Good afternoon and good evening. Welcome to all participants in this special session of Deliver meeting, where we'll have a conversation with the newest Nobel laureates. This session is moderated by me, George Bezeja from Cincinnati Children's Hospital and president of your AASLD, along with Dr. Ray Chung from Massachusetts General Hospital and the president-elect of AASLD, and Dr. Anna Locke from University of Michigan and a past president of AASLD. We are fortunate to be joined today by our esteemed guests, Drs. Harvey Alter, Michael Halton and Charles Rice. They are three outstanding leaders in the field with exceptional accomplishments and the 2020 recipients of the Nobel Prize in Physiology of Medicine. Their groundbreaking research identified the hepatitis C virus, a bloodborne pathogen that causes acute and chronic hepatitis, cirrhosis and liver cancer. In doing so, they laid the foundation for the future development of a cure. So we are living in the future. Let me invite Dr. Locke to introduce Dr. Alter. Well, thank you. It is my honor and my pleasure to introduce my esteemed colleague and friend, Dr. Harvey Alter. Dr. Harvey Alter is a senior scholar at the NIH Clinical Sciences Department of Transfusion Medicine. He's been working at the NIH since 1969, and he's still working there. There, he determined that a transmissible nature of transfusion-related hepatitis is due to a virus which became known as the non-A, non-B hepatitis virus. And cracking a code of Dr. Harvey's well-annotated panel of donor and recipient samples was a prerequisite for claiming discovery of the non-A, non-B hepatitis virus. After many failed attempts, Dr. Halton and his team were the first to successfully crack that code. In 2000, Dr. Harvey Alter was awarded a prestigious Lasker Award in clinical research. And in 2002, he became the first NIH Clinical Sciences scientist to be elected to the National Academy of Sciences, and in that same year also the Institute of Medicine. For his contributions to the discovery of the hepatitis C virus, Dr. Harvey Alter is a co-recipient of the 2020 Nobel Prize in Physiology of Medicine. Thank you. And let me introduce Dr. Michael Halton. He is the Li Ka-Shing Professor and holder of the Canada Excellence in Research Chair in Virology at the University of Alberta. In the late 1980s, he applied recombinant DNA technology and patient antibodies to isolate a single bacteriophage clone that contained a fragment of a virus sequence. Then, piece by piece, he assembled the longer virus genome and identified a new flavivirus, which was named hepatitis C virus. This enabled the development of blood tests to screen for HCV, which dramatically decreased infusion hepatitis throughout the world, and to diagnose HCV in the clinical setting. He has received numerous awards, including the Carl Lindsteiner Memorial Award in 1992, the Lasker Clinical Medical Research Award in 2000, the Robert Koch Medal from Germany, and the Gold Medal from the Canadian Liver Disease Association. For his contributions to the discovery of hepatitis C virus, Dr. Halton is a co-recipient of the 2020 Nobel Prize in Physiology or Medicine. Dr. Chung. I am delighted to introduce Charlie Rice. Dr. Rice is head of the Laboratory for Virology and Infectious Diseases at Rockefeller University. In the 1990s, while at Washington University in St. Louis, he used genetic engineering to study key regions of the hepatitis C virus genome, regulating viral replication, and generated a variant that produced liver pathology and circulating infectious virus in chimpanzees that recapitulated the disease in humans, thereby proving that hepatitis C virus was the causative agent of non-A, non-B hepatitis. Dr. Rice's laboratory was also instrumental in the development of key HCV replication models known as replicons that enabled the development of small molecule antiviral agents even before establishment of a truly infectious tissue culture model. Dr. Rice is a past president of the American Society of Virology, a member of the U.S. National Academy of Sciences, and a recipient of many prizes, including the last year Clinical Medical Research Award. For his contributions to the discovery and ultimate cure of hepatitis C virus, Dr. Rice is a co-recipient of the 2020 Nobel Prize in Physiology or Medicine. Thank you. Well, in a few moments, we'll jump into a panel discussion, starting with a few questions prepared by us, the moderators. We also welcome questions from you, our audience. To submit your questions, please use the chat box, which is located on the right side of your screen. Unlike some other sessions in this meeting that had a question and answer box, we don't have that function for this session. Instead, please send us your questions through the chat box. Let me turn to our distinguished panelists. A question that we all want to ask, and how did it feel? How was it? How confusing? How clear was it when you got a call from Sweden and probably woke you up, either early in the morning or in the middle of the night? Was it a real surprise, or did you have any clue prior to the call? Maybe Dr. Harvey can start sharing how he woke up with that call. George, just before that, I just want to, in the interest of full disclosure, I just want to say that I have never before heard of Michael Houghton or Charlie Rice, and I don't understand why they're on this program with me. I do know, however, they're laying claim to two-thirds of the prize money. The government is claiming the other third, and this seems imminently unfair to me. I've established in our political times, I've established a PAC, standing for Preserve Alters Cash. I'm asking each of you on this Zoom to just make a donation, even small amounts like $10,000, $15,000 will help me and my family to live in the style to which we'd like to become accustomed. But in truth, it's a great honor to share this award with Michael and Charlie, both longtime friends and collaborators. They've taken my early findings and brought them to new clinical relevance and to global impact. There are many others in my story that I am so dependent on collaborators, but particularly to Bob Purcell and Patricia Farsi and Jens Buch, Steve Finestone in the very early work, and to a patient that we've all shared serum from, the initial non-A, non-B case, Mr. Hutchinson, now deceased, but he made tremendous contributions. And lastly, I just want to thank the NIDDK liver service, starting with Jay Hufnagel and Adrian DiBaschelli, all these people famous in AASLD, now Jake Liang and Mark Ghani and a host of fellows, incredible liver fellows who are now the leaders and the young leaders in the AASLD and each of whom who have stuck a needle into the liver of one of my patients. And lastly, to thank AASLD who has morphed me from a hematologist into a hepatologist by osmosis. And I owe very much to this great organization. So, in answer to the question after that long-winded expose, I got called at 4.15 in the morning, as usual, ignored the call, but was very perturbed by it. And then about five minutes later, got a call again, and now getting increasingly angry and certain that it was either a political solicitation or somebody wanted to extend my car warranty. And following the third call, I got up and was about to ball them out when he said, this is Stockholm calling. And that stopped me in my tracks. And then I was just kind of dumbfounded. But eventually told him that was the best alarm clock I'd ever gotten, ever had. That's wonderful. Thank you. And Michael or Charlie, whichever wants to go first. Charlie, go ahead. Well, I can go first, I guess. Yeah, I guess Harvey got the call first at 4.15. My phone rang at about 4.30. And, you know, I was actually my partner is staying at our house in Connecticut, where I am now. And so I was sort of by myself in the apartment in New York City. This is our landline. So I sort of stumbled out of the bedroom to, you know, sort of grab this phone. And I thought, ah, you know, who could be calling at this time of the morning. And so I just sort of turned around and went back into the bedroom. And I hadn't gotten, you know, too far. And the bloody thing started ringing again. And, you know, so I was irked like Harvey, and I was ready to ball out whoever was on that phone. I thought it might have been actually, you know, one of our ultra cold freezers, you know, sort of warming up and we needed to sort of move stuff into the backup freezer. And so I, it was pitch dark. And so I grabbed the phone, I couldn't even see which button to push, I guess I pushed the button that that sort of connected as opposed to disconnected. And yeah, there's a an English voice with a Swedish accent on the other side of the phone saying something about the Nobel Prize for the discovery of HCV. And I thought, oh, this has got to be, you know, a crank phone call. And, and then, you know, he persisted, and then mentioned Mike Houghton and Harvey alternate had, oh, this is, you know, sounding a little bit more, you know, sort of official. And even then, I was skeptical. And he said, Well, if you don't believe me now, you can, you can listen to the formal announcement that's coming up at, you know, 530 your time, which I did. So it came as a total, total surprise. I was done. That's great. And Michael? Well, my story was a little unusual. I was woken up three o'clock in the morning, Pacific time by my colleague at the University of Alberta, Dr. Lorne Tyrell. And like Charlie, I stumbled around trying to find the phone and switch it on. And Lorne said, Well, congratulations, Michael. And I said, Why? He said, Because you've, you're a co recipient of the Nobel Prize. I said, Well, I haven't heard anything from Sweden, Lorne. And he said, Well, go online. It's a bit unusual. And I got the call from Sweden, around six o'clock, Pacific time. So yeah, mine was a little unusual, but obviously very, very nice to get. Well, thank you for sharing that memorable time, early morning. But some of the audience may not know what it looked like to practice medicine in the 80s, a time that was special time in medicine. I was a medical student and resident in the late 80s, and blood was used to save life like we do today. But at that time, we also needed to follow the patient for the potential development of the unfortunate outcome of transfusion hepatitis. That was a reality in the US and throughout the world. Each of you helped solve this problem in different times. So perhaps if I can ask you, who or what inspired you to study the question that ultimately led to the discovery of HCV? And perhaps I can ask Harvey to start that. Yeah, well, it didn't start with the idea that we would discover a new virus. It started with just the realization that a lot of people were getting hepatitis after blood transfusion. So we had established at NIH a prospective study of open heart surgery patients who were multiply transfused, but were very good people to follow because they didn't have underlying immune deficiencies, and usually had nothing else besides their heart problem. And we followed them every one to two weeks for six months, and were kind of astounded to find that 30% were developing hepatitis, most of that asymptomatic. And the only thing we had to judge it was ALT elevations, but they proved to be quite accurate when we went back later. So we looked for elevations of two, and then again, repeated at two and a half times your preliminary normal, and then kept studying these patients. And then we tried to find out why so many people were getting it. And the first thing that became apparent was it was the source of the blood. And that if you receive blood that was paid commercial blood, these donors were not such good donors. And probably sharing needles, we didn't know that at the time. But 1970, we were able to go to an all volunteer donor system and introduce the first test for hepatitis B. We were doing it. It wasn't commercial, then we were doing it by gel diffusion. And but nonetheless, we're able to screen the donors. And the striking finding there that set this whole thing off was that only about 25% of the cases were hepatitis B related, even when better tests came along. And when the hepatitis A tests was discovered by Feinstone, Kapikian and Purcell, who were right here at NIH, we looked at all our non A, non B cases, not one of them was hepatitis A. And then in this brilliant sense of deductive reasoning, we said that these are not A and not B, we will call this non A, non B. Now, we really thought we would find the virus within a short time. As you know, that that did not happen. But we're able to learn a lot about it because we had that great patient, Mr. H, in whom I had gotten a apheresis unit when he was on the upswing of his ALT curve. And that material got titered in the chimpanzee by Bar Purcell. And then we had this infectious inoculum, we had the chimp model. And Steve Feinstone showed that the agent was lipid encapsulated. And then with filtration studies show that it was a small agent. And it was probably going to be a small RNA virus or a totally new virus. And it was Dan Bradley at CDC who first said that it's most like a flavivirus. And to make the rest of the story short, we puddled along until Michael came up with the cloning. And we knew this is one of the big thing we did with the liver services, we showed that this was not just ALT elevations, this was serious liver disease, 20% of our patients got cirrhosis. Several of those died. So we knew we had a potentially fatal disease. We knew we had asymptomatic blood donors that were transmitting a small transmissible agent. And we hung on just before Michael and Steve Feinstone did subtractive cloning. And we're still in the process of doing that when Chiron snuck in with their discovery, which was really amazing. At the time, this was groundbreaking molecular biology, the time when it was just emerging as a discipline. So I leave it to Michael. Michael, what is it that drove you into that quest? Well, I think my story started when I was in high school in England. I had taken exams for college called A levels. I had done chemistry, math and physics. So I was all ready to apply to university, but I wasn't sure if I wanted to be a physicist or something else. So I thought long and hard about it. And then I read a book about Louis Pasteur's career and his personal life. And that made me realize this is what I want to do. I want to do microbiology. And at that time in England, they were showing Sunday morning programs about the elucidation of the structure of DNA by Watson and Crick. And I used to get up early to watch that. And so I think, you know, at late high school, I was committed to doing molecular medicine. Fast forward to leaving England to join a startup biotech company called Chiron, founded by Dr. Vivek Rata and Ed Pentwood. And I had been working on interferon genes in England, human interferon genes, and Dr. Dino Dina, who was the head of virology at that time, said to me, well, Mike, do you think you could use your molecular biology approaches to try to identify the etiology of non-A, non-B? And I was very attracted to that idea and thought we could use molecular biology to identify the virus. And so that's how I got involved. I would like to add that my own contributions to hepatitis C discovery were dependent on two colleagues at Chiron, Dr. Qilin Qiu and Dr. George Kuo. And as Harvey had already pointed out, we had a collaboration with Dr. Bradley at the CDC who supplied us with an incessant supply of chimpanzee materials from 1983 into the 1990s. So without that cast, I would not be talking to you today. Thank you. And Charlie? Well, it depends on how far we go back here. I guess, you know, at least as an undergraduate, I sort of had my focus on developmental biology and was really quite interested in sort of early developmental questions. And then I went to graduate school and I ended up getting placed into a virology lab, Jim and Ellen Strauss's lab that happened to be studying this, what was then a family of viruses called the toga viruses, the togaviridae, and that actually included alpha viruses and flaviviruses. And towards the end of my stint at Caltech, we got interested in the flaviviruses in particular. And we started working with the vaccine strain of yellow fever virus, the 17D vaccine strain that Max Tyler developed in the mid-30s, which he won the Nobel Prize for in 1951. But it's one of the most safe and effective vaccines that have ever been developed and it's been in a half a billion people. So the next step was, you know, sort of having my own lab at Wash U. And then, you know, sort of the science paper, you know, sort of comes out 1989 from Michael and, you know, if you sort of look at, you know, sort of what Dan Bradley had said, this looks like a flavivirus. It looked very much, you know, sort of very similar in terms of genome organization to the yellow fever. And so we, you know, sort of initially, you know, waffled in terms of whether or not to get into this because we figured that, you know, biotech companies like Chiron and pharma companies and others would be, you know, sort of rushing to, you know, sort of do more with the virus and develop vaccines and therapies and what could we, you know, possibly contribute. So it really sort of started off as actually a chance phone call. Steve Finestone, that Harvey has already sort of mentioned for his co-discovery of hepatitis A and also characterization of the non-A, non-B agent, called on the lab line. So I sort of walked out of my office to sort of get this call. I never met Steve, never heard from him before, and he had seen our paper on making an infectious clone system for yellow fever. And he thought, ah, well, maybe we can just sort of park, you know, the envelope proteins of hepatitis C and the yellow fever vaccine background, and then we'll have a vaccine for hepatitis C. And we never got around to doing that, but it did sort of pique my interest. And figuring out more about, you know, sort of where the, you know, where the hepatitis C proteins were, how were they produced, and really that's how we sort of began our work. And then sort of beyond that, I don't want to ramble on too long here, but, you know, one of the things that you need if you're a person studying these RNA viruses is a genetic system in order to study them more thoroughly. And so we attempted to make infectious clones for hepatitis C, and really being limited to testing them in the chimpanzee model because we didn't have a validated cell culture system for hepatitis C despite attempts by many. And that led to, along with Kunitada-Shimitano's lab, sort of the discovery of this missing piece at the three prime end, and then also sort of building, again, using Harvey's, you know, famous Hutchison 877 inoculum, building a consensus sequence based on that, which eventually worked. And that was only the sort of first step, I think, in really getting the sort of molecular virology going. There were many other steps, as you mentioned, the replicon and the complete system that were really the work of many to get those to work. Thank you. Well, thank you so much for sharing your stories. What we would like to hear from each one of you is what would be the message you have for the young investigators and the not-so-young investigators, like Georgie, Ray, and myself, as we start working on our career or as we continue to pursue in our career, what are the secrets to success, and what are the messages that we need to deliver to the young people? Harvey? Well, Anna, I have nothing that I can teach you. You are well beyond that. Every time I've ever won a prize, Anna wins it right after me, so I'm expecting her Nobel soon. I don't say I can follow that. Anyway, for young people, really young people, people just starting out, the things I have emphasized, well, first of all, as I'll talk about this afternoon in our reunion, a great slide I got from Paul Pokras. It was a congratulatory card, but it said, there is no elevator to success. You have to take the stairs, and that, I think, epitomizes research. It's a step-by-step, slow process, not too many eureka moments, a lot of plotting, so you have to be willing to put in the time, put in effort. That's the main thing. For young people, I think you need to find an institution that really fosters research and a mentor. It's very hard to start out on your own with a great project, but get into a good lab, and then you'll find a niche within that lab where you can take off. If you're lucky, you develop, I would advise not to jump around to a lot of different projects. Get into something where you become an expert and where you have a particular knowledge that other people want or a particular patient population or data set or technology that makes you a good collaborator, and then find collaborators because you just cannot do things on your own anymore. It's just too complicated, but collaborations are great because they not only help get the work done, but you learn, and your collaborators become your mentors as well, and that's valuable. Then probably the last thing is to be persistent. I learned that from Dr. Blumberg. The Australia antigen story was a very long, long process, but he just kept at it until eventually showed that this bizarre Australia antigen line was really the surface coating of the hepatitis B virus because that opened up everything. That was the first marker we ever had for any hepatitis virus. He taught me persistence, and I think if you're working on something, follow it out until it's clear it's not going to go anywhere, and keep at it because it's these unknown things, these chance findings that can often have the biggest payoffs. That's my advice to the young. I'd like to be young again. That would be nice, start over again. Well, you're still young at heart and young in the brain. Thank you, Harvey. Mike? Thanks, Anna. I see hepatology as a great field to be in as a young doctor, medical doctor, and as a young scientist because there are many challenges that are very important in the future. As you well know, Anna, we need to make progress on non-alcoholic fatty liver disease. This now is maybe the biggest area in hepatology now that we have some control over hepatitis A, B, and C. There's autoimmune liver diseases that come in different shapes and sizes. We have the challenge of curing hepatitis B patients, of curing them rather than suppressing viremia and disease in them. We have hepatitis C for which we need therapies. Then we need to develop therapeutics to prevent the development of primary hepatocellular carcinoma from cirrhotic livers. I think there are some really big important areas in hepatology that I think would be ideal for young medical doctors and young scientists to study. I think it's a great time to be a young hepatologist. I think the advice I would give is progress depends so much on the technology. You can't emphasize that enough. Our knowledge is growing exponentially, as are our technologies. My advice to a young hepatologist is make sure you keep up to date with all the new technologies. It's very hard to do in your busy lives, but it's absolutely essential. I think spending a morning every week looking at what's happening in the field of molecular biology, immunology and so forth is absolutely key. Keeping your eye on the growing technologies and probably one of the most outstanding examples of that is the RNA vaccine technology that has just come out of nowhere in the last couple of years and is now one of the leading technologies to combat COVID-19 with effective vaccines, which are looking very promising. Thank you, Michael. Charlie? Well, I would just sort of underscore what Harvey and Mike said. I think it's one of the driving forces of success is to identify a problem, be curious. Observations really sort of are important. I think that's obviously key for sort of the contributions that Harvey has made. I agree with Mike on this sort of technology. That is really sort of a driver, but I think at least for me, curiosity and persistence, I mean that was certainly important with hepatitis C, sort of with this sort of mystery virus. I think Mike and his team toiled for six or seven years before they found this sequence and building the sort of molecular virology tools to sort of move forward with drug discovery took a lot of time and effort. So I think persistence really is very important when you believe in what you're doing. You have to be willing to put up with setbacks and come back in the next day and really try the next strategy. So yeah, I think persistence does pay off. Thank you, Charlie. This has just been a wonderful opportunity to hear from you all, and congratulations to each and every one of you. The breathtaking advances that have resulted from your discoveries include, of course, curative regimens that can cure nearly all patients with chronic hepatitis C. So the question I suppose for each of you is what's left to accomplish in hep C is, for instance, elimination achievable? And do we think we could find our way to a broadly effective vaccine while we're at it? Perhaps Harvey, we can start with you. OK, well, I'm going to leave the vaccine part to Michael. As you know, it's been very difficult. The quasi species nature of the virus makes it easy for it to escape the immune response. So I think it's conceivable we will have a vaccine. I think the intriguing question is, do we need a vaccine? My short answer is yes. I think it would be still the best way to get global eradication. But I'd like to think of the possibility that even if a vaccine is not developed, that we could eradicate hepatitis, both B and C, because with B we have a highly, highly effective vaccine. It's a matter of getting it into everybody. And there's been huge global progress in vaccination for B. And that would have to be expanded. And that could perhaps diminish the chance of catching B from somebody else and ultimately rid us of that agent. With C, we now have great testing and we have curative therapies. And the impediment is getting everybody tested and getting those tested positive to get the treatments. So it would take a massive global effort. But if there was the political will and the philanthropic will and the moral courage, we could conceivably over decades get virtually everybody treated, say at least 90% of populations and get those treated, those identified to be treated with drugs that would have to be sufficiently inexpensive that everybody could get them. But I think it could happen. If a vaccine comes along, still better. But I think it could happen. But it would probably take several decades. Right. Thanks, Ray. Well, I think it would be nice if these very potent antivirals to hepatitis C were cheaper and became so cheap that all countries around the world could use them in a reasonably economic way. But I think I think the reality of the past tells us that's probably unlikely. And, you know, a colleague at the University of Alberta, Dr. Stephen Shafran, he has pointed out to me that if you take common diseases, venereal diseases like gonorrhea and syphilis, and if you look at diseases like chlamydia, we have very good drugs to treat those diseases and they're extremely cheap. But we still have outbreaks of those infectious diseases. So I think we're going to need a vaccine, I think, to curb a pandemic and an epidemic like hep C. WHO estimate there's two to three million infections every year of HCV around the world. They estimate 400,000 people around the world are dying from hepatitis C complications. And I think to really impact a disease like that, a global epidemic, you are going to need a vaccine. So is it feasible? I do think it's absolutely feasible. You know, we the field feels that correlates of immunity are based on neutralizing antibodies and cellular immune responses. We know how to elicit both of those using a variety of different technologies. And in terms of the ability to neutralize infectivity of different strains of HCV, the work that we've done has shown that in addition to highly variable neutralizing epitopes, which, as Harvey said, can escape the antibody response, there are several numerous highly conserved neutralizing epitopes. And you can design a vaccine to actually elicit antibodies to those highly conserved epitopes to get very good, or I should say, very broad neutralization of most of the strains around the world. So I'm sure a hep C vaccine will appear over the next 10 years. I see it being combined with hepatitis B vaccine, which will be basically a vaccine against blood borne hepatitis. And I think it will play an important role on curbing the epidemic and potentially eliminating it. Elimination is a really tough task, but I think it's even possible to expect that over the next decades. Thanks, Mike. And Charlie? Well, as usual, these two have said everything, but I guess one thing that I was sort of a little bit naive about sort of being a molecular virology type and not thinking about some of the challenges that we face in public health was sort of with the approval of these miraculous combination therapies that can cure most people of the virus, that you know, it would be a relatively straightforward, you know, fairly rapid implementation of those advances. And I mean, I have to say, I've been, you know, sort of dismayed as to, you know, sort of how slow this process is. And, you know, I sort of agree that, you know, it's you got to find the people that are infected and you've got to get them into treatment and get the job done. And it seems like there's just a lot of variation in terms of how effective we are at doing that in different communities, different countries, different segments of the population. So again, cost has something to do with it. And, you know, there is this huge gap between what it actually costs to manufacture these drugs versus, you know, the sort of market value, which, you know, varies by country. But certainly that is something that I would like to see more of a, you know, sort of a global view of, you know, sort of hepatitis C sort of control and, you know, really a plan to, you know, overcome some of these barriers, because I think that would definitely get the burden down. I also am enthusiastic about the possibilities of developing a vaccine for hepatitis C, you know, particularly when, you know, Mike and his team and others are working on this. I guess one of the problems that we face is that, you know, we sort of don't know exactly what's going to work until we get into people and find out. And I think the trials for, you know, testing the efficacy of a hepatitis C vaccine are potentially quite challenging. So it doesn't make it easy to test a lot of different approaches or platforms. I am kind of hopeful that this unprecedented effort to develop a COVID-19 vaccine with so many different platforms, we're going to have, you know, human data on immunogenicity against spike, and in some cases, other parts of the SARS-CoV-2 genome, you know, how long it lasts and so on. And I think that could maybe inform our thinking about, you know, sort of what platforms might be worth, you know, trying out for hepatitis C. So I'm actually hoping that current events actually sort of feed back into this challenge. Can I add a word? Sure, Harvey. You know, I agree that the vaccine is the holy grail, and maybe these messenger RNA vaccines might be a new pathway to do it. But it also, as I was listening to Charlie and Michael, I can conceive, let's say the price of drugs really came down to affordable for each country. I can conceive of having people come in and have a rapid test, while they're still at the testing facility, be given three months or eight weeks of DAAs to take home with them. The treatments are so good and so uncomplicated that you don't need a doctor, you don't even need a nurse, you can take them yourself, come back in three months or eight weeks and be retested. So it's because the drugs are so remarkable, I think this is potentially achievable. If there was a will to do it, and it would take, you know, take a lot of coordination, but I think it could be done. Well, I'd like to thank all three of you, and many in the audience might not recognize, or hopefully you would recognize by now, that none of them is really truly a hepatologist, although Harvey has been converted. And yet, all three of you have been very closely associated with ASLD, and we certainly appreciate you sharing an hour with us. So we'd like to hear from you how your association with ASLD and with hepatologists have helped in your career, as well as in your work on hepatitis C. And we have, all three of you have been long-term members, as well as being distinguished awardees as well, long history with us. Harvey? Well, you know, it's so unlikely for me to be at a liver meeting. And when I was trained as an internist hematologist, and kind of morphed into liver disease because of what we found by chance. But being in ASLD has been just remarkable, because it's given me so many new colleagues, and so many bright people, and so many great meetings. It's just been, I have slowly stopped going to hematology meetings, and focused only on hepatology. I've been part of the journal. I've gotten some very nice awards from the liver group. And I think maybe what I appreciated most of getting an award was to be a hematologist getting an award from a hepatology group. But it is a great organization. It is, the teaching is astounding. You see what goes on at the meeting, even this virtual meeting. It is, I think, the best teaching group ever, and fosters young people. Just very proud to be associated with it. And my next life, I'll come back as a hepatologist, credentialed. Well, thank you, Harvey. Mike? Thanks, Anna. Well, ASLD, to me, it's clearly a globally leading forum for medicine and the science of the liver. And it's just been an outstanding organization, not only to keep abreast of what's new and the latest information, but also as a discussion forum with peers. And, you know, I'm a molecular biologist, molecular virologist, but I've learned so much from talking to hepatologists. And that is just so important that the scientists work with the hepatologists. And of course, a lot of hepatologists are scientists. But I think that interface between the scientists and the clinicians is absolutely vital. And ASLD has been truly outstanding at doing that. Thank you, Michael. Charlie? Yeah, well, sort of coming into this, I don't think I really sort of knew all that much about the liver. And I think that the, you know, as Mike just said, you know, this sort of interface between, you know, more basic scientists and the clinicians to me was, you know, sort of really, really very important, you know, sort of my sort of clinical partner, you know, over the last 20 years, Ira Jacobson, you know, sort of just getting a clinician's perspective of, you know, sort of what they were dealing with, you know, sort of in the interferon era, you know, sort of through all of this, you know, sort of what are the, what are the challenges and problems that come up. And so I think, you know, really having exposure to that community, you know, through ASLD and other venues was really an important education. And also for me, a very important sort of motivational push, because, you know, again, there were long periods of times when, you know, things were not working the way that we hoped they would. And I think just sort of having an increased awareness of the, you know, the severity of this disease and the problem that it can cause, as well as some, you know, real life, you know, education was very important. And I think that that was kind of a special phase of my career, because, you know, I've been really sort of studying more, you know, fundamental, you know, virus replication stuff, and the sort of involvement with hepatitis C really sort of added, I think, you know, another component to my understanding of medical research, and it was great. Thank you very much, and we're getting close to the muting function, very important. And we have a couple of questions from the audience, and you already answered some of them. One is, what do you think your personal legacy will be going forward? A brief reply, Harvey, would you want to start? Well, I like to think of Woody Allen, who said that some people reach immortality through their accomplishments, through their great works. I want to receive, achieve immortality by not dying. So that's my future perspective. Now, I hope my legacy will be that I played a role in improving the safety of the blood supply to virtual zero risk for hepatitis viruses, that I laid the groundwork with my many collaborators, particularly Bob Purcell, for the work that Michael and Charlie have carried on, and the companies, too. We have to give a lot of credit to the commercial companies. They really took up the ball. They charge a lot, but they did a lot of work. So I guess that's my legacy, my hopeful legacy. And Michael? Well, I would hope my legacy would be to encourage young medical doctors and young scientists to really spend time and effort on difficult areas of unmet medical need. You know, we have so much information today, but I'd still like to see more of that information applied to major diseases. You know, we know so little about diseases like Alzheimer's, like inflammatory bowel disease, multiple sclerosis. We have so many challenges in hepatology, as I mentioned earlier. So I would be very pleased if my legacy was to encourage scientists and clinicians to really focus on important diseases that affect us. And that sounds perhaps simple, but in my experience, it's not, because I think many people, you know, for example, the typical researcher has to work on things in the lab that students can work on in postdocs, and that means there has to be data produced and papers produced to encourage and enable the careers of those young people. And I'd like to see more time spent by those people. Obviously, they can't spend 100% of their time, but some of their time, I'd like to see it focused on very difficult diseases where there's unmet medical need. So I would be very pleased if that was my legacy. And Charlie, thank you very much. Well, I don't know if I have a legacy, but, you know, I think, you know, one of the things that this field has really sort of epitomized has been, you know, a lot of people, you know, working towards a common goal. And, you know, part of this has to do with, you know, sort of the belief that what you're doing is important and it can have impact. I guess another part of it, though, really does have to do with what importance unexpected things can have. You know, I think there is a lot of chance involved, you know, sort of in my career, you know, a series of random walks and sort of encouraged by, you know, colleagues like Mike to, you know, continue working on hepatitis C. And there is a lot of serendipity. You got to keep your eyes open. And I think that, you know, in addition to really being focused on sort of key diseases, as a society, we also have to encourage people to just have a passion for, you know, biological discovery because you just never know, you know, sort of when one of these findings and we're seeing all kinds of examples of that with, you know, CRISPR and other things, you know, what kind of impact that they can have. So I think we need, you know, sort of a multi-pronged approach, you know, sort of target some targeted work and then also some exploratory curiosity driven sort of research. But, you know, in terms of a specific legacy, I don't know. I think in my case, you know, it's kind of difficult for me to figure out how I ended up where I am. Me too. Yeah. It is so successfully and in a transformative fashion. Thank you very much. Well, thank you all three of you for sharing your journey with us. Many of us know that Harvey's accomplishment and legacy is not just in research, but as a poet. And we see a lot of requests coming from the audience that we need to have the poems from Harvey. So Harvey. Well, thank you, Anna. I haven't written a new poem as yet. I hope to maybe I will have a Nobel poem, but I went back to a few oldies. And the one was that I wrote after Michael Houghton and his group cloned my virus. And I, the pangs of not having discovered, I wrote my personal account of this feeling, which I called, there's no sense Chiron over spilt milk. And it was a long poem, but I just read a couple of paragraphs. It was in Dr. Houghton's antiviral prescription to make clones by reverse transcription. Well, Chiron's finance department had another conniption. But Michael said this was not a rehearsal. The RNA had to be changed by transcription reversal. The RNA had to be changed by transcription reversal. Like Jack the Ripper at his most vindictive, he chopped up the codon with an enzyme restrictive. Could these tiny little pieces be of an antigen predictive? Corporate executives prayed that it would on their knees benedictive, showing in science and religion are not contradictive. And I ended that poem, there was more, but I ended it with, as for Chiron, I hold no resentment. In the test support of my claims, I'll find my contentment. For coming second, I make no apologies. I can always turn to the bench and do blood bank serologies. For me, there'll be no Nobel prize, but there's always another virus on the horizon. So I guess it happened. That is terrific. Thank you. Well, you actually did end up getting a Nobel. Yeah, well, that was not expected. I think we should now designate Harvey, not only Nobel laureate, but poet laureate as well. Thank you. Agree. Well, on behalf of Drs. Bazeha and Locke and the entire membership of ASLD, I'd like to once again extend warmest congratulations to our laureates and thank them for their extraordinary generosity in spending this hour with us. And thank you to the audience for joining our conversation with Drs. Alter, Houghton, and Rice. We hope that it was as memorable an experience for you as it was for us as moderators. And as we conclude, we'd like to remind you that if you missed some of this session, all of the content will be available on TLMDX on demand until February 21st of 2021. So I'd like to close by proposing a virtual toast to our newly minted laureates. For all of you attending, I invite you to raise a glass with your nearest beverage at hand. And here's to our newest Nobel laureates who inspired us all with their curiosity, creativity, persistence, and passion. By discovering and explicating the mysteries of hepatitis C virus, they have definitively shown us all that science truly delivers cures. Cheers. Cheers. Stay healthy and do well. Thank you all again.

ASLD meeting

Dr. Alter

Dr. Houghton

Dr. Rice

Nobel Prize

hepatitis C virus

transfusion-related hepatitis

recombinant DNA technology

genetic engineering

vaccine development