Written by Alina Yu
In the midst of Women’s History Month, we thought it only fitting to highlight a few of the female pioneers who have advanced our world of science, technology, and neverending discovery. Specifically, we would like to give special recognition to two women who have recently been awarded for their hard working efforts in providing new technology in the face of gene discovery: Dr. Jennifer A. Doudna and Dr. Emmanuelle Charpentier. In 2020, Doudna and Charpentier received the Nobel Prize in Chemistry for their discovery of CRISPR/Cas9 technology. CRISPR, or clusters of regularly interspaced short palindromic repeats, is a specialized region of prokaryotic, or bacterial, DNA that is able to be mechanically manipulated to help our own cells fend off attacks of specific viruses. This gene editing technology has helped scientists better understand the nature of human and viral DNA and RNA, contributing to countless related scientific projects and fields. CRISPR has also been applied to our understanding of the current COVID-19 pandemic.
The pioneering scientists had incredible journeys to become the researchers they are today. Doudna attended Pomona College in California, earning an undergraduate degree in Biochemistry. Pursuing her graduate degree at Harvard, she worked under Jack W. Szostak, who himself is a Nobel Prize winner, and began her work studying RNA. Postdoctoral work in Colorado and a faculty position at Yale University finally landed Doudna in Berkeley, CA, where she became part of the University of California faculty and continues to head her own lab. In this lab, Doudna and her team not only brought into fruition CRISPR technology but also continue to study the structure and mechanism of CRISPR, find new gene editing tools to use in vitro (in cells) and in vivo (in organisms), and develop anti-CRISPR agents.
Similarly, her co-recipient Charpentier has had a scholarly journey as a researcher and scientist. Charpentier studied biology, microbiology, biochemistry, and genetics as a student at the University of Pierre and Marie Curie in Paris, France, where she stayed to obtain her graduate and postgraduate degrees before moving to New York. In New York and various other institutions around the world, Charpentier conducted research and headed labs, and she currently resides as Scientific and Managing Director of the Max Planck Unit for Science of Pathogens, more of which can be learned at the Max Planck Society website.
So how exactly did these two scientists meet and discover their gene editing technology? Although their work was rewarded in 2020, the CRISPR-Cas9 technology was discovered in 2012.
We have given a brief rundown of what CRISPR and Cas9 is in a previous article. Briefly, CRISPR is a sort of DNA mechanism in bacteria that identifies specific genetic sequences of viruses and uses enzymes to target and destroy those sequences, which are CRISPR-associated proteins (Cas), specifically Cas9. Together, CRISPR and Cas9 act as a bacteria’s defense system, or immune system, and are often referred to as “genetic scissors.” The study of the CRISPR system in bacteria was well underway, and Charpentier, at the time working for the University of Vienna and then moving to Sweden to continue her research, had identified a key element of the CRISPR System: An RNA molecule called tracrRNA that targets the specific DNA sequence in order to disarm and render viruses useless. With these pieces in mind, Charpentier began her collaboration with Doudna in 2011, where they took the system and programmed it to specifically act upon sequences of interest. As every biology student will learn, the core cycle of the cell is the transformation of DNA to RNA to proteins. Thus, with tracrRNA acting as “guide RNA” in conjunction to another molecule called crRNA, Cas enzymes are led to exact DNA sequences. The Cas0 proteins can then cut the DNA strands and effectively “knock out” the expression of that gene.
After this novel method of editing and mechanically manipulating DNA was published in 2012, scientists across the globe jumped at the opportunity to further study the bacterial system and apply the gene editing tools to their studies. By knocking out genes, CRISPR also allows scientists to insert genes into genomic DNA to further study gene expression, making the gene-editing technology crucial in the application of medicine, agriculture, and basic science. Multiple clinical trials are utilizing the technology to treat diseases like sickle-cell anemia and cystic fibrosis, and currently is being used to better target detection of Sars-CoV-2, the virus behind COVID-19. The gene-editing technology creates an efficient and effective manner of detecting gene sequences in question without having to go through a guessing game of the entire DNA genome. Its applications to humans are endless, and Doudna and Charpentier laid the groundwork for future discoveries to come.