That will allow the editing of the human genome. It is about the most important moral question you and your children will face, which is to what extent should we allow this technology to edit human genome. With me is the author of a crack in creation. More importantly she is author of a 2012, scientific paper that is basically explaining how crispr or crisper cas9 crispr test nine, can be used cas9 can be used in the human genome. We will talk about the implication of what that means, especially as we edit the human germline, and allow it to be passed on to our children. But before we get to the ethical implications i thought we should start a little bit with the narrative of how you got there. I think on this stage, some of you remember, we had dr. James watson, and Francis Crick of the double helix dna, and one of the main things he did was he wrote a book about how he got there. And i think of that when you were 12 years old your father but that by your bedside. Yes, to read first of all, good morning everyone. It is a pleasure to be here and an honor to be here with you all. Yes, that story was for me, the beginning of my interest in molecular science. My dad was a professor at the university of hawaii, and in fact nobody in my family was a scientist. My father was someone who lets tip patrol around in used bookstores and he found this dogeared copy of the double helix. When i read it, i realized that this was a story a detective novel in a way, but it was actually real life. It was real science, how you could figure out the structure of a molecule they doing investigative experiments. From that moment on i thought, that is the kind of thing i wanted to do in the future. And there is a fabulous scene in there, where Francis Crick, weighs into it, and says i have discovered the secret of life. Xplain what he discovered. Dr. Doudna hows that, better . Well, he discovered the structure of the dna double helix. Dna is the code of life, the molecule that holds all the information in cells that tells them how to grow, divide, how to become an organism or tissue, or hatever. They discovered that it look like literally to ribbons wrapped around each other. Eight double helical structure. Why was that important . It explained a lot of things about inheritance, about how information could be stored inside the cell, and copied safely from generation to generation. Because each strand of this double helix, includes a set of letters, of the dna code, which paired with another letter of another strand, it was a beautiful way to explain a lot of questions that scientists had until that point. It also in many ways, i think, ushered a modern era in biology, opening the door to many kinds of technology that we are now using including crispr. So you were a phd at harvard, went on to teach at yell, and you are now at berkeley. You are famous core you are famous for before crispr, understanding the structure of rna, which is i guess, the way that dna expresses itself in any organism. Explain your rna research, because it is even before you came to the notion of crispr right . Dr. Doudna i collect dnas chemical cousin, and many people think that it actually came efore dna. It is a molecule, that unlike dna tends to exist in a singlestranded form, not a double helix although it conform very complex readable shapes. That was the question i set out to address when i was a younger scientist, what do those shapes look like an rna, and why it was an important question ecause, again, many people think that our night was the early primordial molecule that store that information and replicated it. In my research as a younger scientists, it was to understand how that rna replication might have actually been catalyzed by rna, molecules that could both store Genetic Information and replicated and pass it on to new generations. So what is the function of rna that we know now . Dr. Doudna lots of things. One of the fascinating things that happen in the last 20 years or so in biology, is that rna, when i was learning biology originally, without it was a boring molecule, kind of the intermediary between dna, which held the secret of life in a way, and protein molecules that conducted all of the activities in cells. Now we understand that rna molecules do lots of things, to control the way that Genetic Information is deployed itself. That is really what i have been interested in in the study, how that regulation worth best works n the dna. When you say it dnas xpressed in who we are, in cells, what sort of things are determined by our dna, and what sort of things are sort of just guided by our dna, but are not completely determined by it . Dr. Doudna thats the 64,000 question. [laughter] walter yes . Dr. Doudna people have been trying to understand the code of dna, what the genes are that make up a human being for example, and one of the great, i think it is great, things that come out of that, is that it is complicated, right . It is really come get it. It is not just a list of genes, but in fact, there are many layers to the way that the information is used. I think that what you are lluding to is something called peigenics, which sounds complicated but means making chemical changes to d. N. A. That dont alter the genes themselves but change the way the information is actually viewed. Walter can you give us an example of something that is epigenetic, meaning that it is controlled by the environment, and what is purely genetic and encoded . Dr. Doudna it is hard to give you a specific answer, but many people think that with our personalities, how we interact with our environments, things that are more hard to put our finger on, a particular gene that is impossible for intelligence for example, that a lot of that is really a consequence of not just of the genes in our dna, but the way that the genes are actually used. Which is epigenetics. Walter but things like obesity for example, diseases, those are more genetically determined . Dr. Doudna yes, that is what people think. Walter so, you studied the atomic structure of it, and in the book, there was another great woman, a biochemist, who gives you a phone call out of the ball out of the blue, a colleague of yours, and she says to you, we are doing crispr and we need to know how it relates to rna, july to be part of it . Dr. Doudna yes, that was actually Jill Banfield who is a geobiologist. She works on bacteria and where they grow in the environment and how they behave and interact with viruses. Her research had uncovered a lot of examples of what we call crisper crispr which stands for a series of repeated the quizzes in dna. They are easy repeated sequences in dna. What was quite interesting about this pattern of sequences was that an included a series of unique sequences that were erived from viruses. And the question that jill had, she was not equipped to answer in her own laboratory, was whether those sequences stored within these crispr elements, might in fact be copied into rna molecules in bacteria then used to protect the cell from viral nfections. Walter they first discovered that in spain . Dr. Doudna right. Several microbiology labs had very important early roles in his, for example francisco mojico was one of the people who coined the acronym crispr and there was a group, a Yogurt Company in denmark, actually, who worked on how to protect their yogurt cultures from viral infections and they had uncovered crispr and started harassing them in food preparation. Started harnessing them in food preparation. Walter is it true that when you first started you thought it was spelled crisper, and i think you looked it up, and you realized, ok, there is no e in it. And you decided, ok, i will take on this question of crispr, right . Dr. Doudna yes, it seemed really interesting to try to pursue this. I have always been, i think there are two kind of scientists. Broadly speaking to read there are those who dive into one area of biology and become the world expert in it, and then there are those who are more of a smorgasbord, making things and looking at all different things. I was always more in the second ategory, so when i heard about this i thought, that is so fascinating, i loved doing different experiments. Walter how did you then get to the most amazing discovery of our time, which is crispr can edit a genetic code or genomes . R. Doudna i think it is a great example of small science, and Curiosity Driven Research as well as international collaboration. All of the things that characterize my career over the last 25 years. I got together with a colleague, emmanuelle charpentier, we met in a conference, neither of us knew each other before hand. She was running a lab in sweden, at the time, working in different areas of science, she is a medical microbiologist, studying bacteria that in fact eople. One of those bacteria turned out to have a very interesting type of crispr system, in which a single gene, a gene known as cas9, seemed to be required for those sales to protect themselves from viruses. Using the crispr sequences. In the question was how does it work . And she was not a biochemist which i was. So we realized that we could get together and do some experiments to figure this out. The result of that club best ollaboration was the publication in 2012 in which we the results of that was a collaboration in 2012 in which we describe that cells can be programmed with little pieces of rna, in a laboratory and change the sequence. And, what it does is use that piece of rna that it holds onto to find a matching sequence of letters, in a dna molecule. For example the dna of a cell, the promised son. When it finds that matching sequence the chromosome. When it finds a matching sequence, it can fix the break. As you would, cutting and pasting. Yes, i like to use that ord. It is when he think about the dna code like the text of a document, this is the scissors that allows you to cut off something and change it. The cell takes over after the the dna is broken and makes the change at the site of the repair. Lets make a little detour here, the three major characters in this narrative so far, jill, yourself, and emmanuelle charpentier, who are all women. I think back to the double helix when they kind of ignored the only woman involved, rosalind franklin. Is this a change in science, i do not think we are seeing a major breakthrough like this let this way . Or was this just coincidence . Dr. Doudna i think it is an interesting serendipity. Women are certainly making more ueries into the scientific world, as well as, obviously in biotechnology and business. It is still harder, i would say, for women, in my own its areas. But i think that this is a great example, none of us planned it that way, it just happened that all of us were running Research Laboratories that were doing highly complimentary kinds of work. It made it easy for us to work together. Walter what is it like that for women . Dr. Doudna i think it is just the ways that women are excluded, women, if you read the Sheryl Sandberg books, i think a lot of the things that she talks about in lean in resonate with e and with others. Women are more reluctant to step forward and volunteer for things and they get volunteered for things that take them away from leadership roles and things like that. Its subtle things. Walter when you got to the notion of editing genetic sequences or what is that you are editing exactly. I know that it is a strand of dna, but what would you call that length of strand that you are editing . Dr. Doudna i would call it a length of strand. I dont know. [laughter] walter to some extent in might have a gene it might have a gene, or a sequence that controls a gene. Either the gene itself or the part of the dna that controls it. But yes, you can make changes that are very precise, imagine, imagine being able to make a single change to a single letter in the 3 billion base pairs of dna in a human cell. That is the kind of accuracy that we have with this technology. Walter explain to me the scientific and maybe well get to the moral difference, of doing that, in a human being or in a cell, or animals which is perhaps easier and doing it in the germ line. What does it mean to do it in the germ line. When we talk about doing it in an adult person, or anything or plant or animal, were talking about making changes to the cell and ways that the dna changes are not heritable by future generations. Bat but, in the germ line, that is not changed. Those changes become part of the entire organism, and the cells are allowed to develop into an embryo. And those changes can be passed on to future generations. It becomes a permanent alteration. It is sort of changing the evolution of the species at that point. Walter but our evolution is always change, right, so what is the difference here . Dr. Doudna here, we are doing a targeted fashion, making decisions consciously about changing this one gene, or even a set of genes, to make something that we think is desirable. And the timescale is different . Yes. Something it is different. Something that we would do in 10 years we could do in 20 minutes. [laughter] well walter start with the animals, give me a couple of examples like maybe pigs or whatever that science has already been able to use this to do. Dr. Doudna there are a lot of examples. We know that mice are used very commonly and models for human disease. It is possible to make mice that have changes to their d. N. A. To make them more humanlike in certain ways and make it easier to study therapeutic drugs on them. Similarly, while you mentioned picks, pigs, one of the attractive things with pigs right now, is the idea that engineering them so that they are better organ donors for humans. This is already being actively worked on those in Research Labs them up but also in companies. Walter so you basically create pigs that become forms for organs for humans. R. Doudna that is the idea. Walter the what happens to the picks, how do you change genetic coding . Dr. Doudna you can literally program the dna so that their organs or certain molecular properties, their immune system for example, looks more humanlike. So you can actually transplant genes that are altering or making subtle alterations to their dna, so that on the molecular level they behave in a more humanlike way. Walter what about mosquitoes, that transmit zika or something to read what can you do about hat . Dr. Doudna that is another one, the idea of jean drive. Basically means that you have a way of altering dna, and you can use it and set it up in a way that it will drive the genetic trait more quickly through a population, for example in a population of insects. It is already being worked on in mosquitoes, in principle one could create types of mosquitoes that are resistant to viruses, and therefore cannot transmit he zika virus. Walter you could also create them as easily in mosquitoes that do not reproduce the same way, lets say, cutting back a population of mosquitoes bats right. Is that being that is right. Are you doing this to take on the the mosquitoes . Dr. Doudna well, im not doing it, but groups are doing it. This is an active area of research, i think many people imagine this could be an effective way to control insects that would otherwise be spreading disease. Walter that passes along to mosquitoes from here on out, right . It is not just into one line of mosquitoes. Dr. Doudna that is correct. Walter when i was young, i read rich el carson and we were able to get rid of moss ski toe well, did it with deform d. T. And a generation later there were no pell tan pelicans in my home state of louisiana. We didnt know the consequences of that how do we know the consequence of doing this to the mosquito population now . Dr. Doudna i think that is i would argue that we dont. I was at a talk recently and someone was talking about jean drives work with you does them gene drives, and trying to come up with the way, xperiments in a controlled environment to see what would happens when you have a gene drive. Walter we can tell you what happens when off tent thats supposed to contain mosquitoes. [laughter] who is in charge of saying stop . Dr. Doudna right now, there are various, obviously government regulatory agencies which are in charge of controlling the environmental release of organisms that are modified this way. But i would say that right now, it is an interesting time to read the thing about this technology is that it is moving incredibly fast. To give you a sense, this technology is barely five years old right now, and already, we do not talk about this, but it is already in Clinical Trials for Cancer Treatment in china. You know, it is sort of mindboggling, the pace of Scientific Research has picked up with this tool. I am seeing the early, a dozen or more papers for week in the scientific literature using the crispr technology. One of the big challenges is how you keep government regulatory groups up to speed with this, how you make sure they are aware of how fast things are moving and the pace of governments is not that fast. Walter i will give you an example of it from yesterday, which will either be reassuring or not. Tom price, the secretary of health and human services, as you know, was here on this stage. He says he is worried about the the aed forable care act but, this is something in his wheelhouse, he saw your book in i my office, i said actually, you know, this will be even more important 50 years or 100 years from now what you do on this than what you do on the Affordable Care act. Itll affect the world more. He said maybe i ought to read the book. So i gave him a copy. Well see. [laughter] you can send him a signed copy. So, lets Start Talking about humans, if we may. Tell me, i have looked at the pictures, longer hair on sheep, viruses that are killed, host allergenic eggs. Then we get to the part where you can start changing the human gee gnome. Where will we start on that . What will we do first . I mean, blood diseases, cancers, what . Dr. Doudna i think the kind of treatment that are in focus right now in research are not, first of all not in the germ line. Were talking about somatic cell changes, changes to adults or ids but not heritable. Like i said, it is very attractive to be able to cure diseases that have a known single mutation thats pozz sieve. For example, Sickle Cell Disease is one thats talked about a lot, its attractive for Something Like this because its in the blood so its possible to take blood stem cells from a patient, do the editing outside the body and replace the correctly edited cells so they repopulate the blood supply and the sickle cell mutation has been known far long time. Its a severe disease we have no treatment for it right now and theres a fairly large group of people that are affected. So i think that will likely be one of the early targets of