>> Okay, good morning, everyone. We have a busy program today so we're going to get started. Thank you for joining. Today is the Library of Congress webinar on the 1918 Flu Pandemic and its impacts and lessons for COVID-19. Throughout today's session we invite you to submit questions for our presenters using the Q&A panel on your screen. We might get to some of these throughout the course of the presentation, but we'll address the bulk of them in the dedicated question and answer segment at the very end of the event. Please note that today's webinar will be recorded and made available online. And we'll share more information about how you can access this presentation and its resources before we wrap up today. So with that, to get us started, please welcome Chief Medical Officer at the LOC, Dr. Sandra Charles. >> Sandra M. Charles: Good morning. And welcome. It is our pleasure, both myself, from the Health Services division and Dr. Tomoko Steen of the Library of Science, Technology, and Business division, to welcome you to this second webinar in our series on COVID-19. There will be for you a most enlightening and intriguing presentation from two preeminent scientists. They will guide us through understanding the [inaudible] responsible for the [inaudible] [inaudible], showing how [inaudible] influenza has [inaudible] most pandemics over the last hundred years and how the [inaudible] [inaudible] virus is making its mark and outlining the concerns, obstacles, and outcomes of the 1918 pandemic, we will note the similarities in public and governmental responses, and how being mindful of them could inform our responses today. [Inaudible] and purported [inaudible] show [inaudible], we learn from history that men never learn from history. I think our scientists today will help us to reassure that that doesn't continue. [Inaudible] being urged to wear masks and social distance are very eerily [inaudible] 1918, with the huge anti-mask rally in Philadelphia almost 102 years-- well actually, 103 years to the day, January 25th, where they were railing against the unhealthy mask ordinance. And then there was the Philadelphia war of [inaudible] parade, which defined all semblance of social distancing. These and other events cost many lives. Our speakers today will make an indelible mark on memories. And I think we'll prove that we can learn from our history. So without further ado, I will turn the program over to my esteemed colleague and co-sponsor, Dr. Tomoko Steen, to introduce our speakers. Thank you. >> Tomoko Y. Steen: Yeah. Thank you. It's my pleasure to introduce our wonderful speakers at this time, two speakers. And I'm going to introduce both of them first and then our speakers are going to continue to speak, one after another. So first speaker is Dr. Jeffrey Taubenberger. He is the Chief of Viral Pathogenesis and Evolution Section and the Deputy, also, and Deputy Chief of the Laboratory of Infectious Diseases at NIAID, which is the National Institute of Allergy and Infectious Diseases at the National Institute of Health. And he and his team members completed the sequencing of the 1918 pandemic viral genome, which is an interesting story and [inaudible]. And also NIAID Director is, most of you know, Dr. Fauci. So second speaker is Professor Marc Lipsitch. He's a Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the TH Chan School of Public Health at Harvard University. And he provided a key estimate of the transmissibility of the 1918 pandemic influenza, which helped to support the use of pharmaceutical and non-pharmaceutical interventions to control the spread of future pandemics. In 2005, he also lectured at the Library on the coronavirus, the last one, SARS, and you can watch the video also at this URL. Without further ado, please join me in welcoming wonderful speakers. First, Professor Taubenberger. >> Dr. Jeffrey Taubenberger: Thank you very much. Thank you, Dr. Charles and Steen for the invitation to participate in this extremely interesting and important webinar, comparing the two greatest pandemics separated by a century. The 1918 flu and the current one that we are all living through. So, I'm going to start-- this is a topic very near and dear to my heart, I could speak for 15 hours, but luckily, I've been limited to 15 minutes. So, we'll have to make some very fast points. Next slide, please. So, I'm going to start off by saying that pandemics have happened in the past. They are currently happening now and will undoubtedly happen again in the future. We have spent all of history responding to and reacting to pandemics. And we're always chasing behind what viruses are doing. And we need to do a better job in the future. So we need to learn from past pandemics, we need to learn from our experiences with COVID-19 to do a better job at predicting pandemics. We need better surveillance at the human-animal interface, we need a significantly better understanding of the basic biology of the viruses that can become pandemic, understanding how they switch hosts, why they cause disease, what their immune responses are, using that information to help us make better diagnostic and prognostic tools, to help us make better treatments and therapeutics. And of course to help us make better vaccines, perhaps vaccines that can be made in advance of pandemics and burgeoning so that rather than chasing after a pandemic and always being at least a year behind in the production of a vaccine, we might have some vaccines that at least would be beneficial at the very beginning of an outbreak. Next. So, just to say that influenza pandemics are something that have been well-known and studied for a very long time. And going back to the medical literature, it looks like there have been at least about 14 or perhaps 15 pandemics in the last 500 years that have been thought to be influenza. They probably are mostly influenza, but I guess given the lessons of the coronaviruses that we'll be hearing about in a minute, that, you know, it's possible that some of these quote-on-quote "influenza" pandemics in the past were indeed coronavirus pandemics. We can't be ultimately certain unless we can find genetic evidence of them. Next slide. So, I'm going to focus my talk on the virology and pathophysiology of viruses that can cause pandemics. Starting with the influenza viruses, which was the basis of the 1918 influenza. Influenza A viruses are an incredibly diverse group of viruses that are present in hundreds of species of animals, both birds and mammals. Their natural reservoir are mostly wild water fowl like ducks, shore birds, geese, seagulls, et cetera. But they have the ability to adapt to and infect other species, including domestic poultry, like chickens and turkeys, and domestic and wild mammals, dogs, pigs, horses, and of course are important for humans. So this is one of the reasons that influenza's such a difficult to control disease and a very important aspect of its biology is its ability to move around between species and adapt to different hosts. Next. Influenza viruses, especially the [inaudible] avian viruses that are the reservoir for all human and future pandemic, past and future, pandemic viruses, are incredibly diverse, both genetically and antigentically. In the middle, you see a phylogenetic tree that is a family tree of the different subtypes of the hemagglutinin gene, one of the major genes of the influenza virus. And I just compared and contrasted this with a sketch from Darwin's notebook on the left where he says I think and is thinking about diversification. Influenza viruses, like coronaviruses, while they're not technically living, they do evolve. They are amazing examples of Darwinian selection, both positive and negative selection. And influenza viruses take advantage of their rapid mutation of these viruses to do things like escape from preexisting immunity, escape from antiviral drug treatment, and specifically to adapt to new hosts. It is this rapid mutation rate that makes them such a threat for not only human influenza on a yearly annual basis but also the movement of animal viruses into humans to cause pandemics. Next. We're going to be spending most of the time in the next few minutes talking about the 1918 influenza and its lessons for COVID-19. And I will start with one important lesson, which is that the 1918 virus caused probably the most severe pandemic on record. Now we're in the most severe pandemic since 1918. But the important thing to note from this slide is that the 1918 virus is really a founder virus. As you'll see, the 1918 virus probably is derived from a bird flu, an avian influenza various, that adapted to humans sometime before 1918, caused the pandemic that killed 50 to 100 million people, but after the pandemic, stayed around in human circulation as its descendants as seasonal influenza, and subsequent influenza pandemic. So that every single human influenza infection in the last 100 years has all been derived in one way or another genetically from this single founder virus. So we're really still in the 1918 pandemic era in terms of influenza. And that not only tens of millions of people died during the pandemic, but tens of millions of people have died in the last century because of seasonal and subsequent pandemic outbreaks of influenza all due to this single host switch event. Next. Coronaviruses have been giving us this similar warning. We're really on strike three in terms of known coronavirus pandemics in the last 15 years. There are a number of coronaviruses that have gotten into humans. Of course, the SARS-CoV-2 at the bottom that we know much about, but there has been the near pandemics of MERS in 2012 and of SARS-1 in 2003. And there are a number of other human coronaviruses that also have ultimately in the past come from animals and may have resulted in pandemics as host switch events at some point in the past. That circulate as sort of cold virus, the human cold viruses. But the coronaviruses have not had the kind of basic research that influenza viruses have had, even though they have very many similar features, an RNA genome that can rapidly mutate being [inaudible] many species of birds and mammals for their ability to host switch and adapt is telling us that these-- both forms of respiratory viruses and humans are key pandemic forming viruses and threats, not only for the future and the present, but the future. Next. So let's talk about the 1918 flu for a moment. Next. As I said, the estimates of mortality are somewhere in the range of over 50 million people. The United States influenza pneumonia deaths in 1918 during the pandemic were about 675,000. In today's population, that would be somewhat north of over 2 million people comparatively. Philadelphia as was mentioned by Dr. Charles, but they had very severe outbreaks, about 16,000 people died, 11,000 just in the month of October 1918. In the US military during World War I, about 100,000 US troops died of all causes, but 40% of those deaths were due to influenza infections, these were healthy 18 to 25 year old men, almost 30,000 US soldiers died in the month of October, 1918. Next. The pandemic spread mostly in the fall of 1918, in the northern hemisphere, but also at the same time, which was the spring in the southern hemisphere, there was some evidence of the pandemic circulation prior to that. But there was no viral isolates so, and very little diagnostics, so it was difficult to find the earliest spread of the 1918 flu, but it does come in so-called waves. But its major wave was in the fall, October through November 1918 in most parts of the world. Some places saw other reoccurrences in early 1919, and then some smaller reoccurrences in the next year or two thereafter before settling into a seasonal flu circulation by around 1921/22. Next. Life expectancy in the United States dropped about a dozen years in 1918 because of the mortality impact of the 1918 flu, especially its impact on young adults. Next. So, back to the things that we started with of what we need to do to learn lessons in history and to do better. So one thing we need to do is understand more about the basic biology, eco-biology, of these pandemic potential viruses, like influenza viruses, like coronaviruses. We need to understand how host switch events occur, what kind of mutations allow adaptations to new hosts, to humans. Why do some viruses cause more severe disease than others? What are their inflammatory and immune responses? Next. So, as was said, my lab started the effort to sequence the genome of the 1918 virus about 25 years ago. The 1918 virus wasn't isolated in 1918, and so therefore by the time influenza A viruses were discovered in the 1930s, it was impossible to go back and find the original isolate of 1918. So there was no way to really directly study the molecular or genetic and viral features of this pandemic. So in sort of a painful process using technology available at the time, in the 90s, it was possible to isolate tiny fragments of RNA of the virus and ultimately sequence and rebuild the virus over about a 10 year period from [inaudible] embedded autopsy tissues from both the US and Europe, as well as from frozen lung samples from a victim of the 1918 flu buried in the permafrost in northern Alaska exhumed with my colleague Johan Hultin in 1997. Next. So, unfortunately, I don't have time during this short talk to talk about the 20 years of work to understand why the 1918 flu behaved the way it did, how host adaptation occurred, why it was so severe, but I'm going to just highlight some recent studies in which we're comparing the fatal pathology of people who died of influenza in 1918 compared to the fatal pathology of people who are dying currently from the COVID-19 SARS-CoV-2 infection. If you, unfortunately we don't have time to show you exposed photomicrographs, but the pictures show that there was a permanent neutrophilic infiltrate and that there was severe damage to the very delicate air space lining of the lung in both cases. They look very similar in the earliest stages. One interesting feature is that both the 1918 and SARS-CoV-2 infection show widespread blood clotting in the lung. But this is not prominent in other influenza pandemics. And SARS-CoV-2 thrombosis or blood clotting is not limited to the lung as in 1918 flu, but systemically. But we don't know the answer to that yet. Secondary bacterial pneumonias were critically important as a factor in fatality in 1918. So you have viral infections followed by a secondary bacterial infection. But even though the pathology at the beginning seems very similar, SARS-CoV-2 cases do not seem to have a high incidence of secondary bacterial pneumonias. This is an important question, and we also don't know the answer to that. Using the modern kind of sort of systems biology approach that we're using to study SARS-CoV-2 infections, we can now go back and use archival material from 1918 to do further comparing and contrasting of these pandemic pathologies. Next. So, one thing we need is a better prognostics screening. Next. So, one of the problems with both influenza and coronavirus is that when you are initially infected, it's very difficult to know whether you will have a benign course, as most people do, or have a more severe course leading to hospitalization or even possible fatal outcome. So one of the things we've been doing in my lab in the last few years in terms of influenza is trying to look at prognostic tools. So here is an example in which you can take people who were infected with influenza at an early stage, one or two days after their infection, before they are really symptomatic, and take a blood sample. Next. And use genetic markers from the blood sample to see if we can make predictions about how their course of disease will go. Next. And what this slide shows is that we can make predictions prior to the onset of symptoms if someone infected with influenza as to who will shed virus along [inaudible]. This of course has important public health implications in terms of isolating and preventing spread of illness. Next. But perhaps even more importantly, we can make very good predictions as to who will have the most severe course of illness prior to the onset of illness. This would help stratify people who are at higher risk who would need more intensive therapy or at least intensive follow-up prior to landing in the hospital without any prior notice. So we hope that this, these kinds of tools can continue to be developed and could be developed for coronavirus screening as well. Next. Of course we'll need better drugs and therapeutics and that's something we don't have time to talk about. And I will end in the last minute or so of my talk by talking about the need to develop in a sense preemptive vaccine. So-called universal vaccines, or broadly protective vaccines. Influenza viruses mutate very rapidly, and as you are all aware, the seasonal viruses mutate so rapidly that the vaccine has to be reformulated every single year to keep up with the active mutation of the virus. So that you don't develop long-term immunity from the current vaccine strategy. And when new pandemics appear, we have no idea what subtype or properties it will have. And so we can't have vaccines prepared in advance. So it's been a long-term goal to have vaccines that would provide such broad protection that you wouldn't necessarily need to get vaccinated every year for seasonal flu, and if a pandemic emerged, a vaccine that could provide protection in advance from any possible strain of flu. Next. So-- sorry, thank you. A number of groups have been working on this. My lab has been working potentially on a broadly protective or so-called universal influenza vaccine for the last few years and it's ready to start its clinical evaluation this year. It was supposed to start in 2020 but has been delayed because of COVID-19 pandemic. And without going into the details because of the time limitation, we have a vaccine that in pre-clinical models looks extremely good. We can offer really significant protection, at least 100,000 full reduction in the amount of virus in the lungs of animals, elimination of pneumonia, there's no inflammatory response. Including a challenge with viruses that are not contained in the vaccine so that you have complete cross protection of very divergent strains of influenza. So, this looks turmoil promising in our laboratory based studies, and we're hoping that this will continue to look promising as we move into clinical evaluation and efficacy of these vaccine candidates. Next. Given the three strikes that the SARS coronavirus family have given us already and evidence that past coronaviruses and [inaudible] from animals, you know, would it be possible to take some of those lessons into broadly protective coronavirus vaccines? And so, my lab is also just beginning to work on this. As of course other labs are. To see if we can take some of the lessons that we learned from the 1918 flu and influenza pandemic preparedness and prevention to make broadly protective vaccines perhaps that would protect against other coronaviruses that are pandemic threats in the future. So with that, I will stop and turn it over to Dr. Marc. Thank you very much. >> Professor Marc Lipsitch: Thank you. Thank you to Doctors Charles and Steen for the invitation. I've known Tomoko for over half my life, I just realized with a shudder. It's a pleasure to be back at the Library of Congress, they do excellent work to share science with the public. I'm going to say many overlapping things with what Jeff said, but also take a slightly different approach. Next slide, please. So I've tried to distill things down to about five lessons from 1918. And I think, importantly, from past near pandemics, can you go back to that slide for a second? Right. Okay. So, I'll be talking not only about 1918 but also about how we've accumulated lessons through history. And I think proven George Bernard Shaw somewhat wrong and somewhat right. Next slide, please. So I think one thing that is very clear is the value of early and sustained action. This is a page from the Philadelphia Inquirer in the spring of this year, but it's a figure adapted from a study performed with colleagues over a decade ago, looking at the 1918 flu and comparing the experiences in Philadelphia to that in St. Louis, shown in the brown graph. And what you see is a very early and very high peak in Philadelphia, which took very little action. And you can see the parade that Dr. Charles mentioned right at the beginning of the pandemic wave in Philadelphia. And by contrast, St. Louis had a bit more warning because the pandemic was moving roughly from the coasts, especially the East Coast, inward to the country. And so St. Louis took earlier action relative to their pandemic wave and had a much better outcome, as you can see. Next slide, please. So that lesson was very much on people's minds not only in the spring of this year, but before, as we've been trying to prepare for a flu pandemic, because we weren't really as focused on coronavirus pandemics. This is guidance that was also accordingly authored by Dr. Richard Hatchett, who was the first author of that paper I just showed. And all of us have heard flatten the curve, we heard it a lot in the spring. And that really looked back to guidance that had been developed based on the 1918 experience. And other considerations about the notion that reducing transmission as it's gearing up in a naive population, at the beginning of a pandemic, not only reduces the total amount, but also delays infections and reduces the peak, all desirable things. Next slide. And in that early study of 1918, what we did was to try to quantify the value of early and combined measures to control the pandemic, so the first graph shows various comparisons, they also show sort of the same thing of places that took many measures early on to close their schools, to close the churches, close their theatres, to remove public gatherings. This all sounds very familiar. These were measures taken in 1918. And those that did so early shown in black had better outcomes in terms of peak mortality and total mortality than those cities in the United States that took later action. I also-- sorry, go back, please. I also ran across this quotation from Stephen Morse in the commentary that was published about that paper, again, in 2007, and thought this was eerily reminiscent of what we're thinking now. "Finally, there are differences-- " and this is thinking about the contrast with the present, "-- in the make-up of the household with increasing numbers being headed by single parents or having both parents working. Closing schools would be far more burdensome for many in our current setting than in 1918." So that turned out to be true. Next slide, please. These lessons were very directly learned. This strategy that was published also in 2007, if I remember correctly, led by Dr. Richard Hatchett and Carter Mecher, two of the colleagues with whom we did the historical studies, really laid out a set of measures. Very much like those that we've taken in the early part of the pandemic and continuing to the present in 2020. And that was all with a very explicit look back to history and what had worked in a setting where vaccines were not yet available, that is 1918. Next slide, please. And the second lesson, which is really closely related to the first, is this notion of Swiss cheese. Many of you may have seen this diagram that was in the New York Times and has been circulating in various places. It's really the notion that at the beginning of a pandemic, we take a lot of measures, all of them imperfect, but which together can make a difference to try to slow down transmission. With the goal, as I mentioned earlier, of low peak, delay, and reduced demand on the healthcare system, as well as reduced total impact on people. And I think a lot of the debate, as we heard in the introductory remarks about whether masks are very effective or not very effective, whether hand hygiene matters, and all the different measures, I think the point is that each of these play some role and we have time as the pandemic goes on to try to figure out how much will, but the point is that we need to put in many measures because each of them is imperfect and then try to understand which of them are most effective and which of them are least costly as we refine our response. Next slide, please. Despite what to me seem like very clear lessons from 1918 and some other past pandemics, there was a lot of controversy in the spring in the United States and elsewhere about what should be done. And this was a dueling, some dueling articles by John Ioannidis from Stanford and me arguing in the first case that we needed more data before we could take decisions about how to control the pandemic and my response that we knew enough that we essentially had a train coming at us and we should jump off the tracks and then figure out how big the train is and whether it would have run us over. It was not the time to start doing research first, it was time to act first and do research at the same time. Next slide, please. I want to mention this parade. Because I found that a very-- that-- occupied a lot of my time and thinking in the very early stages. As Dr. Charles alluded to, there has been a notion that the parade in Philadelphia at the very beginning of the pandemic wave there was directly responsible for causing the takeoff. And I would rather say that there was a temporal correspondence, the parade preceded the takeoff, the parade probably reflected an attitude of not social distancing that went long beyond the parade itself. Next slide, please. And I was actually quite actively trying to convince leaders in Boston and other cities to cancel the Saint Patrick's Day parade that was happening in March of this year. But I was cautious to note the uncertainty about whether the parade had actually been the cause. And this was a little bit of Twitter discussion where I cite the idea that it might have been the cause. I say later on that we don't know what the cause was but that it at least is not a good idea to have a parade in the midst of a pandemic. And that on precautionary grounds, the Saint Patrick's Parade should be canceled. I must say that I was happy that I had been cautious in that way when the protests of the summer broke out, the Black Lives Matter protests. And many people were saying ah, but you said we should cancel the Saint Patrick's Parade because it caused the pandemic in Philadelphia. And those of us who were careful about what we said were able to say no, we didn't say that parades cause pandemics. We said that out of precaution they should be avoided and notably the Black Lives Matter protests were to a very large degree done with social distancing and masking in a way that was certainly not true in Philadelphia. Next slide, please. Sorry, that was the same quote that I used by mistake. The third lesson I think is something that the lesson of the value of basic science. And this is very much concordant with what Jeff said. This is a timeline showing over the 20th century, mostly, when we figured out what was the cause of particular diseases and when we got vaccines. And you see the time scale is mostly decades. In fact, it's all by at least a decade. Except for hepatitis B, which is, sorry, and measles, which are, you know, about a decade. And of course with SARS-CoV-2 we knew what caused it within a month or so of its outbreak being reported. And we had vaccine licensed within a year. Next slide. And part of that is due to [inaudible] scientific work. In 1918, as Jeff alluded to, we did not have a vaccine. And in fact, there was an ongoing debate, which this slide summarizes, about what the cause of influenza was. There was a large school of thought, very intelligent thoughtful people decided it was caused by bacterium, known as Pfeiffer's bacillus at the time and known now as Haemophilus influenzae, in tribute to its mischaracterization as the cause of the flu. And it wasn't until 1934 or so that there was really definitive evidence that there was a viral cause of flu. There was some evidence as early as 1918, but it was controversial. And so vaccines were developed using this bacterium that didn't prevent the-- prevent influenza and it really is a tribute to basic science that we now know very quickly what the cause of particular diseases is. Next slide. And this is a report of the-- from the 1918 newspapers of the use of an anti-grip vaccine, as they called it then, and I was the city bacteriologist who was doing it because of course, they didn't know about viruses at the time. Next slide. So this time, we've had safe and effective vaccines quickly. And I was looking for an image on the internet, and I found this one from Vanderbilt in April where they were predicting that we would have a candidate, or we had had a candidate vaccine, and they were predicting that phase three trial would begin in late 2020. And maybe have licensure in 2021. Their most optimistic scenario. We haven't had licensure, but we've had authorization even faster than their most optimistic scenario. And in particular, it was 42 days or so from the sequence being-- of the virus to having a candidate vaccine. A tribute to technological and scientific progress. Next slide, please. And this is a really nice National Geographic article describing the work at National Institute of Allergy and Infectious Diseases. Which was one of the key laboratories that was pushing forward this technology. Next slide. So, on another positive note, I think this work at NIH and also at many other places around the world really was a case of not just learning from history but learning the right lessons from history from, in particular, the SARS, MERS, and Ebola outbreaks. Next slide. So those are some near pandemics, or not quite pandemics. And because they were not quite pandemics, they could have been seen as evidence that everything was fine. At least for rich countries in the west. But that was not the case. Instead, this really important article in the New England Journal of Medicine in 2015 by Stanley Plotkin and Jeremy Farrar and Adel Mahmoud, suggested that what we needed was to not have the problems that we had with Ebola where we had to get a vaccine that was sitting on the shelf not being developed. And we should have vaccines ready and technologies for vaccines ready in a much more real time fashion. That op-ed perspective led almost directly to the creation of something CEPI, the Coalition for Epidemic Preparedness Innovation. And this worked together, together with other work like that of the NIH, was directly responsible for the fact that we have multiple opportunities to make vaccines in quick succession. Next slide. And in 2019, Richard Hatchett, who at that time had become the head of CEPI, published an article listing the portfolio of CEPI and what's highlighted here, you probably can't read, but what's highlighted is all of the work on MERS vaccines. So MERS of course has not come back, but MERS is a coronavirus, it's caused by coronavirus, very similar to SARS-CoV-2, and so all of that work was directly translatable into the speed with which we've had SARS-CoV-2 vaccines. Next slide, please. And so I want to end on that note of learning the right lessons. It's easy to say it happened this way last time, so it will happen that same way next time. And I think in between learning nothing and learning the right lessons is what often happens, which is that we fight the last war or try to deal with the past vulnerabilities and don't see far enough into the future. So I think the challenge for all of us is to think about how to-- what to learn from history, and not just did we learn anything? Next slide. So for example, I think one of the lessons of history is the disparities in who gets ill and who dies are constant. But the details of that are not. So in 1918, there was this very strange W shaped curve of mortality, where the people in the 25 to 29 age group were the most hard hit in terms of the risk of dying. And the people at the extremes of life the next most hard hit. But it was really a young healthy person's disease. By contrast, there are large disparities in who dies of SARS-CoV-2, but they are much simpler in the sense that they are just an exponentially increasing agent of age, as you see on the right. Next slide. The-- -- Modeler and epidemiologist Neil Ferguson wrote in 2006 that history tells us that poor populations always under a disproportionate burden of disease and death from infectious diseases. That has been true. Next slide. And here, interestingly in 1918, the disparities were more complex by socioeconomic status and especially race. And there's a literature on why that is. So they didn't follow the pattern that we have come to expect and some have come to accept, which we can't do. It's not acceptable, but it is consistent of pandemic diseases hitting the most disadvantaged harder. This is a graph from the 2009 flu pandemic by neighborhood in New York City. By my colleague and friend Sharon Balter, where she showed that the most disadvantaged neighborhoods also had the most hospitalizations for the 2009 flu. This is work by-- from the current pandemic by my friends and colleagues [inaudible] and Caroline Buckee and Steven Kissler, looking at the same thing in New York City, and once again, the Bronx is the hardest hit, or among the hardest hit, and areas of south Brooklyn and southern Queens that are the most disadvantaged as in 2009 are again the ones with the highest burden of disease. And they were able to show that this is very closely correlated to lack of ability to social distance due to-- by reducing travel. So movement continued in those places in the spring in New York and that led to continued infection. Next slide, please. The racial disparities in this pandemic have been dramatic with double the rates and worse in blacks, Latinos, and Pacific Islanders, and indigenous people compared to whites. So that is another enduring lesson. And last slide, I think. I think we learned some-- it's next to last. We learned a lot from the previous viruses and pandemics, near pandemics, about vaccines. I think from this pandemic, we should try to learn about other things that were not such a big problem in the past but have been in this one. So we need to learn lessons about the need for political and technical leadership, need for diagnostics and widespread sequencing. Better information systems, which have been a huge challenge in 2009, in SARS, and in SARS-CoV-2. And the ability to sample the population in a representative way. And then to leave you with a question, which I don't know the full answer to, what else are we missing? What have we not had a problem with this time that would be a big-- it could be a problem in future pandemics? And more broadly, we can learn a lot from the past, but how do we choose to learn lessons? And so hopefully we will have time for that in the discussion. Thank you. >> Tomoko Y. Steen: If you haven't put in a question, please put in. >> Okay, so since we have a few minutes remaining, I'll get started by asking the first question that was submitted. This is actually to a related question, what is meant by a universal flu or coronavirus vaccine? And kind of acts as a template for all flu viruses or would it have to be modified every time there are emergent variants? >> Well, I'll take a stab first at answering that question. So different people could have different definitions of what is meant by a quote-on-quote "universal vaccine," what I'm referring to is a vaccine that would offer some broad protection, not just to a single, unique strain or variant of the virus that you would see, say, as the initial emergent virus of a pandemic or one seasonal flu strain compared to other strains. So that rather than waiting for a strain to appear and then making a completely matched vaccine just for that one strain, which is what we're always doing right now, which is to chase after influenza's evolution, is to try to come up with the strategy that would offer broader protection so that you wouldn't actually need to know in advance what the strain is actually going to look like to conclude that the person would have at least some protection, protection from serious disease, if not complete protection from infection. And you know, this is a very high bar for viruses that are so diverse and can evolve so quickly. Which is why it's been such a difficult problem, but I think that there are data to suggest that such strategies can be possible. And as I've alluded, one strategy that we're working on in my group at NIH is going to start phase one clinical trials very soon, this year, and then hopefully be moving onto important efficacy studies later in the year. I do think these things are possible. And I think that whether or not this particular candidate ultimately moves forward, these kind of approaches, to think more broadly about how we can make better vaccines for viruses that are constantly changing, is a very, very valuable exercise and one of the most important things we can do for public health preparedness. >> Tomoko Y. Steen: Marc, do you have anything to add? >> Professor Marc Lipsitch: No, not much. Just to say I agree and that I think as we watch the variant viruses emerge and challenge our-- in some cases possibly challenge our ability to use existing vaccines, the need is greater than ever. >> Tomoko Y. Steen: Thank you. Next please? >> This is regarding the viral genome, an attendee asks why do this work? Why not just avoid close contact with animals that are known to spread diseases? >> Dr. Jeffrey Taubenberger: Well, let me start again. You know, we live in a closed ecosystem on Earth, you know, in which there are trillions of plants and animals and fungi and microbes all in a closed ecosystem. And you know, microbes of all kinds have been in kind of an arms race evolutionarily with their hosts. That infectious disease, in a sense, is sort of a dance, it's a two-way street. There's the microbe and then there's the host that's infected. And they have driven each other's evolution very significantly. There's just really no way to avoid this interaction. Since we're in this closed system. So that's just not possible. I mean we have billions of people now that were moving all over the planet very rapidly. In 1918, this virus emerged in some way but spread to almost every single person on Earth, including, you know, people in the most remotest villages in the arctic circle in northern Alaska, for example, but by steam ship, and rail, and dogsled in that case. Now we have people crossing continents in hours everywhere. And there's, you know, these kind of interactions in which for whatever reason, the animal viruses can somehow jump into both domestic animal species and then ultimately into humans. It's just unavoidable. And so we just have to face this idea that it's going to continue to happen. And so we can't ignore that, we have to continue to try to do what we can to mitigate against those future outbreaks. >> Tomoko Y. Steen: Anything more to say, Dr. Marc? >> Professor Marc Lipsitch: No. >> Tomoko Y. Steen: No, okay, next, please. >> Thank you. In your experience, is there an appetite among biomedical scientists and epidemiologists and others to learn from history? Many of the lessons you've discussed, especially regarding disparities in the spread of disease, have been quote-on-quote learned over and over again. So what do we do with that? >> Tomoko Y. Steen: Maybe Marc, you can? >> Professor Marc Lipsitch: Sure. Yeah, I mean, I think we're all very imperfect people. And institutions. And I think I had spent a lot of time focusing on the failure to learn. I mean, I've been in the pandemic preparedness area for now 25 years or so. And it does seem like we are quite slow. On the other hand, I tried to emphasize what I think is actually a pretty positive story that certain things we really have learned. I mean, five years ago, if we had had this pandemic happen the same way, I think many aspects of our response might have been better in the United States because we would have been better organized. But the vaccine-- the ability to make a vaccine would not have been anywhere near what it was this year. And 10 years ago, it really wouldn't have been. And that was because a small group of scientists generated support among a larger group of scientists and decision makers and people who have money to spend. That this was not a situation we could tolerate, to have viruses, pandemics emerge and have no vaccine approach. Now the disparities aspect of that is that while the rich countries are getting vaccines, the vast majority of the world is getting them at a much slower pace. And that is, you know, that is a lesson not fully learned. But I'm, as my friends know, I'm a pessimist and tend to see the negative in many things, but I do think that in this case, there's a lot of positives and that really, the parts that have been least well learned are the parts that go well beyond pandemic preparedness. I mean, the fact that we have a disparate level of healthcare in this country is-- was true before the pandemic, it will be true after the pandemic, and I really hope we learn that not only in pandemics, but also the rest of the time, this harms everyone and is not an acceptable situation. But I think it should not have taken a pandemic to teach us that and so I think it's a mixed bag. >> Tomoko Y. Steen: Thank you. Next, please? >> So regarding this question on pandemic preparedness, an attendee asks, with the incredible research you and your colleagues have done, is there any way to predict when future pandemics will occur? >> Tomoko Y. Steen: Marc, can you start? >> Professor Marc Lipsitch: Yeah, I don't think so. I don't think right now that that is even close to something that we can do. And that's because the number of-- well, especially if we mean more than a week or two in advance. So I think as we see the early signs as we did in the early part of 2020, or the late part of 2019, there are-- it is possible to make assessments of how likely it is that what's currently a small problem could turn into a big problem. And many of us were trying to do that. But I think in terms of saying, you know, six months from now or five years from now, this strain will emerge, there-- we can make those productions, but we will make many, many, many false positive predictions. Which, if we acted on them, would exhaust our resources, and if we didn't act on them, would not be very valuable. So, I think the ability to predict very rare events include genetic events in the virus and ecological events, so spillover and other chance events of the spillover, the person who gets infected from the spillover happening to get on an airplane or whatever, I just don't think that we are anywhere near the ability to do that. >> Tomoko Y. Steen: Jeff, do you have anything more to say? >> Dr. Jeffrey Taubenberger: Sure, no, I agree with everything Marc said. I also remain pessimistic currently of our ability to predict pandemic formation in the future. I think that it's important for us to understand how humbling it is to try to study something to complex. It's-- let's take influenza as an example. It's a tiny package of RNA that's being delivered that encodes somewhere between 10 and 12 proteins. These viruses have been studied intensively for 90 years now. And we actually don't know what all the proteins do. Now, not to be anthropomorphic, but the virus knows what it's doing, but we do not know what it's doing. And this is incredibly humbling. And I think that the more important thing is that when you understand what happens at a molecular level in the formation of a particular pandemic, the 1918, and then compare it to what happened in other pandemics, you find that while there are similarities, each pandemic forms in a completely unique way. That the lessons of 1918 at a genetic level are not necessarily the lessons of the 2009 pandemic or the 2072 pandemic, which we don't know about. That each one of these host-switch events is its own independent evolutionary emergent event. And there might be commonalities, and we should continue to look for them, but we should also appreciate the enormous complexity of biology. And it's just going to be very, very difficult to make these kinds of predictions, unfortunately. >> Professor Marc Lipsitch: Can I make one further comment? I think what's important to note, though, is that we don't then throw up our hands, as of course we're not. If you know that a type of threat is in front of you but you don't know exactly when or where it will happen, you can think of that in a national security context, or in many other contexts, you don't just say well okay, let's go home and wait for the bad thing to happen. You design your responses and your preparedness in such a way that whatever happens, your counter measures are more likely to be appropriate. And that's the philosophy behind what a lot of what Jeff was talking about with universal vaccines, it's the philosophy behind CEPI and developing platforms for making vaccines for unknown pathogens. In the national security context, one of the most thoughtful things I've ever read that for me has many, many parallels to disease is something I put in the chat. I don't know if every participant can see it. But it's a publication by Richard Danzig, the former Secretary of the Navy, called "Driving in the Dark." And I-- when it can be shared. I think it's one of the most insightful things that one could read if you think a little bit metaphorically and try to translate from the national security context to the disease context, I recommend it highly. >> Dr. Jeffrey Taubenberger: Yeah, if I could just add to that that you know, just because we can't predict it with exactitude when and how pandemics will occur, as Marc said, there are things that we should and can be doing in the sense of trying to develop mitigation strategies that could be immediately applied after a pandemic emerges in its earliest stages to try to limit its spread and to mitigate its impact. And that is critically important. Again, just like knowing that hurricanes and tornados are going to occur, but that we can't predict when and how and exactly where they will occur, still means that you can still do things to prepare for them in terms of building codes and alarm systems and early warning and so on. So the same with infectious disease. While we are not able at this point to predict when and how pandemic viruses will appear, we can, as Marc said, do things to help prepare us to be better suited to deal with them when they do appear very early, rather than chasing after them after the-- it's completely spread around the world. >> Professor Marc Lipsitch: -- Bring it back to the disparities discussion, one thing that really struck me early on in this pandemic was people have been complaining rightly about the poor quality of ventilation and in our schools and the air quality in our schools and about the fact that many public schools in particular don't have soap in the bathrooms. That was a problem that should have been fixed for many reasons. But among the reasons, it really is important now, as we're seeing, is for pandemic response. So, it goes-- the word building codes, you just reminded me of that. It really is many, many different aspects of life. And we should remember that as we learn the lessons. >> Tomoko Y. Steen: Yes, thank you so much. So time is running out. So last one is the vaccine [inaudible]. [Inaudible] people really concerned [inaudible] side effects and so on. >> Dr. Jeffrey Taubenberger: Well, I mean obviously, the most important thing is to safely evaluate vaccines in early, middle, and late stage clinical development. And have faith in that system and in the governmental oversight and regulation of vaccine development. You know, there are-- there are adverse events that occur with all medications. And vaccines. But we hope to make these extremely rare and understood. And so I think that communication of exactly what we know and the data that supports the safety and use of a therapeutic or a vaccine in humans is critically important. And people, we just need to do a better job communicating those data. >> Professor Marc Lipsitch: Yeah, I think-- scientists are by profession skeptics. And even for vaccines. When we see a new vaccine about which we have no data, we're skeptical. That's what we're supposed to do about everything we are studying. The difference is that as data accumulate that demonstrates safety or don't demonstrate safety, then we move from being skeptical either to thinking this is a vaccine candidate that should not advance and many do not when they get tested, they turn out not to be good and they get put aside. Or as this happened with two vaccines so far and hopefully many more, the data do show safety and effectiveness and then we update our views and instead of being skeptical, we then think this is something that I would want to take. I think that's the-- that's the model that we need to promote. And it's understandable in a time with lots of disinformation from many, many sources, including for a period of time recently from our government, that people have-- are confused. But I think that when the science is out front and the government scientists are speaking in an unfettered way, that people hopefully will see that that is communicating their best understanding of really what the evidence shows and will be sensitive to that. >> Tomoko Y. Steen: Thank you so much for both. Wonderful discussions and wonderful presentations. Could I have next slide, please? So those whose questions were not read, please send over to Ask a Librarian and mark it as January 27th Webinar and we will help you out. And next slide, please. So the presentation is going to be available at YouTube, our YouTube page, as well as our divisions page. So, if you, you know, anxious to see us again, please send a question to Ask a Librarian and also the request, you know, when it's going to show up. So please join me in thanking the two speakers. And thank you so much.