Patty Vest:
Welcome to Sagecast, the podcast of Â鶹ӰÊÓ. I'm Patty Vest.

Mark Wood:
And I'm Mark Wood.

Patty Vest:
In these extraordinary times, we're coming to you from our various homes, as we all shelter in place.

Mark Wood:
This season on Sagecast, we're talking to Pomona faculty and alumni about the personal, professional, and intellectual journeys that have brought them to where they are today.

Patty Vest:
Today, our guest is renowned biochemist, Jennifer Doudna, class of '85. She's Li Ka Shing Chancellor's Chair, and a professor in the departments of chemistry and of molecular and cell biology at the University of California, Berkeley, as well as an investigator of the Howard Hughes Medical Institute. But, she's best known for her discovery, along with French microbiologist Emmanuelle Charpentier of the now famous molecular tool known as CRISPR-Cas9.

Mark Wood:
Welcome, Jennifer. It's good to have you with us.

Jennifer Doudna:
Thanks for inviting me.

Mark Wood:
With us, sort of, here in cyberspace.

Jennifer Doudna:
Virtual, yeah.

Mark Wood:
How are you and your family doing in these crazy times?

Jennifer Doudna:
Well, thanks for asking, Mark. It's been very interesting few weeks, that's for sure. I've been very deeply involved in getting a clinical testing lab running at the University of California, Berkeley, so maybe we'll talk about that a little bit. Also, I've got a son who is graduating high school, so you can imagine that for him and his friends, very disappointing not to have commencement happening, but we have a virtual commencement tomorrow night, and we'll see how it goes.

Patty Vest:
That's exciting and safe.

Jennifer Doudna:
Yeah, exactly.

Patty Vest:
Jennifer, let's start, like they say, at the beginning. You grew up in Hawaii. What was that like, and what were you like as a child?

Jennifer Doudna:
Yeah, Patty, I grew up on the Big Island in a town called Hilo. It's not the kind of place that you probably imagine when you think about Hawaii. Very rainy, not a tourist destination by any means. It's kind of a working class town. My father was on the faculty at the University of Hawaii at Hilo, and literature professor, so I grew up in an intellectual family, but I really found myself captivated by the natural environment in Hawaii, and I was always the kid who wanted to understand how things worked and loved math in school. I was an outsider, certainly culturally in the '70s when I was growing up there, it was definitely not cool to be blonde, blue-eyed, hallelujah with a big nose and the hairy arms and all that. I definitely took my share of teasing and kids saying, "What's wrong with you?" But, I think, like many folks that have faced that, I think it also was an opportunity to kind of understand what it's like to be different, and to try to figure out how to fit in in different ways. For me, it was all about playing soccer, so I became a halfback on our [inaudible 00:03:24] school's soccer team in high school. I got two varsity letters in soccer, which probably, that's one of the things that I'm proudest of in high school. It's interesting.

Jennifer Doudna:
Because of that, it kind of connected me to a whole different community of kids that were people that I might not have known otherwise. That's an example of how I tried to find ways to be cool, even though I kind of wasn't cool at all.

Mark Wood:
You said that you were fascinated by the world around you and you were good at math. Your mom and dad were both in the humanities, so how do you think you ended up in the sciences? Can you trace that back to some point in your life, some time, or some event?

Jennifer Doudna:
I'm a misfit. I'm a black sheep. What can I say?

Patty Vest:
Good answer.

Jennifer Doudna:
Father's big disappointment was I didn't become a literature guru of some kind. Yeah, I don't know. It's one of those funny things. It's just who I am. It's kind of always been part of my personality. I remember, I was probably a junior in high school when the energy crisis was happening in the '70s, and I got very interested in the whole question of how could you come up with ways to not have to use fossil fuels, and started researching that. I can remember sitting in the library looking up articles about geothermal energy and that sort of thing. Yeah, I was just always fascinated by science and technology solutions to problems that we face in the world, and never imagined that I would become a scientist until I think I was maybe 10th grade in high school when we had a lecture series by people around the state of Hawaii who were professional scientists. A number of really fascinating people came through, marine biologists, volcanologists, astronomers, but the one that really caught my attention was somebody who was working on cancer biology.

Jennifer Doudna:
Her work was all about trying to figure out why do normal cells become cancerous. She talked about how she was a biochemist, somebody who studied molecules and tried to figure out how they worked. For me, when I saw that talk, I still remember it, a light bulb went off, and I thought, "That is exactly what I want to do. That sounds so interesting and so fun. I can't imagine anything more interesting than that." That's why I actually went to Pomona, right? I started thinking, "I want to be a biochemist." In those days, this is in the late '70s, I guess, early '80s, right around 1980, there were not very many undergraduate colleges that had a focus, or even a class in biochemistry, much less a major. Pomona did, and so that was something that really attracted me to the campus.

Patty Vest:
You mentioned that biochemistry was what brought you to mainland and to Pomona. Can you tell us about some of the mentors you had while you were at Pomona?

Jennifer Doudna:
Yeah, I had amazing mentors. Just from the very beginning, there were incredible scientists who were welcoming for people like me that knew nothing, and welcoming into their laboratories, and opening up opportunities. Gosh, let's see. There was Sandy [Grabner 00:07:21], wonderful professor of mathematics, and had him for a couple of different calculus classes. Loved talking to him. Used to go to his office hours and he's always very nice and great at explaining things and trying to make it real. Because, sometimes, math can be a little esoteric, right? He was awesome at that. Fred Grieman of course in chemistry was incredible. Then, Sharon Panasenko, I mean, I have to really give her a shout out. I mean, she left Pomona a number of years ago now, but she was... When I was there, she had just been hired as a professor in chemistry whose focus was biochemistry. She just gave us the best background in that topic I could possibly imagine. Her course was very hard, and she expected a lot, and it was great. She was very demanding.

Jennifer Doudna:
Then, I remember, one day, I think it was in the second semester that when I was taking her biochemistry class, she said that she had two openings for students to work in her laboratory over the summer, and that we could apply to do it. I thought, "Well, I'll never get accepted, but I guess I'll apply anyway." It sounds like kind of a bad attitude, but I didn't assume I was the best, or even that great. I don't know. I just didn't really think of myself as being all that talented, but I just really wanted to do it. I applied to her lab, and amazingly, she accepted me. I got this opportunity to work with her over the summer, and really work with her. It wasn't just she threw something over the fence, and said, "Come back in 10 weeks when you're done." It was every day, going in and planning out experiments with her, and it was just the most amazing thing. It was just incredible, and what an amazing opportunity.

Jennifer Doudna:
Then, I guess, the only other person I would like to give a special shout out to is R. Nelson Smith. R. Nelson Smith, legendary at Pomona, right? He's been gone for a while, unfortunately. But, when I was there, he was teaching general chemistry. He was just incomparable. He was fabulous, just incredible, very demanding. It was a tough class. I didn't do very well in that class, and I questioned my ability to be a chemist or a biochemist, but he asked a lot, and he really wanted the students to rise to the challenge, and we did. We did our best. It was amazing to have somebody like that that really kind of, for me, was the door into... It was like opening a door into a whole new world of chemistry that I had no idea existed, and it was hard, but in the end, I embraced it. I loved it.

Mark Wood:
Now, after leaving Pomona, you had either very good luck or very good judgment in your picking your mentors after that too, right? I mean, you have two who, one at Harvard, and one later during your post-doc who went on to win Nobel Prizes. Can you tell us a little bit about working with them?

Jennifer Doudna:
Right. Yeah, after Pomona, I applied to... When I was in my senior year at Pomona, I had just finished the summer of working in Sharon Panasenko's lab, and I was doing a little bit more work with her during my senior year, and I loved it so much. I loved the lab work, and I thought, "I want to do more of that. How can I do more?" I decided, "Well, I'll go to grad school." I ended up getting into the program at Harvard Medical School, and when I got there, it's a big place, and just tons and tons of research going on, and I suppose a little bit lost like how to find the right lab for me, so to speak. I got lucky, because... It really is luck, because I was doing these laboratory rotations, and I worked in two great labs. I loved both of my first rotations. These are two to three months time periods of working in a lab just to get a flavor for it, and decide if that's the lab where you want to do your PhD thesis research. Then, I had to do a third rotation, and so trying to figure out, "Okay, where do I go next?" I happened to hear about this young guy whose name was Jack Szostak, who was in his early 30s, but already a full professor tenured at Harvard and widely rumored to be a bit of an eccentric genius.

Jennifer Doudna:
When I went to talk to him, he was just so passionate about science, and he said, "I'm a yeast geneticist by training, but I'm moving in a very new direction with my work. I'm interested in the origin of life." I thought, "Wow. Probably can't get a much bigger question than that." But, his genius was that he could take a huge question like that that sounds intractable by experimental science, and he could break it down into experiments that we could actually do in the lab. I could just tell that he was the most creative person I'd ever met. I found that very attractive. I joined his lab, and he turned out to be an incredible mentor, and through his mentorship and opportunities that I had while I was a student there, I had the chance to meet the person that became my post-doctoral mentor, Tom Cech.

Jennifer Doudna:
By that point, Tom Cech had actually already received his Nobel Prize, so he was clearly, again, very, very accomplished, credible scientist. I had the opportunity to work with him during my post-doctoral training, which basically, in our field, it's training that you do after your PhD to gain additional experience in the lab, but also to learn a little bit more about what it's like to run a lab, how you manage people, how you pick the right projects and things like that. Again, he's a very different style than my graduate advisor, but equally brilliant, and very gifted at picking the right project, clearly, and teaching us how to figure out what really constitutes good science. How do you do really rigorous, really interesting work, and then how do you communicate it to people, because that's an important part of the puzzle as well.

Patty Vest:
You mentioned that, at Pomona, at the beginning, you had some doubts of whether or not you would get that lab position as a student. By this point, you were working with a Nobel Prize winner. How did that evolution take place? How did you feel about that?

Jennifer Doudna:
How did I feel about joining his lab?

Patty Vest:
Working with somebody so renowned. How did your confidence evolve? You were doing great work already. How did your confidence evolve from them?

Jennifer Doudna:
That's a really interesting question, Patty. That's something I think about a lot, because I think it's very important for a lot of students to understand... I think for students, they might look at somebody like me, and my past might seem unusual or just hard to imagine, like, "How did she get from this little town in Hawaii to where she is now?" I think, for me, one of the key things that my mentors offered to me was experiences that helped to build my confidence in myself, right? Because, I think, for me, when I started out, let's just... I came from a unlikely background, honestly, right? I mean, I was in a small town, and I was lucky that I had a really supportive family, but nobody in my family was a scientist. I certainly didn't know any women scientists when I was growing up. None. I didn't know of any. I didn't even know if it was a career that a woman could do reasonably. I had no idea. I wasn't always the top of my class. I wasn't always the best in every class. I didn't really have sense of myself as special in any way. I felt like I'm one of the pack, I'm trying to do my thing like everybody else.

Jennifer Doudna:
When I got to grad school, I have to tell one little story, because it really illustrates, for me, a bit of a turning point in a way. I had joined Jack Szostak's lab, this, at the time, young, brilliant man who went on to win a Nobel later, and I was doing this rotation project in his lab, and I had told him that, "Yeah, I want to work on this origin of life project." I was, the time, the only person in the lab that was working on this kind of weird, crazy, but really super-cool, really fun, interesting project. I was doing a lot of reading, and I was trying to get up to speed on the work that we were doing and planning out experiments, and one day, I was sitting at my desk in the lab, and my advisor came over to me and he said, "Hey, Jennifer. I've been thinking about an experiment that I think might be really, really interesting to do, but I'm not sure. I want to bounce it off of you and see what you think."

Jennifer Doudna:
Can you imagine, right? This guy who's this genius and the youngest tenured professor at Harvard wants to know what I think about his idea? You're kidding. I think that just was kind of this really cool moment when I realized he cares what I think. He really cares. He wasn't making it up or faking it or anything. He really wanted us to sit down and have a conversation about what did I think about his idea. This just, for me, was like, "Wow. If he thinks that my brain is worthy, than yeah, maybe it's a little bit worthy." I think that's something that I, now, as a mentor, I really try to do that with my students. That's the other thing that's very, very interesting, is I think that creative ideas come from everywhere. I think that the most successful research teams, teams of any kind, really, but certainly in my own running a research lab, I think the most successful labs are labs that enable a wide diversity of ideas, and they enable everyone in the lab from the most experienced person to the least to feel empowered and enabled to contribute.

Jennifer Doudna:
That's something that my mentors, I would say both of them, really, gave that to us. I think they really both created laboratory environments where we all felt empowered to contribute, and we all felt validated. I've asked my share of stupid questions, believe me, many times, right? Things that I haven't understood, or all kinds of things that happened, and I think just making sure that people feel like they're validated and they're empowered in their work is super-important. That's probably the most important lesson I learned from my advisors.

Mark Wood:
Let's move into your research a little bit. Starting off, you focused mainly on RNA throughout your research career. What is it about that? It's seen by most people as the understudy to DNA. What is it about it that's fascinated you through the years?

Jennifer Doudna:
Well, let's just start with what you just said. I love the fact that RNA is the underappreciated, under... People don't expect much of RNA, right? It's kind of cool automatically in my book for that reason. It goes back to my graduate work where my graduate advisor, he was very interested in this question of the origin of life. His hypothesis was that it really all started with RNA. That wasn't his unique idea of course. There's many others that had been thinking about this, but I think that it was something that we started to... We talk about this a lot in the lab, and not just my advisor, but other students that were in the lab. We would talk about, how could you imagine a replicating system, a cellular life form getting started? Increasingly, as I was doing my graduate work, all the pieces were really pointing to RNA.

Jennifer Doudna:
It's kind of relevant to the current pandemic that we're in with coronavirus actually, because coronavirus, many people may know that it's an RNA virus. That means that the RNA of this virus enclosed all the information needed to make more virus and to be very good at infecting human cells. RNA is clearly a very confident, very good genetic material, but what I was doing in my graduate work was studying something that had been unknown until not too long before I got started in grad school, which is that RNA can also work as an enzyme. That means that it can accelerate the rates of chemical reactions. That was a new discovery. That was actually what the work of Tom Cech, my post-doc advisor, had shown. That's what he won the Nobel Prize for. It was a very interesting finding, because it really, for the first time, suggested how a genetic material, in this case RNA, could also potentially be able to replicate itself. It would have the chemical properties, chemical capabilities to make more copies of itself.

Jennifer Doudna:
I found that just incredibly interesting and fun to think about. I still do. Over the course of my career, I've always just found myself drawn to this underdog RNA, and trying to understand what it does in modern biology, and then just always in the back of my mind, I'm thinking, "How do I connect that back to what it might've done in very early evolution, and how it could've given rise all of this.

Patty Vest:
Jennifer, let's talk about the discovery of CRISPR. I know it's a long story, but can you walk us through it a little bit?

Jennifer Doudna:
Well, yeah, the story of CRISPR for me, it really does stem from my interest in RNA, actually. I'll tell you, very briefly, a little story of my career. After I did my post-doctoral work, I took my first [inaudible 00:23:48] position at Yale University. While I was there, I was running a research lab. We were looking at the molecular structures of RNA molecules using a technique called X-ray crystallography. That was incredibly fun, really exciting. We solved a couple of the first actual 3D structures of RNA, so we could see their shape and how they worked, and how they could be involved in chemistry for the first time, which was incredibly exciting. Then, I think I was a few years into that, and I had... Unexpectedly, I had an opportunity to move to the University of California, Berkeley. My initial reaction was, "Gee, thanks for thinking of me, but I'm really happy at Yale."

Jennifer Doudna:
I went out to California, and Berkeley's pretty nice. One thing led to another, and I took the job, and I did move my lab to Berkeley. Frankly, one of my motivations for doing that, beyond Berkeley being a pretty cool place, is that I really wanted my research to expand in some new directions. In particular, I was very excited about moving beyond looking at just the shapes or RNA molecules to really understanding how they worked in cells, and how they help to really control the way that genetic information is used in cells. Of course, viruses do this very effectively, right? That's what a viral infection is, is that the virus takes over the cell and uses the cell's machinery to make more copies of itself.

Jennifer Doudna:
I moved to Berkeley in the early 2000s thinking that I would focus increasingly on how RNA was actually functioning in cells, whether through viral infections or just in uninfected cells do really control the way that genetic material was deployed. That led to a chance meeting with a fabulous scientist at Berkeley named Jillian Banfield, who is in a completely different field from me. She's a geobiologist, so she studies bacteria that you find in gold mines and places like that. She was doing a lot of DNA sequencing of these bacteria, and she had discovered something very interesting. That is that bacteria have a way of recording the genetic material of viruses that have infected them, and storing that information over time in a place called the CRISPR in the bacterial chromosome, in the bacterial DNA.

Jennifer Doudna:
She was very interested in this, and at the time, nobody knew what these sequences of DNA were doing. Why were they hanging out in these bacteria, and why were they being stored over time? But, Jill, again, I consider her a genius. She's a very, very interesting, very creative scientist. She knew that there was something very cool and very interesting about these, and it wasn't something just to be ignored. She reached out to me, because she literally Googled, "Who at Berkeley works on RNA, DNA, who's a biochemist?" My name popped up. She called me and said, "I think I've stumbled across a bacterial immune system that uses RNA, and I don't know how it works, but do you want to work on it?"

Jennifer Doudna:
Anyway, we started meeting, and one thing led to another, and I started to work on it. Again, for me, in my lab over the years, it's always about people, right? It's always about people, and I just got lucky. Again, I'm very lucky that right around the time when I was having those first few conversations with Jill Banfield and she was telling me about CRISPR, and what might this be doing, and how does it work, I met a fabulous scientist, Blake [Wiedenheff 00:28:02], who was from Montana. As a grad student, he had worked on bacteria, and he was probably one of the, I don't know, 10 people in the world at the time that had heard of CRISPR, because he had come across it in his own work. He, like Jill Banfield, wondered, "What the heck are these CRISPR sequences doing, and are they really providing an immune system to bacteria? If they are, how does that work?"

Jennifer Doudna:
Anyway, one thing led to another. He came to my lab, and started walking on this. Eventually, that research was fun, and Blake, he's kind of a work hard, play hard kind of guy, so when I had new students come to the lab, I would ask them, "What would you like to work on in the lab?" They would say, "I want to work with him."

Mark Wood:
Whatever he's working on.

Jennifer Doudna:
Whatever he's doing.

Mark Wood:
I'll have what he's having.

Jennifer Doudna:
Exactly. I'll have what he's having. Exactly. A little team began building up around CRISPR in the lab, and that eventually led to my attending a meeting in Puerto Rico on CRISPR. I was actually meeting about microbiology, but they had little afternoon session on CRISPR where I met Emmanuelle Charpentier. She was a fabulous... Again, just a wonderful microbiologist. She had to come to CRISPR from her own unique angle, and when we met at that meeting, we decided to work together on a very specific question that struck us both as very interesting, which was trying to understand why some bacteria were able to use a single type of CRISPR protein to protect themselves from viruses, and specifically, how did that work. The name of that protein is Cas-9. Emmanuelle and I started working together over 6,000 miles. She was located in Sweden at the time. I was at Berkeley. She had a student working in Vienna who was a student in her lab that started working on this project with us, and I had a fabulous post-doc from the Czech Republic, Martin [Yunek 00:30:15], who was the person in my lab that took on this partnership.

Jennifer Doudna:
I've worked on a lot of collaborations over the years, and my experience, maybe 50% of them work out, and most of them, you get something out of it, but maybe it doesn't really click. But this was just kind of magical from the beginning somehow, because first of all, Martin Yunek and my lab, and Chris [Tylenski 00:30:44], this guy in Vienna who was working with Emmanuelle, they turned out by just happenstance, they had grown up just across the Polish border from each other, and they both spoke the same dialect of Polish. [crosstalk 00:30:57]

Patty Vest:
Oh, wow.

Jennifer Doudna:
Now, they hadn't met in person, but they started communicating over Skype in those days, and they realized this. They immediately had this really cool cultural connection, and then the science just started to click, right? We quickly got this system working. We had purified Cas-9 proteins, and we were doing experiments to figure out how it could find and destroy viral DNA, because that's really what it does. We figured out exactly how that worked, and it was just the coolest thing ever, right? It's literally a programmable protein that uses a little RNA molecule that provides the address label to go to a piece of viral DNA and cut it up. Once we figured that out, that project was just on a fast track, because we realized... This is one of those moments in my life that I'll never forget, is being in my office and having Martin Yunek showing me his data for how this Cas-9 protein was working as a destroyer of viruses and realizing that we could take that chemical activity and use it for something very different, because of all the work going on in, not our lab, but many other labs that had shown that if you could cut DNA at a particular place in the DNA of a cell, then you could induce the cell to fix it, fix the break, and in the process, make a change to the DNA sequence.

Jennifer Doudna:
That's a process called genome editing. There were earlier technologies for doing this, and people all through the field of biology was very, very excited about the potential for this, but nobody had come up with a great way to do it. It turned out nature had, right? Sends out these bacteria, had a wonderful way to do it. They were using it for a different purpose, but we realized that we could just repurpose it as a technology. That really set us on the path of what we've been doing for the last, now, eight years of really thinking about how we're going to use genome editing to do all sorts of really important things in medicine and agriculture, but also to do it in a ethical and responsible way.

Mark Wood:
Since that time, CRISPR's kind of taken the biological world by storm. People are using it all over. What are some of the applications, or research projects that you find most exciting that are using CRISPR?

Jennifer Doudna:
Well, on the research side, I love the fact that when you have a way to manipulate DNA in cells and do it at a precise place that the experimenter can decide, "I'm going to go tickle that gene over there and see what happens," right? Imagine that that just is incredibly powerful tool for understanding fundamental biology. There's just extraordinary work that's been done. People have done all sorts of things with organisms that, in the past, were only possible to study by observation. Now, you can manipulate them genetically, and so you can inquire about the genetics of things like why are snail shells right handed in nature and not left handed. That's one of the longest standing questions in developmental biology, and now we know. We know. There's a gene. CRISPR found the gene, right? That was one of the crazy things.

Jennifer Doudna:
I know another scientist who's working on a fascinating project where she's trying to understand how bipedalism evolved. Why are we bipedal? We are bipedal organisms, but we evolved, clearly, from animals that are quadrupeds. How do we think about that? What's the genetics there? It might seem like an intractable kind of question, except that it's been known for a while that there are these rodents in... I think they're South American, that are bipedal, actually. They really walk on their hind legs, and they're pretty closely related genetically to another type of rodent that is a quadruped. What this scientist is doing is using CRISPR to figure out the differences genetically that allow this organism, this rodent that is bipedal to walk on two legs, and what are the genes that are involved in that. That's the kind of thing that, in the past, no way, right? You would never ever have... You didn't have the tools to figure out the answer to a question like that.

Jennifer Doudna:
For me, as a scientist, as a researcher, I love that stuff, right? I mean, it's just awesome to see that kind of question and answer process enabled with technology. But, I think in a very practical sense, gene editing is clearly going to be really impactful in biomedicine. It's going to be really impactful in agriculture, and it's going to be really impactful in what I would call synthetic biology, being able to manipulate organisms to make chemicals and products that are desired in a technology sense. All of those areas are things that I'm excited about. In my own work, I would say that my own lab, we're primarily focused on biomedical applications and really trying to make sure that the CRISPR technology is the best it can be, that we understand how it works, and I started an institute at the University of California, Berkeley and UCSF Medical School about five years ago called the Innovative Genomics Institute, and that institute is spearheading a couple of clinical trials. We're moving ahead with sickle cell disease and with a rare immune disorder that affects just a very small number of people, not something that drug companies are going to go after, because it's not going to be a money maker, but clearly for people affected with a disease like that, it's their life, right?

Jennifer Doudna:
We're very excited about the potential for CRISPR to be a cure for those kinds of diseases. I'm really wanting to ensure that the technology is safe, that it works well, and that it's used in a responsible way. Also, frankly, that it's used equitably. I think that one of the big topics that's been in the media over the last few years is really about the disconnect between incredible advances in science and technology, but then the price tag being such that almost nobody can afford those. Well, I can tell you, I have no interest in developing things like that. That's not exciting to me. What is exciting is figuring out, "How do you take a powerful technology and develop in a way where it is affordable? Where it is widely accessible to people that need it?"

Jennifer Doudna:
That's a [inaudible 00:38:42] challenge, right? But that's, I think, something that, certainly being at a public university here in California, it's kind of baked into our mission, really. It's something that's really, really important to me personally. I'm very excited about, on the one hand, pushing the technology, but always doing it with thinking that we have to make this affordable. We have to make it accessible.

Patty Vest:
Jennifer, you mentioned using CRISPR responsibly. Are there people using CRISPR today in ways that you would prefer not to see?

Jennifer Doudna:
Well, I think a challenge in science that we see in general is that science is like any other human endeavor, right? People are people. If you have a powerful tool, there is some type of person that wants to use it for whatever, anything, right? Anything that can be done should be done. I think that CRISPR's been no exception to that. What we've seen with CRISPR over the last few years is that there are a couple of things that've been done with CRISPR that are clearly, I think, irresponsible and [inaudible 00:40:00] shouldn't be done. One of them, probably the one that got the most attention was CRISPR babies, right? Using CRISPR to change the genetics of human embryos, not for research, but for actual implantation, and to create a pregnancy. I think that clearly is something that just, at least right now, shouldn't happen, because the technology isn't ready, and we're not ready, right? Society isn't ready for that.

Jennifer Doudna:
The other type of application that I think is important to pay attention to for sure is something called gene drive, which is a way that scientists, some scientists, are using CRISPR to introduce a genetic trait that can be spread very quickly through a population of organisms, like mosquitoes. This could have incredible benefits, because you can use it in a way that would, for example, prevent the spread of mosquito borne disease, like Zika virus or dengue or malaria. But, it could also be an ecological disaster. What if you used it to cause certain types of organisms to go extinct, or be incapable of reproduction? How would that affect the ecosystem? For me, those are two areas where I think we have to be very vigilant about the way the CRISPR technology is being used. This is really the moment for the scientific community to stand up and say, "Certain types of applications are just unacceptable."

Mark Wood:
You mentioned that your lab has been focusing on coronavirus testing. How is that going, and what's involved in that?

Jennifer Doudna:
Yeah. I think, like many scientists, when it was clear that we were facing a global emergency with this pandemic back in the early part of this year, many of us asked ourselves, "What could or should we be doing to use our own expertise in this time of real need?" One of the things that we've done at the Innovative Genomics Institute is we started a clinical testing lab. That has turned out to be a very, very interesting, and I think very important endeavor on multiple levels. First of all, we were doing it on a campus, which my campus is the University of California, Berkeley, which is not a medical school. For us to take clinical samples and report medical results was something that we had to figure that out. It's been a very interesting task, but we did do it.

Jennifer Doudna:
We got it up and running in about three weeks, amazingly. Took going all the way up to the governor of California and the president of the University of California system, and many, many other people who helped get this to go, but now, we have this lab running, and what we're doing is testing samples from people for the presence of the coronavirus, and we're using a standard test. It's not a CRISPR test yet. We hope to develop that at some point, but right now, we're using a standard test. But, we also raised quite a bit of donor support for this. Because of that, we've been able to offer this test for free to many people in the East Bay area of the Bay Area of California, where quite frankly, many of those folks don't have access to healthcare. They don't have access to testing. A lot of our partner healthcare organizations service the unsheltered, the uninsured folks that are first responders, people that work in the California energy sector that are keeping our power plants running, police, firefighters, people working in nursing homes, and it's been really interesting, because we've certainly gotten to know a lot of people in our own community that we wouldn't have otherwise gotten to know.

Jennifer Doudna:
This is one of many, many stories I could tell you, but there [inaudible 00:44:19], very early on, we had just started the testing lab, and we're starting to work with an organization in East Oakland that works with... goes out other homeless shelters, homeless encampments, actually. Not in the shelters. These are just tent camps, and works with those folks to offer healthcare guidance and services. One of our volunteers from our testing lab took a whole box of our test kits over to them and asked them if they would like to submit samples for testing, and then for followup if they were tested positive. The woman receiving the box just hugged our volunteer, just hugged her and said, "This is amazing." She said, "We thought no one cared about us."

Jennifer Doudna:
Yeah, even now, I feel so emotional about it. You realize that there are folks right just within a few miles of our lab who literally feel abandoned by their government and by this country. It's heartbreaking, but it's really makes us... Every day, we have a testing lab meeting seven days a week. Every day, we're on an almost hour long call with our testing team about how we're running the tests for the day or the week, and every day, we remind ourselves, "This is why we do what we do," because these people really need us, and they don't have anyone else. It feels like really important work, and we're proud to be doing it.

Patty Vest:
Do you know how many people approximately that you have tested since you started?

Jennifer Doudna:
Yeah. It's a few thousand that we've tested so far. We're now in the process of ramping up to an automated test, so we started off doing a couple hundred tests a day, and we now have robots that do our tests for us, which is great, and so we're now able to do about 1,000 tests a day. Quite frankly, the bottleneck for us now is not the tests. It's actually the sample intake. Figuring out how to get those 1,000 samples a day has turned out to be non-trivial.

Mark Wood:
We're almost out of time. This is kind of a petty thing to end on after talking about something really important, but your name comes up pretty repeatedly over the last few years among possible recipients of a Nobel yourself. How does it feel to be talked about in that way?

Jennifer Doudna:
Well, Mark, I still, in my heart, think of myself as that young girl growing up in Hilo, and thinking to myself, "Gosh, I wonder if I could be a biochemist someday." I still think of myself that way, right? Honestly, I still have moments when I look around at my colleagues and the people I'm so lucky to work with every day, and I think, "Wow, I'm so lucky." I just feel grateful. For me, that's what it's about. It really is. It's about doing work that I enjoy, where I feel like I'm making a contribution. I think the opportunity to work with so many smart people and a lot of people that are smarter than me is amazing. I stay focused on that, and I leave those... The prize decisions are beyond my [crosstalk 00:47:58] shall we say.

Mark Wood:
All right. On that note, I'm afraid we're going to have to wrap this up. We've been talking with Jennifer Doudna, class of '85. Thanks so much for joining us.

Jennifer Doudna:
Thanks, Mark. Thanks, Patty. Great to be here.

Patty Vest:
Thank you, Jennifer. To all who stuck with us this far, thanks for listening to Sagecast, the podcast of Â鶹ӰÊÓ. Stay safe, and until next time.