Edward Wood, MD
Vitreoretinal Surgery Fellow
Associated Retinal Consultants / William Beaumont Hospital
Jennifer Doudna, PhD gave a rousing talk to a standing-room only crowd for the ARVO/Alcon keynote lecture entitled CRISPR-Cas Gene Editing: Biology, Technology and Ethics. She discussed the history, progress, and remarkable future applications for CRISPR-Cas technology.
Dr. Doudna grew up in Hilo, Hawaii where she was fascinated by the island’s natural beauty at an early age. The amalgamation of her love of nature, a sixth-grade gift from her father of James Watson’s seminal publication “The Double Helix,” and inspiration provided by her 10th grade science teacher Mrs. Wong solidified her passion for science and the concept of pursuing a career in discovery-driven scientific research.
She attended public school in Hawaii and then Pomona College where she studied biochemistry. She subsequently earned her PhD in Biological Chemistry and Molecular Pharmacology at Harvard Medical School, whereafter she interfaced with the University of Colorado, Boulder, Yale University, and ultimately the University of California, Berkley, where she is currently Professor in the Department of Molecular & Cell Biology and Chemistry, an investigator with the Howard Hughes Medical Institute (HHMI), and executive director of the Innovative Genomics Institute.
Dr. Doudna began by introducing CRISPRs (clustered regularly interspaced short palindromic repeats) as families of DNA sequences originally found in bacteria that protect against viral invasion by storing copies of viral DNA to guide cleavage of further invading viruses. CRISPRs interface with CRISPR-associated systems (Cas) that act as molecular scissors to cleave targeted DNA segments. Essentially, the CRISPR-Cas system is an RNA-guided protein complex designed to cleave double stranded DNA with very high specificity. In this way, CRISPR-Cas natively acts as a component of the bacterial immune system.
However, the general method of targeting and cutting specific DNA segments has allowed scientists to reconsider both prokaryotic and eukaryotic DNA as editable, not too dissimilar to how one may alter the text in this blog. The general concept of programmable gene editing down to a single base pair was once the stuff of science fiction, but is now a very immediate reality thanks to the transformational work of Dr. Doudna and her colleagues.
Dr. Doudna discussed the history of discovery and development of CRISPR-Cas spanning multiple continents and institutions. While the history is complex and more thoroughly reviewed here https://www.addgene.org/crispr/history, several highlights discussed by Dr. Doudna include the early conceptualization of CRISPR as an RNA-based immune system by Jillian Banfield at Berkley, the work of Phillipe Horvath at Dupont in France evaluating bacteria used to make yogurt and cheese to verify that CRISPR systems are indeed adaptive immune systems which intimately involve the Cas protein Cas9. By first proposing CRISPR-Cas9 as a genome engineering system, Dr. Doudna’s work marked a paradigm shift in our understanding of CRISPR’s ability, application, and potential impact, for which they won the Breakthrough Prize in Life Sciences in 2015.
While the history of CRISPR-Cas technology is fascinating, it’s future applications will likely revolutionize science and the world as we know it. The technology has already been used to genetically edit both prokaryotic and eukaryotic cells to make modified tomato plants bearing 3x more fruit, frogs with green fluorescent pigment, piglets with decreased immunogenicity so to serve as improved organ donors for humans, and even introduce germline DNA edits in primates to name only a few. She then showed a compelling montage of living organisms that have already been genetically modified with CRISPR.
One can imagine a CRISPR-based reality in which pathogenic mutations may be edited out of somatic or germline cells before the development of or during disease. Taken one step further, medical futurists envision a future in which one may curate DNA sequences (of future children, for example) to maximize ‘positive’ attributes and remove ‘negative’ ones. The ethics surrounding such applications are very complex, and Dr. Doudna discussed the need for ethical considerations to keep pace with scientific progress.
Dr. Doudna concluded her talk by offering two ways in which CRISPR-Cas technology may be clinically useful: (1) As a research tool to characterize the genetic basis of disease and perhaps create specific disease models, and (2) as a clinical tool making therapeutically valuable gene edits. The technology is still relatively young, and incredible progress is being made every day. It was a very high honor to have Dr. Doudna deliver the ARVO/Alcon keynote lecture, and we look forward to learning more about this revolutionary technology in the years to come.