Jennifer Doudna on what it takes to be a good scientist

[MUSIC PLAYING] IRA FLATOW: Hi, it’s Ira. And you’re listening to Science Friday. Over the years, I’ve talked to thousands of researchers on this program, and while their findings, advances, and inventions are interesting and important, I’m also interested in a deeper personal question. And that is, what does it take to be a good scientist? Is it creativity, good ideas, diligence, luck, or all of the above? Then whom to ask?

Well, in 2020, Dr. Jennifer Doudna shared the Nobel Prize in chemistry for the development of the gene-editing technique, CRISPR. CRISPR and related techniques have become essential tools in genetics. It’s an advance that has changed the game in biology. Dr. Doudna has spoken or written about the challenges and rewards of science, so I wanted to get her take on my “what does it take to be a good scientist” question and the path she followed.

Dr. Jennifer Doudna is a professor of biochemistry, biophysics, and structural biology at the University of California, Berkeley, a 2020 Nobel laureate in chemistry, and most recently, recipient of the 2026 Priestley Medal, the American Chemical Society’s highest honor. We couldn’t connect right after the Nobel in 2020. She was just a bit busy. So the Priestley Medal is as good an excuse as any to have her back. Dr. Doudna, welcome back to Science Friday and a belated congratulations.

JENNIFER DOUDNA: Well, hi, Ira. Great to be back. Thanks for the congrats. I’m looking forward to the conversation.

IRA FLATOW: Great. Well, in doing my research for this interview, I noticed that you get asked this question a lot– what is good science, and how to do it? Why do you think you get asked this all the time?

JENNIFER DOUDNA: I think when you have science that is in the public eye the way CRISPR is, there’s a natural curiosity about how it came about, how the people behind the scenes were involved in the science as it was developing. I think it is a fascinating question. What does it take to do interesting science? And how do we think about it now, especially in this era of AI and AI scientists?

IRA FLATOW: Yeah, I hope to get into this because I know you seem very eager and happy to talk about this all the time, so–

JENNIFER DOUDNA: [LAUGHS] Whether I want to or not, Ira.

IRA FLATOW: [LAUGHS] Well, let me go right to the beginning. Do you remember the moment when you decided you wanted to be a scientist?

JENNIFER DOUDNA: Well, I sort of do. It really goes back to when I was in 10th grade in high school.

IRA FLATOW: Really?

JENNIFER DOUDNA: Yeah, because we were given a standard aptitude test that, for me, came back saying, well, the thing you’re probably best at is being a civil engineer. I had no idea what that was, [LAUGHS] but it was the first, I guess, data point for me that suggested that there could be a scientific angle to my interests, and that maybe that was something I could consider for my future career. And that made me start thinking about what areas of science I might find most exciting. And frankly, I got really interested in the question of chemistry underlying the evolution of life and understanding modern biology from a more chemical evolutionary perspective, if that makes sense.

IRA FLATOW: Yeah.

JENNIFER DOUDNA: And so I went to college with that goal in mind, had no idea, really, what I wanted to work on. But I’ve been very fortunate that over the years, I’ve encountered a number of great mentors who have exposed me to different kinds of science. And I think through that process, I’ve really had the chance to observe some wonderful scientists up close, how they think about science, how do they pose a question, and then how do they go about addressing it. And I think each of us has our own personal approach to science, and yet, we absolutely benefit from observing what other people have done so successfully.

IRA FLATOW: Yeah, that was my next question, because when I talk to scientists, a lot of them say, you know I had a mentor somewhere along the line who kept me going. And did you have anyone in particular? Because you didn’t grow up in a family of scientists, did you?

JENNIFER DOUDNA: Didn’t, no. Nobody in my family on either side was a scientist. And it made me have to break out a bit on my own. I was lucky that my father, who was a professor at the University of Hawaii, exposed me to science through his good friend and colleague, Don Hemmes, who was a professor of biology at the university, now emeritus. And Don gave me the opportunity to do some research in his lab when I was still in high school. So that was my first exposure to what it might be like to work in a real research lab where there wasn’t a cookbook set of experiments with a defined answer like you get in a lab course, but where you were literally asking and trying to answer a question that maybe nobody had ever answered before.

IRA FLATOW: OK, so then walk me through the backstory a bit of how you came to be working on CRISPR in the first place. Where did the idea come from? How did you decide this was something that was for you?

JENNIFER DOUDNA: It was an indirect path, to say the least. I started off in graduate school working on probably one of the biggest questions you could imagine in biology, namely, how did life evolve on our planet? And I was working with a fantastic advisor, Jack Szostak, whose question about the origin of life boiled down to, could we come up with ways of, in the laboratory, testing how molecules could perform both the function of carrying genetic information and copying that information? So doing both of those things, but within the context of the same type of molecule.

And that was, frankly, the beginning of my interest in how RNA functions across biology in different ways. So when I eventually started my own lab at Yale University in 1994, I was, at that time, building off work I had done during my postdoctoral research in Colorado with Tom Cech to figure out how RNA molecules are structured three-dimensionally to give them the ability to, potentially, at least, serve as a replicating enzyme.

And then when I moved my lab to UC Berkeley in 2002, I, again, was taking my RNA lens to my thinking and projects that we were starting to work on there, including understanding how the machinery in the cell that makes small RNAs that are involved in a process called RNA interference, are using RNA to control the way that proteins are expressed in different cells.

And it was, frankly, that line of work which led me to CRISPR, because that led me to my initial meeting with Jill Banfield, a colleague here at Berkeley who was one of the first researchers to discover that bacteria have what looked like an RNA-guided immune system, an adaptive immune system that allowed them to acquire sequences of genetic material that could be used, in turn, to defend themselves against infection by viruses that bore those sequences. And so that was the basis of CRISPR and how we got interested in investigating how it might be working as an RNA-guided system.

IRA FLATOW: What is it, though, about your personality that actually got you through all of this?

JENNIFER DOUDNA: I’m pretty stubborn.

[LAUGHTER]

IRA FLATOW: That’s an important ingredient, it sounds.

JENNIFER DOUDNA: Well, I think there’s that. I think it’s also, I do think back to my upbringing in Hawaii because I felt a bit like an outsider in the culture there. Being a haole, or white girl, there in the 1970s, I was kind of, by definition, an outsider. And also, as we discussed earlier, growing up in a family of non-scientists and a girl to boot, I felt like there wasn’t any particular expectation put upon me to go in a particular direction professionally.

And in a weird way, I think that gave me a sense of freedom, too. I didn’t feel like I had to please anybody or perform for somebody’s expectations. I could literally just explore ideas I was interested in. And if they didn’t pan out, well, that’s just how the ball would bounce. And that’s how I’ve approached my work, I think, throughout my career, is that I really try to focus on questions that I think are really exciting and interesting. And I try to always have the thread of evolution underlying our projects because I do think that is truly the foundational aspect of biology on our planet.

IRA FLATOW: On the Nobel page, it says, quote, “Embrace your interests, your passions, and really give it your all.” Is that your philosophy of research?

JENNIFER DOUDNA: Oh, 100%. I think you really have to be willing to take risks. I think you have to be willing to try things that maybe other people say are a bit crazy. I think you have to be interested enough in a project to be willing to work through all the tough times that are going to come because that’s how research is. There’s lots of experiments that fail or ideas that don’t pan out. And you have to be willing to work through that to answer a question that you are driven to address.

IRA FLATOW: Yeah, let’s talk about failure, because whenever I talk to scientists, I’m always impressed by the role that failure plays in their work, that failure is an absolute necessity. But it’s something that’s hard for the public to embrace, I think.

JENNIFER DOUDNA: It is, isn’t it? Because it’s counterintuitive. You look at a project that has had success, and it can look from the outside as though it was an idea conceived brilliantly somehow, and that every experiment went as predicted, and that led to the outcome. But I think that’s probably rarely true, if ever. In my experience, I don’t think I’ve ever worked on anything that didn’t have a series of failures associated with it.

IRA FLATOW: Did you have that on the way to CRISPR, also?

JENNIFER DOUDNA: Yes, because when we started working on CRISPR, one of the first things that we were doing in the lab was trying to figure out how this enzyme, a protein called Cas9, how it could use a molecule of RNA to grab onto a particular DNA sequence and cut it, much like you might cut a rope, except this is occurring at a molecular level. And all of the initial experiments just completely failed. They just didn’t work.

And so we thought, well, either our hypothesis about how this protein is working is completely wrong, or we’re missing something in our experiments. And that really led to a whole wide-ranging set of efforts, both in our lab and our collaborators’ lab, Emmanuelle Charpentier’s lab, to figure out what that missing element might be. And that led to the discovery, in fact, that the RNA used by the Cas9 protein in bacteria, it comes in two segments, not one. So we had one of the segments, but we were missing the other one. And as soon as we had the other one present in our reactions, suddenly, we started seeing DNA cutting, and things started working.

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IRA FLATOW: We have to take a break, and when we come back, continuing the conversation and looking at the role of science and scientists in society. Stay with us.

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IRA FLATOW: One of the ingredients, it seems to be, that you need to be a good scientist is to have courage through uncertainty and not to give up. You talked about you being stubborn. And this sounds like some portion of that.

JENNIFER DOUDNA: Right, and it is. And I think, to me, one of the biggest challenges in science is knowing how stubborn to be. You know what I mean? You have to decide at what point– because certainly, we’ve had plenty of projects in the lab over the years where we eventually realized that we’re barking up the wrong tree, and we need to move on, or we need to pivot in a big way.

And there’s often that question that will come up in a project, is, am I just one experiment away from this starting to click, or am I really on the wrong path here, and I need to redirect or even drop this project and work on something different? And I still struggle with that. I think it’s always a judgment call.

IRA FLATOW: Do you have to have a team that believes with you to keep going, instead of throwing up your hands and saying, we’re wasting money here?

JENNIFER DOUDNA: Definitely, and science is a team effort. It is. And there often are differing points of view. And we often have this discussion in the lab. People are not entirely in agreement sometimes about should we keep going on this project, or should we pivot? And/or should we try a different approach? And so it’s often a debate and a discussion. And you have to have people that are willing to take a risk and try things that they might not be fully on board with, but are willing to try because they’re ultimately interested in answering a question together.

IRA FLATOW: That’s my next point about how important is being open to different perspectives, different minds, being surrounded in your work by these people.

JENNIFER DOUDNA: Oh, incredibly important, in my view. I couldn’t emphasize that enough, really. And I’ve just seen this over and over again. It’s really exciting, actually. This is one thing I love about research and I love about running an academic lab at a major university with great students coming in the door every day. It’s that you never know where the next great idea will come from. And in my experience, it often comes from unexpected directions.

More often than not, it comes from people who are perhaps not yet very experienced in a field, but they have an idea that they want to pursue, or they’re linking together ideas that come from other fields, other labs, other experiences that they’ve had that are seemingly unrelated and yet, end up being, oddly connected to the project that you’re trying to work on together. I find that really fun.

IRA FLATOW: Yeah, and is fun a necessary ingredient to have fun with what you’re doing?

JENNIFER DOUDNA: I feel it is. I do. [LAUGHS] I emphasize this a lot in the lab. I want people to have fun. I’m not saying that every experiment is fun or that every day in the lab is fun. Like we were saying, there are frustrations for sure. But I do think that overall, there has to be a feeling of joy in one’s work. I think it makes the work better in the end. I think it makes us more creative and inventive with what we’re doing. I think it makes us more resilient when we have failures, is if, ultimately, we have a sense of joy in the discoveries that we hope are going to happen.

IRA FLATOW: But you also need a bit of serendipity, as you were mentioning, of luck coming into play, perhaps, being in the right place at the right time, right?

JENNIFER DOUDNA: Yes, I do think that that’s true. And it’s always hard to grapple with that, in a way, because it makes it sound as though there’s some unpredictability to our work. But I think that’s the reality, is that things are a bit unpredictable. There are opportunities that come up, discoveries that come up.

I think there’s a timeliness to science. I’ve often thought with CRISPR that, in a way, it came along at the right time, when there were a lot of genome sequences being presented and posted publicly right around the time that we were working on CRISPR. Hence, there was a desire to have technologies, tools that would allow manipulation of that code of life. And what CRISPR did was to provide that kind of a programmable, readily accessible toolbox for manipulating genomes, right at the moment when there was a need for that.

IRA FLATOW: I love Louis Pasteur’s definition of luck when he was asked about luck, and he said, luck prefers the prepared mind. In other words, if you’re looking for it and your mind is there, you’ll find it. You’ll be lucky.

JENNIFER DOUDNA: Yes, I think there’s a lot to that. That’s certainly been my experience.

IRA FLATOW: The PR people like to talk about a breakthrough. Can you point to any one thing that was an actual breakthrough moment in your career, or is that term just something for press releases, because you’re really standing on the shoulders of other people?

JENNIFER DOUDNA: Well, certainly, science is built on the shoulders of other people. There’s no question about that. That being said, I do think that there are certain moments that happen in research where you have a feeling or a recognition that you’ve just made a very interesting discovery of some kind that might have broad impact. And I think for us with CRISPR, it was really twofold. I think it was the moment, as I mentioned before, where we had found the missing component that suddenly activated our Cas9 enzyme, and we could see DNA cutting going on in our test tube, which was great, very exciting.

But the other component or aspect of that work that was also equally important was recognizing that those two segments of RNA that are the guide for Cas9 could be linked together artificially by us in the lab to form a single segment of RNA that would have all of the functions that we found in bacteria, but be much easier to manipulate as a technology. And I think that was really also an important moment for us, realizing that we could control the activity of Cas9, but in a way that was a lot easier to manage than what nature has done.

IRA FLATOW: I hear what you’re saying. So looking back and looking forward, I mean, has CRISPR given us the fruits of your labors that you had expected or predicted? Are you happy at how it has worked out?

JENNIFER DOUDNA: I mean, it’s just incredible, isn’t it? Who would have thunk that just over 10 years after that original publication with Emmanuelle’s lab, that we would have an FDA-approved therapy for people that have sickle cell disease, using the same enzyme that we had worked on? No way I could have predicted that.

But I have to say that from the very beginning, it was pretty clear that having a readily programmable tool for manipulating DNA sequences with precision in cells was going to be– there was no question that was going to be a very powerful way to advance science.

IRA FLATOW: And of course, you recognize, then, that there are ethical, moral limits to the use of gene editing.

JENNIFER DOUDNA: Indeed. I mean, this is an ongoing challenge in the field, is to figure out how do we manage the risks with a powerful technology that clearly has capabilities that go beyond what I think we have the current infrastructure socially and societally to manage. And I guess, I’m thinking in particular here about two things. One is germline editing, meaning making heritable changes in human beings. And the other is environmental challenges, whether we are going to be comfortable allowing CRISPR to be deployed to control populations of mosquitoes and things like that. It sounds like maybe a great idea, but we clearly have to manage it carefully.

IRA FLATOW: Right. You created the Innovative Genomics Institute, which adds planet Earth to your portfolio, bringing CRISPR not only to medicine, but to agriculture, microbial ecosystems. What inner thoughts drove you to do this?

JENNIFER DOUDNA: Well, when I started thinking about what kinds of impacts CRISPR would have, especially when we think very broadly, globally, in terms of large, grand challenges that we’re facing as a species, really, I kept coming back to the idea that having a technology that allows manipulation of microbes, of plants, and of their ecosystem in the environment would be incredibly impactful when we think about the challenges we’re facing with climate change and with population growth.

And so our institute, from its beginning, has been focused on not only human health, but also planetary health and specific aspects of planetary health where I think CRISPR can make a difference. And then, in particular, we’re focused on methane emissions, how to reduce those from cattle, and other agricultural applications of CRISPR, and also thinking about carbon sequestration.

IRA FLATOW: “are we seeing advances past CRISPR? Are there new CRISPRs out there that are possibly even better?

JENNIFER DOUDNA: Well, there’s lots of people looking.

[LAUGHTER]

There’s no question. And now there are AI tools to help look for new things that maybe nature hasn’t even discovered. So there’s lots of efforts on that front.

IRA FLATOW: Tell me more about the AI tools that– how they might happen.

JENNIFER DOUDNA: Right. So yeah, I mean, I think there’s clearly going to be an ongoing, evolving toolbox of tools that allow genome manipulations. That being said, CRISPR is pretty good. And nature’s been experimenting for a lot longer than any of us have been around. So I think it sets a high bar, I’ll just say that.

But look, I think it is very exciting to think about the way that AI could advance some of this. These AI tools are as good as the data they’re trained on. And so what we’re seeing in the lab, at least so far, in our experience, is that it can be very effective at doing things like, obviously, predicting protein structures. That was also a Nobel Prize-winning piece of work, as you know, and even starting to help predict new kinds of proteins that have particular functions. I think that’s very exciting.

And predicting the ways that proteins interact with each or other kinds of molecules, that’s also moving forward with AI assistance. These are all great, but I think we’re not at a stage right now, and maybe not in the foreseeable future that I can see, where AI will really be taking over in terms of coming up with those kinds of ideas and hypotheses that, as we discussed earlier, really, in my view, drive new breakthroughs.

IRA FLATOW: Why not?

JENNIFER DOUDNA: Well, because I just don’t see the– I don’t think these AI tools are thinking. They’re great at analyzing data. They’re great at pulling together disparate pieces of information. That’s very helpful. They’re not, though, able to generate something completely new that they’ve never seen before.

And I think that’s partly because biology is extraordinarily complex. It’s very hard to predict lots of things in biological systems today. And I don’t think we’re going to be able to get the data to do those kinds of predictions easily or anytime soon, again, due to the complexity. And in many cases, we don’t even how to collect those types of data.

IRA FLATOW: And speaking of collecting data, is it getting more difficult to find support for basic science these days?

JENNIFER DOUDNA: Well, it is. And I think it’s unfortunate that that’s happening at a moment when we’re arguably on the verge of seeing a real acceleration in the way that we can make breakthroughs because of the assistance with AI and other associated technologies.

And I would just like to point out that I think a lot of the work that’s been done, certainly, in my lab and many of my colleagues over the years and by all of our students and trainees, a lot of that work has been funded by taxpayers, in different ways. That’s really how the United States research enterprise has been working for several decades, really, since the end of World War II.

And to pull away that support at a moment when we’re on this incredible technical trajectory, I think, is– there’s a sad irony there to me. I hope we can turn that around because I do think that if it continues, it will really impact the pace of science in a negative way.

IRA FLATOW: Do you think that scientists should then speak out? I know that scientists in general, Carl Sagan aside, and other prominent scientists have always been reticent about speaking out. Do you think we need more scientists talking about what needs to be done?

JENNIFER DOUDNA: I think we need better science communication. I mean, I love Science Friday because I think that’s a very important role that you play, is explaining what science is all about. And what are scientists all about? How do we do our work? And why do we do our work? How do we do our work? I think that’s incredibly important.

But it’s challenging because scientists are– we’re geeks. [LAUGHS] We like to be working away in our labs, for the most part. And so I do think that there’s a real need for more open discussion about science and why it’s valuable and why it matters in our country.

IRA FLATOW: Any advice for young people looking at a career in science?

JENNIFER DOUDNA: I always tell my students, I think science is a wonderful career when you’re starting out. I think it’s a career that allows you to make the kinds of discoveries that really can change the trajectory of life on our planet in principle. And it’s not necessarily one breakthrough. It’s the whole collection of the data and the knowledge that comes from it that, I think, builds a future and a new picture of what our biology is really all about. I think that’s what’s so exciting about doing science, is making those new discoveries, even very small ones. There’s a thrill to it.

And there’s also a real joy to working with other people who have an aligned interest in a question or a problem that you’re working on together. There’s something very special about that. And I think this is a career that encourages that kind of fundamental investigation with our fellow humans.

IRA FLATOW: Well, Dr. Doudna, I want to thank you for taking time to be with us today. And good luck to you in the future and anything that you do.

JENNIFER DOUDNA: Thanks, Ira. Real pleasure.

IRA FLATOW: You’re welcome. Dr. Jennifer Doudna, professor of biochemistry, biophysics, and structural biology at UC Berkeley, 2020 Nobel laureate in chemistry, 2026 winner of the Priestley Medal.

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This podcast was produced by Charles Bergquist. And if you, like Dr. Doudna, have joy and curiosity and discovery, why not share this episode with your friends? It really does help. Thanks for listening. I’m Ira Flatow.

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