At the aspen ideas festival this year. [laughter] it is about the most Important Technology that will affect our technology Crispr Technology that will allow the editing of the human genome. Importantt the most moral question you and your children will face, which is to what extent should we allow this. Echnology to edit human genome with me is the author of a more and creation. Importantly she is author of a 2012, scientific paper that is basically explaining how Crispr Crispr testas9 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. 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. Read first of all, good morning everyone. It is a pleasure to be here and an honor to be here with you all. 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 everybody 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, s into it, and says i have discovered the secret of life. Explain what he discovered. 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 whatever. They discovered that it look like literally to ribbons wrapped around each other. Eight double helical structure. Why was that important . Of thingsed a lot 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. Think, in many ways, i 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 areous core famous for before crispr, understanding the structure of rna, which is i guess, the way that dna expresses itself in any organism. Your rna research, because it is even before you came to the notion of crispr right . Collect dnas chemical cousin, and many people think that it actually came before 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 because, again, many people think that our night was the that primordial molecule 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 , howested in in the study, that regulation worth best works in the dna. When you say it dnas expressed 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 that is the 64,000 question. [laughter] walter yes . 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 alluding to is something called at the genetics, which really means making chemical changes to dna, that do not alter the genes themselves, that change the way that the information is actually used. 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. Like obesityhings for example, diseases, those are more genetically determined . That is whates, 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 blue, a out of the 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 field who is aban 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. Was quite interesting about this pattern of sequences was that an included a series of unique sequences that were derived from viruses. Had,he question that jill she was not equipped to answer in her own laboratory, was stored those sequences within these crispr elements, might in fact be copied into rna molecules in bacteria then used to protect the cell from viral infections. Walter they first discovered that in spain . Dr. Doudna right. Several microbiology labs had very important early roles in this, 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. Instarted harnessing them 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,. K, 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 category, so when i heard about this i thought, that is so 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 . Dr. 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. Sweden,running a lab in at the time, working in different areas of science, she is a medical microbiologist, studying bacteria that in fact people. One of those bacteria turned out to have a very interesting type which ar system, in single gene, a gene known as , 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 collaboration 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 word. 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. 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 kind of ignored the only woman involved, rosalind franklin. Science, ihange in 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 queries 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 me and with others. Volunteering for things, they get volunteered for things that take them away from focusing on leadership roles and things like that. So i think it is a lot of that all 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 mean [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. 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. 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 . 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. Is different. T something that we would do in 10 years we could do in 20 minutes. [laughter] well, somewhat. Science has already been able to use this to do, can you give us an example . Dr. Doudna there are a lot of examples. We know that mice are used very commonly and models for human disease. To make my site have changes to their dna 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. Dr. Doudna that is the idea. Theer the what happens to 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. Mosquitoes, about that transmit zika or something to read what can you do about that . 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 the 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 welcome miami not doing it, but there are other groups who are doing that. This is something that people believe could be an effective way to control insects who are otherwise breading 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. Readr when i was young, i rachel carlson, and we were able to get rid of mosquitoes. , andd it with ddt generations later there were no population of pelicans in my home state. We did not know the consequences of that. What are the consequences of what this is doing to the mosquito population. I. Doudna i think that is would argue that we dont. I was at a talk recently and someone was talking about jean drives work with you does them and trying to, come up with the way, experiments in a controlled environment to see what would happen when you have a jean ves a we had laces that were supposed to contain mosquitoes in louisiana too. [laughter] so who is in charge of saying stop. There are right now, 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. Dozeneeing the early, a 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. I will give you an example of it, from yesterday. I guess you could say, tom price, the secretary of health and human services, as you know, was here on the stage. He says he is worried about the if for double care act, but he is also, this is something you should think about, they saw your book in my office, and he starts asking about it. He said, you know, actually this would be even more important, 50 years or 100 years from now, that then what you do on the Affordable Care act. It will affect the world more. And he said, maybe i ought to read the book. [laughter] so i gave him a copy. [laughter] copy. N send them a signed [laughter] so, lets Start Talking about humans, if we made. Tell me, i have looked at the pictures, longer hair on sheep, killed,that are hypoallergenic ax, then we get to the part where you can actually start hypoallergenic eggs, then we get to the part where you can start changing the human genome. Where would you start, what would you do first . Blood diseases . Cancer . 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 not where talking about what we call somatic cell changes. Not heritable. Like i said, it is very attractive to be able to cure diseases that have unknown single mutation that is causing it. For example, Sickle Cell Disease which is something people talk about a lot. It is attractive for disease gene,his, by editing the and replacing the correctly edited cell so that you can repopulate the blood supply. Sickle cell mutation, has been known for a long time. It is a severe disease that we have no treatment for at this time, and there is a fairly large group of people that are affected by it. So i think that will likely be one of the early targets of gene editing. And as we do, and our moral spectrum, that is pretty solidly , yes, lets do that. It will not affect the germ line, it will not affect children but it will save people from a bad disease. Hou, china is apparently a