudna has advocated for a moratorium on attempts to alter the human germline for clinical purposes, though she believes basic research in this area should continue.
In addition to new possibilities for the treatment of human disease, precision engineering of organisms and cells is poised to broaden the capabilities of biofuels and agricultural products, among other revolutionary applications. Doudna’s lab is currently working toward delivering Cas9 protein-RNA complexes into specific tissues and on uncovering the mechanisms of target search and binding in live cells.
In addition to the 2016 Dickson Prize in Medicine from the University of Pittsburgh School of Medicine, Doudna is a recipient of the 2016 Canada Gairdner Award, the 2016 L’Oréal-UNESCO for Women in Science Award, the Breakthrough Prize in Life Sciences, the Gruber Genetics Prize, the Lurie Prize in Biomedical Sciences, and many other honors. In 2015, she was named one of Time magazine’s 100 most influential people. She is a fellow of the American Society for Microbiology and a member of the National Academy of Inventors, the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences. Doudna holds the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences at the University of California, Berkeley, where she is a professor of molecular and cell biology and a Howard Hughes Medical Institute investigator.
Doudna is scheduled to deliver the Dickson Prize in Medicine Lecture on Thursday, October 20, as the opening plenary session for Science 2016, the University of Pittsburgh’s annual celebration of science and technology.