 All right, we're going to resume the open session. One of the NHGRI is involved in multiple common fund programs. One of them that we have a very close association with is the Human Health and Heredity in Africa, or H3Africa initiative. NHGRI provides co-funding to this initiative. And for that reason, we think it's particularly important to keep Council apprised of progress in that. So Jennifer Troyer, program director at NHGRI, is going to give you an update on H3Africa. Apparently people in the back can't hear me. Can you hear me now? All right, excellent. And so at the NIH, this is a common fund program. But I just want to say at the beginning that it's actually a collaboration between the NIH, the Wellcome Trust, and the African Society for Human Genetics. And before I start telling you about the program, I'd just like to acknowledge that while there are a lot of people that are involved in making this work and everything that you're going to see, several of them are in the room or have been in the room in the recent past. And so first, Eric Green, the chair of our working group, of course, and then Jane Peterson and Mark Geier, who have both retired. Mark stays involved in the program, however, who really got this going. And Jeff Struing, who is still here. Ebony Madden leads our ethical legal social implications research program for H3Africa. Ken Wiley is walking in and involved in the bioinformatics and several of the research projects. I would be remiss in not mentioning our amazing grants management folks, Chris Darby and Diane Patterson, who have done Yeoman's work in making sure that all the funding gets where it's going and everything gets pulled out as it should. That has not always been easy. That we get progress reports that we need and so forth and then Laura Scowl, who is our program analyst for the program and make sure that everybody's where they're supposed to be, when they're supposed to be there and keeps things running. So H3Africa is a program that was established actually that we're now in the fourth year of funding. So the first funding happened in 2012 for really discussions about H3Africa. Several years before then and the vision for the program is to enhance capacity for genomics in Africa on the continent by African researchers. And so when the African Society of Human Genetics NIH and Wellcome Trust started talking about this program it was recognized while there was a sort of rich source of genomic diversity and material and interesting diseases to study. There was not always the capacity available and the resources available for the scientists on the ground to direct research programs in this area and to conduct them and that a lot of the collaborations were going outside the continent rather than inside the continent. And so the overarching goals are to increase the really ability of researchers in Africa to be internationally competitive in this field. In part by increasing the amount of intercontinental collaboration that goes on and also to expand infrastructure, both physical infrastructure and human resources on the continent and work on recognizing that there are particular ethical considerations when working with highly underserved and under-resourced communities and to try and solve some of those issues in a genomic content text for Africa. As are all common fund projects, this meant that the bar of being high risk but high reward and having long-term goals. And I will say that at the beginning there was a lot of doubt I think about whether this was feasible, whether this was the right time for this program, whether it would move forward, it was funded for five years, as I said, we're in our fourth year. Common Fund has now given us permission to propose the next stage, the next five years, which is one of the reasons for bringing the council now to get some comments about where we're going and where we are. And but I think that it is now seen as quite successful. However, our goals were long-term and another five years will greatly benefit the program. So I'm going to talk about that a little at the end. But first, where are we now? And so where are we physically and where are we in terms of science? I'm gonna talk a little bit about both of those things. Before I start though, I'd like to tell you a little bit about the kinds of awards there are for those of you who don't know already. There are infrastructure awards and those consist of H3Africa Bioinformatics Network and biorepositories. And the primary awards, the stars that I'm gonna show you are where the primary awards have been made. However, most of the projects I'm gonna show you have collaborating sites and those will come up later. So the H3Africa Bioinformatics Network or Bionet and one of the biorepositories are located in South Africa and then two other biorepositories are one in Kampala and one in Abusia, Nigeria. The next kind of set of awards that we have are research projects and these are investigator research, initiated research projects looking at genetic and environmental influences of disease. And the diseases can be communicable. So we have projects that are looking at tuberculosis, at HIV or the interaction with the HIV and tuberculosis. There's pharmacogenomics, there's trypanosophiasis, so pharmacogenomics, particularly for some of the drugs that are treating some of the infectious diseases. And then there are research projects that are non-communicable. We have a kidney disease project. We have schizophrenia. So several different kinds of cardiometabolic diseases. So non-communicable disease research as well and that was a very important component of this going in that it not just be limited to diseases that are in crisis at the moment, but really be the full range of biomedical research projects. Our research projects come in two different sizes and flavors. They're the collaborative centers which are about a million dollars a year and require that there be at least three different African institutions collaborating on the project as well as many more as they want both in and outside of Africa. And most of those are cohort studies that are doing collecting and developing cohorts and doing traditional association, genetic association studies with disease. And then, and those are awarded as U-54s, they're cooperative agreements. And then independent research projects which are U-01s which are sort of your equivalent of an R-01, so a smaller amount of money given to an individual investigator or sometimes a few collaborators. And those are the primary award sites for those projects. Then there's ethical, legal, and social implications research. And these have been awarded sort of staggered over time so we're now up to six of them and they're rather small awards and we might talk a little bit more about that later. But these are looking at issues such as stigma, communicating genomics concepts in different languages, under the understanding of genetics in under-resourced communities, the ethics of bio-banking and those are the primary awards there. And then when you add all the collaborating sites, you spread out over Africa and you'll notice that the purple dots which are our nodes for the bioinformatics network really span the continent pretty well. And there are at this point 35 nodes and 17 different countries that are developing the capacity to do genomics analysis. And then also, as I mentioned before, there are projects that are funded by the Wellcome Trust and those are in orange. So this is a lot of people doing a lot of different things but all focused around genetics and genomics in Africa and there's a governance structure. So we have several different bodies that do some oversight. One of those is our independent expert committee and members of this council have served on this including VAL right now. It's one of our independent experts and they come to our meetings, they meet by teleconference to discuss the program and provide advice to Wellcome Trust and NIH about how it's doing and what we should be thinking about. The steering committee consists of members from PIs from all the projects sit on the steering committee and that committee meets twice a week by telephone which is challenging sometimes, but we do it. And then now there's forming because there is now data deposited in the in the informatics network and there are biospecimens starting to be deposited in the biorepositories and so we're putting together an independent access committee that will review requests for data and specimens. And then finally, of course, members from NIH and the Wellcome Trust. There are several working groups and actually our composition of working groups is sort of always changing as we identify new needs. So in addition to this list of working groups there are now developing an HIV-AIDS specific working group. So some of our working groups are around scientific areas, some of them are around regulatory areas. I think cardiovascular disease working group is not on this list yet. And then what we're calling a sustainability working group to look towards funding in the future beyond what the Common Fund and Wellcome Trust provide. All of these working groups also meet either once or twice a month in report into the steering committee and they've developed several policies and guidelines that are followed by the entire consortium. So what are our accomplishments at this point? I really think the biggest accomplishment comes in this area which was one of the major goals of collaboration. This is, and I hope Val will attest to this as well, an extremely active consortium and very collaborative and work really hard despite the different time zones and barriers and being able to get on the telephone to communicate well with each other and to move things forward in a collaborative way. And so all these working groups have produced policies that now everybody is abiding by. They are working to coordinate training to make sure that their trainees in different projects have the opportunity to benefit from training that's being offered by somebody else. And then there are new scientific collaborations being established as well, which is what I think was the original hope for all this. Training is also one of the major goals and so there's a large group of trainees across the consortium, which includes students, postdocs, your traditional types as well as junior investigators, technicians and actually administrators. Administrative training is a really important part of this because many of the institutions have never received NIH grants. And then the Bioinformatics Network offers many courses which are taken both by H3Africa members but also by outside folks at participating institutions. So those workshops that they offer are open for additional people to learn. And then many of the trainees have opportunities to spend time at Roe, JCBI, Bail or Sanger, some of the best genetics and genomics institutes and bring back to their home institution what they've learned. Another place where there's been a lot of progress is this area of capacity building that I heard mentioned earlier this morning as well. And so while many of our sites are at centers that have a lot of resources, a lot of them are places which don't. And so there's limited resources, there's limited connectivity to the internet, ability to communicate, ability to get samples from one place to another. And then there have been issues like Ebola, like doctor strikes. And as you see, many of the projects span multiple countries and have to work through the regulatory issues for multiple countries. And despite all these sort of challenges, our investigators are really making good progress and have a great attitude about it and figure out ways to make things happen. And so there is science going on as well. And so this is actually a slightly old slide. We now have, at this point, 35,000 uncounting samples that have been accrued and over 40 publications with many more on the way. A lot of these are conceptual. What is this project trying to do? But some of them are quite deeply in the weeds of science and bioinformatics. Ebola was one of the things that many of our investigators worked on. And then policy. And all of this is leading towards sustainability, which is something that we're really focusing on, moving forward, leveraging resources and building knowledge and reputation and interest from other organizations. So I wanted to show you that not only do we have samples, but we also have some genetics data. And so this is from some whole genome sequencing of some samples from Botswana. And as you might expect, there are about 15% of their SMDs that are not seen in 1000 genomes. And then not only are there novel variants, but there are novel populations that are not currently represented in our data that's publicly available to date. And so if you look actually two different populations from Uganda, one falls sort of where you would expect it to up there in the red circle and then another one is completely unique down here in the green circle. And then also projects are starting to correlate genomic data with phenotypes, which is the ultimate goal. So this is looking at transcript analysis in asymptomatic and symptomatic and uninfected people and try panesomatic. Finally, in the area of capacity building, Christian Happy in Nigeria has an award and to look at papers of unknown origin, including Lasaviras and Ebola. And this was long before the Ebola outbreak, but he works in collaboration with parties to be at the road. And they had a site in Sierra Leone. So we're sort of front and center of the outbreak when it started. And most of the samples were taken and sequenced at the road, but at the same time there was money from H3Africa for training. And so they trained a bunch of scientists from Africa at the road that summer on those samples and then continued sequencing them back in Nigeria when they were able through the effort of a lot of organizations, not just H3Africa, to get their lab set up. And so near the end of the outbreak, they were sequencing in both places at the road end in Nigeria and now they're all set up to go on their own next time. There's an outbreak. So that's sort of where we are in this first stage and ultimately if everything goes as planned, what we'll have at the end of five years is a lot of resources and a lot of potential. And so there's the infrastructure that's being built. I'm not gonna read through all of this, it's very wordy. And the samples and genomic data and I will say different projects are collecting different types of genomic data. So there's some genotyping, whole genome, exome, microbiome, viral sequencing. There are some epigenomics. So there's a lot of different kinds of data. But a large number of the samples will actually be genotyped on a pan-African genotyping array that is being developed right now that has included several populations that are unrepresented in many of the other SNP chips. So I think that will be very useful, not just for these projects, but for other projects moving forward. In addition, there've been a lot of work on guidelines, policies, SOPs and some work on broad consent on bio-banking in different African countries. The ethics working group has been very active. The community engagement working group has been very active, really proactive in trying to push forward conditions under which genomics research can be done fairly and equitably in Africa. So that's where we are. Where do we wanna go? So I'm not gonna go into this in great detail either except that each of those lines is sort of an award and when it was made and when it ends. And this is the first stage of H3African. It's really been a capacity building stage. It's taken quite a while and quite a lot of work to get to where we are, which is that we're sort of at a steady state now of sample and data collection. We're able to store DNA, bioinformatics support and training is there and ethical legal social implications research is going on. What we'd like to do in stage two is move on to implementing this capacity. And so rowing the sample and data collection into analysis and publications and new projects and not just DNA storage but actually sharing of the DNA samples and other samples involved that are being collected, increasing the amount of bioinformatics capacity and having the people that are learning now actually out there doing bioinformatics and training new folks which is beginning to happen actually they're getting hired at other institutions for instance and then doing more in the area of LC research but also applying the best practices that people are learning. And the goal of this is that when it's all done there's a really big round of support for projects of interest both to the institutes and centers here on NIH but also other funders because this is not in a vacuum and we certainly H3Africa can do a very small part to make this happen. It has to happen with input from a lot of other people. So just briefly this is the consortium as we see it now which is that there are the eight collaborative centers seven biomedical research projects the Bioinformatics Network actually also serves as the coordinating center and works closely with the steering committee and working groups. There are the LC projects and the biorepositories and what we'd like to do in the next stage are some modest we think increases in funding in particular areas. One is to separate out the coordinating center from the Bioinformatics Network and let them do analysis which is what they're really there for and have the capacity to grow. Increase the types of samples that are being collected in the biorepositories so that they're useful for more types of research. Provide more funding for the LC projects which were actually substantially underfunded in the first round. Add a training program, a specific training program and the ability to have ethics research in collaborative centers, something like the CRs and also some research projects that focus on biorepository issues and bioinformatics analysis methods and then hopefully grow the research portfolio as well because of contributions from other institutes and centers. So moving forward, we know as I said that we don't do this in a vacuum and there are actually a lot of organizations within NIH, other funding agencies and then organizations that are growing up in Africa that recognize that while funding and a lot of sort of the direction of research has been pushed from the outside and there needs to be more of it pushed from the inside in terms of both collaborations and support. And so we hope to be able to work with a lot of these organizations, welcome GSK, Gates, governments of African countries, and then coordinate with the things that are going on in Africa already to turn a lot of the challenges that there are in conducting this research in Africa into opportunities. So as I said, there are a lot of people that are involved in this and this list of both institutes and centers and folks that are working on this grows every day. I do wanna acknowledge, I think Regina James is in the back of the room and she's been a big help and has really supported a lot of the administrative training that I was talking about and I'm happy to take any questions. So on your last slide, you list a number of African organizations. Can you give an example of how the interaction with both? I'm really interested in your picture with the internal cycles of enhancing that rather than the external sources coming in. So how to build the internal ones. So those organizations you cited, I don't know anything about those. Can you talk about how? Yeah, absolutely. So one of the big things that's happened actually in the last year is the formation of this organization called AISA, which is accelerating excellence of scientific research in Africa. And it is an offspring of the African Academy of Sciences and the African Union, which were two of the other ones listed. There's also NEPAD, which is a new something partnership for development. Lawn, do you know what NEPAD stands for? No, I'm only asking Lawn because GSK has actually been doing a lot of capacity building in Africa and we've been in conversations with some of their folks about some of the research that they're supporting there, particularly around non-communicable diseases and potentially pharmacogenomics. So anyways, the organization AISA is an attempt by some of the agencies, the outside agencies that fund in Africa to move the center of gravity of both decision-making for what gets funded and the management of the grants to the African continent. And so it is based in Nairobi and Tom Karyuki is the director and he was appointed probably about a year ago now. And he has come to our H3Africa meetings and we have gone to their launch and met with them. So there's some collaboration going on now. Welcome Trust, as I said, funds some of these awards and some of the H3Africa projects and they are moving a lot of their programs to AISA and it's possible that their part of H3Africa will actually be managed through AISA when they continue. Gates is awesome managing some programs through there. So it's just an attempt and then AISA themselves are pushing because they have the African Union connections to get governments to honor their commitment to commit 1% of their GDP to scientific research and things like that. So there's movement in that direction there. Since you alluded to GSK a couple of times, I think council might be interested in something that's going on there because it's relevant to H3Africa. Absolutely. So GSK is a big pharmaceutical company and has taken the long view of the aim of developing new medicines for Africans in Africa rather than repurposing existing medicines and taking them over to Africa. And so in doing that, there are a number of partnerships and near term relationships being built. And I think it's a real testament to what you've done with H3Africa that GSK has decided to learn from you and to build on the infrastructure that you've set in place and the policies and the capabilities and the relationships in fact, rather than try to do that de novo. So it's great to see this happen and it's great to see you take the lead on that. And I will say that we're, so a mutual compliment here is that one of the things that GSK has done that allows us to have this kind of conversation and collaboration is that they are relinquishing all rights to any IP and making their data public and impact many of their resources publicly available as well for this project. Yeah, thank you guys. I think this is a very exciting program. The slide that you showed the other programs like MAPI and the Fogarty training programs, some of them have ended. How is it, you know, is there planning so that they will be refunded or reviewed? So we're actually in the next round gonna work a lot more closely with Fogarty to have some of the, so there is a version of MAPI, it's not the same as it used to be, but and they're actually now doing more training in the area of research and Fogarty is actually going to manage the training portion of H3Africa and make it integrate better with some of the programs that they run there. So those, they're not entirely, they're not gonna be disconnected, they're gonna be integrated more and we're trying to continue to build on what resources have been put into it rather than start from scratch. Yeah, I just have a few brief comments. I am on the independent expert committee of H3Africa, I'm comfortable with the independent part, not so comfortable with the expert part. However, in listening to your talk, I just wanna point out a few things. Some of the successes from my perspective is definitely the involvement of young African scientists. There's, it's really been amazing. Very excellent young trainees and their involvement's great. Another thing is the collaborations, you mentioned it, but the culture of collaboration has definitely changed from the first year to the current year. People really are collaborating and you do see really a shift in the culture there, which I think is a great success. There's obviously a lot of logistical problems, a lot of them have been overcome, but there's even things like culture-specific consent forms that we don't necessarily think about so much here. Their bio net is first rate. Yeah, I didn't talk a lot about that. And there's a lot of increase in the training opportunities both in Africa as well as some collaborations here during the states and probably in the UK. There are diseases that are being approached that would probably be disorders that would be approached in this country 50 years ago and are now still being studied there and need to be studied there. For example, rheumatic heart disease is very prevalent in underdeveloped countries and African countries. And so maybe going along the lawn's point, maybe penicillin is still a drug that has a purpose there and doesn't need to be repurposed, but there are some issues, some things that have been sort of slower than expected. For instance, there was a goal to make an African, specific or an African-enriched snip array, high density array. I'm still not sure where we are with that. So current projection is that it will be in hopefully April, May timeframe. So before the next consortium meeting it's supposed to be there, but there's still negotiations going on. Yeah, so that's an area where that's the same answer that would have been given two years ago. It's always four to six months in the future. And sometimes that perfections the enemy of good and another issue that I've raised in some of the committee meetings is really the need for the snip array with technology improvements and going to, OX, Omo Genome Sequencing. People are still in favor of the snip, but that's... Yeah, and I would say one of the other areas where things really lagged was referred in. I think most recruitment. So getting IRB approvals and actually getting things going. There was a while when it looked like people wouldn't be able to meet their goals and really in the last year that changed. Yeah, I was gonna bring up that too, but the numbers you gave here 35,000 is pretty good. Yeah, very, very big difference. Yeah, that was a terribly interesting presentation. Thank you. It's very exciting and the notion that there will be data from Africa about genetic variants that aren't seen necessarily here or in these larger collections, it's very exciting. But my question is about thinking about Africa as a site, it seems ridiculous, right? Because there's so many countries and so much variation across the countries. But I wonder if some of the ways that we think about programs or research projects that are in the realm that I'm more expert, not really expert, but more expert in the LC program might really be quite inadequate to the task of thinking about the issues in H3 Africa. Now, it's also likely that I, because I don't know a lot about the LC grants for them, they're probably very focused on particular countries and particular issues with consent, et cetera. But it really strikes me that this is an opportunity to think creatively about barriers and facilitators which are more organizational, which are more political, which are more economic, which not so much, how somebody explains genomics in a population that they're really not at all familiar with that the scientific concept. Or that people are afraid of donating blood because blood is a very special commodity in some parts of Africa, et cetera. But whether you are thinking maybe about recasting LC research in a way that I think could be quite creative. And I didn't see any of your other working groups that might encompass that. But anyway, just a question, whether that's come up. So Gail, that's a great question. And I don't know if Ebony wants to talk about this at all, if she's in the back. But I will fill in unless she comes up to a microphone, which is that, you're right, the individual projects are very specific. But there's an ethics working group that has really taken on this challenge of the bigger questions. And so some of the first work that they did was in tackling the question of broad consent and sample and data sharing across the continent. And one of the things that was very clear at the beginning was that there was a huge difference in the way different IRBs or research ethics committees were viewing this. And so they actually applied for and got some funding to bring together research ethics committee members from all the different sites. So I think we had, and Ebony might remember exact numbers, but something like 35 to 40 research ethics committee members in the room talking about their concerns and what they would consider acceptable and not acceptable. And then they were brought back a year later and the tenor in the room had changed so much just in spending that period of time, both in the room and then the intervening year with emails and updates and the report back from the meeting to not, we don't like broad consent, but how would we be willing to accept broad consent? And their recommendation at this last meeting was that the next time this happens, which will be in Senegal in May, we bring policymakers. And so that's what's happening in May is policymakers from different countries are coming to the table. The other area that that group has tackled and Ebony, I said you might want to come to the microphone and add to something if I missed something. But one of the areas that that group has tackled now is the different regulations about biobanking. And so they've taken, yeah, so they've taken where they could find them guidelines or policies or national statements about biobanking that exist and compiled that and are doing some analysis and some writing about that. So they are looking at, I don't know if that's exactly what you meant by these bigger issues. This is also the reason why we wanted to have a collaborative center for ethical, legal, and social implications moving forward rather than just having individual projects. So go ahead. Yeah, I mean that's sort of logistics and development in a working group isn't quite research projects, but it's very interesting. And that has a flavor of the kind of thing I was talking about. I'll be quick to help Rudy's blood pressure. As you move towards implementation, what are phenotypes that are shared across the various centers that you could actually put together cohesive, you know, continent-wide would be ideal, but probably not that far. But multiple centers working toward a shared goal. So that's a great question. And so we have another working group that Jeff's ruling works with. Which is a phenotype harmonization working group. And they have identified eight core phenotypes that everybody is looking at. And you know, some of the, they're not very deep or complex, but then they've also set standards for measures for additional phenotypes that could be explored. And then there are five through the consortium. There are five really six grants now that are looking at various aspects of cardiovascular disease. So they're coming together around hypertension as a phenotype that they can explore. So that is going on. I would echo the positive comments that have already been made about ACE through Africa, but also I think piggybacking on a comment made by Gail is about the one issue you raised about the rather limited amount of funding that goes to the LC program within this initiative. And I just wondered if you have any thoughts about a strategy for how to get more money to allocate to this particular component? Well, I can be useful too to help you do that. Our current strategy has been to ask common fund to more than double, I think almost triple that budget, that portion of the program. But I don't, we don't have an answer from them yet of what they are and are going to fund in the next round. And so we should know by April. And then if they don't, it's a conversation that we're gonna have to come background to institutes to ask for additional funding to get some of these activities going in a more robust way because they really do have limited budgets now. So I think this all sounds great. I was curious about how you think about, so the challenge of balancing bringing in expertise from outside of Africa where dealing with research, issues that come up with the research that aren't, where there's not expertise within Africa to contribute. And yeah, I was just wondering about how you sort of think about the balancing act of growing expertise internally versus contributing to projects. You know, that hasn't been as big a concern as you might think in that, I mean, we all know what we do in genomics now. It requires all sorts of expertise from all over. And certainly, there is no policy in H3Africas that says you can't tap into expertise from anywhere. But there's also a lot of expertise on the ground. It just hasn't had the resources to do what they need to do. So it hasn't been as hard a balancing act as you might think. Okay, thank you very much, Jennifer. We probably need to move along now.