 So we wanted to have this be an interactive round table style exchange, and I've asked all three of our speakers to come prepared to talk about two subjects. And the first one is about should we, as a government, of many different constituent parts, should we make a special effort now to better unify, to better integrate our R&D efforts in the area of tuberculosis? And if so, why? And in what critical areas and what are the concrete steps that we need to take? So we're going to start with asking, we'll start with Tony and Eric and Peter, and try and dig into that subject and we'll take a portion of our time to cover that. And our second topic that we'll turn to is really about one of the points made in the report and made in the paper that Peter was lead author on, which is about thinking strategically in long term about the need to build bigger and better long term platforms with emerging outcomes are going to be found. And should that be a priority of our strategy? And if so, what is it going to take to make that happen? So those are the two, those are the two start-off, the two questions that we're going to use as a frame here. Tony, would you like to leave off? And that first question? Yeah. Thank you very much, Steve. I appreciate the opportunity to be here. I couldn't help but think when you asked the question, and I actually just checked it on my iPhone, of we go back because I've heard much analogies and relationships between the HIV effort and the effort which all of us would like to see done with tuberculosis as an individual disease in and of itself and the obvious overlap with HIV. And at the end of about 20 years of a phenomenal effort that we put into HIV AIDS, my colleague and I, Greg Fokers at the NIAID, wrote a commentary in JAMA in 2001. And I entitled it just almost as if I was planning on this meeting. And it was the HIV AIDS pandemic, a model for diseases of other global health importance. And I was thinking specifically of TB as number one malaria and then neglected tropical diseases, which actually gets right to your question. Should there be a concerted effort in the arena of R&D? And the answer is yes and be careful because one of the things is that when I think about the R&D effort, I just have this picture in my mind which I translate into slides of fundamental concept development all the way on the left upstream through the early preclinical development, understanding pathogenesis, developing a concept with the thought in mind of three interventions, diagnostic treatment and prevention, and as you work your way from upstream to downstream, you get to phase one, you get to phase two, you get to early product development, advance the product development and licensure. So when you look at that spectrum, the answer is if you take it as a whole, yes, we could benefit from unification, coordination, a lot of which we're doing, but we're doing it in a way that I think is very productive but that we could benefit from doing it better and doing it a little bit more intensively. The only caveat that I have about attempts in other arenas to unify, coordinate, develop some ZAR that's on top of it all is that that gets pretty dangerous when you're doing the concept development and the fundamental research because that almost invariably gets in the way of that spontaneous creativity that you need, but as you go further upstream, clearly you want to synergize and utilize all of the possibilities that are available. So you said three minutes, I'm at three minutes, may summarize by saying that I think it is a good idea depending upon what stage. When I wrote that article 13 years ago, I was referring to the entire spectrum and as I said early on you still need new concepts, investigative initiated ideas that don't need to be coordinated. Once you get into the line towards developing something then it becomes more and more productive to do that. Thank you Eric. Well thank you Steve, it's a pleasure to be here with my friends and colleagues, mentors for this discussion. I think that the importance of coordination at all levels has been echoed all day to day in many of the discussions. But I think that we have under-emphasized the real importance of coordination at the ground level. We can be coordinated in Geneva, Washington where we really need to converge our effort is at the country level and holding our colleagues in country responsible for the planning and implementation elements of putting and realizing the benefit that the science affords but needs to be put to ground in a program so individuals who are burdened with the disease can take advantage of it. I think that we need to take that to heart and look at what are the elements that we currently have in our toolbox to support that definition of the problem, the ability for us to define and understand the geomapping of where the populations are in each country, how that country's medical delivery system does or does not interface with those populations and are they able to identify, enter and retain those individuals in care over the duration of what is in the case of TB a cure intervention. We're not talking about a long period on antiretroviral drugs like with HIV but we have a disease here that we know how to prevent, we know how to diagnose it and we know how to treat it to cure it but we are unable to put that machinery in place to kind of orchestrate and ensure that impact. Yeah, so let me just make two quick points. I mean, I think the first is that we're at a critical juncture in global TV control and this is a juncture in which research and development is particularly important. I mean, we heard it from Mario and I don't think he can say it better. You know, 56 million people treated, 22 million lives saved. I mean, that's an enormously successful enterprise and yet this TV situation is evolving rapidly with the drug resistance, TB, HIV, other comorbidities, we've got migration, we've got increasingly complicated health systems and so if we don't move with the epidemic, we will not get on top of things and I think that we desperately need innovative tools and we need new approaches and what's great is that after decades of neglect, I think we're starting to see some really remarkable progress and I think if we look at what the NIH has done, the funding is bringing in some of the brightest young minds using the coolest technology and this is really transforming the field. Equally importantly, we're looking at public-private partnerships who are taking that knowledge and turning it into products which are already affecting people's lives and I know that because when I was in India for a couple of years, I met people whose lives were literally saved by the gene expert. I think the second point that I would make is that the U.S. has, I'll just say it, we've always been the unsung hero in global TV control and I think that we are poised to actually drive global efforts to modernize TV control and in the report it's pointed out that almost 60% of the world's R&D is funded by the United States and I think that's fantastic. I think that's an incredible, incredible good investment. What we've seen from that are a number of new diagnostics, two entirely new drugs and we've seen a growing pipeline of vaccine candidates. I'm super excited about PAMSI. This is a new drug regimen which will, within five years of launching the Phase 3 trial, we will know whether this is going to be able to change the lives of hundreds of thousands of people with drug-resistant TV and if I could just make the one specific recommendation is I think that we all need to really rally behind that Phase 3 trial, fully fund it as quickly as possible because this is a truly transformational progress. So if you are trying to make the case to the White House that the R&D issues are prioritizing, giving visibility, giving energy, better coordination and unity of effort at the right stage and what would the case look like? How would you make the case to a political leadership that the R&D sphere is an area where we already are in a strong leadership position, where the returns are there and the U.S. national interests have reached a point where you could feel comfortable making that case? Yeah, what do you think, Tom? Well, I'll tell you what I've been talking about for a really long time. Yeah. Multiple times a year and testifying before the Congress, multiple times and testifying before the administration everywhere from the department level up through and including the White House and OMB. You know, and sometimes it's not on the radar screen that you'd like it to be on, but when it is, it's the time to jump on it. The argument I make from the standpoint of the U.S. government is that something that we really began to realize in its full form when HIV came along and that is that we live in a global community and we cannot just think of other people's diseases and our disease. And it's more than just humanitarian, it's enlightened self-interest, it's economic, it's security, it's all the things that many people in this room have spoken about. And I bring examples of the extrapolation of how we went from fundamental basic research to extraordinarily dramatic interventions that anybody and everybody would agree have been essentially game changers. And I think that we should use the HIV story, not in a competition with TB, but as a phenomenal example of what you can do when you make an investment of basic research through early clinical research through product development. I think that the drugs that have been developed over the years for HIV, they just speak for themselves. That's the first thing. The other point that I make is I use the issue of the history of vaccinology with diseases that have now disappeared. I mean, the obvious one is smallpox and hopefully soon polio, but also what we did not too long ago with some fundamental basic science observations and development with the conjugated homophilus influenza B vaccine, which went from a disease which was the leading cause of bacterially related deafness and mental retardation to disappearing. Those are the things that they listen to. Things disappearing. They don't like things lingering. They like things disappearing. And I think the point that Eric made is a good one because the thing about TB that we can really argue for is that you can cure it. You can actually cure it. And that's the reason why there's a lot of activity right now talking about vaccine and cure for HIV. Because those are the ones that are the showstoppers. You cure, you don't have 35 million people that you need to keep on therapy forever. You get a vaccine and then you turn the dynamics of the epidemic around. Those are the kind of arguments you make that there's an end game here. It's not just give us more money and check with me in a few years. We're going to put an end to something that's an extraordinarily plague. It's about argumentation and the atmosphere. I mean what I hear from Tony is that there is an excitement around the return to a much more scientific focus discussion around HIV. It greets an open. People have an appetite and an openness to talking about these issues in a new and different way. As Peter was saying you've got options in development that you can push hard on that are specific and concrete. Well I would really emphasize what Tony is saying. I think that our political colleagues have different metrics and different pressures on them to produce. We, and I think that Tony was really central in this kind of epiphany that occurred, where scientists began a different dialogue with HIV with the political elements in our country that resulted in accelerating our ability to take a scientific finding, a discovery to the individuals that would benefit from it. And I think we saw in HIV the convergence and orchestration as Mario was saying of the critical role that civil society plays in facilitating that glide path. It takes all of it and without any one component we cannot put program on ground to benefit those that are suffering or dying from the disease that we now may have an understanding that has true application that can drop morbidity and mortality. I think TB is a frustration in that we have had answers to many of those questions for a very long time but have been unable to move it to benefit those who carry the heaviest burden of disease. 33% in India is a shocking statistic. Peter has been there for the last few years trying to understand on a more granular level what are those bottlenecks that prevent the benefits that we already have identified from being realized. And it's the orchestration and all of those components that need to converge in the same time period to make it happen. I think our inability to turn up the volume on the elements of implementation that allow you to put program on ground from my perspective remains the rate limiting step. Joanne alluded to what's the rate limiting step? The rate limiting step is really not the science. It's not having models or examples of high impact or efficacious interventions. It's the variety and variation in the substrate you can use in any given clinical community, medical delivery system interface that allow you to put that program in front of the person who needs it, when they need it, on every day that they need it. And I think TB has evaded our ability to pull those all together to have the impact that we know we can produce. The political will is critical. Without it, it stops. The science without it, it doesn't happen. The community orchestration without it, we do not have the feedback loop created that comes back to both the scientists, the providers, and the political layer to continue, maintain or change, augment, discover something new that allows the changing needs of that population to continue to be addressed. Let's shift and talk a bit about the emerging economies. We've posited in the paper and in the summary paper and the overview and in the R&D paper that Peter led on that it's important that we think long term about building research partnerships and platforms in those key emerging economies which are heavy burden. Peter can you talk a little bit about that and what is it going to take? If we agree to that proposition, what is it likely to take? It's not like we're starting from scratch by any means. Well, first of all, let's recognize they're one and the same, right? The emerging economies are all high burdened TV countries. They just take India, China, and South Africa and you're talking already about roughly 40% of the world's TV and maybe 60% of the world's drug resistance. But I think we have to give them credit for more than their disease burden. I think what we're seeing is that they have increasing R&D capacities. They have growing science and technology budgets. They are increasingly seeing themselves as leaders on a global stage and showing leadership in particular, I think, some on TV. I think that the key is really to foster local expertise and platforms. And it was mentioned several times today and I think what we just have to really double down on our efforts to increase the R&D capacity amongst key partners, these emerging economies, these are not short-term projects. We have to make long-term commitments, nothing less than a decade. But I think that if you do that, you will bring in some brilliant new minds. I think you will find that R&D is much more locally relevant. The products are likely to be much more frugal and globally applicable. And I think ultimately you're going to bring in the support of the countries themselves to sustain it. I couldn't agree more with what Peter said. We found from my perspective that I operate in as the director of an institute that the interaction with low-income and to some extent middle-income countries that don't yet have a research capacity that are really in their own incipient stages, we can get a lot done by helping build up that capacity as well as back and forth training. With the BRICS countries, it's a different experience and it's actually a very energizing experience. It's something different because you have in those countries some really, really good people who really need the collaboration. I mean, we've done it in three separate ways. One that I think the audience is familiar with, the report international, which is the regional perspective on observational research in TB, which involved the countries that Peter mentioned. It's an observational cohort study, but it really kind of opens the door to two separate approaches that we've been taking that are synergistic. One is to take our intramural scientists and develop country-to-country and individual-to-individual collaborations, where we have people in Brazil, in South Africa, in China, in India, in South Korea doing development as fundamental as basic to screening drugs to developing clinical trials. And we also have a program now where we're funding extramural investigators in an interesting way of collaborating. That's somewhat novel, and that is instead of funding our investigators to go to one of those countries or giving money to do work here that's relevant there, we make a deal with the country in question, and we have this with China, we have this with others, in which the Chinese funded investigator, we funded investigators, so we both have skin in the game, but we're working on a collaborative project. And that's really been very successful, and I think that's the kind of thing that's going to lead to enduring results and enduring collaboration, so I totally agree with what Peter said. Eric, what are the political obstacles, do you think? We've seen the sensitivities around Russia, right? I mean, it's the complications of trying to make sure, in the midst of a very turbulent situation, that you don't sacrifice those standing relationships, and we're seeing, the nature of this is that you're going to have sovereign sensitivities, you're going to have tensions, you're going to have to anticipate those and deal with those as you work ahead, how do you do that? Well, I think the long, I think you have to have a familiarity on part of the political leadership with the challenges that are present in the healthcare delivery systems that they are responsible for. I think that comes from activities like the co-principal investigator, one in one country, one in another country, working on a common project. It comes in elevating the scientific investigation agenda in the political campaign, political party that comes from a grassroots understanding of the importance of that for themselves, for their children, for their people. It is almost as if a light bulb goes off for some leaders in countries where they realize that this is their electorate and that if their electorate isn't healthy, that it impacts their political viability, longevity, but it is a threshold has to be reached on part of that political leader where they realize that they are the individual who's responsible for investing in their people through health and education, and I've seen it in country after country. If that understanding is not there, you're often talking to an individual who doesn't take your information and move with it. It's a delicate convergence of information, understanding, pressure, and fear that I think has to be generated in that political leader to act. It comes from the World Health Organization, the United Nations, making these issues important and relevant. It comes from our ability to describe that with epidemiologic surveillance data that is not at one point in time but continuous. The 17 years that Mario showed on the reports allowed us to have high levels of confidence in saying that this is where we are at this moment in time with all of the problems in sampling errors. And it then takes somebody close to that political leader to translate the jargon into here's the bottom line common sense act that you need now to put in play. It is rare that a political leader, even political leaders coming from medical backgrounds, see the political utility of focusing on the health of its population. It's not the first thing they think of. And I think it takes that ongoing narrative to get them there and keep them there. Thank you. We're going to turn to the audience for some comments and questions. We're thrilled to be joined today by Debbie Burks, the new Global AIDS Coordinator. Deborah, thank you for joining us. If you care to offer any comments, we welcome that. Sorry to put you on the spot, but since you're here, maybe you'd like to say a few words. And then behind you, I think, Tiaji, did I see you? Yes. Yes. So, Deborah. Well, excuse me. I just flew inside. I just came to support this illustrious panel. So they're all mentors of mine. We just came from South Africa with our annual meeting. And the gap even among the TB identified in clinic patients between them and access to ART is still a phenomenal gap. Because it's not an excuse. We no longer have the excuse of not having the patient. The patient is in the clinic. It's getting, patient is getting dots every single day. Yet they've not been tested for HIV and they're not receiving ART. And that gap is between about 45% as a mean to about 80% coverage. So there's still, even though we have the patients and we've had that dialogue, we still have that gap. So from my perspective, from where I sit, that's still inexcusable that we have that gap. Now when Ambassador Goosby took over that gap was huge. It was more like only 10% or 15% were on ART. But with the new WHO guidelines, 100% should be on ART. So that gap is quite compelling for us. And we worked very hard in discussing that and what we need to do. So sometimes you can have all the tools and all the knowledge and all the ability and you still have this programmatic pieces Ambassador Goosby was saying. So I think we still have our work to do to even implement what we're supposed to be doing right in this very moment. The gene expert pieces in South Africa, we heard report after report that there's a backlog of about 50,000 diagnostics that have not led to patients being treated. So the samples have been run, but the patients have not been, have not, and then they had MDR and they have not received MDR treatment. I think sometimes our technology is superb, but we don't often follow that with program. And I think we have to ensure that as we roll out these really amazing instruments that we have the program behind it to ensure that that happens. So it was a great meeting. We had our annual PEPFAR meeting, but it was also still sure that we have a lot of work to do together. Thank you. Tiaju? Other hands. Thank you all for coming. My name is Tiaju Salam Blyther. I'm with Congressional Research Service. I just want to say I'm such a DC nerd because I'm so excited to be in the room with the current and former ambassadors of a PEPFAR. So it's just like exciting. Thank you for being here. So I would like to say I want to thank Ambassador Goosby for mentioning something that I think, I don't know if it kind of, he kind of said it so smoothly. I don't know how many people picked up on it, and it's the health systems piece. I think part of the reason we're seeing such a challenge with TB is because if any of us who have been out in the field know much of the resources, the health resources are concentrated in the cities and in the major cities and in the capitals. And TB is a problem that obviously hits the more vulnerable people. So when you get to the rural areas and when you get to the peri-urban areas, there's a lack of diagnostic capacity as well as human resource constraints. I wanted to ask the panel, since this is about R&D, what type of field-based research is happening that may excite us like maybe how we've seen the use of vinegar to detect possible cancer in women if we could possibly talk about something like that, some low resource research happening in the field with TB. Also not just in terms of clinical research, but also operational research, how we may be able to get around basic diagnostics in areas with human resource constraints and diagnostic constraints. Thank you. Thank you. Let's take one other in this round. Yes, sir. Thank you. It's working. It's working. Peter Hale, Foundation for Vaccine Research here in Washington. I think we all agree that political leadership and political will is critical, as Eric said. But so I'm very concerned that there seems to be a disconnect between the administration and Congress on increased funding for TB. My special concern is a recommended budget cut of 18% by the administration for USAID. It's not just USAID. What do we do about that? Okay. Thank you. Who would like to start off? There's a couple of different questions on the table, Peter. The health systems issue, you know, maybe it was 20 years ago, but when I was doing NIH funded research, I thought that few things could be as complicated as my bacterial genome. And having spent two years in India, I'm sobered by the complexity of health systems. And I spent months really just putting my head in the space of the patient who's sick and poor in India. And the completely insufficient choices that they're faced with. And from that perspective, and I think Debbie mentions it as well, when you actually look at the realities on the ground, you wonder how anything is actually happening. And it's possible to get incredibly depressed. And I won't say there aren't many days that I was. But for me, the focus on implementation science, implementation research, how do we roll these things out here? How do we change those anecdotes to data and then track that data and actually hold ourselves accountable for it? And I'll just mention one project I'm super excited about, and that are standardized patients. So beginning in a few months, we'll be having about 400 trained patient encounters in Mumbai and in Patna, two big Indian cities. These are people that go in and say, you know, I've been coughing for like three weeks and I'm coughing up blood, you know, what should I do? And the shocking data that comes out of that is that only 8% of the doctors are even talking or thinking about tuberculosis, right? So this is enough to make a person who's spent their whole life in TB completely morose. And then you think, well, but at least we have something to track now, we know what the challenge is. So I do think that this issue of implementation science is really critical and that rather than getting depressed by the early results, we just look at like how much easy, how, what a low hurdle we've got for ourselves right now. Eric, do you want to speak to the issues around programmatic, what Deborah was arguing about? Well, it's really gratifying to hear the current global aid ambassador speak to the undone part of this effort, because it is going to take that kind of intellectual honesty on part of our USG efforts, but also our colleagues as a multilateral sector. But mostly our colleagues in the ministries around to look at what they're doing, what they aren't doing. And to be willing to ask for the technical assistance to put the program in place. We need to be able to be ready to respond to that request in a way that allows for a sustained relationship to capacity expand that ministry or that planning body in country. It may not be the ministry in other settings to implement. And so I really want to echo the importance of that. There are many efforts that PEPFAR has already initiated, trying to look at the elements of identification, entry and retention of individuals over time. Both Zambia, Kenya, Tanzania, South Africa have at kind of the site level studies going on that will give us insights into where those bottlenecks are. I'm old enough to know that the solutions often are idiosyncratic and country specific, almost site specific. So a one size fits all approach is not going to work, but what we need to do is to support, nurture and create that creative mind in the country who's there all the time, who sees a new wrinkle on a problem, but has the ability to take that in, fold it back out with a solution. We need to be in a supportive role, but a constant role with it. It's not going to happen with a two week technical assistance visit. The question that Peter raised about the budget cuts and a gap between Congress and ministers, I mean the bigger problem it seems to me is that we're in a constrained budgetary situation in which there's going to be further tightening and it's going to be more difficult looking forward and there's just many competing priorities, right? There's many good work to be done and so TV is competing, right? It's competing against a whole bunch of other things. So how do you think about that and how do you proactively energize and make sure that the priorities are aligned with what you think is really important? Steve, I'm glad you asked that question because when you talk about R&D, it's a different picture than the question that was just asked because when it's R&D, I mean real research and real development, TV isn't a line item. So I think what people don't appreciate is that the administration or any of the Congress could not, unless they do something extremely unprecedented, cut TV research. The perverse aspect of what's going on with a flat budget is that you can't take advantage of scientific opportunities that are more intense in TV now because we're in such an incipient phase. We felt so far behind when I became director of NIAID a really long time ago, the budget for TV I thought was a typo. It was like $600,000 for two grants that we had. It's now $165 million, $170 million. And the reason we were able to do that is because when the research, and I'm talking not about TV implementation and USAID, I'm talking about the fundamental NIH type research. As the NIH budget increased dramatically over years from the usual, the NIH budget doubles generally every 10 years from 1998 to 2003. It doubled in five years that when it increases, you have a lot of flexibility in jumping on scientific opportunities. So I have a slide, Steve, that you've seen that has what we do is balanced by the scientific opportunity and the public health imperative. So right now TV is smacking with scientific opportunity and public health imperative. So I was able to do a lot of pushing towards TV research without hurting anybody else because there was an increase in the NIH budget, particularly during the doubling years. When we used to get 14-13% per year increase, for the last 10 years the NIH budget has been flat. So with a 2-plus percent inflationary index, we have lost in the last 10 years 25% purchasing power. The budget that I had to defend before the Congress last month and the month before was a 0.7% increase for NIH. So it isn't that I'm going to cut anything, it's just that I have no flexibility to jump on opportunities with TV research unless I, okay, you pick it. I was at an influenza meeting before I came here. Should I tell the influenza people we're not going to go for a universal flu vaccine? I'm talking a little bit longer than I usually do, but I just want to make the point. The solution is one, no, I didn't say the solution. A solution in my mind is to change how we in this country think about innovation and research. It is part of the discretionary bucket of our budget, which means that it doesn't keep up with inflation during difficult times. And I have been arguing with somewhat deaf ears, except for a few people who are starting to listen now, some good people in the Congress, that if you really value innovation as part of an important part of ourselves as a nation, that innovation, particularly in the biomedical sciences, but also in the physical sciences, should be a set formula like cost of living increases on the paycheck. So that if you have an X percent of inflation, biomedical research inflation is 2%, add 2 to 3% on that, and make it almost automatic. So you don't spend time arguing about it, but we're not there yet. So I think the only way you're going to be able to have flexibility in taking advantage of scientific opportunities if you have even a modest increase in the biomedical research budget. I'm not saying double the NIH budget every five years, because that's non-sustainable over decades. But what is sustainable, and we've proven it, is a modest increase each year to keep up with inflation and to take advantage of opportunities. That's how I think we're going to meet the scientific challenge. Other comments? I'm also going to invite Mario to offer a thought, and then David has his hand up. Mario, do you want to offer a thought? Not easy after this, because this is very clear, but just to emphasize once again what I said before. Without new tools, we are not going to get to that level of ambitious targets that have been highlighted in the new strategy. That is very clear, and this is based not on speculation. It's based on the fact that, as we well know, the maximum ever reached in TB is what was reached in the Netherlands or in some other countries of Europe, a bit in North America, I believe it was not 10%, it was slightly less, 7%, 8%. In the 50s and 60s, when the new chemotherapy became available, when there was access, and that's why we insist so much on universal coverage and social protection. These were all elements that were put into especially the European portfolio of the governments, you know, social protection, universal coverage and things like that. That is when the maximum possible 10% decline was reached. Now we know that this is going to be very difficult and a challenge in BRICS, because they dominate, Peter said it again, but they dominate tuberculosis, 45% of cases are in the BRICS, two-thirds of MDR are in the BRICS. So in these countries it's going to be very difficult to reach something that is near 7%, 8%, 9% as it was in Western Europe or in North America half a century ago. We need new tools, that is very clear. So the investments have to be presented under that logic. I believe the US government cannot do it by itself, because we just heard the difficulties in getting more money. Here you need a major investment in basic research that has been underlined. You need a pipeline that is constantly like the HIV pipeline. You know, if I open a parenthesis here, if I look at HIV, I came to this country in 1984 to train. So at the time we didn't have the HIV test. The AIDS was described in 1981, if I recall, in 1983-84, after that, 85 is when the HIV test became available, because I got a needle stick and I was tested in 85, I remember. ACT was available in 1986-87, so four or five years after we had drugs, we had the test, we had everything. And 15 years after, we had the triple therapy as it was called at the time, heart and so on and so forth. So that means that if you invest, you can achieve. Now AIDS is probably different from TB, I think it's less complex in certain ways, but it's something that you can address if you invest. If you don't invest, if you maintain the status quo, it's going to be very difficult to progress in a rapid way. And so, again, it's an appeal that perhaps the leverage issue that was raised with the BRICS, because they have major institutions and the technical assistance that can be given to improve further. The mobilization of resources from other entities, for instance, the European Commission, $27 million is what they spend every year in the Horizon 2020 project now, $27 million. That's what we're talking about. The Gates Foundation spent 150, 160 NIH with just 30, 160, 170. So that cannot be. So it's really an issue of mobilization of opinions and pushing others, using the leverage that the United States can have in order to really get to the point that we need to get to, because otherwise it's not going to work, in my view. Thank you. David Briden. Yeah, David Briden with the results. I mean, I think this is a really urgent discussion. I think we should find it morally offensive that we're out distributing medications that, yes, save people's lives, but cause psychosis and hearing loss, permanent hearing loss. That we should find morally problematic. So this investment that Mary was talking about is just extremely important. I want to just differ a little bit, and correct me if I'm wrong, with Dr. Fauci, but I think that the reduction for USAID would impinge on R&D resources in the sense that USAID is tasked with providing funding for late-stage trials. So that would constrain the amount of money, as I understand it, for late-stage trials for the PAMZ combination, for instance, or for the stream trial, other medications that would be much faster acting and would not cause psychosis and hearing loss. And so I think that it is an important point. I don't know what the strategy is. I'm not sure it makes the best sense for USAID to be tasked with those late-stage trials if its funding is going to be cut in this way. But I'd be interested in your reaction and also children. I mean, when we talk about the interest of the administration, maybe that's the answer. What do we do about this? Maybe we emphasize the impact of TB on children and the need for medications and vaccines that will address their needs and get them diagnosed and treated and cured. I was going to just comment on the role the diplomatic side of things plays. The reason that the Global AIDS Coordinator had an ambassador title was really because every relationship that PEPFAR had in moving into countries, 36 in a big way, 78 total, it really comes in through a relationship of one country through another. And I think that there is a growing appreciation of the opportunity that a diplomatic discourse affords in that bilateral relationship. I think that Debbie and the State Department with Leslie Rowe's office, the Global Health Diplomacy Office is learning how to better prepare our AIDS ambassadors, all of our ambassadors to be AIDS ambassadors in each of the country's settings, and take a leadership role in making sure the disease is understood, the prevention and treatment opportunities are understood. And as Robert was saying earlier today, that that happened at the embassy level, orchestrated through our agency, networks in country, but with a new and invigorated dialogue with country leadership, ministries of health mostly, but also civil society to crystallize the advantages and the gains that can be won with putting the science that's known on the ground. Our relationship with that effort needs to be increased, strengthened, as not a primary implementer as the United States, but as a partnership. And I think that's really right in front of us right now. Peter? No, I agree. You had one more intervention. I'm speaking too much, but there is one issue that has not been faced. We talked a lot about governmental structures putting money into Gates Foundation because Peter is there. What's the strategy for the industry? We are learning a lot of interesting things now with expert monopoly, the factor, and you know, push down the price, push down thanks to again US government and Gates Foundation in unity. We are learning now from the two new drugs that after 40 plus years have been made available, Bedakulin and the Lamanit, both obviously developed by industry. There is no other major development entity except for the TB Alliance that is now working on the new regiments and so on. But what's the strategy? Shouldn't we think about again a strategy with the industry? I think in 2009 there was the Pacifica summit where there was a purpose of a name there, was that of getting the industry involved. I think that in TB we have a major challenge there because that is probably the most unattractive disease that we can think of for industry to invest. And without industry, I'm not so sure if public agencies, under the situations we are in, in the rest of the world and not only in the United States, so what are we going to do? So this is one of the things probably several you can do that we've been doing with pharmaceutical companies. One of the big pharma and little biotechs is that in that spectrum of upstream to downstream that I spoke about, it's the question of de-risking the company's efforts. So if a company makes a decision about whether they want to get involved in developing a new drug, they look at the investment they have to make and what the chance of what their return is going to be. And if they're taking a risk on an unsuccessful drug, as we all know, everybody in the room knows, it's anywhere from 700 million to a billion dollars per intervention at the drug level. So what we've tried to do on the upstream level is to provide for companies by things that we do on contract or all the time research resources, sequencing and informatics capabilities, proteomic capabilities, clinical trial networks. We've just started a leadership group for clinical trials in antimicrobial resistance. And one of the reasons for that was to provide for companies the capability of doing clinical trials for new drugs. We've integrated TB into our HIV AIDS research networks. And again, that's TB with or without HIV. We just, you know, hopefully get as much TB mileage out of it as we can. So there are things you can do on that end of the spectrum. The other thing is that when we were dealing with trying to get companies involved with HIV, even when there's much, much more of a return on HIV drugs, even when you tear price it for the developing world, you've got to try and figure out what the companies really, really want. What they really want is tax benefits, but even more so, they want extensions on patents. So you go to a company and you say, you have a blockbuster that's making you $4 billion a year. It's going to cost you $700 million to a billion to fund a new TB drug. I tell you what, you go into the TB business and we'll extend your patent for another year on your blockbuster. So they wind up making three to four billion that one of the billion goes away there. That sounds great. You do the math, it's great. Except that somebody is going to have to pay for that drug being an extra year being an expensive drug. And the insurers are the ones that pay that and that's the wall you hit when you want to make that suggestion. I would not stop trying. One of these days we'll get a sympathetic ear, but that's... Peter, your reflections on this? I alluded to tools and approaches and I think this falls in the category of approaches. How do we actually use IP and legal and business practices which were frankly developed in another space with another intention and adapt them for promoting the Global Health Agenda and TB in particular? It's something that Foundation has thought a lot about. I think right now what I'm particularly excited about are some of the branded generics companies where you can't get some big companies to touch a 40, 80, 100 million dollar a year market. There are other companies who are actually credible, very competent manufacturers who will jump right in. So I think that that's another thing and then it also becomes a domestic product in some of our high burdened countries and that also gives it a lot of steam. Good. We're getting towards the end of our hour. Is there any closing comments or questions? Yes, please. Then we'll come back to our panelists for one last round of thoughts. So please jump in. Yes, please. Newlymore with American Thoracic Society. So we've discussed this at different points today but I think this last panel you may be uniquely positioned in your various positions to try to come back to one of the central recommendations of the report which is increased funding and prioritization and maybe even just getting to the point where this big funding cut for USAID is not outlined every year. There's a lot of advocates in the room. So if there's any couple of central messages that we can use including this report to try and make TB stick more and get that prioritization more, what do you think those would be? That's a great question to close the hour. Why don't we start with Eric and Tony and Peter just sort of top-line thoughts around messaging and communications themes and looking forward to it? Well, I guess I would focus on the fact that we know a lot about the natural history of the disease. We know a lot about the pathophysiology of the disease. We know a lot about the epidemiology of it. We know how to map and identify where individuals are within a population. The ability to identify the individual, establish that they're infected, bring them into a relationship with a medical delivery system to cure them is I think the critical piece that I would emphasize, matched with the inherent risk to the United States government and its people with MDR and XDR TB and the importance of keeping and helping our colleagues in country who are in front of that outbreak to be successful in containing it with the elements of implementing it in their country because it will move across the border and come to our country. So I think that we know the science. We know how to respond to it. We need to help our colleagues in country who are burdened with high burdens of disease to be excellent in their ability to do that. So I agree totally with Eric's message. My contribution to the dialogue is that in the multiple times that I've beseeched the Congress and the administration, I don't think I have ever gotten what I wanted the first time I asked ever. It's like never, hey, what a great idea, Tony, let's do that. It's always been going back and back and back. So take word for word with Eric said and you just got to keep going back and back and back because nothing gets done the first time around. You get the benediction. Well, in the presence of these guys, I'm not going to even hazard a guess as to how to talk to Congress. But I know what compels me. And frankly, I get tired of the sky falling and the doom and gloom and I know that motivates some people. But for me, I get totally energized by the successes that we've had in this field and saving 22 million lives. And then the U.S. role in this, which is truly phenomenal. I just think about the gene expert. And I have a really close association with that because I myself got a gene expert when I was coughing from the air pollution in India. And after spending two weeks chugging cough medicine and quietly in self-denial assuming that I'd contracted MBRTB. And I'll tell you, you know, the experience of thinking you're having TB and knowing you don't is a phenomenal thing that this government has enabled the world in. And there's no part of our government as best I can tell that hasn't touched it. I mean, I think DARPA put a lot of money into it. You guys put a lot of money into taking the DARPA thing and turning it into a public health thing. You know, I think that USAID put a lot of money into making an affordable thing. And I believe that CDC has done a lot in terms of, like, how do you put that thing out there? And OGAC has really put a lot of these things out there. So, I mean, here's a real thing that is changing lives. And that's a story that just hasn't been told. So I'd start with that. Thank you. That's a wonderful endpoint for this. Please join me in thanking our speakers today.