 Good morning. I'm Francis Collins, the director of the National Human Genome Research Institute at the National Institutes of Health, and it is my privilege to welcome you to today's press conference. In April 2003, an international consortium of scientists from six countries announced the completion of the sequence of the human genome with all of the data placed in the public domain. Today, a different international consortium with an equally dedicated and creative cast of scientists from six countries announces the production of a very different map of the human genome, but one that ultimately may prove even more powerful for medical applications. This is the HAPMAP, and yes, all the data has once again been placed in the public domain. The genome project gave us the letters of the DNA code that we all share, but variety is the spice of life. HAPMAP investigates those spelling differences in the human instruction book that predispose some to diabetes, others to heart disease, others to cancer, others to mental illness, others to asthma. It's a long list. The HAPMAP reveals the way in which this genetic variation is organized into chromosomal neighborhoods, and now we can use it to uncover virtually any heritable cause of virtually any common disease. I'm a physician. Since the early deliberations about the genome project 20 years ago, I have dreamed of the day when we would be able to apply the tools of genomics to the diagnosis, treatment, and prevention of those common diseases that fill up our hospitals, clinics, and doctors' offices, causing untold suffering, misery, and premature death of our fellow humans. Today's HAPMAP announcement brings us a major step closer to the realization of that dream. This project could never have succeeded without the dedicated and selfless efforts of more than 2,000 scientists across the world. The sun never went down on this project. Our regular team conference calls always forced someone to be up way too early or way too late or sometimes both, but this remarkable group of creative scientists set ambitious timetables, insisted on data of the highest quality, and delivered on every promise. In fact, they did even better than that. The HAPMAP that we announced today is three times more detailed than what we thought would be possible in the brief three-year lifetime of this project. In this press conference, you will be hearing from several of these project leaders. It is perhaps a bit unusual to have so many presenters, but the composition of the international team is itself an important part of the story. Let me introduce the scientists that you see seated here in front of you. And I'll start in the back with King Zheng, who is the professor at the Beijing Genomics Institute, a part of the Chinese team. Next to her, Clement Adamobowo, who is the professor of oncology at the University College Hospital in Ibadan, Nigeria. Mr. Puyang Kwok, who is the professor of dermatology at the University of California, San Francisco. Continuing in the back row, Kazuhiro Shigetu, who is the minister of the Director for Advanced Medical Science, Ministry for Education, Culture, Sports, Science and Technology, and representing the Japanese funding agency. Next to him, David Barker, Vice President and Chief Scientific Officer of Illumina, a company that played a significant role in this project. In the second row, Lincoln Stein, who's professor at the Cold Spring Harbor Laboratory and who managed the Data Coordination Center. Next to him, a familiar face to Salt Lake City residents, Professor Mark Leprich, who is professor and co-chair of the Department of Human Genetics here at the University of Utah. Next, Ellen Wright Clayton, who is the Rosalind Franklin Professor of Genetics and Health Policy at Vanderbilt. Coming across to the other side, Aravinda Chakravarti, who is the Director of the McCusick-Nathans Institute for Genetic Medicine at Johns Hopkins University. Next to him, and the person who will be giving a presentation this afternoon in the plenary session of the ASHG meeting, Peter Donnelly, who is professor of statistical science at the University of Oxford in the UK. Next Richard Gibbs, who is the Director of the Human Genome Center at the Baylor College of Medicine in Houston. Now coming down to the front row, and you will be hearing from each of these people, but let me briefly say who they are. Juan Ming Yang, known to many of us, is Henry, who is the Director of the Beijing Genome Institute in China. Next, Bartha Knoppers, who is the Canada Research Chair of Law and Medicine at the University of Montreal. Next, Kelly Frazier, Vice President for Pearlogen Sciences, which did a significant part of the work in phase two, you'll hear about. Next, David Altshure, who is Director of the Program in Medical and Population Genetics at the Broad Institute of Harvard and MIT in Cambridge, Massachusetts. Next, Professor Yusuke Nakamura, who is the Director of the Human Genome Center at the University of Tokyo, and who did this work through the organization called RECAN. I will come back to the Secretary in a moment, going to the far end. Thomas Hudson, who is Director of Genome Quebec and McGill University Innovation Center in Montreal. And then Panos De Lucas, who is a Senior Investigator at the Sanger Institute, supported by the Wellcome Trust in Hingston, United Kingdom. And Charles Rotome, who is the Director of the National Human Genome Center at Howard University in Washington, D.C. A distinguished group, I hope you will agree, and I hope you appreciate, as we all have, the wonderful contributions of so many countries, six of them, to make this possible. Now it is my great honor and privilege to introduce to you a man who leads the Department of the Health and Human Services for the United States. Just coming to this Cabinet post earlier this year, Secretary Michael O. Levitt has proved himself a very able leader in the face of a host of challenges, from financing of health care to growing global concerns about pandemic flu. Secretary Levitt has also shown exceptional interest in the study of genes, environment, and health interests he developed while serving previously as Governor of this very state of Utah and as Administrator of the Environmental Protection Agency. In less than an hour, he will be speaking across the street to a plenary session of the American Society of Human Genetics, but it is a great pleasure and honor to have him here also today as part of this HapMap press conference. Secretary Levitt. On behalf of the government of the United States, and may I say ministers of health from around the world, may I express warm congratulations to Dr. Collins and his colleagues from around the world. This is a profound step forward. It is a triumph for collaborative science. It's my opportunity to express how this will benefit mankind. As Dr. Collins indicated, this is by happy coincidence also my home. Over the years I have become deeply interested in the scientific possibilities of genetics. I was intrigued enough that on occasion I would invite leaders of medically significant families to come to the Governor's Mansion in an effort to persuade them to participate in medical research related to genetics. After dinner, Dr. Steve Prescott, who happens to be here, would stand and give them a lesson on genetics. And then we would invite their participation. At the conclusion of the meeting on one occasion a man stood and he said, there's something to this genetics thing. He said a few days ago I had my 70th birthday and on that day my doctor told me I had macular degeneration. On my father's 70th birthday he was told the same thing and his father before him. He said I have a grandson and if there's anything I can do that will spare him from that problem you can count me and my family in. Well, this is a landmark achievement. I learned recently that Dr. Ho from Yale University using the HAPMAP was able to identify a specific gene variant that contributes to an increase in the risk of age-related macular degeneration. One of the variants occupies a protein called the complement factor H, which immediately becomes an exciting therapeutic target for my friend's grandson and the 7.3 million people like him who are at risk for AMD. This is an exciting possibility. We now move toward possible preventions that could save sight and save life. It is a profound step forward, a triumph for collaborative science. Thank you for very appropriate remarks about this connection to macular degeneration. Next we're going to hear from Professor Yusuke Nakamura. So first of all, I'm very delighted to be here as a member of the International HAPMAP Consortium, particularly because this is this city. The solar city is my second hometown where I spent five years between 1984 to 1989 at the University of Utah. Twenty years ago, I participated in the project to construct the first generation genetic linkage map using DNA polymer markers. The usefulness of such genetic markers for discover of genes for layered diseases was completely demonstrated by this Utah map. At the time, those several hundred markers in the first chromosomal map represented it a major advance. However, today we can announce that our international group has established a high-density genetic map consisting of one million single nucleotide polymorphisms or SNPs as they are now commonly called. We thought in the first strategy meeting of this project held in October 2002 that the construction of a SNP map containing one common SNP every five kilobase would be a very ambitious goal. After the intensive discussion, however, we decided to accept this challenge and assigned each center some chromosomes or chromosomal lesions for which they would have responsibility for generate the SNP data. After the project launched, we faced a number of high-hardness to overcome but we had regular telephone conferences and discussed each problem intensively and found the solution one by one. The three years of hard work generated data for more than one million SNP markers of which 80% show common variation in the 269 individuals we examined. The quality of the data was exceptionally high as demonstrated by close validation of several thousand markers by each center three times during this project. The error rate is estimated as only three per thousand. The hard map is a phenomenal tool that makes possible the research that was impractical only a few years ago. While the original UTA map was helpful in finding genes for rare diseases, this new map provided unprecedented power for finding the genes for common diseases like diabetes and hypertension. It offers the scientific community an enormous savings reducing the expenses and times of searching the genome who are hereditary factors in common diseases by a factor of 20 to 30. I'm very proud to be a member of this international group and to be able to give hope to the patients suffering from various diseases through the progress of medical research using this tool. I salute all the people participating in this historic project. Thank you. Thank you Dr. Anakamura and Dr. David Altshuler from the Broad Institute. It is my great pleasure to share with you some of the exciting results presented in the paper published today in Nature describing the data and analysis of phase one of the HapMap project. I want to first share a few personal thoughts as a physician and a scientist about why so many of us choose to spend our professional lives studying DNA variation and its role in human health. Despite spectacular progress in biomedical research, it is sobering to realize that we remain largely ignorant of the underlying root causes of common diseases, responses to the environment and variation in treatment outcomes. Until we can explain why one person gets bipolar disease and another does not, why one person given anti-hypertensive medication has a satisfactory lowering of blood pressure while another has a devastating side effect, will be at a great disadvantage in trying to improve methods to prevent, diagnose and treat medical problems. One thing we do know is that perhaps half of the inter-individual risk of most diseases is due to inherited differences in DNA sequence. As one of the most promising clues in all of biomedicine and one made tractable to study by astonishing advances in genomic science, the identification of genes that contribute to human health is a remarkable opportunity for biomedical research. The paper in Nature describes a resource and set of analyses that help make possible a new approach to this fundamental problem. The approach has deep roots in the history of human genetics and epidemiology and was first conceptualized in its current form nearly a decade ago. The approach is utterly simple to systematically test each genetic variant in the population for its frequency in people who do and don't have a clinical endpoint. While a complete version of this test is not yet possible, recent advances have shown that if we can sample a subset of all genetic variants, the vast majority of information about common variants can be extracted. What was missing was a catalog of common variants with information about the frequencies and patterns in the population and technologies to test these variants efficiently in large patient samples. The paper in Nature documents a number of findings that the vast majority of all genetic variants in each individual is due to a finite set of common variants and that the public database now contains enough information to capture essentially all of these common variants. Moreover, we find that variants are nearly always correlated to many of their neighbors. Such that testing a subset is adequate to capture the information about the whole. Finally, the genome-wide map has made possible the selection of so-called tag SNPs that efficiently and powerfully capture this information for application and disease studies. All this information is exciting, but we would be of little practical relevance if we weren't able now to test the tag SNPs in large patient samples. Technology has been spurred on by and in turn made possible the HapMap project and so many such studies in patient samples are now ongoing. The other set of results I'd like to highlight from the paper relate to human evolution. When a mutation improves the evolutionary fitness of those who inherit it, a fossil record is left in the DNA. Until now, scientists searching for such fossil records had to start with a hunch that a particular gene might have been important to evolution and then try to build a case. Since there are some 20,000 genes, however, and our hunches aren't that good, this was a piecemeal approach. The data from HapMap and others like it make it possible to search for evidence without preconceived notions about which genes might have been important. In essence, we can peer into the data and let it tell us which genes matter to the evolution of our species. As shown in the paper, two of the top results in such an analysis are already known to have been important in human evolution. The beta-globin gene responsible for sickle cell anemia and protection from malaria and the lactase gene that explains the ability to eat dairy products into adulthood. The positive results from our analysis for these well-validated examples are reassuring that an analysis based on the HapMap data can reveal examples of natural selection. What is truly exciting is that dozens of other genes are identified for the first time as possibly also having been important in human evolution. And while much additional work is needed to confirm and extend these findings, they represent the start of a new era in which scientists can unveil important factors that mattered in human evolution and possibly in medicine today directly from the DNA record. These two advances that we now have the information and technology to perform more powerful studies of the root causes of common diseases and insights into the genes that were shaped by human evolution are why I'm so honored to have been a part of this project along with my international colleagues here today. Thank you. Thanks. Next we're going to hear from Dr. Panas Delucas from the Sanger Institute in Cambridge, United Kingdom. As you heard from the previous speakers, HapMap has defined a crossroad in the field and moving forward we want to apply the tools that are being generated by this project to study the common diseases and variable response to drugs. In the UK, we have set up a consortium, the Wellcome Trust Case Control Consortium, that it has initiated an effort to study almost 11,000 people testing 675,000 SNPs to identify causative variants that they underlie a couple of eight diseases like type 1 diabetes, type 2 diabetes, hypertension, but also susceptibility to tuberculosis. I think it's very important that we also look for the infectious diseases like malaria as well, and this is an additional project that we are pursuing at the Sanger Institute. Thank you. So as you can hear, already HapMap is being put to good use in many parts of the world. Dr. Henry Yang will speak next from the Beijing Genome Institute. At this moment, and by this moment, I cannot hide my expectation. My Chinese colleagues, especially those from Hong Kong, are very honored to have been a part of this internationally collaborative project, which has been carried out by scientists from both developed and developing countries. In the same way as that for human genome project, history will witness what we have achieved, will not only benefit the public health of all of the people in the world, but also contribute to the international solidarity and the global harmony. I do hope that we will have more opportunities to collaborate under the spirit created by the human genome project that is owned by all, done by all, and shared by all. Thank you. I think we all share those sentiments. Thank you, Henry. Next from Miguel, Dr. Thomas Hudson. I want to thank all my colleagues in the room. This is a wonderful achievement for us all. It's a pleasure to have led the Canadian team involved in the HAPMAP project. My team is excited by the rapid incorporation of HAPMAP tools and strategies in our own Canadian disease studies such as colon cancer, asthma, and diabetes. Currently, for example, we're screening 2,500 individuals to identify gene variants that predispose to colon cancer. These hereditary factors will make it possible to screen individuals to determine who is at risk for colon cancer and then catch the tumors in high-risk individuals while they're still small and curable. I'm thankful for the support of Genome Canada, Genome Quebec, to the HAPMAP project. Thank you. Thank you, Tom. Thanks. Next, we want to hear from Kelly Frazier from Prologant Sciences. Just as a little preview, we're mostly gathered here today to celebrate the publication of this paper describing Phase 1 of the HAPMAP, the data, and the analysis, but we have a surprise for you. Dr. Frazier. The laboratory work for the Phase 1 of the HAPMAP project was finished last May, and that analysis has been occurring over the last five months and was completed. It's that work that's presented in today's issue of nature, and it represents an incredible scientific achievement. However, I have an additional surprise for you all. During the same period of time, the laboratory work for the second phase of the HAPMAP project was continuing. The SNP data for this phase was released two days ago publicly on Monday, October 24th. The second phase of the HAPMAP project was highly successful, tripling the number of genotype, single nucleotide polymorphisms in the population studied. Detailed analysis of this data set will be occurring over the next few months. When this analysis is completed, the combined work of the HAPMAP Phase 1, HAPMAP Phase 2, and a previous study done by Prologin Sciences will have examined a significant fraction of all common single nucleotide polymorphisms in the human genome. It's important to note that during the HAPMAP project, and in part because of it, huge advances in genotyping technologies occurred which resulted in cost reductions the order of more than two magnitudes for genotyping. These advances in technology not only paved the way for the HAPMAP Phase 2 project, but will allow for an explosion in the number of follow-on association studies. Through these studies, the HAPMAP will be utilized to advance our understanding and ability to use genetic information to improve health care. Speaking not only for myself, but on behalf of all my colleagues at Prologin Sciences, it was a privilege and honor to participate in the public-private effort to complete the second phase of the human HAPMAP. We're looking forward to continuing to work with the public sector and association studies of medical relevance in an effort to use the information discovered in the HAPMAP project to improve health care. Thank you. Thank you, Kelly. Next, we're going to hear from Professor Charles Rotome from Howard University in Washington, D.C. Thank you. I'm equally excited about this wonderful international achievement. The HAPMAP project, I'm here to talk to you about the future where we are going. The HAPMAP project studied 269 DNA samples from four different populations. We believe that the haplotypes are sufficiently similar across world populations that the information from these four populations will be used across multiple groups. But we need to check this data. In this regard, in the very near future, samples from seven additional populations will be collected and tested. This will include two additional African samples, which I will be contributing in terms of sampling strategy, and five additional samples with assentry from different parts of the world. The plan is to genotype these samples sometime in the spring and summer of next year. And the overall goal of the strategy is to test how well the haplotype and tag SNPs that we identify from these four major populations work in terms of association study across multiple groups. And this will be systematically done. Preliminary studies support the fact that indeed these tags' names are transferable across populations, but we need to test this in a systematic way. In addition to all of this, the overall goal of the HAPMAP project is really to make this data freely and publicly available in the way to encourage research and also that as additional data become available from people doing studies using the same strategy that the HAPMAP data is going to get even better and better. So our goal, of course, although this will take some time, is for the HAPMAP to eventually benefit all human populations in terms of understanding health and not just the majority populations that happen to have the monetary resources to do the four initial populations. In this regard, we are indeed committed to global inclusion. Thank you. And final presenter is Professor Bartha Knoppers from the University of Montreal who has co-led our efforts to be sure that the ethical, legal, and social implications of this project receive the necessary attention that they deserve because since that's such a critical part of research and genetics, Professor Knoppers. The approach taken by the International HAPMAP Consortium's Ethical, Legal, and Social Issues Group is as unique and diversified as the project itself. Unique in that communities were consulted and involved prior to sampling. Unique in that they continue to participate through community advisory groups set up to monitor future uses and through HAPMAP newsletters and quarterly reports. Participants understood the fundamental nature of this research. They understood that such a study on genomic variation would build a research tool for the benefit of others and for future generations. Indeed, to quote from the Yeruba community of Ibadan, Nigeria, the people of Ibadan are proud to be participating in this very important project. We feel that we are helping to improve the health of people all over the world. Diversified in that every community had different responses to the recruitment and sampling strategy as well as to the consent process. Researchers and donors had input into the wording of the consent and the choice of the naming of the community and initiating the requirement to receive a statement of research intent from those wishing to access and use their samples. Finally, any community advisory group could ask that samples be withdrawn if inconsistent with their values. The lessons learned from these innovative and participatory strategies are useful for the studies of genetic variation to follow. They are also particularly instructive for the many population biobank projects emerging around the world. These projects, too, aim to build research infrastructures and can profit from the unique and diversified approach of the HAPMAP project. Thank you for the opportunity to serve. So thank all of the speakers for providing the context of this remarkable international project. And it's now time for us to take questions and answers from the press. I understand there are press on the telephone as well and we'll come to you. Secretary Leavitt has indicated he would be willing to answer one or two questions before he has to go across the streets to prepare for his presentation to ASHG. So let us begin then if there are specific questions from the press for the secretary. Yes. Yes, we'll need to give a microphone to those asking questions so people on the phone can hear. And please identify yourself. Hi, Joe Baumann from the Deseret News. Hi. Can you give us any sort of an idea when people might be able to see any kind of therapies developed because of this? Well, I think I mentioned the one already with macular degeneration but it was really only the identification of a target, a very formidable target and one that will be pursued. The others could answer that question better than I. I think it's fair to say that the discovery of genetic variations that are associated with common disorders is about to take off as a consequence of HAPMAP being available as a resource and a tool to make that possible. You should expect in the next two or three years a outpouring of discoveries of such genetic variants that play a role in diabetes and heart disease, hypertension, asthma, the common cancers. But it's already true that some of those variants have been discovered already using other methods not nearly as many as we would like but there are good indications that this is a strategy that has a lot going for it. And in fact, I should say some of those discoveries are made here in Utah. Discoveries of genes, for instance, that contribute to breast cancer or to colon cancer or to diabetes, all of which have already occurred. The challenge is to take those observations and turn them into clinically applicable tools. They are wonderful ways to validate targets for drug discovery. They also provide the opportunity to come up with individualized preventive medicine strategies and you're going to see a great proliferation of activity in that area and now that we finally have the tools available to make those discoveries possible. I will add this, Joe. One of the barriers to personalized therapy strategy is that our regulatory system is not established or well-suited to deal with it. We're going to have to reinvent our regulatory process as this technology rolls forward so that as individualized therapies, particularly drugs, are offered that we have a regulatory system capable of approving them. Thank you. Other questions for the Secretary? Yes? This is Erica Czech with Nature. I'm Secretary Levitt. We're talking about the studies that we'll need to do to follow up on the HAP map to convert it into good therapies and I have a question about the budget for the NIH which played a large role in this and we'll do a lot of the follow-up work and we're hearing there's probably going to be a cut in the O6 budget. What is the administration's expectation for the budget going forward? Important to recognize that the NIH budget has doubled over the last five years and that we're in a position right now where we're working to assure that those investments are well utilized. I'm not able at this moment to forecast future budgets but I think it's clear that the investment strategy of the administration has been very clear and that is to enhance our investment in science. Any other questions for the Secretary? Yes, in the back. If there's a way to get a microphone. Secretary Leavitt, I wondered what kind of ethical questions this could raise. I don't know if we're getting to the point where a doctor may be able to look at someone's genetic mapping and tell them what kind of risks that they would have in having a child or if insurance companies will take a look at this and say maybe you're predisposed to a certain disease. Could you talk about some of the ethical concerns? I think it's significant that two people represented here come from the community of representing privacy and ethics. This is a question that isn't just reserved for genetic mapping. It has to do with anything related to access to information that needs to be held confidential. As we deal with electronic medical records in particular, this is an issue. But we deal with it in every aspect of our lives. We deal with our credit cards. We deal with all of our financial information. That information is already available. This is a... These are 21st century dilemmas that we're wrestling with. The important thing is that we do wrestle with them and that we use conscious, deliberate strategies to resolve them. Thank you. Mindful of the fact. You have a question on the phone for the Secretary. We'll take one more question and then I know he will need to step out. So can we hear the question from people on the phone? Hello? That's all the excuse I need. Okay. We'll try to get that attended to before we go on too much further. But thank you very much, Mr. Secretary, for being part of this. Thank you. Congratulations. Appreciate it. But the floor remains wide open now for questions to any of the people who are up here, including those in all three rows. So please, from the press, can I see who would like to ask a question? We'll come to the phone as soon as we can figure out how to get it hooked up correctly. Yes. Microphone. Meredith Salisbury with G&M Technology. You've mentioned phase one and phase two so far. Is that, well, phase two by the end of HAPMAP or are you considering more phases after that? So phase two, which you heard about from Dr. Frazier, basically takes all of the known polymorphisms that are in the public database called DBSNP and attempts to genotype them on these 269 samples. I think we could say that that is sort of bringing to closure what we have called the International HAPMAP Project, but there are all kinds of follow-ons which will be attached in some way to the HAPMAP name. You heard from Professor Rotimi about the need to look at additional populations and many other parts of the world will be doing that too. I see Gerardo Jimenez-Sanchez who is here from Mexico who is carrying out his own HAPMAP project there on mestizos, which is a very interesting sort of spin-off of this kind of approach. So there's lots more to do, but as far as saying what was the HAPMAP project intended to be? Phase one, phase two. We still need to do that data analysis that hasn't been accomplished yet for the merge set since the data's just now been completed, but that will be essentially what we call the HAPMAP project. Other questions? Okay, now from the phone should we try this? Kelly, can you answer this? Kelly Frazier from Perlogen. Yes, phase two genotyping is completed. That data is publicly available and it has been, it was released last Monday, two days ago. The total number of genotypes that passed all through the quality filters, the initial quality filters was about 2.8 million and so that data is all available. And that's all available at www.HAPMAP.org. Go there and have a party. Clarification. David Altshuler, one clarification. The 2.8 million number was the phase two data, but the amount of data available on the web today is 3.8 million SNPs in each of the 269 individuals. Right, 1 million from phase one, 2.8 from phase two, grand total 3.8. Yes, and please, others jump in if there's a clarity question. Another on the phone. So is that Steve Sternberg? Okay, Steve Sternberg USA today in terms of specific disease research. Tom, do you want to say a little bit more about what's going on in your Canadian center? I think that if we were to go around the room here, we probably would hear that most common disease has a HAPMAP project in phase. Many of them actually collecting the samples because we're talking thousands of samples of cases and thousands of samples of controls, whether it's Parkinson's disease, Alzheimer's, autism or diabetes. And so there's a phase of collecting the samples, collecting the phenotypes and then going to genotyping. And what we're hearing today is that the technical part of the project in producing the genotyping is actually feasible. And I would dare to say it's easy compared to actually getting the cohorts organized and analyzed at the end. So the HAPMAP project is provided an essential tool for this. I've mentioned the example of colon cancer because I lead one of the projects which actually is looking at 1,200 people with colon cancer, 1,200 people without colon cancer. And we started using HAPMAP tools this year. And just in McGill, we're going to produce over a billion genotypes this year on the various technologies to actually really scan every haplotype block, every barcode haplotype in these blocks to actually find where those hot haplotypes are. And then to actually know which ones are real, which ones are not. We have another 5,000 cases from various cohorts in North America and France which are available to validate. So it's actually going to be a hard difficult year in terms of producing the genotypes. But I think that the data is going to come forward as it will happen in autism, diabetes and other projects. I'd like a couple of others to answer Steve's question as well. So Professor Nakamura can tell you about Biobank Japan. Yeah, basically the Japanese government supported our Biobank project. And we started the collection of the DNA samples. And our goal is the collection of 300,000 patients. So far, we collected already more than 170,000 cases, covering 47 different kinds of diseases. So basically, we started large scale genotyping five years ago. But by having these two, we selected the tag snips of 250,000. And we now started genotyping of all 47 different kinds of diseases by collaboration with Parogen. And we are planning to finish all genotyping within three years. And we already have some candidate genes and I think these kinds of data would provide quite useful resource for the development of prevention and diagnosis and treatment of various diseases. Let me also ask Peter Donnelly who's been leading an effort in the UK that will also be utilizing the HAP map to go after a number of common diseases. Thank you very much. Peter Donnelly from the University of Oxford. As you heard earlier, there's a very big study underway in Britain looking at the genetics of eight common diseases, type one and type two diabetes, hypertension, cardiovascular disease, bipolar disorder, Crohn's disease, rheumatoid arthritis, and susceptibility to tuberculosis. And in addition, there are projects on malaria and obesity. And that project facilitated by the HAP map resource is already at the stage of genotyping. In each case, 2,000 individuals with each of the diseases and a combined set of 3,000 control individuals, our assessment is that the project will take a couple of years and we very much hope as you've heard from others that that'll give us really important insights into the genetic basis of each of those diseases. Great, thank you. So I hope you get the sense from this that this is an example where a project because of it giving up its data and the public databases all the way along has already inspired a great number of follow-on activities of very significant scale even though we are just today publishing the analysis of the work. And I think that's a great credit to the people you see here and many others who are here in the room who are part of the HAP map project that they agreed to this kind of immediate data access to anybody who needed to be able to use the information to begin to tackle these problems in medicine. Another one on the phone? Just a quick follow-on. Yes? Go ahead, Steve. Oh, maybe not. Go ahead, Steve. I'm sorry. Is there information available on the specific project that you're calling to distract? There is in terms of the Welcome Trust case control consortium you just heard about from Peter Donnelly. I assume that's up on the Welcome Trust website. Yes. Yes? So you could learn about it by going to that website in terms of Biobank Japan. Yusuke, is that something that's also on the web? Yeah, on the web but literally in Japanese if somebody can lead the Japanese that you can get all kinds of information. And Genome Canada and Quebec. Genome Canada has a website with all the products, diabetes and pharmacogenomics colon cancer. They're on the website genomecanada.ca and they're in English and French. Very good. Yeah, let's go to the room if we have other questions from people who are here. All right, back to the phone. We'll come back to you in a minute. Who's on the phone? Go ahead. Well, believe me, that is a question that many people have been asking. And I think HAPMAP has certainly attempted to sample various geographic parts of the world. But perhaps I'd ask Professor Knoppers to start with an answer to that. Others may want to jump in as well. So what does HAPMAP tell us about the biological basis of race? As a social scientist, Barbara Maria Knoppers University of Montreal. We had an excellent session on that very question this morning and certainly it is a question that comes up very often and is very present in the minds of most citizens. We heard that race is an imprecise biological term but nevertheless socially as a variable, very important in terms of socioeconomic or health disparities. What the HAPMAP project shows us however is commonality. In other words, 90% of commonality in genomic variation around the world. So we are beginning to get some evidence where we can begin to refute the biological basis but nevertheless the social aspects of race still remain a very great challenge. Let me ask Professor Rotini to also address this important question. Yeah, that's a very important question for the work we do again at Howard University and at personal level also. I think what the HAPMAP is telling us and most studies of genetic variation is that our understanding of genetic variation is really that this variant are continuously distributed across all human populations and in a way that is difficult to draw these claim cycles about the way we use demographic definitions of various groups. So that is a very powerful message that is coming out from studies like the HAPMAP and similar projects. So I think that is a message that we need to communicate to the community and to our scientists in particular and to journalists that human genetic variation is continuous and that we share a lot of things. For example, during my presentation I indicated that preliminary data from the HAPMAP project shows that most of the tax names that we have indeed are portable. They cut across multiple populations and they will indeed be useful for most world populations because of this common history that we all share. Thank you. Let's go to question in the room from Nature. Yeah, I just wanted to follow up. We've heard about the Biobank in Japan and the UK and you talked a bit about this morning the concept of the US Biobank. Is that happening? Is that close to happening? Could it happen? The idea of having a large-scale population-based cohort study in the United States appeals to many of us because it would be a wonderful resource for discovering and validating and quantitating genetic and environmental contributions to disease. There are a wonderful series of such projects going on in other parts of the world in the UK, in Japan, in Estonia, in Iceland, in Canada. But the US obviously has a different mix of populations and a different mix of environmental exposures and so it won't be possible to completely extrapolate from those other studies. Just the same, this is a very large undertaking if you're going to have a study large enough to accumulate enough cases of particular diseases, even common diseases. This would involve enrolling potentially hundreds of thousands of people as you've heard is already going on in Japan and is about to start in the UK. And that is expensive and at a time where biomedical research funding is tight. It's not clear that this could get underway without a great deal of enthusiastic support from lots of different quarters. And I think we're just having that discussion now about exactly what could you learn from this that you wouldn't learn in other ways? There was a whole session on that, also this morning at ASHG. The Secretary's Advisory Committee on Genetics, Health and Society has been looking at this issue and just had a meeting last week to discuss this. And I think they were uniformly enthusiastic about the scientific value of such a study. They also recommended strongly and certainly those of us who've been thinking about this embrace the recommendation that one needs to begin before going much further with this idea with an extensive degree of public consultation to find out what do people who live in the United States think of such a study if they were being asked to participate. Would they welcome that or would they have concerns? How would we protect confidentiality? What would we do with the information that was derived and so on? And that process, I think we should start even if we're not quite sure exactly what the long-term possibilities are of mounting such a study. I think there's a question on the phone. There were a few variations that seemed to be identified in particular to your grad or ethnic populations. And I'm wondering if you could comment on what those might be and the significance of those. And I'm sorry, this is business week? Yes. Okay, thanks. Dr. David Alczur. So I think it's important that we try and talk about this issue in a nuanced way. As Dr. Knoppers and Dr. Rotimi have already emphasized the great shared nature of human genetic diversity and it is clearly the case that most genetic variation is shared. There are some genetic variations that arose more recently since the migrations out of Africa to different parts of the world or maybe a small number that have been subject to particular natural selection in one part of the world or another that led their frequency to be different. And so I think that there's actually no conflict between these messages. We can't, just as there are no sharp demarcations as Dr. Rotimi said between populations it's also the case there's not an either or answer here. Where either everything is entirely shared or everything is entirely different. We do know for example that a classic example of a genetic variation is quite different between groups is the Duffy blood group antigen which is involved in protection against malaria. The relevant factor there not being what we might classically consider race but more who was exposed to the malaria pathogen and therefore evolved to defend against it. So the small number of genetic variations is a very small number out of a million typed. There were perhaps a hundred on the order of a hundred of variations that were extremely different between groups. They may provide clues that could help us understand better diseases and actually help everyone who suffers from those diseases but it's too early to say what their function might be because we only recently have learned that they exist. Another very dramatic example is the lactase gene that allows people to drink milk into adulthood which shows very strong differentiation between different parts of the world. Obviously something that's been subject to selection based upon diet. Are there any more questions from within the room? I think we've answered all the ones on the phone. Is that right? Yes? Yes. I just would like someone to... Sorry. I'd like someone to once again just talk about what types of therapies might eventually be possible because of this knowledge. I'm not talking about just early detection but is it possible to someday cure some of these diseases? Well that would be our strong hope. I'll take a crack and others would like to jump in and I may do so. If you really want to treat a disease effectively you want to develop a treatment that goes right to the heart of the problem. For most of the common diseases that currently fill up our hospitals and clinics the treatments we have are frankly inadequate. They oftentimes are treating some secondary problem instead of the primary difficulty because we don't know what the primary difficulty is. Genetics provides you a powerful beam of light to shine into this mysterious area of disease causation. If you can identify that a specific variant and a specific gene confers a heightened risk of susceptibility to a disease say diabetes or hypertension that tells you that that particular pathway is critically involved in the disease coming about. It is hard to come up with a better way to validate a drug target than that. So pharmaceutical companies in the biotechnology industry are big fans of the HapMap project and what will follow shortly afterward because they've been looking at all of those genes in the genome trying to figure out which of those would be the most appropriate next steps for drug development without necessarily having the clues they need to make wise choices. This is a very powerful way to make those wise choices. When you look for instance it's what's happening in cancer therapy so many of the drugs that we're most excited about from Gleevec to Aresa to Tarsiva these are drugs that are based upon a molecular understanding of what's wrong in that particular cancer and then the development of a drug that goes right to that particular target in order to have the effect that you hope for. That's the kind of rational drug design that we hope to now see inspired by the application of the HapMap to a long list of diseases that we currently describe but don't fully understand. So while people point to these discoveries of variation as a way to practice better individualized preventive medicine and I do believe that will be beneficial in many instances I think you're selling the whole thing short if that is the focus I think in fact in the longer term the real payoff here is going to be treatment. Another spectacular example that took a long time to unfold but I think speaks to the promise of this is that of cholesterol therapy. So if you ask how did we end up why is it you go to your doctor and everyone has their cholesterol measured it's because of the insight from population based studies of the sort we're describing but not ones that could measure all the genetic variations they could measure the cholesterol in the blood because that's what they could measure so that led to the understanding cholesterol tracks with heart disease and then a genetic discovery that of familial hypercholesterolemia that's a rare genetic discovery that's what was possible to discover led to the pathway the set of chain of events that led to the statin drugs which now are used by millions upon millions of people extend life and one of the main reasons if you look at the public health figures the decline in heart attack death one of the main reasons is the treatment of this sort of activity and so this is an example that took decades to unfold and I don't want to I think we'd be careful not to promise quick answers even if we know the genes involved in the pathways it might take 20 years to use that but how long will it take if we don't know what the root causes of disease are? Tom did you want to add something? Actually I just want to reaction to the question which had the word cure in it and very often for chronic diseases we don't necessarily think we're going to cure for example I don't necessarily think we will cure someone's predisposition for asthma be there for life but the new treatment better understanding biology new drugs inhalers and so on it will give patients a better life decreased emergency room visits prevent some deaths give more physical activity to kids so actually the disease may still be there the predisposition will be there but actually we'll have much better management individualized to the profiles of the patient and just to add one other thought about this the whole area of pharmacogenomics is going to be another major beneficiary of the HAPMAP we know that if you give a hundred people the right drug at the right dose for the disease that they've been correctly diagnosed is having not all of them will benefit some will get a good result some won't some of them will have a toxic side effect some just won't actually get much of a response a lot of that is encoded within DNA we have not been able systematically to look for the variations that are responsible for that because we haven't had the power tool well the HAPMAP has the power tool so you do not be surprised if you find yourself in the next four or five years being asked by your physician for a DNA sample to check out whether this is in fact the right dose of the right drug for you in that circumstance or whether the dose ought to be altered or whether maybe some alternative drug ought to be tried because you're the person for whom the usual drug isn't going to work are there any other questions well if not I want to thank you all thank all the speakers thank the press for a wonderful moment here of unveiling and here we go we'll see what HAPMAP will bring us in the next few years thank you very much I'm sure all the speakers would be willing to talk individually with members of the press if you'd like to meet with them up here we'll stay around for a little bit well done