Technology and Innovation, Vol. 20, pp. 475-482, 2019 ISSN 1949-821 • E-ISSN 1949-825X http:// Printed in the USA. All rights reserved. dx.doi.org/10.21300/20.4.2019.475 Copyright © 2019 National Academy of Inventors. www.technologyandinnovation.org THE NAI FELLOW PROFILE: AN INTERVIEW WITH DR. JENNIFER DOUDNA Jennifer A. Doudna1-7 and Kimberly A. Macuare8 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA 2Department of Chemistry, University of California, Berkeley, Berkeley, California, USA 3California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, California, USA 4Innovative Genomics Institute, University of California, Berkeley, Berkeley, California, USA 5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA 6MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA 7Gladstone Institutes, University of California, San Francisco, San Francisco, California, USA 8National Academy of Inventors, Tampa, FL, USA In a recent interview with Technology and Innovation, Dr. Jennifer A. Doudna, pioneering biochemist and renowned research scientist, discusses the potentials and pitfalls of genome editing, the importance of diversity for pushing perspectives, and what Frankenstein might have to teach us about the boundaries of science. INTRODUCTION This issue’s NAI Fellow Profile features the pio- neering biochemist and renowned research scientist Dr. Jennifer A. Doudna. After starting her career as a research fellow at the University of Colorado, Boulder, Doudna went on to serve as the Henry Ford II Professor of Molecular Biophysics and Biochemistry at Yale University before joining the University of California, Berkeley, where she currently serves as a professor of biochemistry, biophysics, and struc- tural biology and is the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences. In addi- tion, she heads the Innovative Genomics Institute and is a Howard Hughes Medical Institute Investigator. Doudna received her B.S. in chemistry from Pomona College and her Ph.D. from Harvard University in biochemistry. She is the author of over (Photo courtesy of Jennifer A. Doudna) _____________________ Accepted: November 1, 2018. Address correspondence to Kimberly A. Macuare, Ph.D., Associate Editor, Technology and Innovation Journal of the National Academy of Inventors® at the USF Research Park, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612. E-mail: [email protected] 475 476 DOUDNA 200 technical papers and inventor on 24 U.S. pat- stages, CRISPR genome editing promises a revolu- ents with more than 100 published applications. Her tion in our ability to treat everything from fungal pioneering contributions to the life sciences have crop diseases to human cancers. been recognized with numerous honors, including In a recent interview with Technology and fellowship in the National Academy of Inventors, Innovation (T&I), Dr. Jennifer A. Doudna discusses the American Academy of Arts and Sciences, and the potentials and pitfalls of genome editing, the the American Association for the Advancement importance of diversity for pushing perspectives, of Science as well as membership in the National and what Frankenstein might have to teach us about Academy of Medicine and National Academy of the boundaries of science. Sciences. Among her many prizes and recognitions, she has received the Japan Prize, the Kavli Prize, and INTERVIEW the Medal of Honor of the American Cancer Society. T&I: Please tell us a little bit about some of Early on in her career, Doudna became inter- the projects that you are working on currently. ested in RNA, specifically its catalytic activity. Her first efforts in this area were devoted to understand- Doudna: Well, I would say there are really two ing the structure and function of RNA, including major types of projects that we’re pursuing. One her breakthrough discovery revealing the defined is we’re hoping to understand more about the and organized structure of RNA molecules and her fundamental biology of CRISPR systems in na- important work on ribozymes and how they perform ture. So, we want to know how it is that bacteria their protein-like roles. In addition to expanding use these kinds of pathways. As you may know, our understanding of these molecules, Doudna’s they evolved as viral defense mechanisms, but we work in this area has had important potential clini- also think they probably help bugs to talk to their cal applications, especially as regards hepatitis C and neighbors in an environment and help regulate other viruses, where her discoveries of how RNA genes, so we’re trying to figure out those pathways. is connected to the production of viral proteins Of course, we’re very excited about opportunities may allow for the development of drugs that target to use genome editing for various applications. We this process and thus treat these conditions. Most have several partnerships with academic colleagues recently, Doudna’s work on RNA led to her work on who are clinically inclined working on two major CRISPR, which serves as a natural defense against focus areas: immune diseases and brain cancer. viral invasions in bacteria. This system evolved as an adaptive immune response in microbes. After T&I: Is this in partnership with clini- exposure to virus, the cell saves a memory of the cians who are working at your universi- viral DNA. Cas9—a DNA-cutting protein—patrols ty, or is this a cross-university partnership? the cell, carrying that memory around in the form of a guide RNA molecule. Upon the virus’ reappear- Doudna: This is actually people who work ance, Cas9 checks to see if its guide RNA matches at the University of California, San Fran- the viral DNA, and if it does, Cas9 cuts the DNA cisco, so our neighbors across the bay. in two. The CRISPR-Cas9 system thus eliminates the viral threat while leaving the bacterial cell’s own T&I: Obviously, everybody wants to talk about DNA untouched. Realizing the amazing potential, CRISPR and learn more, so let’s dig in here a little Doudna and fellow scientists showed that Cas9 could bit. What has the discovery of this method done for easily be programmed with a custom guide RNA and both the practice and the applications of genome directed to cut specific DNA sequences. This makes editing in terms of speed and efficacy as com- CRISPR-Cas9 a powerful genome editing tool that pared to the methods that were being used before? lets scientists change the genetic code of any organ- ism. This technology has already revolutionized the Doudna: It’s remarkable. I haven’t really experienced pace of biological discovery. While still in its early anything like this in my career—where a technology, THE NAI PROFILE 477 within just a few short years, has really transformed Doudna: Well, you mentioned one already, which is the kind of science that is going on across different the idea of engineering organisms that would have areas of biology. an impact broadly in the environment. People have I’ll just give you a couple of examples. One of been very excited about the potential to use gene the things I hear quite frequently from colleagues drives, which are a way of using genome editing to who work with animals, and especially with mice, spread a genetic trait quickly through a population, is that it went from taking anywhere from a year or such as the population of mosquitoes or other kinds two, sometimes more than that, to engineer mouse of insects. I’m excited by the possibility of using it to strains that mimic genetic disease in humans so that control the spread of mosquito-borne disease, which they could be studied in the laboratory. Now, with is an amazing opportunity. At the same time, I think CRISPR-based genome editing, it takes a matter of we have to be careful about releasing organisms into four or five weeks. You get a sense of just how the the environment that might have unintended con- pace of science has ramped up incredibly with the sequences, either on their own populations or on ability to manipulate the genome. And this is true species that depend on them. I think that’s one area not just in animals but also in plants, so there are that requires thoughtful consideration. opportunities in plant biology to really understand Another is the potential for human germline edit- the underlying genetic causes of plant traits and sus- ing and the opportunities there. There are really grave ceptibilities to disease and things like that. risks and ethical challenges. We have already seen one It’s really exciting to see how the pace of research scientist in China forging ahead with this and rais- has opened up as well as the ways that people are ing a lot of questions about how to maintain control using genome editing and creative opportunities to over this technology in the future. explore the genetics of organisms that in the past The third would be the tremendous opportunities, would have been intractable. It used to be the case— but potential risks, with using genome editing in agri- certainly when I was a graduate student and learning culture. It’s a great tool that is available now to plant about science and initially as a professional—that we biologists and geneticists for research purposes but were taught that there were just a few types of organ- also to create plants that are adapted better to their isms that most scientists would study because they environments or have other properties that might be were genetically tractable: things like fruit flies or desirable to humans. At the same time, we don’t want tiny worms called nematodes. Now those limitations to inadvertently do things that will introduce plants are taken away.