Insight: Nobel winner at cutting edge,
Jennifer Doudna, who shared the Nobel Prize in Chemistry with Emmanuelle Charpentier a few days ago, grew up in Hilo on the Big Island of Hawaii. Turning over rocks in the tidepools and leaves in the rainforest to see what was on the other side, she already as a child displayed the curiosity that would drive her later science.
I first met Jennifer when she was a graduate student at Harvard and stopped by my Boulder office on a cross-country trip.
She explained that her PH.D thesis involved the catalytic RNA molecule we had discovered here at the University of Colorado Boulder. I must have passed this informal interview, because in 1991, Jennifer joined my lab as a postdoctoral scholar to tackle a formidable problem: determining the atomic structure of a domain of this catalytic RNA by X-ray crystallography.
Knowing the structure would illuminate the molecular function. Her work in Boulder displayed her special talent: She would choose an important problem that everyone else thought to be too difficult and then visualize a path where creativity and a great deal of perseverance might allow it to be solved.
The RNA structure was solved by Jennifer soon after she started her independent faculty position at Yale. She later moved from Yale to University of California Berkeley, where she and her husband Jamie Cate (also trained at CU) could both be professors. RNA crystallography soon blossomed into a small field, with Jennifer as a key leader.
She was elected to the National Academy of Sciences at age 38 on the basis of her RNA and Rna-protein structural biology, all PRE-CRISPR.
So, what is CRISPR? Just as humans are under constant attack by viruses, so are bacteria, and they, too, have developed immune systems. Bacteria store a snippet of the DNA from each virus that’s infected one of their ancestors, which serves as a sort of memory and allows them to cut up that viral DNA if it ever shows up again.
This is absolutely fascinating biology, but the story gets even better.
Jennifer and her collaborator Emmanuelle discovered that the CRISPR system of the pathogenic bacterium S. pyrogenes is simple — just one protein to snip the DNA and two RNA molecules to guide the snipper to a matching DNA sequence. They simplified it further by fusing the two RNAS into a single guide RNA.
As they modestly predicted: “Our study … highlights the potential to exploit the system for Rna-programmable genome editing” (Jinek et al., Science 2012).
Why is it so important to be able to cut specific sequences of DNA? Sometimes it’s useful to cut and thereby inactivate a
“bad” gene, such as a gene from a pathogen or a mutant human gene. But more often, we’d like to repair mutant genes.
It turns out that all cells have machinery that uses DNA of a matching sequence to repair cleaved DNA. For example, using a gene from an intact chromosome 5 to repair a broken chromosome 5. If you introduce an artificial repair strand of DNA at the same time that CRISPR is cutting the site you want to repair, then the cell does the rest of the work.
Here’s an analogy: The human genome is like a small library with a million pages of books. CRISPR allows you to find one specific page in one of the books and then to rewrite one sentence while keeping all the other verbiage intact.
Scientists around the world now routinely use this CRISPR genome editing to understand everything from how cancers metastasize to how plants grow in drought to how the immune system fights off pathogens. Furthermore, therapeutic applications are easy to envision. Because so many diseases have a genetic component, the ability to alter genes is huge.
Now that gene therapy is becoming so easy, we cannot escape the ethical implications. Society needs to consider what sort of restrictions should be placed on re-engineering human heredity. Jennifer Doudna has been an outspoken leader in these conversations as well.
The first award of a science Nobel Prize to two women is thrilling and encouraging for women scientists around the world and for girls who will become tomorrow’s scientists. More generally, however, we still have much work to do to remove the barriers that women and other under-represented groups face in the research positions that give them a shot at such awards.
Yet, for all those little girls turning over rocks and leaves and wondering in amazement at what’s underneath, this Nobel Prize was a great event.
Thomas R. Cech, a distinguished professor at the University of Colorado Boulder, won the Nobel Prize in Chemistry in 1989.