On November 18th, BenchSci had the honor of being joined by Nobel Prize winner and co-inventor of CRISPR, Dr. Jennifer Doudna, for a virtual fireside chat. As a company working at the forefront of biomedical technology, it’s incredibly inspiring to have such a prominent figure in the scientific community share some of her unique experiences and perspectives with us. Led by our SVP of Science and Product, Casandra Mangroo, this engaging conversation delved into Dr. Doudna’s work, her many extraordinary accomplishments, where she finds inspiration, and what she has in store for the future.
CM: Tell us a bit about how you got into science and scientific discovery.
JD: It all started on the big island of Hawaii, where I grew up and got excited about studying chemistry as applied to biology. I dreamed of making a career around investigating the chemistry of living systems. Like many kids, I was fascinated by the natural world, but I also wanted to understand things like how we get sick and why. Those were all motivators for me in those early days.
CM: I got involved in virology for that very reason, to understand how something so small could have such a huge impact in the world.
CRISPR/Cas 9 is an incredible, pioneering technology. For those who may not be aware, can you tell us a little about what it is and how it works?
JD: It started as a bacterial immune system—a system in microbes that allows them to defend themselves against viruses. Studying how it worked led to the realization that the molecules that are part of this CRISPR system can be harnessed for a different purpose in human, animal, or plant cells—namely, to alter DNA sequences precisely. Importantly, these systems are truly programmable at a molecular level, which is what makes them so powerful. It’s a wonderful property as a technology because it means that scientists can program CRISPR molecules to recognize and edit different DNA sequences in all sorts of different cell types.
CM: Was there a moment in your research when you had that “aha” moment—when you knew this was going to be something special that ultimately led to a Nobel Prize?
JD: There were two moments. One was when we first began investigating CRISPR molecules in the mid to late 2000s. We were uncovering functions of these CRISPR systems that made us think they would very likely be useful as research tools. This was before all the Cas 9 work—we were just thinking in terms of how these systems recognize DNA and RNA molecules selectively. That was when I first began thinking about how they might be harnessed as technologies.
The other moment was when, a few years later, in 2011, we started working with Emmanuelle Charpentier to investigate the function of a specific protein called Cas 9 and figure out how it was using an RNA molecule to find and cut specific DNA sequences. It was truly a highlight of my life when we figured out that Cas 9 is a programmable protein and that we could control its activity in terms of directing DNA cutting. It very clearly connected with lots of other research that had been going on regarding how to engineer genomes using double-strand DNA breaks to induce DNA repair. Those seemingly very different lines of investigation suddenly converged in that kind of proverbial moment, and it was really, very exciting.
CM: That’s an amazing story. What was it like to win the Nobel Prize and be one of the first women to win in this category?
JD: It’s kind of unbelievable in a way—I still sort of pinch myself. Growing up with dreams of being a scientist someday, I still remember just hoping that I could contribute scientifically. To then receive the call from the Nobel Committee was just extraordinary. Nobody goes into science to win prizes—they do it because they’re passionate about discovery, which is certainly true for me. But a lot of people have asked what it means to me to win a prize like that—for me, it’s really a recognition of a field and a moment in science that is impactful, and I had the great honor to be a part of it.
I also really hope that it encourages other people who are much earlier in their educational process but who might be thinking about going into STEM to recognize that anybody can do this. You just have to be committed; you have to be passionate. There’s an element of luck to it for sure, but I think it really does speak to the excitement of doing the kind of work that we do.
CM: Can you tell us a little bit more about the mission of your institute, the Innovative Genomics Institute, and some of the future work that’s happening there?
JD: Back in 2014, it was clear that CRISPR was accelerating the pace of fundamental science and was also moving quickly in a direction where it would be applied in medicine, agriculture, and other areas. It seemed to me that one of the most important ways that I could spend my time was to make sure that, as CRISPR continued to advance, we had a group of people that were working together to ensure that, in the future, it would become affordable and accessible for people around the world. I think it’s very important for nonprofits like our institute to take a leadership position and a role in assembling teams that are working towards equity and access. That’s really what our institute was founded to do.
Since then, we’ve established two big areas of focus. One is in rare disease—in particular, we have a clinical trial running right now for sickle cell disease and a trial that will go forward, hopefully, in 2022 for a rare disorder that affects the immune system of a large number of people belonging to the Navajo population.
The other area that we’re working in is climate change. I think one of the greatest challenges we face as human beings is how we’re going to deal with it, and I think CRISPR will play a big role. It’s very relevant to the conversations that are happening right now across the world.
CM: How do you think CRISPR will play a role in climate change? Could you give some examples?
JD: I’ll give you two specific examples. We’re working on one project right now with rice, which feeds much of the world but is one of the big offenders when it comes to carbon release. We’ve figured out a way to engineer rice so that it requires fewer nutrients and is also more tolerant to drought. But we know that will never have an impact if it’s only going on in a research lab—we have to be able to work directly with farmers as well. We have a number of relationships with groups around the world that are working with farmers so these types of crops can get field-tested. That way, when they eventually go through the approval process, we’ll be working in parallel with the folks who will actually be growing them.
The other area that I’m really excited about and I think has a lot of potential is using CRISPR in its natural setting. Specifically, using it in microbes found in the soil that metabolize methane, which is another big offender when it comes to climate change. We think that there are going to be exciting ways to use CRISPR to edit the genomes of those organisms to basically supercharge their ability to metabolize methane. We’re already seeing early evidence of this, so I’m really encouraged that this is going to be a very exciting area for future work.
CM: That’s really exciting. We know that microbes out-populate any other cell type in the world, so that would be amazing to see as an application.
Tell us a little bit about what inspires you. How do you think about what to do next?
JD: Well, I’m certainly inspired by my students. And by other scientists who are working either in our area or doing things that are completely different. It’s been fascinating to see what’s happening, for example, in plasma physics. I’m interested in understanding how we might deal with climate change, and I wonder if fusion energy will be possible in my lifetime. It’s hard to tell, but looking at what’s happening in other fields is really inspiring. It’s exciting to see science moving forward in so many different directions. It gives me hope for the future.
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