Prof. Doudna gained international renown when she and her colleagues at UC Berkeley were the first to develop the CRISPR-Cas9 genome editing technology that enables scientists to edit the DNA of any organism. The implications are revolutionary.
By Leah Sherwood.
Jennifer Doudna, professor of molecular and cell biology and chemistry at the University of California, Berkeley, and author of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, gave a lecture titled “CRISPR Systems: Nature’s Toolkit for Genome Editing” on Monday at the University of Hawai‘i at Hilo.
Doudna gained international renown when she and her colleagues at UC Berkeley were the first to develop the CRISPR-Cas9 genome editing technology that enables scientists to edit the DNA of any organism. Based on a naturally occurring process used by bacteria to fight viruses, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system provides scientists with a tool to make precise changes to the DNA of the genes, thereby modifying the function of cells in specific ways.
Roots in Hilo
Doudna was born in Washington, DC, and moved to Hilo with her parents when she was seven years old. She is a 1981 graduate of Hilo High School. Her father, Martin Doudna, was an English professor at UH Hilo, and her mother, Dorothy Doudna, taught history at Hawai‘i Community College.
Doudna credits UH Hilo biology professor emeritus Don Hemmes with inspiring her curiosity about the living world by giving her a chance to work in his lab on campus. Hemmes is an internationally known expert in fungi, notably mushrooms.
“I still remember working in his lab that summer,” says Doudna. “I couldn’t wait to get up in the morning and head to lab because I really wanted to do an experiment.”
CRISPR-Cas9 technology is expected to have revolutionary implications through its human and non-human gene editing applications, including advances in agricultural methods, medical treatments for illnesses like Huntington’s disease, and mitigation of environmental damage.
At a reception before her lecture, Doudna cites the example of the ʻōhiʻa trees on Hawai‘i Island, which are rapidly dying due to the ceratocystis fungus, as an example of an environmental problem that could one day be solved through gene editing.
In her lecture, Doudna notes that early in the history of genetics, the idea of gene editing seemed fanciful, but in retrospect one can see the progression of technology that led to the CRISPR discovery.
“At that time scientists already started to imagine what you could do if you could read the code of life and write that code and eventually rewrite that code,” says Doudna. “What if you could actually make changes to the DNA of the cells that would allow understanding to the genetics of who we are as humans and the natural world and the genetics of all the organisms that we interact with in our environment, and also be able to manipulate that code by making precise changes?”
“Over the years, you can look back at what’s happened over the last several decades there has been a progression of technology for doing exactly that, namely manipulating DNA in different ways,” she explains. “What the technology really does is give scientist a really easy tool for making very precise and accurate changes to the DNA. So precise that we can change one letter in the code of the entire human genome if we want to.”
Doudna tells the audience how she felt the moment she realized that CRISPR-Cas9 could be used for genome editing.
“You can change this piece of RNA on this end to any desired sequence and program the Cas9 protein to identify a sequence of DNA to make a cut at any desired sequence that we decided on in the lab by simply changing the 20 letters on this end of the RNA,” she says. “That is one of the moments I’ll never forget in my life because I really felt chills going down my back thinking this is going to be an Incredible tool for working with DNA. Scientists can now harness this ability to do something very different, namely genome editing.”
Doudna says historically, the RNA molecule was considered less important than the more glamorous double-helixed DNA molecule and the cell proteins.
“DNA encodes all the information to make the cell or to make an entire organism. Information is transferred, transcribed into molecules of RNA and then ultimately translated into proteins. The proteins, we were taught were the real business end of the process. They do all the interesting things themselves. The DNA is very important because it has the code that makes the proteins, and then in the middle are these very boring, uninteresting molecules of RNA. They are kind of a throwaway copy of the genome.”
Today, however, it is understood that RNA molecules that are made in cells have interesting functions and three-dimensional shapes that allow them to do chemistry. In the CRISPR-Cas9 technology, RNA plays a central role, with scientists creating a small piece of RNA with a short “guide” sequence that binds to a specific target sequence of DNA in the genome.
Doudna notes that she had studied RNA for a decade, asking questions about the fundamental nature of biology and investigating the functions of RNA molecules. It was during these studies that one project led into an unexpected direction that led her to the CRISPR discovery.
View entire lecture
Rose and Raymond Tseng Distinguished Lecture Series
Doudna’s lecture was the inaugural talk of the Rose and Raymond Tseng Distinguished Lecture Series at UH Hilo. The series is supported by an endowed fund started by UH Hilo Chancellor Emerita Rose Tseng.
About the author of this story: Leah Sherwood is a graduate student in the tropical conservation biology and environmental science program at UH Hilo. She received her bachelor of science in biology and bachelor of arts in English from Boise State University.
About the photographer: Bob Douglas is a local artist, photographer, and sometimes part-time student who volunteers his photography skills to the Office of the Chancellor and UH Hilo Stories.