One of the pleasures and privileges I have as president of the American Association for the Study of Liver Disease is to select the speaker for the President's Choice Lecture. And I'm honored to introduce this year's presenter, Dr. Tachi Yamada. I selected Dr. Yamada because he is an innovative scientist, a gastroenterology scholar, and shares in AASLD's mission to advance the science and practice of hepatology. Dr. Yamada has an expansive background in medicine and in the healthcare industry, having spent time at the University of Michigan, GlaxoSmithKline, Decatur Pharmaceuticals, and as president of the Bill and Melinda Gates Foundation Global Health Program. While at the Gates Foundation, he oversaw the Global Health Grant Portfolio, totaling over $9 billion in programs directed at applying technologies to address major health challenges. Focused in the developing world, including TB, HIV, malaria, and other infectious diseases, malnutrition, and maternal and child health. Dr. Yamada currently serves as venture partner on the life sciences team with Fraser Healthcare Partners, focusing on company creation around innovative therapeutics, and as chair of the board of the Clinton Health Access Initiative, where he continues to help people in low and middle income countries gain access to essential medications, diagnostics, and health services. In this lecture, Dr. Yamada will share lessons from global health by exploring potential strategies to prevent the loss of life in some of the world's poorest nations. He will highlight the challenges and opportunities to overcome these challenges to accomplish this task. Dr. Yamada has always been a force in our field, and I am very honored to have him join us today. Ladies and gentlemen, Dr. Tachi Yamada. Thank you, Michael. I'm really honored to be here today. I'm delighted. In fact, when Michael first asked me to join this meeting, I wasn't quite sure if I was an appropriate speaker for this meeting, but as it turned out, the work that I've been doing with the Clinton Health Access Initiative, and in particular, our initiative to eradicate hepatitis C, gave me an opportunity to talk about the lessons I've learned in global health and how they've affected the way I work today. Now, as with many of you, I enjoyed my career as a physician, as a physician scientist. I got to the point where people were asking me to be a dean of a medical school. Now, to me, that was about the closest thing to dying that I could think of, and with all due respect to deans out there in the audience. So, I had another alternative, and that was to join a pharmaceutical company, and the idea of making medicines that would affect the lives of millions of people was very enticing, and I chose that option. But when I was working with SmithKline Beecham and then GlaxoSmithKline, something happened that fundamentally changed the way I looked at the world, and that was that GlaxoSmithKline, which is a large manufacturer of antiretroviral medicines, was party to a lawsuit against Nelson Mandela himself over the pricing of HIV medicines. Now, this was a shock to me. I couldn't imagine a company suing a near saint over an effort to save the lives of his people, and so I looked more and more into this problem and became a scholar on global health, and for the first time, I realized what it meant to talk about global health equity, that is, that all lives have equal value. Now, during the course of my discussions with GlaxoSmithKline, it changed the way the company was. We started a research unit in Tres Cantos, Spain, that focused on medicines for malaria and TB and other infectious diseases with the idea that there would be no profit to be derived from this effort, and we entered into partnerships with the Gates Foundation, and sometime thereafter, I had a chance to visit the Gates Foundation, and to my surprise, before I left, I had an offer I couldn't refuse, to join the foundation in its efforts to apply science and technology to address the most pressing problems of the poorest people in the world. It was an offer I couldn't refuse. I joined the foundation, and very quickly, I learned some very important lessons. The first lesson I learned is about urgency. Now, urgency means different things to different people. I've always felt I had an urgency about what I did every day. I always felt like I was busy. I was trying to do everything I could to maintain my career, to push forward on behalf of my patients, but the level of urgency achieves a macro scale when you see a problem at its very core. One of the first trips I took when I was at the Gates Foundation was to the southern region of Mozambique, where we had a malaria program. The place was called Manjissa. In Manjissa, there was a subdistrict hospital, and if you think about a hospital in the United States, of course, it's a big, modern-day cathedral, but in the field, it's really just a bunch of tents and Quonset huts. I passed the intake area of this subdistrict hospital, and I saw a mother and child there. The child was very young, perhaps six, eight months old, and I could see the child was very sick. I noted that the mother was very concerned, and then we went on to look at other parts of the hospital. By the time we got to the pediatric service, such as it was, it was a bunch of beds, and each bed, there were two, three, sometimes four children. All of them had malaria, and in one bed, there was the baby that I saw in the intake area, and between the time that I saw the baby there and the time the baby was in the pediatric ward, the baby had deteriorated rapidly. It was breathing at the rate of 60 times per minute. It was pretty clear to me that the baby wasn't going to survive, and unfortunately, he didn't. But what got to me were two things. First, that if that baby were my child or my grandchild, in the United States, that baby would probably not have died. The baby was not dying of malaria so much as neglect of malnutrition, of repeated infections, of diarrhea, a weakened immune system, tropical gut, you name it. The baby was set up to die, and unfortunately, he did. The second part of it that is unimaginable is that this is occurring six million times a year. This isn't just one baby, that there are still six million babies dying each year, unnecessarily from diseases that could be treated or prevented. That gave me a sense of urgency. Now, why is it that recognizing this problem and understanding it, the world couldn't do anything about it? The reality was there just wasn't enough money. And so what happened often was people would apply for grants, they would do a demonstration project in some community and write up the project and said, if we did these 10 things in this community, we could save some lives, and then they would go home. In Native American parlance, it's called counting coup. It's a pyrrhic victory. You get a publication, but nothing happens. Well, something changed around the turn of the century, and that was with the advent of the Millennium Development Goals where the world decided there were some very important challenges that the world wanted to and needed to undertake, including reduction of child mortality by a third, a reduction of maternal mortality by three quarters. There was a very tangible goal that was set up, and that resulted in an influx of money as global health has never seen. Today, there are upwards of $40 billion available to address global health problems. And in fact, we can undertake, be very ambitious and undertake projects that seem impossible, like eradication of polio, eradication of malaria. These are really difficult, complex problems because we don't really have great solutions for those problems. We do have vaccines, however, and vaccines are amazingly effective. As you know, with the hepatitis B vaccine, you can prevent cirrhosis and liver cancer. It's a wonderful, wonderful tool that today can be available for as little as 15 cents a dose. Well, the Gates Foundation put a major foot forward to address this problem. It was party to the initiation of a new project called the Global Alliance for Vaccines and Immunizations. And this program was very effective. It started out with vaccines for hepatitis, but has gone on to vaccines for rotavirus and cervical cancer and all manner of vaccines. It's estimated to have saved 5 million lives. But at one year at the foundation, we learned that this organization was going broke. It was spending a billion dollars a year and raising $300 million a year. It doesn't take much math skill to understand that this can't proceed. So I presented the problem to my boss, Bill Gates, and I said, Bill, we have a problem. And he was sometimes very mercurial. Sometimes he can go through the roof. And on this occasion, he was quite calm. And he said to me, he said, Tachi, so what is your triage plan? I said, triage? What do you mean, triage? He said, if we can't give vaccines to all the children, tell me which children you're going to save and which you're going to allow to die. Now, I can tell you, that gave me a sense of urgency that I've never felt before. The idea that we can have to be selective on who lives and who dies with technology that we know will save lives. And all we have to do is find a way to make it available. And that, of course, was a challenge that took almost a year to resolve. But eventually, with a partnership of many, many people, a willingness of some to suspend disbelief, and some to give more than they perhaps rightfully should have given, and we solved the problem. And GAVI is a very strong, vibrant organization, still giving vaccines to millions of children all over the world. Now, let's take Hepatitis C. I read somewhere there are 70 million people living with Hepatitis C, 400,000 dying each year, perhaps more. And unlike almost any infectious disease, in almost any disease, we actually have a cure. We can cure this disease. And yet, we haven't done anything about it. We've signed agreements to say, yes, we should probably get rid of this problem. But nothing has been done. And I am really pleased today that I think we're going to be part of an initiative where something will be done and this problem will be rid of once and for all. Now, the second lesson I learned is about innovation. If the old ways don't work, you don't just keep doing the old ways. But amazingly enough, in health, and in particular, in global health, we kept doing this over and over again. In global health, some of the biggest problems are HIV, malaria, TB. You know, we have one medicine for malaria, and now there's resistance developing to it. We don't really have a vaccine for malaria. One has been developed. I've been part of that effort, but it's not a very effective vaccine. TB, there's no vaccine. You know, we now have one or two new medicines, but until just recently, there weren't new medicines for over 50 years. And HIV, despite all the years and all the billions of dollars that have gone into research, NIAID and industry alike, we still don't have a vaccine for HIV. And yet, we keep doing this. Something has to change. And that's innovation, true innovation, not incremental evolutionary innovation, but revolutionary innovation. You know, the example that I always refer to is my own experience. I've worked a lot on acid secretory mechanisms, the receptors, molecular biology of the receptors engaged in control of acid secretion. You know, the miracle drug was Tagamet. Tagamet fundamentally changed the way we treated peptic ulcer disease, and we thought, wow, we've got a cure. What we learned was the day you stopped treating people with Tagamet, their ulcers come back. We never really thought about this problem. We kept making better antacids, PPIs. They were great, but the day you stopped the PPI, the ulcer came back. Then there were a couple of scientists in Western Australia who said, no, no, it's not acid. It's an infection. Excuse me. You know, as investigators in the field, we hated those guys. I mean, they were just bothering us because they were challenging our dogma. And that challenge to dogma was irritating. We should have embraced it. Of course, the Nobel Prize committee did embrace it and they've won the Nobel Prize for their finding. And they fundamentally transformed peptic ulcer disease and beyond that gastric cancer, that you can prevent gastric cancer by treating H. pylori. That kind of innovation is needed to solve problems like malaria, HIV, TB. And so at the Gates Foundation, we started this program called Grand Challenges Explorations. The whole idea was that you could submit an application to us, two pages in length, no preliminary data. You didn't even have to have an advanced degree. If you had an exciting hypothesis and a way to test it, we would give you $100,000 a year within three months of receiving your application. What a fantastic program that was. We got incredible ideas. You know, we had ideas, for example, some that came from Nobel scientist labs. For example, Leslie Voshall out of Richard Axel's lab had this idea that you could block the odorant receptors on mosquitoes so they could not recognize human beings as food. And in fact, they demonstrated this. And that concept has been taken up by a German chemical company that's making not repellents, but confuses. They confuse mosquitoes. They don't recognize you as food. Other projects were really outlandish. We had a project proposal by a physicist who was from Edward Teller's lab, and he was the architect of the Star Wars program, the U.S. Defense Department. And his idea was to create an electrical field between two telephone poles that you would put up in a village. And when a mosquito crossed that field, you could detect that it was a mosquito, even a female mosquito, by the wingbeat frequency and the pattern of the wingbeats. And that was hooked to a laser which would hit the mosquito and pulverize it. Now, actually, I saw the machine in action. There's nothing so satisfying as seeing a mosquito pulverized. But these ideas sound crazy, and they are. But crazy ideas are what we need to make things work, to make change, to advance medicine beyond where it is today. But another element of this is about innovating ways of financing these things, innovating how to deliver these things, innovating how to produce results, not just have a treatment available. And so we did some pretty amazing things, like using the Gates Foundation balance sheet, which was upwards of $100 billion, to guarantee key markets for companies to invest in the production of new treatments for diseases of the developing world. We worked very closely with a company like Sumitomo. Sumitomo had a way to treat bed nets so that they would actually kill mosquitoes at night. And they recognized that this was something that they couldn't make financially viable for them, so they gave the intellectual property for free to a local manufacturer in sub-Saharan Africa. And this is a company called A to Z Textiles. And this company now provides the vast majority of bed nets to people in sub-Saharan Africa and can deliver the nets for $5, and another $5 to actually transport the nets from their manufacturing facility to the place where they work. Now when we think about hepatitis C, we actually have had the innovation in the science side. What we haven't had is innovation on the financing side. For example, what if the treatment for hepatitis C, which started at $80,000 per course, could be brought down to $80 per course? Does that sound outlandish? Does that sound impossible? I can tell you, it's done. It's done. So innovation is possible in financing of the eradication of hepatitis C. Also in how to deliver. Do we need specialists? No. Can we use the existing systems? Everywhere possible, we would use existing systems. The idea to integrate the hepatitis C treatment, simplify it, make it broadly available is a critical way forward in eradicating hepatitis C. It's not just the medicine, it's the financing, it's the delivery, it's the application of the strategy. The third lesson I learned is about measurement. I actually worked for a CEO, my first CEO, and when I joined SmithKline Beacham was a man named Jan Leshley. And Jan Leshley was a professional tennis player. He actually entered the semifinals of the U.S. Open, so he was a pretty good tennis player. And he used to say, if you're not keeping score, you're just practicing. Now how often do we do that? How often do we just practice? We do things because they look good. We do things because they feel good. But do we actually measure the impact of what we do? Now I tell you, at the Gates Foundation, we were acutely aware of this because we were spending upwards of $2 or $3 billion a year on our programs. It's easy to think that because you're spending so much money, you're doing a lot of good. But when you actually measure the impact of what you've done, some things are actually doing things and others are not. So we started investing very heavily in information. How do we capture information? We started the IHME, the Institute for Health Metrics and Evaluation. We started the Health Metrics Network. We contributed to the IIIE, International Initiative for Impact Evaluation. If you don't measure what you're doing, you're actually not getting very far. And I think this is also true in hepatitis C. We can give the medicine but if we're not affecting liver deaths, incidence of cirrhosis, liver cancer, we're not getting very far. And we really have to have that information wherever we implement these programs. Finally, the most important lesson I learned is about partnership. See the Gates Foundation was very wealthy and it was entering into the field of global health like a nouveau riche, maybe investment banker walking into a neighborhood and building the biggest house. And of course, everybody hates you. And you realize in the world of global health, you can't do anything unless you have partners. The WHO, UNICEF, UNH, all these agencies and all these people have to be your friends and have to be willing to work for you to get anything done. There's an old African saying, if you want to go fast, travel alone. If you want to go far, travel together. And that is what I learned when I was there. And I will tell you a story about that. You see, meningitis A was a terrible scourge that swept through Central Africa every couple of years. It would kill hundreds of thousands of people. But the people who survived were not unscathed. Many lost mental facilities. Many had seizure disorders. Many had neurologic deficits. Many had markedly diminished IQs. It was a terrible disease. And so the health ministers from the Central African states came to the Gates Foundation and said, can you help us? And the WHO was very much behind this. So we undertook this project to create a vaccine for meningitis A. And in this, we got help from many different places. The Dutch company had some IP they gave us, intellectual property they gave us. The FDA actually had some intellectual property. The NIH helped us. We enlisted the support of PATH, Programs to Advance Technologies in Health, an NGO that does many different implementation programs in the field in global health. And we got an Indian manufacturer to make the vaccine. And after seven years, which is a remarkable time if you understand the timelines in the pharmaceutical industry, in seven years from beginning to end, we had a vaccine that worked first time every time. And it was 50 cents a dose. And I went to the launch of this program in Ouagadougou, which is the capital of Burkina Faso. And I can remember giving the very first dose of the vaccine to a young seven-year-old girl. Now, many physicians out there will probably relate to this, but I've never given a vaccine injection in my life. And my fear was that I would screw this up somehow, and the girl would cry or go into hysterics and was very nervous. But I gave her the injection. She had a big smile on her face. And that moment I thought, this is why I became a doctor. Everything I learned in science and medicine and business, everything I learned went into that moment. And I knew that little girl was not going to get meningitis A. What a wonderful feeling. Ladies and gentlemen, this is possible. As Bill Gates mentioned in his commencement address at Harvard some years ago, he said, humanity's greatest advances are not in its scientific advancements, but in how those advancements are applied to address inequity. It took 15 years for hepatitis B vaccines to be made available to people in Africa, 15 years after the product was available to all of us. How many people died in that time unnecessarily? Hepatitis C treatment, Sovaldi, was approved five years ago. Each year that it takes us to get that product out to the people who need it, 400,000 more people will die. Is that acceptable? Of course it's not. The challenge of global health is one of the greatest problems that society faces today. I've seen it for myself. It's not a game. The battle against death and misery is stark and real. But we can do something about it. And to do this, we have to work with a sense of urgency. We have to seek innovation. We have to measure the impact of our work. And we have to always partner to get things done. Thank you very Dr. Reno Ganeen, Asian Pacific Association for the Study of the Liver. Professor Philip Newson, European Association for the Study of the Liver. And Dr. David Rippon, Clinton Health Access Initiative. Well, thank you very much. It is a great honor to be here with the leaders of our sister global hepatology society for the call to action for liver associations to advance progress towards viral hepatitis elimination, a focus on simplified approaches to HCV testing and care. The original concept for this document came by way of an invitation from the Clinton Health Access Initiative this summer. Recognizing that we share the same goals with other international hepatology associations and that we can accomplish much more together, as we have just heard from Dr. Yamada, globally we extended the invitation to ALE, APOSL, and EASL. ASLD acknowledges the contributions to this effort and underscores how much we value our longstanding relationships with these hepatology associations. The joint call to action commits AASLD, ALE, APOSL, and EASL and its members to work together alongside primary care physicians, primary care providers, towards the common goal of testing for and curing hepatitis C globally. This statement will be followed by a similar call to action for elimination of hepatitis B. Each society will develop actionable steps to succeed in the elimination of hepatitis C that are applicable to its regions. The way forward, though, includes four common critical components. Simplifying diagnostic and treatment algorithms towards the goal of a one-stop test and cure for hepatitis C. Integrating hepatitis C treatments with primary care and other disease programs such as TB, HIV, and outreach settings. For example, harm reduction. Decentralizing HCV services from large urban referral hospitals to local level care. And task sharing. HCV care for uncomplicated cases with primary care clinicians, medical officers, advanced practice clinicians, nurses, pharmacists, and trained community healthcare workers where available. I would like to express AASLD's gratitude for CHI, for the initial invitation, and to the leadership of ALE, APOSL, and EASL whose dedication and efforts have contributed to this implementation of this call for action. In closing, I am confident that through our joint efforts and commitment, we will harness the energy and expertise of our respective members and work together to achieve elimination of HCV globally by 2030. There will be a press conference following this signing in room 309 of the convention center starting at 5 p.m.

global health

Tachi Yamada

Clinton Health Access Initiative

innovation in healthcare

disease eradication

HCV testing and care

partnerships in healthcare