Berkeley Talks transcript: Jennifer Doudna on gene editing and the unthinkable power to control evolution

Carol Christ: Good afternoon and welcome. I’m Carol Christ. I’m the Chancellor of Berkeley and it’s a delight to welcome you to this event this afternoon. You’re here to hear a conversation which has the title The Future of Humans: Gene Editing and the Unthinkable Power to Control Evolution.

That title, to me, recalled the 200th anniversary of the publication of Mary Shelley’s Frankenstein in 1818. Frankenstein is the prototypical text of the human ability to create new life, and it’s really a prescient text, particularly at the moment when scientists have the power to manipulate the blueprint of life. This is a bold topic, and a perfect way to kick off Berkeley’s sesquicentennial, which we’re celebrating with the official motto Fiat Lux, or Let There Be Light.

This motto inscribed in the university seal and on the five-pointed star that adorns Sather Gate reminds us that it’s our duty to create new knowledge and bring it to light, to illuminate solutions for the world’s greatest problems, and find solutions for bettering the human condition.

As we celebrate 150 years of light at Berkeley, and we anticipate 150 years of light in the future, the discovery of CRISPR by Jennifer Doudna, and the global impact that this will have comes immediately to mind. Few breakthroughs in science have had the kind of sweeping, immediate impact that CRISPR has, bringing monumental change to the way scientists approach key questions of life, and holding unlimited promise for the future.

It’s exhilarating to imagine the transformations we’ll see as the result of this technology in the coming years. Our special guest Dr. Mukherjee is an oncologist at Columbia University and Pulitzer Prize winner for his book, The Emperor of All Maladies, A Biography of Cancer. His most recent book, The Gene and Intimate History, chronicles the history of the gene and what becomes of humanity when we can read and edit our own genetic information.

A Rhodes scholar, he has earned degrees from Stanford University, the University of Oxford, and Harvard Medical School. Dr. Jennifer Doudna has been a member of the Berkeley faculty since 2002, and is the founding executive director of the Innovative Genomics Institute, a joint endeavor of UC Berkeley and UCSF, and I’d like particularly to welcome UCSF’s Chancellor Sam Hawgood to this program.

Since her days as a graduate student and postdoc at Harvard and the University of Colorado, Jennifer has always been interested in structural biology and the biochemistry of RNA. In 2012, she and her colleague Emmanuelle Charpentier discovered CRISPR, and that’s a game changer. It holds potential to cure genetic diseases, overcome climate change, and address global food security, among many other transformational applications. Dr. Doudna’s contributions, her light, are significant and worthy of celebration. Please welcome Jennifer Doudna and Dr. Mukherjee.

Jennifer Doudna: Well, thank you, Chancellor Christ, for that very warm introduction, and thank you to all of you for coming today. We’re really looking forward to this conversation. We will talk for about 45 minutes and then we’d like to open up the floor to questions to answer thoughts and ideas and give you a chance to share those with us. I’d like to start off by pointing out that humanity has always had a desire for improvement. Cars, improved transportation, penicillin, improved health. The internet improved the spread of information, or misinformation, in some cases.

Now it appears that we’re entering a new stage of improvement, artificial intelligence, to improve efficiency. Self-driving cars to improve safety, and the improvement of our own bodies. So we have to truly ask ourselves, what are we improving? Do we need improving? And even, what is improvement? So gene editing technologies and cancer therapies are forcing us to look at these questions and also to look at ourselves. Cancer, for example, is a natural and common cause of death. Genetic diseases are too numerous to count and a natural result of our being human. A new wave of biomedical advances are giving us the ability to push back cancer and erase genetic diseases, but at what cost? So I’d like to start this conversation by asking you, Dr. Mukherjee, are we transitioning from natural to unnatural, or is this just the next step in human evolution?

Siddartha Mukherjee: So, again, I think the question of what natural and unnatural is or are has been really brought about in the last decade or so in a way with an urgency that really didn’t exist before. Oscar Wilde famously said, “Being natural is sometimes just a pose.” And the question is, how are we posing? What pose are we on? I do think that the capacity to change something as elemental as our own DNA, even if it’s in somatic cells, certainly in stem cells and certainly in embryonic cells, really raises the question about what we’re doing with our own evolution.

These are unprecedented technologies because they allow us to hold the horns of our own destiny in some ways, even though we understand destiny is more than DNA, but a powerful element of destiny is in DNA. You gave the example of cancer and genetic diseases. So really the question of what is natural and what is unnatural, the boundaries, I think, have been redrawn or are being redrawn today.

My own thoughts about this, really, are the thoughts of a physician. That’s my brain. I have a physician’s brain. And that is that as we do this, as we enter this arena of new technologies, it seems to me that there are, and I talk a little bit about this in The Gene, that there are a triangle of ideas, which we should keep in focus.

The first one is when we intervene, when we’re intervening on human genetics, is there extraordinary suffering involved? You and I can then open up a debate saying, well, what is extraordinary suffering? But at least there’s a sense, there’s a hard line that we draw and say that when we move forward that that remains a certain line in the sand, that we invade on what is natural versus unnatural only when we think that there’s extraordinary suffering involved. In a second, I’ll tell you that there are people who don’t buy this argument. We’ll talk about that in a second, but that’s one line of the triangle.

The second line of the triangle is loosely I’ve called it, in the book, I’ve called it penetrance. The idea is, we can call it certainty, that when we make genetic changes, when we do tamper with evolution, particularly with our own evolution, that we have a strong degree of certainty that there’s a powerful relationship between the gene and the phenotype, or the ultimate manifestation that’s involved. So things that we’re uncertain about, things that have effects that we don’t understand, cascading effects, pleiotropic effects, we probably should avoid since, obviously, we don’t want to intervene on things that we cannot ultimately control.

And the third line of the triangle is, I’ve called it, justifiable choice. People have used different words for it, and that is that when we intervene between what is unnatural and what is natural, that the intervention bears some justification, that we can justify it, and that it’s not done by state mandate, that individual choice is involved. People are able to do it or not able as they should choose. Now, it doesn’t take an extraordinary complicated bit of thinking to realize that each of these is fuzzy territory. Who defines extraordinary suffering? Who mandates choice? If our cultures push us towards manipulating our children, is that really a choice? Even if it’s a passive choice, does it really become a choice?

Doudna: And, by the way, different cultures might make different choices.

Mukherjee: Exactly, and you know better than anyone else, the rules that apply for interventions on embryos in China are not the rules that apply for intervention in the United States and other cultures. So I fully understand this is complicated territory, but as we move forward, if we don’t draw some stakes, this is going to become, I think, even more complicated than it is. So it is absolutely true that we’re passing a boundary between the natural and the unnatural. Those terms were never easily defined, never easily definable, but the technologies are forcing us to define them. And my argument is that we should use a kind of more sympathetic way, humanistic way, to try to breach those boundaries. What do you think? In fact, some of these recommendations have been made. You’ve been on panels that made these recommendations for intervention with human embryos. What are your thoughts about the breaching of the natural?

Doudna: Well, while you were talking, I was thinking that we had a meeting in 2015 in the Napa Valley that was the first meeting that was organized by the Innovative Genomics Institute and UCSF to think about the ethical and societal implications of human genome editing. And there was a fairly small group of people. We had two of the scientists who’d been involved in the 1970s discussions in Asilomar about the ethics of molecular cloning, Paul Berg and David Baltimore. And even in that group of scientists, there was a very active discussion around the table, heated at times. People really disagreeing and debating about, in particular, human embryo editing, so making changes that would become inherited in future generations, and what would be the implications of that.

And at one point, somebody leaned across the table and said, wait a minute. There might come a moment when we will consider it unethical not to do that, at least for certain kinds. And it’s like you’re saying, if there’s severe suffering due to genetic disease, this might, in the future, be something that we would societally agree should proceed. You know it’s interesting for me, because I have found that my own views have been evolving over time.

Mukherjee: Yes, you’ve written about this. So tell us about the evolution.

Doudna: Yeah, I guess I started off, when I first started thinking about the implications of gene editing back in sort of the early days of this work, which was actually only a few years ago now, and started thinking about this. I felt initially very opposed to using gene editing in embryos, not necessarily forever, but I certainly felt that the time wasn’t now to proceed to do that. And why did I think that? Well, it seemed to me, it seemed unnatural. It seemed something that you were sort of messing with something that maybe you shouldn’t mess with, and as a scientist, I also appreciate that in many cases, a gene, and you know this better than anyone probably, but a gene that we think has a certain function might only play that role in a particular context of other genes.

So how can we ever really be sure that something we’re altering might not have unintended consequences? And that would have consequences in not only a person, but all of their kids, and their kids’ kids, and it seemed kind of a profound thing. But what’s happened over the last few years for me, and for those of you that don’t know me, so I’m a biochemist and I’ve always done very fundamental research.

So unlike you, Sid, I’ve always just been working on molecules rather than patients or people. But what’s happened over the last few years is I’ve been coming into increasing contact with people that have genetic disease, either themselves or in their families. I recently got an email, and this is very typical for me these days, but I got an email from a woman who explained that her beautiful, young boy has a genetic disease that had just been diagnosed, and she sent me a picture of this little baby in his little carrier. He’s cute, and it just broke my heart. It really broke my heart and I guess I just found myself recognizing that when there is severe suffering and we have an opportunity to change that, it may be worth doing.

Mukherjee: Well, you know, one line that philosophers have tried to draw is between emancipation and enhancement, and they have tried to draw a strong line. Of course, in real practice, once you practice medicine, those lines also become fuzzy. What is emancipation for one person can be enhancement for the other. The extremes are quite obvious. It’s very easy to think about extremes. Manipulating genes for cosmetic purposes seems very obviously far outside the realm of what we want to do, but on the other hand, there are certainly examples where the conflicts are more real.

The question that occurs to me, I’m gonna frame the question, and then maybe subdivide it a little bit. One question that occurred to me while I was thinking about this is we’re always, in medicine, straddling the line between treating and curing. But now we are beginning to think about altering DNA as a mechanism or a means to treat and cure. Is that reasonable? And maybe you can speak about it in three categories, and divide it up as you wish, but it seems to me that there are three broad categories.

Number one is editing genes of other organisms, very widely speaking, so all other organisms. That’s a little bit like saying humans and all other organisms, but really, imagine the question of editing genes in other organisms, in crops and plants and pests. The second is somatic gene editing, so particularly things like, I’m a transplanter, so in stem cells, blood stem cells, and other kinds of stem cells. And the third, of course, is gene editing in either sperm or eggs or embryos. So tell us about what you think the prospects are in these three categories, and is it reasonable? What is reasonable and what’s unreasonable maybe in the three categories? Or pick one of them which is most provocative for you.

Doudna: Well, I think you’re touching on an important point, and that is that gene editing is used now widely sort of across the biosphere, I guess you could say. It’s really being used in plants, animals. It’s enhancing the pace of research. It’s opening up organisms for study that in the past really could not be investigated at the genetic level. So it’s a very exciting time, really, as a biologist, I think, to be living in the midst of this transformational opportunity with new technologies.

And it’s not just gene editing. It’s other things, too, of course, that are converging to give us ways that we can manipulate organisms that were unthinkable in the recent past. So just having the ability to sequence the entire genome and all the DNA in the cell of an organism and start understanding what that code means, how it dictates what an organism becomes is really profound. So just to quickly touch on those three areas. So if we think about using gene editing in organisms other than humans, clearly this is going to have a big impact on humanity, right? Because it’ll allow us to change plants, for example, to be more nutritious, or to grow in environments where they otherwise wouldn’t thrive.

Mukherjee: Mosquitoes.

Doudna: Get rid of mosquitoes, maybe. Maybe, or at least control spread of disease by insects. In terms of editing what you referred to as somatic cells, and just so that everyone’s on the same page with that, that term just means that we’re editing cells that are not germline cells, meaning they’re not cells that are eggs or sperm or embryos. So they don’t cause heritable changes in future generations of organisms, but this could still be incredibly impactful for the clinical application of gene editing, and the type of research that you do, for example, being able to edit, let’s say, immune cells so that they’re more effective at targeting cancer would be amazing if we can do that. Editing blood cells so they no longer carry the disease-causing gene for sickle cell anemia would be incredible. And there’s many, many other examples like that.

Then the third category is the one that is more kind of ethically fraught, or could be, which is, should it be okay or is it okay to make changes in the germline of humans. Believe me, scientists are already doing this in the germlines of other kinds of organisms quite routinely, but in humans, not yet. And should we go there? And I personally think that it’s going to happen and it’s partly gonna happen because of the fact that different cultures view this question differently, and I think we’re seeing already in the scientific world that the pace of research, at least, on human embryo editing is proceeding differently in different countries.

Mukherjee: So, just a quick follow-up on that question, and then we can move on. How long ’til the first transgenic human?

Doudna: Um, oh dear, I’m on the spot here. I don’t know, is the short answer. I think that, again, so that everyone out there sort of understands what’s happening. I mean, we saw, just in the last six months, there have been two very prominent publications in scientific journals from highly respected research labs, one here in the United States, and one in the United Kingdom, who both showed that you could use gene editing in viable human embryos to change, to alter the genome, to make a very precise change to a particular gene in these embryos.

Mukherjee: There’s been some question about–

Doudna: There’s been questions about the details of how that’s working, but I think the overarching thing that I take from that is that this research is proceeding, and I think the pace will accelerate. I recently heard from a colleague in China who is coming to visit me here at Berkeley next week who wants to give me an update on his own research in human embryos. So it’s moving forward. I can’t tell you when I think it’ll be actually used to create a CRISPR baby, for example, but I think we’re seeing steady progression in that direction.

Mukherjee: I mean, just to give you one example, I work with blood stem cells and immune cells. That’s mostly why I’m a biologist, leukemia doctor. As of last week, we were just talking about this earlier on, as of last week, in cord blood stem cells, we are getting gene editing successfully in 90% of the stem cells. In fact, we’ve gotten to a place where we’re wondering if we should even sort these cells because the efficiency of sorting is getting to the efficiency of editing. So basically I suspect that the blood system is open for business. The entire blood system is open for business. There’s many, many questions, off target effects, whether we will get weird leukemias that arise because we’ve made an edit in the wrong place, but essentially speaking, it’s staggering. We couldn’t do this six months ago.

Doudna: So this is a very important point. In the field of this technology and all the things that are being done with it are moving forward incredibly quickly. And one of the things that’s been on my mind is how do we explain to people that are not down in the weeds doing the work, working in the clinic or working in the laboratory? How do we explain what’s happening? Because I think we appreciate that this is ultimately going to affect everyone’s life, and I think that one of the ways that people learn about science, they learn about technology, is actually through the media, through Hollywood, through books, of course, and through fiction and nonfiction, but they start to understand what’s happening. We’re seeing this, of course, with artificial intelligence has been all over the media lately, and self-driving cars and things, and a little bit genome editing is creeping in there.

So I wanted to ask you what you think Hollywood has done well and what have they done poorly? And how do we work with people that like to tell stories and they do that for a business and professionally, and work with them to get science right?

Mukherjee: Well, it’s always a struggle. One of the strangest experiences of my life was being a small consultant on Logan. It’s true. If you were to sit through the final credits, I have a small, and that’s because, I mean, I think I’m speaking correctly. I barely enter particularly the Hollywood world. But I was approached by a friend of a friend of a friend who showed me the script, and I said, well, you know the script is really fundamentally about a dystopic vision of what happens when human beings start reaching for certain kinds of perfection. It pushes towards the enhancement debate away from the emancipation debate. And my only thought about it was I thought it’s not dystopic enough.

There’s a moment in that film, which actually I watched a very early version of, when you suddenly realize, there’s a moment in which the characters are walking through a corn field or something, and you suddenly realize that the entirety of the world has now been transformed for human benefit because the corn is growing 10 times as high. I think that was my input in the film. I said make it more dystopic.

But just to remind ourselves that I think the media has a big responsibility here. I think, again, it would be very helpful for us from the media to get a road map of what the pulse of public thinking about this is. Because the media reflects back to a large extent what a much larger public view of all of this is. That would be what’s helpful. Not to set guidelines, not to tell us about the science often, but to tell us, and that’s what I think is important about the films.

The film may get the science wrong. They may get it too far off, et cetera, et cetera, but what they often get right is they get the pulse of what people’s fears are. What are they afraid of the most? What are the concerns?

Doudna: Or what are they excited about?

Mukherjee: What are they excited about? A film like, I’m just thinking off the top of my head, a film like Lorenzo’s Oil is a great example. We could disagree about the science. We know that it’s very complicated. People had disagreements, agreements, but what it got right very much was the obsessive hunting of a parent for a cure for their child. That’s what it gets very right.

And as long as the pulse is right, it reminds us, it keeps us, I think, as physicians, as scientists, honest about what we’re writing about. What are the concerns? Sure, we’re talking about powerful technologies. Who’s gonna draw the limits? How are we going to move forward? And I think that’s what ultimately helps. In some ways, Hollywood gets it right when its moral compass is right, when it sets our moral compass right. Hollywood gets it wrong when it tries to tell us about science, I suppose, in a way that doesn’t make any realistic sense.

Doudna: So for me, I thought the movie The Martian was a great film that really kind of captured the excitement of an adventure and the challenges that one might imagine happening if you tried to actually survive on Mars. And it’s sort of just beyond where we think we are right now in terms of technologies, but I noticed that it captured a lot of people’s attention and imagination. I have a teenage son and just hearing his chatting about this with his friends. You could just kind of sense this buzz. So I think films like that are great because they actually make people think about science. They think about the opportunities. If we develop technologies, that might allow us to explore our solar system in ways that we haven’t been able to.

Mukherjee: Well, sometime in the next few years, there’s gonna be a fictionalized version of a Jennifer Doudna movie.

Doudna: Oh dear. Horrifying thought.

Mukherjee: What would you like to ensure is in that film?

Doudna: Is in or is not in?

Mukherjee: Tell us both, tell us both. Make it exciting.

Doudna: Again, I guess, to me, I like it when films capture the passion that somebody has for work they’re doing. The struggles. Students now will often ask me, I feel almost a little bit embarrassed because I think they think that I’ve reached some pedestal or something and I don’t think of myself that way at all. I think of myself growing up in this little rural town in Hawaii and struggling through general chemistry in college and trying to figure out, can I really be a scientist?

I think a movie to be true, if it wants to be true, and maybe it doesn’t, but if it really wanted to capture anything that’s true about me, it would have to show those struggles. And it would have to show, again, it’s back to the human spirit. All of us, I think, we have passions for certain things and that’s one of the things you learn in college is you kind of learn about yourself and what you find exciting. For me, it was about realizing I was just a person that loved to think about molecules. I loved to think about how life works at the level of molecules. But it hasn’t been a straight path at all and I would definitely want a story to capture that.

Mukherjee: A lot has been written about the initial series of conversations that you had with Emmanuelle at the start of this. Actually, I’ve never read about the kind of moment. Was there a moment when things crystallized for you?

Doudna: Well, I think there have been a few of those. When I think back on–

Mukherjee: Pick one.

Doudna: Pick one, okay. Well, probably I should pick the first one, then, which is really when I met her and we met at a meeting in 2011. It was a meeting I almost didn’t go to because it was a meeting for microbiologists, which is certainly not me, and I was busy and I was teaching here at Berkeley and I was juggling all the usual things that we juggle. I almost canceled it, but then I decided to go, and it’s good that I did because that’s where I met Emmanuelle Charpentier, and she is a microbiologist, so she had a legitimate reason to be there.

When we met at this meeting, we met there because we were both working on what at the time was a very obscure area of biology, namely understanding how bacteria fight viral infection using a system called CRISPR. It’s an adaptive immune system in bacteria. So we were both giving talks at this little session at this meeting and afterwards we went out to lunch, and we started chatting and we started walking around the old cobblestone streets of old San Juan, Puerto Rico, and in that conversation, we talked about starting a collaboration to work together to figure out the function of one protein, just one protein, that’s part of this immune system, a protein called Cas9.

It was a project that really brought together expertise from her lab as a microbiologist and my lab as a biochemist, and I do remember feeling a real sense of the hairs on my neck standing up because I could sense that there was something very exciting about this project. In some ways, the rest of it kind of flows from that.

Mukherjee: So I can tell you my story about that story is that I heard about, from all people in the world, I heard about your early results from Paul Berg. I went to Stanford for another visit. I have collaborators there. I trained with Paul, and Paul, as you very much know, was among the many people who discovered how to clone, make recombinant DNA, stitch two pieces of DNA from two foreign organisms together, and was instrumental in the Asilomar meeting, which was an important milestone in all of this. Once in a while, since becoming a physician and a scientist myself, I’d go back to Stanford, and I would always have lunch with Paul.

And these were very precious to me. He’s now 90 years old. This was about when he was 87 or something, and he told me, you know, I just heard a seminar from someone and she talked about an enzyme that allows you to modify DNA in a site-specific manner. And I thought, my God, the old man has finally lost it. I said, wow. Because it was a little unfathomable. People had been thinking about this for a long time and it was unfathomable and, of course, the fact that it was borrowed back from Just to move the conversation along, flipping over the question of Hollywood is a very pertinent political question today, which is, we are living in times where the amount of distrust for science is phenomenal and I have to tell people constantly that science is not fake news, that there’s a strong line between one and the other.

Evolution is not fake news. Bacterial evolution is not fake news. So what do we do about this moment? Do we have a responsibility? We have really an unprecedented moment in human history, in American history, a country that grew to some extent politically out of scientists and engineers. I’m an immigrant, so the history of this country is a country that grew out of the aspirations of humanists, scientists, and engineers. What do we do about this today? What are you doing, Jennifer? How does the world look to you?

Doudna: I’m very concerned about this. I think it’s a big challenge. I think we have to start by encouraging scientists everywhere to get out of the lab at some level and engage in conversation. We have to talk about science. We need to bring science back into the discussions that we have at cocktail parties and things like that. I think that books like your books are doing a lot. I think you’re very good at telling stories that are very human and that people can identify with, so they don’t necessarily think about you, I mean, hopefully they think about you as a scientist, but they read the book because it’s really interesting. It’s really engaging, right? It’s not a textbook. It’s something that is very human.

I think the more that we can do that and use language to describe scientific ideas that isn’t filled with acronyms and doesn’t sound like a foreign language, but we try to really just explain ideas. Because I think, in the end, a lot of the ideas that we’re having and thinking about are not really complicated. They’re not. It’s just maybe the details are, but I think the concepts and ideas are not, and this is something that we just have to work at more than I think we have certainly in my lifetime as a professional scientist. How would you answer that?

Mukherjee: I can’t agree more. I think what I worry most about is that there’s a dispiriting quality for young students, for my students. There’s a dispiriting quality in all of this, and the dispiriting quality lasts generations. It carries through. And I think this is an especial time. I’m not gonna say it’s not go hug a scientist day, but I think there’s an especial time when we need to remind ourselves that the contributions of science to this debate. I mean, for instance, look at climate change. Before we have arguments and conversations, we need data.

Data comes from laboratories, from scientists who’ve spent time gathering it. We need to respect that idea that we can’t enter these debates without data. So just be careful, be cognizant of the fact that the scientists in your life around you are dispirited and try to encourage them. It might be philanthrophically, it might not be. It might be personally, but it’s a tough time for the graduate students and the postdocs in my lab. I don’t know if you’re feeling that as well.

Doudna: So has your work and especially maybe your writing, has that led you to have conversations and interactions with new groups of people that have sort of taken you in new directions?

Mukherjee: Well, certainly politically, yes. As you know, my first book on the the history of cancer was well read, but then Ken Burns made a documentary out of it. The Gene is also going to be made into a documentary by Ken Burns. You should probably not tweet that until it’s formally announced.

Doudna: No tweeting.

Mukherjee: It’ll be announced in a week or two. But we’re in the middle of filming. In fact, we filmed you, Jennifer. And so I think that the transition into serious documentary, these are three hours, or in the case of Emperor, six hour documentaries, allowed us to reach a group of people.

I think one of the most interesting conversations I’ve had recently is with people who work on education for children. How do you take textbooks, which are becoming more and more outdated in some ways, how do you convert that into education for children? How do you make it possible to put that on the web to some extent, but supplement that with books that are more readable? And that’s an issue that I’m very interested in. How do you make a kind of simultaneous storytelling as well as didactic education for AP, for instance, which is much more accessible, and doesn’t remain boring or textbook?

Doudna: I think kids are actually a great way in, too. I had this great experience a couple of years ago. My son was in seventh grade at the time and he was just taking a class. They were teaching the kids about DNA and so the teacher asked me if I would come and talk to the kids a little bit about my work. So I went to the school and we did it after school, so it was just voluntary.

We just asked the kids who would like to do it and my first shock was I walked into this room thinking there might be two, three kids. There were 20 kids there, and 15 of them were girls. It was cool, yeah. The other thing was, so I thought, how am I gonna get these 12 year olds interested in what I do?

So I thought, well, I’ll take this 3D-printed model that I have of the Cas9 protein. It was actually made by Jacob Corn, who’s here in the audience, here at the Innovative Genomics Institute. It’s printed on a 3D printer, but it’s based on an actual crystallographic structure of the Cas9 protein, which is the scissors that cuts the DNA and the RNA molecule that programs it to find and cut a particular sequence of DNA. That’s what makes it a powerful tool, and then the DNA itself getting cut. So I took this model. It’s about this big. It’s about the size of a football or so. I took it in. The model was designed by Jacob very nicely so that it can be pulled apart. You can actually pull the DNA out.

Mukherjee: You should’ve brought it.

Doudna: You can see where the DNA got cut. I should have brought it, would’ve been fun. But I took it to the kids and I thought, well, I won’t actually take it apart. I won’t show them actually how the DNA gets cut ’cause that might just be too complicated for the kids. So I had this model, but it’s brightly colored and it looks kinda cool. So the kids said, well, can you pass it around? So I started passing this thing around and I was describing it to them. Within five seconds, of course, they had pulled, they’re like, oh, cool, the DNA comes out. Hey, we can pop this piece off. You know, they were dissembling it and they were looking at it and they were figuring it out, and they were asking tons of questions. Actually, they asked a number of really interesting ethical questions.

I think one of the kids at that little meeting asked me about the ethics, not really using that language, but asked me, what does this mean for changing embryos, humans, and doesn’t that mean that you could decide to make somebody taller or smarter or wow? Just kind of grappling. You could see the thought process going. So I really think that the more that we can reach out to kids because kids are natural scientists. They love questions. And the more that we can do that and get them engaged, they don’t think about science as a thing. It’s something that’s interesting that’s entered their world.

Mukherjee: Are we getting ready for questions?

Doudna: We want to turn it over to questions from the audience, but before we do that, I just want to cover one more thing with you, Sid, and that is, I would love to hear the motivation that you had for writing your first book. Because I think, for me, The Emperor of All Maladies, your first book about cancer, it really is a profound work. It’s very, in some ways, very depressing, but it’s also incredibly interesting to look at the history of how humans have grappled with this really intractable disease. I’d love to hear what motivated you to do it, what was most surprising to you about that process, and was it fun? Was it hard? Tell us about that.

Mukherjee: So I had never thought I would write a book. I was trained as a physician scientist, very nose to the ground, and The Emperor of All Maladies really grew out of a patient’s question, and the patient’s question was, she was in the middle of chemotherapy for sarcoma, and she said, why are we doing this and where are we going? And it seemed to me just astonishing that here was this disease that has occupied our culture.

Cancer has become more than a disease. It is a metaphor. It is an allegory. People use it to describe states of mind. Very few illnesses in human history have ascended to this kind of space in human culture. And yet we had no real history, we had no book about it in the same sense. People had written about cancer in a thousand ways. There were a million textbooks on it. So that was really the beginning of that book. I started as a fellow and during the day, I would be in the clinic and in the evenings, I would write. It was just a journal to start with and it grew and grew and grew, and at some point of time, I decided that I would show it to a publisher.

Someone said to me, you know there are gonna be two readers for that book, your mother and you? 600 pages on cancer. When it was first delivered, someone said it was like a phone directory, from in the days when there used to be phone directories, a phone directory from hell. it had a black cover. In the back, in white, it had cancer written on it, and it was 1,800 pages long. It had cut down to 600 pages. So that’s how I started. That was my first book.

Doudna: Fascinating, yeah. Sounds hard, working in the clinic during the day and writing at night. Wow, I’m amazed that you could do that. And your second book? So, well received as well. Many people have read The Gene that I’ve run into just sort of randomly. But also you encountered some criticisms about the book. Tell us about that experience.

Mukherjee: So, again, it’s the experience of distilling very complex science to simple. You can’t satisfy everyone. The simplification is absolutely necessary. Again, it was delivered at 1,800-odd pages. It had to be cut down to 600 and I have to do most of the cutting. So things get left on the floor. Things have to be cut off and left on the floor. So you have to have a radical simplification in many places and scientists don’t like being simplified. They don’t like their work being simplified, but in order to communicate with a much wider audience, you have to take away terminology, take away even people. Too many names becomes word salad. Readers get switched off. If you use too much terminology, people get switched off. So that’s one.

So there’s the criticisms of omission is one area. One of the controversial parts the book involved questions like race and IQ. I really thought that for this book, it was odd. This was long before these questions had become very central. So there’s a chapter on race and a chapter on IQ, both of which were read by people I respected in the field. Actually, Marcus Feldman over at Stanford, who you know very well, was a very important person who read the chapter on race. The chapter on IQ was also read by many, many people in the psychiatric community. I really felt that those were important to put in. In retrospect, I feel even more strongly that they were important to put in, but there are disagreements about some of these fundamental questions. So it’s part of the territory.

Doudna: Yeah, absolutely.

Mukherjee: So maybe I’ll continue this, since we’re speaking about books and words. You know, I’m very sensitive to the idea of words around, words like war on cancer, battle on cancer. Some people, some patients don’t like it. One woman famously said to me, you go fight the war. This is not a word that I want to own. Others want to own that word. It somehow helps. The idea of them fighting something in their own bodies helps them. What do you feel about the word gene editing? Tell us what the various words have been and what did you coin yourself? What do you say yourself when you use these words? Genetic surgery has been used to describe this. What’s your sense of any of this?

Doudna: Yeah, I think we’ve seen, I’ve noticed an interesting evolution in language around gene editing. So it started off as people would pretty much universally call it genome engineering, right? Genome engineering. Obviously CRISPR was not the first way to modify genomes. There were earlier technologies for doing this, and they really were engineering in the sense that you actually had to engineer proteins individually to make targeted changes to DNA in cells, and that involved a lot of work and a lot of engineering in the lab, engineering of proteins.

When CRISPR came along, initially the same language was applied to it, but what’s happened, and this wasn’t me at all. This just sort of happened organically, I think, in the field, is that people began to adopt the language gene editing. Why? Well, I think it’s because it sort of reflects the maybe simpler nature of this technology in the sense that it doesn’t require a lot of engineering for this tool to be employed in–

Mukherjee: When did you hear that phrase first, Jennifer?

Doudna: Gene editing?

Mukherjee: Gene editing, yeah.

Doudna: Gene editing. I think it started sometime back around the time that we had the first international conference in Washington at the end of 2015 on gene editing, and I think we used that language for that meeting. Maybe at some level, that started to permeate the language that was used to describe it in other contexts. But I started to ask people, people like George Church, when do you use editing and when do you use engineering? And I think it was George that said, well, I really think that the new ways of modifying genes are much more like editing than engineering because we don’t have to engineer anything to do this. We can just use the tool.

Mukherjee: Right, and do you think, moving forward, this term will stick? Is it easy for you now to use this? Do you find there’s a facility with it?

Doudna: I think so. I mean, I’m curious to know, and I try to ask this question of people that are not scientists, ask them how they react to that. What does that mean to you when someone says gene editing? Does that mean anything or is it just opaque? But I think it’s fairly descriptive of what it is that we’re really doing. Because if you think about it, it’s really a tool, really a technology that’s all about rewriting DNA. We’ve been able to synthesize DNA. So we can write it, we can erase it, we can cut and paste it, and now we can rewrite it. So I think it really is sort of analogous to having a text editor that you’re using on the genetic code.

Mukherjee: One of the astonishing things, I don’t know how many people have worked with the CRISPR-Cas9 system. One of the astonishing things as a user in human biology is how simple it is. It is very, very simple, and maybe that’s part of the captured in this idea of gene editing. It seems to me, one thought I had is that for a long time, I struggled with it to figure out how it would help us therapeutically in cancer. Of course, to elucidate targets in cancer, to genetically manipulate cancer cells, it’s really, really simplified, but could we use this therapeutically in cancer?

And I struggled with that for awhile, and, of course, the answer has now come to us. You can’t necessarily use it in cancer cells because evolution is working against you. You have to essentially get it, we think, in 100% of the cancer cells. Otherwise, the ones that have not been edited will evolve and take over. Maybe you can do it over and over again, but the fact that the immune system has now become quite clearly one of the mechanisms of controlling cancer, and immune cells, you can manipulate and edit, and thereby reintroduce them.

So it’s really given us a powerful way to think about cancer, not from the standpoint of cancer itself, but from the microenvironment around cancer. Couple of questions that arise. One is it seems to me that editing sperm and eggs, or sperm and egg making cells, is going to be easier than doing it in the entire embryo. What do you think are the prospects of that and is that something, do you see yourself, your own lab, ever moving in that direction? Making edited human sperm and eggs?

Doudna: So I think you’re absolutely right, and my disclaimer is that I’m not a human developmental biologist by any stretch, but I think that from what I’ve come to understand from talking to people that are experts in this area, I think that this is absolutely coming, that it’s going to be possible, and it’s gonna obviate the question of editing human embryos because you won’t need to.

Mukherjee: Which is much harder.

Doudna: Right, you won’t need to. You’ll edit the sperm and eggs. And would I ever do this in my own lab? No. Not for any reason other than that’s not the kind of biologist that I am. That’s not the kind of expertise that I have. But I think that you’re right that in terms of thinking about future clinical impacts, this is an area of very active development where there’s likely to be real advances.

Mukherjee: One piece of conversation we were having earlier, which is an important thread to pick up, is that it seems that a lot of the conversations have focused around gene editing, but we’re also seeing the simultaneous development of other technologies. You mentioned one of them, embryology, stem cell biology, and the third one is artificial intelligence, deep learning. I have a couple of thoughts about deep learning and genetics, particularly from the standpoint of cancer, but I’d love to hear your thoughts as well.

One thing that occurred to me was deep learning is beginning to elucidate things about our genome that I did not think possible before. I read this fascinating study of early cardiovascular disease. So if you take cardiovascular disease and you ask the question, how many patients with early cardiovascular disease can be explained by single gene mutations? And this is how we grew up as biologists. We thought about mutation in a gene affecting a pathway, thereby causing the change that leads to a disease. Very classical genetic model of thinking. And cardiovascular disease, familial hypercholesterolemia, you get elevated cholesterol. You have all sorts of problems.

This study looked at if you take 100 people, only two of them, two of those 100, can be explained by these sort of powerful single gene mutations that will increase risk. The question is, what about the rest? What about the other 98? And for a long time, we didn’t really know how to solve that problem. My colleagues in complex genomics tell me now that deep learning is beginning to solve these kinds of problems, that, in fact, it turns out that complex human phenotype can often be explained by what I would call not shove effects. So those single genes were like shoves. They would push you strongly in one direction. But by nudge effects. Often hundreds or often even thousands of gene variants that nudge you towards, you know, have small effect in and of themselves, but as a network, or maybe in the context, move you even a little bit, even slightly towards your ultimately.

So the question really arises is that if that’s going to be the case with most human diseases, does gene editing help with nudge effects? Can you imagine ways or would it only help with shove genes? Are we gonna reach some kind of biological limit, as it were, to the capacity to manipulate human phenotype? It’s a complicated question. So I don’t know what your thoughts about that are.

Doudna: Well, I have two thoughts about that. I mean, one is that I think that CRISPR and gene editing technologies that are coming from that are going to help with nudge effects in the sense that they’re gonna help us uncover all the genes that are in those networks, and that’s already happening. So there’s lots and lots of laboratories now that are using gene editing, not in the clinic, but they’re using it to understand the genetics of human disease. And they’re doing it both in human cells and organoids, which are cultured bits of organs that you can grow in the lab, as well as in animal models of disease.

So I think that’s gonna be a very powerful way. And frankly, I totally agree with what you’re saying about using artificial intelligence or machine learning to help us understand those networks ’cause they’re often complicated and you have to really understand all the players that might be contributing to a particular trait, for example. But the other way that I think that gene editing will potentially have an impact clinically in the future, and we’re not there today, but I think the technology is going in that direction, is being able to edit or modify multiple genes at once.

Mukherjee: What’s up with that?

Doudna: Well, sometimes these genes are found in very disparate parts of the genetic material, but sometimes they’re actually co-localizing in three dimensional space, and there’s more and more that’s being learned about how that works in cells. So I’m thinking that in the future it may be possible to use gene editing to alter multiple genes at once, maybe to remove whole segments of a genome that aren’t necessary for certain kinds of developmental pathways, for example, in particular cell types. I think the opportunities for using it as a real tool of understanding of the genome are still really very much out there to be captured.

Mukherjee: So let me turn the question that you asked me in the beginning of the conversation back to you. What does the phrase human evolution mean to you in 2018?

Doudna: What does the phrase human evolution mean to me in 2018?

Mukherjee: How has that changed for you?

Doudna: Well, I think we’re on this incredible continuum. It really is an exciting time. I feel many days a sense of wonder. I feel amazed that I’m alive at this time when we’re at this moment when all these technologies are coming together and, for the first time, we can do things. Like we said, in Chancellor Christ’s introduction, we really have now the power to control evolution, and it’s not just in principle our own. That’s obviously still on the leading edge, but to control evolution of other organisms in our environment. It’s a really profound opportunity and a profound responsibility. So I hope that we can all work together and work as you’re doing to educate people about the science behind this so they can think about it and really contemplate what this means.

Mukherjee: Is it possible to have an international moratorium until we decide this is conceivable?

Doudna: No. No, it’s really not, because as we discussed earlier, I think culturally there are just many differences in the way people approach these things, and how would you enforce such a thing? But I think what one can do is engage in discussions that are international, invite people to share their views, try to understand where they’re coming from, and I think that’s what universities should be doing. We should be encouraging that and be really leading that conversation. Not dictating it, but just inviting it and welcoming different points of view.

So I would like to now open up the floor for questions, ’cause I know that some of you may have questions, and we’d really like to hear what you’re thinking and try to answer them. So we have runners with microphones that are coming around and if you raise your hand, they will call on you and we will bring a microphone to you. And who’s calling out the…

Audience member 1: Hi, thanks, it was a great talk. My question is sort of quick. I’m just wondering what have been the three most influential-slash-favorite books for both of you.

Mukherjee: Well, it’s interesting that you ask because we were just saying, this week, I think, is the 50th anniversary of The Double Helix, Jim Watson’s famous and at one point infamous book, which actually was really a trailblazer for me as a young reader, showed the human process of science, warts and all, and I was very influenced by it. I was also very influenced as a young reader by Orwell. All of Orwell’s books were very influential to me, in fact, have influenced my thinking.

And then I would say, I discovered in writing The Gene, I discovered someone I had weirdly neglected, and I wrote about him recently in an essay for The New Yorker, Chesterton. Now, you could say, well, what about Chesterton and gene? In fact, Chesterton wrote very deeply about eugenics. He was one of the great skeptics of eugenics. I discovered his writing much later, and realized that there’s something wonderful about his very bracing skepticism about eugenics. So those would be three books sort of picked out of a basket of thousands. How about you, Jennifer?

Doudna: Yeah, fascinating. Well, I have to say that The Double Helix also for me was incredibly influential. That book was probably the first book that I read back when I was in grade school about science, and it kind of blew my mind. For those of you that have read it, it’s really a very personal history of the work that Watson and Crick and their colleagues did to discover the structure of DNA. It was really very eye-opening for me, and really made me think about becoming a scientist for the first time.

And then the other two might surprise you. Maybe not. One is I would have to say The John McPhee Reader. I don’t know if anybody here knows John McPhee, but he’s a fabulous writer and he writes about all sorts of topics, and what he does is he basically travels around and talks to interesting people. A lot of them are scientists, but some of them aren’t, and he writes about it. I found his writing to be incredibly captivating and interesting, again, in my formative years.

And then more recently, I read a biography of Dorothy Hodgkin that was also just fantastic. Learning about her life and she had multiple kids and she was working at a time when it was very difficult for women in science in particular, and she prevailed, and she won the Nobel Prize. She did really just incredible, groundbreaking work. So that was also incredibly inspiring for me.

Mukherjee: There’s a little note in The Gene. I actually met Dorothy Hodgkin years ago. There’s a little note in The Gene, where when she won the Nobel Prize, the subtitle in one of her photographs was A Housewife From Sussex, or wherever she lived.

Doudna: Oh, wonderful.

Audience member 2: Hi, I think I’m the next questioner. You talked earlier about the cultural differences or the difference in cultures in terms of their approach to the opportunity and responsibility of gene editing. Can you kind of talk a little bit more about China or other parts of the world and what their approaches are? And I think that’s an interesting piece for the public to understand where things are going in other parts of the world and what your opinions are about what’s happening in other parts of the world.

Doudna: Well, okay. Again, this is really just my personal observations, right? But I think that what I’ve noticed is that in certain parts of the world, and I’m not putting any particular country on the spot here, but I think there are parts of the world where there’s an incredible eagerness to be engaging in the scientific process. People that have felt maybe not included in that in the recent history and wanna get into it, and wanna be recognized for their work. They wanna be prominent. They wanna attract attention. They want to make progress.

So I think there are motivations that go beyond the simple joy of discovery, which I think all scientists share. There also are people that are thinking about really putting their country or their culture on the map in terms of international recognition. So I think that we’re seeing that there is some of that that’s driving the push towards certain kind of edgier, I would say, applications of something like gene editing. And that’s where we just need to be careful. Again, what I’ve observed is that there’s a desire on the part of scientists to be respected by their colleagues, to be accepted by their colleagues.

So I think there is a willingness and an interest in engaging in sort of an international consensus around what we all consider to be appropriate use of technologies. That’s just my observation and I think that’s what we should be encouraging. Because culturally people do approach these things differently.

Mukherjee: And I would say even the microcultures in science are different. We were talking about, you know, once in a while, I’ll speak with someone like George Church. I actually had a public conversation with George. I talked about, George is a big enthusiast of really opening this field up. I think it’s fair to say he would be an enthusiast of making directed manipulations in human sperm and eggs. And he thinks, that’s his brain. I think like a physician first. My first thing that comes out of my brain is, “Are we ending suffering?” “How can I first do no harm?” is the first thing that comes out of my brain.

People’s brains are hooked up differently, and I do think that people’s cultural brains are hooked up differently. Yes, there’s a need for provocation. Yes, there’s a need to do as you work to put people on the map, but someone who’s grown up in, I grew up in India, the cultural brain, you know, what we think is permissible and not permissible is different. We have different understanding, for instance, of where life begins. And that is important. And it’s so important that, in fact, there will be places, there are places that are drawing lines, which then the lines don’t exist across the border.

Science will move in accordance to that. If you wanna make genetic changes in human sperm and eggs, as a scientist, you would relocate to a place, if you badly wanted to do that, you’d find a place to do it in the world. So that’s why I keep coming back to this question. We need to have some sense of boundary. That’s my physician brain speaking, first do no harm brain speaking. We have to have some boundaries. I don’t know how to reach them, but I think they’re important.

Audience member 3: Hi, question up here. So one of the most surprising things about genetics for me was that effectively 97% of DNA itself is noncoding, right? And for awhile, there was sort of the dead space and you just assume that introns were there for no reason, and every time I look at the literature still, it’s always kind of vague and confusing, and it’s like, well, introns may do something, they may have some role. But I guess my question is, what is the current attitude towards introns in general, with respect to DNA, and do you think CRISPR will ever become so advanced such that these kinds of concerns are going to become necessary in whether we’re gonna understand something else about that? I understand that’s kind of theoretical.

Mukherjee: Well, let’s explain some terminology first, just to widen out the question. So one of the surprising things that we learned as biologists, in fact, this happens to be the 40th year of the discovery of gene splicing. And there was a big symposium, I went to it. So it turns out that, in fact, a gene in the genome is often broken up into parts, and they’re long parts that are spliced out or removed when that gene finally becomes a mature RNA, which then gives a protein. So introns are those long parts that are removed. Exons are the parts that ultimately make their way into becoming protein, and the question has to do with, well, what about all those introns and also the other space, the intergenic spaces, which for a long time were called junk DNA?

That’s a terms that we inherited from the 19… The history’s interesting of that term. We inherited that term for really no good reason. We inherited that term from the 1960s and 1970s when our understanding of the genome was much, much more limited. My one thought about this is for cancer, it’s turning out that those introns and that the intergenic spaces are turning out to be extraordinarily important. Not all of it, but much of it.

Jennifer, you refer to some of this. It’s not only important in terms of regulating gene function. It is important in terms of the way DNA folds in space and that also regulates gene function. Some parts of it will turn out to be unimportant. There are lots of viruses that sank their way into the genome, which have been silenced. In fact, there are whole systems to silence these viruses that might pop their heads up from the genome.

So it’s an active space, but all I can tell you is that in cancer, these previously nonfunctional elements of DNA are turning out to becoming extraordinarily important. And, by the way, how are we finding out that they’re extraordinarily important? By using CRISPR. By chucking them out and all of sudden seeing that they, in fact, influence gene function in ways that we hadn’t thought about before. In cancer, that’s a huge area of research, but I don’t know what your thoughts are.

Doudna: Yeah, I don’t have anything to add. That’s exactly right.

Audience member 4: My question is regarding the accessibility of gene therapy and CRISPR systems. I mean, currently a treatment with antisense oligonucleotides is $400,000 a year, and do you ever see these technologies helping the entire world, or just more well-developed nations?

Doudna: Yeah, well, it’s a great question. It’s a really important question, and something that I am thinking about a lot. I think this is on a lot of people’s minds, and whenever there’s a new technology, you ask, what is this doing to really help people globally versus creating even more inequalities, right? And I think we’d all like to see it do the former and not the latter. But inevitably when you have new technologies, it’s expensive to develop those and if you want to motivate companies especially to do the work that’s necessary to create a therapeutic and go through all the clinical trials that are necessary, there is a big investment involved, and that does lead to high costs of those kinds of treatments. How do you deal with that?

So one of the things that I’m involved in right now is some very active, very exciting discussions with our clinical colleagues at UC San Francisco. So through the Innovative Genomics Institute, we’ve been working on something called the Genome Surgery Center. It’s in its fledgling stages, but the real idea behind this is to address exactly the issue that you’re raising. I think none of us want to see these technologies develop to help the .01%. We really want to see them develop to help a much larger swath of people. And so how do you do that? How do you get there and deal with the realities of the costs of development?

So there’s some really creative ideas that are coming out of this. We have here, of course, at UC Berkeley, we have a lot of people that are thinking about this from the standpoint of economics, sociology, history, philosophy that we’re engaging with. Also at Stanford University. And so, we have this great intellectual community here in the Bay Area to really tackle this, and I’d really like to see us take that on very directly, and find ways to develop, for example, just to give you an example, what if you could find a way to treat a large swath of people that have a particular genetic disease using one configuration of a gene editing technology that wouldn’t require individual clinical trials for each one? This would really reduce costs.

So we’re looking into ways that we can streamline that, and to do that, we really need to bring together people that are doing the technology development with those that are clinicians. They know their patients and they know what the technology needs to be able to do. It’s a great challenge and we’re, I think, on the cusp of being able to tackle it.

Mukherjee: I mean, sickle cell disease is going to be one of the first examples of this. How we tackle it is really gonna be one of the models. Because, as a hematologist, I’ve taken care of hundreds of patients, young men and women, often African-American men and women with sickle cell disease. It’s a devastating disease, debilitating disease. You know, pain crises, opioid addiction that comes with dealing with these pain crises. So it’s a tough disease. It is a disease that I think is going to be very amenable to gene editing based technologies and transplantation. It is on the cusp of becoming very amenable to all of these, and the question is, how are we gonna price that? And will we create a gene therapy overclass and a gene therapy underclass? So that’s one area that I think that at least people like me are very actively watching. Thalassemia is another area. We’re on the cusp of these, and I think those will be models of trying to figure out, can we offer gene editing to people who really need it without excluding them with cost barriers? You have the mic, yeah?

Audience member 5: That was a really fascinating discussion just now because from reading the book The Gene and also just thinking about what we’re going to do. The first thing that comes to mind, this wasn’t my initial thing I was going to talk about, but it’s wonderful to solve diseases, but is the first disease we’re going to solve be a white disease? And that’s just an aside based on what you were talking about here, and what you presented about, underprivileged or where the money is, et cetera, Dr. Doudna.

Mukherjee: The quick answer is I don’t think so. I think that the first disease that we’re gonna solve, I hope, is a disease of true suffering, which is most amenable to these technologies, don’t you think, Jennifer?

Doudna: I do.

Mukherjee: I think that that’s the first disease.

Audience member 5: I hope so, and won’t it be fantastic when we solve that first disease? But then my question was, or where I was fantasizing, and let’s fantasize for a minute. Our first trip to Mars was a little bit tough, okay? There was a certain group of people who went there. A number of people died there. This is the fantasy, right?

And didn’t really come out the way they wanted it to. But we’re going back to Mars. Shouldn’t we be pre-adapted? We need to modify our corneas so we’re not blind when we get there through extended space travel. Maybe we need to modify our gut so that we can eat this simple organism that we can grow on Mars. Perhaps we should also address the issues about our bones so we won’t collapse and break like pretzels when we get on Mars.

Doudna: You should come to our workshop on astrobiology.

Audience member 5: Pardon me?

Doudna: Come to our workshop on astrobiology. We’re gonna talk.

Audience member 5: But now we’re pre-adapting a group of people that becomes almost like a plaid of people, if you will, that are different from everyone else because they are going to Mars, and that just opens up the thought about other plaids of people as well for different purposes, and really puts you into a territory that could be quite scary.

Mukherjee: So I can give you my two bits on this. Lots of people disagree. I don’t want to go to Mars right now. I’d rather focus on cancer. To me, the question is, yes, the fantasy’s lovely. Lots of people disagree with me. I actually got into a strange argument with Jeff Bezos about going to the moon. The moon is a far away place, which is very toxic for human beings. It’s not a great place to carry heavy things to because it’s very expensive. It’s not a great place to put anything in. There’s a reason we aren’t going there. It has no atmosphere. So I’d rather focus on curing cancer and other diseases, but I understand it, that there is a desire to escape these earthly coils. It doesn’t fascinate me as a question. I don’t know. Are you fascinated by the question?

Doudna: I’m fascinated by the question, but I’m even more fascinated by asking the audience to ask us one more question and then we’re going to bring this to a close. So do we have one more burning question? Yes?

Audience member 6: Hi, thank you for the great talk, first of all. I can already foresee many ways in which genetic editing could be beneficial to curing diseases and just ending suffering as you were mentioning. But what I was wondering is from what I know and what I learned, a lot of mutations occur just naturally within evolution. So I was wondering how, or what your thoughts were on how genetic diversity could be affected by editing and changing our genome.

Doudna: Well, the short answer is not much anytime soon. Because what we’re talking about is making very targeted changes to the DNA of cells that would be, at least in the near term, this is gonna be done in people in cells where it’s not a heritable change. So you’re really making a targeted change in a tissue or an organ in a patient, or in blood cells, for example, for sickle cell disease and that sort of thing. If you think in the longer term, I still think that there’s always gonna be a background number of mutations that are occurring.

Every cell division leads to some random changes to DNA that happen due to various natural processes. And what we’re talking about here is really just making one individual or maybe just a handful of individual targeted changes. So if you think about that in the context of evolution, they’re sort of intermeshed, and you’re always going to have this background set of changes that are happening. I think the potential to control those changes and introduce changes that are gonna have a real impact on disease is a powerful one. But I think, as you get from this conversation today, this is not going to happen in any kind of a large sense in the human population anytime soon. I don’t know how you would address that.

Mukherjee: I would put a word of warning on that. I think it’s a very important question. The question of diminishing human diversity and having respect for human variation is an incredibly important point. I just often like to give you the following example. Privatized eugenics in the hands of the citizens of some parts of Northern India has already created a disgenic state where because of infant neglect or because of selective abortion, the gender ratio in these parts and some parts of the world has now moved to 800 women, 800 girls, to 1,000 boys. It’s a profoundly abnormal, unnatural, nowhere in human history have we had 800 girls to 1,000 boys. And that’s mainly, because of a combination of reasons, but mainly driven by the idea that one genetic makeup is inferior quote unquote to the other genetic makeup. There’s no state mandate.

In fact, the state prevents you from doing this, but privatized eugenics has already diminished human diversity radically in some places. So I have to say, we have to be extraordinarily careful, even in handing over to private individuals, private citizens, the capacity to select their own genomes or the genomes of their children. This is such a primeval desire. To have the best children is a primeval human desire, and it is so primeval that left in the hands of people without cultural guidance, without broad dialogue, without inclusivity, without equality, there is a rapid chance of it devolving into a diminishment or a reduction of natural human variation and diversity. Thank you for saying that because it’s a very important point. And we’ve seen it happen. Shall we?

Doudna: I think we’re at the end of our discussion, but we want to thank all of you for coming. Thank you to the chancellors of UC Berkeley and UCSF.

Mukherjee: Thank you for hosting me.

Dounda: And our hosts and all of you for attending, and we hope that you’ll continue the conversation. Thank you.