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[MUSIC PLAYING]
KEVIN DAVIES: Hello, everyone and a very warm welcome to you for this fourth and final installment of our Women in Science Webinar Series. It's 1 PM in New York, 10 AM in Berkeley, California. And we're very pleased you could join us. I'm Kevin Davies, the Executive Editor of The CRISPR Journal, editor-at-large at GEN. I'll be the host for today's discussion with the one and only Jennifer Doudna, the 2020 Nobel Laureate for Chemistry. I'm also contractually obliged to say that I'm also the author of Editing Humanity, the best book on the CRISPR revolution since A Crack in Creation that Jennifer co-authored a few years ago, just out.
KEVIN DAVIES: We're thrilled to be joined by Jennifer Doudna. She'll be joining us live in about 10 minutes, so we'll have a good 30 minutes to ask her questions. In the meantime, I'm thrilled to be joined by four of her past and former colleagues. I'll introduce them in just a second, also by Karla Shepard Rubinger, the Executive Director of the Rosalind Franklin Society, who will be my co-host today, and John Sterling, the Chief Editor of Genetic Engineering News.
KEVIN DAVIES: Among Jennifer's colleagues joining us are Dipali Sashital from Iowa State University, Ross Wilson from the IGI in Berkeley, California, Blake Wiedenheft from Montana State University, and Rodolphe Barrangou from North Carolina State University, and the Chief Editor of The CRISPR Journal. Hello to each of you. Thanks for joining us. We'll to you in just a second.
KEVIN DAVIES: One housekeeping thing I have to-- a couple of housekeeping notes I have to take care of first. The Women in Science Series, if you're new to this, you've just found out about it because of Jennifer's participation today, it's been a four-part series that kicked off with an absolutely spectacular lecture about six weeks ago from Matthew Cobb of the University of Manchester in England on the life and times of Rosalind Franklin. We're doing this series because this year is, of course, the 100th birthday of Rosalind Franklin.
KEVIN DAVIES: We've also had great presentations and discussions with RFS President Rita Colwell, the microbiologist, and MIT President Emeritus, Susan Hockfield. All of those can be found on on-demand links at the Genetic Engineering News website and the RFS website as well. We need to thank a couple of companies who've made this series possible. Horizon Discovery and OnRamps Bio, Horizon Discovery drives the application of gene editing and gene modulation to enable you to identify the genetic drivers behind human disease, develop diagnostic workflows, and deliver new therapies for precision medicine.
KEVIN DAVIES: Horizon offers innovative tools and services based upon the ability to modulate or alter the function of almost any gene in mammalian cell lines. And OnRamp Bio is the San Diego-based genomics company that develops the Rosalind Discovery and Collaboration Platform, named in honor of-- you guessed it, Rosalind Franklin. The Rosalind Platform simplifies the complexity of bioinformatics, so that scientists can harness the potential of multi-omic data interpretation.
KEVIN DAVIES: OnRamp is a founding member of the Rosalind Franklin Society Council of Corporate Leadership, which supports the scientific careers of women and underrepresented minorities. So we're thankful for their support. So before Jennifer joins us which we hope will be punctual on time in about 11 or 12 minutes, we have a chance to get some observations and recollections from four of her current and former colleagues.
KEVIN DAVIES: Maybe I can start with Blake. Blake Wiedenheft, you are legendary in that you literally brought CRISPR to Jennifer's lab. Is that a fair statement?
BLAKE WIEDENHEFT: I don't know. I was one of the first people to work on CRISPR in Jennifer's lab. I came from MSU where I am now. We were studying viruses in the hot springs in Yellowstone National Park. And that wasn't a space that Jennifer's lab had previously worked in. But she had been introduced to the concept of CRISPR by Jillian Banfield, a colleague there at Berkeley, so I think was just the right guy at the right time.
BLAKE WIEDENHEFT: And it worked out in my favor to have a shot at working in Jennifer's lab and kicking off the CRISPR project, I suppose. But I mean, a lot of the early work really focused on type 1 systems. And it wasn't until some of the other members of the lab got involved. It's quite the-- it's quite the experience to come in as a new postdoc into a lab where nobody works on the project that you're proposing to work on, and then leave five years later.
BLAKE WIEDENHEFT: And this huge machine, everybody in there is really focused on CRISPRs. It was incredible, somewhat intimidating but exhilarating all the way.
KEVIN DAVIES: Yeah. Yeah. Well, I wanted to ask all of you to maybe share a story or your biggest takeaway from working with Jennifer and your reaction to her winning the Nobel Prize. Of course, with Emmanuelle Charpentier, we mustn't forget Emmanuelle. Dipa, tell us your-- what did you take away from working with her? What are your memories of working in the lab?
DIPALI SASHITAL: I would say my number one memory is what an incredible team of scientists she always put together. It was just absolutely thrilling to be in that lab. And by far, I would say the most exciting science that I ever got to do. Just in general, she was very, very good at fostering good dynamics in the lab, especially, I think at the time that we were there, there was a lot of new exciting projects, the CRISPR project.
DIPALI SASHITAL: At the time, there was still quite a lot of work going on in other areas. And it was-- one of the things I always found really exciting was how much we were all invested in each other's projects, so I felt like I could describe other people's projects as well as I could describe my own.
KEVIN DAVIES: Yeah.
DIPALI SASHITAL: In terms of her winning the Nobel Prize, I was absolutely thrilled. And I was also excited, because when I first joined the lab, I felt like that there was a chance that she would win a Nobel Prize someday. But it was actually for her work that she had done prior to me joining the lab, which was for RNA structure. That's my passion. That was the reason I joined her lab, not to work on CRISPR, but because she has done such pioneering work in another area as well.
DIPALI SASHITAL: So this is quite nice to have her win for yet another major discovery that her lab has made.
KEVIN DAVIES: Well, that doesn't preclude her from winning another one, right?
DIPALI SASHITAL: Who knows?
KEVIN DAVIES: You're not going to make any bets. Have you-- you run your own lab now. Have you-- did you absorb anything in the way that she needed her group together and mentored her grad students and postdocs? Any lessons that rubbed off on you that you feel have made you a better PI?
DIPALI SASHITAL: Yeah, absolutely. I would say that the thing that I learned the most from her is how to be focused, how to make sure that the research that you're doing is going to end up having an interesting result from it, and how not to pursue things that might end up taking you down a rabbit hole. And she was very good at doing that for her students and her postdocs, making sure that they stayed on track, recognizing when they were struggling and putting them onto something else that could potentially bring them results.
DIPALI SASHITAL: And so those are the biggest lessons that I've taken away is how to make sure that everyone in the lab is doing something that's productive, while they're also potentially pursuing something really ambitious and a new direction.
KEVIN DAVIES: Right. Ross Wilson, you were a member of her lab, and now you're a member of this imaginative 21st century institute that she's built and is building. What are your impressions of working with Jennifer for so long now?
ROSS WILSON: Yeah. Coming into the lab was very intimidating for me. I was kind of a humble grad student from Ohio State. And I came into Berkeley and people like Dipa and Blake were there, doing their postdocs and just completely doing completely incredible science and working so hard. So it was a little bit intimidating but also very, very inspiring. And that environment has pervaded this institute I'm working at now in collaboration with Jennifer.
ROSS WILSON: And yeah, it's just very inspiring to be part of that kind of world. And I guess, I'd like to share one anecdote, which is a little bit silly, but I think it ties back to the Nobel Prize. One tradition in group meetings was that you'd show your data and then Jennifer would give you some feedback. And one thing that almost became her catchphrase was, did you try adding RNA to that?
ROSS WILSON: So if you had a crystal structure that wasn't quite coming together and you needed a better crystal, she might say, did you try adding RNA? And it seems to have worked in a lot of cases. And it was kind of funny. That was like her catchphrase. And every PI seems to have one. One of my trainees have told me that mine is should be easy, which I think is almost troubling.
ROSS WILSON: But in her case, I think this catchphrase really paid off, because for people that really know the story of Cas9, it's part discovery, but it is part invention too. And the real invention at the core of turning Cas9 into this powerful genome editing technology is taking two pieces of RNA and adding RNA to RNA. So in adding RNA to that, she inspired, I think the fusion of the tracer RNA and the CRISPR RNA, making this single guide which is now the heart of the most convenient CRISPR tool that we have.
ROSS WILSON: So I hope that her ability to take a catchphrase and make it useful pays off, because she and I are working on CRISPR delivery now together. And that is certainly something that is not easy and should be easy. So hopefully, our collaborations there follow that same lucky trend.
KEVIN DAVIES: Yeah. Sam Sternberg, welcome to you. Thanks for joining. I know you just hopefully have seen a happy graduate student defend his thesis or get his thesis or something like that.
SAM STERNBERG: Postdoc-- postdoc's last day. But yeah, I'm sorry to hop in a couple of minutes--
KEVIN DAVIES: That's quite a while. We've already plugged your book, just so you know. Sam was a colleague of Jennifer's and is now an assistant professor at Columbia University and doing some fantastic work. Quickly give us your recollections of working with Jennifer and what she's meant to you in terms of her-- what's rubbed off on you as you launch your own independent research career now?
SAM STERNBERG: Yeah. I was thinking about that today as I was organizing this last day for the postdoc and-- in the chat I have with Blake a few weeks ago, I think we realized that so many of the practices and the habits you bring into starting a lab, running a lab, no one teaches you to do that, except then you realize that I've actually acquired and inherited all these fantastic ideas and traditions that come from the labs you graduated from.
SAM STERNBERG: So I think, in Jennifer's case, I can think of a lot of different styles that I take in the lab here that directly were inspired by how she ran the group. And I think the number one thing I would say I took away from Jennifer was how to tell a story with your science. It's something I think about all the time. Publishing an article, it's not a series of facts organized into figures.
SAM STERNBERG: You need to blend them together and weave a narrative, because that's what we all want to read. We want to learn about a story. And I think Jennifer has just dialed in how to do this in a way that makes your science come alive as a reader. And also strategically, as a graduate student, as a postdoc, how do you go from a series of different experiments into getting that published and getting that CV item.
SAM STERNBERG: You need to think very strategically about how to put together your scientific discoveries into a narrative that can be published, that can be presented. And I think Jennifer is the person where I learned how to do that. And it's something that I realize now as a new group leader, if I don't know how to do that, I can't really be successful.
SAM STERNBERG: And she's just the master at it.
KEVIN DAVIES: Yeah. Yeah. Well, it rubs off on you, because you do a beautiful narration when I've heard you give talks. So Thanks for joining us. Hopefully, you can stick around a little bit. Rodolphe, you've seen another side of Jennifer of course, a more entrepreneurial side. Tell us about that.
RODOLPHE BARRANGOU: I mean, absolutely. So I think everything we've heard about the greatness in the lab, the greatness of science, as I mentioned, the greatness of storytelling and mentoring across the board as is obvious here. Most people don't know and should know and maybe even must know especially today that not only is she a woman of many talents in the lab and scientifically and in storytelling, but also she has the vision to make an impact with the real science.
RODOLPHE BARRANGOU: And one of the reasons I'm convinced that she got the momentous call from the Nobel for 2020 Chemistry is because she's had a real impact. And to have a real impact for the world, you need to have business impact and business success. It needs-- it's going to be medicines to address disease, it's going to be breeding for food and egg and livestock and forestry and the like. And she knew that at the outset, even when it was not obvious to everyone, because unbeknownst to most people, she founded the first ever CRISPR company, not just as a founder or an inventor, but out of her lab right one of her own.
RODOLPHE BARRANGOU: Students, who I'm sure wishes were with her with us today--
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: The great Rachel Haurwitz, likewise was the first ever CEO, fresh out of the Doudna lab, running the first ever CRISPR startup. And after that, there was Intellia. After that there was Editas. After that, there was Scribe and Mammoth and others. And I think really having the vision of not just great science and technology but great potential to translationally translate science into products that will cure disease.
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: Right? That will feed the world, that are building financial value and the economy, and also the training of all those great graduates that come from the Doudna coaching and mentoring tree, so to speak--
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: Bring that to the real world and have a real impact is I think underappreciated, is very important, very valuable, very impactful. And moving forward now, I think with the platform of the Nobel and the credibility and the visibility beyond just the scientific realm to share those narratives with the public. Right? To inspire the next generation of scientists, the next generation of women, the next generation of entrepreneurs, the next generation of inventors and investors, I think is very important.
RODOLPHE BARRANGOU: And I think, as I said in an article actually wrote to that effect, she's very much uniquely positioned to do that in ways others are not. And I think science is part of the story. But entrepreneurship, vision, business mind, and mentorship and mentoring is very much on par for the course and equally impactful, I would argue.
KEVIN DAVIES: Well, that's a perfect segue, because look who's joined us. Hello, Jennifer. Welcome.
JENNIFER DOUDNA: Hi, everybody.
KEVIN DAVIES: Great to see you you're joined by five of your closest friends who wanted to throw you a surprise little party and more than 1,000 people who are watching us now. So I know we only have you for a very compressed amount of time. So we better bombard you with some questions to make the most of the time we have together. Anyway, congratulations, of course, from everyone watching on the 2020 Nobel Prize for Chemistry. We should have champagne going--
JENNIFER DOUDNA: Thank you so much Kevin and everybody.
KEVIN DAVIES: That's wonderful. You got the traditional early morning wake up call but not from Sweden, I understand, it was from a reporter?
JENNIFER DOUDNA: It was from a reporter, how embarrassing that I missed an important call like that? But that's what happened. So I did get a call from Heidi Ledford at Nature who popped the question and-- [LAUGHS] Yeah. It was quite a moment.
KEVIN DAVIES: Do you get to go back to sleep after that? Or that's it, the day is ruined?
JENNIFER DOUDNA: No. That's the start of the day.
KEVIN DAVIES: So what's happening with the actual ceremony? I guess it's going to be a virtual ceremony this year, which is a bit of a damper on it. But hopefully, they're going to make up for it somehow.
JENNIFER DOUDNA: Well, yes and no. I think the interesting silver lining is that it probably means a lot more people can participate than would normally be the case. So I think that's-- and that's what we've found this year. I think many of us who have been to scientific meetings virtually, we're finding that there's just a lot more participation because of the Zoom format.
KEVIN DAVIES: Yeah.
JENNIFER DOUDNA: But you're right. I mean, that's how it's happening, and all of the Nobel lectures have already been recorded, and they're going to be broadcast, I think it's December 8, along with a small celebratory ceremony in Stockholm.
KEVIN DAVIES: Oh, fantastic. I understand that before I pass the microphone to Karla Shepherd, the Executive Director of the Rosalind Franklin Society with whom you've spoken and presented in past years, one of the great privileges now of winning the Nobel Prize is you get free parking on the Berkeley campus?
JENNIFER DOUDNA: So they say. Yeah.
KEVIN DAVIES: It hasn't materialized yet?
JENNIFER DOUDNA: Not yet but-- KARLA SHEPARD
RUBINGER: Everything
RUBINGER: is delayed with COVID.
KEVIN DAVIES: OK. Well. OK. That's it. All right. Karla, I know you want to-- obviously, the series here is about celebrating women in science and championing women in science. I know Karla has a few questions she wanted to ask, so I'm going to pass it to her.
KEVIN DAVIES: Pass it over to you.
KARLA SHEPARD RUBINGER: Mostly, thank you Jennifer, for doing this. There are 4,000 people signed up to listen to this. So we're excited to share it. So your award is seen as an important moment for women in science, as Kevin was just saying, but following the award, Emmanuelle said, I think it's very important for women to see a clear path. The fact that Jennifer and I were awarded the Prize today can provide a very strong message for young girls.
KARLA SHEPARD RUBINGER: What lasting message do you think that awards can send?
JENNIFER DOUDNA: Well, I think certainly that both Emmanuelle and I felt proud of our gender that morning and just happy that we were sending a message collectively to girls and others who have felt excluded from the STEM fields that their work can be recognized. And that there's a celebratory feeling about science no matter where it's done or where it comes from. I think that's a really, really important message, especially of this particular award.
KARLA SHEPARD RUBINGER: Right. And real clear publicity, which is attached to this worldwide, including our webinar today. One fascinating aspect of your CRISPR story is that a year before you met Emmanuelle, you actually left Berkley to take a senior position in biotech at Genentech.
JENNIFER DOUDNA: Right.
KARLA SHEPARD RUBINGER: And that's an interesting story. And without the awakening of your returning to Berkeley, history might have been different. Can you talk a little bit about that awakening?
JENNIFER DOUDNA: And some of my colleagues on the grid here were with me at that time in the lab, so you remember it intimately. But basically, yeah, it was a very interesting experience. Because I had an opportunity to join one of the arguably best biotech companies that's famous for its fundamental discovery research. And that was a very exciting opportunity for me and I embraced that opportunity. However, once I actually got into the company itself, I realized that I missed my Berkeley colleagues, and I really missed the discovery science that we almost take for granted, or at least I had come to take for granted in the university environment.
JENNIFER DOUDNA: And so very kindly, my colleagues at Berkeley were happy to welcome me back to the fold. And the lab hadn't actually physically moved at the time. So it was easier to go back fairly quickly. And my colleagues at Genentech were also understanding. I think many of them had come from academic backgrounds, so they understood the challenges of making that cultural shift.
KARLA SHEPARD RUBINGER: Well, clearly, colleagues are central to all science, but particularly noteworthy in your work as well. So back in 2011, you were already highly accomplished researcher fielding numerous offers and partner opportunities to collaborate. What was it that you saw in Emmanuelle when you first met her that really set the stage and for that transatlantic collaboration that it would work and it did?
JENNIFER DOUDNA: I loved her sense of adventure. Her desire to understand the secrets of the CRISPR pathway, I think that was very, very interesting. We both shared that passion, but we were coming to it from different backgrounds. And I think that really made for a very interesting and exciting collaborative opportunity. I've been involved in almost countless collaborations now over my-- I don't know, 26 years of running a lab.
JENNIFER DOUDNA: And I'd say at least half of them, fizzle. They don't really go anywhere. And so it really speaks to the fact that Emmanuelle and I think shared a vision for what we wanted to do together, scientifically, as well as to the folks in our labs, Martin Jinek and Krzys Chylinski, in particular, who were able to forge very quickly a scientific connection across thousands of miles and start doing science together.
KARLA SHEPARD RUBINGER: Yeah. I think it's an important, really important testament to worldwide cooperation of science and partnerships. And it's wonderful to be able to showcase that.
KEVIN DAVIES: Speaking of Martin, we've just been joined by Martin, presumably from Zurich. Thank you for-- I know it's suppertime over there, but thanks for joining Martin, hello. You're mute, I think.
MARTIN JINEK: Hi and good evening from Zurich. Great to see you all.
KEVIN DAVIES: Great to see you. Jennifer, have you had a chance to speak to Emmanuelle in the last few weeks just to compare notes and share congratulations with each other?
JENNIFER DOUDNA: We have. Yeah. A couple times. And I think her she's in the same whirlwind that I'm in a bit. But it's been really, really fun to celebrate the science that we did together and discuss what this award means and how it will be viewed, especially by other up and coming scientists. And I also had very recently a great discussion with Krzys Chylinski, as well, who's still in Vienna.
JENNIFER DOUDNA: And again, same feeling that I think, Martin, you and I have talked about of just the joy of fundamental discovery.
KEVIN DAVIES: Yeah. Yeah. Yeah. The big project that's dominated your life this year of course, has in a way little to do with CRISPR, it's been about COVID-19. And so before I bring in John Sterling, the editor of GEN, who will have some questions, I'm sure for you and let the other guys ask some questions too. Can you tell us a little bit about what prompted you to almost take matters in your own hands and get this very important testing facility off the ground on your campus?
JENNIFER DOUDNA: Well, I'm a strong believer that science needs to be proactive, as well as reactive. We need to, as scientists, we need to be ready to pivot our expertise where it's needed. And boy, what a case in point with COVID. So back in March, like many of us, I had the growing feeling that life was about to change, maybe dramatically. I had no idea how dramatic, honestly.
JENNIFER DOUDNA: And so with a group of colleagues at Berkeley, and I was astounded at the response to this, we put together a small meeting that ended up being 60 people who got together mostly virtually to talk about what we could do scientifically as scientists to address this pandemic. And everybody unanimously said, well the most important immediate thing we can do is set up a testing lab.
JENNIFER DOUDNA: And so I think none of us certainly, I didn't have any idea how to really do that, how to run a clinical laboratory, but we figured it out. And we got that lab going in three weeks. And, now we're actually doing all of the testing for the UC Berkeley campus, as well as with several important community partners. So I'm really proud of the team.
JENNIFER DOUDNA: It's been an extraordinary journey. We went from running the lab with volunteer students and postdocs, initially, who did all of the R&D to get the test up and running to now a whole professional team, including an M.D. who runs the clinical aspect of the work that we do.
KEVIN DAVIES: This is not a CRISPR test, just to be clear, this is using old fashioned relatively traditional methods. But you obviously, I think most people watching know that you among several companies that you founded or launched, one is called Mammoth Biosciences that is developing CRISPR diagnostic tests. How are you optimistic that technology will eventually be able to provide an at home test, if not for this pandemic, then for the next one?
JENNIFER DOUDNA: Well, at home is tough. It maybe was going to get there. I think, initially, what I'm seeing-- and it's from a number of folks, including Blake is doing a lot of this work, and I'm sure many others who are listening here are involved, but there's a lot of effort to develop CRISPR as a point of care test that would be able to provide real-time surveillance testing. And that's something that I think is very likely to happen during the current pandemic.
JENNIFER DOUDNA: I mean, I think it's pretty clear that we're going to need robust and widespread testing for at least the next several months, if not longer, for COVID-19. And then obviously, having the ability to take a test like CRISPR, which is programmable and then target it to other viruses. It will be very valuable for, I would say, pandemic preparedness in the future.
KEVIN DAVIES: Yeah. Great. Let me bring in John Sterling from the Chief Editor of GEN, John.
JOHN STERLING: Hey, Jennifer. Congrats again. I saw that video on that morning that's the day you're never going to forget, so congrats. And one of the things that's always interested me covering biotech for about 35 years is how people get into certain fields. One thing that's been very clear to me in a lot of medical scientists is that they get into the field because one of their relatives, one of their friends, somebody has some disease and they pursue that.
JOHN STERLING: You, on the other hand, were living in beautiful Hilo, Hawaii and walking through the rainforest and all looking at the local flora and fauna. What turned you on to science there that is carried you through all these years to where you are now?
JENNIFER DOUDNA: Well, I think it was a combination of things. I certainly, I grew up in a family that was intellectual. And my father-- nobody was-- nobody was a scientist, but my father loved doing puzzles, and he loved reading about science and talking about science, so we did a lot of that, even though nobody was practicing it professionally. So that was going on in the background. And then I loved math. And I also, I think I was highly influenced also by that island environment of just being aware of all of the plants and animals that evolve in that environment to have particular properties.
JENNIFER DOUDNA: And I couldn't help wondering, how does that work? And so I've always been driven by those how questions in science, and really wanting to understand in molecular detail what we observe in biology.
JOHN STERLING: Well, yeah. That's basic science. So regarding women in science, a real interesting question here from someone in the state of [INAUDIBLE],, which is I guess in Brazil, and we're a country with a history of female maximum leaders which sounds like anthropology, but we, as women, are still underrepresented and under recognized. What's your advice to women who want to be excel in basic science, biotechnology, and happened to be in a developing country where there are very few-- well, she says incentives.
JOHN STERLING: I guess, I'd say maybe support for them to go into science. And she has a great question, could we dream with being awarded a Nobel Prize?
JENNIFER DOUDNA: Well, absolutely. And I think that I would just say that my experience, certainly, has been that the people that I see who are most successful in science tend to be those who are just laser-focused on their passions, and they don't let anyone dissuade them from what they want to do. And people here that know me well, know that I'm a have a stubborn streak, right?
JENNIFER DOUDNA: And I think that's sometimes been a strength in science is to be absolutely committed to an idea that you have and pursuing it to see if it'll pan out or not. And that I can think of a number of times in my career when that's been true for me. And it certainly, before CRISPR came along, there were things that I wondered about, questions that I had about a biological system that I wanted to answer.
JENNIFER DOUDNA: And there were plenty of naysayers saying that's either a silly idea or that will never work. And I did it anyway. And I did. I wasn't always right, but but at least I satisfied my question and my passion.
JOHN STERLING: Yeah. My final question again, is from somebody online, and I know you're very much involved with this because a lot. We talk about the scientific and medical implications of CRISPR, but you're saying I wonder about the ethical implications of this technology. What are the ethical limitations? And is that something you can talk about?
JENNIFER DOUDNA: Right. Well, I think it's a very interesting challenge that we have right now in this field, because the technology clearly opens the door to many opportunities. That include applications in the environment, in agriculture, and of course in medicine that are very exciting, but also bring along with them, I think important questions and challenges that we have. And we just have to, when I say we here, I mean, everybody, because ultimately, we're all affected.
JENNIFER DOUDNA: But I do think the scientific community in particular needs to step up. And I've been quite pleased that that's I think we've really seen that in across the spectrum of applications. And for CRISPR certainly, it's an ongoing challenge, I think, to keep that conversation going and to keep the transparency going. Earlier in this discussion, we talked about international collaboration, and I think that is absolutely critical in terms of managing the use of a technology like CRISPR, non-trivial to achieve that kind of cooperation but essential to work at it.
JOHN STERLING: OK. Thank you. Wonderful. Kevin, back to you.
KEVIN DAVIES: Yeah. Thanks, John. I want to see if any of our we now have six great friends of yours here in the speakers room, so to speak, Dipa, Rodolphe, Ross, Blake, Sam, Martin, any stories you'd like to share? Any questions you have for Jennifer?
SAM STERNBERG: How's the big alumni trip to Hawaii? [LAUGHTER]
JENNIFER DOUDNA: I'm saving my pennies for that one, Sam.
SAM STERNBERG: Or maybe I'll add a little bit of story, which was when the lab turned 20 years old, I was fortunate enough, alongside Ross, I think is the only other one on the call on the panel here, to be in the lab at that time. And we had Jennifer-- actually, Ross was the organizer, I think Ross organized the Doudna Lab Conference, I think you had a name for it, Ross, I don't remember what it was.
ROSS WILSON: The Pacific RNA Research Symposium or something like that.
SAM STERNBERG: Yeah. But fantastic trip, a couple days. And we talked a fair amount of science. I think what was really fun there is everyone had carte blanche to present anything they wanted, so we had certainly some talks that were relevant for their research, but we had other memorable talks that were about completely new research topics. And then we did some hikes in the crater and the volcanic craters, some kind of hanging out and dancing in the evenings and good food, good drinks, good natured explorer.
SAM STERNBERG: But I think, always a good reminder that the science needs to be balanced by building a community of people that enjoy spending time together. And I have to say, having started my lab here, it's another thing that I took away from my experience in Jennifer's lab, how fun I-- how much fun I had working with Ross, Martin, Dipa, Blake, these are some of my best friends in science. And that's actually not always the default.
SAM STERNBERG: I see other labs in my building and other buildings on campus where you can really tell that the lab hasn't really synergized and formed that community of friends and colleagues. And I think it doesn't happen all on its own. You need to set up the lab in a way that cultivates that and nurtures that. So that's something that I really look back very fondly on all my time in the lab.
SAM STERNBERG: A lot of good memories.
KEVIN DAVIES: Of course. Any other comments or questions?
RODOLPHE BARRANGOU: I'm going to ask one too.
KEVIN DAVIES: Yeah, sure.
RODOLPHE BARRANGOU: So Blake mentioned earlier today, we all did how exhilarating the research has been, how exciting the original CRISPR days were. But when did it hit you that this was going to be real, life-altering, world-changing, not just and your lab but a lot of other people. Did something happen or was there a moment in time where you realized it was bigger than you thought?
BLAKE WIEDENHEFT: And can I add on to that question a little bit? I mean, since this is the Rosalind Franklin Society discussion, I wonder if you could couch the answer to that question in the context of what's your version of Photo 51, Rosalind Franklin's historic photograph? And I was gone in the lab when I had just left or was on my way out when you and Martin were kind of having these daily epiphanies, and so I missed the first hand, some of that first hand excitement.
BLAKE WIEDENHEFT: And I don't think I've had a chance to chat with you and Martin, in particular, about how that went down and maybe you could just share a little bit of the play by play?
JENNIFER DOUDNA: Yeah. Well, we have Martin here too, so Martin, you can comment on this. But I think, for us in the lab, there was really a pivotal moment, and it was kind of building, because we could see that there was a lot of really interesting biochemical activity of this CRISPR Cas9 protein as an RNA-guided DNA cutter. But I think for us, that pivotal moment of the project going from pure curiosity-driven investigation to something that we could see would have much bigger, broader implications, was when we were in-- I think we were in my office, Martin, and we were talking about your biochemical data defining what the essential components of the Cas9 DNA targeting mechanism really were, especially on the RNA side.
JENNIFER DOUDNA: And that led to the idea that the RNA molecules could be combined into a single guide format that we thought was really cool and fun that, wow, we understand enough about this to be able to redesign it. And if that works, we'll know we really understand how this thing operates with its RNA guide. But beyond that, it would also create a much simpler system, a two-component system for DNA cutting that would be programmable.
JENNIFER DOUDNA: And being from thinking of my graduate work in the 1980s, I was imagining that New England Biolabs catalog, of all of the available restriction enzymes being compressed into one protein that could be trivially reprogrammed with its RNA guide. It was a profound idea. And having that going on in the context of all of the other work that was going on far beyond our lab both on DNA repair and on genome engineering with engineered proteins, all the pieces started to come together.
JENNIFER DOUDNA: And I think that was really that proverbial moment. And if there is a Photo 51, I think what it is in my mind, I'm curious if Martin has a different answer, but Martin, I think it would be a slide-- I still show this slide in some talks, because I just love the data, but it was the experiment that you did where you designed five different single guide RNAs that would target parts of a plasmid sequence. And you did in a way the simplest experiment in molecular biology of cutting that plasmid DNA with these different single guide RNA-programmed Cas9 complexes and a separate enzyme to chop out these pieces of DNA.
JENNIFER DOUDNA: And you have this beautiful agarose gel that shows all of these DNA fragments of different sizes corresponding to where the guide RNA was cutting. So it was just one of those, wow, that just right there that encapsulates what this protein is capable of doing.
KEVIN DAVIES: You agree, Martin? You concur?
MARTIN JINEK: Yeah, I think, I would agree. Yeah. I think the discussions basically about the experiments that we had in the office, that was probably the eureka moment. But then I think the real excitement then came when we were able to follow up on all these ideas with actual experiments and really prove that. We had a programmable one protein, one RNA system. And just like Jennifer said, basically, that experiment where we designed different RNAs for the same target.
MARTIN JINEK: And we could just see exactly that the RNAs pair, guiding the complex to cut the DNA in exactly the place where we were expecting it to cut, that I think was the pivotal moment where we-- from that point, we knew that this was a technology that was going to change things.
KEVIN DAVIES: Jennifer, you've just-- I believe you're the co-founder of a relatively, a company that's just come out of stealth mode called Scribe Therapeutics. Their logo looks suspiciously like it was derived from Photograph 51. So I think it was a great reference, Blake. Clearly, it hasn't been forgotten. Let's just-- we have about five minutes with you left. CRISPR has come so far in the last decade, it's now, I guess you could say it's approaching puberty as it enters its second decade, what are some of the most exciting projects that you're really excited about going on in your lab now?
KEVIN DAVIES: And I think the other part of that question is maybe looking forward to the next decade, what are some of your big hopes for the technology, not just from your lab but from the international community that's using your technology?
JENNIFER DOUDNA: Well, I think certainly, thinking about how the technology will be deployed and how it will actually have impact around the world is something that lots of people are thinking about. But I certainly what really keeps me up at night right now is the idea that as a field, we really need to go from the proof of principle that we're all-- we've all been working on, which is that type of experiment, demonstrating the capabilities of the technology, and that's certainly been extraordinarily exciting over the last several years to increasingly thinking about how we actually make the technology widely available to people that need it.
JENNIFER DOUDNA: And a great example of this is the work that's been done with sickle cell disease. And I think many folks are aware that sickle cell disease is a monogenetic disorder that CRISPR is in a way perfectly suited to treat or even cure by making corrections to or changes to a specific gene that could mitigate the disease phenotype in affected patients. And in fact, that's been done now by a company called CRISPR Therapeutics that Emmanuelle founded, and other groups are working on this.
JENNIFER DOUDNA: And the question that I think we ask ourselves and Ross Wilson is very involved in this right now is, how do we make sure that a technology that clearly works for a disease like that, which is just extraordinary and very exciting becomes affordable and available to those that need it? Right now, that CRISPR therapy is going to cost worth of $1 million a patient, which is just not sustainable.
JENNIFER DOUDNA: So in the Innovative Genomics Institute where we're working at Berkeley and UCSF, this is front and center in our minds. And so we're working on different ways of delivering the CRISPR molecules and coming up with strategies that will avoid having to use a bone marrow transplant for these patients, for example, as well as investigating new CRISPR enzymes that are potentially going to be easier to deliver, because they are either smaller or have other advantages in their chemistry that make them easier to get into particular cell types or tissues.
JENNIFER DOUDNA: So that's really one of the big areas that I personally am focused on at the moment.
KEVIN DAVIES: Yeah. Yeah. What's going on in your lab that's really exciting right now?
JENNIFER DOUDNA: Well, so in addition to working on these delivery strategies, we do a lot of work currently with Jill Banfield at Berkeley, so she is the person who told me about CRISPR originally back in the day and continues to work on the discovery of new CRISPR systems in various microbial communities. And with her lab, in addition to that discovery work, we're also very excited about being able to manipulate the genomes of communities of bacteria.
JENNIFER DOUDNA: And this is something that I've talked a lot to Sam Sternberg about. And he's also very interested in this. And hopefully, when we're post-COVID, Sam, we will be meeting up in your lab to work together on this as we discussed. But this, I think is a very exciting direction for the future. Why?
JENNIFER DOUDNA: Because I think if it were possible to manipulate microbes, specific organisms within their natural communities, whether it's the human gut or whether it's soil or water, environmental niches, this will absolutely change the way microbiological research is done, where it's not necessary to cultivate individual organisms in laboratories to study them, but you can actually do investigations or even manipulations in a natural setting.
JENNIFER DOUDNA: And I think that's very exciting. That's something we're working on quite closely with Jill.
KEVIN DAVIES: Well, we've been bombarded with questions from the audience. We had a whole bunch more we would have loved to have gotten to and hopefully, maybe when the dust settles, if it ever does, we could have back and for a slightly longer period. But our heartiest congratulations again and best of luck going forward not only for the celebrations in a few weeks' time. But in the post-pandemic world, when as you say you can get to see your friends in the flesh again and build these wonderful collaborations.
KEVIN DAVIES: So Jennifer, thank you so much for joining us.
JENNIFER DOUDNA: Thank you, Kevin and Karla and John. And thank you, everybody that's attending and of course, my colleagues here on the grid, it really means the world to me. And you guys are-- you're awesome, all the work that you're doing, most appreciated. Thank you.
KEVIN DAVIES: Thank you so much. So we'll hang around for the next 5 or 10 minutes with the guys, if they don't have to rush. Ross, you're working at the Innovative Genomics Institute. Maybe tell us a little bit about what the big plan of that Institute that Jennifer co-founded, if I'm not mistaken.
ROSS WILSON: She absolutely co-founded.
BLAKE WIEDENHEFT: Is it too early to suggest that delivery is the next Nobel Prize? [LAUGHS]
ROSS WILSON: Well, I'll tell you what, whoever fixes the delivery problem will not get credit, because progress on this front will not get you flashy publications. And I think that's one of the reasons that-- there's two reasons that it's underappreciated. It's maybe three. It's very, very hard. You don't get a lot of academic credit. And in industry, they're not doing research, they're doing development.
ROSS WILSON: So basically, they pluck anything that looks promising from academia and just push it as fast as possible into something that can make money. And so there's this major incentives problem. And I think one of the major pushes at the Innovative Genomics Institute is that we're trying to really fix this translational problem by being creative.
ROSS WILSON: And I don't want to sound too hubristic, this is a very hard problem. But we're trying to really think about it in an end to end way without letting all these corporate incentives steer us off course in between. But overall, the goal of the IGI is to make an impact exactly like Rodolphe was talking about. And the other places we're really interested in doing this is on the agricultural front, which ties into climate change, and on the society and ethics and education front, I think that we're really trying to distinguish ourselves there by making CRISPR something that the world can understand, hopefully not fear.
ROSS WILSON: But also, making people aware of the ethical considerations that we should be talking about. So I think those are a lot of the things that drive us.
KEVIN DAVIES: Great. Great. I saw a question flash up. We didn't have time to ask it of Jennifer. But the big story in the last 24 hours in science circles has been this extraordinary paper, which I'm sure is about to be retracted, if it hasn't already been, in Nature Communications, that seem to suggest that women can't act as mentors or something. Absurd.
KEVIN DAVIES: I mean, Dipa, Rodolphe, Sam, would welcome anyone's thoughts on that, we've just seen the most spectacular example of a woman who's inspired legions of scientists and former mentees. If any of you have a reaction to that, I'd love to hear it?
RODOLPHE BARRANGOU: So I love your use of the word absurd. Right? Especially in the context of the Rosalind Franklin Society where I've had the pleasure to speak before. There are examples over and over and over and over again of great women across, not just science but the world, have had tremendous impact, that are great mentors actually mentioned that as Jennifer joined us today. So I think it's nonsense, whatsoever, whether there's going to be retracted and how quickly it will be retracted time will tell.
RODOLPHE BARRANGOU: But I think it's an urban legend that has been debunked a number of times. And but this is a reminder to me of the world that we're living in. And I would compel people. No matter the science inclination or not, the data expertise or not, their extensive knowledge or not of a lot of things that whenever you hear data or you hear stories, we heard about storytelling for the right reasons, there's a lot of storytelling with the wrong reasons nowadays.
RODOLPHE BARRANGOU: Right? People seek attention. People twist, misinterpret data all the time, even people fake data, occasionally, as we know as editors. So I think we have to learn to take things with some degree of skepticism but healthy skepticism and know when to interpret data firsthand, and not always let other people interpret data for us.
RODOLPHE BARRANGOU: I think that's an important lesson that sadly enough 2020 has taught us over and over and over again. But in this case, it's so, so absurd, as you said that, I think it speaks for itself.
KEVIN DAVIES: Yeah. Any other comments on that? Dipa? Dipa then Ross.
DIPALI SASHITAL: Well, as a female scientist who had an incredible female mentor, obviously, agreed with Rodolphe, that this is an absurd paper. When I was looking at postdocs, my PhD mentor was helping me to decide between two labs of the lab of Jennifer Doudna, of course, and another lab which had a male mentor, and he specifically said, you've been in my lab, I really think that you would benefit from having a female mentor for your postdoc.
DIPALI SASHITAL: It didn't really strike me at the time how right he was about that. I do think that it made a huge difference to me to have somebody like Jennifer who really is honestly one of the most impressive people I've ever met in my life, so a true inspiration, somebody to really look up to. And somebody who helped me to develop myself as a mentor and to be able to mentor the people who are in my lab now.
DIPALI SASHITAL: So I agree with Rodolphe that there's data and then there's interpretation of data. The data itself does say something. It says that the metrics that we use to judge success are biased and are not the metrics we should be using to judge success. But the interpretation in the paper is obviously exceptionally flawed.
KEVIN DAVIES: Yeah. Yeah.
ROSS WILSON: Yeah. I just wanted to say basically what Dipa did. The results can be whatever they are, and I think there was dubious work in that paper to get to the results but to see that outcome and conclude that your response should be to advise everyone to avoid working with women in science is criminally negligent and just wildly irresponsible. So yeah, I can't wait to see that paper gone from anyone's discussion.
ROSS WILSON: I mean, it's got to go.
KEVIN DAVIES: Yeah. Yeah. Well, we don't have much time left. But maybe we could just each of you give a quick closing summation and ask Jennifer what her hopes for the second decade of CRISPR and genome editing might be, what are you most hopeful for or looking forward to either from your own group or from the field as a whole? Blake, maybe we could start with you.
BLAKE WIEDENHEFT: Well, one of the things that I think each of us articulated a little bit was the influence Jennifer had on our careers. And I think Sam did a better job of doing that than I possibly could. So I won't try to follow that. But I think-- I think that one of the things that strikes me is, I don't think I fully appreciated what Jennifer was doing and how hard it was until I was on my own and had to do it myself.
BLAKE WIEDENHEFT: It sounds like an ungrateful child almost, but I think it wasn't until I tried to recreate that atmosphere here in my own group that I really appreciated how hard it is to do and how graceful she is in doing that.
KEVIN DAVIES: Yeah.
BLAKE WIEDENHEFT: Yeah. There's lots of different aspects of the work in the lab, some of the-- as Jennifer mentioned. I've tried to follow in some of those footsteps a little bit as well, trying to develop some new diagnostics and more to the point maybe just pivoting the research interests in my lab at touch from CRISPR into some SARS Coronavirus work, and that's an interesting new puzzle and an adventure maybe that we've been excited to chase.
KEVIN DAVIES: That's great. Great. Sam?
SAM STERNBERG: Yeah. Maybe to dovetail on that, Jennifer what she's famous for now is not the same thing as what she was famous for 15 years ago. But she was famous 15 years ago for being the first to crystallize structured RNAs that weren't tRNAs, which really opened up a whole new world of RNA biology. So one thing that I'm thinking about a lot in the lab is how to continually pivot, reimagine what the science focus of your group is and not get stale by focusing on the same things and digging deeper on the thing from five years ago, but what's going to be the next breakthrough?
SAM STERNBERG: So I think there's a lot of that in CRISPR. There's a lot of that outside of CRISPR. And that's something that I think is always a fun challenge to wrestle with.
KEVIN DAVIES: Yeah. Great. Ross? Can't hear you. There you go. What's the big adventure for your group and IGI over the next five years?
ROSS WILSON: Sorry. The delivery challenges remain but the thing that I'm really excited about is changing a lot of non-genetic diseases into things that could be tractable with genetic cures. So there's a lot-- I mean, there's a crisis coming in with an aging population. Neurodegenerative diseases are going to have an ever increasing impact. And right now, even if you could CRISPR the brain, I don't think we know exactly what to do.
ROSS WILSON: And fortunately, I think CRISPR is going to have a huge impact there, because it has the capacity to let us model disease and probe genetic pathways in a way that is just totally transformed, thanks to the technology. So I think making incurable diseases tractable at the fundamental understanding level is very exciting.
KEVIN DAVIES: Thanks. Rodolphe?
RODOLPHE BARRANGOU: I mean, yeah, so as far as I'm concerned, I think medicine is great. It's going to save lives. But there's only a couple hundred million people maybe that benefit from it in short term, at least. But if we use it for food and ag, we're going to revolutionize the whole world and impact everyone. So think from microbiomes and fermented foods and crops, all the way to engineering trees in the forest, I think is where the future is going to be to some extent to replicate the success in medicine.
RODOLPHE BARRANGOU: But to me, the biggest challenge that we all have to take on is not science anymore, right? Science is almost trivial, feasible, thanks to CRISPR, Jennifer and her great work. But I think engaging the public and addressing scientific skepticism, and we won't be able to use it until there's acceptance of science by the public and anti-vaxxers and anti-GMOs, and anti-science bias is arguably an all-time high as mentioned by the great Tony Fauci as well.
RODOLPHE BARRANGOU: So unless we start training scientists to address that, and until scientists dedicate at least some of their time to address that with the public, I think it's going to be hard to really benefit as much as we should from great science technologies like CRISPR. And this is also why I'm excited about Jennifer being uniquely positioned, and equipped to address that with the narratives that Sam mentioned with the great mentorship and storytelling and attributes that she has as a communicator.
RODOLPHE BARRANGOU: And I think but it's going to take more than just the great Jennifer Doudna to do that. And we should all embrace that challenge hopefully to some extent.
KEVIN DAVIES: Nice. Thank you. Martin?
MARTIN JINEK: And I think this is becoming a very hard act to follow. But I would really echo some of the sentiments here that, of course, I think-- yeah, the educational aspect of what we do is something that is increasingly important and for our future, this is this is going to be key, not just in the context of CRISPR, but of course, here as well.
MARTIN JINEK: One thing I wanted to maybe also follow up on is what both Blake and Sam was were saying is that-- yeah, Jennifer is kind of inspiration was for me the way that she continuously keeps reinventing herself, scientifically and how she basically looks for new problems, new questions, new ways to approach problems. And so this is for me, this is if I want to develop as a scientist, as PI, this is for me, this is the greatest challenge looking into the future.
MARTIN JINEK: And I hope I can live up to the great inspiration and the great example that she gives to us all.
KEVIN DAVIES: Don't think you're doing too badly on that front, Martin but time will tell. And Dipa?
DIPALI SASHITAL: So I would say that since we're here celebrating this Nobel Prize, this Nobel Prize really came about from basic science research and just a sense of inquiry, trying to understand how a bacterial immune system works. And that's so important. Doing that type of research continues to be important. So in the future, going forward, I think we will never know what our research will tell us until we've actually done the research.
DIPALI SASHITAL: And there's tons of exciting work being done in the same area discovering other phage defense mechanisms or defense mechanisms against phage and the warfare between phage and bacteria, I think that that area of research is really exciting and has proven to provide a lot of biotechnology tools and may continue to do so as we move forward. So that's an area I think that is really exciting to watch as we move forward.
KEVIN DAVIES: Good. Well, thanks to all six of you for making time. You've got hectic schedules and lots going on, so but it speaks volumes that you want you wanted to do this to be part of this meet and greet with Jennifer. And apologize to everyone who tried to ask a question. And we didn't have time, we'll try to find a way to relay them to Jennifer or answer them in another format.
KEVIN DAVIES: But that's pretty much the end of our program. Karla, I'm going to let you close things out.
KARLA SHEPARD RUBINGER: Well, thank you. I hope you're all as breathless as I am this was a whirlwind of great discussion. And this is a wonderful way to conclude our series on Women in Science. I warmly invite all of you to join us for our virtual meeting, which will be held on December 16 and 17. And please visit our website to get details about that. This was supposed to be an in-person meeting at HHMI, which obviously will not happen this year, but hopefully next.
KARLA SHEPARD RUBINGER: Obviously, we thank Jennifer Doudna, our newest Nobel laureate for her time today and for all of you for joining and celebrating her work and yours. We are terribly grateful for the support from Horizon and OnRamp, from GEN, without whom this would not have been possible. And all of you as panelists and guests and the 4,000 people who registered to hear this as well.
KARLA SHEPARD RUBINGER: So it's a wonderful testament to the importance and the interest of science. And we really appreciate this interest, especially in this particular time from all of you. So for GEN and the Rosalind Franklin Society, I'm Karla Shepard Rubinger. I hope you all stay safe and healthy. And good bye for now. Thanks.
KARLA SHEPARD RUBINGER:
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KEVIN DAVIES: Hello, everyone and a very warm welcome to you for this fourth and final installment of our Women in Science Webinar Series. It's 1 PM in New York, 10 AM in Berkeley, California. And we're very pleased you could join us. I'm Kevin Davies, the Executive Editor of The CRISPR Journal, editor-at-large at GEN. I'll be the host for today's discussion with the one and only Jennifer Doudna, the 2020 Nobel Laureate for Chemistry. I'm also contractually obliged to say that I'm also the author of Editing Humanity, the best book on the CRISPR revolution since A Crack in Creation that Jennifer co-authored a few years ago, just out.
KEVIN DAVIES: We're thrilled to be joined by Jennifer Doudna. She'll be joining us live in about 10 minutes, so we'll have a good 30 minutes to ask her questions. In the meantime, I'm thrilled to be joined by four of her past and former colleagues. I'll introduce them in just a second, also by Karla Shepard Rubinger, the Executive Director of the Rosalind Franklin Society, who will be my co-host today, and John Sterling, the Chief Editor of Genetic Engineering News.
KEVIN DAVIES: Among Jennifer's colleagues joining us are Dipali Sashital from Iowa State University, Ross Wilson from the IGI in Berkeley, California, Blake Wiedenheft from Montana State University, and Rodolphe Barrangou from North Carolina State University, and the Chief Editor of The CRISPR Journal. Hello to each of you. Thanks for joining us. We'll to you in just a second.
KEVIN DAVIES: One housekeeping thing I have to-- a couple of housekeeping notes I have to take care of first. The Women in Science Series, if you're new to this, you've just found out about it because of Jennifer's participation today, it's been a four-part series that kicked off with an absolutely spectacular lecture about six weeks ago from Matthew Cobb of the University of Manchester in England on the life and times of Rosalind Franklin. We're doing this series because this year is, of course, the 100th birthday of Rosalind Franklin.
KEVIN DAVIES: We've also had great presentations and discussions with RFS President Rita Colwell, the microbiologist, and MIT President Emeritus, Susan Hockfield. All of those can be found on on-demand links at the Genetic Engineering News website and the RFS website as well. We need to thank a couple of companies who've made this series possible. Horizon Discovery and OnRamps Bio, Horizon Discovery drives the application of gene editing and gene modulation to enable you to identify the genetic drivers behind human disease, develop diagnostic workflows, and deliver new therapies for precision medicine.
KEVIN DAVIES: Horizon offers innovative tools and services based upon the ability to modulate or alter the function of almost any gene in mammalian cell lines. And OnRamp Bio is the San Diego-based genomics company that develops the Rosalind Discovery and Collaboration Platform, named in honor of-- you guessed it, Rosalind Franklin. The Rosalind Platform simplifies the complexity of bioinformatics, so that scientists can harness the potential of multi-omic data interpretation.
KEVIN DAVIES: OnRamp is a founding member of the Rosalind Franklin Society Council of Corporate Leadership, which supports the scientific careers of women and underrepresented minorities. So we're thankful for their support. So before Jennifer joins us which we hope will be punctual on time in about 11 or 12 minutes, we have a chance to get some observations and recollections from four of her current and former colleagues.
KEVIN DAVIES: Maybe I can start with Blake. Blake Wiedenheft, you are legendary in that you literally brought CRISPR to Jennifer's lab. Is that a fair statement?
BLAKE WIEDENHEFT: I don't know. I was one of the first people to work on CRISPR in Jennifer's lab. I came from MSU where I am now. We were studying viruses in the hot springs in Yellowstone National Park. And that wasn't a space that Jennifer's lab had previously worked in. But she had been introduced to the concept of CRISPR by Jillian Banfield, a colleague there at Berkeley, so I think was just the right guy at the right time.
BLAKE WIEDENHEFT: And it worked out in my favor to have a shot at working in Jennifer's lab and kicking off the CRISPR project, I suppose. But I mean, a lot of the early work really focused on type 1 systems. And it wasn't until some of the other members of the lab got involved. It's quite the-- it's quite the experience to come in as a new postdoc into a lab where nobody works on the project that you're proposing to work on, and then leave five years later.
BLAKE WIEDENHEFT: And this huge machine, everybody in there is really focused on CRISPRs. It was incredible, somewhat intimidating but exhilarating all the way.
KEVIN DAVIES: Yeah. Yeah. Well, I wanted to ask all of you to maybe share a story or your biggest takeaway from working with Jennifer and your reaction to her winning the Nobel Prize. Of course, with Emmanuelle Charpentier, we mustn't forget Emmanuelle. Dipa, tell us your-- what did you take away from working with her? What are your memories of working in the lab?
DIPALI SASHITAL: I would say my number one memory is what an incredible team of scientists she always put together. It was just absolutely thrilling to be in that lab. And by far, I would say the most exciting science that I ever got to do. Just in general, she was very, very good at fostering good dynamics in the lab, especially, I think at the time that we were there, there was a lot of new exciting projects, the CRISPR project.
DIPALI SASHITAL: At the time, there was still quite a lot of work going on in other areas. And it was-- one of the things I always found really exciting was how much we were all invested in each other's projects, so I felt like I could describe other people's projects as well as I could describe my own.
KEVIN DAVIES: Yeah.
DIPALI SASHITAL: In terms of her winning the Nobel Prize, I was absolutely thrilled. And I was also excited, because when I first joined the lab, I felt like that there was a chance that she would win a Nobel Prize someday. But it was actually for her work that she had done prior to me joining the lab, which was for RNA structure. That's my passion. That was the reason I joined her lab, not to work on CRISPR, but because she has done such pioneering work in another area as well.
DIPALI SASHITAL: So this is quite nice to have her win for yet another major discovery that her lab has made.
KEVIN DAVIES: Well, that doesn't preclude her from winning another one, right?
DIPALI SASHITAL: Who knows?
KEVIN DAVIES: You're not going to make any bets. Have you-- you run your own lab now. Have you-- did you absorb anything in the way that she needed her group together and mentored her grad students and postdocs? Any lessons that rubbed off on you that you feel have made you a better PI?
DIPALI SASHITAL: Yeah, absolutely. I would say that the thing that I learned the most from her is how to be focused, how to make sure that the research that you're doing is going to end up having an interesting result from it, and how not to pursue things that might end up taking you down a rabbit hole. And she was very good at doing that for her students and her postdocs, making sure that they stayed on track, recognizing when they were struggling and putting them onto something else that could potentially bring them results.
DIPALI SASHITAL: And so those are the biggest lessons that I've taken away is how to make sure that everyone in the lab is doing something that's productive, while they're also potentially pursuing something really ambitious and a new direction.
KEVIN DAVIES: Right. Ross Wilson, you were a member of her lab, and now you're a member of this imaginative 21st century institute that she's built and is building. What are your impressions of working with Jennifer for so long now?
ROSS WILSON: Yeah. Coming into the lab was very intimidating for me. I was kind of a humble grad student from Ohio State. And I came into Berkeley and people like Dipa and Blake were there, doing their postdocs and just completely doing completely incredible science and working so hard. So it was a little bit intimidating but also very, very inspiring. And that environment has pervaded this institute I'm working at now in collaboration with Jennifer.
ROSS WILSON: And yeah, it's just very inspiring to be part of that kind of world. And I guess, I'd like to share one anecdote, which is a little bit silly, but I think it ties back to the Nobel Prize. One tradition in group meetings was that you'd show your data and then Jennifer would give you some feedback. And one thing that almost became her catchphrase was, did you try adding RNA to that?
ROSS WILSON: So if you had a crystal structure that wasn't quite coming together and you needed a better crystal, she might say, did you try adding RNA? And it seems to have worked in a lot of cases. And it was kind of funny. That was like her catchphrase. And every PI seems to have one. One of my trainees have told me that mine is should be easy, which I think is almost troubling.
ROSS WILSON: But in her case, I think this catchphrase really paid off, because for people that really know the story of Cas9, it's part discovery, but it is part invention too. And the real invention at the core of turning Cas9 into this powerful genome editing technology is taking two pieces of RNA and adding RNA to RNA. So in adding RNA to that, she inspired, I think the fusion of the tracer RNA and the CRISPR RNA, making this single guide which is now the heart of the most convenient CRISPR tool that we have.
ROSS WILSON: So I hope that her ability to take a catchphrase and make it useful pays off, because she and I are working on CRISPR delivery now together. And that is certainly something that is not easy and should be easy. So hopefully, our collaborations there follow that same lucky trend.
KEVIN DAVIES: Yeah. Sam Sternberg, welcome to you. Thanks for joining. I know you just hopefully have seen a happy graduate student defend his thesis or get his thesis or something like that.
SAM STERNBERG: Postdoc-- postdoc's last day. But yeah, I'm sorry to hop in a couple of minutes--
KEVIN DAVIES: That's quite a while. We've already plugged your book, just so you know. Sam was a colleague of Jennifer's and is now an assistant professor at Columbia University and doing some fantastic work. Quickly give us your recollections of working with Jennifer and what she's meant to you in terms of her-- what's rubbed off on you as you launch your own independent research career now?
SAM STERNBERG: Yeah. I was thinking about that today as I was organizing this last day for the postdoc and-- in the chat I have with Blake a few weeks ago, I think we realized that so many of the practices and the habits you bring into starting a lab, running a lab, no one teaches you to do that, except then you realize that I've actually acquired and inherited all these fantastic ideas and traditions that come from the labs you graduated from.
SAM STERNBERG: So I think, in Jennifer's case, I can think of a lot of different styles that I take in the lab here that directly were inspired by how she ran the group. And I think the number one thing I would say I took away from Jennifer was how to tell a story with your science. It's something I think about all the time. Publishing an article, it's not a series of facts organized into figures.
SAM STERNBERG: You need to blend them together and weave a narrative, because that's what we all want to read. We want to learn about a story. And I think Jennifer has just dialed in how to do this in a way that makes your science come alive as a reader. And also strategically, as a graduate student, as a postdoc, how do you go from a series of different experiments into getting that published and getting that CV item.
SAM STERNBERG: You need to think very strategically about how to put together your scientific discoveries into a narrative that can be published, that can be presented. And I think Jennifer is the person where I learned how to do that. And it's something that I realize now as a new group leader, if I don't know how to do that, I can't really be successful.
SAM STERNBERG: And she's just the master at it.
KEVIN DAVIES: Yeah. Yeah. Well, it rubs off on you, because you do a beautiful narration when I've heard you give talks. So Thanks for joining us. Hopefully, you can stick around a little bit. Rodolphe, you've seen another side of Jennifer of course, a more entrepreneurial side. Tell us about that.
RODOLPHE BARRANGOU: I mean, absolutely. So I think everything we've heard about the greatness in the lab, the greatness of science, as I mentioned, the greatness of storytelling and mentoring across the board as is obvious here. Most people don't know and should know and maybe even must know especially today that not only is she a woman of many talents in the lab and scientifically and in storytelling, but also she has the vision to make an impact with the real science.
RODOLPHE BARRANGOU: And one of the reasons I'm convinced that she got the momentous call from the Nobel for 2020 Chemistry is because she's had a real impact. And to have a real impact for the world, you need to have business impact and business success. It needs-- it's going to be medicines to address disease, it's going to be breeding for food and egg and livestock and forestry and the like. And she knew that at the outset, even when it was not obvious to everyone, because unbeknownst to most people, she founded the first ever CRISPR company, not just as a founder or an inventor, but out of her lab right one of her own.
RODOLPHE BARRANGOU: Students, who I'm sure wishes were with her with us today--
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: The great Rachel Haurwitz, likewise was the first ever CEO, fresh out of the Doudna lab, running the first ever CRISPR startup. And after that, there was Intellia. After that there was Editas. After that, there was Scribe and Mammoth and others. And I think really having the vision of not just great science and technology but great potential to translationally translate science into products that will cure disease.
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: Right? That will feed the world, that are building financial value and the economy, and also the training of all those great graduates that come from the Doudna coaching and mentoring tree, so to speak--
KEVIN DAVIES: Yeah.
RODOLPHE BARRANGOU: Bring that to the real world and have a real impact is I think underappreciated, is very important, very valuable, very impactful. And moving forward now, I think with the platform of the Nobel and the credibility and the visibility beyond just the scientific realm to share those narratives with the public. Right? To inspire the next generation of scientists, the next generation of women, the next generation of entrepreneurs, the next generation of inventors and investors, I think is very important.
RODOLPHE BARRANGOU: And I think, as I said in an article actually wrote to that effect, she's very much uniquely positioned to do that in ways others are not. And I think science is part of the story. But entrepreneurship, vision, business mind, and mentorship and mentoring is very much on par for the course and equally impactful, I would argue.
KEVIN DAVIES: Well, that's a perfect segue, because look who's joined us. Hello, Jennifer. Welcome.
JENNIFER DOUDNA: Hi, everybody.
KEVIN DAVIES: Great to see you you're joined by five of your closest friends who wanted to throw you a surprise little party and more than 1,000 people who are watching us now. So I know we only have you for a very compressed amount of time. So we better bombard you with some questions to make the most of the time we have together. Anyway, congratulations, of course, from everyone watching on the 2020 Nobel Prize for Chemistry. We should have champagne going--
JENNIFER DOUDNA: Thank you so much Kevin and everybody.
KEVIN DAVIES: That's wonderful. You got the traditional early morning wake up call but not from Sweden, I understand, it was from a reporter?
JENNIFER DOUDNA: It was from a reporter, how embarrassing that I missed an important call like that? But that's what happened. So I did get a call from Heidi Ledford at Nature who popped the question and-- [LAUGHS] Yeah. It was quite a moment.
KEVIN DAVIES: Do you get to go back to sleep after that? Or that's it, the day is ruined?
JENNIFER DOUDNA: No. That's the start of the day.
KEVIN DAVIES: So what's happening with the actual ceremony? I guess it's going to be a virtual ceremony this year, which is a bit of a damper on it. But hopefully, they're going to make up for it somehow.
JENNIFER DOUDNA: Well, yes and no. I think the interesting silver lining is that it probably means a lot more people can participate than would normally be the case. So I think that's-- and that's what we've found this year. I think many of us who have been to scientific meetings virtually, we're finding that there's just a lot more participation because of the Zoom format.
KEVIN DAVIES: Yeah.
JENNIFER DOUDNA: But you're right. I mean, that's how it's happening, and all of the Nobel lectures have already been recorded, and they're going to be broadcast, I think it's December 8, along with a small celebratory ceremony in Stockholm.
KEVIN DAVIES: Oh, fantastic. I understand that before I pass the microphone to Karla Shepherd, the Executive Director of the Rosalind Franklin Society with whom you've spoken and presented in past years, one of the great privileges now of winning the Nobel Prize is you get free parking on the Berkeley campus?
JENNIFER DOUDNA: So they say. Yeah.
KEVIN DAVIES: It hasn't materialized yet?
JENNIFER DOUDNA: Not yet but-- KARLA SHEPARD
RUBINGER: Everything
RUBINGER: is delayed with COVID.
KEVIN DAVIES: OK. Well. OK. That's it. All right. Karla, I know you want to-- obviously, the series here is about celebrating women in science and championing women in science. I know Karla has a few questions she wanted to ask, so I'm going to pass it to her.
KEVIN DAVIES: Pass it over to you.
KARLA SHEPARD RUBINGER: Mostly, thank you Jennifer, for doing this. There are 4,000 people signed up to listen to this. So we're excited to share it. So your award is seen as an important moment for women in science, as Kevin was just saying, but following the award, Emmanuelle said, I think it's very important for women to see a clear path. The fact that Jennifer and I were awarded the Prize today can provide a very strong message for young girls.
KARLA SHEPARD RUBINGER: What lasting message do you think that awards can send?
JENNIFER DOUDNA: Well, I think certainly that both Emmanuelle and I felt proud of our gender that morning and just happy that we were sending a message collectively to girls and others who have felt excluded from the STEM fields that their work can be recognized. And that there's a celebratory feeling about science no matter where it's done or where it comes from. I think that's a really, really important message, especially of this particular award.
KARLA SHEPARD RUBINGER: Right. And real clear publicity, which is attached to this worldwide, including our webinar today. One fascinating aspect of your CRISPR story is that a year before you met Emmanuelle, you actually left Berkley to take a senior position in biotech at Genentech.
JENNIFER DOUDNA: Right.
KARLA SHEPARD RUBINGER: And that's an interesting story. And without the awakening of your returning to Berkeley, history might have been different. Can you talk a little bit about that awakening?
JENNIFER DOUDNA: And some of my colleagues on the grid here were with me at that time in the lab, so you remember it intimately. But basically, yeah, it was a very interesting experience. Because I had an opportunity to join one of the arguably best biotech companies that's famous for its fundamental discovery research. And that was a very exciting opportunity for me and I embraced that opportunity. However, once I actually got into the company itself, I realized that I missed my Berkeley colleagues, and I really missed the discovery science that we almost take for granted, or at least I had come to take for granted in the university environment.
JENNIFER DOUDNA: And so very kindly, my colleagues at Berkeley were happy to welcome me back to the fold. And the lab hadn't actually physically moved at the time. So it was easier to go back fairly quickly. And my colleagues at Genentech were also understanding. I think many of them had come from academic backgrounds, so they understood the challenges of making that cultural shift.
KARLA SHEPARD RUBINGER: Well, clearly, colleagues are central to all science, but particularly noteworthy in your work as well. So back in 2011, you were already highly accomplished researcher fielding numerous offers and partner opportunities to collaborate. What was it that you saw in Emmanuelle when you first met her that really set the stage and for that transatlantic collaboration that it would work and it did?
JENNIFER DOUDNA: I loved her sense of adventure. Her desire to understand the secrets of the CRISPR pathway, I think that was very, very interesting. We both shared that passion, but we were coming to it from different backgrounds. And I think that really made for a very interesting and exciting collaborative opportunity. I've been involved in almost countless collaborations now over my-- I don't know, 26 years of running a lab.
JENNIFER DOUDNA: And I'd say at least half of them, fizzle. They don't really go anywhere. And so it really speaks to the fact that Emmanuelle and I think shared a vision for what we wanted to do together, scientifically, as well as to the folks in our labs, Martin Jinek and Krzys Chylinski, in particular, who were able to forge very quickly a scientific connection across thousands of miles and start doing science together.
KARLA SHEPARD RUBINGER: Yeah. I think it's an important, really important testament to worldwide cooperation of science and partnerships. And it's wonderful to be able to showcase that.
KEVIN DAVIES: Speaking of Martin, we've just been joined by Martin, presumably from Zurich. Thank you for-- I know it's suppertime over there, but thanks for joining Martin, hello. You're mute, I think.
MARTIN JINEK: Hi and good evening from Zurich. Great to see you all.
KEVIN DAVIES: Great to see you. Jennifer, have you had a chance to speak to Emmanuelle in the last few weeks just to compare notes and share congratulations with each other?
JENNIFER DOUDNA: We have. Yeah. A couple times. And I think her she's in the same whirlwind that I'm in a bit. But it's been really, really fun to celebrate the science that we did together and discuss what this award means and how it will be viewed, especially by other up and coming scientists. And I also had very recently a great discussion with Krzys Chylinski, as well, who's still in Vienna.
JENNIFER DOUDNA: And again, same feeling that I think, Martin, you and I have talked about of just the joy of fundamental discovery.
KEVIN DAVIES: Yeah. Yeah. Yeah. The big project that's dominated your life this year of course, has in a way little to do with CRISPR, it's been about COVID-19. And so before I bring in John Sterling, the editor of GEN, who will have some questions, I'm sure for you and let the other guys ask some questions too. Can you tell us a little bit about what prompted you to almost take matters in your own hands and get this very important testing facility off the ground on your campus?
JENNIFER DOUDNA: Well, I'm a strong believer that science needs to be proactive, as well as reactive. We need to, as scientists, we need to be ready to pivot our expertise where it's needed. And boy, what a case in point with COVID. So back in March, like many of us, I had the growing feeling that life was about to change, maybe dramatically. I had no idea how dramatic, honestly.
JENNIFER DOUDNA: And so with a group of colleagues at Berkeley, and I was astounded at the response to this, we put together a small meeting that ended up being 60 people who got together mostly virtually to talk about what we could do scientifically as scientists to address this pandemic. And everybody unanimously said, well the most important immediate thing we can do is set up a testing lab.
JENNIFER DOUDNA: And so I think none of us certainly, I didn't have any idea how to really do that, how to run a clinical laboratory, but we figured it out. And we got that lab going in three weeks. And, now we're actually doing all of the testing for the UC Berkeley campus, as well as with several important community partners. So I'm really proud of the team.
JENNIFER DOUDNA: It's been an extraordinary journey. We went from running the lab with volunteer students and postdocs, initially, who did all of the R&D to get the test up and running to now a whole professional team, including an M.D. who runs the clinical aspect of the work that we do.
KEVIN DAVIES: This is not a CRISPR test, just to be clear, this is using old fashioned relatively traditional methods. But you obviously, I think most people watching know that you among several companies that you founded or launched, one is called Mammoth Biosciences that is developing CRISPR diagnostic tests. How are you optimistic that technology will eventually be able to provide an at home test, if not for this pandemic, then for the next one?
JENNIFER DOUDNA: Well, at home is tough. It maybe was going to get there. I think, initially, what I'm seeing-- and it's from a number of folks, including Blake is doing a lot of this work, and I'm sure many others who are listening here are involved, but there's a lot of effort to develop CRISPR as a point of care test that would be able to provide real-time surveillance testing. And that's something that I think is very likely to happen during the current pandemic.
JENNIFER DOUDNA: I mean, I think it's pretty clear that we're going to need robust and widespread testing for at least the next several months, if not longer, for COVID-19. And then obviously, having the ability to take a test like CRISPR, which is programmable and then target it to other viruses. It will be very valuable for, I would say, pandemic preparedness in the future.
KEVIN DAVIES: Yeah. Great. Let me bring in John Sterling from the Chief Editor of GEN, John.
JOHN STERLING: Hey, Jennifer. Congrats again. I saw that video on that morning that's the day you're never going to forget, so congrats. And one of the things that's always interested me covering biotech for about 35 years is how people get into certain fields. One thing that's been very clear to me in a lot of medical scientists is that they get into the field because one of their relatives, one of their friends, somebody has some disease and they pursue that.
JOHN STERLING: You, on the other hand, were living in beautiful Hilo, Hawaii and walking through the rainforest and all looking at the local flora and fauna. What turned you on to science there that is carried you through all these years to where you are now?
JENNIFER DOUDNA: Well, I think it was a combination of things. I certainly, I grew up in a family that was intellectual. And my father-- nobody was-- nobody was a scientist, but my father loved doing puzzles, and he loved reading about science and talking about science, so we did a lot of that, even though nobody was practicing it professionally. So that was going on in the background. And then I loved math. And I also, I think I was highly influenced also by that island environment of just being aware of all of the plants and animals that evolve in that environment to have particular properties.
JENNIFER DOUDNA: And I couldn't help wondering, how does that work? And so I've always been driven by those how questions in science, and really wanting to understand in molecular detail what we observe in biology.
JOHN STERLING: Well, yeah. That's basic science. So regarding women in science, a real interesting question here from someone in the state of [INAUDIBLE],, which is I guess in Brazil, and we're a country with a history of female maximum leaders which sounds like anthropology, but we, as women, are still underrepresented and under recognized. What's your advice to women who want to be excel in basic science, biotechnology, and happened to be in a developing country where there are very few-- well, she says incentives.
JOHN STERLING: I guess, I'd say maybe support for them to go into science. And she has a great question, could we dream with being awarded a Nobel Prize?
JENNIFER DOUDNA: Well, absolutely. And I think that I would just say that my experience, certainly, has been that the people that I see who are most successful in science tend to be those who are just laser-focused on their passions, and they don't let anyone dissuade them from what they want to do. And people here that know me well, know that I'm a have a stubborn streak, right?
JENNIFER DOUDNA: And I think that's sometimes been a strength in science is to be absolutely committed to an idea that you have and pursuing it to see if it'll pan out or not. And that I can think of a number of times in my career when that's been true for me. And it certainly, before CRISPR came along, there were things that I wondered about, questions that I had about a biological system that I wanted to answer.
JENNIFER DOUDNA: And there were plenty of naysayers saying that's either a silly idea or that will never work. And I did it anyway. And I did. I wasn't always right, but but at least I satisfied my question and my passion.
JOHN STERLING: Yeah. My final question again, is from somebody online, and I know you're very much involved with this because a lot. We talk about the scientific and medical implications of CRISPR, but you're saying I wonder about the ethical implications of this technology. What are the ethical limitations? And is that something you can talk about?
JENNIFER DOUDNA: Right. Well, I think it's a very interesting challenge that we have right now in this field, because the technology clearly opens the door to many opportunities. That include applications in the environment, in agriculture, and of course in medicine that are very exciting, but also bring along with them, I think important questions and challenges that we have. And we just have to, when I say we here, I mean, everybody, because ultimately, we're all affected.
JENNIFER DOUDNA: But I do think the scientific community in particular needs to step up. And I've been quite pleased that that's I think we've really seen that in across the spectrum of applications. And for CRISPR certainly, it's an ongoing challenge, I think, to keep that conversation going and to keep the transparency going. Earlier in this discussion, we talked about international collaboration, and I think that is absolutely critical in terms of managing the use of a technology like CRISPR, non-trivial to achieve that kind of cooperation but essential to work at it.
JOHN STERLING: OK. Thank you. Wonderful. Kevin, back to you.
KEVIN DAVIES: Yeah. Thanks, John. I want to see if any of our we now have six great friends of yours here in the speakers room, so to speak, Dipa, Rodolphe, Ross, Blake, Sam, Martin, any stories you'd like to share? Any questions you have for Jennifer?
SAM STERNBERG: How's the big alumni trip to Hawaii? [LAUGHTER]
JENNIFER DOUDNA: I'm saving my pennies for that one, Sam.
SAM STERNBERG: Or maybe I'll add a little bit of story, which was when the lab turned 20 years old, I was fortunate enough, alongside Ross, I think is the only other one on the call on the panel here, to be in the lab at that time. And we had Jennifer-- actually, Ross was the organizer, I think Ross organized the Doudna Lab Conference, I think you had a name for it, Ross, I don't remember what it was.
ROSS WILSON: The Pacific RNA Research Symposium or something like that.
SAM STERNBERG: Yeah. But fantastic trip, a couple days. And we talked a fair amount of science. I think what was really fun there is everyone had carte blanche to present anything they wanted, so we had certainly some talks that were relevant for their research, but we had other memorable talks that were about completely new research topics. And then we did some hikes in the crater and the volcanic craters, some kind of hanging out and dancing in the evenings and good food, good drinks, good natured explorer.
SAM STERNBERG: But I think, always a good reminder that the science needs to be balanced by building a community of people that enjoy spending time together. And I have to say, having started my lab here, it's another thing that I took away from my experience in Jennifer's lab, how fun I-- how much fun I had working with Ross, Martin, Dipa, Blake, these are some of my best friends in science. And that's actually not always the default.
SAM STERNBERG: I see other labs in my building and other buildings on campus where you can really tell that the lab hasn't really synergized and formed that community of friends and colleagues. And I think it doesn't happen all on its own. You need to set up the lab in a way that cultivates that and nurtures that. So that's something that I really look back very fondly on all my time in the lab.
SAM STERNBERG: A lot of good memories.
KEVIN DAVIES: Of course. Any other comments or questions?
RODOLPHE BARRANGOU: I'm going to ask one too.
KEVIN DAVIES: Yeah, sure.
RODOLPHE BARRANGOU: So Blake mentioned earlier today, we all did how exhilarating the research has been, how exciting the original CRISPR days were. But when did it hit you that this was going to be real, life-altering, world-changing, not just and your lab but a lot of other people. Did something happen or was there a moment in time where you realized it was bigger than you thought?
BLAKE WIEDENHEFT: And can I add on to that question a little bit? I mean, since this is the Rosalind Franklin Society discussion, I wonder if you could couch the answer to that question in the context of what's your version of Photo 51, Rosalind Franklin's historic photograph? And I was gone in the lab when I had just left or was on my way out when you and Martin were kind of having these daily epiphanies, and so I missed the first hand, some of that first hand excitement.
BLAKE WIEDENHEFT: And I don't think I've had a chance to chat with you and Martin, in particular, about how that went down and maybe you could just share a little bit of the play by play?
JENNIFER DOUDNA: Yeah. Well, we have Martin here too, so Martin, you can comment on this. But I think, for us in the lab, there was really a pivotal moment, and it was kind of building, because we could see that there was a lot of really interesting biochemical activity of this CRISPR Cas9 protein as an RNA-guided DNA cutter. But I think for us, that pivotal moment of the project going from pure curiosity-driven investigation to something that we could see would have much bigger, broader implications, was when we were in-- I think we were in my office, Martin, and we were talking about your biochemical data defining what the essential components of the Cas9 DNA targeting mechanism really were, especially on the RNA side.
JENNIFER DOUDNA: And that led to the idea that the RNA molecules could be combined into a single guide format that we thought was really cool and fun that, wow, we understand enough about this to be able to redesign it. And if that works, we'll know we really understand how this thing operates with its RNA guide. But beyond that, it would also create a much simpler system, a two-component system for DNA cutting that would be programmable.
JENNIFER DOUDNA: And being from thinking of my graduate work in the 1980s, I was imagining that New England Biolabs catalog, of all of the available restriction enzymes being compressed into one protein that could be trivially reprogrammed with its RNA guide. It was a profound idea. And having that going on in the context of all of the other work that was going on far beyond our lab both on DNA repair and on genome engineering with engineered proteins, all the pieces started to come together.
JENNIFER DOUDNA: And I think that was really that proverbial moment. And if there is a Photo 51, I think what it is in my mind, I'm curious if Martin has a different answer, but Martin, I think it would be a slide-- I still show this slide in some talks, because I just love the data, but it was the experiment that you did where you designed five different single guide RNAs that would target parts of a plasmid sequence. And you did in a way the simplest experiment in molecular biology of cutting that plasmid DNA with these different single guide RNA-programmed Cas9 complexes and a separate enzyme to chop out these pieces of DNA.
JENNIFER DOUDNA: And you have this beautiful agarose gel that shows all of these DNA fragments of different sizes corresponding to where the guide RNA was cutting. So it was just one of those, wow, that just right there that encapsulates what this protein is capable of doing.
KEVIN DAVIES: You agree, Martin? You concur?
MARTIN JINEK: Yeah, I think, I would agree. Yeah. I think the discussions basically about the experiments that we had in the office, that was probably the eureka moment. But then I think the real excitement then came when we were able to follow up on all these ideas with actual experiments and really prove that. We had a programmable one protein, one RNA system. And just like Jennifer said, basically, that experiment where we designed different RNAs for the same target.
MARTIN JINEK: And we could just see exactly that the RNAs pair, guiding the complex to cut the DNA in exactly the place where we were expecting it to cut, that I think was the pivotal moment where we-- from that point, we knew that this was a technology that was going to change things.
KEVIN DAVIES: Jennifer, you've just-- I believe you're the co-founder of a relatively, a company that's just come out of stealth mode called Scribe Therapeutics. Their logo looks suspiciously like it was derived from Photograph 51. So I think it was a great reference, Blake. Clearly, it hasn't been forgotten. Let's just-- we have about five minutes with you left. CRISPR has come so far in the last decade, it's now, I guess you could say it's approaching puberty as it enters its second decade, what are some of the most exciting projects that you're really excited about going on in your lab now?
KEVIN DAVIES: And I think the other part of that question is maybe looking forward to the next decade, what are some of your big hopes for the technology, not just from your lab but from the international community that's using your technology?
JENNIFER DOUDNA: Well, I think certainly, thinking about how the technology will be deployed and how it will actually have impact around the world is something that lots of people are thinking about. But I certainly what really keeps me up at night right now is the idea that as a field, we really need to go from the proof of principle that we're all-- we've all been working on, which is that type of experiment, demonstrating the capabilities of the technology, and that's certainly been extraordinarily exciting over the last several years to increasingly thinking about how we actually make the technology widely available to people that need it.
JENNIFER DOUDNA: And a great example of this is the work that's been done with sickle cell disease. And I think many folks are aware that sickle cell disease is a monogenetic disorder that CRISPR is in a way perfectly suited to treat or even cure by making corrections to or changes to a specific gene that could mitigate the disease phenotype in affected patients. And in fact, that's been done now by a company called CRISPR Therapeutics that Emmanuelle founded, and other groups are working on this.
JENNIFER DOUDNA: And the question that I think we ask ourselves and Ross Wilson is very involved in this right now is, how do we make sure that a technology that clearly works for a disease like that, which is just extraordinary and very exciting becomes affordable and available to those that need it? Right now, that CRISPR therapy is going to cost worth of $1 million a patient, which is just not sustainable.
JENNIFER DOUDNA: So in the Innovative Genomics Institute where we're working at Berkeley and UCSF, this is front and center in our minds. And so we're working on different ways of delivering the CRISPR molecules and coming up with strategies that will avoid having to use a bone marrow transplant for these patients, for example, as well as investigating new CRISPR enzymes that are potentially going to be easier to deliver, because they are either smaller or have other advantages in their chemistry that make them easier to get into particular cell types or tissues.
JENNIFER DOUDNA: So that's really one of the big areas that I personally am focused on at the moment.
KEVIN DAVIES: Yeah. Yeah. What's going on in your lab that's really exciting right now?
JENNIFER DOUDNA: Well, so in addition to working on these delivery strategies, we do a lot of work currently with Jill Banfield at Berkeley, so she is the person who told me about CRISPR originally back in the day and continues to work on the discovery of new CRISPR systems in various microbial communities. And with her lab, in addition to that discovery work, we're also very excited about being able to manipulate the genomes of communities of bacteria.
JENNIFER DOUDNA: And this is something that I've talked a lot to Sam Sternberg about. And he's also very interested in this. And hopefully, when we're post-COVID, Sam, we will be meeting up in your lab to work together on this as we discussed. But this, I think is a very exciting direction for the future. Why?
JENNIFER DOUDNA: Because I think if it were possible to manipulate microbes, specific organisms within their natural communities, whether it's the human gut or whether it's soil or water, environmental niches, this will absolutely change the way microbiological research is done, where it's not necessary to cultivate individual organisms in laboratories to study them, but you can actually do investigations or even manipulations in a natural setting.
JENNIFER DOUDNA: And I think that's very exciting. That's something we're working on quite closely with Jill.
KEVIN DAVIES: Well, we've been bombarded with questions from the audience. We had a whole bunch more we would have loved to have gotten to and hopefully, maybe when the dust settles, if it ever does, we could have back and for a slightly longer period. But our heartiest congratulations again and best of luck going forward not only for the celebrations in a few weeks' time. But in the post-pandemic world, when as you say you can get to see your friends in the flesh again and build these wonderful collaborations.
KEVIN DAVIES: So Jennifer, thank you so much for joining us.
JENNIFER DOUDNA: Thank you, Kevin and Karla and John. And thank you, everybody that's attending and of course, my colleagues here on the grid, it really means the world to me. And you guys are-- you're awesome, all the work that you're doing, most appreciated. Thank you.
KEVIN DAVIES: Thank you so much. So we'll hang around for the next 5 or 10 minutes with the guys, if they don't have to rush. Ross, you're working at the Innovative Genomics Institute. Maybe tell us a little bit about what the big plan of that Institute that Jennifer co-founded, if I'm not mistaken.
ROSS WILSON: She absolutely co-founded.
BLAKE WIEDENHEFT: Is it too early to suggest that delivery is the next Nobel Prize? [LAUGHS]
ROSS WILSON: Well, I'll tell you what, whoever fixes the delivery problem will not get credit, because progress on this front will not get you flashy publications. And I think that's one of the reasons that-- there's two reasons that it's underappreciated. It's maybe three. It's very, very hard. You don't get a lot of academic credit. And in industry, they're not doing research, they're doing development.
ROSS WILSON: So basically, they pluck anything that looks promising from academia and just push it as fast as possible into something that can make money. And so there's this major incentives problem. And I think one of the major pushes at the Innovative Genomics Institute is that we're trying to really fix this translational problem by being creative.
ROSS WILSON: And I don't want to sound too hubristic, this is a very hard problem. But we're trying to really think about it in an end to end way without letting all these corporate incentives steer us off course in between. But overall, the goal of the IGI is to make an impact exactly like Rodolphe was talking about. And the other places we're really interested in doing this is on the agricultural front, which ties into climate change, and on the society and ethics and education front, I think that we're really trying to distinguish ourselves there by making CRISPR something that the world can understand, hopefully not fear.
ROSS WILSON: But also, making people aware of the ethical considerations that we should be talking about. So I think those are a lot of the things that drive us.
KEVIN DAVIES: Great. Great. I saw a question flash up. We didn't have time to ask it of Jennifer. But the big story in the last 24 hours in science circles has been this extraordinary paper, which I'm sure is about to be retracted, if it hasn't already been, in Nature Communications, that seem to suggest that women can't act as mentors or something. Absurd.
KEVIN DAVIES: I mean, Dipa, Rodolphe, Sam, would welcome anyone's thoughts on that, we've just seen the most spectacular example of a woman who's inspired legions of scientists and former mentees. If any of you have a reaction to that, I'd love to hear it?
RODOLPHE BARRANGOU: So I love your use of the word absurd. Right? Especially in the context of the Rosalind Franklin Society where I've had the pleasure to speak before. There are examples over and over and over and over again of great women across, not just science but the world, have had tremendous impact, that are great mentors actually mentioned that as Jennifer joined us today. So I think it's nonsense, whatsoever, whether there's going to be retracted and how quickly it will be retracted time will tell.
RODOLPHE BARRANGOU: But I think it's an urban legend that has been debunked a number of times. And but this is a reminder to me of the world that we're living in. And I would compel people. No matter the science inclination or not, the data expertise or not, their extensive knowledge or not of a lot of things that whenever you hear data or you hear stories, we heard about storytelling for the right reasons, there's a lot of storytelling with the wrong reasons nowadays.
RODOLPHE BARRANGOU: Right? People seek attention. People twist, misinterpret data all the time, even people fake data, occasionally, as we know as editors. So I think we have to learn to take things with some degree of skepticism but healthy skepticism and know when to interpret data firsthand, and not always let other people interpret data for us.
RODOLPHE BARRANGOU: I think that's an important lesson that sadly enough 2020 has taught us over and over and over again. But in this case, it's so, so absurd, as you said that, I think it speaks for itself.
KEVIN DAVIES: Yeah. Any other comments on that? Dipa? Dipa then Ross.
DIPALI SASHITAL: Well, as a female scientist who had an incredible female mentor, obviously, agreed with Rodolphe, that this is an absurd paper. When I was looking at postdocs, my PhD mentor was helping me to decide between two labs of the lab of Jennifer Doudna, of course, and another lab which had a male mentor, and he specifically said, you've been in my lab, I really think that you would benefit from having a female mentor for your postdoc.
DIPALI SASHITAL: It didn't really strike me at the time how right he was about that. I do think that it made a huge difference to me to have somebody like Jennifer who really is honestly one of the most impressive people I've ever met in my life, so a true inspiration, somebody to really look up to. And somebody who helped me to develop myself as a mentor and to be able to mentor the people who are in my lab now.
DIPALI SASHITAL: So I agree with Rodolphe that there's data and then there's interpretation of data. The data itself does say something. It says that the metrics that we use to judge success are biased and are not the metrics we should be using to judge success. But the interpretation in the paper is obviously exceptionally flawed.
KEVIN DAVIES: Yeah. Yeah.
ROSS WILSON: Yeah. I just wanted to say basically what Dipa did. The results can be whatever they are, and I think there was dubious work in that paper to get to the results but to see that outcome and conclude that your response should be to advise everyone to avoid working with women in science is criminally negligent and just wildly irresponsible. So yeah, I can't wait to see that paper gone from anyone's discussion.
ROSS WILSON: I mean, it's got to go.
KEVIN DAVIES: Yeah. Yeah. Well, we don't have much time left. But maybe we could just each of you give a quick closing summation and ask Jennifer what her hopes for the second decade of CRISPR and genome editing might be, what are you most hopeful for or looking forward to either from your own group or from the field as a whole? Blake, maybe we could start with you.
BLAKE WIEDENHEFT: Well, one of the things that I think each of us articulated a little bit was the influence Jennifer had on our careers. And I think Sam did a better job of doing that than I possibly could. So I won't try to follow that. But I think-- I think that one of the things that strikes me is, I don't think I fully appreciated what Jennifer was doing and how hard it was until I was on my own and had to do it myself.
BLAKE WIEDENHEFT: It sounds like an ungrateful child almost, but I think it wasn't until I tried to recreate that atmosphere here in my own group that I really appreciated how hard it is to do and how graceful she is in doing that.
KEVIN DAVIES: Yeah.
BLAKE WIEDENHEFT: Yeah. There's lots of different aspects of the work in the lab, some of the-- as Jennifer mentioned. I've tried to follow in some of those footsteps a little bit as well, trying to develop some new diagnostics and more to the point maybe just pivoting the research interests in my lab at touch from CRISPR into some SARS Coronavirus work, and that's an interesting new puzzle and an adventure maybe that we've been excited to chase.
KEVIN DAVIES: That's great. Great. Sam?
SAM STERNBERG: Yeah. Maybe to dovetail on that, Jennifer what she's famous for now is not the same thing as what she was famous for 15 years ago. But she was famous 15 years ago for being the first to crystallize structured RNAs that weren't tRNAs, which really opened up a whole new world of RNA biology. So one thing that I'm thinking about a lot in the lab is how to continually pivot, reimagine what the science focus of your group is and not get stale by focusing on the same things and digging deeper on the thing from five years ago, but what's going to be the next breakthrough?
SAM STERNBERG: So I think there's a lot of that in CRISPR. There's a lot of that outside of CRISPR. And that's something that I think is always a fun challenge to wrestle with.
KEVIN DAVIES: Yeah. Great. Ross? Can't hear you. There you go. What's the big adventure for your group and IGI over the next five years?
ROSS WILSON: Sorry. The delivery challenges remain but the thing that I'm really excited about is changing a lot of non-genetic diseases into things that could be tractable with genetic cures. So there's a lot-- I mean, there's a crisis coming in with an aging population. Neurodegenerative diseases are going to have an ever increasing impact. And right now, even if you could CRISPR the brain, I don't think we know exactly what to do.
ROSS WILSON: And fortunately, I think CRISPR is going to have a huge impact there, because it has the capacity to let us model disease and probe genetic pathways in a way that is just totally transformed, thanks to the technology. So I think making incurable diseases tractable at the fundamental understanding level is very exciting.
KEVIN DAVIES: Thanks. Rodolphe?
RODOLPHE BARRANGOU: I mean, yeah, so as far as I'm concerned, I think medicine is great. It's going to save lives. But there's only a couple hundred million people maybe that benefit from it in short term, at least. But if we use it for food and ag, we're going to revolutionize the whole world and impact everyone. So think from microbiomes and fermented foods and crops, all the way to engineering trees in the forest, I think is where the future is going to be to some extent to replicate the success in medicine.
RODOLPHE BARRANGOU: But to me, the biggest challenge that we all have to take on is not science anymore, right? Science is almost trivial, feasible, thanks to CRISPR, Jennifer and her great work. But I think engaging the public and addressing scientific skepticism, and we won't be able to use it until there's acceptance of science by the public and anti-vaxxers and anti-GMOs, and anti-science bias is arguably an all-time high as mentioned by the great Tony Fauci as well.
RODOLPHE BARRANGOU: So unless we start training scientists to address that, and until scientists dedicate at least some of their time to address that with the public, I think it's going to be hard to really benefit as much as we should from great science technologies like CRISPR. And this is also why I'm excited about Jennifer being uniquely positioned, and equipped to address that with the narratives that Sam mentioned with the great mentorship and storytelling and attributes that she has as a communicator.
RODOLPHE BARRANGOU: And I think but it's going to take more than just the great Jennifer Doudna to do that. And we should all embrace that challenge hopefully to some extent.
KEVIN DAVIES: Nice. Thank you. Martin?
MARTIN JINEK: And I think this is becoming a very hard act to follow. But I would really echo some of the sentiments here that, of course, I think-- yeah, the educational aspect of what we do is something that is increasingly important and for our future, this is this is going to be key, not just in the context of CRISPR, but of course, here as well.
MARTIN JINEK: One thing I wanted to maybe also follow up on is what both Blake and Sam was were saying is that-- yeah, Jennifer is kind of inspiration was for me the way that she continuously keeps reinventing herself, scientifically and how she basically looks for new problems, new questions, new ways to approach problems. And so this is for me, this is if I want to develop as a scientist, as PI, this is for me, this is the greatest challenge looking into the future.
MARTIN JINEK: And I hope I can live up to the great inspiration and the great example that she gives to us all.
KEVIN DAVIES: Don't think you're doing too badly on that front, Martin but time will tell. And Dipa?
DIPALI SASHITAL: So I would say that since we're here celebrating this Nobel Prize, this Nobel Prize really came about from basic science research and just a sense of inquiry, trying to understand how a bacterial immune system works. And that's so important. Doing that type of research continues to be important. So in the future, going forward, I think we will never know what our research will tell us until we've actually done the research.
DIPALI SASHITAL: And there's tons of exciting work being done in the same area discovering other phage defense mechanisms or defense mechanisms against phage and the warfare between phage and bacteria, I think that that area of research is really exciting and has proven to provide a lot of biotechnology tools and may continue to do so as we move forward. So that's an area I think that is really exciting to watch as we move forward.
KEVIN DAVIES: Good. Well, thanks to all six of you for making time. You've got hectic schedules and lots going on, so but it speaks volumes that you want you wanted to do this to be part of this meet and greet with Jennifer. And apologize to everyone who tried to ask a question. And we didn't have time, we'll try to find a way to relay them to Jennifer or answer them in another format.
KEVIN DAVIES: But that's pretty much the end of our program. Karla, I'm going to let you close things out.
KARLA SHEPARD RUBINGER: Well, thank you. I hope you're all as breathless as I am this was a whirlwind of great discussion. And this is a wonderful way to conclude our series on Women in Science. I warmly invite all of you to join us for our virtual meeting, which will be held on December 16 and 17. And please visit our website to get details about that. This was supposed to be an in-person meeting at HHMI, which obviously will not happen this year, but hopefully next.
KARLA SHEPARD RUBINGER: Obviously, we thank Jennifer Doudna, our newest Nobel laureate for her time today and for all of you for joining and celebrating her work and yours. We are terribly grateful for the support from Horizon and OnRamp, from GEN, without whom this would not have been possible. And all of you as panelists and guests and the 4,000 people who registered to hear this as well.
KARLA SHEPARD RUBINGER: So it's a wonderful testament to the importance and the interest of science. And we really appreciate this interest, especially in this particular time from all of you. So for GEN and the Rosalind Franklin Society, I'm Karla Shepard Rubinger. I hope you all stay safe and healthy. And good bye for now. Thanks.
KARLA SHEPARD RUBINGER:
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