This will be about one of the most moral questions you and your children will face which is to whether or not allow this technology edit a human genome. Our guest is the author of cracking creation. One portly, she is the author of a 20 2012 scientific paper technologyns how the can be used to edit the human genome. Now, before we get into it, you can even start now thinking about the implications and what that means. Specifically, talking about editing a human germ line which would allow it to be passed on to our children. First, i would like to start a little bit of how you got there. , we had dr. This day who discussed the double helix and dna. Among the great things he did, like jennifer, he wrote a book about how he got there. Were 12 years old, your dad for that book by your bedside, so lets start with that. First, good morning, everyone. It is an honor to be here with you all. Was thet story, for me, beginning of my interest in molecular science. I dad was a professor at the university of hawaii. Somebody who liked to troll around in used bookstores, and he found this dogeared copy of the double helix. Realized this, i was a story, almost a detective was reala way, but it life, real science on how you could figure out the structure of a molecule by doing investigative experiments. From that moment on, i felt that was the kind of thing i wanted to do in the future. Statement a wonderful here. I have discovered the secret of life. Explain what he discovered. Well, he discovered the structure of the dna double helix, so dna is the code of life. It is the molecules that hold all the information which hold the information on how to grow, divide, grow tissue. They discovered that it looks like to ribbons wrapped around each other in a double helix structure. It is important, because it explained a lot of things about inheritance. Explained the way information could be sorted in the cell and copied from generation and generation. Each strand of the double helix encodes and includes a set of letters for dna code. On there are other letters the other strand, so it is a beautiful way to explain a lot of questions that scientists had up to that point. In many ways, it helped to usher in the modern era of biology, because it opened the doors to many of the types of technology we are now using. A phd at harvard, and you went on to teach. You are now at berkeley. Your famous role before the technology was understanding the structure of rna which is the way dna expresses itself. Explain your rna research. It was even before you came to that notion of your technology. Many people think it actually came before dna and is a chemical husband chemical cousin. Toshows that organisms tend hold in a single strand dna form. To it was a question i said i set out to answer as a younger scientists. What did the structure look like when it was rna, and why do we care . Many people think it was the first type of molecule that could store Genetic Information and replicate it. My 80 research as a younger site my research as a younger scientist wouldve been to understand how rna could be internalized into dna. Moleculesrket rna could store information and pass it on to a new generation. What is the function of rna now . One of the fascinating things that has happened over the past two decades or so in biology is that we have appreciated how rna when i was learning analogy originally, we thought it was learning biology originally, we thought rna was a sort of boring molecule, protein molecules that do all the activity. However, we now understand that rna molecules do lots of things to control the way Genetic Information is deployed. So, that is what i have been interested in studying over my career. How does that type of regulation work with rna. When you say dna is expressed in cells which means expressed extentwe are, to what are things determined by dna . What sort of things are just sort of added by our dna but are not completely determined by it . That is the 64,000 question. [laughter] tol, people have been trying understand the code of dna and what is in dna, all the genes that make up a human for example. One of the great things that has come out of that is that it is complicated. It is really complicated. It is not just a list of genes, but there are many layers to the way that information is actually used. I think that is what you are alluding to. Whicha type of genetics makes chemical changes to dna without altering the cells themselves him up but it changes the way the information is used. Can you give us an example of a trait that is more controlled by the environment and what we do . And what is purely genetic or encoded . It is hard to give you a specific answer, but many people think traits having to do with our personality and how we interact with our environment. That is a consequence not just of the genes in our dna but the way those genes are used. Things like particular diseases or Childhood Obesity is more genetically determined . That is what people believe, yes. Said you are doing study on dna and atomic structure, and as i read from the book, another great woman, a biochemist, give you a phone call out of the blue. She said to you, we are doing c krispa and how it relates to rna, do you want to be a part of it . Yes, she was a june biologist, not a biochemist. She works on bacteria and where. Hey go in the environment her research has uncovered a lot answers about the series of sequences in dna. What was quite interesting about this pattern of sequences is that it included a series of unique sequences which were derived from viruses. The question that she had but was not supposed to answer in her own laboratory was whether or not those sequences stored elementsese crispr might be copied into rna molecules and bacteria to protect the cells from i o infection. It was first discovered in spain i think . Yes, there were several microbiology labs which had important early roles in it. Many of them were in spain. It is where the acronym crispr was made. Denmarkere was a lad in looking to protect yogurt from bio infection. Crisprarted harnessing in the use of food preparation. When you first heard it, you thought it was spelled like er and you had to look at up to find out there is no final e in it. It was just one of those things that sounded so crazy to me. It seemed so interesting to try and pursue this. Ive always been there are two kinds of scientists, broadly speaking. There are those who died very deeply into one area of biology and become world experts in it, and there are those who are more of a smorgasbord, and they are picking out Different Things and trying things. I have always been sort of in the second category. When i heard about it, i thought it sounded so fascinating, and i wanted to take part in the excrement to find out if it is true. How did you get to the most amazing discovery of our time which is that crispr can edit our genetic code . I think this is a great example of small science and Curiosity Driven Research as well as international collaboration. All the things which have characterized my career over the past 25 years. I got together with a colleague who i met at a conference. Neither of us knew each other before him. She was running a lad in sweden at the time. She was working in a seemingly different area of science to me. She was in medical microbiologist studying bacteria which infects people. One of those bacteria turned out to have a very interesting type of crispr system in which a single gene seemed to be required for the cells to protect themselves from viruses using the crispr sequences. The question of how that so, the question was how does that protein work. So, we got together to do some experiments to figure out that question. The results of that collaboration was the paper we published in 2012 in which we stated that the protein was amazing and could be programmed with little pieces of rna which laboratories could easily change or sequence. It uses that piece of rna to find a matching sequence of. Etters in a dna molecule for example, the dna of a cell, a chromosome, and what it finds the matching sequence, it holds onto the dna and makes a decisive doublestranded break. It is like cutting and pasting. Yes, i like to use the analogy of word, because it is very analogous to this. It is the scissors that allow you to cut up text and change it. The cell then will make a precise change at the site of the repair. We will have to take a slight detour here, because the three major characters in this narrative so far are all women. I think back to the double helix the they sort of ignored only woman involved. Is this a change in science . I do not think we have seen major breakthroughs like this led this way. Or was this just a coincidence . An interesting, serendipitous event. I think more women are starting to make headway in science. None of us played it this way, but it just so happened that all of us were running Research Laboratories doing highly, metairie types of work which made it easy for us to work together. Why is it still harder for women in some ways . I think it is still some bias in this. There are some unintended i think it is still some biasness. Some unintended bias in the field. Women may feel more reluctant to step forward and volunteer for things, and so they get volunteered for things which takes them away from leadership roles. So, i think it is a lot of subtle things. When you got to the notion of editing genetic sequence, what is it you are editing exactly . I noticed a strand of dna, but what would you call that strand length that you edit . I would call it a length of strand, i guess. But it might have a gene function . A gene, or itve might have a sequence that controls the team. The gene. So, you can make changes that are very precise down to imagine that you could make a change to a single letter in the 3 billion base characters in the dna of a human cell. That is the type of technology we have now with this technology. That is the type of accuracy we have now with this technology. Next so, get to explain to me the world difference of doing that to a human cell and doing it to a germline. If we talk about doing it in an adult anything, plant, animal, person, we are talking about taking changes to cells in ways that those dna changes are not inheritable to future generations. In a germline, that is a different scenario where the changes made to begin a become part of the entire organism in the germ cells are allowed to develop into a whole organism. Be passedges can then on to future generations, and it becomes a permanent change. It is really changing the evolution of the species at that point. Evolution has always changed, so why is it different here . The difference here is that we are doing it in a targeted fashion. We are making decisions consciously about changing a set of genes which will do something we view as desirable. And the timescale is different. It would take well, proverbially. In theory. Starting with the animals, give like babye examples, that scienceever, has already been able to use this to do. Well, theres a lot of examples. So mice. You know that mice are used humanly as models of disease. Its been possible to make mice that have changes to their them moret make makelike in certain ways, it easier to study the effects of therapeutic drugs, for example, on genes. Similarly in well, you mentioned pigs. Make it easier to study the attractivee of the things with pigs right now is so theyrering them better organ donors for humans. Actively being worked on in Research Labs, but also in a startup company. You basically create pigs that become farms for organ treatments. Thats the idea. Right. What happens to the pigs . What do you do . How do you change their genetic coding . You can literally program the their organs or Molecular Properties look alike, making subtle alterations to at a d. N. A. So that molecular level they behave in a more humanlike way. What about mosquitoes that carry zika oring what . You do to fix that . Gene drive. Of just means if you have a way to alter d. N. A. , you a way that will drive a genetic trait through a population of insects. If one does this in mosquitoes, already being worked on create aple, you could mosquito that cannot transmit a virus. Mosquitoescreate that dontily reproduce the same way, that you cut back on a population of mosquitoes. Yeah, thats right. That being done in response to the zika virus . You using Crispr Technology . Im not, but many people believe this is an effective way to control insects otherwise spreading disease. That passes along to here on out,om right . Its not just a specific mosquito, but part of the germline of the mosquito experience or whatever. Thats right. Young, i read rachel carson, and we were able of mosquitoes, and a werenton later there any. We didnt know the consequences. How does science know the consequence of the mosquito population . We dont. To proceed with caution. I was at a talk ream, and about genes talking drive for mosquitoes, and they of building a large structure, maybe the size of this tent, designed to modifiedhese to dotoes, and really experiments in a controlled environment to what happens when gene drive if you have a tent like this, mosquitoes. Ontain we have nutria in louisiana, places that were supposed to contain them too. Its a big job. In charge of saying stop . Right now there are regulatory agencies in charge of controlling the environmental release of are modified this way. Right now were at an time, because the thing about this technology, its moving incredibly fast. Sense, this you a technology is just barely five years old. Its already in Clinical Trials china. Cer treatment in its mindboggling how the base of the Scientific Research has this tool. Ith theres a dozen or more papers a scientific the literature using the Crispr Technology. One of the big challenges how do you keep government regulatory groups up to speed with this, fast thingse how are moving . The pace of government is not that fast. Example ofive you an it from yesterday, which will not. R be reassuring or tom price, the secretary of health and human services, as know, was here on this stage. The worried about Affordable Care act. Office. Our book in my he started asking about it. He said this will be more important, 50 years, 100 years from now, on what you do on this, than what you do on the act, it willre affect the world more. Toaid, well, maybe you ought read the book. I gave him a copy. Well see. [laughter] a signed copy. M lets Start Talking about humans, if we may. Me you know, looking at longer hair on sheep. Viruses in pigs. Hypoallergenic eggs. Whereen theres a part you can start changing the human genome. On that . L we start what will we do first . I mean, there are blood diseases, cancers, what . Yeah. The kinds of treatments that are focus right now of research are not first of germline. N the right . We calllking about what kids,hanges to adults or but not inheritable. Its attractive to think of cure diseases that have a known single mutation causative. Sickle cell disease is one thats talked about a lot. Treatmentctive for a like this, because its in the blood, and its possible to take from a patient, do the editing outside the body, and replace the correctly edited so they replate the blood supply. Sickle cell is severe disease, treatment, and theres a fairly large group of people affected. Will be likely one of the targets of genetic we do moral spectrum, thats pretty solidly in the yeah, lets do that. Affect the germline. It wont affect children, but it will save people from a bad disease. Time is ahead of us now on this, fact that were spending not enough on research so china istry, taking the lead. What . E now using it for i think youre referring to using it in embryos, correct . Correct. In china, theyre asking the question, does this Technology Work in developing human embryos . Could we actually imagine some day using it to you know, to correct the sickle cell mutation, but do it hasin someone who already this disease as an adult, but we want to do at the stage of embryo genesis. The first paper now theres several actually published published about this topic was of 2015d in the spring using nonviable human embryos. Know,lly sparked you it attracted a huge amount of attention, because i think it forefront the idea, you know, that this technology is on our doorstep, decisionve to make a as a society are we going to elect to proceed with the embryos, it meant that it would be all future generations would have this fix. If those embryos were implanted, if they were viable and implanted, in principle yes. Were not viable was just a small choice. Use could have chosen to viable ones. Correct. So this is ready to go . Well i mean in the next 5 to 10 years. Certainly in that period of time, yes. If you were thinking of doing things youuld be the would say i want to apply it to this . In embryos . Yes. I personally am not ready to say. Ere yet, i have to first of all, i think there societalbe a broad consensus about whether that type of use of gene editing should proceed. There obviously hasnt been the opportunity knew that somebody genetically an embryo was going disease,fatal blood you would not fix it . I would advise other think, today. Somaticthe use of it in cell application should happen , and partly for safety to give ust frankly grappling withrt this issue. Are we going to edit the germline . Honestly it will be hard to stop. Everybodys feelings will be different. Who decides . For it . Pay responsible people will grapple t do it till we grapple. Your coauthor was a graduate student of yours. Yes. Ah, its aman i assume assume by the pseudonym named anstina, i assume entrepreneur type, this is very recently yeah. To him and says lets do it. Shes trying to commercialize this. She would, i would assume, make our children taller and smarter. Mean, its pretty easy to do lets take a specific withle that you could do the gene, which i think is have stronger bones. Thats Pretty Simple genetic thing, right . Or bigger muscles. Bigger muscles. Things that people would say, i want my kids to have and biggernes muscles. Thats scientifically areeivable, because those truly things you can find on the genome that you could change . Right. So kristina goes to your lets marketays this. Yeah. What happens . By the way, thats a true story. You wont give us her name . Want her last name . Yes. Well talk later. Going to go there, but this is something that ought to be talked about more. If there are Silicon Valley entrepreneurs trying there, but this is something that ought to be talked about to hire you graduate students to make peoples kids have bigger muscles or stronger muscles, it ought to be to my knowledge, thats not happening today, but that doesnt mean it wont in th