CRISPR in Context: The New World of Human Genetic Engineering

Summary

Highlights

• Jennifer Doudna and Emmanuelle Charpentier's discovery of CRISPR's gene-editing capabilities marked a revolutionary moment in science 🌟.
• CRISPR enables precise genetic editing by using an RNA guide and a protein called Cas9, marking a significant technological advancement 🚀.
• The controversy surrounding the first gene-edited babies in China sparked global discourse on the ethics of genetic engineering 🌍🗣️.
• There are both great opportunities and serious ethical challenges associated with using CRISPR technology responsibly ⚖️.
• Open discourse, rigorous ethical standards, and international agreements are essential in guiding the future of genetic editing 🌐📜.

Key Takeaways

• CRISPR technology offers profound capabilities for altering genes with precision, allowing for potential breakthroughs in various fields like agriculture, medicine, and technology 🌾🧬🤖.
• The ease of use and relative affordability of CRISPR makes it accessible to many researchers, but this also presents ethical challenges and concerns about misuse ⚗️❌.
• There is potential for great advancements, such as tackling genetic diseases or enhancing crop resilience, but also a risk of pursuing ethically fraught areas like 'designer babies' 🚀🤔.
• Engagement and open discourse within the scientific community and with the public are crucial to responsibly manage and regulate the use of CRISPR 👥💬.
• Billions of dollars are poised to fuel CRISPR-related research and applications, emphasizing the need for robust ethical frameworks to prevent exploitation and misuse 💰🛡️.

Overview

Chapters

• 00:00 - 02:30: Introduction and Historical Context This chapter, 'Introduction and Historical Context,' explores the dual-edged nature of human innovation. Starting from the harnessing of fire, it highlights how technological advancements have consistently presented both opportunities and challenges. The invention of the printing press in the 15th century is used as a key example of this duality, as it enabled widespread knowledge sharing, sparking the Age of Reason, yet also posed significant social challenges.
• 02:30 - 05:30: Significant Biological Discoveries The chapter discusses how significant biological discoveries and technological advancements have dramatically changed human society and the world. It mentions the challenge to the established religious order and authority by human exploration and scientific achievements. The exploration led to global navigation and the unfortunate spread of diseases to populations that had no prior exposure or immunity. It also touches upon the momentous event of the 20th century when humans split the atom, which opened up immense power potential but also posed the threat of human annihilation.
• 05:30 - 10:00: CRISPR Technology Overview The chapter provides an overview of CRISPR technology, highlighting its advancements and implications. It begins by discussing the rapid progress in machine learning and artificial intelligence, raising concerns about a potential future where AI surpasses human control. This sets the stage for introducing a significant breakthrough in genetic engineering: the birth of genetically engineered twin girls in China. These twins were modified using CRISPR-Cas9, a powerful gene-editing tool, and their altered genes will be hereditary, impacting future generations. This development underscores the profound and far-reaching consequences of CRISPR technology, not only in gene editing but also in ethical, societal, and futuristic domains.
• 10:00 - 15:00: Genetic Engineering in Agriculture and Medicine In the chapter titled 'Genetic Engineering in Agriculture and Medicine', the discovery of a tool that bypasses natural selection is discussed. This tool, which provides direct control over the levers of evolution, poses a significant challenge to humanity. Depending on how it is used, it has the potential to bring about great good, such as more food and less disease, or significant harm. The chapter questions whether we can learn to use this powerful tool wisely.
• 15:00 - 26:00: Ethical Considerations and Challenges The chapter begins with an introduction to Jennifer Doudna, a professor of chemistry and molecular and cell biology at the University of California, Berkeley. She is noted for receiving numerous awards, including the Cavalier prize in nanoscience. The focus of this chapter is on the ethical considerations and challenges in biology, particularly how to responsibly use emerging technologies in the field. The conversation hints at the implications and decision-making processes involved in advancing scientific research and its applications.
• 26:00 - 31:30: Global Impact and Future Prospects The chapter titled 'Global Impact and Future Prospects' discusses the decision-making process surrounding technology and its use. It emphasizes the importance of venues and discussions aimed at understanding, describing, and debating scientific advancements. Participation is encouraged from all those who will be impacted by future technological developments. The chapter raises questions about which entities—such as the scientific community, politicians, or global organizations—should be responsible for guiding and making decisions about technology.
• 31:30 - 58:00: Panel Discussion: Regulation and Moratorium The chapter discusses the need for international collaboration in the regulation and understanding of new technologies, specifically mentioning the World Health Organization and National Academies of Sciences. It highlights the potential role of the UN in overseeing technological advancements and emphasizes the importance of understanding the fundamental aspects of such technologies. The discussion involves a demonstration using a 3D printed model as a tool to better understand and communicate the technology in question.
• 58:00 - 86:00: Conclusion and Future Outlook The chapter 'Conclusion and Future Outlook' discusses the CRISPR-Cas9 protein, which acts as a molecular scalpel. It is a sophisticated tool used by scientists to make precise cuts in DNA and induce targeted changes in genomes. The mechanism of CRISPR-Cas9 includes an RNA molecule serving as a guide, matching letters in the DNA code, which determines the specific genome location where the protein acts.
• 86:00 - 92:00: Audience Q&A The chapter 'Audience Q&A' discusses the mechanism by which a cell can make precise cuts in its DNA, triggered by a process that evolved in bacteria over eons. The conversation highlights the contributions of the main discoverers, including Emmanuelle Charpentier, and emphasizes the microbial origin of this genetic editing method, which was used by microbes as a defense mechanism against viruses.

CRISPR in Context: The New World of Human Genetic Engineering Transcription

• 00:00 - 00:30 [Music] since the first humans harnessed fire our big brains have been presenting us with challenges innovations that can bring us great good and also great harm in the 15th century the printing press allowed people to share knowledge sparking the age of reason and also
• 00:30 - 01:00 appending the established order and authority of the church learning to master the winds and navigate the Seas humans conquered the globe and spread deadly microbes to populations with no resistance in the 20th century we split the atom unleashing a power hitherto unimaginable 'ti of our own annihilation
• 01:00 - 01:30 the speed with which our machines can learn has raised the prospect of the so-called singularity the moment artificial intelligence balls beyond us creating the world in which we are no longer masters and now twin girls have been born in China who are genetically engineered with the powerful gene editing tool called CRISPR caste 9 their altered genes will be passed to their children and to their children's
• 01:30 - 02:00 children we have discovered a tool that bypasses natural selection giving us direct control over the levers of evolution and again we are challenged this tool can bring us great good more food less disease or greet harm can we learn to use it wisely [Applause] one of the most significant discoveries
• 02:00 - 02:30 in the history of biology professor of chemistry and of molecular and cell biology at the University of California at Berkeley the recipient of numerous prizes including last year the Cavalier prize in nanoscience please welcome Jennifer Doudna so welcome so let's start with the question from the end of the film so how do we figure out how to use this
• 02:30 - 03:00 technology wisely and who actually gets to make those decisions well I think it certainly starts with venues like this honestly where we talk about it we describe what the science is what it means where it's going and we invite participation from all of us who will be affected by it in the future and so as we go forward is that the scientific community is it politicians is it global groups how are we going to decide technology and guidance of it
• 03:00 - 03:30 well I think it's all of the above I I favor the work of the World Health Organization and the National Academies of science right now that have put together international groups to look into the technology and make recommendations but I think we may also need a group such as the UN to get involved as well so that obviously requires knowledge and understanding the technology and really the basic fundamentals of it so let's start with that so tell us about it well I have right here a 3d printed model of a
• 03:30 - 04:00 molecule this is a protein the white part of this is a protein called CRISPR caste 9 and it's a molecular scalpel it's literally a tool that scientists can use to cut DNA and trigger targeted changes to genomes and the way it works is that it has another molecule in it called RNA this orange piece that provides a script it's a set of letters that match the DNA code in a genome and when that match occurs this protein is
• 04:00 - 04:30 able to make a cut in the DNA and that triggers the cell to make a change at that precise position in out of all of the the DNA inside the cell so this process even though you and your collaborator Emmanuelle Charpentier were the worthy discoverers of it in the modern sense I mean it evolves so it actually existed in bacteria that's right it evolved over over eons in microbes because of the need to use it to protect themselves from viruses so in
• 04:30 - 05:00 in bacteria this protein is programmed to find and destroy viral DNA but when a manual sharp on ta and I did research to understand how that works we recognize that this tool could be this this ability of the protein could be harnessed as a technology for genome editing and other kinds of cells so the technology as everybody now knows it's CRISPR so what actually is CRISPR what does that stand for clustered regularly interspaced short palindromic repeats
• 05:00 - 05:30 you don't make me say it again promise so so so what what does that mean the palindromic part of it means what well the palindromic part of it is the is the repetitive elements and the way this part of DNA in bacteria was first recognized was actually by a japanese group in 1987 they didn't know what it did but it was distinctive because it had these repeated sequences that flanked other DNA sequences that were at
• 05:30 - 06:00 the time of unknown origin and later in the mid-2000s three different research groups that were studying these figured out that these sections of DNA with between the palindromes were actually coming from viruses and so these CRISPR elements are in fact a molecular vaccination card for bacteria it's a way that bacteria can store pieces of DNA from viruses that have infected them over time so that's at least two points for jeopardy or Trivial Pursuit crisper
• 06:00 - 06:30 and palindrome whoo-hoo so so but people have been manipulating genes for a very long time right so we have a brief film talking about that as well as how CRISPR really has changed the game humans have been engineering genes for centuries the vegetables in a modern supermarket and the staple grains that sustain us bear little resemblance to the ancient plants they derive from our domestic animals to
• 06:30 - 07:00 have been transformed through generations of breeding the variety of dogs is a testament to our power long before modern biology to transform genes beginning in the 1970s we learned to directly manipulate the genetic code stored in the cells of every living thing but for decades the technology remains cumbersome expensive and imprecise then came CRISPR in 2012 a
• 07:00 - 07:30 manual sharp on TA and Jennifer Doudna discovered they could hijack a mechanism that bacteria use to protect themselves from viruses with a piece of RNA acting as a guide and a protein called Cass 9 acting as the scissors scientists can now target remove and replace any stretch of the double-stranded DNA molecule in any living thing easy quick and expensive and so precise scientists
• 07:30 - 08:00 can switch out a single base pair in the more than three billion base pairs that make up the human genome so let's move now to why there's so much excitement about this technology as well as frankly speaking why there's a little bit of trepidation so some of the things that it can do and also in your opinion some of the things that maybe it can't do so starting off food so how can CRISPR help
• 08:00 - 08:30 the worldwide food chain imagine being able to make changes to the DNA of plants that introduce traits that can protect them from drought protect them from infection by pests make them potentially more nutritious in the past these kinds of traits would have had to be introduced by random mutations to seeds and then many years of selection for plants that have desired traits often bringing along undesired
• 08:30 - 09:00 properties along with them and then going through the whole process of getting getting that plant to into a market where it could be useful now with CRISPR there's the opportunity to make targeted changes to the DNA only manipulating genes that have the power to control the traits that were interested in changing and doing it much faster so obviously great agricultural potential benefits maybe not in Berkeley
• 09:00 - 09:30 but once in a while in New York you still find somebody who eats meat or fish our animals fish are those populations potentially advantage absolutely yeah yeah same kind of manipulations happening in animals that are used agriculturally as well making hornless cattle for example and other other ways of protecting livestock from pests and and probably in the future making other manipulations that will be useful as well are there are there risks
• 09:30 - 10:00 in terms of changing genes that were putting out into the agricultural world and the biological world well I think we always have to be careful you know thoughtful about how how we're manipulating animals that were using and in the environment animal welfare of course is an issue but also thinking about the human health risks that might come along with that and what about so let's move on now because obviously this is a genetic manipulation so what about the possibility of genetic diseases so what are some of the genetic diseases
• 10:00 - 10:30 that come to mind that most readily lend themselves to this type of technology well there are a number of human diseases that are known to be caused by a single genetic mutation a single gene that has gone awry and so these are I think the first targets for something like CRISPR because we can imagine how to alter those individual genes now to have an impact on a patient's health so some of those would be in terms of well sickle-cell disease is an obvious one muscular dystrophy is another cystic
• 10:30 - 11:00 fibrosis these are all examples Huntington's disease is a neurological disorder and there's a large number of relatively rare genetic diseases that result from individual changes that happen sporadically that right now we really don't have any anything to offer patients and in the future hopefully we will have a tool that can actually correct those disease-causing mutations so single gene disorders being prevalent Notah I mean we all remember from
• 11:00 - 11:30 struggling through University biochemistry that people have sickle cell where they don't have both genes where they have one gene it provides some protection against malaria correct so how do we make sure we understand the genetic conditions well enough to know when to intervene well I think we have to take it step by step so it's that great to start with diseases like sickle cell that are fairly well understood but as you point out you know I think we have to be cautious because genes typically don't have a single role in
• 11:30 - 12:00 our health they have you know they interact with lots of other genes so we do need to be thoughtful about how we manipulate them so what about so say you've got a gene you've got a patient population and you have a manipulation so what are the ways that how do we introduce that into human patients who were trying to treat what are one of the ways that we can go about doing that in terms of doing it in vivo ex vivo and what that means right well there's really two ways I think it's shown on this slide here where where you can
• 12:00 - 12:30 introduce the gene editing molecules in cells that are taken out of a patient's so it's done ex vivo outside the body and the edited cells are then replaced and that would be for example to treat sickle-cell disease that's how it would be done or we can do it in vivo where you use something like a virus to deliver the gene editors and then the virus can hone in to the tissue where the editing is needed any thoughts on whether one of those will be particularly more effective or efficient or is it going to depend on
• 12:30 - 13:00 different diseases well today you know we're at a point where the ex vivo type of delivery is really I think almost there it's really a feasible thing to actually do and there are trials clinical trials that are on Dec to move ahead using that kind of strategy in vivo delivery however as you can imagine it's a lot harder and to be sure that it's done right and safely so I think that's still a ways off but in the end you know that's gonna be obviously the more powerful way to be able to do gene
• 13:00 - 13:30 editing so but most traits that we deal with in in medical centers are not monogenic they're polygenic they're very very complicated I mean some of the most common things we deal with are things like HIV and all sorts of different forms of cancer so how can you take an approach like this and think about how you targeted for more complex polygenic conditions like that well for something like cancer I think the the excitement there is about being able to manipulate
• 13:30 - 14:00 the immune system imagine we could edit immune cells so that they are they have the right properties so that they can target tumors I think that would be a very exciting way to treat cancer and then for for HIV infection there's the potential to rather than targeting the virus itself actually target the molecule that is necessary on t-cells the immune cells that get infected by HIV so that HIV can't get in so there's been lots and lots of speculation about what
• 14:00 - 14:30 CRISPR technology maybe can do what are prospects for the future so if we're gonna break things down into yeah I think this is probably gonna happen relatively soon yeah you know it's gonna take a lot more work but this is realistic or this is kind of Harry Potter fantasy world probably never going to happen so let's just run through a few so how about life so the thought that humans at most humans we all think I have we have an age span I
• 14:30 - 15:00 take care of a lot of patients in their 80s and 90s and I've kind of figured I'm okay with the 80s 90s I'm not so sure but lobsters supposedly don't age like humans they're resistant to a lot of the aging effects so are you going to be able to help me want to want to hit well I hope so I mean I think I think you know the potential for gene editing to be impactful in terms of quality of life I think that that potential is high whether it you know I get asked regularly can-can gene editing extend
• 15:00 - 15:30 the length of my life and I think we're a lot farther from that so but so how when you look think about it you say okay how's that how is it going to improve the quality of life of somebody who's 50 in the third row now or we'd they've got an average life expectancy of 35 more years well I would say yeah I think there's potential to improve quality of life by protecting us from from infections by again back to the
• 15:30 - 16:00 cancer example being able to provide a way of tuning up the immune system so that it's more effective at fighting cancer so I would say those are probably the things that I think are not you know they're not here today but they're not completely science fiction either but being able to you know tweak a gene or two and add another 50 years I think that's that's probably sci-fi what about a designer babies so not fixing medical problems or genetically predisposed
• 16:00 - 16:30 conditions but you know I want my kids smarter I want my kid taller I want my kid to be able to jump like Zion Williamson I mean so what about designer babies well you know the thing about designer babies is that for the traits like the ones that you mentioned they're they're all they're all going to be things that result from most likely you know hundreds or thousands of genes and we don't for the most part know what those are so I think the reality of
• 16:30 - 17:00 being able to do that kind of manipulation in human embryos is quite a ways off and what about soldiers so improving memory improving endurance just being used for purposes of things like building armies or making your armies more efficient again I think that's that's you know in the future maybe but it's certainly not coming anytime soon there are easier ways to improve your
• 17:00 - 17:30 armies than using CRISPR right now that's probably a relief what about the concept of either maintaining very endangered species improving on their viability or even the possibility of rejuvenating a species that's been lost yeah I think that's a really interesting idea I mean there's a number of people I know in academic you know research who are interested in using CRISPR to bring
• 17:30 - 18:00 Brack extinct species they're not talking about bringing back velociraptors by the way but but but thinking about bringing back things like the carrier pigeon you know which isn't that different genetically from birds that are alive now and where you could have the potential to rebuild genomes for organisms that have gone extinct in recent times so help us understand the concept and what the term means of a gene drive so if you talk about trying
• 18:00 - 18:30 to find a way to for instance eradicate malaria how would you go about that and what does that gene drive term mean well you know the idea of a gene drive has actually been around for quite a while I can remember thirty years ago or so when I was in graduate school people talking about the possibility of using technology to drive a genetic trait through a population quickly faster than it would ever happen by Mendelian inheritance but in those days it was it really was a fantasy we didn't have any
• 18:30 - 19:00 way of actually doing that and the thing about CRISPR is that this this provides the the means of doing that because if you if you couple a trait a gene that you're interested in introducing across a population to the the tool that does the insertion then you you have a way to introduce it very quickly and very broadly across a population of organisms that are reproducing rapidly such as mosquitoes and so this has attracted a lot of attention because we now have a
• 19:00 - 19:30 tool that could do things like maybe genetically prevent mosquitoes from spreading diseases through human populations it's recognizing that obviously one of the greatest vectors worldwide of disease that would be a huge tremendous accomplishment in terms of global health right so let's move let's talk a little bit about how you got to where you are now so as mentioned before so 2012 you and professor sharp NTA came up with
• 19:30 - 20:00 this realization that bacteria were using this strategy so but but after that discovery and along the way there were times when you were haunted by it a little bit and so you wrote an article in Nature in 2015 called my whirlwind year and I'll just quote you said by the spring of 2014 I was regularly lying awake at night wondering whether I could justifiably stay out of an ethical storm that was brewing around a technology that I had helped to create so
• 20:00 - 20:30 talk about what that was like initially as well as scientists phd's even physicians with all our interactions were not really trained for that kind of limelight so maybe you could address both of those issues a little bit yeah I think you know many people me included go into science partly because we're not gonna be in the limelight you know so we can sort of work away in our laboratories and work with students but but really not not receive public
• 20:30 - 21:00 attention for that for the most part and and so for me going through this kind of realization that you know this technology was going to be impactful not only in in research labs but also for the kinds of applications that we're discussing here and potentially for things that you know might really have ethical issues and challenges such as human embryo editing so in 2014 early in 2014 I was sitting in my office at
• 21:00 - 21:30 Berkeley I got a call from a reporter who said have you seen the latest paper out in the journal Cell which is one of the top science journals in our field and I said no and he said well it's from a group that has used CRISPR in monkey embryos and has created CRISPR edited monkeys and they seem to be fine they just have a you know at one gene tweaked and and I think it was that that event that article reading that paper that made me realize oh my gosh I mean
• 21:30 - 22:00 if people are doing this already in monkeys there's no reason to think that somebody won't try to do it in human embryos and that's when I started thinking about this a lot and really struggling with the the you know debate within myself about you know do I do I really want to get involved in this kind of discussion no I don't but I didn't really feel that it would be responsible not to so how do you make that day to day just cognitive shift from being you know and an eminent scientist who is
• 22:00 - 22:30 really focusing on one little part of of the plant kingdom and animal kingdom and then all of a sudden you're looking at at global topics of massive ethical proportions I mean I'd how do you make peace with that well the first thing I did was I had founded an organization that was kind of a virtual at the time called the innovative genomics Institute at Berkeley and UCSF and so through that
• 22:30 - 23:00 organization we convened a meeting that was held in the early part of I think it was January of 2015 with scientists some of whom had been involved in the 1970s discussions around the ethics of molecular cloning and we had a conversation for a day about human genome editing and human germline editing in which we debated you know is it would it be right for anyone to do that and if they did you know what would the issues be and the upshot of that was that I think everybody felt that you
• 23:00 - 23:30 know this was a very important topic that needed to be brought to the public attention so we wrote a perspective that was published in April of that year in science very very shortly before the first publication in a scientific journal of human germline editing in human embryos that was published in a in a you know in a science paper using using CRISPR and and then you know what happened next which is that you know there were a series of meetings that were held by different groups including the National Academies a report that was
• 23:30 - 24:00 issued in the spring of 2017 and these all were essentially calling for moratorium on any clinical use of CRISPR in human embryos meaning any use to implant an edited embryo for the purpose of creating a pregnancy and yet that clearly didn't stop a junkie from his work fortunately plenty of time to talk about that a little more with other other other guests in a bit so you've been at some of the most amazing academic hot spots in the country
• 24:00 - 24:30 Harvard Yale Berkeley but you actually it all started for you in Hawaii right so you grew up on the Big Island and one of the most beautiful places in the world unbelievable biological diversity so how did that impact you as you were moving forward in your career and then also with this discovery well I grew up in a very rainy part of Hawaii town called Hilo it's not what people usually think of when they think of sunny beaches and all that it was we had a very rainy very rainy town and I was
• 24:30 - 25:00 you know I didn't I didn't think too much about it at the time but I was really influenced by the native environment there and I was fascinated by all of the plants and animals that I encountered growing up that had clearly evolved to adapt to that Island environment you know help that I had moved there when I was seven so I had you know lived in Michigan before that so kind of a big change between Michigan and Hawaii and I didn't I didn't think about DNA in those days but I I definitely wondered about the chemistry
• 25:00 - 25:30 I always you know I had a great chemistry teacher in high school and so I started to wonder about the chemistry of these plants and animals and what had to be different to allow them to adapt to those environments so I I really credit that with my early interest in biochemistry so in an environment like that I mean you see the natural diversity of animal plant life in particular that's there so when you think about that now and you think about okay how much do we understand how
• 25:30 - 26:00 evolution came about to generate that world and how do we make decisions about okay now we have the possibility to manipulate that yeah it's it's kind of profound you know and I think that but I guess it's important to point out to everyone here that this isn't something that happened suddenly in a way you know I mean I think scientists have been thinking about manipulating DNA and manipulating the code of life for for a very long time and certainly in
• 26:00 - 26:30 agriculture you can go back millennia right people plant breeders have been working for a long time they didn't necessarily know they were manipulating DNA but that's exactly what they were doing more recently of course there have been technologies previous to CRISPR that gave scientists tools to manipulate DNA the challenge was that these tools although very effective and they got a lot of people excited they were hard enough to use that most labs didn't have access and that's really what CRISPR does it brings a powerful technology to
• 26:30 - 27:00 a point where it's you know it's just it's democra sizing because it's available to people you don't have to have particular expertise to use it and it's it's inexpensive and it works well so you've written about how you've had some pretty crazy dreams along the way when you realize the power of this technique dreaming that you met Hitler dreaming that you were inundated by a tsunami so obviously you're thinking about the fact
• 27:00 - 27:30 that there's incredible potential but also the other side of this a little bit so talk a little bit about that aspect yeah I think you know I've written about this dream I had about Hitler it was you know I was walking into a into a dark room with a figure kind of silhouetted and a colleague of mine said I want I want to introduce you to someone and and and they want to learn about CRISPR from you and the person turned around and as they turned around I realized that it was Hitler and he had sort of a pig face it was almost like this horror of
• 27:30 - 28:00 someone who maybe had already been sort of CRISPR you know and it was it was just it was really it sounds funny now but it was it was one of those terrifying you know wake up sweating kind of kind of dreams and I think for me it really stuck out in my mind because it it's really highlighted you know it sort of brought to a head a lot of the thoughts I had had about my responsibility and made me think yeah I really need to start publicizing this
• 28:00 - 28:30 people need to know about this technology and they need to think about how we're going to be responsible using it so before we move on to that a lot more and particularly talking about the the Chinese children and things so you know you've been involved in a fairly extensive and not just you because we all work for universities and universities have a lot of the intellectual property rights to any work we do in those universities so obviously you're at Berkeley it's a very strong state school this is a this is an
• 28:30 - 29:00 amazing technology and a lot of people are looking saying okay a technology like this is going to form big companies there's a lot of intellectual property here so I don't really want to get into the the whole issue of who's who's on what side with all this because it's all written plenty of places people can find it it kind of there's a fundamental conflict there because as a scientist you're going and you're trying to make discoveries and you want to share those discoveries in a way that makes the world better the academic community stronger everybody's knowledge by all of
• 29:00 - 29:30 us sharing we all grow and we all come up with ideas off of each other and yet on the other side you've got patents and potential profits and huge amounts of money I mean when I first came to Columbia the medical school was being supported by a single patent over many many years it was generating so much royalties and so so I mean how do you balance that in terms of saying look if this is my obligation to share scientifically but at the same time
• 29:30 - 30:00 okay now maybe somebody's gonna scoop me so what do you do with that well it gets down to you know why do we have patents right why do we have a patent system and you know if you'd asked me that question a few years ago I would have said I don't know but you know the purpose of patents is really to provide protection for companies that are going to invent investors you know who are going to invest a lot of money in products that will take potentially years to come to market such as therapeutics is a great example where it might take you know it
• 30:00 - 30:30 might take 10 years to develop a therapeutic and so the company wants to know that they've got some protection around that so when they bring their drug to market they can actually recoup money from what was invested and and make a profit and so that's the purpose of patents I think you know the challenge for patent the patent system with something like CRISPR and this you know CRISPR is not unique in this way right it's true for any technology that's kind of broadly enabling is that on the one hand as you said you know you want to you want to provide protection
• 30:30 - 31:00 for those companies because you want you know you want those companies to get involved in commercializing the actual application of the technology but on the flip side you want to make sure that the technology is widely available and in its and many hands as possible so that it can be made better and that it can be used to do all sorts of new things and I think you know the good thing about the university system right now is that you know the the universities really do make these technologies available to researchers and that's always been true
• 31:00 - 31:30 so right now even yes there's a patent dispute going on and and with CRISPR the good news is that it hasn't I don't think really embodies ability to use the technology certainly for academics they can get it very easily from a nonprofit organization called AB gene and that's been one of the reasons why it's taken off the way it has but it also brings up a topic that would come back to a little later which is that you know you're running a high powered lab you have
• 31:30 - 32:00 unbelievably talented grad students who are working like dogs in an environment where not just your line I'm saying globally where it's an incredibly competitive environment and you know it's very rare that people remember somebody who went first but wasn't a hundred percent accurate they remember who went first and that in and of itself in the scientific environment is fostering some of this need to be the first to be ahead and I mean how do you
• 32:00 - 32:30 even with your own students how do you get the message across to them yeah you know it's it's really important to be early but it's more important to be accurate well I say exactly that basically I tell them that you know it's a it's most important that we are correct in our work that we're scholarly in our work and we work as efficiently as we can but you know the primary purpose of what we do is to is to double and triple-check ourselves and be scholars about what we're doing so one last point before we move on to
• 32:30 - 33:00 the topic of gene editing and particularly human gene editing can you help us understand a little more about in humans germ cells versus somatic cells what happens when you apply gene editing technologies to one set versus the other and the ramifications of that yeah that's really important to understand so somatic cells are cells that are fully developed and when edits are made to the DNA of those kinds of cells then they only affect that one
• 33:00 - 33:30 tissue or that one individual or that could be could be stem cells in an individual that develop into a certain tissue type but but but it's quite distinct from germ cell editing that's where we reading DNA of eggs or sperm or embryos where the genetic changes become part of the entire organism and those changes are heritable they can pass the be passed to offspring and that can be done in plants it can be done in animals and it can be done in humans so so germ cell things
• 33:30 - 34:00 are going to be passed on generation to generation so so looking at some of the things we talked about before so single gene disorder sickle-cell muscular dystrophy you would want to target what well there we would want target we would do somatic cell editing but we would do it in germ cell and not germ cells but stem cells taken from an individual but they wouldn't be creating heritable changes and in cancer or HIV type setting same thing right because you're just looking to target something in a
• 34:00 - 34:30 somatic cell population right whereas if you're trying to for instance when we'll talk more about in a minute but what was actually done in China was to do it well to do germ cell editing so that was editing in embryos where the genetic changes become part of the entire organism the entire person in that case so when you're using this technique is it perfect what's the fidelity how often are there genetic mistakes that happen when you're
• 34:30 - 35:00 trying for a result and what are the potential ramifications of imperfection in the biological system right well you know the remarkable thing about this this this tool is that it's it's had to evolve to be pretty good at what it does because if it makes a mistake in a bacterium then it can kill the bacterium so that's a pretty strong Selective pressure for accuracy but that being said of course is not perfect and there are you know definitely are potential opportunities for it to make mistakes
• 35:00 - 35:30 and make create off target edits and that's been quite thoroughly investigated by by scientists I think one of the interesting things that's happened over the last few years is that people have gotten better and better at using the technology and today it's possible to do things like limit the length of time that Castine is in cells and the the amount of it in cells and also to select the target sites in DNA carefully so that they don't close match anywhere else in the genome and by
• 35:30 - 36:00 doing those kinds of things it's now possible to make really very accurate genome edits using this tool as well as by using versions of this protein that have been engineered in a lab to be even more accurate so I I currently I think that I the way I think about off target editing is something that needs to be monitored carefully but it's probably not one of the major bottlenecks for using it in the future even in the clinic so let's move on now to a topic that many people are familiar with through the popular press as the video
• 36:00 - 36:30 earlier said November 2018 I think it's fair to say that a lot of the world was shocked to hear and see the news of huijiang Cui's work in China with as you were saying with germline gene editing and two children and so first let's have a short video describing that it was a birth announcement that shocked the world to beautiful new Chinese girl named Lulu and Alana came crying into
• 36:30 - 37:00 the world as healthy as any other babies a few weeks ago Chinese biophysicist ha Jean qui workin largely in secret had used CRISPR to knock out a gene called ccr5 in too early human embryos then returned the embryos to their mother's womb ccr5 plays a key role in HIV infection and the girl's father was HIV positive huh said his motive was Noble as a father of two Gor I can't think of
• 37:00 - 37:30 a date were beautiful and wholesome for the society then giving another couple a chance started looking feminine but the scientific community did not cheer at the International summit on human genome editing that huh attended shortly after the announcement the reaction was shock and condemnation will be commercial but I believe family need this technology
• 37:30 - 38:00 and I'm willing to take the criticism what thing so joining us now for this part of the discussion is a bioethicists physician and research scholar from Stanford University who also happens to be a friend of hood Jiang cui from his time at Stanford please welcome William Holman also joining us is a futurist and
• 38:00 - 38:30 a member of the World Health Organization Advisory Committee on human gene editing he's author of the recently released book hacking Darwin genetic engineering and the future of humanity please welcome Jamie Benson so bill let's start with you so hood John cui goes by JK so we'll just refer to him as that because it's a lot easier for me and he left Stanford went to China where he was carrying on this work
• 38:30 - 39:00 you guys were friends there while you were there and you've been in communication with them so how much either directly or indirectly did the scientific community know about what he was actually doing well I actually first met JK at the meeting that Jennifer and I organized in January 2017 subsequently he emailed me two months later and said I'm coming through Stanford could I talk with you so I I had nothing on my calendar that afternoon fortunately so we've met for lunch and talked much of
• 39:00 - 39:30 the afternoon and then subsequently came back several more times and we talked in great depth but I I did not understand that he was pushing quite so fast now he's it I think to back up a little bit he was under a lot of pressure in the environment he's and he he works in Shenzhen and there is this concept called Shenzhen speed everything's happening fast there's lots of push for scientific discoveries and young scientists in China under pressure as a are elsewhere but I I realized very
• 39:30 - 40:00 quickly that he did not have much of a background of thought on ethical issues so I was trying to get to know him a little better seed in ideas and concerns but in the end he went faster than I realized and I did not know that he hadn't planted embryos although the last time I met him I strongly suspected it and Jamie you've written a book on genetic engineering which obviously covers gene editing as part of that so CRISPR it's easy relatively speaking for
• 40:00 - 40:30 talented scientists it's inexpensive is that what makes it dangerous well it's dangerous and it's incredibly exciting you're right my book is on the future of human genetic engineering and when you think of if you think of genetic engineering as a PI gene editing is a slice of that pie and CRISPR is a sliver of that slice and CRISPR is incredibly important and revolutionary and it's going to change a lot of things but we are part of this process of really a genetics revolution that other people have mentioned it's going to change a
• 40:30 - 41:00 lot about our lives it's going to change the way we do healthcare from moving from a world of generalized medicine based on population averages to precision health care to predictive healthcare and life and it's going to change a lot of things and including the way we make babies and the nature of the babies we make that's going to bring real dangers and we need to be mindful of that and it's going to bring real wonders and we have to be open to curing a lot of these afflictions that have plagued us for millennia but using your PI analogy it's kind of a pie in an oven
• 41:00 - 41:30 that's cooking with uneven temperature right because I mean Christopher's a pretty good piece of pie and the rest of the pie may not be as readily applicable or as broadly applicable I would disagree with that because as we understand and increasingly unlock the secrets of the genome we're going to be able to make a lot of interventions and one I talked about predictive healthcare and that's going to touch everybody here in many more significant ways than CRISPR at least in the near term what
• 41:30 - 42:00 will will touch us it's going to change the way we procreate moving increasingly and over time towards procreation in vitro rather than them through sex and so there are a lot of pieces a lot of them are moving quickly and they're going to touch us in a very intimate way and CRISPR is incredibly an important example of that we're going to back us up a little bit yeah so obviously Jennifer you know more about this technique and probably anybody in the world JK's a biophysicist not a geneticist he
• 42:00 - 42:30 was able to learn the technique to get the technique to work so how hard is it how hard is it to learn for one of your average students how much wood how difficult would it be for any one of them if they weren't they weren't working in your lab they're working in something totally far afield may say you know what this would really help me I'm going to learn this technique what's it gonna take well I mean today you can go to Amazon and you can buy a CRISPR kit to use it in bacteria not in human embryos but right so it's you know it's something
• 42:30 - 43:00 that we you know in my lab at Berkeley we have every summer we have summer students that come in for ten weeks and you know nowadays you know they come in there they're typically editing human cells that are cultured in the lab within a few you know a few weeks so they you know I can learn it very fast I think with respect to JK what I would say there is that you know I was sitting after you know this announcement was made in Hong Kong we were all there bill was was there and you know we were at this meeting and and
• 43:00 - 43:30 I was sitting with one of the the meeting organizers and he said to me well you know two things are clear from this announcement one is that it's really not very hard to do this because JK is not a you know he's not a specialist he doesn't work in an IVF clinic he doesn't work with human embryos himself but he like you said he figured out how to do it he got collaborators to help him and the other thing is it's really very hard to do it well and that was true because the Dean when you look at the details of how the
• 43:30 - 44:00 editing was actually done in these girls you know the changes that were made were in fact not changes that have ever been seen before in the human population and have not even been tested in animals so that's kind of what makes it very dangerous is that it's a tool that's relatively easy to use very hard to do it well so that brings up a logical question for all three of you coming from very different perspectives you've got a relatively easy tool or somebody can say I got this without as you say
• 44:00 - 44:30 really being expert in it so even if the global science community decides you know what we're gonna regulate that how do you ever enforce a regulation where somebody can go learn it through Amazon well maybe Jamie wants to come in on that because the World Health Organization you know that was actually the first to step up with an international team right yeah so it's such an important question and the scientists actually led by Jennifer and Bill and others have done an incredibly
• 44:30 - 45:00 great job of being responsible but what we are talking about is the future of life and as wonderful as the scientists are it can't be just up to the scientists this has to be regulated in many ways on a national level and on an international level on a national level every country needs to have a robust regulatory infrastructure and the u.s. is pretty good we have a dysfunctional healthcare system more broadly which makes things more complicated the UK I think is in my mind the gold standard or
• 45:00 - 45:30 a gold standard every country needs to have something but then how do we think about global regulations and we need to come together the World Health Organization is trying to do that and as important as that is it's really a drop in the bucket and we've seen how even with the high level of attention we have on issues like climate change it's been really difficult to get international consensus we're going to need that kind of big international push to bring everybody to the table including the scientists to say how do we have a regulatory infrastructure that at least
• 45:30 - 46:00 sets some limitations it can't be a genetic free-for-all and we can't have restrictions that impede the very beneficial development of these technologies how do we find that balance and how do we bring everybody together to try to get there so bill obviously you're bioethicists and one of your many skills and talents so if we think of the analogy of the w-h-o kind of like the United Nations countries can opt out so how do you think about this problem as a
• 46:00 - 46:30 bioethicists in terms of how do we tackle it well I think the first thing to say for that and and this is one of the reasons that jennifer and I started the programs that we we initiated is that we have to we have to have a sensible approach to this that doesn't undermine the great positive good that can come from it there are perhaps as many as 10,000 known genetic diseases single gene diseases 95% of them have no
• 46:30 - 47:00 treatments no cure whatsoever it's an amazing opportunity for medicine but if we if we hype this and frighten people maybe that gets the dialogue going but what we have to do is approach it very sensibly the CRISPR and related technologies are really more a revolution in the lab than they are germline genetic engineering which would I think will ultimately be moderately a fringe application the the real revolution is in understanding
• 47:00 - 47:30 biological process and this has provides fantastic tools the 20th century was about molecular biology the ingredients that that make up the organism in the 21st century it's shifting to developmental biology and this tool gives us a chance to probe and alter and examine how natural development takes place both healthy and and pathological development and then we need to very sensibly assess what are
• 47:30 - 48:00 the potential tools including the potential dangers of this and I think that's the way to go carefully not hyping it but also taking seriously the way it might be Mis applied what about the concept so you all have touched on a little bit differently between you but Jennifer brought up the concept that in the in here in the United States you could never do a human trial unless you had a pretty good idea of what your predict is going to happen what the genetic changes are going to do
• 48:00 - 48:30 preferably with an animal model first very strict guidelines in terms of institutional review boards for human trials informed consent all of those issues that are such mainstays in our scientific community but maybe a little more relaxed and when you combine that with scientific pressure and competition to succeed it seems like it like like it's a setup for a maelstrom what do you what do you do to dampen that and and to take that on globally maybe if I can
• 48:30 - 49:00 just say the first thing that our World Health Organization committee did was call for the w-h-o to establish a global registry for anyone doing germline edits edits to any germline cell and so at the very first step that we need to do is to try to make sure that nothing or as little as possible is happening in the in the shadows but then we need to try to build norms I mean there are a lot of things that could happen that don't happen and one of the reasons is that there are global norms of what is and isn't okay and and this is so new the
• 49:00 - 49:30 challenge we're facing is that the science is advancing exponentially but all of the systems that we're going to need to regulate it wisely don't yet exist and that's that's the race that we're in bill what are your thoughts on that and also particularly in relation to JK because you know and so you know I think it's easy for somebody to look back and from afar and say oh you know what this there must be an element of bad science here or because of the fact that it's not the way we would do it but well I mean what was his reputation at Stanford as a
• 49:30 - 50:00 scientist when he was there as a grad student very intense he was focused in the lab when went on when we were having lunch together he was talking about how he had to move forward because there's so much suffering in the world and I said yes JK but carefully and I I said there's a lot of good in nature a lot of harmony a lot of beauty and I mentioned the redwood trees that are in the back of my backyard and that cool I have redwood trees in my backyard and he looked kind of blank and I I said have you never seen a redwood tree and he said no and so I said oh come on
• 50:00 - 50:30 we're gonna go look at a redwood tree I took him for a walk in the redwoods he just loved it but you know what it indicated me was while I was at Stanford he the redwood trees are five minutes behind Stanford and he was in the lab the whole time working working working and we need a broad view of of life of nature a reverent and respectful appreciation John Muir said that when we try to pick out anything by itself we
• 50:30 - 51:00 find it hitched to everything else in the universe and that's a really crucial concept because none of this is going to be as easy as it's portrayed in the journalistic accounts it's going to be required subtlety great care we don't want to do any harm either materially physically but we also don't want to upset the balance of normal human life that one of the things jennifer and i realized right away was we need to address this to the to the whole human
• 51:00 - 51:30 species the whole human family and all of its individual diversity and cultural diversity that way we can appreciate what it is who are operating on we don't want to turn procreation into production we don't want to radically alter the meaning of Medicine we don't want to create social problems in the process and we don't want to do ecological disturbances that are damaging to the setting in which we live and you know a deep appreciation scientifically for who we are and where we've come from
• 51:30 - 52:00 includes the fact that that we are fine-tuned and complementary to an existing natural world and if we change that whole natural world so dramatically that we don't recognize our place in it will be losers that essentially even if we gain medically so but that brings up an interesting point your training obviously top-notch hyper-competitive students I'm sure postdocs in your lab must be highly sought after so are people coming after your postdocs saying
• 52:00 - 52:30 hey you know bacteria aren't really that much fun why don't you move up the food chain a little bit I mean I mean what are you noticing and what's what's what's the ear to the ground now on that well a few years ago I wrote a book called a crack in creation with a former graduate student Sam Sternberg who's actually now colleague of yours at Columbia and and and Sam you know we one of the things that we talked about when we were starting that book was a meeting that I had had with somebody who came to
• 52:30 - 53:00 me and Berkeley and and was actually had approached initially people in my lab and then eventually got to me but wanted to was asking people in my lab if they could help her to have a crisper baby because she wanted to start a company and she want to be the first person to to bare a crisper chris bird baby and and this is this is not this is one sort of isolated example but you know we pretty regularly are approached by people maybe not quite that extreme but
• 53:00 - 53:30 people who want to have access to CRISPR they want to know how to get into clinical trials they want to understand better the technology so it's a challenge and I think you know I try to work with my students to not only you know focus on doing great great science but as bill said you know I think it's really critical especially now that people take take a more holistic view of their work and especially the kind of work that we're involved with that does have these much much broader implications bill juice do you remain in
• 53:30 - 54:00 touch with JK and do you have any idea where he is right now because at least you know the word and the popular press is that he's lost his job and nobody's heard from him for a while and the China as now passed new rules just came out recently in the news and do you happen to any continued contact with him after the jeans summit he emailed me and asked if we could talk and over through January December in January we had numerous long conversations two or three
• 54:00 - 54:30 hours I heard the whole story I confronted him on all the questions about what she was being criticized and I I have had some contact with JK as to your specific question I I'm just really not at liberty to say what the situation is we take a right now but I'm worried about and hoping that he doesn't suffer more opprobrium than he actually deserves because he is to a certain extent a product of a global scientific culture he did not do
• 54:30 - 55:00 what he did alone people knew about it it it wasn't in secret it was you know like it was sort of in line with what people do except the seriousness of it demanded that he'd be more careful but quite a few people in the United States and people in China knew what he was doing and yet he did not stay in in conversation with a larger scientific community which I think was a mistake one time when we were talking I said to him I felt like he was using his own
• 55:00 - 55:30 judgment too much and so I said well JK the strength of American society and Western society is that is the dialogue that we we conduct together that we complement and correct one another's understanding and I cited for him the Gettysburg Address of the people by the people for the people and and after after that I sent the Gettysburg Address in an email I sort of wonder what the Chinese authorities thought about that
• 55:30 - 56:00 but you know I I was saying to John Cohen a writer at science magazine that I think the biggest problem was not JK's he wasn't just seeking fame and fortune I made that maybe part of it but it's part of it for a lot of scientists but he was also very well intended when the full story comes out people are going to be amazed by what he actually wanted to have happen here but the biggest problem as I said that John Cohen was it it was sort of a
• 56:00 - 56:30 failure of democratic process he needed to stay in conversation he needed to to be more transparent and and this is such a monumental moment that it needed to be one that was adjudicated by the deepest wisdom of the human species so building on that Jennifer you've obviously been very involved since 2015 and then 2018 with the global response to this so can you comment on both you had at the earlier introduction there was a slide
• 56:30 - 57:00 showing that I think there were 18 scientists in nature who all were backing a moratorium in this area and can you talk about what your feeling is on how we best handle that is a moratorium an answer well you know we we called for effectively a moratorium although we didn't use that word back in the spring of 2015 and that really you know started the the process of these international groups triggered by the
• 57:00 - 57:30 National Academy team putting together international summits on this topic and a report that was released in the spring of 2017 by that group which again without using the word moratorium effectively called on scientists globally not to use genome editing in the human germline in human embryos clinically until and unless it had been thoroughly vetted both scientifically and and societally and here's where we
• 57:30 - 58:00 are today so to me to call a note for another moratorium sounds kind of to me a little bit ineffectual and I think it would be better to actually invite a more open discussion I think that many people think that there are going to be opportunities at least on the research front and maybe someday in the future clinically as well to learn from this experience and the kind of research that a few labs are conducting in human
• 58:00 - 58:30 embryos as well as an obviously many other kinds of embryo systems and animals so for I would I would rather not see that conversation shut down and when you call for a moratorium effectively you're saying we're not going to do that and it's very hard to then continue an open conversation I feel and I don't I would like to not see that conversation shut down Jamie your thoughts I agree I had a piece on this in the Financial Times I totally understand why people are concerned I
• 58:30 - 59:00 think we all need to be prudent we all need to be careful but to create a moratorium that first creates a set of stakeholders that you're going to have to convince people to end the moratorium and so that's going to be really difficult and what we need to do is to apply our best values in making decisions in cost-benefit analyses and so one of the reasons why I differ from Bill I actually think that ho-chunk way is quite a villain and the reason is because the first step in applying genetic gene editing to a human embryo
• 59:00 - 59:30 of a child taken to term needed to be totally defensible it needed to be transparent it needed to you need to explain why the intervention was made and by doing that in a race for glory and theirs in his eye are be application which wasn't even to his primary hospital there was all of this this garbage about bringing glory to China and so in this race he didn't just potentially harm these two these two now little girls he undermined global
• 59:30 - 60:00 confidence in using this incredibly powerful tool to actually do good if the first step had been extremely careful well-thought-out public transparent with a target that everybody agreed made sense most likely to eliminate a potentially deadly risk that would have been a much better first step I think ho-jon Quay has harmed us on the other hand he's raised the alarm that we have a big problem and certainly the w-h-o committee venom on probably wouldn't exist had this step not been taken so
• 60:00 - 60:30 let me ask a hypothetical for any of you I mean he did this in November of 2018 given the global climate scientific pressures and everything else without a worldwide moratorium how long do you think it would have taken somebody else to do it let me just respond to the idea of the he's a villain okay I agree with all your criticisms of them but he was 34 years old he is under a lot of encouragement from other forces around him and he believed I mean let me tell you this is a humble
• 60:30 - 61:00 guy he grew up in a very poor village he told me that when he wanted to invite the girl out that later became his wife he was embarrassed to invite her out because her family owned the restaurant so this is a guy who's come up all the way from the very most rural poverty up to the highest reaches of of global science and I think that's why he needed to stay in conversation but I would not label him a villain but having said that I also talked with him about where he
• 61:00 - 61:30 was going and afterwards why he went so fast and it was clear to me that as one after another the statements that were being made publicly for example the Nuffield Council issued a report and I sent it to him through a popular article and the reference to the report and the the popular article said Knuffle council approves germline genetic engineering including possibly enhancement some day and JK wrote me back excellent
• 61:30 - 62:00 female excellent he saw the global society coming into keeping with what had been called for in the National Academies moratorium and one after another he felt like he was checking off the boxes and I think he was wrong and I tried to tell him he wasn't doing it adequately but having said that after the fact I asked him if he would have done what he did if there had been a moratorium and he said no he wouldn't have done that it was a mistake and I'm
• 62:00 - 62:30 not I'm not taking a position on the moratorium I'd like to hear the arguments more thoroughly I'm not a political scientist I'm I'm a physician and a scientist and ethicists but I I still think that there are reasons why we might consider a moratorium and that's because jakey's not the only person out there who would use these technologies and appropriately well that's why I was asking the question right because it's somebody told me a long time ago if you walk around with a really good scientific idea for other
• 62:30 - 63:00 people in the world minimum have it it's just who's working on it and if you go to the Society for Neuroscience and the first time you go there and there's 25,000 you know I got it and you walk up and four people have the exact same poster at the exact same time none of whom you've ever met and so in a situation like this the response to this as you all are saying you can call him whatever you want but the response is what's raised awareness and maybe in some ways caused everybody to take a step back and say
• 63:00 - 63:30 hey wait a minute we as a world we need to be looking at this and the question is whether or not as a global community we're going to be able to enforce that and I think that still remains but I do I want to before we move on I want to ask you what any of you also do you think he did me harm what do you think they already think are the chances so two questions first off because Jamie in in speculating and and saying your opinion on him you said you know he didn't tackle a big enough problem but a lot of people would say well he was trying to keep his keep
• 63:30 - 64:00 daughters on a family with an hiv-positive dad from getting HIV so what's a big enough problem yes so that's wrong actually so certainly there were parents where the father had HIV and the mother didn't there are lots of ways to have that scenario and not have a child who is born with with HIV so there's Washington sperm there's a lot of things so what he was doing even by his own admission was an enhancement and that's so certainly if the the divide between therapy and enhancement we're
• 64:00 - 64:30 talking about revolutionary gender genetic technology this is not always as clear as people would like it to be but this was a pure enhancement and the chances that it did harm nobody really knows yet and there's been very little transparency so there's a chance it helped something there's a chance that he did nothing and if there's a chance that it did considerable harm and that that this first step into gene-editing human embryos is so unknown that's why I think that this was such an unfortunate first step you know you might show the
• 64:30 - 65:00 slide that I I have of the picture I have of the message he got from an infertility clinic yeah that would be great I think that really opens up the I'm gonna read the text yeah okay so congratulations on your recent achievement of the first gene editing baby delivered by your application I am the business directors assistant at fertility and gynecology Center in Dubai our embryologist is interested in partaking in a course regarding CRISPR
• 65:00 - 65:30 gene editing for embryology lab application does your facility offer this type of course I sort of think that there is momentum in that direction you know I mean I've been approached by people in the US who are interested not you know with sort of the same sentiment as you just heard in that in that email so that that person is certainly not alone and and I think there there is a lot of interest in human embryo and human germline editing and it's not always for the right reasons in my view
• 65:30 - 66:00 you know it's for you know clinics that would like to make money selling this to people and and I don't know how we stopped that I think that it's very important to have groups like the the WHO and and the National Academies Forum put together that will put forward what I think ought to be very very specific and very restrictive criteria for anyone that in the future wants to use or even contemplate using genome editing in in
• 66:00 - 66:30 you know for the clinical use of editing human embryos and then you know how you enforce that is it's a very difficult challenge I'm not sure how you do that I think it has to be it has to begin with inviting I think an open global discussion I think it has to engage with not as you said Jamie not just scientists and clinical clinicians but also other stakeholders and you know I think we probably all certainly bill and
• 66:30 - 67:00 I hear from people almost daily who have genetic disease and their families who are desperate and they want are trying to get help any way that they can including with CRISPR so we need to be also respectful of that and as you said the desire to see the technology advancing as quickly as possible but without doing harm and that's you know that's the medical oath and it's always that I think of the challenge that we face yeah and we need to be honest of where this is going and more and more
• 67:00 - 67:30 humans forever are going to have kids through IVF more of us forever are going to be screening our embryos prior to implantation and we as a species are going to be gene editing our embryos prior to implantation and maybe that's in ten years maybe that's in 20 years but I it's unimaginable that a hundred years from now we're going to be making babies the way that we that we do it now and so we can argue about what the time frames are going to be but what what I think we need to do is one have an inclusive really as a global species
• 67:30 - 68:00 wide dialogue on these technologies because they are going to touch all of us we need to try to build norms and standards and regulations and frameworks so that we can do the cost-benefit analysis because if we just say we're holding the line that these technologies can't be applied in human procreation that line will increasingly be increasingly being defensible it has to be is what are the better applications and what are the worst applications and how can we create an infrastructure that facilitates the good stuff and minimizes the bad stuff I assume when you speak of
• 68:00 - 68:30 the normalization of IVF and the commercialization of reproduction that you're thinking in terms of more than then disease treatment but in terms of human enhancements as I said in my in my remarks I think it will be very very difficult to keep a clean divide between what is therapy and what is an enhancement because it all exists within the context of us you know certainly it's hard sometimes to even define diseases there is a disease in the
• 68:30 - 69:00 textbooks of the antebellum South called Dre Peter mania which meant this a slave that was had a tendency to run away so there's cultural construction of disease categories having said that you may be right people may buy into efforts to enhance their children but I think they're making a terrible mistake every time I speak publicly somebody asked me if we're not heading toward a great divide the rich on the one hand biologically enhanced and the poor on
• 69:00 - 69:30 the other side and I my comment is that at least for the next few decades it's going to be the children of the poor that are the fortunate ones because their parents want experiment on them well so let's let's take it back a step from that not quite all the way on that extreme because we do have a health care system that let's face it it is a two-tier system and we have a huge
• 69:30 - 70:00 amount of our GDP we're spending on health care when you start talking about screening embryos for genetic traits that may predispose to disease whether or not they enhance these are going to be expensive technologies companies are going to invest not millions billions of dollars to make this technology work so how do we keep it from becoming something like becoming a 5 foot 2 volleyball player at USC that you can only do that if you have a lot of
• 70:00 - 70:30 resources how do we actually because I think saying oh well you know people are going to sign up for experimentation there's a lot of cultural aspects where people don't seek health care in a system where they either can't afford it or they're confused by it so how do we make this if it becomes a technology that we find a globally accepted use how do we make it a technology that becomes accessible well I think I think to me it's important to address that question
• 70:30 - 71:00 with respect to somatic cell editing because that's honestly at least for any kind of applications in humans that's the one that's going to be you know here and in a reality much sooner than any broad use of human germline editing and for somatic cell editing that and again that just means making changes to an individual that are not heritable they're you know I think these questions of access cost you know sustainability
• 71:00 - 71:30 they all come into play because and we all read in the media now about you know new treatments and they're not gene therapies necessarily but other kinds of drugs that are just you know so expensive that you think you know who is really going to be benefiting from this except for the very very wealthy and and so I increasingly am asking myself you know how do we ensure that this technology as it does move forward in the clinic especially for somatic cell use for rare diseases and things
• 71:30 - 72:00 like that how do we ensure that it is accessible and affordable and it's gonna again it's gonna require a lot of you know pulling together of different interest groups to get that to happen it's really it's a question of values and systems if we have the values that have the incredible health disparities that we either have here in this country or between everybody in this room and average person in Central African Republic those if those are our values now those are the values that we're going to bring into the future if we want to have better values realized
• 72:00 - 72:30 through our systems let's articulate what those values are and look critically at our systems so they can be realized I agree with this significance of the values and by the way suffering is not the only value that goes into ethical equations there are other principles involved it's it's not like the argument from suffering has no bottom if you you can argue for anything a compliment to that sense of values is a realistic scientific appraisal of what goes on at the level of genetics I was
• 72:30 - 73:00 very good friends with Nobel laureate baroque Bloomberg I taught a course with him and he used to tell our students over and over except for very obvious disease genes there it isn't like they're good genes bad genes genetics is a very very fragile balance where a species that has millions and millions of years of field testing were packed for all kinds of weather all sorts of circumstances that we can't see in this current environment there's lots of reasons to be cautious here it's not
• 73:00 - 73:30 like genes are like Legos or or mr. Potato Head where you just change a trait by changing a couple of genes genes interact with one another so we need to have a very realistic scientific appraisal of what we're doing certainly there's plenty of work to do for the next half a century or a century before we even ponder anything with regard to genetic enhancements so that brings up an interesting point yeah you bring up the point that you know natural selections been doing this for as long
• 73:30 - 74:00 as we can count time maybe even back in Brian Greene's black holes and so in the situation here you've got a you can call it survival you can call whatever you want but these things are being biologically tested in a system where you don't have to know all the answers the system figures out the answers but now we're talking about an ability to return what we know about the answers and so how do you balance that so so we are as a species for the
• 74:00 - 74:30 first time taking these powers that in the past we have attributed to our gods the ability to recast life and our knowledge of these unbelievably complex biological systems is minuscule is miniscule and yet now we have the ability to go and and muck around and that's why we need a just an enormous level of humility and if we had that humility we would follow the timeline that bill just articulated let's wait a
• 74:30 - 75:00 century and see how we apply things but we are this crazy group of monkeys who climbed down from the trees and we're not going to wait where this hubristic species that grabs on to these technologies and now it's not like in the old days where you have your nuclear power and you need a small group of people supported by the state I mean Jennifer I'm certain we'll win a Nobel Prize for developing the CRISPR caste 9 system I don't want to jinx it but good luck the people who are the people who
• 75:00 - 75:30 are applying it you just get an a-minus in your high school biology class so these technologies are out they are out in the world and this crazy group of primates us we are going to start using it we need to be cautious we need to build systems we need to try to build norms that can make sure these technologies are used in the most helpful and positive ways possible but this this is it's out of the bag and that's that's the challenge that we face
• 75:30 - 76:00 but but it's such a challenge I mean Jennifer you're working in bacteria you find out that a system that the only thing on the planet lower in life than a bacteria which is a virus has been using to try to take over bacteria and bacteria have a defense mechanism that's been there for probably a million years and you find it in 2012 and we say aha we can figure out how to use it but it reminds me of when I went to medical school my dad said the great thing about it you're
• 76:00 - 76:30 gonna learn all this wonderful stuff the bad thing is two thirds of its going to prove out be proven to be wrong you just don't know which two thirds they got to learn at all and the assumption that we have the knowledge I mean it's it it's it almost defies logic and so so what do we do with that I mean I mean you're talking about that in 10 or 20 years everybody's going to be making designer embryos and Bill saying we got a half a century of hard science left to do I
• 76:30 - 77:00 mean maybe I do maybe I'm gonna well I think I think what we'll see is this is my prediction is that I think over the next couple of years we'll see a few clinical trials getting going for things like sickle-cell anemia and we'll see how those play out hopefully they do no harm first and that they actually are beneficial to patients and I think with that kind of progress that will you know
• 77:00 - 77:30 we'll start to see that we'll start to see other diseases of that type that are monogenic it caused by a single gene you know being treated increasingly using genome editing and and it'll largely you know kind of build from there and with respect to human embryo editing it's hard to know honestly I can't really predict how that's going to play out at this at this moment there certainly is a lot of interest in it that's for sure and you know I think that research on
• 77:30 - 78:00 embryos will of course continue one thing that I said earlier but I just want to point it out again and that is that in my opinion the technology is just not suitable right now for use in embryos and I think ho-jon Cui's experiments actually showed that you know very clearly it's just not ready for use in embryos and I couldn't tell you when it will be but certainly more research is needed and I don't think it
• 78:00 - 78:30 needs to be done on human embryos I think it could be done on other kinds of embryos to understand how a manipulation works in those settings so to me I think a lot more research needs to happen for that kind of use and in the meantime we should focus on where it's really going to have an impact clinically which is in somatic cell editing as well as in all the other kinds of applications like in you know controlling mosquito-borne diseases and and improving agricultural products around the world where it's gonna have
• 78:30 - 79:00 frankly a much broader impact than any kinds of the applications we've been discussing in biomedicine so we're gonna because we're running a little bit short on time so we're gonna finish up with one question that Brian brought up at the very start these editorials and New York Times that are looking 25 50 years down the road and writing back so each of you you each get to have your editorial 25 years down the road saying this technology CRISPR technology so a
• 79:00 - 79:30 as big an impact as we're predicting now even bigger smaller and in the overall huge spectrum of where we are is it going to give us a better future a more complicated future or a more dangerous future so let's start we're gonna first Jamie so first we have CRISPR as this it's our best gene editing tool it may not be the last word in gene editing so gene editing is going to be an increasingly important part of our lives
• 79:30 - 80:00 and I think it's going to be bigger in many ways but it won't be all the ways that we are predicting I mean that and it's going to change a lot and our culture will change because we introduce new ideas and everything I mean when you the first IVF baby everybody was so stunned this is not natural and then things normalize so this is going to normalize the technology is going to continue to get better as it has it's hard to imagine that it was six years from Jennifer's discovery to hoe junk
• 80:00 - 80:30 way I mean that's really nothing and given that we're the technological change is often happening onto this J curve 25 years from now that's a long long time so I think we're going to be using it it'll be new ways it will be signaling altering the world within and around us but it'll be different from what we're imagining though and the potential for nefarious uses global terrorism essentially is huge for nefarious uses and it's even greater for
• 80:30 - 81:00 positive uses uses I am an optimist I did we certainly have some bad humans knowing in this in this room but I think in general we have a drive to use technology to do good thing I think the smartest people in the world are not terrorists they are people who are thinking how can we use this technology to do good and I think that we will but if we don't have an honest conversation now about the downsides then it's the rest of the world is going to have that conversation and it's going to dominate
• 81:00 - 81:30 our discourse and we can't let that happen and we need to do it by talking about this by having an engaged global dialogue and by being honest about the harms and the dangers and working to minimize them so I would just like to know you are a futurist yes and being a pessimist futurist might be a short career path you know you just get depressed and crawl into a hole and it ruins your career so bill so the the great physicist Niels Bohr said we are both spectators and actors in the drama
• 81:30 - 82:00 of existence and the way this program opened was to speak of the emergence of human intelligence operating over and against nature really amazing considerations the Roman physician Galen said the physician is only nature's assistant and I think we need to pay attention to that nonetheless John Stuart Mill said if nature and man are both the works of a being of perfect goodness that being intended nature as a
• 82:00 - 82:30 scheme to be amended not imitated by man so we have to find our way who we are and what kind of a species we are that's not just a simple matter of of scientific prowess and possibility it's a it requires a broad fundamental examination of the source and significance of the natural world the meaning of our individual lives and our collective lives as a society and as a species and in that process when we
• 82:30 - 83:00 blend those two I think we over the next 25 years come to a far deeper understanding one might even say reverence for that order of that amazing natural world that Jennifer grew up in that we as physicians see operating in the imminent powers of health that emerge from the natural human body I think over this course of time this fantastic new tool will be applied for a great deal of good and the complexity of
• 83:00 - 83:30 the of the misuses of it or most of the misuses of it will prevent us from misusing it nonetheless I think we're going to have to have a very comprehensive view that goes beyond science to include ethics and broad social discussion and I think the watchword there is it in every way we should we should follow CS Lewis's admonition that we should answer all of our problems with more love not less
• 83:30 - 84:00 love so Jennifer first off I'm not going to jinx you by saying you're gonna win a Nobel Prize but I will speak on all of our behalf for thanking you together with Professor Sharpe NDA for this discovery and we all do hope you in it and you do get the last word we're twenty five years from now you're writing your editorial all right well 25 years from now I have to say I think what will happen is that we were
• 84:00 - 84:30 going to have technologies that support genome editing in ways that currently we find to be bottlenecks and I'm talking here about delivery we spoke a little bit about that how we introduce these gene editors into cells and tissues right now that's a big challenge whether it's in humans or plants or anything else so I think that's an area where I suspect over the next 25 years there will be breakthroughs that will also be incredibly enabling for genome editing and the other thing is that that you
• 84:30 - 85:00 know I think we're gonna continue you know you're just looking at the rate of advancing advancements made in the technology of genome editing just over the last few years I think that pace of that is not slowing down so you know we're gonna see incredible opportunities to do things even better than we can do them today and that does raise this challenge of how we're going to use this in a way that is maximizing good and
• 85:00 - 85:30 minimizing any any dangerous or unethical uses and I keep coming back to the only way that I think there's a opportunity there is we have to be really proactive about catalyzing these discussions and inviting people to get involved and frankly you know over the time that I've been a scientist practicing scientists I've seen increasing distrust of science and scientists and I think it's it's frankly it's at least in part scientists fault you know I think a lot of people I know and I you know
• 85:30 - 86:00 certainly was this way and most of my career too focused on our work and talking to our colleagues and not explaining why we do what we do to anybody else and I think that the more we can get scientists to engage and participate in conversations like this the better I'd love to see science become more integral to our society and people understand how it works and what its limitations are so that we can grapple with these really big challenges that are coming not only with genome editing but also artificial intelligence
• 86:00 - 86:30 and other rapidly advancing tools that have great potential but also have great risk all three of you for your viewpoints your intelligence your opinions your differing thoughts on where we may end up thank all of you [Applause] [Music]