 Thank you. It's an honor to be invited back in this capacity. It's nice to be able to reconnect with my friends from the Genome Center from the early 90s. I am now reminded why I've been making armor non-stop ever since I left. But it doesn't have anything to do with being in the ELSI program. It has to do with being in the National Center for Human Genome Research. I mean, working there, whether you're Betty Graham or Jane Peterson or me, is like skating on thin ice in your underwear with people on both banks shouting directions at you and throwing snowballs. It was exciting for a little while, but it got cold. And I'm just amazed that these folks have stuck it out for a decade in this role, and my hat goes off to them. Well, you remember that Walter Gilbert early on in the debates over whether to do the Human Genome Project called it the holy grail of human biology. That's actually an interesting metaphor if you go back to the Vulgate cycle of Arthurian legends and the grail quest that it tells. I'm tempted to spin out the allegory since there are so many knights of the round table sitting in the audience, but I won't go through the whole thing. Just suffice to say that it's actually a nice metaphor for some of the moral lessons that guided the ELSI program during the genome project proper. That is, we, like the knights of the round table, had to learn to ask the right questions in the beginning. Remember, the knights got off on entirely the wrong foot when they forgot to ask, what is the grail and whom does it serve? In a sense, the ELSI program is an effort to ask the right questions right at the beginning. Because they got off on the wrong foot and the kingdom fell into a wasteland, they had to divert themselves from their quest to protect the innocent, maidens and such. ELSI has also partly done that in the efforts to make progress towards protections for genetic privacy and discrimination. And finally, the knights had to learn to spurn false grails. That's a feature of our discussions as well when we warn each other in the scientific community against being too deterministic, against painting false expectations, et cetera. But now the quest is over. We have at least a first draft of the holy grail. And we have to figure out how to live with it. That's really what I want to talk about, living with the grail once we've found it. And the legends are absolutely no use on that score since after Gala had finally looked into the grail, he's transported directly to heaven. And the other knights, well, one goes off to a hermitage and gets a PhD in philosophy and those sorts of things. We don't know how to live with the grail. The quest was all. And in fact, of course, what we do know is that this grail is a set of quests itself. That's what it's given us, a new set of quests. Here's a diagram that is modified from Francis' favorite diagram, it's at least a distant cousin, turned on its head for that grail effect. And these seem to me to be the three major paths, the three major directions in which genome research from my lay person's perspective is going to be taking in the next 20 years. I was glad to see it confirmed here and there in the talks that have preceded us because I think each of these pathways raises issues that we will have wished we had talked about in 2020 if we haven't talked about them. And so they are the issues that we'll want to get a head start on over the next five years in the five-year plan. Those are all pathways or pipelines to good destinations. I think the issues are not the constrictions of the pipeline from inside. That is, we the genomics community clamping down on ourselves. I do count the LC research community as part of the genomics community. But rather, it's a matter of watching for the leaks in the pipeline, the branches in the pipeline, the other things that are going on around the pipeline that are potential side effects or collateral social impacts, if you will, of having this path going to these beneficial outcomes. So that's how I'd like to frame it. The first one, what can we expect looking down the road to 2020 about the sorts of issues that this new biodetection technology, whether it's gene chips or microarrays or rapid resequencing or biosensors, the whole array of abilities to pick up clues to people's physiology. Well, these are probably the most familiar kinds of issues. The first important set of issues we'll want to get a grip on is how to translate these technologies, most of which are invented and developed for basic research use, into clinical tools. That does seem to be happening willy-nilly. DNA chips useful for genomic studies get translated into multiplex testing chips in clinical settings. In order to do that responsibly, there are three things at least we're going to need to work on. One is the question of how we decide when one of these new tools, a DNA chip, is ready for primetime clinical use. When is it appropriate to let it loose as it were on the community? Here we're at risk of course of being paternalistic if we set ourselves up as saying, I'm sorry, this tool is still too immature for you patients, risk-taking patients and risk-taking physicians to use. On the other hand, it does seem appropriate for the scientific community and I'm sorry this is a work in progress, let us finish please before you start using this still unfinished tool. What does it take to finish the validation of a new genetic testing tool? Well, more than technology development obviously, it's got to work in the clinical setting and that's where the line of research that we've already started doing on a gene by gene basis on the clinical integration of genetic tests is going to have to move to the next level of difficulty. How do we integrate tests, if we can call them tests, that scan multiple loci at one time for multiple mutations at one time? And then once we do, how do we explain the results to patients? That's the genetic counseling issue and it means we're going to not only have to figure out some standards for that criteria, how should we lump these tests, how should we package them, what are the limits of their use, should we for example profile all newborns at birth as well as do their PKU tests? And who's going to do this interpretation? I think the manpower, person power issue that was just mentioned is growing more urgent. The second sphere of issues in this area will be, again, a spin-off or a sideline from the biomedical pipeline and that's the use of these same technologies for non-medical purposes, primarily personal identification purposes in the context of law enforcement or census taking or immigration screening, terrorist searching, you name it, where we're interested in having an accurate way to pinpoint people's identities, these are the technologies we'll want to use. That's not necessarily bad, but it does raise a set of questions about how we want to deploy those technologies and what sorts of civil liberties questions they raise. Finally, I guess I'm in concert with all the other speakers to at least raise as an issue the problems that will come up through the commercialization, the commercial R&D route with which these tools get to market. I was interested this morning in the way in which the phrase haves and have nots was used. You were talking about the haves and have nots within the biomedical research community yesterday at the LC planning group, we used the same phrase, but we were talking about, I guess on a global level, the haves and have nots, the poor and the wealthy. The question is one that was just raised by one of the questioners. Do we need to take any responsibility for access to these technologies, not by other scientists, but by the poor and disenfranchised around our country, around the world? That is for those basic justice questions that the market can address. Well, I have a couple of suggestions for goals just to be provocative. Here's a specific five-year policy goal. Use the research on those topics. Presumably the topics provide a research agenda. Use that research to inform and promote the establishment of some kind of public forum or process for evaluating new genomic clinical tools. So this is Kathy's job for the next five years. And this acronym or abbreviation that I've listed there is the Secretary's Advisory Committee on Genetic Testing, an example of a kind of group that's already ongoing designed to address this general goal. Here's the blue sky 20-year policy goal, the fantasy goal for Francis to Chew on. Can we find ways to use genomic medicine to leverage improved access to healthcare in America? That is by taking our stand as a genomic community about the importance of improved access and as we insinuate ourselves into all branches of medicine carrying that with us into the healthcare system. Second pathway through functional genomics into these very interesting new possibilities of messing with the transcription factors and tuning switches here and there, all that great ooze and dithering of the cells. That's going to raise a set of issues as well. First of all, it will help us unpack some of these complex traits, both complicated diseases, but also eventually psychiatric conditions, behaviors, neuro pathways, personalities. Sure, that will raise some philosophical questions about freedom and responsibility and how our minds are connected with our brains. What I'm mostly concerned about are the issues that will follow that when we move past the descriptive science to an ability to tweak those complicated complex traits, particularly the behavioral ones. If we can tune those genes in people, which direction should we tune them in? Leroy Walters has suggested it might not be a bad idea to tune down aggressiveness. On the other hand, he's not a very aggressive guy to start with. So that's a set of issues we'll face, whether it's through pharmaceuticals or other fancier methods, we will be able to tweak our personalities increasingly. The second set is another set of complex traits, if you will, that will slowly become unraveled, but that's the whole phenomenon of human development. That's where the genome project and the stem cell controversy will collide. At one end of the spectrum, one end of the life cycle, but at the other are the interesting questions about the unpacking of the aging process at the molecular level and the questions that will come up for us about whether we want to support this fellow's lifespan that includes 21 children. Whether or not age stabilization is an appropriate goal for medicine in the first place, if aging is a natural part of the life cycle, as we've always said, how does it count as a healthcare need? And if it does, where the cut-off should be? When does premature aging set in, after all? We see pictures of Frank dramatic examples, but I don't know, hair loss in the mid-40s sounds premature to me. Inevitably, if in fact our work at the early stages of human development, embryo research, moves forward, and our work in gene therapy moves forward even a little bit, we will have to face the questions about using these same technologies in the germline to produce inherited genetic modifications. In fact, that's not 20 years away. That's right now. Last week I was at the RAC meeting, the Recombinant DNA Advisory Committee, where the issue was, right, this has always been a firm line we've drawn in the sand. We've been over backwards to insist that investigators prove that there's no transduction of the germline from risk in their protocol. But now we have a situation in which we've treated patient for hemophilia with a promising gene therapy intervention, and sure enough, there are signals in his semen of the vector. It got at least as far as his semen. Is that enough of a germline risk that we should shut down the protocol? Well, in fact, FDA did put it on clinical hold, and the point of this RAC discussion was what to make of it. First of all, of course, we don't know whether the signal's coming from the sperm or just the seminal fluid. That'll be sorted out. But the background question was, so what if it is in the sperm? At what level of germline transduction are we willing to live with if this actually does help the patient with hemophilia who's in front of us? We live with mutagenic risks of therapies in other settings, chemotherapy and radiation therapy. Why not in gene therapy? So, thus, the debate is joined, and I think we will continue to have that sort of how much inadvertent or side-effect germline transduction can we live with? Behind all these are some basic questions that I think the exciting science is going to push for us. The interesting and increasingly complicated causal pathways between genes and phenotypes are going to make us rethink our rather linear model of pathogenesis and disease. Up until now, we've been able to work pretty much with a kind of modified germ theory of disease and thinking about genetic disease, one germ. You can either be a carrier or a victim, and you can spread it on to the next generation. I think this is going to lead us to a paradigm shift there, and that will lead us to rethink what we mean by a disease and by normality and health. Good philosophical questions, but also questions for the genome community if, in fact, our goal is to get from sequence to improved health. We're going to have to understand what that goal is supposed to look like. So here are a couple of policy goals. Five-year goal, produce the groundwork, scholarly, scientific, and public, to use in the necessary and inevitable and coming social deliberation about these basic value issues. Should we treat aging? Is it okay to influence the germ line? There's a lot of scholarly and scientific work that needs to feed into that, and the PBC, well, the President's Bioethics Council, whether it's that body or another, there are going to be suitable policy targets to give this information to. And the blue sky goal, here is where my talk blends with the last one. In fact, our goal should be, just as he said it happened, a public clarity on the values, risks, direction, and destination of genomics by 2020, that is reduced fears where they're inappropriate, protections where they're appropriate, and I said the benchmark here is that we should be about as comfortable, society should be about as comfortable with genomics in 2020, as we are now with recombinant DNA research, which went through its eight years of repressive restrictions from the scientific community's point of view and public hubbub, but finally built enough public confidence and trust, partly by going through that process, that it was able to flourish. We're here today because of it. So it sounded like the future history is about right on target, eight years of, well, trust building, willing to give a little, and then, in fact, public acceptance that pragmatic physicians and patients are bringing it right into healthcare. Okay, finally, the last route through population genomics, this is, I think, what we're beginning to wrestle with now in the haplotype mapping project, and it also has some pretty basic questions involved in it. If we're going to have to get to tailored healthcare through some level of comparative genomics, group level genomics, looking for increased frequencies of alleles in particular populations, we really do need to decide how to define a population. At the moment, we do it in a kind of haphazard way. Oh, I work with the black freedmen who live with the Native Americans in Oklahoma. I'll collect samples from them. Oh, I work with an immigrant population in an eastern city. I'll collect samples from them. Well, by what definitions are those populations? There's a mixture of social categories, political labels, and maybe some biological commonalities, but it seems to me that's a basic conceptual issue the field needs to wrestle with. How do we want to define these populations, which ostensibly we want to study as genetic populations, as collections of more or less common alleles? Whether or not we define that successfully, maybe we can do the research without that effort, we need to think about how to protect the group's interests, particularly if we are going to collect and label them by social categories, since those are the categories by which political and social decisions are made about them, and that's where the issue of genetic discrimination gets ratcheted up to the group level. And then finally, by the same token, the burgeoning interest in various non-medical uses of these so-called population-specific alleles. There are journal articles in the forensic genetics literature, as I'm sure you know, interested in collecting and searching for so-called population-specific alleles for the purpose of ethnicity affiliation estimation for use in forensic settings. Well, what are the populations? What are the ethnicities? They're the most practical ones for police to use. The old four flavors of humanity, the 19th century racial groups, which we keep telling the world, don't map very well onto the real extended genealogies of all our families. So those are issues that are going to bear some thought. Here's my suggestions for this. There is now a draft U.N. Convention being circulated in some circles. It's called the U.N. Convention on the Preservation of the Human Species, and it's designed to outlaw species-altering experiments in humans. Well, I have no idea what that means. And I don't think they do, but they know what they don't like, and that's uses of genetics that have potential to abuse human rights, creating a subspecies of slaves, and that sort of thing. Okay, well, let's drop the science fiction aspect and focus on the fact that that's right. We do want to respect people's moral equality even in the face of what we're learning about our diversity. We do want to respect people's human rights in the face of genetic diversity. If there's some political momentum for a statement or a declaration to that effect at the international level, let's jump on it and make that move in the short term. In the 20-year blue sky goal, maybe we can leverage that into a general loss of interest in using genetic markers as indicators of group identity. And I guess the benchmark I would suggest there is if we could get it down to the level of significance you give to someone's name, that would be doing pretty good. Sure, names do give you. You import some meaning to that about which groups you come from, but not too much, at least in America. You don't want to go to the bank on it because you're bound to be badly wrong. So in summary, we, the genomics community, that's all of us, I think we should look beyond the ambit of health applications, look beyond the pipeline that we want to promote to issues that are in some sense none of our business, reforming the healthcare system, making sure that civil liberties are protected, worrying about philosophical concepts like health and disease. That's not something philosophers can do alone, particularly when it's being fueled by these interesting developments in biology. At the same time, I think we should look within the ambit of genome science to issues that underlie our business. That's the definition of health, the worries about what should count as a genetic test, et cetera. And of course, don't want to forget, we need to produce the students that can combine the skills capable to do that looking in the same way we need students with computational skills and biological skills. In the other wing of our university, we need students that combine genomic and social science skills. And finally, we should take the responsibility to host the public dialogue necessary to address the policy issues that are looking will inevitably raise. So I'll stop with, since Francis gave his, my favorite cartoon from the Genome Project, it's finally apropos after a decade of using it in talks. Apologize to those who've seen it many times. We finally finished the complete map of the human genome. Now we just can't figure out how to fold it. I think that's where we are. We're about to finish the map and we need to figure out how to fold it so we can get to where we want to go. If you've ever been barreling down the interstate with a badly folded map, you know how dangerous that can be. Well, thanks. First, I'd like to thank you for a wonderful presentation. I have a question which has to do with the definition of a population, as you mentioned before, which I think is crucial. And I think that as time is passing, there is a separation between the definition from the census, like if you look at census 2000, the definitions are mostly cultural. So for instance, looking at one group that I belong to according to the census, if you look at Hispanics, if you look at any body of any race, any ethnicity, any kind of background, so how do you do the genetics of that? Also, for example, if you look at another group, Native Americans, you can belong to the exactly same tribe. If you're born on the U.S. side of the border, you are a Native American. If you're born in Mexico, you are Hispanic. And you have the same genetic background as, you know, your brother or your cousin. So how do you, what do you suggest we should do to define populations in a way that could make some sense for study? Well, I ain't a scientist, but I, the tension there is that I can see one theoretical way that should work because it seems to work in field biology when you're studying genetic variation among spiders. You don't ask them which group they belong to. You put a grid across the field and collect samples randomly from each square, a certain number of samples, and then genotype them and let the genetic variation bubble up as it will. We could do the same thing with the human species. The Human Genome Diversity Project wanted to do something like that. They made the mistake of targeting labeled populations in the end, but that doesn't do much good for the other side of the equation, because there's a practical applications of that information because the public health authorities still use these social categories for good reason. Social categories tend to cluster different kinds of health risks and behaviors, et cetera. And so just knowing where the deems are in the human species is not going to, I think, be of much use to medicine. So somewhere in there there's a negotiation between the way we classify ourselves and our extended, intertangled genealogies. I don't know. Maybe some of you who actually do this research have some better ideas. Artie? Artie Wright, University of Pennsylvania. I guess I want to take issue a little bit with the disjunction you seem to be drawing between access issues, I should say, in the scientific community, and access issues for the public at large. And I think those two are actually intimately related for several reasons. First, to the extent that access problems in research actually prevent the development of a particular therapeutic, it obviously has access consequences for the public at large because there is no therapeutic then that has been developed. But a little bit less, obviously, the more toll collectors you have along the research path, if you think of research path, you know, simplistically is somewhat linear, and you have a toll collector at every stage asking for money for their particular research tool, the greater the cost of your R&D, and of course there isn't an exact correlation between the cost of an R&D and what's charged by a pharmaceutical company, but if we tune our patent system right, there will be some correlation, and so the greater the cost of the R&D, the greater the cost of the end product, and hence all the access issues at the population end come to bear. And then, last but not least, there's a very simple and clear example of this in the context of diagnostics. You know, we've seen some debate about how costly gene testing is, and that's because of patents. Patents that are somewhere in between the research stage and the population stage, but because in that context, the timeline is very compressed. You go immediately from the research to the population testing. It has a very immediate impact on access at the population stage. Thanks. I didn't mean to draw a disjunction there because you're absolutely right. That's a bottleneck in the pipeline that is access, researchers' access, is a bottleneck that's in the same pipeline of access. So it's mainly a matter of just taking the access issue one step further beyond the scientific community. The issue of patents, I'll just say one thing, and that is something that Lori Zoloff said at our meeting yesterday, and that is that it's hard to know what to do in the face of our market economy and the decisions that have been made about technology transfer and patenting. She said the best that the community can do is a liturgical lament. I don't know if that's the best we can do, but it does remind me that one time, somebody said, what does this LC stand for? Lost cause? I'm Ellen Rothenberg from Caltech and could I please ask you a naive question as a molecular and developmental biologist? I wonder if you'd like to comment on what I see as another kind of civil liberties issue that could arise over the next 20 years, which is the possibility of legislation restricting permissible behavior by people who have genotypes that are thought to pose some risk to their health. We've already seen some examples of this and I'd like to see you develop that argument a little bit. I mean, there's an issue about how much evidence there needs to be that a certain genotype needs to be associated with a certain kind of risk before the population will feel impelled to legislate against that person's freedom of action. So if you wouldn't mind commenting on that. Are you thinking about reproductive decision making? I saw all of the above. For example, to take a counter example, if I had a genotype, I don't smoke, but say I had a genotype that was very strongly protective against lung cancer. What then is the force of the laws that say in the state of California that it's almost illegal to smoke on someone like me if I'm not going to get lung cancer from it? And conversely, could I take that to court? And you could argue with the other way around if someone says that I have a bizarre disease so that I will die at age 55 instead of at age 75 by drinking one glass of wine a day. Am I going to be legislated against on the ground that I'll cost the state of California money for my health care if I drink a glass of wine a day? Yeah. Interesting, I think usually on the one side we try to make public health laws, bring them down to the lowest common denominator so that everybody is protected, even some people unnecessarily. And we don't worry about your super resistance in those settings. On the other hand, actually coercing people to do things they wouldn't otherwise want to do is an infringement of individual autonomy that our legal system would take very seriously. I was surprised by your answer to the population question. The fact that we define populations by some overt phenotype, whether you're balding or not, for example, is a terrible characteristic when there are known criteria, like you said for spiders, for example, for clustering different populations. One would think with the rule of 2005, the law in 2005 that prevents genetic discrimination, that in fact clustering of human populations is actually incredibly informative for various disease states. And the fact that you recognize deems that are socio-economic deems is a lousy criteria because those are all environmental. And I don't think we're talking about whether you make $10,000 a year or $100,000 a year, whether you're going to get cancer. But this crowd is more interested in whether you have specific genotypes which prevent or enhance the probability. So I would think that we would encourage accurate population descriptions. Right. I would think so, too. Hi, Robert Green, Boston University. I'm a newcomer to this area of physician scientists with the first ten years very much in the physician camp, and I'm struck by both Rick's talk and yours about how quickly you're anticipating the integration of genome principles and products into physician behavior. And I think that's really true. I think some of the examples like psychoanalysis, which was the purview of psychoanalysts, and then became the purview of psychiatrists in general, and now is practiced not only by physicians, but by sitcoms, is one example. Prozac before from only psychiatrists and now is given by not only physicians, but by neighbors is another. So I think we can see all of these principles and products moving extremely rapidly, as you guys have indicated. And it strikes me that the issues that you're bringing up also go beyond just genetics. For example, whether the gene mark or whether the gene itself predicts disease or the gene protein predicts disease is going to be somewhat irrelevant if you're predicting disease and the ethical issues associated with it. So if you set up your secretariat's oversight council and you restrict it to genetics, you're going to leave some huge loopholes. In my field, for example, structural and functional imaging is looking like it may predict Alzheimer's disease as well. So there's quite an opportunity for genome to lead the way, but I think to lay down ground rules that everyone should really be following. And finally, I just reflect back to you a review I got from a reviewer when I sent a paper into a family medicine journal on some educational issues in genetic testing. And the reviewer said, I'm tired of getting these papers about the genetic revolution. It doesn't affect me at all. It doesn't affect what I'm doing at all. And it reminded me of what my new colleagues in LCR are trying to teach me as an investigator, which is that the context of information, what it means to the person who's getting it, is going to be critical. Now, the 300,000 physicians in this country who are out there are the shock troops for genome and for National Institute of Health if I think we treat them correctly. If we don't just provide oversight, and I know you weren't limiting your remarks to that, but if we don't just provide oversight, but ask them what they need. If we don't just impose values, but ask them what values they have that need to be recognized. And if we recognize the constraints they're under from economics to time constraints and the entire structure of the healthcare system, I think we'll do a better job of getting the message out. Great. Thanks. I agree. Same goes for patient groups as well. Hi, Tim Leschen with the Genome Institute. You talked about the public dialogue at the end, and I thought I'm very much an advocate of having a public dialogue, but I was wondering if you could expand a bit about that and talk about what should that dialogue be, why should we have that dialogue, and who is the public? Well, it's a good question, because it's hard to... easy to say, but hard to design that kind of project. I guess I'm not so ambitious. I'm not thinking about, you know, cyber conferences beamed into every library in the country and things like that. I'm thinking about the way we usually do it, which is a public conversation of the sort that the National Commission might have where they, you know, have open meetings, publish their results, people can comment. It's not town meetings in every corner of the land. It's not a plebiscite. It's the usual democratic process at work. But still, that's the way we do things and should do things. Oliver Ryder, San Diego Zoo. I like your talk too, and I especially like the blue sky parts of it, and I just like to put a thought out there that's maybe farther out than blue sky, but I think that between now and 2020, there's going to be great benefit that accrues to humankind and the studies of our closest relatives, the chimps and the gorillas, they are endangered species, species endangered largely at the hands of humans, and it's actually illegal to commercialize of these species, yet they hold and it's well recognized in the research community as seeking appropriate access to the genetic information from them because it will benchmark, it will landmark, it will anchor the human genome. And I just wonder whether you think there's room in the ELSI process for societal discussion about whether there's a responsibility in any way to these other species. Sure. Interesting. That's a new topic that hasn't been on the agenda. I'm sure the institute would be happy to take it on. It's legitimate. Adrian Ash, Wilson College. Well, I'm right in line here with Blue Blue Sky. It seems to me that that question, a very important question, and some of our conversations yesterday in the EPPG meeting, we can get animal rights and world peace in the same project. But it seems to me that good conversations could be had about the biological, political and philosophical questions involved in sameness and difference. And that's where it seems to me at its best science and ethics need to get together. A lot of our trouble arises from concerns about sameness and difference. I'm just wondering if you could talk about that. Oh, I think it's a great point. It's right on point in terms of our needs to figure out what we mean by normality and abnormality or difference. What we mean by differences between different populations. The well-worn phrase now is that there's much more variation within populations and we're all virtually identical at the genetic level. That's true, and maybe to a Martian, we would all look the same. But for whatever evolutionary reason, we seem to be equipped to make the subtlest, finest distinctions between people based on appearance. Maybe there was another hominid clan we needed to be very careful of in our past. Because we do zero in on subtle appearance differences to differentiate ourselves into in-groups and out-groups. That's a scientific phenomenon that's well worth studying because it does really have implications for the kinds of social policies we set up. Some ways we've been fighting against that for most of this century. That's a conversation I'd like to see happen under the auspices of genome. Barby Secker from NHGRI. For a philosopher, you're an awfully applied philosopher and I applaud you for that. I think one of the things that you've done successfully over the years, Eric, is use real examples in order to help us think through what some of the potential adverse effects of genome research are. I really applaud you. I'm standing up here actually taking a little advantage of that because my response is really to the last talk more than yours and Karen Rothenberg set me up a little bit. I'm struck by repeated comments about improved risk perception or improved risk identification leading to improved disease outcomes. I think there's not a lot of social scientists in this room but the field of behavioral medicine has existed for 20 or 30 years and not dealing with Mendelian traits dealing with complex disease, heart disease and cancer risk. People do not make changes in their behavior once they get good information and more precise risk estimates. People are very complicated and that's why this research is very interesting. We have fears, we have beliefs, we have values, we want to be socially accepted. We don't stop smoking even though we know there are risks to our health and a lot of psychologists understand the reasons why we don't. So we need a lot of meshing in these next few years between behavioral medicine and the medical impact of genome research and I hope the people in the medicine breakout sessions will think a lot about that. As the research moves on in the story inevitably gets more complicated it'll seem even less urgent to make those behavioral changes. So maybe we ought to really scare them now while we can. One gene, one disease. Any other questions? If not I'll turn the mic over to Francis and say thank you to Eric.