 Good morning ladies and gentlemen, welcome to the Welcome Trust Human Heredity and Health Enactica Media Briefing Conference Tour. My name is Dave and I'll be your coordinator for today's conference. For the duration of the tour you will be on this one only, however at the end of the tour you will have the opportunity to ask questions. If there's any time that you need assistance please press star zero on your telephone keypad and you will be connected to an operator. I'm now handing you over to Dr Eric Green to begin today's conference. Thank you. Good morning my name is Eric Green. I'm the director of the National Human Genome Research Institute, part of the U.S. National Institutes of Health. As the moderator said, this is being video cast and those of you who are interested in calling in later to ask questions of any of the participants, let me give you that number now. If you want to call and ask questions, you dial 444-203-003-2666. That's 444-203-003-2666. Today the National Institutes of Health and the Welcome Trust are announcing a new partnership to fund and conduct population based studies in Africa. The initiative is called Human Heredity in Health in Africa or H3 Africa. It has several goals including using new research tools to help us understand the relationship between genes in the environment and health and disease. The effort also intends to build capacity on the African continent so that African researchers can conduct these types of studies on their own populations. The partnership as you will hear also includes the African Society of Human Genetics which is helping get the effort off the ground. I'm here from the National Human Genome Research Institute because my institute will manage NIH's portion of the partnership. But now to help you understand the NIH's involvement in this, I'd like to introduce the director of the U.S. National Institutes of Health, Dr. Francis Collins. Francis. Thanks, Eric. It's a real pleasure to be here this morning and I think this is a very significant announcement of a major project which in many ways is timed nicely at the 10th anniversary of the announcement of the draft of the human genome sequence in June 2000. Here we are 10 years later now with major advances in technology that have occurred over that timetable with the intention as a joint effort between the National Institutes of Health and the Welcome Trust and the African Society of Human Genetics to try to put together a really bold program to understand genetic and environmental contributions to common diseases in sub-Saharan Africa. The U.S. recognizes that the global is not the opposite of domestic and domestic is not the opposite of global. We live in a global world and if we want to understand the causes of illness we need to investigate them all over this globe. And Africa is a special place to carry out those kinds of studies because there is more genetic variation in Africa than anywhere else on earth and Africa is the cradle of humanity. And things that we learn in Africa will undoubtedly have broad implications for peoples in all other parts of the planet. And so we're delighted to be part of this. The focus is going to be both to try to understand genetic contributions to infectious diseases but also to non-communicable disorders like diabetes, heart disease, and cancer which represent the most rapidly growing causes of morbidity and mortality in Africa even though infectious diseases continue to be an enormously high priority. Because these are important goals and the payoff is potentially large NIH has already invested $750,000 this year just to get this project started and the project is going to be called H3Africa for human heredity and health in Africa. Starting in October of this year the U.S. government will invest $5 million a year over a five-year period for a total of $25 million in this program. Now we expect that out of this research there will be broad studies carried out to understand the genetic contributions to both infectious and non-infectious disorders as well as surveying the initial ways in which those diseases come about. We hope that this will also provide an opportunity for African investigators to collaborate with each other. The intention here is to empower scientists in Africa to take the lead on this program. That means that the resources will be also including efforts to improve training in that area. And out of this this will become a community resource project. The idea is that the data that comes forward from this project will be broadly accessible so that all the bright brains on the continent of Africa and elsewhere can work together in trying to discern from this the insights that we hope to obtain about health and disease. So again, I'm delighted to be here on this signal moment of announcing a program that I don't think we could have imagined even a few years ago. And the time is right now to get this going and with our partners at the Welcome Trust we're delighted to have a chance to support it. Thank you. Thank you, Dr. Collins. I'd like to now introduce the director of the Welcome Trust, Sir Mark Walport, Dr. Walport. Eric, thank you very much indeed. Well, first thing to say is how delighted I am that we're announcing this program today. And of course we've worked in close partnership with the National Institutes of Health from the beginnings of the Human Genome Project. And so this is a very logical continuation. And the last 10 years have seen the most extraordinary progress. So the technology has now changed. So the first human genome talk about 10 years to do and cost roughly a billion dollars. They're now sequencing in the major genome centers more than one human genome every day. And the challenge now is to take that from the laboratory to the clinic. And so this fits very well with the Welcome Trust has been supporting. And in a similar way to NIH, we've been supporting research in Africa for very many years. And there are different elements of it. Firstly, the study of the diseases themselves. The major killers in Africa, malaria, tuberculosis, HIV, childhood infection. But as Francis has said, noncommunicable disease is rising up the agenda as well. And so diabetes, obesity, heart disease, cancer are all becoming major problems as well. So one element is obviously looking at the disease. The other, and this is highly relevant to public health actually, is the study of cohorts of people through time. And it's very important that studies similar to the Framingham study in the United States, the Biobank study in the United Kingdom. Studies like these happen in Africa as well. And that's highly relevant to the health of the population because information from those studies contributes not only to studies of how the human genome interacts with the environment variation to increase susceptibility to disease, but this tells you about the health of populations and will direct health interventions as well. It's also about people. It's about developing capacity in order to make the most of human genetics now. One needs people who are skilled in bioinformatics. So it's about training people so that the data analysis can happen in Africa. And it's also about building institutional capacity, the institutional capacity to provide an environment for this sort of research, for first class health research. And so this is in fact an extremely important initiative and it builds on the type of investment that we've made in institutional capacity where we've now funded seven networks of institutions across sub-Saharan Africa, involving more than 50 institutions. The Wellcome Trust will be contributing approximately £8 million over the next five years to this initiative and I think probably rather more over time. That will include fellowships, it will include training, it will include capacity development, it will include the phenotyping and the genotyping. And we will be allocating that through a transparent grant funding mechanism. So it couldn't be more timely in the 10th anniversary week of the completion of draft human genome and I'm really excited to be making this announcement today. Thank you Dr. Walpert. I'd now like to introduce Dr. Charles Rotimi who has been a driving force in creating H3Africa. Dr. Rotimi has an unusual background. He was born in Nigeria and he earned his professional degrees in the United States and is now an intramural researcher at the National Human Genome Research Institute where he directs the Center for Research on Genomics and Global Health. Dr. Rotimi is also the President of the African Society of Human Genetics. Dr. Rotimi? Thank you very much. Again I'm going to try to contain myself here because of your excitement level. This is something that we've been talking about H3Africa under the bigger umbrella, what we're thinking in terms of human genome projects for Africa, what we call African Genome Project at that time. But this discussion really started under the umbrella of African Society of Human Genetics in 2007 in Cairo where we felt as geneticists and epidemiologists and clinicians and other types of researchers from Africa that we needed to make sure that whatever benefit that we are going to accrue from using genomics to understand health and human history that that doesn't go past Africa like a lot of other revolutions have done in the past. So we started the discussion without necessarily knowing where the outcome from and how we're going to do this but we wanted to make sure that we at least try to put this in place and hopefully we will get the attention of key funding agencies. And I'm very, very happy to be here today to say we are now launching human heritage and health in Africa, H3Africa. And this is extremely exciting to me. And we wanted to get the attention of the National Institute of Health and also the WorldCom Trust to provide initial momentum and significant funding for this for this effort. So under this umbrella, although we now have expanded this initiative to go beyond just understanding genetics, like Mike and Francis said, we are indeed going to build large cohorts of thousands and thousands of people. If you heard recently about how genomics is being used, you know it requires a lot of people to be able to understand imaginative variation, how that relates to health. So we are not just going to be looking for a way, we are going to set up clinical cohorts, going to set up clinical centers around Africa to be able to gather this kind of huge number of individuals to do this kind of study. So this is again extremely exciting. So we are going to set up resources to enable us to do gene environment interactions. There are unique environmental characteristics of Africa that you have to do it with Africa to be able to understand how these interactions occur. So again, we are going to start to talk about the fact that this funding is really going to start to change things in the way we do research in Africa. Traditionally what occurs is that African scientists participate in the development of scientific projects, and most of the time those resources end up outside of Africa. We are hoping under this umbrella that we are going to do things differently, where those resources are primarily going to remain in Africa, but it will be open to global collaborations and to create that sense and to foster intra-Africa collaborations between scientists. So the issue of building biorepositories, the issue of building centers of excellence, the issue of training of young investigators or not so young investigators to be able to do the science in a way that they can truly be first authors of this major type of publications. Right now if you look at science and nature genetics of nature, most of the research is coming from Africa and indeed not led by African scientists. And I don't think that's because of lack of intellectual capacity, but it's just again not having the necessary infrastructure and resources to be able to do that at this present time. And I'm hoping that under this umbrella we can begin to do things differently. Again to end my comment I'd like to really thank the Welcome Trust and the NIH for stepping up to create this kind of big umbrella that we can begin to put things in place to really change the way research is done on the continent. So I'm extremely excited about this opportunity. Thank you Dr. Rotimi. So it's important to recognize that the efforts to date in planning H3 Africa have been sort of a tripartite collaboration between the African Society of Human Genetics, the Institute of Health, and the Welcome Trust. And various of us have been working to try to plan some of these activities might be. And so far we have divided the tasks in terms of formulating the scientific plan into two working groups. One focused on the genetics of communicable diseases and the other on non-communicable diseases. So I'd now like to turn this over to one of the chairs of one of these working groups to describe what's been done so far. Dr. Bangadi Mayosi is chairman of a working group focused on non-communicable diseases. He is professor of medicine and head of the department of medicine at the University of Cape Town, South Africa. Dr. Mayosi. Thank you very much Dr. Green for the opportunity to be at this meeting. I also want to share my excitement with this particular initiative from the National Institutes of Health and the Welcome Trust. And I want to point out as a person working in Africa that it actually indicates a very, very important shift in the way science is done in Africa. Up until now I think we've been operating almost in a colonial mode of doing science where people from outside Africa have been coming to collect samples and then processing them outside Africa, publishing the papers and generally promoting the careers and the knowledge of people who are outside Africa. What is different about this initiative as Dr. Rotimi has said it is that it seeks to do science in Africa by Africans and for Africans. And I think that's a key shift. It's an historic step forward I think in the science making of the world and is a response to the calls that many of us have been making about what needs to happen to in fact change the costs and the fortunes of Africans. For most people when they think of health problems in Africa they think about malaria AIDS and tuberculosis it is true that Africa is still blighted by these formidable communicable diseases. But of late we have observed arise in non-communicable diseases so that once we still do battle with communicable diseases we must now begin to focus our understanding on the role of genes and environment and the rise of disorders such as heart disease, obesity, diabetes, cancer as well as mental health. The committee that I chair seeks to identify the diseases which will be most fruitful for work through the H3 Africa projects. These are very difficult questions and we are still working to identify the sorts of populations and the sorts of diseases that will be amenable to a genetic approach. The work groups which are under the auspices of the African society of human genetics, they will also provide a network through which individual researchers will learn as well as develop. My working group which is working on non-communicable diseases has already met several times and we have identified a range of possible studies that can be tackled and we are busy formulating the roadmap for this project. There is a meeting that is planned in Oxford in early August where both the people working on non-communicable diseases as well as those working on communicable diseases will meet to share their thoughts on how best to take this opportunity. It is likely that there will be quite a lot of overlap between those two groups working on communicable as well as non-communicable diseases but it is also likely that there will be unique topics that will become obvious. For example, in sub-Saharan Africa, there are certain diseases that are unique to the region that still persist such as rheumatic heart disease which in fact straddles the infectious and the non-infectious divide and that condition still exists there and humanity has got an opportunity to understand its genetic origins so that as we try to eradicate it we can learn its unique secrets that it keeps for biology. Overall, I think this project is not only significant for the people of Africa for investing in the intellectual capital of Africa but I think it is also going to be important for biology and for lessons for the global community at large. Okay, I would now like to open the floor for questions. Please introduce yourself and let us know who your question is directed to and if you're asking a general question then I will find someone to answer it for you. Thanks, Mark. I've got a few questions here. Probably the different people. First of all, could I ask Dr. Atimi and Dr. Mayosi? Perhaps. We've learned an awful lot about the genome in the last ten years but the majority of that has been focused on populations of European and to a lesser extent Asian origin. Do you feel that the genomic revolution has until now perhaps passed Africa by a little bit and how do you hope that this project will address that? That's the first question. The second question and I don't know who is best placed to answer this but the genomic study do you have in mind? Are we talking about GWAS? Are we talking about further re-sequencing studies? Do we need to do a new version of the 1000 Genomes Project with very large numbers of African genomes given the diversity of the African population? And then further for Dr. Collins, when I interviewed Hal Varmus last year he mentioned that GWAS has diplomacy and has a way of promoting the US, the UK et cetera abroad. How does this fit into that? So why don't we start with Charles? I think you can make a very strong case that in this until now that at least the way we have applied the genomic science to understand health has for the most part Africa has been left out of that. A good example to look at that is only one genome-wide association study has been published so far that is solely based on African population and that is the malaria gene publication. So out of hundreds of genome-wide associations that has been done one can say is pretty tragic to think that the whole of continents of Africa only one has been done so far. So we have not equally applied the tools of genomics in terms of trying to understand health. There have been various attempts to try to rectify that recently. For example the 1000 genome has now included more African populations in the arrogant. But again that science like my colleagues and everybody on the table has been indicating most of those are science that are indeed been driven in the west and in Asia. So again this umbrella that we are creating here we are hoping again to begin to change that dynamics in a way that we can actually apply genomics to diseases that are relevant to African population, important to African populations. Taking advantage of a unique environment a cultural environment that exists there to understand the environment interactions. And perhaps equally as important is to study neglected diseases genomics to understand neglected diseases. For example with funding from NIH and the work contrast we are currently looking at podoconiosis in part of Ethiopia which is a disease that looks like elephantiasis but it is not. It is a completely neglected disease. It used to be in Europe but it is not here anymore. And we are trying to use the genome wide association approach to try to understand the disease. There is genetic study because you don't wear shoes. So it is a truly classic genomic interactions that cannot be studied anywhere else but in that environment. So that is the kind of opportunities that exist on the continent to understand and solve African problems. And in the hope again to solve global problems because Africa is a trunk and root of human evolutionary history. So what we get from there is going to be also equally important to different parts of the world. So your second question was what exactly are you going to do? Are we doing genome wide association studies with sequencing genomes? I'll yield to anybody who I'll take the first pass and just point out that advances in genomic technologies and as Dr. Wohlport mentioned the plummeting costs. The fact that the cost for genome sequencing are plummeting, are opening up opportunities so that the answer your question is we are going to do all those things. I mean that's the bottom line because we can and importantly though we're going to build a broader based approach for collecting individuals, getting good phenotyping done of those individuals and bringing contemporary genomic technologies to bear on those collections which is going to provide the opportunities that you heard two of our speakers in particular talk about projects that otherwise have been neglected but now they're empowered by genomic advances. Anybody want to add to this? I agree with that completely. I mean I think actually the most difficult bit in many ways is the phenotyping so the sequencing is changing dramatically and it's changed dramatically in the last five years. It's likely to change equally dramatically in the next five I suspect in terms of cost reduction so as Eric says it is all of the above the phenotyping, the actual really detailed clinical analysis is very hard and I think that's going to be the biggest challenge actually. There is a scientific point here that hasn't been made yet and maybe should be pointed out that there are unique aspects of the African population that empower this ability to track down genetic contributions to common diseases. The African population is older than Europe and Asia which means that the neighborhoods where genetic variants travel together in lockstep are smaller. That turns out to be really useful because if you're seeking a genetic variation that's functionally involved as a risk factor for diabetes or high blood pressure and you find that in a European or an Asian population, well you are finding generally dozens of those variants that are all equivalent in terms of their predictive power because they're all in lockstep in this larger neighborhood and your resolving power is limited by that. In Africa because the population has been around longer, the neighborhoods are smaller, there's been more recombination and therefore the ability to shine a bright light on what the functional variant is that's actually responsible for that diabetes risk or that high blood pressure risk is substantially better. That is a resource that will help in tracking down these ancient variations that are probably present across the world but in Africa will be more easily delimited to a more precise interval. That's going to help us a lot in certain circumstances where we have hundreds of these variants that have been identified in general but for very few of them actually know which specific letter of the DNA code is responsible for the risk. Africa will help us with that. Now let me answer your question about sciences diplomacy because I feel quite strongly about that as a really exciting opportunity that we have right now and that was one of the motivations when I decided what the five areas were of this opportunity in science right now at NIH, global health is one of those five and it's because the science is exciting and because things have come along in the last few years that have made it possible to tackle global health problems both infectious and non-infectious in ways that we couldn't have contemplated but it is also this opportunity to reach out to the rest of the world with what has been called soft power or maybe smart power to be able to draw the peoples of the world together in a shared effort to try to understand the causes of illness and the means to prevent and treat disease surely that emphasizes our shared humanity surely that is part of what a society should try to do for other societies surely that fits with what the welcome trust has been doing for decades and what the national institutes of health stands for but we have a special opportunity right now to do that and I think H3Africa is a wonderful example of how to take resources and apply them in that way other questions from individuals in the room yes Kate from Reuters you mentioned that you might be setting up similar things to the UK Biobank do you have any details yet on where those kinds of things will be set up and also you were talking about collaboration within the continent and collaboration is quite limited at the moment as far as I know and I think South Africa will actually way ahead of the rest of Africa in terms of research how are you going to be able to spread that network through this so I might suggest Dr. Rotimi take the first question and Dr. Maylisio take the second question right again the first question was how do we where are the biobank where are the repositories we have set up two working groups that one of the terms of reference for them is to help us to identify first of all to understand what is currently on the continent in terms of infrastructure and as part of that evaluation process they are going to make recommendations that will guide us to say these are areas where something like a biorepository can indeed be facilitated either because there is something that can be improved upon or that the environment lends itself to that kind of support to support that kind of infrastructure but it has to be located in such a way that we are creating a sense that all African investigators feel that they can actually send their samples there in a way that they can still maintain ownership but to be available for large collaborative effort and I think that will go a long way to foster intra-Africa collaboration between African scientists you don't worry that that is going to basically focus the new stuff where the old stuff is already looking at where the infrastructure is already in place isn't there been a risk there there is definitely that risk but we are sensitive to that and that is not to just continue to give to those that already have so there are going to be opportunities it just depends on the activity for example if we are setting up clinical centers which is going to be critical like what Mike and others have indicated here that phenotyping is really going to be the rate limiting step in all of this and if we set up clinical centers it will really enable us now to be able to engage more African institutions more African countries because we need large numbers so we are going to set up the centers around so the molecular labs may not be as widely spread around the biorepository we cannot build multiple maybe one or two strategically located but there are going to be opportunities to engage more institutions more centers based on different activities and the best one I think in terms of developing this large-scale epidemiological type cohort that really is needed most of the data we get out of Africa today are really challenging because we don't have this large cohort that really says how many people really die from certain conditions and why are they dying from those conditions and we have a systematic way to track these things so there is a lot of emphasis here in terms of genetics but I do see a very very important aspect of this study that is not necessarily going to be genetic but setting up this large cohort that will enable us to understand cost of mortality mobility in a very comprehensive manner and really engage multiple centers across the continent I just want to comment because there is actually more infrastructure than you might think so there are demographic surveillance sites which are actually spread across Africa many of which are looking at quite large populations about half a million people so actually there is a lot of infrastructure there and of course you can't build infrastructure out of nowhere so you do have to build science on strength and I think that the network of demographic surveillance sites are very important they collect vital information about health and disease, about causes and mortality in countries where there isn't always vital registration so they are a pretty good place for many phenotyping studies to be done actually. The point is very well taken and I think H3Africa has the opportunity to build upon a number of other programs where African scientists and clinicians are being encouraged to participate in research in new ways. The Welcome Trust has their network already of such centers of excellence we have just started in the U.S. something called the Medical Education Partnership Initiative which is partly sponsored through PEPFAR and partly through the NIH which is aiming to try to build capacity in terms of research capabilities and training. There is an effort through the G8 meeting going on in Canada this week to focus on the needs for more research and other efforts in sub-Saharan Africa the Global Health Initiative President Obama's effort is now also potentially going to include some research activities and again focused in sub-Saharan Africa so it is sort of a moment where a lot of things are coming together and I think H3Africa can serve as a really helpful umbrella to bring many of these ideas in a coordinated way instead of having them all be disconnected. So the second question related to how we are going to sort of change the collaborative style of African scientists, Dr. Mayos? Yes, I just want to pick on the issue of the strength of genetic science in Africa and point out that although there appears to be areas of activity such as South Africa when you look at South Africa's contribution although it accounts for 30% of all the publications and genetics from Africa but actually the South Africans over at least the past 30 years have only been producing an average of 100 papers on genetics a year that for about 50 million people is in fact not a lot so that the existing genetic capacity even in those areas that are considered to be strong is actually relatively in the early stages of development and the need of strengthening when it comes to the networks I think as has been pointed out by Sir Mark the demographics of alien systems are there there's also been quite a lot of good work done by the African society of human genetics in terms of improving intra-African collaboration and they have also been more progressive funding funding initiatives that have led to institutions within Africa working together, universities such as the initiatives from the Wellcome Trust to build research capacity the initiative from PEPFA and NIH to try to encourage and build capacity within medical schools so more recently there's actually been quite a lot of intra-African crosstalk which I think is to be encouraged the universities are organized the academies are becoming more organized and this particular initiative will find an environment that is in fact ready to move forward other questions from the floor if not are there any questions from any phone callers I don't have anyone online just for the moment will there be any pathogen sequencing of this I would imagine definitely that there would be again if you were dealing with the genetics of infectious diseases I think you have to look at both the pathogen I would definitely imagine that would be part of this effort and maybe even the vectors please I wanted to ask about the chronic disease elements you said quite clearly that one of the things that you think you're going to guess out of this is the more original causes of some of these chronic diseases do you think you're going to find key differences in the way that these diseases develop in different populations as well is that what you're I know you don't know the answer yet but you've kind of got a suspect what the answer is is that the sort of thing that you're going to be investigating as well as are we looking for things that will help the rest of the world or are we looking for only things that will help African populations in dealing with what is a very fast growing problem but somebody could add more I can try to add some more to that I think again it would depend on the disease that you're looking at there are certain diseases that we have unique environmental factors that you can't do it in another place you have to be in that local environment to take advantage of what is it for example if it is a diet that has the implication of studying then you need to collect the data information within that environment to understand if you want to for example see the impact of salt on hypertension then you need to see how people are cooking their food and one of the things that is really interesting in the context of doing this kind of work in Africa we did a trial a sodium trial in rural Nigeria to see how reducing salt can lower blood pressure and it turned out that it was actually a much easier study to do in rural Africa than in urban Chicago or London because the source of salt in diet is limited most of the salt come as a result of adding boyan cube to your soup and teaching women how to reduce that or eliminate it significantly draw blood pressure by four millimeter of mercury that is a unique environment which we can do that kind of salt and also the fact that like what Francis and others have indicated is that at the genetic level you do have this opportunity to find map to use the African small haplotype structure to find map and to better localize signals that may otherwise be not so clear in European or Asian populations so the answer is that we are going to do things that would directly benefit African population but because we all share common history as humans that information I think for the most part we directly be relevant to other human populations other questions we have no questions coming from the panel at the moment have we not mentioned anything that anybody on the panel wanted to make sure we said or we got across all the points I thank all of you for participating we look forward to talking with you more about this as the program progresses and thanks again