The title of the upcoming Symposium at ASCB 2015 is okay, says Jennifer Doudna. A Howard Hughes Medical Institute (HHMI) investigator and a professor of biochemistry, biophysics, and structural biology at the University of California, Berkeley, Doudna is most prominently a key player in the discovery and development of CRISPR Cas9, the hottest new gene editing technique in cell biology today. “Bending Nature to Our Purposes” will be the sign at the Symposium door in San Diego on December 15, but Doudna says that she thinks of her work less as “bending Nature” and more as “learning from Nature” what is possible. “It’s trying to figure out how Nature does things and every now and then realizing that I might harness this for another purpose,” she says.
“[Research is] trying to figure out how Nature does things and every now and then realizing that I might harness this for another purpose.”
Nature benders or learners, Doudna will be joined at the podium in San Diego by two noted biology repurposers: Angela Belcher, a biomaterials engineer at the Massachusetts Institute of Technology (MIT), whose lab has demonstrated, among other things, how viruses can be used to improve the efficiency of lithium-ion batteries, and Kristi Anseth, University of Colorado, Boulder and HHMI, whose lab is developing biomaterial scaffolds for multiple purposes including assembly in situ of “cell carriers” by polymerization inside patients.
CRISPR in the Limelight
CRISPR Cas9, though, is the biotechnology of the hour, and Doudna has reached that rare status in cell science—she is well known outside cell science. The news media have come calling,1 and last year Doudna and her early collaborator Emmanuelle Charpentier, now at the Helmholtz Center for Infection Research in Germany, each received a $3 million Breakthrough Prize in Life Sciences.2 Doudna reports that there is already a tremendous amount of curiosity about CRISPR Cas9 among the general public. Does the public get it? “Mostly they don’t,” she laughs. “I’d love to change that. People are fascinated with this idea. I do think that scientists have to explain technology well enough so that society can make informed decisions.”
Doudna says she’s also been struck by the number of people who have contacted her from the “creative” community—writers, artists, screenwriters, and television producers. “I got invited to speak at the Science Fiction Writers of America meeting. Unfortunately I couldn’t do it, but CRISPR seems to inspire people well beyond the scientific community.” The fascination is not about her personally, Doudna says, but about how a discovery like CRISPR can change societal thinking. “More broadly, it makes people think about what’s possible and about how we as humans can employ this kind of technology to do things that were not even thinkable in the recent past.”
Starting with the Basics
Doudna says that CRISPR demonstrates both the value and the unpredictability of basic research. CRISPR began for Doudna with a request from a Berkeley colleague, geomicrobiologist Jill Banfield, to sequence a bacterium sampled from the highly acidic wastewater of a mine in northern California. Recently Doudna told Andrew Pollack of the New York Times, “I remember thinking this is probably the most obscure thing I ever worked on.”3 Genomic sequencing revealed “clustered regularly interspaced short palindromic repeats,” or CRISPR, that turned out to be a fundamental bacterial mechanism for tailoring innate immunity to counter viral intruders. Working with Charpentier, Doudna harnessed CRISPR to a gene now called Cas9 to come up with an amazingly accurate way for scientists to edit genomes.
Confronted with her “obscure” quote, Doudna explains, “I guess my point there is that for all of us in science who are doing basic research, we don’t set out with a practical goal in mind beyond the goal of understanding how things work. That was certainly true here. For me and for my lab, the idea of working on a bacterial immune system and studying how bacteria deal with viral infection was a fun, fascinating project that I certainly never anticipated would lead to something like this.”
Doudna continues, “But that’s such an important thing for people, particularly for non-scientists to appreciate. That’s the nature of science. It’s about looking under the proverbial rocks and every now and then you find something. By just paying attention, you’ve found something that has broader implications.”
It’s a message she intends to stress at ASCB 2015. “This to me underscores the importance of funding basic research. For ASCB, this is preaching to the choir but it’s such an important message for all scientists to put across to the outside world. I don’t think anybody at ASCB would argue with the value of funding basic research. This is clearly an organization that is front and center in that.”
CRISPR in the Real World
In San Diego, Doudna may also touch on the unintended consequences of CRISPR, including the possibility of its premature and, in her opinion, dangerous use at this time in human genetic engineering. “I’m trying to lead a conversation about the responsible use of this technology. I certainly don’t advocate anything that inhibits legitimate research,” says Doudna. Still she believes that the basic science of CRISPR is not ready for clinical applications, particularly for any use on human germ line cells where changes would be inheritable. “Especially if you’re talking about making changes in the [human] germ line, changes that can be passed on to subsequent generations,” says Doudna, “that is a profound thing and something we need to study.”
Doudna is not against the eventual clinical development and commercialization of CRISPR Cas9. The reality is that funding for basic research is likely to remain problematic for the short and long term, Doudna believes. “We, as scientists, have to do a better job at thinking creatively about ways to fund research. We need a better model for cooperating with drug, technology, or commercial developers.”
Over the years, Doudna says, “I have had productive collaborations with big companies and small ones. When you get it right, it’s really fun and exciting. I’ve learned more from some of these collaborations than from anything else. The problem is, how to do it. Sometimes we in academia get distracted. We need to bring our expertise to bear on real world problems. In many of these diseases, people are suffering and we need to solve this.”
“I’m trying to lead a conversation about the responsible use of [CRISPR] technology.”
But the discovery of CRISPR Cas9 has also pitched Doudna into the contentious world of intellectual property disputes. The University of California is pressing claims on her behalf against Feng Zheng4 of the Broad Institute and MIT, who obtained a “fast track” patent on the key elements of CRISPR.5 Doudna finds the whole business tiresome and beside the scientific point. “There has to be a creative collective solution to this that allows collaborations to move forward in a less burdensome manner than in the past. I don’t know the answer to that but I do have the feeling that we need new answers.”
Doudna notes that her sudden fame has been anything but sudden. She has run her own lab for 25 years, she says, and there were times when things were not turning out as expected and the next step was not obvious. “I always say that you have to take the long view. This is not a sprint. It’s a marathon. Somehow I’ve always kept going by thinking that there’s something around the corner that’s going to be interesting. So far, that’s worked for me,” says Doudna. CRISPR cas9: some corner, some rock.
An earlier version of this story appeared in the ASCB Post on September 15, 2015.
References
1Connor S (November 6, 2013). “The more we looked into the mystery of CRISPR, the more interesting it seemed.” The Independent. http://ind.pn/1LcEQHI.
2Howard Hughes Medical Institute (November 10, 2014). Jennifer Doudna shares Breakthrough Prize in Life Sciences. HHMI News. http://bit.ly/1K9QcYN.
3Pollack A (May 11, 2015). Jennifer Doudna, a pioneer who helped simplify genome editing. The New York Times. http://nyti.ms/1QAw2M6.
4Szalinski C (March 25, 2014). Yogurt shows the way for a revolution in genome editing. ASCB Post. http:// bit.ly/1KOzPXi.
5Rood J (April 3, 2015). Who owns CRISPR? The Scientist. http://bit.ly/1FvEibb.
About the Author:
John Fleischman was the ASCB Senior Science Writer from 2000 to 2016. Best unpaid perk of the job? Working with new grad students and Nobel Prize winners.
