Jennifer Doudna and Sid Mukherjee in Conversation

Jennifer Doudna and Sid Mukherjee in Conversation

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Good. Afternoon and, welcome I'm, Carol Crist I'm the Chancellor 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, recalls. The. Anniversary. Of the 200th. 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 a Berkeley sesquicentennial. Which. We're celebrating, with the official model Fiat, looks 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, a hundred and fifty years of light at. Berkeley, and we anticipate, a hundred. And fifty 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, through. Few, breakthroughs, in science have had the kind of sweeping. Immediate. Impact, that. CRISPR, has bringing. Monumental. Change 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., mukajee is an, oncologist. At, a University. And Pulitzer. Prize winner for his book the Emperor of all maladies a, biography. Of cancer. His most recent book, the. Jean and intimate, history, chronicles. The history of, the Jean Jean, 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, Chancellor, Sam, Hager 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 can compact, a, colleague. Emmanuel, sharp on chez 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.. Daoud s contributions. Her, light are, significant.

And Worthy of celebration, please. Welcome Jennifer Doudna and dr. mukajee. Well. Thank you, Chancellor, crimped for that very, warm, introduction, and thank. You to all of you for 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 so. I'd like to start off by, by. Pointing. Out that you know humanity, has always had, a desire. For. Improvement. Cars. Improved. Transportation, penicillin. Improved. Health the, internet, approve, improved, the spread of information or misinformation in. That 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 but at what cost, so. I'd. Like to start, this conversation by asking, you, dr., mukajee, are. We transitioning. From natural. To unnatural. Or is this just the next step in human evolution. So. Again. I think the question, of what natural and unnatural is. Or our 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 opposed, and. The. Question is how are we posing what what 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 in. Embryonic. Cells really. Raises, the question about how 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, 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 might I have a physicians 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 talked, a little bit about this in the gene that, they're a triangle. Of, ideas. Which. We should keep in focus. The. First one is. When. We intervene, when we are intervening on human. Genetics. Is their. Extraordinary, suffering. Involved. You. And I can then, open up a debate saying well what is extraordinary suffering. But. At least there is a sense, there's a hard line that we draw and say that in, a when we move forward that. The that, that remains, a certain line in the sand that we. Invade, on what is natural, versus our natural only when we think that there's extraordinary suffering, involved in, a second I'll tell you that the people who don't buy this argument right I'll tell you what 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, I've called it the ideas we, can call it certainty, that, when we make genetic changes, when we do tamper. With evolution, particularly, with our own own evolution, that, we have a strong. Degree of certainty that there's a powerful. Relationship. Between the gene and phenotype. Or the or the, ultimate, manifestation that's. Involved, so things that we uncertain, about things that have.

Effects. That we don't understand, cascading. Effects like tropic effects we probably should avoid, since. Obviously we. Don't want to intervene on things that we don't ultimately we cannot ultimately control. And. The third line of the triangle, is is. Is is I've, called a justifiable. Choice people have used different words for it and that, is that, when we intervene, between. What is unnatural what is natural, that the, intervention, bears some justification, that, we can justify, it, that. It and, that it's that, it's not done by state mandate, that individual, choices involve, people people are able to do it or not able to do it as they should choose now. It. Doesn't, take an extraordinarily. Complicated, bit, of thinking to realize that each of these is fuzzy territory. Who. Defines extraordinary, suffering who mandates. Choice who decides. You know if, the world if our culture's push us towards. Manipulating. Our children. Is. That really a choice even if it is if it's a passive choice has really become a choice, different. Cultures make, different choices for instance exactly, and you know just to give you you 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, so. I fully, understand, this is complicated territory, but, as we move forward if we don't if, we don't draw some stakes this, is going to become I think a even. More complicated, than it than it is so. It. Is absolutely, true that we're drawing, we're, passing a boundary, between matched. Between the natural and beyond our natural those, were those terms were never easily defined, never. Easily definable but. The technologies, allow us to they're forcing, us to define them and and my argument is that we should use a kind of more sympathetic, way a humanistic, way to, try to breach those boundaries yeah. What. What do you think in fact some of these recommendations have been made you've been on panels that have been that made these recommendations, for, interventions of human embryos what are your thoughts about about, these the, breaching of the of the natural well I well, you talking I was thinking that you know at the we had a meeting, in 2015.

In The Napa, Valley that. Was the first meeting, is organized by the innovative, genomics, Institute and, UCSF, to think. About the ethical. And societal implications of, human genome editing and there, was a you know it was a fairly small group of people we had two, of the scientists. Who have been involved in the 1970's. 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 you know people really disagreeing. And debating, about in. Particular about human embryo, editing, so making changes. That would be become, inherited. In future generations, and that what would be the implications. Of that and, at one point somebody, leaned across the table and said wait a minute there. Might become a moment there might come a moment when we, will consider, it unethical, not to do that at. Least for certain kinds, of you know and it's like you're saying about you know if there's severe, suffering, due to genetic, disease this. Might in the future be something, that we, would you. Know our societal, II agree, should. Should proceed so, my own views you, know it's interesting for, me because I have found that my own views have been evolving yes I think about, this a talk talk tell us about the evolution tell. Us yes. I you know I started. Off you know when I first started thinking about the. Implications of. Gene editing back in you. Know in sort of the early days of this, work which was actually, only a few years ago now, and. Started. Thinking about this I I felt, initially very, opposed, to using. Gene. Editing and in embryos, not. Necessarily. Forever, but I certainly felt that the time wasn't wasn't, now to proceed to do that and. Why. Did I think that well I just didn't seem to me you, know it seemed unnatural, you know it seemed something, that you know you're sort of messing with something that maybe you shouldn't, mess with and as a scientist, I also appreciate, that in many cases, Jean and you know this better than anyone. Probably but you know a gene that. We think does, 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's something where we're, altering might, not you, know have unintended, consequences, and that would have consequences in not only a person. But all of their kids and their kids kids you know and it seemed it seemed kind of a profound thing but, what's happened over the last few years for me and you. Know for those of you that don't know me so I'm not you know I'm a biochemist. And I've always done very fundamental. Research so I'm like unlike, you said I you know I've always, just been working on molecules, rather than than patients, or people and but. What's happened over the last few years is that 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 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, his little little, carrier, you know and it's cute, and and and, you. Know it was just it broke my heart it really broke my heart and I I just I guess I've found myself recognizing. That you, know when there is severe. Suffering and we have an opportunity, to change that it. May be worth doing right well. You know one, line that philosophers. Have tried to draw. Is. Between. Emancipation. And, an. Enhancement. And. They have tried to draw a strong line between emancipation. Of course in real practice, once. You practice medicine the those, lines also become fuzzy, what, is you, know what is emancipation, for one person can, be enhancement, for the other some, the, extremes are quite obvious it's, very easy to think about extremes, you know, manipulating. Genes for, cosmetic. Purposes seems, you know very obviously.

Far. Outside the realm of what we want to do with, but. On the other hand there, are certainly examples where, where the conflicts, are more. Real I mean, the question, that occurs to me I'm gonna frame the question and then maybe, divided a little bit one, question that occurred to me while I was thinking about this is. You. Know we're. Always in medicine straddling, the line between treating, and curing sure. 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 sort of three categories. It's. Divided 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 and that's, like. Saying humans. And all other organisms but but. Really they, imagine, the entire you, know the question of, editing. Genes and other organisms, and crops and plants and pests the, second, is somatic. Gene. Editing so particular things I'm a transplant, ER so in. The in in stem cells blood stem cells are, the kinds of stem cells and the third of course is gene editing and either sperm or eggs or embryos so. Tell. Us about. What. You think the prospects, are in these three categories and and. And, is it reasonable what, is reasonable what's unreasonable, maybe in the three categories or pick pick one of them which, is most provocative for you well. So I think I think you're touching on an important point and that is that gene editing is, is used now widely, in, a you, know sort, of across the biosphere. I guess you could say you know it's really being used in plants animals its, 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 that. So it's you know it's a very exciting time really. As a biologist. I think. To be, you. Know living, in the midst of this. Transformational. Opportunity with. 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. Pass so just having the ability to sequence the entire genome you, know all the DNA and us in the cell of an organism, and. And start, understanding what all the what that code means well how it how it, dictates, what an organism, becomes this is really profound I think. That, you. Know so just. To quickly touch on the points that you those three areas so so if we think about using gene editing in. Organisms. Other than than humans clearly this is going to have a big impact on on humanity. Right because it'll allow us to change, plants. For example to be more nutritious or, to grow in environments, that where they otherwise wouldn't thrive is, Kito's get. Rid of mosquitoes maybe, maybe or at least controlled spread, of disease by insects. And. You. Know and then in terms of editing. What you're 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 not. 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 in the, type of research that you do for example right, being able to edit. Let's, say immune. Cells so that they're more effective at targeting cancer would be 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 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 which is or could be which. Is you know should it be okay, or is it okay to make changes, in the germline of humans, people. Are believe me scientists. Are already doing this in the germ lines of other kinds of organisms quite, routinely but in humans no, not not yet and and should we should, we go there and I personally, think that that. It that will that it's going to happen and it's probably going to happen because of the. Fact that you know different, cultures view, this question, differently and I think we're seeing already that. In a scientific world that the pace of, research. At least on human embryo editing, is proceeding, differently, in different countries, so just, a quick follow up on that question and then we. Can move on but how. Long, till. The first transgenic, human oh. Dear. I'm on the spot here I don't. I don't, know is the, short answer I think that you know just again. Just 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 and it, has been some question about there's, been questions, about, the details of how that's working but I think, the the overarching.

You. Know thing. That I take from that is that this, this. This. Research, is proceeding, and it's, going to it's going to 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 is wants, to give me an update on his own research in human embryos so you know it's it's 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 but, I think we're seeing steady. Progression in, that direction I mean, just to give you one example I, work. With blood stem cells and immune cells that's most of my my leukemia 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, edited. Gene. Editing, successfully. In 90%, of the stem cells, in. Fact we've, gotten to a place where not we're worried worried wondering whether we should even sort these cells because, the, the, efficiency, of sorting, is getting, to the place where the, efficiency, of editing, so. That so, basically, I. Suspect. That the blood system is open for business the. Entire blood system is open for business we. We. There's many many questions off. Target effects whether, they will get weird. Leukemias, that arise because we've you know, made. And I. Read. It in the wrong place but essentially, speaking, it's. It's staggering. We. Couldn't, do this six. Months ago this is this is a very important point I mean the field of this. Sort of this technology and, all the things are being done with it are moving forward. Incredibly. Quickly. And one, of the things that that's been on my mind is, how do we how, do we explain to people that are not in in, the you know down in the weeds doing the work working, in the clinic or working in the laboratory, I'm 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 you know people learn about science, they learn about technology is actually through through, the media through Hollywood, through. Books of course and. Through, through, fiction and nonfiction but, they you know they sort of start to understand, what's, happening we're seeing this with of, course artificial, intelligence, has been all over the media, lately and self-driving, cars and things and a little bit you know genome, editing is sort of creeping in there so I wanted, to ask you what, you think.

Hollywood. Has done well and. And what what if they what have they done poorly, and and how do we how. Do we how do we work with people that like to tell stories and they do that for a business and, for you know professionally. And work with them to get, science, right, well. It's it's 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 if you were to sit through the final, minutes. There. I have. A small band that's because. The. I, think, I'm speaking, correctly you know I, barely, enter this particularly. 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 this script is really fundamentally. About a dystopic. Vision. Of what, happens when human beings start, reaching for certain kinds of perfection, it it pushes it, pushes towards the, enhancement. To it debate away from the emancipation, debate and my, only thought about it was I say it's not disturbing enough. And. I think. I think. That in so. So, there's. There's a moment, in that. Film. Which. Actually what's, in very early version of there's, a moment in the film when you suddenly realize. There's. A moment in which the. Characters, are walking through a cornfield or something and you, suddenly realize that the entirety, of the world has. Now been transformed. For human benefit because the corn is growing ten. Times as high I think that. Was my input in the film as I'd make it more disturbing, but just to remind us just to, remind ourselves that, I, think, I think the media has a big responsibility, here. I think. Explaining. That, I think again it would be very helpful, for. Us from, the media to get a roadmap 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 you know and that's what I think is important, about the. Films the film a get, the science wrong they may get it too far off etc etc 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. What are they excited what, are they excited about, you. Know, a. Film. Like I'm just thinking of 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 were you. Know sure. We're talking about powerful. Technologies. Who's. Gonna draw the limits how are we going to how. Are we gonna you know how. We're gonna move forward, and. I think that's what that's what the ultimate that's, what ultimately helps it keeps 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 you, know tell. Us about. Science, I suppose in a way that's - you.

Know It just, doesn't. Make any realistic. Sense, so. For me like 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 and. It's sort of just, you, know beyond, where. We think, we are right now in terms of technologies, but it I think it you know I noticed that it captured. A lot of people's attention. And. Imagination, and you know I have a teenage, son and just you know hearing his chatting. About this with his friends, and you know you could just kind of sense this this, sort of buzz so I think films. Like that are great because they they actually they, maybe you people think about science they, they think about the the. Opportunities. You know if we develop technologies. That might allow us to explore. Our, solar. System, in ways that we haven't been able to but sometime, in the next few years there's, going to be a fictionalized. Version of a Jennifer Doudna movie. What. Would you what would you what would you like to ensure, is. In. That film if. The Ender is not in. Make. It exciting. Well. You, know again, I guess to me I. Like. It when films, capture, the passion, that somebody, has for work they're doing. For. You. Know the sort, of the, struggles. I mean you know I think you, know as students, now will often ask me you know I I feel, almost a little bit embarrassed, because I think they think that, I'm, you. Know sort of reached. Them 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 you know struggling. Through general chemistry in college and, trying to figure out can i really be a scientist. And and you. Know and I I I think a, movie, to be true to, if it wants to be true maybe doesn't but you know if it really wanted to capture anything. That's true about me it would have to show those, struggles, and and, it would have to, you. Know show, the. You. Know it's again it's kind of back to the human spirit isn't it it's about you know all of us I think you know 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, and you, know for me it was about you know realizing, that I was just a person that loved to love. To think about molecules you know I love to think about how how, life works at the level of molecules. And and so I you know but but it's it, hasn't been a straight path at all and I would definitely want a story, to capture that and and just just, tell.

Us About and. Tell, us about a, lot. Has been written about, you. Know the the, initial, series. Of conversations that you had with the man well. It. Was at the start of this tell. Us about the. Actually. I've never read, about. The, the kind of moment was. There a moment when. Things. Crystallized. For. You well. I think I think there have been been a few of those I mean you, know when I think back on take, one pick one pick one okay. Well. Probably, that I should pick the first one then which is really when I met her and you know we met, at a meeting in 2011. It was a meeting I you, know almost didn't, go to because, it was a meeting, for microbiologist. Which is certainly not me and and, I was busy and I was teaching, here at Berkeley and I was you know juggling all the usual things that we juggle, and I. Almost canceled, it but then I I decided, to go and it's good that I did because that's where I met, Emanuel. Sharp and TA and and, she. Is a microbiologist so, she had good legitimate. Reason to be there and, when. We met at this meeting we met there because, we were both working on what. At the time was a very obscure. Area biology, namely, understanding. How bacteria, fight, viral infection, using a system called CRISPR, it's an adaptive, immune system in, bacteria, and so. We were both giving talks of this little session at this meeting and afterwards. We went out to lunch you know and we started chatting and we started walking around the old, cobblestone. Streets of Old San Juan Puerto, Rico and, in. That conversation you, know 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, Cass 9 and, it. Was a project that really kind of you know brought, together expertise. From her lab as a microbiologist, and. My lab is biochemist, and I. Do, remember, feeling a, real sense of sort of the hairs on my neck standing, up because I could I could sense that there was something very exciting. About this project and you know in in some ways the rest of it is you. Know it's kind of a I, can. Tell you my, story about that story is that I heard about from up from of all people in the world I heard about the. Your early results from Paul Berg I was I went to Stanford. For, another visit I have collaborators, there I trained with Paul and Paul. As. Paul, had as you very much know there it, was among the many people who discovered. How to clone, make. Recombinant, DNA stitched to pieces of DNA, from two foreign organisms, together, and. Was instrumental in the Asilomar meeting which was an important milestone in all of this and I. Would once in a while like 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 you know very precious. To me and he's. Now 90, years old because 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 a 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. Because. It was it was it was a little unfathomably. People had been thinking about this a long, time and, it, was a little unfair move and of course the fact that it was borrowed back from bacteria would 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, we. 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 I mean do we have a responsibility, there are, 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. The. The history of this country I'm an immigrant so the, history of this country is a country that grew out of the aspirations of humanists. Scientists, engineers, what, do we do about the student what are you doing Jennifer what how does the world look to you I'm, very concerned about this I think I think it's a it's it's a big challenge I think we have to start by encouraging. Scientists. Everywhere to get, out of the lab at some at some level, and and, engage, in conversation. We have to we, have to talk about science we need to bring science back into, the kind of the you, know discussions. That we have at cocktail parties and, things like that I. Think, that that, you, know books like like like, your your books I think are doing, a lot to kind of you know 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 as a you, know I mean hopefully they I'm sure 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 text book it's something that is very human, and I, think. The more that we can do that and show people that you, know and use language. To, describe, scientific. Ideas, that isn't, you know isn't filled, with acronyms, and there 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 you know the 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 in certainly. In my lifetime as, a professional, scientist. What. Would you how would you answer, all. I can't. Agree more I think there. Is 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. In. All of this and. The, the dispiriting, quality lasts generations. It's not as it's not why it's like I'd say it. Carries, through and. I think this is an especial, time. You, know, I'm. Not gonna say it's not it's not go hug a scientist, day but. But. I think there's an especial, time when, we. Need, to remind ourselves that. That. The contributions. Of. Science. To this debate to this car we look at for, instance look at climate change. We. Need debt before we have arguments, and converse it we need data data, comes from laboratories, from scientists who spend time gathering, it we need to respect that idea that we don't we, can't enter these debates without data, so. So. Just. Be just, be careful, be cognizant, of the fact that yeah the scientists, in your life around you are Industry. Spirited, and try, to encourage them a might be philanthropically, it might not be it might be personally. But. It's it's it's a tough time for the graduate students and their postdocs, in my lab I don't know if you're famous so has your has, your your work and especially maybe your writing, has, that led, you to have conversations, and interactions with new groups of people that you you know that have sort of taken you in new directions. Well. Certainly, politically, yes I mean Emperor. As. You know you. Know the ones, the fur my first book on history of Kent on cancer.

It. Was 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. Will. Be announced in a week or two so. 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 certain, group. Of people. I think. One. Of the most interesting conversations that I've had recently. Is. With, people who work, on. You. Know. Education. For children how, do you how do you take textbooks. Which, are which are becoming more and more outdated in some to 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 with books. That are more readable, and. That's, one initiative, that I'm very interested in how do you make a kind of, simultaneous. Storytelling. As well, as as, didactic. Education for. AP. For, instance which, is much more accessible and doesn't. Remain you know the boring old textbook I think kids are actually a great way in - you know I had this great, experience a couple of years ago where I you know I 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 what if I would come and talk, to the kids a little bit about my, work and so, I went. To the school, and we did it after school so we just it was just voluntary, we just asked the kids you know who would like to do it and for. My first shock was I walked into this room thinking there might be two, three kids there were twenty kids there and, 15. Of them were girls it. Was cool yeah and, the other thing was so I thought okay how am I gonna get these you, know twelve year olds interested, in what, I do so, I thought well I'll take this this, 3d printed, model that I have of the cast nine protein, it's 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. Cast nine 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 and so I took this model it's about this big it's about you know sort of a football or so I took it in and the, model was designed by Jacob very nicely, that it can be pulled apart you can actually pull the DNA out you can see where the DNA, got cut I should have brought it would have been fun but, but I took it to the kids and I thought well I won't, I won't actually take. It apart I won't to show them actually how it how the DNA gets cut because that might just be too complicated for the kids so, I have this model it but it's brightly colored and you know it looks kind of cool and 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 right they had pulled it they're like oh look cool the DNA comes out hey we can pop this piece often you know they were dissembling, it and they, were looking at it and you know they were figuring, it out and they, were asking. Tons of questions and actually they asked a number of really, interesting ethical questions, I think one of the kids at that that, little.

Meeting Asked, me about the ethics of, not. Really not, really using that language but asked me you know what what. Does this mean for changing. Embryos. You know humans, and doesn't that mean that you know you could you could decide to make. Somebody taller or smarter or, you know Wow and you know 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 I think kids are natural scientists, you know they love they love questions and the more that we can do that and get them engaged they don't think about science as a as a thing you know it's just it's just sort of you know it's an it's it's something that's interesting that's entered their world. Should. We should, we be, getting very four questions, we, want to turn it over to questions from the audience but I want, to before we do that I just want to I 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 you know for me the. Emperor of all maladies you, know your first book about cancer and it really is a profound, work. It's very very in, some ways very. Depressing. But it's also incredibly. Interesting. To look at the history of you know how humans have grappled with this this this really intractable, disease, I'd. Love to hear what you what, you what motivated, to do it what, was most surprising to you. About that process and what, was it fun was it hard, tell. Us about that so, you, know I hadn't, 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. You. Know. It. Is cancer. Has become more than a disease it is a metaphor it, is an allegory. It is a people. Just use it to describe states. Of mind. Very, few illnesses, in human history have, ascended, to, this kind of space in human culture. So. 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 million. Text books on it so. That was really the beginning of that book I, started, as a fellow, in. And. I, would work do in during, the day I would we be in the clinic and. In, the evenings I would write and it was just a journal to start with, and. They grew and grew and grew and at some point of time I decided, that I would show. It to a publisher and someone said to me that you know they're gonna be you know you know they were there with two readers for that book your mother in you. 600, pages on cancer you know when it was first. When. It was first delivered it, was like someone, said it was like a, phone. Directory from in. The days that there used to be phone directories a phone. Directory from hell, it. Had a black cover. In. The back it had in white it had cancer, written on it and it was 18. Hundred pages long and cut down to 600, pages so, that's how I started. That was my that was my first book 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, and in your second book so, well-received, as well and. You know many. People have read the gene that I've run into just sort of randomly, but. But also you. Know you you encountered some criticisms, about the book tell, us about that experience what's. The main again. It's the experience of distilling, very, complex, science too simple you can't satisfy everyone this, simplification, is absolutely, necessary. You. In, the first draft again, it was it was delivered in 1800 or pages it, had to be cut down to 600 now I have to do most of the cutting and so, things get left on the floor things have to be cut to cut off and left on the floor so. You. Know you have to have a radical, simplification in, many places and people don't scientists. Don't like being simplified they don't like they're working simplified, but. In order to communicate with 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 you know the criticisms, of a mission, is. One area, the. The controversial, one of the controversial parts the book involve questions, like race and IQ, and. Those. I. Really. Thought that for this for this book it, was it was odd this was before long. Before these questions had become very central. So. There's a chapter, on race and a chapter like you 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 race chapter and race the, chapter nah he was 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 their, disagreements, about some. Of these fundamental questions so you, know it's part of the it's, part of the territory yeah. Absolutely. Maybe. 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. The. Words like war on, cancer, battle, on cancer. Some. Some people, some. Patients, don't like it one woman famously, said to me you. Go fight the war. You. Know. This. Is not a word that I want to own others want, to own that what it somehow helps the the, idea of them fighting something in their own body such them, what. You feel about the word gene-editing, what you feel about the word. You, know the various words tell, us what the various words have been and. What. Did you coin yourself, how do you use you what, is a book 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 yeah. I think you know we've seen it interesting, I've noticed a kind of 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 and, and. This. Kind. Of came about I think due to their you know they were 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 and cells and that involved, a lot of work and a lot of you know, you. Know engineering. In the lab engineering, proteins and, and. Then with when when CRISPR came along initially. This. The same language, was applied to it but but what's happened, and it's you know and this wasn't me. At all this was sort of just sort of happened very organically I, think in the field is that people began to adopt the language gene. Editing why. Well, I think that 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. 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 and maybe. At some level that you know started to started, to you, know permeate, the the. Language that was used to describe it in other contexts. But I started, to ask people well why you know white people like George church you know do, you use why do you use you you know when do you use editing and when do you do this engineering and I think it was George that said well you, know 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, right.

And And. Do you think moving. Forward do you think this term will stick is it is it easy for you now to use this do you find it there's a facility with it I, think so I mean I I'm, curious, to know you, know and I try, to ask this question of people that are not scientists, you know ask them you, know how they react to that what does that mean to you if someone says gene editing does that mean anything or does it just you know is it opaque but, I think it's 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 it's really a technology that's all about, rewriting. DNA. Right we you know we've been able to synthesize DNA, so we can we, can we can write it we can erase, it we can cut it and paste it and now, we can rewrite it and so I think it really is sort of analogous to having a text. Editor that you're using on, the genetic code one, of the astonishing things I don't know how many people have worked with the. CRISPR has nine system one, of the astonishing things as a user, in in human biology is how, simple. It is, it. Is very very. Simple and maybe that's part of the captured. In this in this in this idea of gene editing. It. Seems to me you, know one one, thought I had is that for. A long time I to, figure out how it would help us share purity in cancer. You, know of course to elucidate targets, in cancer genetically. Manipulate cancer cells it's, really really simplified, but, could we use this therapeutically. In cancer, and, I struggled with that for a while and of, course the answer has now come to us it's you can't necessarily use, it in cancer cells because. Evolution is working against you you know you have to essentially. Get it we, think in a hundred percent 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 a powerful, way to think about cancer, not, from the standpoint of cancer itself but, from the microenvironment around cancer a 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 and is. That something do, you see yourself, as your own lab ever moving in that direction making. Sperm. And egg edited sperm, and eggs human, sperm and eggs so. You. Know I think you're absolutely right that my and. I you know disclaimer, is that I'm not a I'm not a human developmental, biologist. By, any stretch, but I think, that you know from what I've come to understand, from talking to people that are experts in this area I think that that, this is absolutely, coming you know that it's going to be possible to and it sort of it's going to obviate, the question, of editing, human embryos, because you won't mean to write you won't need to you'll edit the sperm and eggs and. You. Know would I ever do this in my own lab no. Not. Not for any reason other, than that's, not the kind of biologist, that I am you know it's not the kind of expertise, that I have but, I I think that you're right that you know the in terms of thinking about future, clinical impacts, this is an area of very, active. Where, there's likely to be real advances. It. Seems. One. Piece of conversation we were having earlier which is an important threat, to pickup 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 other technologies. You, mentioned one of them embryology stem, cell biology and the, third one is is artificial, intelligence deep, learning I. Have. A couple of thoughts about. Deep. Learning and and genetics, particular, 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. So. 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 right very, classical, model very classical, genetic model of thinking and cardiovascular, disease, you know familial, hypercholesterolemia, you, get elevated cholesterol you, have all, sorts of problems. This. Study looked. At. If you take a hundred people. Only. Two of them two. Of those hundred 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 sort, of 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. Shout not shove, effects so, you know those single genes were like shops 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 as in in. The context, move, you even, a little bit even slightly, towards. Your. Ultimate Lea so. The question, really arises, is, that if that's going to be the case with most. Human, diseases and. Does. Gene editing help with nudge effects, can you imagine ways, or it should be will, it only help with shove genes are, we going to reach some kind of biological. Limit. As it were to. The capacity, to manipulate human fingers it's a complicated question so I don't know what your thoughts about that well I have two thoughts about that I mean one is that I think that CRISPR. And sort of gene editing technologies. That are you, know 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 right and that's already, happening, so there's lots and lots of laboratories, now they're 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 organs, which, are cultured, you know 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 and frankly I totally, agree with what you're saying about using, artificial intelligence or, machine learning to, help us understand. Those networks because they're often complicated, right we have to you have to really understand, all the players that might can 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 you know the technology, is going in that direction is being, able to edit. Or modify multiple. Genes at, once and, you know sometimes these genes are with it well, sometimes, these genes are found in, very. Disparate, parts of the of the, genetic material but sometimes, they're actually. Co-localize. Immense. Pace and there's more and more that's being learned about, how, that, works in sells and so I'm thinking that in the future it may be possible to. You. Know 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 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, 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. What. Is the phrase human evolution. Mean to me in 2018, I think that was changed for you well, I think we're on this incredible. Continuum. Of you, know it's a it really is an exciting, time I, feel, many. Days I just sort of feel a sense of wonder you know I feel amazed, that I'm alive at this time when you, know we're, sort of at this moment when, all, these, technologies. Are coming together and, for, the first time we can do things we. You know like like we said like in Chancellor, christe's introduction, you know that we really have now the power, to. Control. Evolution. It's not just not just in principle our own that's obviously, still kind of you know on the bleeding edge but but, but to control, evolution. Of other organisms, and are in our environment and I think that's a it's a really profound, opportunity. And, a profound, responsibility, so, I hope, that we can all you know 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, this. It's possible, to have an international moratorium. Until we decide this is it conceivable no. No, it's really not because you know as we discussed earlier I mean I think you know 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. You know should be doing, we should be encouraging that and being the, you. Know really leading that that conversation, not dictating, it but just inviting, it and and welcoming, different, points of view so. I would like to now open. Up the floor for questions because, I know that some of you may may have questions and we'd really like to hear. What you're thinking and try to answer them so will, we have runners. With microphones, that are coming around and will if you raise your hand they, will call. On you and we will bring a microphone to you and. Who's. Doing that who's calling out the. Okay. Like. The lights are in our faces excuse us if we that's right turn to you late yes I do just hi. Thanks there's a great talk my. Question is sort of quick I'm just wondering like what have been the three most influential, /, favorite books for both of you. Well. And, it's, interesting that you asked because we were just saying today this, week I think is the 50th, anniversary of the double helix. Jim, Watson's. Famous. And at, one point I'm 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 I was very influenced, by it, I was.

Also Influenced. As, a young reader by, I'm a I was very, influenced, by Orwell, all, the warworld's books were very influential to me in fact it influenced, my thinking and, then, I would say I. I've decided, 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 Jean 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 you know 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. No Jennifer, fascinating well I have to say I have to say that the double-helix also, for me was incredibly, influential. I mean at that that book was probably the first book. That I read you know back when I was in grade school about, about, science, and it kind of blew my mind you know if you vet for those of you who read it you know 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 or maybe not one is I would have to say that 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 and I found his writing, to be incredibly, captivating. And interesting, again sort of in my formative. Years and then more recently I read a. Biography of Dorothy Hodgkin, that, was also just fantastic. And you know learning about her life and she had made 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, you know she she. Won, the tool belt prize and you know she did, really, just incredible groundbreaking work so I that book, was also just a, incredibly. Inspiring. Three there's. A little note in the gene actually met Dorothy Hodgkin years ago, there's. A little note in the gene where when she won the Nobel Prize the, the. Subtitle. In one of her photographs was a housewife, from Sussex or wherever shield. Hi. I think I'm the, next questioner. Where. Are you and to. Us wave to us. You, talked, earlier about the cultural, differences or, the cultural, the, difference in cults in cultures. In terms of their approach to. The opportunity. Responsibilities. Of gene. Editing and 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, well. You take that one first well okay so so. There's. You know and again this is really just my personal. Observations. Right but I think that what I what I've noticed is, that I. Think in certain parts of the world where, and, I'm not putting any particular. Country on the spot here but I think there are parts of world where there's an incredible, eagerness, to be engaging. In, the, scientific. Process right. People that are very you know maybe have felt not included. In that in the recent history and want to get into, it and want to be recognized. For their work they want to be prominent, they want to they want to attract attention. They. Want to you, know make progress. So I think there are motivations. That go beyond. Simple. This you know those sort of the joy of discovery which I think you know all science is kind of share but you know there also are people that are thinking about, you. Know really. Kind of putting their country, or their culture on the map in terms of you know 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. And. And that's where we just need to be be, careful and. And, I I think, that it. Just requires, and. 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 a international, consensus. Around what we all consider, to be appropriate use. Of technologies. That's what that's just my observation. And. I think that's what we should be encouraging. Because you know culturally, people do approach these, things differently. And, I would say even the micro, cultures and science are different we were talking about. You. Know once in a while I'll speak with, someone. Like George church I actually the public conversation with George and. George. Is a big I talked about you know George, is a big enthusiast, of really. Opening, and opening this filled, up, heap. I think he would I think it's fair to say he would be an enthusiast, off making. Directed, manipulations, and human sperm and eggs and. He. Thinks, that's, his brain I. Think. I think like a physician, first. My. My, first thing that comes out of my brain is is. This are we ending suffering, or you know how. Can I first do no harm is, the first thing that comes out of my brain, people's, brains are hooked up different yet I do think, that. People's cultural, brains are hooked up differently, yes. There's a need for provocation, whoo, yes there's a need to need to do as you work to, put people on the map but 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 we, have. Different. Understanding. For, instance of where life begins. And. That is important

2018-02-06 18:36

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Excellent and thoughtful conversation.

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