Saluting Jennifer Doudna
In 2020, University of California, Berkeley, biochemist Jennifer Doudna won the 2020 Nobel Prize in Chemistry, along with colleague Emmanuelle Charpentier, for the co-development of CRISPR-Cas9, a genome editing breakthrough that has had great significance in biomedicine. Doudna and Charpentier, director of the Max Planck Institute for Infection Biology, shared the 10 million Swedish krona (more than $1 million) prize.
In the spring of 2012, the Doudna and her collaborators turned a curiosity of nature into an easy-to-use tool that can edit DNA. CRISPR-Cas9 enables scientists to rewrite DNA — the code of life — in any organism, including human cells, with efficiency and precision. The power and versatility of CRISPR-Cas9 has opened up new and wide-ranging possibilities across biology, agriculture and medicine, including the treatment of thousands of intractable diseases.
Doudna and Charpentier were recognized by the Nobel Foundation for their discovery that a gene-cutting molecule, Cas9, used by bacteria to kill viruses, can be re-engineered as a precise and easy-to-use gene-editing tool. The CRISPR-Cas9 system is guided by an RNA molecule to bind a specific region in the DNA, and the Cas9 protein then acts like a pair of molecular scissors to cut the DNA, allowing it to be altered in a precise fashion.
According to Doudna, “This great honor recognizes the history of CRISPR and the collaborative story of harnessing it into a profoundly powerful engineering technology that gives new hope and possibility to our society. What started as a curiosity‐driven, fundamental discovery project has now become the breakthrough strategy used by countless researchers working to help improve the human condition. I encourage continued support of fundamental science as well as public discourse about the ethical uses and responsible regulation of CRISPR technology.”
Although women have conducted research at UC Berkeley that won them a Nobel Prize after they left the campus, Doudna is the first woman on the UC Berkeley faculty to win the award. She is the campus’s 25th Nobel laureate. The 24th winner, Reinhard Genzel, won the Nobel Prize in Physics the previous day. The honor represents another first: Doudna and Charpentier are the first women to win a Nobel Prize in the sciences together, which sends the message, Doudna said, that “women rock.”
She added, “Many women think that, no matter what they do, their work will never be recognized the way it would be if they were a man. And I think (this prize) refutes that. It makes a strong statement that women can do science, women can do chemistry, and that great science is recognized and honored. That means a lot to me personally, because I know that, when I was growing up, I couldn’t, in a million years, have ever imagined this moment.”
Doudna said she is “really, really proud to be representing Berkeley, … a public university that supports great science and great education, … a place that welcomes everyone, people from all over the world.” She added, “It’s a great feeling to have such incredible colleagues who are part of this.”
Doudna, who is the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and a Howard Hughes Medical Institute investigator at UC Berkeley, is president and chair of the board of the Innovative Genomics Institute (IGI), a faculty scientist at Lawrence Berkeley National Laboratory (Berkeley Lab), a senior investigator at the Gladstone Institutes and an adjunct professor of cellular and molecular pharmacology at UC San Francisco. Charpentier, who in 2012 was affiliated with the University of Vienna and Umeå University in Sweden, was appointed director of the Max Planck Institute for Infection Biology in Berlin in 2015.
Doudna was focusing on RNA, a partner to DNA in carrying genetic information and a key part of several molecular machines (such as the ribosome and telomerase) that help DNA do its job. She became interested in CRISPR because of her long-standing interest in such RNA-based machines. Her attention was first drawn to CRISPR by a UC Berkeley colleague, Jill Banfield, who encountered it while studying bacteria living in extreme environments. The system intrigued Doudna, who wondered how exactly an unusual repeating sequence of DNA in the bacterial genome enabled bacteria to mount a successful defense against viral infections. What they and other researchers pieced together is that when viruses invade bacteria, the bacteria cut up the viral DNA and place these pieces in their genome, like “most wanted posters.” If similar viruses invade again, roving enzymes with RNA copies of these bits of viral DNA examine the virus and, if the RNA and DNA match, cut the DNA and kill the virus.
Charpentier was focusing on the Type 2 system (CRISPR-Cas9) and, in a paper published in Nature in 2011, described an unusual RNA not found in other CRISPR systems — the tracrRNA (pronounced “tracer RNA”) — and how it works together with the Cas9 protein to help generate the RNA copies of the “most wanted posters.” She and Doudna then considered how the Cas9 protein might also be involved in the final step of CRISPR immunity: surveilling the cell and cutting up invading DNA. The two began their collaboration that year after meeting at a scientific conference in Puerto Rico.
A year later, in a seminal 2012 Science paper, Doudna and Charpentier rocked the scientific community by showing that the protein Cas9 is guided by both the tracrRNA and an RNA matching a viral sequence, which it uses to seek out and destroy matching viral DNA. The two scientists also demonstrated that this cellular defense system had applications beyond killing viruses. They engineered the two-piece RNA into a single RNA and showed that it could be designed to pinpoint any gene in any species, not just bacteria, allowing the Cas9 protein to cleave at that spot. Doudna and Charpentier then made the proposal that CRISPR-Cas9 can be repurposed to be an exceptionally powerful tool for editing plant or animal genomes, including human genes, and customized to delete or add specific strands of DNA.
“Jennifer has, for many years, been a pioneering structural biologist in determining the 3D structure and function of RNAs,” said Robert Tjian, a UC Berkeley professor of molecular and cell biology and former head of the Howard Hughes Medical Institute. “Her development of the fused, single-guide RNA was crucial in enabling the efficient and practical use of CRISPR-Cas9 as a highly efficient gene-editing molecular tool. Her further work determining structures of the Cas9/guide-RNA complex has been crucial in further refining this powerful technology.”
