Lucien Crowder. Bulletin of the Atomic Scientists. Volume 74, Issue 5, September 2018.
In this interview, Tom Inglesby—director of the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health—discusses an array of issues surrounding infectious disease outbreaks, from preparedness measures to detection of novel pathogens to response by the public health system. He delves into why, in the 100 years since the 1918 Spanish flu, the world has experienced no pandemic of similar proportions. He assesses whether the next major pandemic will more likely be associated with a naturally occurring or an engineered pathogen; describes the tension between desirable and feasible levels of preparedness; and shares his experiences briefing senior government officials on national biosecurity challenges.
If deaths amid a novel pandemic might total 150 million, the threat is vivid indeed. To make it more vivid yet, Inglesby recently spoke at length with Bulletin senior editor Lucien Crowder on questions ranging from the threat of maliciously engineered pathogens to just how many ventilators a hospital really needs.
Bulletin: Let me start with a pretty basic question. It’s been 100 years since the 1918 Spanish flu, a pandemic that killed tens of millions of people. Why hasn’t something on that scale happened since?
Tom Inglesby: Well, we’ve seen in the last century a few smaller flu pandemic events, which didn’t reach that scale. What we don’t know about flu is exactly when the next flu pandemic will occur, but I think all flu virologists and public health experts believe that it’s a matter of time. I don’t think anyone can explain why it hasn’t happened in the same form. There were particular conditions that existed back then that were important in spreading the novel influenza around the world. Certainly, the conditions now are very different. In many ways we’re better prepared, but in many ways we have the same vulnerabilities or different, new vulnerabilities.
Bulletin: Could you expand a bit on which vulnerabilities have improved and which new ones have emerged?
Inglesby: Sure. The clinical care for influenza has obviously vastly improved. Back in 1918, we had no antibiotics. We had no antivirals, we had no mechanical ventilators, we had no oxygen or medical gases. We had no intensive care units. All the things that we have now to save the lives of critically ill patients—none of those were available back then. We also have surveillance systems in place to try and detect early novel cases of influenza as they emerge. We have a vaccine development program in the United States and elsewhere in the world, involving the World Health Organization, that identifies strains early. In the US, as we saw in 2009 [with] H1N1, we can make decisions to rapidly produce flu vaccine in a crisis. None of those things were available 100 years ago. We have communication systems in place to try and inform people about how to take care of themselves, what their triggers for going to the ER should be, and [we have] better informed political leaders. On the vulnerability side, we have a much larger population in the world. We still have an extraordinary number of people living in places where there are no medical resources available. So we have the high-income countries with many medical assets—and low-income countries with few assets. So those medical vulnerabilities certainly exist in many places in the world. A continued vulnerability is the length of time that is still required to make a new flu vaccine. Even with all the advancements in medicine and in science, it still took more than four months to make a vaccine for H1N1 in 2009. Even when we get flu vaccine in a pandemic in the future, presuming we do successfully create a vaccine, there would still be the problem of mass manufacturing the vaccine, and distribution of it. So if the vaccine is made in Country A, would Country A feel like it should vaccinate all of its people first, or would there be some obligation to share? If there would be sharing, would it be sharing with allies? Would it be sharing with all countries? Those things haven’t been worked out, and ultimately what we really need is the ability to mass-manufacture and then mass-distribute the vaccine globally. And those systems do not exist now. So we still have vulnerabilities on the medical side. On the clinical side, we have vulnerabilities in access to vaccine. The other vulnerabilities are kind of in the context of the world [today]. We now have the ability to move around the world in 24 hours, whereas in 1918 people still moved around by boat, so it took certain periods of time to get this novel strain around the world. In today’s world, a virus moving around in one part of the world can be on the opposite side of the world in a day. So that’s a new vulnerability as compared to the old days. There are a lot of very susceptible people in the world—the world is four times as large as it was, in terms of population, in 1918. So we have kind of on the one hand many things to be happy about, and on the other hand, even in the United States, many challenges. Even a high-income, comparatively well-prepared country like the US, which has made substantial investments in preparedness—we still, at the peak of a pandemic with the same characteristics as 1918, would have more people needing ventilators than we have ventilators on hand. Even in high-income countries that have made investments to be prepared for these kinds of events, there still would be a mismatch between demand and the ability to care for people.
Bulletin: Would you be willing to venture a guess—this is pretty speculative, but imagine that the 1918 flu hadn’t emerged then, but emerged now—what do you suppose the mortality would be today?
Inglesby: I think that would be highly speculative. Hopefully it would be reduced overall given all the things on the high side of the ledger, on the medical assets side—early detection, vaccine production. So I certainly would hope we would do better. Even in 1918, there was a discrepancy between the case fatality rate in higher-income countries versus other countries which had less access to medical care. So I think in today’s world there would be a range of mortality depending on where you live in the world, unless we’re able to begin to solve some of these inequity problems. But even a flu that was half as lethal as 1918 would still be more lethal on a large scale than anything else we’ve seen in this century in terms of a novel respiratory-spread virus.
Bulletin: Let’s move on to the tabletop simulation that the Johns Hopkins Center for Health Security conducted in May. It involved a pandemic that was spreading across the globe, and government officials, played by people such as former Senators Tom Daschle and Jim Talent, were trying to contend with the progress of the disease. The results weren’t very encouraging. A hundred and fifty million people died. Could you explain, for people who haven’t read about the exercise, how the disease progressed and why so many people died?
Inglesby: Sure. [But] first of all, I’m going to say a little bit about why we did this exercise. The purpose of the exercise was to make vivid to senior policy makers the potential consequences of a novel pandemic and to identify some of the policy dilemmas that they would be confronted with—as well as some of the policy solutions, the investments that might be made that would reduce the impact of an epidemic like this. The other thing to say is that we have a new administration. We have relatively new leadership in the World Health Organization. We have a number of problems that have surfaced in past epidemics which remain unresolved. So we believed that a simulation that looked at how National Security Council-level policy makers responded to a novel pandemic would create experiential learning in the senior policy makers, who would then communicate to their networks and help influence and improve preparedness. So that was the overall goal. It is the case that this story proceeded rapidly, and that the final outcome of this story was case fatality rate and overall mortality rate. If you adjusted for population, it was on par with the mortality of 1918. So we thought it was important to try and help people understand the case fatality rate of an event like 1918—or a modern version of a novel virus. We also thought it was important to shine a light on the kinds of things that could help change the outcome of that event.
Bulletin: But proceeding to how the disease progressed, though, and why you ended up with the outcome you did…
Inglesby: Yeah. For people who are interested in the particulars of the disease that we use in the exercise, there’s a section on our website called Clade X, and it’s about a 10-page discussion of the model that was used for the spread of the disease around the world. For people who have a particular interest in that, that’s a more detailed resource. But we used a model that [included the] respiratory spread of a novel pathogen that had characteristics somewhere between the SARS virus of 2003-2004 and the influenza virus. The difference between SARS and influenza is that SARS was contained in 2004 after about 8,000 cases and [after spreading to] almost 30 countries. Influenza is not a containable disease. Every year there’s an influenza epidemic that moves around the world. Usually the case fatality rate is on the order of one in 1,000 to one in 10,000. Usually it’s closer to one in 10,000. The world deals with it, but it is a disease that’s difficult to contain. By the time the disease is recognized in our story, given the absence of a vaccine for this novel pathogen, the disease moves along in the world and ultimately is not containable.
Bulletin: Now, if I understand it correctly, the pathogen you were imagining in the exercise was a virus engineered in a lab by a terrorist group. How likely do you think such a scenario is? I mean, if a pandemic on the scale that you had in mind does emerge, what probability would you assign to its being engineered as opposed to, say, just mutating among pigs or chickens and jumping to humans?
Inglesby: I think we have to be ready for both possibilities. Given the statistics up until this moment, you would say a natural event is more likely to cause a pandemic. Influenza, certainly, is the most likely pathogen to cause a pandemic. So I think if you were a betting person, you would certainly put a lot of your preparedness resources into preparing for diseases like H7N9, which every year in the past five years has been a major threat in China, but hasn’t become an efficient spreader. On the other hand, as we see what science is now capable of, and we see the kinds of changes that are now possible to make within viruses, we need to adjust to the possibility that, either accidentally or on purpose, novel strains can be developed even now that could have the potential to self-propagate or spread. It’s not that we have a prediction that that’s the most likely thing to occur, but we certainly believe that science has the power to create novel pathogens. There’s a lot of debate about what level of expertise would be required to construct such a pathogen. At this point, we would agree for the most part that terrorists who don’t have sophisticated training—this would be beyond the reach of those kinds of groups. On the other hand, if scientists with high-level skills in virology were recruited to work for terrorist groups, and then were given resources…. In our story it was actually more cult-like than [like] a terrorist group, but in either case—we believe that [scenario] is now within the realm of possibility, even though we certainly don’t have any special knowledge that any such group is planning that kind of event.
Bulletin: I see. Now, would you be willing to hazard a guess where the next truly worrisome pandemic might strike first, or were it might strike hardest? I suppose I’m talking about a naturally emerging pathogen, not an engineered one.
Inglesby: In terms of geography?
Inglesby: Well, if you skip back before 2009 H1N1, [to] about the 10 years before that, I think a lot of the world’s virologists and public health experts were concerned about emergence of a pandemic virus from Asia. That was in part based on some of the novel influenza strains that have emerged in Asia, including H5N1, as well as the emergence of novel coronavirus in SARS, which emerged in Asia as well. A lot of the surveillance systems that we had at the time, and still have, had been designed around trying to identify new changes in the virus in various parts of Asia, and there are a number of really good laboratories in the world doing that kind of work. But what we learned in 2009 H1N1 is that those kinds of rules are relatively. well, how should I say this? They are guidelines that have some evidence behind them, but they are certainly not dictates that should direct behavior, because 2009 H1N1 appeared in North America first. Some studies have looked at land-use changes in the world. We know from virologic evidence and ecologic studies that the risk of novel virus emergence increases in places where humans and animals have a lot of interface. One of the risk factors for increased interface is human encroachment into areas which were previously pristine ecosystems, or basically ecosystems in which humans really were not participating. So studies are now going on which are showing where the most dramatic land-use changes are occurring, and there are attempts to try and correlate those land-use changes with changes in viral patterns. I think that’s an area of importance.
Bulletin: I see. So the answer to my question seems more complicated than it would have seemed 10 years ago.
Inglesby: Exactly. When we look at the emergence of Zika, we know Zika existed in Africa in the ’40s, and then basically [there was] not much evidence of it in other parts of the world. Then we again see it in the Pacific a year or two before it really emerges in Brazil. Then in Brazil it takes off, and then spreads through South America, Central America, and then begins to move into other parts of the world. So where do we start counting with that? Where’s the emergence? Certainly the pattern changed entirely once it got to Brazil. So I think most people would say that was the place for emergence, but it’s an interesting question. Toni Fauci and the National Institute of Allergy and Infectious Diseases would call this the realm of emerging infectious diseases and re-emerging infectious diseases. They would categorize as re-emerging infectious diseases things that we’ve known about for some time but now are appearing in either a new place in the world, or with a new pattern, or with new lethality, or new vaccine or drug resistance. So, for whatever reason, we knew about that disease, but that disease is acting in a very different way, and it could cause terrible problems.
Bulletin: Is it understood why Zika took off in Brazil while it hadn’t really taken off in the other places before?
Inglesby: That’s still being studied. There are theories about whether there were virologic changes, or [whether] parts of the population were more vulnerable, but I don’t think we have conclusive evidence about why there was such a dramatic change at that time.
Bulletin: My next question circles back to something you mentioned earlier—in a recent Atlantic article called “The Next Big Plague Is Coming. Is America Ready?” you were quoted as saying that if a pandemic along the lines of the 1918 flu hit, your hospital “would need in the realm of seven times as many critical care beds and four times as many ventilators as we have on hand.” On one hand that sounds like inadequate preparedness for a flu pandemic, but on the other hand, if health care systems devoted their resources to the best possible preparedness for the worst imaginable pandemics, wouldn’t they be giving short shrift to the work that needs to be done every day? With pandemics, aren’t you in some sense forced to hope for the best?
Inglesby: I think you’re right, and I didn’t mean to imply in that article that we should therefore buy seven times as many intensive care beds or four times as many ventilators. That kind of change would not be possible in terms of budget or personnel—even more important than the equipment is the people that run the equipment. I think what it says, though, is that we need to do whatever is feasible, through investments and medicines and vaccines and diagnostics. So we [may] still have a severe pandemic in the future, but if we can diminish by 50 percent the number of people who get the novel strain of influenza, for example, because half the population is vaccinated in time to prevent that, or we have antiviral medications that can diminish by a third the number of people who need to be in intensive care units. A number of partial solutions could get us to a point where we would be better prepared. We can’t completely change our health care infrastructure. We can’t build units that are just standing by for emergencies. But we should be thinking about how a hospital would react to this kind of event. It may be the case that we don’t have vaccine or antivirals. We don’t have enough ventilators, in which case we need to make some very, very difficult choices about the allocation of scarce resources. How does that work? How do the people of a city or a country continue to have confidence in their health care leaders and their political leaders when we don’t have enough to go around? [What would] society think was most just? Because you’re right—we can’t prepare for all scenarios. We can do better than we’re doing now—by getting to a point where we can more rapidly produce vaccines and antivirals as needed. But even if we do that for influenza, there will be other possible pandemic threats in the future, and so we need to move forward with the work that’s going on [regarding] flu vaccine—both the universal flu vaccine as well as pandemic vaccine stockpiles that are being developed on occasion, when we have a particularly frightening influenza strain such as H7N9 in China, which we referenced earlier. So not only do we have to go forward with influenza planning, but we also need to innovate and accelerate the ability to make new vaccines for other diseases. If you think about what we did with the 2014-2015 Ebola response in West Africa, the US and other countries and their pharma partners were able ultimately to develop an Ebola vaccine. They did it in what many people would say was a very rapid time frame, as compared to the timeline it takes to develop new vaccines for other problems. On the other hand, even with the time frame being more rapid than most vaccine development projects, it still was not ready in time to be of value for that Ebola epidemic in West Africa. It’s now on hand to be used for future epidemics, but throughout that time it just wasn’t ready. [It was only] as close as it was because the US government had been working on it for some time, kind of in the background as a biological threat. So there had been investments in the Department of Defense. There had been investments in Health and Human Services. So there was a research base which could be drawn upon for accelerating and finishing the development process. For many infectious diseases, we don’t have that kind of base yet. There is the possibility, of course, of novel diseases [emerging]—either naturally occurring or deliberately created diseases—for which we don’t really have much in terms of research base and we need to be able to move very rapidly. Those are the kinds of things that the government is thinking about, that the big pharma companies are thinking about, that other governments are thinking about. How do we keep shifting the timeline faster? Exciting things have happened along those lines in the last couple of years. One was the partial excitement [of] the Ebola vaccine, although it wasn’t fast enough. But there’s a new organization, created about a year and a half ago, called the Coalition for Epidemic Preparedness Innovations (CEPI). That was created with the recognition that there was no market pull for many infectious diseases, and that it was very difficult to get those kinds of products going unless there was a commercial market. CEPI was created with support from governments and from major foundations. The goal of CEPI is to develop vaccines for infectious diseases that have no market, that create either pandemic risks or regional epidemic risks. They are working with biopharma companies around the world to try and make progress on diseases like Lassa fever and MERS and Nipah.
Bulletin: What’s Nipah?
Inglesby: Nipah is a viral disease that naturally appeared in Malaysia and India and Bangladesh over the last 15 years, initially in pigs. It does not spread rapidly or easily between people, but it did spread between pigs and people and killed a number of people in a variety of outbreaks—[though it was] a relatively small number compared to, for example, Ebola. What’s important about Nipah is that the case fatality rate in human infections is 70 percent. So whenever there’s a virus that has case fatality rates really above single-digit percentages—even if it isn’t an efficient human-to-human pathogen—that is something that people sit up and pay attention to as a very dangerous virus. Nipah was the cause of an outbreak in India [in June], which caused quite a bit of alarm in the area where it was occurring. Another encouraging development along these lines is that the World Health Organization (WHO) last year came out with its own research and development blueprint, which they called the R&D Blueprint. It lists eight diseases that they believe are very important R&D priorities for the world. They don’t have money to allocate for those resources, unlike CEPI, which has money from donors. WHO is calling for the science communities of the world to invest in these diseases to better understand them to make more progress. It’s the same list as CEPI, but it’s a little longer—and one of the diseases on their list is Disease X. By that they mean that a future epidemic or pandemic could be caused by something that we’ve never talked about or recognized before.
Bulletin: Making preparation for it rather difficult?
Inglesby: Rather difficult, although what it argues for is investments in platform technologies—technologies that would broadly accelerate the process for vaccine or medicine development. It’s not something that there’s been a lot of success with, but there was some success with one of the Zika vaccine candidates using a platform technology, and there are many, many scientists and companies that are interested in developing the process broadly. There are now tools in the world—scientific tools, biotechnology tools—that, at least in principle, could allow us to really accelerate the development timeline even for things that we have not seen before. You’re right that in some ways [Disease X is] difficult to prepare for, but [certain] principles are common between diseases. The principle of infection control for preventing respiratory spread of diseases, for example, is something that would be common across many diseases. The kinds of things that you do for Ebola would be similar [to the] precautions that you’d take for things like a coronavirus that was spread person to person. So in some preparedness investments, there’s a lot of commonality. The supportive clinical care in high-income countries would be very similar—ventilators, and supportive care in a hospital. But the particulars, particularly diagnostics and rapid diagnostics, [and how we would] quickly differentiate this disease from something that looks like it—that would be novel for Disease X. A vaccine would be novel. There’s a report from 2016 by the President’s Council of Advisors on Science and Technology (PCAST). The PCAST report related to improving biodefense for the country and they meant biodefense writ large—natural diseases or deliberate diseases. And they called for setting a national goal for the development of vaccines for novel viruses. We don’t really have codified targets yet. What are we driving for? Is it in the national interest to develop a process of making a new vaccine for novel disease in six months, in a year, in five years, in 10 years? The normal vaccine development timeline is five to 10 years, probably more toward the latter. Is that our current position for new emerging infectious diseases? No, but what is the position? What is the goal? What are we trying to get to? On the influenza side, we have a national goal of being able to create vaccine for the country within six months of the recognition of a novel pandemic flu virus. We don’t have a similar goal yet codified as national policy or science policy for how quickly the country needs to be able to respond to a novel pathogen that’s not influenza. So I think calling out Disease X at the WHO kind of elevates that so hopefully we pay attention, and that we structure our R&D programs in ways that are amenable to novel surprises.
Bulletin: Could you tell me a bit more about universal flu vaccine? That’s something I haven’t heard of before.
Inglesby: The way that flu vaccine works now is that every year there are changes to the dominant couple of flu strains that are in the world. So every year the vaccine that is created for annual flu vaccine coverage is created based on the latest changes in the dominantly circulating vaccine or viruses in the world. So there’s surveillance going on, people’s viruses are submitted to laboratories, they’re studied, then we modify the flu vaccine [for] that year. Similarly, if H7N9, a particularly serious bird flu strain, was able to make a shift from predominance in birds and began spreading in humans, we would need to take that particular strain and create a vaccine out of it. The high side of that is that you have precision, but the low side is that it’s slow—many, many months later even in perfect conditions. [And] of course everyone needs to line up and get vaccinated every year for seasonal flu, which is expensive and logistically complicated, and some parts of the world can’t afford it.[With] a universal flu vaccine—there are different definitions of what that [term] would mean—but ideally a universal flu vaccine would create immunity to portions of the flu virus that are common to all flu strains, [such] that when you do develop immunity to your universal flu vaccine, the threat of seasonal flu goes away, and the threat of bird flu goes away, and the threat of pandemic flu goes away. That would be a perfect world where one immunity or even a series of shots, all timed in a certain way, basically took flu off the table as a human infectious disease threat. That would be the goal. That would be the faraway dream and vision. We are many years away from a universal flu vaccine at this point, despite lots of investment, and lots of very talented scientists trying to develop that. In the meantime, there could be flu vaccine developments that are partial solutions. So perhaps we develop a flu vaccine that covers more seasonal influenza strains, but we’d still need to get a new flu vaccine for pandemic strains like H7N9 or H5N1, or perhaps we get a flu vaccine that lasts for three years or five years instead of needing to get a new flu vaccine every year. There are different permutations of what a universal flu vaccine could look like, with the perfect one being [a solution to] the flu problem in the world. That’s not close, but that is a national goal. That’s an international goal, and there’s a lot of work going on within the [National Institutes of Health] and the universities and companies around the country to try and pursue that goal.
Bulletin: I see. It’s not that you’d stamp out the pathogen. You’d just immunize everyone in the world indefinitely. It’s not like smallpox, where you’d actually wipe it out.
Inglesby: Exactly, exactly, because influenza infects all sorts of animals, particularly pigs and birds, but also large cats, and they have different strains that infect different animals, but there’s a mixing that goes on. So the difference between smallpox and influenza is that, for smallpox, there was no reservoir of virus outside of humans. But in the case of influenza, there are huge reservoirs, so influenza would continue to circulate in the world. If we had a universal flu vaccine and it was distributed around the world, it would protect those who had been vaccinated. It would also protect many, many people who weren’t vaccinated because the spread of flu would be interrupted by all these buffers of people who were immunized. That phenomenon is called herd immunity. If you can get a large portion of the human herd vaccinated, then they become the buffers that prevent human-to-human spread for the people who couldn’t get vaccinated for whatever reason.
Bulletin: Got it. Now, I see from your Johns Hopkins bio that you’ve briefed officials from the last four presidential administrations on national biosecurity challenges. What do you tell officials in briefings like that, and how do they react?
Inglesby: Well, sometimes those discussions are happening in the midst of some particular crisis, like during anthrax or SARS. Sometimes those discussions are happening when the main question on the table is “How do we prepare?” They’re in between crises or in between epidemics. So it’s kind of hard to generalize. But I think a general principle is that epidemics [fall] outside the usual thought process for many political leaders. Policy makers are often very familiar with classic national security crises, or even perhaps natural disasters, where there’s a certain rhythm to the disaster and a kind of lead-up and then a recovery. But when people are either in the midst of responding to an epidemic or are thinking about how they would respond to a future epidemic, there are a lot of differences in how they might think through a problem. For example, in an epidemic, if it’s a disease like SARS or influenza, often the problem is going to get worse before it gets better—as compared to a natural disaster where sometimes, [as with] an earthquake or a hurricane, the full extent of the problem is often visible relatively soon after an event. Another thing that sometimes is unfamiliar for political leaders thinking through these issues for the first time is how to communicate effectively about risks, how to balance concerns about the public’s fear of epidemics versus the real, very clear need for the public to understand all the facts, and to be trusted [as] adults who are capable of [handling] bad news. It’s also the case that many political leaders or policy officials don’t realize how little we have [for response] to certain epidemic threats. I think there’s a presumption, given all the scientific progress and prowess in the United States, that we would have vaccine or medication solutions for most or all infectious diseases. But as we talked about earlier in this [conversation], for many important, very serious infectious diseases, we don’t have that investment yet. We don’t have products. We might have research that heads in that direction, but we don’t have products that are ready to go. So I think it’s been surprising for many to realize how vulnerable we are to some diseases—how challenging it would be to distribute things rapidly if we had a pandemic six months from now, how challenging it would be to get people vaccines and medicines quickly, how difficult it would be to make decisions about priority groups if we had to, such as who would get vaccines and who wouldn’t, and all the political considerations that might be a problem. So the value of those discussions often is that people get a broader sense of what’s going on, and then can turn around and ask their own agencies and their own colleagues what they think of those problems, and if necessary, push things along, generate a little extra momentum toward investment [in] new vaccines or generate more attention for the public health system. The public health system is kind of the glue that is important for every large-scale infectious disease response. The public health system includes the disease detectives or epidemiologists who are putting out the surveillance systems, looking at laboratory data, and trying to find evidence of new disease. It includes the top-level and local-level risk communicators who have to tell people what they can do to prevent themselves from getting infected, or where they might go for information, or what to do if they’re sick and they need to go to the hospital. There are the laboratorians, the people who actually make the diagnosis—especially in new diseases that are complicated, and [for which] we don’t have the right test yet. Places like the Centers for Disease Control and Prevention (CDC) or our public health laboratories around the country—they’re the ones who are trying to find the needle in the haystack when something new is happening, and they’re also the ones that a lot of the rest of the world turns to when there’s something new and serious happening. The CDC, in situations like that, is a global resource, a global treasure. They have such talented scientists who have been working on these problems for a long time, and they’re willing to go places to get to the bottom of things, and try and make the right diagnosis and the right plan for containing a new outbreak.
Bulletin: When you brief officials, do they seem to take what you say to heart and begin to take the steps that you wish they would?
Inglesby: It depends, but usually if there is a briefing going on, there’s a good chance that they are willing listeners. They usually they take a briefing [because] they are interested in learning more and thinking about what they might do. So I’d say as a general trend, I’ve been very happy when involved in those discussions because it seems like there’s an interest and willingness to get the country better prepared to try and respond better. It’s hard to remember any situations where there was any kind of serious rejection of the problem, or rejection [of the idea] that the US should be a big part of the solution. I do feel, because epidemic response and prevention [are] at the intersection between national security, science, public health, and governance, that people feel like there’s a lot we can do. We should be doing it. This isn’t in the realm of the impossible. The US has scientific leadership. It has health leadership. So let’s keep pushing that forward and see what we can do.