Hello my beautiful internet friends. I am not great with words today because my brain is not in a great place But here's the thing. I always have and hopefully always will believe in sharing the truth I'm not in a great mental place and I haven't been for a while I want to talk to you about something that's been helping me because I know that not everyone is always doing great all the time And so maybe this will help you too. I am not month eight post amputation. I am in pain I have no movement forward. I'm waiting on surgery, which will be happening and that has taken a Pretty hard hit on me. I know it'll be okay I know it'll work out eventually that doesn't numb the grief or the sting of it and just having a rough time, right? So I'm in counseling. I'm gonna stay in counseling because I think that's really important for me right now And I've been dealing with a lot of depression like the dark scary kind at the same time I've been learning about something called positive psychology kind of like positive thinking except it actually works I I don't love positive thinking positive thinking is that whole idea of being like Replace every negative thought with a positive thought and you'll do great or like just stop thinking negative Stop dwelling in the past or whatever. It's just it's oversimplified thinking, right? And also a lot of the concepts that positive thinking talks about aren't logically or Psychologically sound now positive psychology absolutely does have research backing it up it has to do with it has to do with moving towards more optimism and becoming more resilient and Savoring the good things in life and knowing that things can suck and they're also gonna be hope at the same time So kind of holding that duality of life And that's what I've been trying to do and a practice that my counselor shared with me was something called savoring I was like, what is that? It sounds like eating delicious food Which if that's the case I am totally on board for no what it actually is is let's say you like coffee I'm gonna use as an example because I love coffee and I have coffee every day If you usually grab coffee on your way out the door It's something that you enjoy instead of grabbing it on your way out take three minutes literally three minutes and sit down to actually enjoy it and focus on the way it tastes and smells or if you really like Dancing to music or you really enjoy a certain, you know album that came out or playlist or whatever Spend the time doing nothing spend three to five minutes just listening to that just immersing yourself in that music like rocking out To it or whatever that is and then move along with your day everyone can find three to five minutes I promise you I promise you somewhere in your day. There is three to five minutes I often feel like I don't have time, but it's never true You can make it and so I've been trying to do that and it's hard to get in the habit of it I like actually let the rest of things go and it's okay. If you can't let everything else go It's okay if your mind is still in other places, but it's a good practice to have and something when I started yesterday was Art here's the thing with art for me. I'm an artist I would classify myself as an artist because artist something I love something I enjoy and I'm sold pieces before now that you have to sell pieces to be an artist But I haven't participated in being an artist for a very long time at least nothing significant a few sketches at most It's it scared me because I'm so like paralyzed by it not being perfect. I just don't do anything I just don't I just don't pick up my pen I don't open my box of supplies that I don't do anything And I think that's a real tragedy because art is not about perfection art is about interpretation It's about expression and it's something that I used to love doing it's something that really helped my mental health before And I've totally cut it out of my life And you know what that's not a super smart thing to do because it's something I'm physically capable of doing right now That helps me and so yesterday I sat down at this art desk and started drawing for drawing sake I'm drawing silly little circles and filling them in with different designs and you know what it helps for a few seconds For a few minutes. I don't take a lot of time I'm just taking a few minutes on my lunch break today to draw a little bit more in a chat with you guys But it is a quick break for a few minutes from all the challenging hard dark heavy things And I think we can all use that things are heavy right now And they don't feel like they're going to lighten up anytime soon and that is uncomfortable But I also can't predict the future I also don't know what's coming and so I'm gonna spend the time that I have Investing in the things I need to invest in like actually taking care of my mental health so that I stick around I'm not sure what it's like for you But there's a lot of emphasis in my life on Achieving things I'm getting things done on like checking things off the to-do list because I always feel like I'm behind I always feel like I'm drowning in things I think like okay if I get this list of things done then I can relax but actually the list of things will never be done and That's something I'm trying to actually realize a little bit more. We don't have to check everything off the to-do list We don't have to achieve something before we earned time to enjoy life We can just actually take time to enjoy the things that make life worth it I get so caught up in going and going and going I think coming back to the things that that make us stop for a second that make us realize where we are We become mindful that we actually exist in this moment are worth spending time on so what is that for you in your life? What is something that you enjoy? I was going to say it can be something really simple But I think it almost not should be but like should be something really simple. What do you enjoy in your day? What is something that doesn't suck? What is something that you like that you could spend just a little bit more time actually absorbing actually focusing on for me? That's gonna be coffee and drawing a little bit more. I'm speaking of drawing a little bit more I've also started a campaign on my patreon that if you join a certain tier in the next few days I will actually send you a little piece of art It's gonna be sketch for me to you just for you in an actual original piece of art So hop over there if you want to check it out Let me know what is something that you can spend time savoring Like I said, this is something that there's actual psychology behind and apparently it does work And I actually have felt positive effects in my own life so far So I would love to hear what those things are for you or what that thing is for you I am really really grateful that you're willing to spend a few minutes of your day listening to me talk to you guys It means a lot to me and it really helps So thank you and a huge thank you to all of my patrons over on patreon You guys really help me more than you know, I love you guys all I'm thinking of you and I'll talk to you in the next video By the way tomorrow, it's taboo Tuesday, you know cool new series I have on my channel that I'm actually really enjoying. We're talking about shoes See if you can figure that one out I look forward to hearing your reaction on that video too. Hang in there guys. I'll talk to you soon


Good morning and thank you all for coming. I'm Steve Morrison from CSIS, the Center for Global Health Policy. This is part of our ongoing speaker series here at CSIS in which we've attempted to find and enlist many of the leading voices in global health across the spectrum of issue areas, opinion leaders and those who are the strategic thinkers to come and give us concise focused presentations on topics that we think are terribly important. And today we are very blessed to have Seth Berkeley, Dr. Seth Berkeley with us here. And I will say a word in a moment about Seth's background and how we'll be using this time. And one housekeeping item for your attention later today at 2 p.m. we'll be joined by Dr. James Hakeem who's Chairman of the Department of Medicine at the University of Zimbabwe in the College of Health Sciences in Harare to speak about the conditions, health conditions and status of the medical infrastructure, health infrastructure in Zimbabwe. Do you know an ongoing cholera epidemic there? Many big issues at play. And so Dr. Hakeem will be with us at 2 p.m. here at CSIS. Please join us if you can. Seth is known to, I'm sure to, all of you in the room here. He's the President and Founder of the International AIDS Vaccine Initiative, IAVI. He's a medical doctor specializing in infectious disease epidemiology and international health. And he's an indefatigable contributor to debates and to keeping very important issues at the forefront of discussion, writing editorials, delivering speeches, creating new institutions that further expand the reach and capacities of IAVI and the like. And he has been at IAVI since founding at 96 prior to that. He was the Associate Director of the Health Sciences Division at the Rockefeller Foundation. He's an adjunct professor of Public Health at Columbia University and adjunct professor of medicine at Brown. Comes with his undergraduate medical degrees from Brown and trained in internal medicine at Harvard University. He's worked at the Center for Infectious Diseases at U.S. CDC, the Massachusetts Department of Public Health and the Carter Center, where he was assigned as an epidemiologist at the Ministry of Health in Uganda. He's the author of over 85 publications, has written extensively on infectious disease. As I said earlier, he is a very recognizable and esteemed opinion leader across a spectrum of issues around infectious diseases, health technology, development, tying all of these things towards long-term benefits, AIDS, and international health. We've asked Seth to do a couple of things today. We thought it was appropriate for him to come and give us an update on the core business that concerns IAVI, the development of vaccine for HIV, AIDS, status of efforts. It's always a difficult and confusing subject area that Seth is particularly good at illuminating, giving us a sense of where the key moments are right now and the development of new technologies and what lies ahead in the future. And the second part that is a subject that Seth has taken the lead in trying to get us to think more clearly is around the question of building scientific research capacity in developing countries, in partner developing countries, so that we overcome that gap and so that the project, the enterprise of seeking new vaccines and other technological tools becomes more significantly embedded within a long-term developmental process in which these countries themselves are invested in benefiting and contributing. These are two big topics, and Seth, I realize it's going to take a little bit of... They're not simple topics or short topics, but please, thank you so much for coming with us today. The floor is yours. After you're completed, we'll move to some questions and comments from our audience. So, welcome. Thank you so much. So, thank you so much for the brave who come out on a Monday morning to see this talk. You've already heard what I'm going to try to do, so let me go ahead and jump right into it and then make sure we have lots of times or questions at the end. Just to remind you, I don't think I have to remind this particular audience that HIV hasn't gone away. And one of the problems is that we hear a lot about how, you know, with treatment, it can be controlled as just a chronic disease, but it still is having a dramatic effect around the world and women are bearing the brunt of the epidemic, now representing almost 60% of the people infected in Africa and half the adults worldwide. And so this continues to be a major problem despite what some of the pundits are saying. And when we think about an AIDS vaccine, and I'm going to come back to, you know, where we are with it, the critical issue is that we've got to deal with today's interventions. We've got to, you know, have the tools we have, we've got to get them out, we've got to prevent further spread of the virus right now for every two people put on treatment. There are five new infections. We must slow that down. We've got to treat everybody we can who's already infected and we have to mitigate the societal impacts. But if we are going to be successful, we've got to create new tools. And so this means an investment in innovation for new technologies. And we'll talk in a second about what those are. And it's critical to keep in mind that if we're going to meet this universal goal of access for all by 2010, you need better prevention. AIDS vaccines is the best of these, but otherwise we're not going to meet that commitment. So when we think about the toolkit that's required in black are the tools that we have today and red are tools that are under development. Some of these have had studies that have been negative and people have gone back to the drawing board. But I think the point to take away from this is that this is the way we have to think about it. It isn't one intervention. It's a whole range of interventions. And what's critical is that you've got to have them prior to exposure at the point of transmission and after infection. And a lot of new stuff is going to happen in the next few years. Preventative vaccines. We'll talk about what's happening. Pre-exposure prophylaxis. There's going to be new data coming out later this year on that. And that may be a game changer in terms of how we use that, what we do with it in the north and the south. Microbisides, you've heard there's been positive data in clinical trials in humans. A relatively modest effect, 30%. But that should be validated in upcoming studies and there's next generations of those. And obviously there's continued research on ways to deal with the integrated virus. Could you actually learn how to cure people with HIV? We're not anywhere close to that, but that would obviously be a game changer as well. So this is really the toolkit that we're talking about. And a vaccine would really change, in a sense, a lot of things. Now, you might look at this graph of where the world is on infections and you see it going down so dramatically. That is assuming that we get universal access, that everybody has preventive technologies, that everybody's on treatment. And even in that circumstance, a vaccine would have a dramatic effect, including with a relatively ineffective vaccine. So one of the challenges for us is to make sure that we keep at this and the first vaccine may not be perfect, but it may have implications for use in very high-risk groups and then of course you want to continue to improve it until we get a high-impact vaccine. Now, I'm not going to talk a lot about science, but I can't not talk a little bit about it. So this cartoon just says to you there are two major ways that one can deal with an infection's organism and the immune system. Neutralizing antibodies is the traditional way vaccines work. This is how you can get sterilizing immunity, very specific. Cell-mediated immunity is a way the immune system deals with an infectious organism that has already gotten into the body, is reproducing, and what it does is it goes in and kills the cells that are infected with this. So these are the two mechanisms, and I'll tell you why that's important in a second. So obviously, why would we be talking about AIDS vaccines? Well, I think the most important thing to say is an AIDS vaccine is possible. We know that immune control is possible. The majority of people are able to suppress viral load. What happens is people get infected. They get a high-viremae, and then the virus load comes down and stays down for a very long period of time, sometimes 15, 20 years, sometimes longer. And during that period, that is the immune system controlling it. We also know that there are populations resistant to HIV infection. There's long-term non-progressors. There's highly exposed uninfected. Children of infected mothers obviously all don't get infected. But as important, there is experimental candidates. There are experimental candidates that protect. And so if you take the best model we have today, it isn't a perfect model, but the best, which is the simian immunodeficiency virus, which is a virus that affects monkeys, and you go ahead and use a live attenuated, live weakened vaccine, you can get complete protection of a rigorous challenge. You also, if you take neutralizing antibodies that neutralize a broad range of strains, and you put them in a cache, you can get sterilizing immunity. So we have animal data, we have human data, that immune protection is possible. This is why we're optimistic. There's also been a huge change. And if you go back to where we were 10 years ago, there wasn't a lot of interest in AIDS vaccines. We now have a lot of people who care a lot about this and an enormous amount of political commitment. We've also had a huge increase in spending. So the world started out at about $150 million globally. That's public and private sector. You can see here a graph of where the world is today, $960 million. Hard to say that all of that is directed really at kind of product development. There's a lot of stuff that is thrown into, you know, this overall budget for HIV vaccines. But what's important, if you see here, is that the United States is the largest funder by far. In fact, one of the public policy challenges we have is to try to engage other governments at the degree that the U.S. government is engaged. And most of this, of course, is the U.S. NIH, which is, of course, the largest biomedical research funder in the world. So a big change, you see on the bottom, that pharmaceutical companies really do not put a lot of money into this. They did initially, they realized that this was a product mostly going to be for the developing world, politically controversial, and difficult science. And as a result of all of that, they've pulled away from it and are really waiting for breakthroughs before they enter the game in a big way. So those are some of the good news things. The bad news is that finding a vaccine is really tough. And there are a whole bunch of science challenges. I'm not going to go into great detail, but this virus integrates in the chromosome and attacks the very immune system that needs to protect it. It's highly variable. If you look at, if flu was my fist in terms of variability, we know that flu varies, you know, HIV would be, you know, the size of this room. And it's enormously variable. We still don't really fully understand the immune correlates of protection. We don't have a perfect animal model. And as a result, you've got to go into humans and that makes clinical trials long and possibly. So we're tackling an aggressive and fast moving target. We have to test it in people and success is going to take time. We like to say it's a marathon, not a sprint. But it's not just science. It's policy and political will. Because of that, we've got to have not only a long-term effort, which requires a long-term commitment, but it has to be global. Why we need the best science in the world, not just the best science in the U.S. or in Canada and France. It has to be the best in the world. We need to have incentives for industry. We need to understand the regulatory issues and ethical issues and intellectual property issues to make sure we have a good environment for those and obviously the challenges in health systems. So sustained political support, private sector engagement, and optimize the environment. This is what is required to get there. We put out a blueprint. Some of you I saw were reading it. It's outside, at least a summary of it. And what we talked about are really the three waves that have occurred of AIDS vaccine development. So to start with, when this agent appeared in the early 1980s, we had just finished with a hepatitis B vaccine. Everybody said, aha, we have hepatitis B model. We'll just make this like hepatitis B. We'll go ahead and take a small piece of the outer part of the envelope and make a vaccine with it. And that's really what happened. A lot of investment went on that. And although 100% of people got antibodies to that particular vaccine, the problem was because of all the variability it didn't work against the strains that were circulating. Despite this, a charismatic and wonderful leader said it was safe. We should test it. And there was an efficacy trial of this product. And that really ended the sense that this particular product and neutralizing antibodies of these types of products were where we were going to go. The next phase really started after that. People said, we don't know how to do antibodies yet, but we're going to do cellular immunity. They took about 30 vaccines forward. Again, there wasn't a perfect animal model, so they decided to go to large-scale efficacy trials. This also had the beginning of an effort really to engage on some of the key science challenges. And at the end of this was the Merck candidate failure, which you all heard about. And this really ended the second wave. And let me just point out that there's only been two vaccine trials in efficacy, despite what you hear about all the failures. Finally, harnessing innovation is what we're calling the third wave. This is really trying to hone in, go upstream a little bit, solve some of the major scientific challenges. One of the things is, since we have to go into humans, how do we think about doing trials differently to make them quick and iterative rather than slow and long and expensive? Harnessing innovation, and I'll talk a lot about that, and getting the next generation of scientists. So this may sound obvious, but the next major advance in AIDS vaccine development is going to be showing protection in humans of an HIV vaccine. Once the protection isn't very robust, it will then allow us to validate the animal model. So as a result, what we really want to do is design, develop, and advance to efficacy trials candidates that elicit broadly neutralizing anybody. So not just one strain, broadly neutralizing, and controls HIV as well as in the monkey model, this SIV vaccine protects it. And we're particularly interested in vaccines that can get protection on the mucosa because it is mostly transmitted, as you know, by anal intercourse, by vaginal intercourse. Obviously, we also have to pay attention to IV drug use, but most of the transmission is through the causal membrane, and I'm going to talk about replicating vectors. And lastly, one of the things that came out of this Merck trial was that we really don't have good assays. We need better ways to measure immunity, and so there's a whole role to try to get better assays. So with that, where is the AIDS vaccine pipeline? There have been two efficacy trials, as I said. There is a third efficacy trial that's ongoing. Data is probably going to be in the third quarter. This is a huge trial. 15,000 people in Thailand. I've got to say the field is pretty negative on the possibilities of this being a big success. Obviously, we all hope that there's some signal here because that would give us a clue. It is a combination of a vaccine called AllVac, a canary pox, and the VaxGen vaccine that's listed above that had no efficacy. Why is the community somewhat less optimistic about this? AllVac is not a very potent vector. It only gave strong immune responses in about 30% of people. As we've already said, the GP120 did not work, tested alone, so most people feel the combination is unlikely to be a really robust combination, but we'll see. There's a range of other candidates that are ongoing, and some of these should move into some type of trial screening test and concept trials, but what's important is there's no candidates in trials that are producing and neutralizing antibodies, or a combination of the two, which is really what you'd like to have. You'd like to have a vaccine that can get it right away, and if it doesn't work, then one that could mop up cells that got infected. Now, what's really exciting now, and we're really entering a renaissance, is the following. I'm not going to go into the following monkeys, and all six of these approaches look better than the Merck candidate. Now, again, that doesn't guarantee success, but what we've got is a whole range of new candidates, and the challenge is going to be how to accelerate these and drive these forward as fast as possible. There also are real big advances in neutralizing antibodies, and I'm going to talk about that in detail. And finally, there is work now to create better assays that we're going to have to decide what to move forward with. And so if you think about it in a schematic fashion, this is really what it looks like. On the left is solving and initializing antibody problem, is getting some immunogens, getting one or a few out into a vaccine, and then getting a bunch of vaccine platforms on the right, and again having one come out and bringing them together into a vaccine, and obviously going through a whole series of steps to prioritize those and so let me just say a word about IAVI, because I'm going to mix it up now on what's IAVI and what's the field, but our mission is to ensure the development of a safe, effective, accessible, preventive HIV vaccine for use throughout the world. Ensure is critical because this type of mission means that we don't care who succeeds. So if Merck is going to move forward a candidate, why should we move the same candidate forward? So we think of the vaccine as a portfolio, and then we try to move into higher risk approaches or things that we think we can add value. As a result, our core principles are one, we focus only on preventive HIV vaccines. Speed is our focus, so we have to trade off investments. Going fast is more important than necessarily trying to take the most economical route if it means stretching it out over a very long time. The flexibility of being a small not-for-profit model allows us to jump on something if it's exciting, drop something if it's not. Willingness to take informed risk will often take products forward that industry might say, well, regulatory wise it's too hard for us, or intellectual property isn't quite wrapped up. And then finally, access is always a part of our mission. And we move across the whole chain. We have an integrated model of R&D, and it's interesting, we're operating now at about $105 million a year, 250 people, but if you include who's working in Africa, we're about 1,000 people. And there's a lot of people in our African-India sites not working directly for HIV, but working for our partner organizations and fully being paid for. And these are the people doing the trials and laboratory technicians and nurses and counselors and outreach people, et cetera, et cetera. Now, this idea of product development, public-private partnerships really were started around the positive area. And since then, there's been a whole range of them. There's also a group of, below the line, our other public-private partnerships working on health issues. And the reason I wanted to put this up, I know that you guys are policy wonks, and I think it's important to think about this mechanism of ways of working. There are more drugs and vaccines and diagnostics for diseases of poverty now in the pipeline than ever before, and this movement is interesting because HIV started as an advocacy organization. It then moved into gap-filling science. It then started to do serious vaccine development when we had enough money and credibility to do that. But we did it virtually. We realized that if you work with small biotech companies, they don't necessarily have the expertise. So we ended up staffing across the entire value chain and bringing people from industry and not in-depth. We don't have like Merck's regulatory department, but we've got our people with each of the skills. We then moved into having validated laboratories because we wanted to make sure that any study we did anywhere in the world was the same and could be compared to any other. We then set up a professional policy program because we thought this was critical. Applied research consortia I'll talk about, and most recently we've created our own laboratories. This is an interesting transition, and it'll be interesting to see how some of the other product development partnerships go through a transition like this, and it's something that is going to be debated out there and I think is quite important. We're very different than a typical public sector organization or even a funder, and I guess that the closest correlate in the federal government would be the Vaccine Research Center of NIH. So let me just take you into depth. Again, I don't want to talk about the science, but I want to talk about how you can really work on a problem like this. So the neutralizing antibody challenge is that this is how most vaccines work. We know that you can protect with this in an animal model, and we know that humans can make broader neutralizing antibodies, and down here these things with letters on them are there are four known broader neutralizing antibodies. They're not incredibly potent, but they work. People can make them so. We know that people can make the right type of antibodies. And what we did is we started off with a small group for institutions, and that's grown now to around the world that are working together. They share science. They share data. They also share intellectual property in an interesting way. Those institutions agree that the inventor of a new idea technology will get a higher level that everybody else shares in it, and they'll be accessed for the developing world of any technologies that are developed. So it's an interesting model. And the challenge has been this has been something that's been done in people's laboratories, you know. A couple of lab techs going slow, and how do you turn this into a high throughput? This is what industry does for drugs, but hasn't been done for vaccines before for biologic. So broken it down into some of the challenges if there's four neutralizing antibodies, there's probably more. So a protocol, gee, I'll talk about that in a second, get some more. We then said, okay, how do you do the structure? This is a really slow process. We built a custom high throughput robot at the Scripps Research Institute in La Jolla. Very expensive, but this can do the work of, you know, an army of graduate students in a week. And so you can really move through in a high throughput fashion. The third would be, once you've got the structure, you've got the antibodies, now you want to try to make potential vaccines that will induce those antibodies. And how do you do that? Well, we went to India. We said, look, in India, they're making a lot of medicinal chemistry, particularly for generics. They're not doing it so much on biologics, but there's a lot of them available. So we got a group of them together, some companies, to try to work on focusing full time on immunogen design. There's also being done across the NAC and the Innovation Fund, which I'll talk about. And then finally, once you've got a lot of these immunogens, you're making hundreds of them, how do you test them? Well, an interesting company, Vax Design, is trying to create a immune system in a petri dish, basically, so you could at least do some of the screening. So this is the challenge, how do you do high throughput? And this hasn't been done before, but this will, the reason I'm so optimistic, I'll show you in a second. So we said, all right, if there's more, if there's lots of antibodies, let's go out and we went across the world, 2,000 people infected more than three years, and it turns out that about 10% of them have broad neutralizing antibodies. We don't know if it's one or multiple, and even more interesting, about 1% are elite neutralizers. These are people that have very potent serum. And we've just isolated our first two new broad neutralizing antibodies out of these people, and they're very much more potent than the old ones. And so we're, you know, hard at work now, beginning to look at how to turn those into an immunogen. Now, the reason that's exciting is it isn't going to be just two, there's going to be a whole new toolkit of potential antibodies, structures that can help us really drive forward, trying to solve this problem. And so this is really, really exciting. I mentioned before this idea of a replicating virus in monkeys. If you look down on the bottom of the chart in blue is a cartoon of what a live attenuated monkey AIDS vaccine looks like. So you get a little blip of virus and then sterilizing immunity goes away.  If you take that replicating but weakened vector and you turn it into a one cycle replicant, so it just replicates once, it actually ends up in the middle there. So there's something about replication that matters. Now, why is that important? Well, up until now we haven't moved replicating vectors forward in the AIDS vaccine space. Mostly because people have been concerned about safety and obviously the less things replicate, the less alive they are, the safer they are. And so most of the work has been on the left side of the chart here. Nobody would move the ones on the top that are in brown up there. Nobody would talk about taking a live attenuated HIV vaccine forward because if it reverted to wild type you'd be infecting somebody with a fatal disease. That little space in the middle replicating viral vectors we think is where the sweet spot is and that's where we're focusing now on trying to move candidates forward that will look like these SIV vaccines but have the safety profile that allows them to be used. This is again from a regulatory point of view a riskier place to be. And so what we're doing is moving a whole bunch of these forward and then, you know, based upon scientific hypotheses and then, you know, can we make them? Do they work in small animals? Do they work in the non-human primate model and pick the best one so this is kind of the technique of how to move forward in a systematic way. I have a tries to and I'm going to come to the other part of the talk now I'm going to begin to interface it we believe fundamentally to do this type of work. You have to work in the developing world but you've got to do it as real partners and this is more of a development approach than it is a parachute research approach. It's building long-term relationships. It's getting them engaged in access. It's creating an enabling environment for research so that they feel they own it and that it's, you know, they're part of the team to do this. And this is important because, you know, as you can imagine there's a reluctance to be involved in research unless you feel the benefits are going to be there for you. So this is something we've been doing for a while. It's also critical to bring developing countries to the global call for investment and, you know, we've had for example AIDS vaccines have been declared a national goal in India, and in Uganda, Rwanda, South Africa even with all the problems in South Africa they supported vaccines. So how do you really keep this kind of dialogue going and engaging them? And that includes both at the local community level where you've got to work with people to do trial type design. It also includes adapting, you know, each country learning from each other and adapting both on how to train staff, how to do vaccine literacy, how to do leadership, working with vulnerable populations is a big deal. When I lived in Africa it was not known that there were clusters of men who have sex with men for example in Africa. We now have a cluster in Kenya north of Mombasa large cluster, very high incidence of men who have sex with men and it's unbelievable the stigma that's associated there. We brought the researchers from the community there and the researchers didn't even want to deal with it. So it's something that really training has to go on. And an example of how proud we are of this. This is in Uganda a clinic site. We rebuilt and put a clinic there. Afterwards they did multiple phase one trials and showed that they could do them fast. They expanded to field sites and amazingly they not only validated their laboratory but then went ahead and got it accredited and now is a worldwide reference laboratory for the Gates Foundation's network. So, you know, for me one of the most extraordinary things is to see how these researchers can become engaged and do work that's as good or higher quality. I didn't put it up because it's a very technical slide but we recently had a QAQC program across the world and lined up all the different sites and the ones in Africa did better than the ones I won't name them in Europe and some of them in the United States. So, I mean it's a really interesting thing from when 10 years ago people said you couldn't do these types of trials in the developing world. And the good news now is that, you know, if you look at where the infection is there's now a lot more trials at the beginning there was an engagement now there really is a global effort to try to move AIDS vaccines forward. One of the problems though with the slow down in science is scientists alone can't solve a problem but how do you keep people engaged when the pipeline slows down? So, how do we sustain that capacity? You know, we've had this debate. Do we drop sites, you know, during this time period? And the answer is this is the most valuable thing. People who have experience doing trials. So, we're doing everything we can to make sure we keep sites going and keep them engaged in research, keep any communities engaged and not over promised. We probably did a bad job at the beginning.  How do we have that advocacy platform go on and you know, what can this do to move forward capacity in these countries? So, these are some of the questions we're answering. One of my favorite quotes from Albert Einstein on Saturday is doing the same thing over and over and expecting different results. So, we really have to drive forward innovation now. And this is some of the toughest science that we've ever had a deal with. So, how do we do it at IAVI? Well, I've mentioned these consortia. I mentioned one but there's a bunch of them. We've now built a laboratory that can move an innovation fund, which is a really interesting concept and we've done this jointly with the Gates Foundation. This preceded their setting up their new innovation fund and the idea there is to go to companies that are not working in HIV vaccines, have no interest in working in HIV vaccines, look for technologies that might be useful and bring them in and we do that working with a group of venture capitalists who help us identify them and then help us convince the management team that we should do that. We've also worked with Innocentive and put prizes on the web and really trying to change the way one does clinical trials. And this is the laboratory that I told you about. We just moved in in October. It's a beautiful BSL3 laboratory, 36,000 feet with really unlimited growth potential and it's, you know, a whole new thing. It's an industrial style but not for profit applied research laboratory that's just dedicated to this cause and we're looking at how we link this laboratory to laboratories in India South Africa, other places to really try to get scientists engaged in accelerating this. Let me just finish moving into the policy realm a little bit. There's a range of policy issues that get raised when we talk about the science. Obviously at the end of the day we have to have adequate resources, we've got to target fund strategically, we've got to engage the private sector, we've got to push innovation and so IAVI's policy team is working on all of these for a lot of the engagement part. We use a push-pull strategy and you know, GAVI has been key here in terms of working on advanced market commitments and some of these, you know, the IFM, long-term funding strategies and so one of the challenges is how do we work with these, how do we work with others on this? The FDA vouchers that just came out, another mechanism. There's a lot of innovation that's going on in this space. It's not directed right now at AIDS vaccines and how do we make sure it is because AIDS vaccines are important but they're longer timeline and so that's one of the real challenges for us and we've been having a set of conversations on the innovative financing. Remember, I showed you that chart of all the product development public-private partnerships, we've been working with the malaria vaccine people and the DB vaccine people to ask the question what are the ways to create innovative funding mechanisms that are not just yearly. Some of our donors are multiple year but many of our donors are single year so I go around every year with a cup and that's hard to support long-term financing of research particularly in the developing world so some of the ideas that have been talked about is adding R&D windows in the global fund or GAVI or UNITADE having an industry type fund and neglected R&D funds some public sector bonds the IFM we used and so these are being investigated as different mechanisms. I mentioned the innovation fund that we had we've done a number of different awards to companies out there we have a number more that are coming out now and this is really an interesting mechanism to engage new players but this is very labor intensive because it's not RFPs this is proactively going out reaching out to venture capital is saying what companies do you know have something and then talking to them and figuring it out and we've gone to hundreds of companies for the small numbers that we've pulled out but we already have a spalted deck which has been renamed Theraclone as the company that isolated these two new broad-neutralizing anybody so already we're beginning to see some success from this. So just to summarize and to give you an idea of what we can do as a product development public-private partnership we're developing a large age vaccine and design and development program working in 25 countries our management team all of them come from the vaccine industry we have a network of global labs and research centers and a lot of accomplishment first vaccine trials in a number of countries trials in 11 countries first vaccines designed for Africa seven seven novel candidates from concept to clinic first accredited human immunology lab are neutralizing existing neutralizing anybody's but now has identified new ones and these new labs are coming out so a lot of success for the model but to remind everybody we're a little teeny player compared to the rest of them so for us the challenge is to use speed efficiency and the willingness to take calculated risk to be able to leverage and make our money go further than it would from our proverbial share of the pie lastly let me just end with a couple of comments on the human development aspects of this and we know that reversing the spreads of AIDS is one of the eight millennium development goals and we know why for the things it does but I just want to bring up another point to you and that is if you think about what's happened the AIDS activist community have been very successful at getting funding for AIDS and here's what has been suggested is required for the amazing commitment at Glen equals to provide universal access by 2015 $4 billion a year and if you take that and kind of think about what that would look like in 2007 it's about 10% for AIDS by 2010 it would be 33% for AIDS it would actually the calculations aren't clear on what ODA is going to look like in 2015 but some calculations take it up to 50% it's not likely to happen and I think we all understand that but one of the challenges unless we create new tools we have created now a long-term program that you can't stop you can't stop treatment funding so we've really created a program that is going to challenge all of us in the ups and downs of financing and so not only is it the right thing to do but economically we've got to deal with creating better tools and for me science and technology is an incredibly important tool not only is it a global public good and it feels critical need in terms of saving lives improving health etc but it's also one of the best forms of development aid if you think about it and Steve and I were talking about this before you know in the old days you go in you build dams you build roads you build infrastructure well countries can do that now in fact even if they can other developing countries can come in and do it for them but Malawi is not going to be able to make an AIDS vaccine it's not going to be able to do the biotechnology to create a new seed strain and so one of the best things we can do is use our comparative advantage which is science which is engaging in these problems in addition to that obviously working on research in those countries where they can having exchange of science and technology across the borders and one of the things that really does that's important is it stops brain drain if you have good scientist that are doing important work they'll stay and then they become role models and that's really important and obviously as they're there and new scientists get trained then they have the capacity to move forward and no country has moved into the industrial age without building their own science and development base so we think this is a really important argument so at the end a preventive vaccine is the only way to end the AIDS epidemic obviously I have to thank our donors which have been extraordinary and supporting the flexibility of this organization the speed and the way we've been working we're supported by governments around the world private individuals and foundations and I think I'll stop there open it for questions sure my name is David Shown thank you Dr. Berkeley is a fantastic presentation one quick statement then a question just looking at the therapeutic vaccine side we now have published data showing a vaccine that in a phase 2 trial has kept people off of ARVs for up to 5 years and has an average patient response of 31 months without antiretrovirals and I'm wondering why you wouldn't move your organization into the therapeutic side and if you can comment on that my name my name is Dan Leifer I'm a student at Stanford University I was curious there's some scientific literature coming out that shows that or suggests that antiretrovirals reduce the virulence of the AIDS virus I'm curious why you don't focus some of your research focus towards that reduce the what the virulence thank you investment in a development strategy as a public good as something that is to involve a long term investment in communities and building up skills and jobs and capacity how do you make that case in our system here where the boundary lines have been drawn differently it requires you to move folks to think in quite different fashions around institutions and committees and funding streams and authorities we can talk about that should I jump into those maybe and then we'll do another second okay on the therapeutic vaccine side I believe that at the end of the day the way we'll deal with the large number of infected people out there are through therapeutic vaccines there's a number of reasons one is there is a market out there for therapeutic vaccines a lot of money that's been invested in therapeutics in general and corporations are interested in moving for therapeutic vaccines they may not be funding as generously as we'd all like but there is a place one could go secondly one of the real dangers early on was that people would test a vaccine therapeutically it's much easier because you're testing it if it didn't work in that setting then people would throw out the vaccine they would say well now to take it back in and do a preventive trial so on the other hand obviously if it worked it would be fabulous but that's one of the second issues for us and third really was that the greatest need is in creating new prevention tools because you've got now 6 odd billion people out there many who are going to be at risk some time in their lives how do you deal with prevention for that large population the combination of all those three let us focus in on prevention but I think therapeutic vaccines are really important and ultimately once you prove that a vaccine works and you know how to do an immune response certainly you'll want to go back probably treat people really aggressively drive the virus low down and then be able to get the immune response back up and then be able to withdraw the therapy because obviously there's a problem we're trying to have therapy going for a long time in terms of the roles of treatment it's really complicated and interesting we're actually going to do a small pre-exposure prophylaxis study intermittent pre-exposure prophylaxis study and one of the things we'll look at there is what is the immune response of people when they have exposure to virus and or on antiretrovirals do they get boost in their immune system may this be a way to trigger a more effective immune response and those are important questions you know the problem with drugs although they certainly keep people alive you can still transmit virus even though you're on drugs and one of the interesting things is a lot of different compartments so what happens in the you know in the semen is different than what occurs in the blood is different than what occurs on the because of surface different what occurs in the brain and so people are just beginning to understand now the compartments and how things move so it isn't, I mean people have thought gee if you just treat people and there's a discussion treatment is prevention then the epidemic should go away now it may be that that works but if you think about the US experience we had no treatment and then over the last decade most people get put on treatment and if you look at what's happened to numbers of infections CDC increased the number but not because the infections increased because they had a better account but we've basically been stable we're virtually 100% and you're still operating at about 60,000 infections a year suggesting that treatment is not a major way to work as prevention but I think that needs a lot more studies and certainly has been interesting modeling Steve's question on science and technology that's absolutely right I mean one of the issues is that our science and technology community it's our engine of development and I think the number is something like venture capital is 7% of investments but it's something like VC driven companies is like 15-20% of US output I mean it's a really important part of what we do and how do we get the government to think differently about science and technology as part of development policy, as part of diplomacy certainly it becomes an issue on intellectual property there's been huge battles fought over that but it's a much broader conversation in the science community of course but it hasn't moved into the developing world the way it should and one of the things that's been really tough is that and I am for this, the single most important development thing we can do is mothers education it's early education primary education for mothers is the best so that's something that we're all focused on and as a result people have moved away from tertiary education it used to be that there are a lot of institutions that invested in universities and high tech education and a lot of politically that moved away for a while, it's beginning to come back but I think that's a really important question and how do you make sure that there are people to train the next generations, the leaders the educators to do the high level work that's going to be needed to transition these countries so you're absolutely right it's broader than AIDS vaccines it's broader than just science and technology it's a much more a much more different conversation and Alex just walked out but Gavi is focused on vaccines governments should fund their immunization programs 100% then donors could come in and say we'll fund your universities what tends to happen is donors say we're not interested in universities we're only interested in immunizations so they fund immunizations and then governments end up funding universities and don't do it adequately and so how we rethink our whole structure I think is a really interesting question please Thanks, my name is Janet Fleischman I do a lot of the work on gender for the Center for Global Health Policy and I'd love you to address some of the issues that Gavi has confronted in terms of getting women on some of the trials I know that early on you had some of the issues the very social and economic reasons that women have had trouble accessing treatment or adhering to treatment and I wonder if you could speak to that and where you're at now with the Obama Administration Global Health Budget and some of the issues that seem to be arising in terms of treatment versus prevention and some of the broader global health priorities that are out there and how do you see ways that we can make better arguments for the broader prevention agenda which as you've noted is critical to sustaining this in the long term Jennifer Cook with the Africa Program here at CSIS I had a question I was interested to hear you say that that enthusiasm is still extremely high on vaccine development and I wonder would you say that's broad, you know, popular support, congressional support or kind of within the community because you know there were the high profile failures if you want to call them that for a vaccine that may be partially effective and there's new new technology and circumcision that are shown to be equally effective as possibly the less effective vaccine kind of thing and so kind of a bird in the hand versus the long term I just wonder how that momentum is being sustained how broad it is So let me start here if I can and say first of all one of the problems and one of the reasons I talked about the toolkit is it's fine to stand up and say well circumcision works great and so everybody ought to have it but not necessarily everybody wants it about choices that you want to have different choices and certainly when you're talking about young women you know a preventive strategy that can protect them under any circumstances is really what you need and that's why vaccines would be so important for that constituency you're absolutely right I mean in a sense one of the problems is we and others the way we got vaccines up the agenda was by promoting how important they were and then when there's a failure it becomes you know above the fold front page news which is not true for like a malaria vaccine there's been 40 odd failures and if it's ever reported at all it's reported in page 40 so in a sense we made a mistake but I think what happened was that that was mostly if you looked at it the dismay was from all of this attention the reporters were giving it and not understanding where we are product development is about failing not going through learning from these because you can only do it in humans that's the problem since we don't have the perfect animal model and you know this was an unreasonable expectation that your second candidate would have been a home run I mean at IAVI we actually built our program assuming that Merck candidate would fail so we had hoped there would be some signal but we certainly didn't build it as if that was going to be the vaccine to end vaccines and so I think really the challenge is resetting expectations for the field and what you describe is exactly why it's so hard for us a politician stands up and says I'm only going to be here for a few years I can hold up a baby I can treat somebody and show the Lazarus effect that's really exciting to me do I really want to invest in something that I'm not going to see the result for 5 or 10 years when I'm not in office anymore and getting people to buy in but that is why it's important for government to think over these long term issues on the medical trial side we started out with having more women volunteer than men remember we said this at that previous sessions here and then by the time we got actually at the end of the trial women ended up being the minority and we had to go and really look carefully why that was and so the women were motivated but then they had to deal with permission issues with their husband they couldn't get pregnant during the trial which was a big issue for a lot of women they had issues in terms of care and other issues that allowed us then to go back and focus on engaging women and doing everything we could to encourage them and support groups and so now we've got very good gender balance in our trials and not only in that true in Africa but also in India we again took the lessons learned and brought those over so it is a huge priority for us and one of the questions that people ask is what about young women and we haven't felt there was a candidate or anything exciting enough to move into but I think that's going to be a huge priority and it's going to raise a whole bunch of issues on the ethics side but you're really going to want to be going into adolescence in the future and how do we do that and not wait till after the vaccine is approved and then you've got to go back and it's delayed. In terms of the Obama priorities I would leave that to my team it's much more familiar now with the whole range of that program one of the challenges that we see in front of us is that AIDS is going through a period of reassessment it's going to go through a period of reassessment both treatment versus prevention and I used it versus it shouldn't be it should be treatment and prevention but there is going to be in a world of limited assets some thought process across the two and then also the broader health areas because AIDS has gotten enormous attention and I think this is going to be really important for all of us to keep our eye on the prize and I think if we just hold the dikes back and say we don't want to be part of the conversation it's all what Jeff Zaks says is expand the pie that's the only answer you've got a problem we're going to have to engage in those debates to make sure that the debates go well and there was recently a study for example a g-finder study that was supported by the Gates Foundation looking at priorities across different diseases and I personally didn't like the way that study was done because of some methodological issues but that study came out and said much too much money is going to AIDS and not enough to these other diseases there were some big methodological problems but I think we're going to see more and more of this and how we put that into context and deal with it is going to be a critical priority over the next year or two we're slowing working in Russia on HIV AIDS control as you know in Russia the main transmission is through injecting drug use are you doing any work particularly with injecting drug users and secondly is it a different mechanism than the transmission from the cellular standpoint so excellent question and a complicated one it turns out so years ago people believed that certain types of the virus so called clades species of the virus had adapted to be heterosexually transmitted and so people believe that the B-strain which was in the US and Europe was mostly spread by blood and that blood included having men who have sex with men where there's some you know mucosa that's very thin and there's some bleeding with anal intercourse etc so and they said that clave C for example which is the one that's spreading mostly in the south is adapted for heterosexual transmission and so some studies came out of Harvard on that and it turned out that those weren't able to be reproduced but now there's a whole new set of data that's actually coming out to suggest that in fact there are differences in transmission or differences in virulence between the different strains and so it may be that they're slightly different in terms of what's being transmitted and how there was data in Thailand that suggested that the type B was transmitted through variety of drug uses type E was transmitted heterosexually and it was almost like two epidemics that were moving at the same time although there was some mixing at the end of the day we need protection against all different types we've been working mostly in heterosexual epidemics and the reason we've been doing that is you know our primary focus is to try to make sure Africa was included and that's what most of the epidemic is there but there is an enormous need and a number of the trials are going on in IV drug users that was true with the Vaxgen trial it's true with some of the work that's going on in the Thai trial and and so I think the answer is we've got to look at both and we need to make sure we have a vaccine ultimately it does work in both the other thing is is that the vaccine is much higher in intravenous drug use than it would be normal heterosexual transmission it's probably just one or two viruses getting through it's a very small inoculum that actually makes it through and some new science that came through recently whereas when you're obviously giving intravenously it's a different game probably much harder to protect yeah some of your partner scientists from Africa and elsewhere my question is how do you build a better constituents a more vocal and visible constituency for science from Africa and the other partner countries I think from much of the debate that's been absent here you don't have visible prominent personalities that are pushing on this particular very important sort of set of opportunities and if there were it would change the context significantly here for the way the issues are debated so I wanted to ask you to talk about that and if I may add also you opened the door here in your suggestions around where we are now in this with the president's program we're at a new moment in debate around US global health strategies and I wanted you to say a little bit more as to how much has to change in the way we think and articulate our priorities looking forward because certainly you seem to be moving in that direction that there is a game changer that has happened here with the economic recession with the change of administrations there's a recalculus going on and how do you see that moving forward so it's really two questions so yeah where are the champions coming from in Africa the institutions I mean it's an interesting question starting off in the champion issues I don't have a magical answer and the reason I don't is exactly the question you asked before which is how prominent do you want the discussions to be let me give you an example so in Kenya which is the first place we really started working we brought the first AIDS vaccine designed against strains that were in Africa and there were three scientists there who were prominent doing the work and the Kenyan paper had headlines, three scientists three musketeers going to save Kenya and again because of this unreasonable expectations we've really gotten a little shy on how prominent do you want it to be do we dial it back do you want leaders to come pounding on the table and say we demand this this is critical because then you again have this problem of expectations so we're struggling with what the right balance is between you have to have a voice you've got to have people saying that you've got to keep it on the agenda but you also don't want to be put back in a position where if there is another failure of a candidate which there will be people don't say oh my god it's hopeless this is the end of the world and so how you get that balance right is really the tough issue the other part of it is how much of it is at the political leadership level and how much of it is at the scientist level and then the community level looking for ways to connect those pieces is absolutely critical but if you go back five or seven years ago there was the first AU only AU summit on AIDS we went to that summit there was a 50 page document it didn't mention research it didn't mention HXS it was the document for Africa and so one of the challenges is how do you kind of get it in there and keep it in there I don't have a magic answer for that so the thing we're doing this afternoon is we're bringing some very prominent wonderful researchers to come and talk about it and talk about the effects I love hearing South Africa that was a really interesting person you can't measure this stuff but we set up a program to do quality assurance quality controls around the laboratories in South Africa the other labs in the area thought this is really interesting these labs have that the labs lifted up quality in the area how do you measure that but that's what we're really looking for is that effect that occurs much broader and we've tried to document some of it there's an article out there on science in Africa but how do you really capture that type of stuff and to go back to your question it's not our job is to find an AIDS vaccine so I gotta be really careful if I'm out there saying gee I'd like to be working on better tertiary education for scientists we can comment on it but we can't invest in it although we've actually we've toyed with the idea if we could get money to do fellowships and things like that would we be able is there a way we can align it with what we're doing to help make a difference in there so I think in a sense we'd like to be part of the conversation but we can't be the leaders of the conversation because it really isn't in our mission in terms of the timing I think it's an extraordinary time thinking about this because we are going to have a rethink of foreign aid times have changed completely look at the the Brentwood institutions the world's changed World Bank for example is not well set up to do social programs we know that lending is not the right mechanism to deal with education and a number of these other issues so we've got a lot of rethink that has to go on now and I think it's an important time to really ask the question what is development going to look like in the next 50 years what are the requirements going to be what are these countries going to need how are we going to move them and what type of relationships are going to be required and I think even for the United States the idea that we're a knowledge based society that we need science education and better trained people and better workforce you're hearing it although it's pretty scary where we rank among OECD countries and as you know China and India are out there producing massive numbers of PhDs and engineering and other scientists and they're going to be forming relationships more and more with the developing world so I think it's a completely shifting landscape and for our own survival as a country that's leading in some science and technology we're going to have to do it for ourselves but this type of dialogue this type of engagement can keep us in the forefront and bring something that others can't bring and that to me is the most interesting part of innovation corridors and all the other things they haven't been able to magically reproduce what happened in Silicon Valley and Silicon Alley and the Cambridge Corridor and others and whatever that je ne sais quoi is something we ought to be thinking about for developing countries and these problems because some of these problems aren't going to be solved without scientific innovation some are we've got the innovations we just have to get them out there some of them require much better innovation and boy if we could get focused on that we can really make a big change great, one more question Laura Eom, I'm a freelance reporter for Deutsche Welle one of them is if you could talk a little bit more about this potential vaccine and the antibodies that seem to have some promise here and the other thing would be you did talk about if people are on antiretroviral treatment that they may still be transmitting because my understanding was that it just knocks down the viral load so low that they aren't transmitting so in a sense another solution which would probably break the economies of most countries is to pay for everyone gets the antiretrovirals and it just knocks down that virus you prevent the infection that stops, that's a preventive treatment so on the second first there was a paper published in the Lancet by a team coming out of WHO that suggested treatment for prevention and they did some mathematical modeling what they said is well if we treat early we treat hard and we constantly test so that we're constantly identifying new people we could do this now they did a mathematical model what it hasn't been is really tested and whether it will be and we're able to do that and financially sustain it is a different question but the point I was making is that even people who have very low viral load you can still isolate a virus from semen it's a protected compartment now at the end it looks like there's some data coming at it and it looks like when you're on treatment it does reduce transmission so whether it reduces zero or not how much goes on one of the problems is that probably the highest risk transmission time is actually within a few weeks of being infected when you're not going to be HIV positive when people are not going to necessarily know there and would be unlikely to be under treatment so you'd have to put the entire population on all the time catch every new infection it's very hard to do but people will study this and understand better what it will play in public policy on the antibody based vaccines there isn't a vaccine yet what's exciting is that the way other vaccines work is they produce neutralizing antibodies and if we could find antibodies that were very potent and that would be easy to produce then of course you'd want to take those candidates the four antibodies that have been known for 15 years are kind of weird they have long arms they're very hard to know how to produce them they reach behind the virus to where they bind onto the cell and that's how they work that's why they can be conserved across trains nobody's succeeded in making an immunogen that is a thing that you would inject that would make those antibodies we know people can make them the hope is that some of these new ones that are coming out will not only be more neutralizing conserved but will be much easier to produce structures that are simpler and if that's the case then rapidly turn those into vaccine prototypes and as soon as we have an immunogen that will give us our bar is 50% moderately resistant to neutralized strains to neutralize 50% of those that will fast track it into humans we're hoping for that but we are waiting for a breakthrough on that and we don't know when that's going to occur but I'm optimistic given all the new tools and all the exciting science that's going on I wonder a couple of years ago there was the Chinese American David Hu he did something at that time it looked like a good job for the AIDS so you know when you put something with the wine get something I mean what I'm sorry I'm listening I wonder there's a doctor here in the United States a couple of years ago I haven't heard anything after that it looks like he did a good job a couple of years ago he found something specifically for the cured AIDS I wonder is right now nobody talking about it that doesn't work the wine with the put into something that can totally cure the AIDS I don't know you said David Ho initially we work with David Ho he supported him on AIDS vaccines I don't know any work he's done on wine there are some fabulous compounds in wine that do act as antioxidants they're very good protecting of course you have to drink a lot of wine and some people have argued that they're happy to try to drink a lot of wine but I haven't heard anything in terms of its role in curing HIV and one of the problems is that you know given the magnitude of this disease around the world and the problems associated with it and the lack of good treatments and things that can cure it people have tried many many different treatments that show different you know effects in different places but we know we've got some reasonably good drugs for it now in fact there's more drugs for HIV than for all the viruses put together and I think that's going to be the main mainstay of treatment at least until we come up either with a way to cure it or a better way to prevent it Steve well I mean it's a really interesting point I actually wrote an editorial a few years ago in Newsweek on the relationship this was about avian influenza and you know avian influenza vaccine attempts and the relations to HIV vaccines these are very similar in what's needed and what do I mean by that there's obviously been a big market for flu vaccines but not as big as you'd think I used to years ago be on the company a company board of a traditional egg-based flu manufacturer the second largest manufacturer in the world and we used to have a discussion around the boardroom table that went something like this flu vaccines are a commodity vaccine you know it's relatively inexpensive we know we need better technology with amounts of money and there's no justification because you won't get it back since your other competitors will be able to sell the vaccine very inexpensively there's no way to do that so people didn't invest in new technologies then when avian influenza came all of a sudden there was panic and there was an investment in new technologies a lot of the investment went into building more egg-based plants because the idea was they could then produce vaccine egg-based vaccines are terrible I mean it's a 50 year old technology obviously if there was a massive avian influenza and it got into the bird stock you'd have no eggs so I mean it's not your ideal way of doing it there are new technologies that could be used the problem is how do you really accelerate them now the market will take care of it you can argue let the market do it but the market is going to do it through venture capital and those are going to be much slower approaches than what they would be if there was a new approach or funding stream and I think now we're in exactly that thought process around avian H1N1 Mexico City 2009 so one of the questions is WHO had already chosen its trivalence strains there are three strains normally in a flu vaccine there are two influenza A and one influenza B they've already chosen them manufacturers were producing it all of a sudden this epidemic occurs and everybody says wait a second there's a couple of possibilities one you could just drop this new flu strain in so one of the A's take out the old one put the new one in this particular virus doesn't grow very well on eggs so you'd have to get one that was close to it not exactly and then you could go ahead and make a trivalent the world can make about 450 million doses of trivalent vaccine and that would be ready a little bit late but it would be ready for the season the other choice would be trivalent and so it would make just the H1N1 Mexico City 2009 and then we could make 1.3 billion doses let's say and in fact if you put adjuvants you might even be able to stretch it further now you wouldn't protect against B you wouldn't protect against other A strains that were circulating so that's a huge policy decision to be made and the question we were talking about before which is really interesting is if you're in 1918 what happened was the flu season came roaring in and during that particular pandemic the estimates are 50 to 100 million people were killed but the point is they were killed in places that didn't normally have lots of flu deaths like Africa we don't know what the numbers were so if that happened again who's supplying vaccines for Africa who's thinking about that and for other poor countries there just aren't adequate supplies so what's the mechanisms to do that that you need new technologies that can produce large quantities and the same thing by the way goes for avian influenza if it was to shift over as you know they've stockpiled egg based avian influenza vaccines but if there's a little antigenic shift it's probably not going to work so what we need to do is have a thought process again on how we prepare for these types of issues what's the role of the private sector what's the role of the public sector how do you drive the science how Zambia is not sitting there saying let's try to make better vaccines for flu they can't they don't have the capabilities so in a sense this is where they would be really dependent upon the west and are we thinking about it in the best ways and I think not so these are issues that really need to be dealt with and they have answers but there are trade-offs on these where are we on microbicides I gather it was very promising about a year ago and then it didn't come through and when do you see it there are promising microbicides there's a product that just went through a small phase 2 trial that had about 30% efficacy it didn't reach statistical significant but if you looked at the sub-analysis of the study it looked like it would if it had larger numbers every bit of the data pointed to that it was going to work then there's a whole movement now there's a second generation of microbicides and those are going to be microbicides that are actually using the antiretroviral drugs either used as gels or even on rings that may be sustained release and those are now moving forward so I think we will end up with microbicides of one type or another whether they will be as useful and useful to all populations or not I think only time will tell there's been a huge problem with how adherent people are to using them because at least the ones that require daily use not everybody is able to prepare for their sexual encounters and take the time to do it and have supportive partners etc etc so again a very important part of our toolkit but a loan is probably not going to solve the problem good thank you all


Milo Bailey, I think I could regain free speech again on Twitter, but it will be difficult. Yeah, if Musk takes it over, and there's serious free speech, maybe I'll go back to Twitter? I'm not 100% sure yet. I don't trust Musk. Not as far as I could throw him, right? I'll look at Twitter is too liberal for me to use again. Free speech or not? Indeed. It's got to be full-on free speech. I can say whatever I want. End of story, right? Yoshi. Buying Twitter isn't for the website and servers only. It's the number of users and the hundreds of thousands of presidents, politicians and people of power, even Taliban. Here's the thing, Yoshi. If Elon Musk comes out and says, no, I'm going to these other platforms, I will no longer be posting on Twitter. How much of the activity on Twitter is because of Elon Musk? Seriously. It's got to be, my guess is, Elon Musk is the top Twitter celebrity out there, right? If he comes out and says, I'm out, gone, right? I'm willing to bet a lot of other politicians, celebrities, music, a lot of other people will go as well, especially when they realize Twitter is just a bloody echo chamber and a lot of it is bots and it's losing ground. Like, look at Twitter. One of the top, one of the main technocratic sites that came online that went on Wall Street, right? If you invested money in Twitter when they had their IPO, you would have lost a lot of money as of two weeks ago, right? And you're probably breaking even right now. Compare that to investing in Google when they had an IPO, Facebook when they had an IPO, who else? Etsy when they had an IPO, some of these other companies when they had IPOs. What a waste of money.  The real dialogue is taking place outside of Twitter because Twitter censors, right? Once, and people are leaving Twitter, that's the data I'm seeing because I'll follow some of the other new tech platforms and I'm seeing their rankings go up. Their rankings are not going up because there's more kids being born or people deciding to join social media. They're going up in large part because the technocratic censored sites are bleeding users, right? Are bleeding users. Look at the numbers on Rumble. Seriously, it's the most beautiful chart you've seen. It's growth. Rumble is like this. Like one of the most stable. If you're investing in a stock, that's the company you would invest in, guaranteed. You look at some of the other new tech, they go like this a little bit, right? Rumble? This. That's not happening to Rumble because there are all these new content creators coming online that are deciding to upload to Rumble only. That's happening to Rumble because a lot of content creators, me included, are uploading more content to Rumble, BitShoot and Odyssey than we are to CensorTube. Like this live stream is not going to go on CensorTube and it's an important live stream. It's an important discussion that we're having about world events, current events that will reshape society during the most important period, as far as I'm concerned, in human history is taking place right now, right now. From monetary issues, right? To geopolitical issues, to social issues, societal issues, religious issues, huge, unbelievable, and it's not taking place on technocratic sites.


What effect does a catalyst have on the rate of reaction? What I have here is hydrogen peroxide H2O2, and I'm going to put about 50 milliliters in each one of these containers Next I'm going to add some manganese dioxide in the first one and manganese dioxide is often used as a catalyst So let's see what happens to the rate at which this reaction occurs I'm going to stir it just a little, I'll do the same to the other If you look closely you can see little flakes of the manganese dioxide A catalyst lowers the activation energy but doesn't get consumed in the reaction So after the reaction is complete You can recover the catalyst and use it again


Today, I wanted to share with you guys my thoughts regarding the free software movement and gun rights because I find a lot of similarities between the free software movement and second amendment supporters. One of the cornerstones of the free software movement and the open source movement as well is that you can't prevent people from using that software for whatever purposes that they choose to use that software for. So whether they use your software for quote ethical purposes or unethical purposes, it really doesn't matter and free software and the various free licenses, they don't have any say in this, you know, to qualify as free software or open source software. You can't tell people what purpose they use your software for. They can use it for whatever purpose they want. And this is for good reason because what exactly is ethical or unethical? Well, it depends on who you ask. It's entirely subjective. And if I license a piece of software in a way that states that the software can't be used for this purpose or that purpose or by this group of people, maybe for political reasons, you know, I don't want the military using my piece of free software or the NSA. Well, I can't license it that way. Well, I could license it that way, but that license no longer qualifies as a free license. My piece of software will no longer be considered free software or open source software if I license it in that sort of way. And I really love that the free software definition and the open source software definition protect people in such a way that they can use this software in whatever purpose they want, because I think that's very important. I think that's very important as far as people's freedom. But I see a disconnect because I've noticed that many people in the free software community tend to identify as liberals. And many of those folks are in favor of some form of gun control. Now, I understand that many people get trapped in the whole Democrat, Republican, liberal, conservative, left, right dichotomy. You know, they join a team and they're going to go along with everything that their team wants. But really, I mean, when was the last time that you met a person in real life and you agreed with 100 percent of everything they ever said, right? It's never happened. But when it comes to political party affiliation, well, all of a sudden, you know, people just agree with everything that their party leaders tell them. Now, I expect more from the free software community and the open source community, because we wouldn't be part of these communities if we weren't afraid to go against the norm, right? Simply by being part of these communities, we're we're kind of already identifying ourselves as nonconformists. So why are some of you guys conformist when it comes to two party politics? If you are a believer in the free software movement, then you probably subscribe to the idea that we as humans have some basic fundamental rights that should never be infringed upon, for example, the right to privacy. Most of us that are supporters of the free software movement strongly support digital rights and digital privacy and think those to be unalienable rights as the founding fathers of the United States would put it. In fact, the right to privacy is kind of implied in the very First Amendment and the Bill of Rights. It's so important the right to privacy. And that's why it's the First Amendment. The First Amendment guarantees things like freedom of the press, freedom of religion, freedom of assembly, the freedom of expression, rights so important that they had to be the very First Amendment. And you know what basic human right was so important that the founding fathers of the U.S. thought it needed to be the Second Amendment, the right to bear arms. And I see similarities between the kinds of freedoms that the free software movement fights for and the freedoms that the pro Second Amendment people are out there fighting for because software, as we've talked about, is just a tool and really guns are just a tool and having the freedom to do what we want with our software and with our guns, both are paramount to having a free society. So software is just a tool, guns are just a tool. How that tool is used ultimately is up to the user, right? It's up to the discretion of the user of that tool. The same thing can be said about firearms. A gun is simply a tool. It's an inanimate object. It does nothing on its own, right? It really can't do anything.   But I've never heard anyone suggest that hammers kill people. No one's ever said that. So why the double standard when we talk about guns as opposed to other tools, such as hammers or software, in my opinion, everyone should own a gun. Everyone that hasn't disqualified themselves in some major way.  But every law abiding citizen should own a gun and not just one gun. You should own several guns back to the tool analogy. You wouldn't buy just one wrench or one screwdriver, right? Because you have to have several different kinds of wrenches to get all the jobs done. The same is kind of true for guns. You need to own several different guns to have all of your bases covered. So if you currently don't own a gun, my suggestion would be first buy a nine millimeter handgun and learn how to use it. By far the most important reason to own a gun is for self-protection. So buy a handgun chambered in nine millimeter, which is the most popular handgun caliber and start carrying it and learn to use the thing. Now, when I say start carrying it, it will depend on your location, because obviously those of us that live in free states, you know, we can conceal carry or open carry, you know, depending on whether you need a permit or not, but, you know, it's an option.  Technically it's possible, but they just won't issue you one. So it's next to impossible for you guys to actually carry. So my suggestion in that case is really you have two options. A move out of that state, right? And no, I'm not kidding. Move out of that freedom-hating communist state and move to one of the free states. Or if moving really isn't an option for you, what you could do is try to remove those politicians that took your right to bear arms away. Now, after you buy a handgun, the next thing I would suggest buying is a 22 rifle. So buy a rifle chambered in 22 long rifle because it's a great survival gun. Twenty twos are perfect for shooting small game. The ammo is really cheap. It has absolutely no recoil. It's great for practicing on how to actually use a rifle and it's great for children as well. Next, I would start buying what I call freedom rifles. So go buy yourself an AR 15. This is sometimes dubbed America's rifle. It shoots a really nice caliber 556 or 223. So it's a 22 caliber round, right? But it's a much more powerful 22 round than the 22 long rifle. So AR 15s are actually very capable as far as hunting rifles. They'll take game up to deer sized game. And it's a good self-defense round, of course. And because AR 15s are so popular, maybe America's most popular rifle and they're so cheap, nobody ever buys just one. And I suggest you don't buy just one either. Buy two. Buy two. That way you can arm a friend or a family member in a it's the fan kind of situation. Another freedom rifle worth getting is, of course, the AK 47. Now, the AK shoots a bigger round. It shoots a 30 caliber bullet, but the ammo is very cheap and very plentiful. AKs come in a lot of sizes and shapes and calibers. This beauty here, this is a Russian VEPR chambered in 308. I'm very proud of this rifle here being a Russian firearm, though it is no longer something that you can get. So it really is a collectible item. And this one here is a Russian VEPR chambered in 12 gauge. Now, think about that for a second. This is a semi-automatic rifle that has a 10 round magazine that fires 12 gauge. There's a reason that groups like Antifa hold their protest in the communist states rather than the free states, because they wouldn't want to step on my lawn. Now, I don't like getting political on this channel because, honestly, I think that everyone that participates in the U.S. government and U.S. politics, quite frankly, they're crooked as hell.  But it's not the politicians necessarily that disturb me. It's you guys, the people, because I see too many people willing to give up their freedoms just to go along with the current political wins. So hold to your principles, just like sticking to your principles when it comes to the free software movement and all those First Amendment rights that you love so much, such as the right to privacy. Stick to your principles when it comes to your Second Amendment rights as well. Even if you don't personally own a gun, maybe you don't like guns. Maybe you live in one of the communist states. You can't even have a gun or carry a gun, right? It doesn't matter, though, because it's not just about you, right? The right to protect oneself from things like the rioters in Oregon, those of you that live out West, or maybe you need to protect yourself from looters after a storm. I've certainly dealt with that in my life, or maybe you need to just protect yourself from your government. And that's a real situation. It has happened many times in history, including US history. People have had to take arms against their government. One thing we've learned over the course of history is once you give up a right, you never get it back. So guys, no matter what, fight for this right and be prepared to defend it with your life if necessary.


TfNN, headline news update. Hi everyone, Basel Chapman here, the host of the Tiger Technicians Hour coming up straight after this TfNN noontime update. The dial is up at 6.90 at 24,822 and coming off the low this morning of 24,701, 3,000 points off the low that was made back in December. It had gone 5,000 points up, so we've lost 2,000, we're up 3,000. This is going to be a very interesting week and I'll show you why. Look, there's a chance here that the dial is ready for at least a bounce. It could be dates, it could be a price, it could be a combination, but I'm only going to get a bounce because I think there has to be more testing of the 24,000s before we can really start to look at the upside as a more intermediate term or longer term rally potential. So here we are. The low that needs to be held is 24,000, I would put it at 24,680 if we go below today's low. That's going to be a big negative for the next couple of days. I suspect that if the dial closes up today, even if it's not very much but modestly higher, there's a chance we could rally into Tuesday, Wednesday, that's my thinking that's what I told subscribers to my opening call, my daily newsletter. Let's go to the S&P. The S&P right now, he's up, oops, now it's down, it's down 1.41 at 2750. It made a low this morning of 2738, it's trying to rally, it's having a difficult time but it's got a candle here, a potential doji candle that says if tomorrow we can start to trade in the S&P, tomorrow to Wednesday, the S&P can start to go to 2765, 2770, that's going to be good for at least a couple of days. Now the QQQ, this is the problem, the QQQ is down $1.77 to 172.18. It's made a low, a low, it's really struggling and this is going to be part of what I'm looking at here that not all the sectors are in rhythm and that says that the Qs need to be the index 100 trading vehicle, needs to get over the 200 period moving average of 174, let's call it 174.70 to show at least a modicum of strength. The IWM is holding quite nicely, it's up 41 cents at 146.28, we'll see whether it has a rally. I'll be talking about gold in my show coming up in a few minutes, it's up $13.00 or $13.24 and the dollar's pulling back some, not all that much but the dollar is pulling back down 23 ticks at 97.55, Baselchap and Tiger Edition's hour, I'll be right back in a few minutes otherwise I'll see you tomorrow for the next update at noon on Tuesday.