Pandemic Preparedness: Lessons Learned 100 Years After the Spanish Flu Outbreak

Tuesday, December 5, 2017
Eric Gaillard/Reuters
Speakers
John M. Barry

Distinguished Scholar, Center for Bioenvironmental Research, Tulane and Xavier Universities; Author, The Great Influenza: The Epic Story of the Deadliest Plague in History 

Laurie Garrett

Science Journalist; Author, The Coming Plague: Newly Emerging Diseases in a World Out of Balance; Former Senior Fellow for Global Health, Council on Foreign Relations

Anne Schuchat

Principal Deputy Director, Centers for Disease Control and Prevention

Presider
Sheri L. Fink

Correspondent, New York Times

Panelists discuss the 1918 Spanish flu pandemic as we near its centennial and how this historic outbreak informs our responses to global health emergencies today.

FINK: Hello, everybody. I’d like to welcome you to today’s Council on Foreign Relations Malcolm and Carolyn Wiener Annual Lecture. It’s entitled “Pandemic Preparedness: Lessons Learned 100 Years After the Spanish Flu Outbreak.”

I’m Sheri Fink. I’m a correspondent for The New York Times and the author of “Five Days at Memorial.”

And we have a wonderful panel assembled here today. Starting at the far end, your far right, we have Dr. Anne Schuchat. She’s the principal deputy director of the CDC, just came off of six months being the acting director. And she’s been around for a lot of the past couple of decades’ pandemic responses, infectious disease responses, so a wealth of experience there.

And our other two panelists have really had amazing careers bridging both the more academic and technical world and the policy world with the journalistic world. And I think these two are responsible for a lot of what we know today about infectious disease outbreaks.

And so they include Laurie Garrett, a science journalist and the author of “The Coming Plague: Newly Emerging Diseases in a World Out of Balance.” And as many of you know, she until very recently for many, many years has served as the senior fellow for global health at the Council on Foreign Relations, until very recently.

And we have John M. Barry, who is a distinguished scholar at Tulane and Xavier Universities, and is author of “The Great Influenza: The Epic Story of the Deadliest Plague in History.”

So we’ll start with you, John, since you wrote this book. (Laughter.) Give us a couple of minutes’ just background. What was the Spanish Flu? How deadly was it? Do we know? And why should we care?

BARRY: Well, we certainly should care.

Yes, in 1918, right now the generally accepted death toll was probably between 50 and 100 million. That was, of course, in a world with a population less than a quarter of what we have today. So you simply adjust for population and you’re talking about 150 to 400-plus million comparable death toll. Well over half the deaths occurred in healthy young adults and middle age, generally between 18 and 45 or 50. And probably two-thirds of the deaths were concentrated in a 10-week period. So that was an extraordinary event.

And there’s a lot of focus on the young adult population, but they of course are not the only people who died. Elderly, who are normally vulnerable to influenza, escaped almost unharmed. Ninety-nine percent of the excess mortality was actually below 65. But children between one and four, the death toll was equivalent to all caused deaths today over a 20-year period. And so, in 1918, in approximately 10 weeks, children one to four died equal to all caused deaths for children that age over 20 years.

So, in terms of psychological impact on families and things like that, it was a horrific event, and there are a lot of lessons to learn from that that we are applying and trying to apply. In 2009, through somewhat of a curve—but I don’t want to dominate the conversation.

FINK: OK. Thanks.

BARRY: You know, I’m sure we’ll end up going into the other subjects.

FINK: Let’s go to Dr. Schuchat next. I just want to go to you, since you’re focusing on the current threats in our public health system, and finding them and fighting them. So why should we care about flu? It’s the modern era. Could we possibly be vulnerable, like they were back in 1918?

SCHUCHAT: Yeah, you know, you think about how bad it was in 1918, and you think surely our modern medicine and our technology will save us. But influenza is the—you know, the Hollywood movie writer’s worst nightmare because a pandemic can affect virtually everybody in a very short period of time. We have many more tools than we had before, but they’re imperfect tools, and we have a lot more work to do to improve them. And we’re, of course, even more interconnected than we were in 1918.

So we know that in 2009, within a six-week period, the new strain, the H1N1 swine-origin influenza strain, got to 122 cities, you know, just in six weeks. It was essentially everywhere. So we really know, between the density of cities and the travel and trade, that these pathogens can spread really quickly. And the concept of an influenza pandemic is it’s not like an AIDS pandemic that can take—you know, can have a huge, huge death toll over decades; it’s over a very short period of time. Even with the 2003 SARS respiratory virus, in one quarter that virus, that was much less contagious than influenza is, led to about $40 billion of economic loss because trade and travel to Asia stopped during that quarter.

FINK: So, Laurie Garrett, you have been keeping us informed all through these recent years about the various threats that are out there. What do you see right now? What is it that is on the horizon? What keeps you up at night in terms of these influenza strains?

GARRETT: Well, Sheri, as long as I can remember in my professional life, there’s been something out there that we’re worried about. Fortunately, most of the time it hasn’t materialized in the form that we most were concerned would, in fact, threaten us. But this year we have a couple of things lurking that are worrisome.

One is a strain called H5N6, which emerged, like almost all influenza does, out of Asian migratory birds, and now is very rampant in the poultry population in South Korea. And just recently, two human cases of this have emerged, and it’s right outside of where the Olympics are going to be in a few weeks. So that’s—you know, that’s sort of perfect-storm possibility: The entire world comes to one place, they all stay in a little village, and there’s a circulating influenza, and then they all go home. I don’t think this has actually turned into the strain that we need to worry about.

However, there is a lot of concern about another strain, H7N9, which first emerged out of migratory birds in the Asia flyway in southern China in 2013, with a huge toll in Shanghai. And it was unusual because we hadn’t really seen these avian influenzas make that big jump in an urban setting. They typically had sort of slowly percolated in rural areas, where people are directly, you know, close to wildlife, and their livestock is close to wildlife, so there’s a possibility of transmission from a wild bird to poultry to person, or wild bird to swine, what have you. But in this case it was just suddenly exploding in Shanghai, and caused a great deal of concern. Then it seemed to go endemic, and you just see a handful of cases here, there, and everywhere. And all of a sudden, since roughly August, we’ve seen a real surge in H7N9 human cases, and with about 45 percent mortality rate in people. So, when you consider that the 1918 strain is generally, averaged over the world, thought to have had a 2.2 percent mortality rate, though in some places such as such rural areas of Iran were documented at 47 percent mortality, but overall it was not anything close to what we see now with H7N9.

A new—two new papers just published show that this new strain does have a mutation. It may be that the strain is adapting to mammalian hosts. A very prominent scientist in the field, Yoshi Kawaoka at the University of Wisconsin, has done some genetic testing on it, and he thinks that it is, in fact, a mammal-to-mammal transmissible strain. So that would be worrying.

FINK: So clearly—OK. So clearly the problem did not go away 100 years ago.

So, John Barry, you looked a lot at what was done to try to counter the epidemic, and I think you have a lot of thoughts about what might or might not be useful. The same kinds of questions come into play whenever there is an emerging infection. I reported a lot on Ebola. So did, I think, all of us. And some of the—you know, there’s this balance between the civil rights of the society and the economic, you know, kind of functioning of a society, versus this desire to tamp down on the spread of an infectious disease. So what did you draw from your study of how that went 100 years ago?

BARRY: Well, first, before answering that question, just to give you all a sense of scale, between—you know, Laurie was talking about these avian influenza viruses. Between 1959 and 1997, there were two documented instances in which an avian virus infected people. Between 1997 and today, there are about 2,300. And neither of those two died, and we now have approximately a thousand deaths, a little over that, out of roughly 2,300 infections. And each infection, you know, you have an opportunity for it to adapt. So it is a real threat.

Now, after another avian virus—H5N1—surfaced I guess about 15—well, 1997, then it resurfaced in 2004, a lot of Western governments got very serious about trying to deal with influenza as a threat. They put a lot of money into—you know, Anne can testify to that a lot better than I—a lot into the hard sciences, into vaccine production. But they also started planning for what they call non-pharmaceutical interventions, since they knew the vaccines aren’t that effective and it takes months to get one. You don’t have any antiviral drugs that are really effective. So there is an effort to plan what kind of social measures might be taken that could mitigate the impact of a pandemic.

And since most of that was based on an analysis of what did happen in 1918, I was pretty involved in a lot of those efforts. You know, they are—

FINK: So are they useful? Like, is there anything—

BARRY: You know, I think there—you know, there—right.

FINK: If there’s a big outbreak that’s on the horizon, what should we do? What shouldn’t we do? What do we know?

BARRY: Right. I think common sense would tell you what would be involved, and the phrase is social distancing and all sorts of different things that would implement any kind of social distancing. I think that I support those—the NPIs. I think they’ve been oversold by the modelers.

I think one of the most effective things you can do is going to be wash your hands. I mean, it’s something as simple and fundamental as that. I remember the very first meeting we had on NPIs. They had a gentleman there who ran the infection control at the hospital in Hong Kong that had the best result in SARS. Most of the deaths in SARS were health care workers who infected themselves. And what he did was—everybody knew what to do, but people did not execute it. It went back to Vince Lombardi, blocking and tackling, that in his hospital he made certain that people were absolutely rigorous in terms of washing hands and protecting themselves, taking off their personal protective equipment—which, if somebody says PPEs, that’s what they’re talking about personal protective equipment. You know, it just goes back to the simple, fundamental things. They actually were pretty effective.

 Other stuff like school closings, you know, staying home and working at home, don’t go to work, don’t send your kids to school if they’re sick, don’t be a hero, whoa, that becomes very dangerous, all sorts of things like that are recommended. I do support them. The idea is if you layer them, if you have four or five of these interventions, they all take a little bit off the top, and cumulatively they have some impact. But I do think it’s overstated.

On masks, I don’t think there is any real evidence that masks do any good, unless you put a mask on somebody who’s sick. And in 1918, they actually did experiments and proved that even in 1918. A healthy person wearing a mask is not going to do much, if anything—probably nothing—to protect themselves. But if you have someone who’s sick and you put a mask on them, it is effective.

FINK: Thank you.

So, Dr. Schuchat, I think you may want to respond to some of what’s been said.

SCHUCHAT: Yeah, just—yeah, just to say, you know, one thing that came out of the 2009 pandemic was an enormous amount of data. And then a lot of studies and follow up, because there was a lot of uncertainty about which measures would work, in combination, alone, and which measures were worth it. You know, you may remember at the beginning of the 2009 pandemic in April and May there was temporarily school closures, quite a lot of them, maybe some of your own kids or grandkids had to stay home. We found out since then that school dismissals or delaying the opening of school if it’s in the fall can definitely delay the peak or the blunt—you know, or blunt the peak of influenza rises. But it comes at a cost.

And so we now try to think about the non-pharmaceutical interventions in a balanced way. There’s some that we recommend for seasonal flu every year. You know, you’ve seen us say, cover your cough, you know, wash your hands, stay home when you’re sick, keep your kids home. You know, it’s like a broken record during flu season. Those are good, evergreen, do them every year. They’re good for other respiratory viruses too. But things like school dismissals, teleworking, canceling mass gatherings, those types of interventions have second- and third-order consequences. And we really need to balance those.

So what we really learned in 2009, that we knew but we learned the hard way, was how much uncertainty there is at the beginning of an emerging pandemic. You don’t even know if it’s going to be a pandemic. You have people dying in Mexico. And then you have mild disease and a huge school outbreak in Queens. You don’t know whether taking extreme measures is going to be lifesaving or going to create a big, big backlash. And so what we’ve done since 2009 is updated the evidence base, and updated those practices to say we’re going to continue to—we’re not going to have a strategy for an entire period. We’re going to look at the data, come up with interim recommendations, relook at how severe the disease is, how efficient it is at spreading, and modulate based on what societies can handle.

FINK: So, Laurie, there—

GARRETT: If I may, there’s a few things I’d like to bounce off of here, because first of all—

FINK: Well, I was going to actually ask you, because in Foreign Affairs this fall the new director-general of the WHO, he was—there was a question and answer with him about his priorities for global health. And he was asked: What keeps you up at night? Kind of the question I asked you. And he said, epidemics or pandemics. And he spoke of serious gaps in the ability to respond. So I would love for you—you’ve looked very closely at the health systems. I know Dr. Schuchat has talked a lot about this priority that we need to sort of help countries around the world to get more prepared. But where do you see the big gaps right now? Where do you see the work needing to happen? There are a lot of these meetings. You’ve been speaking at them around the world for the hundredth anniversary. But, you know, what should we be thinking about?

GARRETT: OK. Well, first of all, you know, I think that John said 10 weeks a few of you gasped, that the bulk of the death toll occurred in 10 weeks. Think of it this way. In New York City in 10 weeks 31,000 children became orphans. In 10 weeks, 20,000 people died in this city. And there were stories of individuals who got a subway at Coney Island and—feeling perfectly healthy—and their dead body was found when the subway pulled into Columbus Circle. I’m just—that’s as graphic as we can put it.

There are huge gaps in our knowledge about 1918 and then as we move forward and try to understand what we face those translate forward. We still don’t know—and it was an ongoing debate for decades—how much—and I’d love to know what you think of this—how much of the death toll would have been lowered had there been antibiotics in 1918. In other words, what percentage of those deaths were secondary infections with respiratory bacterial infections.

We do know that coroners in London—and you know this all too well—said they found bodies that were—where the lungs were filled with blood. And that individuals didn’t die of secondary infection. They died from the flu. We don’t really have a clear understanding of that. And we don’t have any system in place that I know if any country that could handle an event that could have a toll proportionally like that in 10 weeks. Within 10 weeks, you know, the White House would have called Atlanta a couple of times, maybe. (Laughter.)

And then we have to add to that—we have to add to that the horrible political reality of where we are right now. We are in a world that’s becoming increasingly isolationist, not globalized. Increasingly protectionist, not in solidarity. Among the data and the lessons we have from 2009, countries horded N95 masks, even if they don’t work. Countries horded Tamiflu, even if it doesn’t work. Countries horded vaccine as it became available. Most of the people of the planet didn’t get access to vaccine until after the epidemic was over.

There’s no way we would have vaccine in 10 weeks—no way. For anybody, I don’t care how rich you are. And as the epidemic might make another circumnavigation and come back in another form and maybe, finally, some vaccine might be helpful for some people. It would be for the rich people in the rich countries. There is nothing—there’s no platform in existence that could mobilize vaccine on that kind of timetable. Now, you may have heard recently that WHO says now we can make, like, 6 billion doses of flu vaccine. Yes. We can, but diluting it. (Laughter.)

And we now are in a situation where Australia just has ended its flu season. It was the worst flu season in recorded Australian history. The highest death toll they’ve seen. It’s a strain of H3N2 which is on its way here. And there’s a lot of questions. Why was it so bad in Australia? Was it something inherent in the virus? Something different about how people responded? Was the vaccination rate low? It looks like the vaccine just basically didn’t do any good.

A paper just published in New England Journal of Medicine says it has a 10 percent efficacy rate. So for all of you that take comfort every year in the idea of, oh, I got vaccinated, pay attention to washing your hands. (Laughter.) Because, yes, 10 percent is better than zero percent. I got vaccinated. But it’s not going to be a panacea that will protect you. We are a long way from knowing how to effectively make influenza vaccine.

And just recently, we have a study—many of you, I’m sure, already know that the way we make flu vaccine is on chicken eggs, which is not the way most vaccines are made today. And they have to be special chicken eggs that are sterile, that don’t have bacterial contamination and are raised on special chicken farms and blah, blah, blah. So there’s a limited amount of possibility.

FINK: All right. Well, I want to know, we’ve been talking about this problem since you started as a senior fellow here, so—

GARRETT: Well, let me just finish. The point is, we now know that passing through chickens the vaccine actually becomes less efficacious—

FINK: Exactly. So why aren’t we—what are the factors that are preventing us from using all these new technologies that we’ve invested in, that’s we’ve been talking about for years?

SCHUCHAT: Yeah, there’s some—there’s some things that have changed. It used to be that you needed to have an egg-produced strain to make a vaccine, that that was part of the regulatory framework. And that has been changed. So now vaccine virus—a virus that’s grown up to be the basis for the vaccines can be developed through cell-based work as well, and now there’s recombinant approaches as well. So there was a little bit of a regulatory gap. You know, there are lots more manufacturers and there’s many more approaches being used, but most of them still do begin with the eggs. So I think the last few seasons have people really, really thinking about that and trying to understand what are the levers that could diversify the platforms that are used.

But I think—one thing I just wanted to say was it’s really easy to get doom and gloom when you talk about influenza. And then it’s easy for everybody to think you were Chicken Little. Sorry for the pun. (Laughter.) But the—you know, because 2009 wasn’t as bad as we thought. But I think the more that we think about what we do with seasonal flu can help with a pandemic, and what we do with what we’re calling global health security can help with that—you know, that terrible pandemic that’s coming out.

And one of the things that really has gotten better, but isn’t finished, is the detection piece. You know, in 2009 if we had recognized that it was a novel strain in Mexico just a few weeks earlier, the supply of vaccine in the fall would have come at least a few weeks earlier. And that would have made a big difference in the availability of vaccine before the peak, after kids went back to school. With the Ebola epidemic, we really learned the lesson that, you know, diseases on the other part of the world can be here very quickly. And stopping an Ebola outbreak is a lot earlier if you detect it and respond rapidly and surge effectively.

And so right now we’re really emphasizing improving surveillance, improving detection, improving the response capability, so a cluster of deaths in, you know, the Congo is worked up quickly and we figure out what it is so that the appropriate responses can be made. You know, with influenza one of the reasons we have all those strange strains that we’re finding, the animal-source influenzas—is because we have much better surveillance. You know, I think the H7N9 situation in China was detected in people first, because it was not causing symptoms in animals. But because we had really invested in influenza surveillance there.

FINK: And I’ll ask Laurie Garrett this question too, because for years you’ve been keeping us posted as to what the emerging threats are. And fortunately, we haven’t had the big catastrophe. So what do you think? You know, what does work? Have there been some things that have worked? Asian markets and—

GARRETT: Well, the single biggest thing that has made a difference is a decline, but still not 100 percent out of the—we’re not out of the woods on it yet—but a decline in how much of Asia is reliant on live animal markets to obtain their meat. This is our biggest problem, is that all across—from Mongolia down to southern Vietnam, Cambodia, Laos, people prefer to buy a live chicken, a live duck, take it home, slaughter it and cook it. And there’s a lack of electricity for refrigeration in many areas, so you can’t safely buy already-slaughtered meat and take it home, put it in the fridge.

So the human exposure to live birds that may carry the virus is very high. And if you add to it that most of the strains of influenza are carried by birds that are on the Asian flyway, which stretches from basically northern Australia into Siberia, then you begin to understand why all influenzas are all basically coming out of China and circulating in Indo-China and all the way up. And so as we confront the wild animal market problem, and the poultry animal market problem, you get a decline in the amount of transmission. And indeed, in 2013 I think what China—we dodged a bullet there. When H7N9 first emerged, China ordered the live animal markets closed. And wherever they ordered a closure, you got a stop in transmission.

FINK: Well, great to know there are some steps that can be helping them.

So I would like to open the question and answer period, and invite members to join our conversation with your questions. A reminder that this meeting is on the record. So it could be—your questions will be heard outside of this room. So please wait for the microphone. Speak directly into it. Please stand, and state your name, and affiliation, and please limit yourself to one question. And keep it a question, keep it concise, to allow as many members as possible to ask questions.

So we’d like to open it up to you, members. Yes, ma’am.

Q: Gail Gerhart, Columbia University.

John, I wonder if you could give us some specifics about the geography of the 1918 flu. You generalized, but you didn’t give us any idea of what—did they have it in Norway? Did they have it South Africa?

BARRY: It was pretty—it was universal. It—now, in terms of what Laurie was saying, Asia is the most likely source for most influenza viruses. But there’s a possibility—I advanced a hypothesis that 1918 erupted first in the United States, although I’m not—I’m not wedded to that by any—you know, but there’s evidence that may have. Obviously, swine flu was in North America. There are at least 11 pandemics in history that we know about, in the last 300 years. There were probably many events like 2009, but there was no surveillance, so we have no knowledge of them. And it travels all over. Even in 1700, when it took—1698, actually—when it took several months to cross the Atlantic Ocean, it managed to get from Europe to North America.

1918 was universal. It got essentially everywhere—interior villages in Africa, Eskimo villages in Alaska, everywhere except a couple of Pacific islands that completely sealed themselves off, and one or two towns in North America that I know about, and perhaps elsewhere in the world, that also completely sealed themselves off; extremely widespread. And ’57 and ’68 were also very widespread.

FINK: Question. Yes, over here. Please wait for the microphone.

Q: Dan Sharp with the Board Institute.

I’d like to explore the notion of vaccines with you a little bit in more detail. I remember, when we were working on this project together some years ago, the global capacity was a few hundred million total for—if other vaccines were stopped. Has the total global capacity been increased? And, if so, to what?

Number two, if a vaccine were to be produced, taking a few months, you mentioned, Laurie, that it’s—present vaccines are only about 10 percent effective. What is the likelihood that a vaccine would make any difference if, in fact, enough were made available?

And the third part of that is, what is the mechanism for allocating the very limited number of vaccines that would be produced?

FINK: OK, we’ll let you have three because they were all—they were all good questions.

Q: It’s all about vaccines.

GARRETT: Do you want to take part of it? I’ll—

SCHUCHAT: Yeah. I can try to remember which parts. Capacity has increased. But besides just how many manufacturers there are and what they’re making, there have been some things that have been done to keep that warm base going. We now actually have primarily a quadrivalent supply of influenza vaccine in the U.S. for seasonal flu.

FINK: Tell us what that means for the—

SCHUCHAT: That means four different types of flu are targeted—two A’s, and now we have two B’s. We used to only use one B. And so that actually added a fourth strain every year, and each year the manufacturers are kind of cranking it up to produce that much.

FINK: So that gives you more of a chance that you’re going to hit the right one, the one that ends up being—

SCHUCHAT: Well, for the—it turns out that you really have a 50/50 chance of picking the right B strain. So it made sense to put two B’s in there. And it’s often more of a problem in children. And there were reasons that it made sense to expand the annual formulation. But it also means that the manufacturers are producing more vaccine, because each type has to be grown up as if it was its own vaccine.

What you do in a pandemic is either replace the seasonal vaccination or what we did in 2009, you may remember. We all got our seasonal flu vaccines and then we made a monovalent vaccine just against the type. So there is more capacity.

I think the thing with the 10 percent is, you know, that was very—it’s very unfortunate that we’ve had years where it’s zero or it’s extremely low. In 2009 it was about 60 percent effective, the monovalent vaccine we made. The problem wasn’t the effectiveness. The problem was the supply, that it just took too long to get it. We had a spring wave that was a good warning. The manufacturers and developers tried to make product. It took a long—it was very difficult to produce the quantities that they were trying to produce. So we missed much of the fall wave.

So I would say, you know, that it’s always worth trying to produce vaccine, but you have a lot of work to do while you’re waiting for that. And that’s where those non-pharmaceutical measures become important.

FINK: And that was a good question about how we prioritize. And—

SCHUCHAT: Oh, right. For—

FINK: —different communities have looked at that question, right?

SCHUCHAT: Yeah. Well, one of the—one of the interesting things that was done before the 2009 pandemic, in the sort of run-up of pandemic preparedness, was community engagements, to figure out how should you use scarce resources. And it was very interesting to me that the medical groups that looked at this did a very analytic approach. They said where are the deaths going to be? So vaccinate the elderly, because they’re more likely to die. Vaccinate, you know, maybe the very, very young. They’re more likely to die. Or vaccinate people who have underlying medical problems. They’re more likely to die.

When communities were asked that same question—there’s not enough; who should get it first; well, we’re making more—and this is—I know some of you are just back from Puerto Rico—this might hit home for you—they said keep society going. You know, people are going to die from this pandemic. But if we don’t have electricity or we don’t have the banks—or, you know, maybe now we would say the Internet—make sure those critical workers are—and the health-care workers—are actually protected first. And then we’ll, you know, wait in line or something. But they said don’t go for the elderly, even if a lot of us are elderly. Go—because the second- and third-order effects will be so bad if health-care workers and other critical workers aren’t protected.

GARRETT: But I think when we go to the global level, we don’t have a good plan.

SCHUCHAT: It’s a catastrophe, right.

GARRETT: We have a catastrophic situation. The bottom line is that if you’re from a rich country that makes vaccine, you’re going to get more supply or some supply. And the further down the pecking order you are, the less likely your nation is to receive meager supplies, even if they are only 10 percent effective, much less truly effective.

And we need a radically new approach to this whole vaccine issue. It’s not just flu. I mean, the world ran out of yellow-fever vaccine this year in the midst of outbreaks. And the only way we stopped the African outbreak in Angola and Congo was by diluting available vaccine supply five-fold and loading in adjuvant. Those of you that know any immunology know adjuvant is just a polite way of saying here’s some gunk that makes the immune system react more strongly when it’s exposed to the particular antigen, the agent that you’re trying to build a response against.

And that’s one of the things that’s now happened with influenza vaccine supplies. In order to create a greater sense of fairness in the world and try to have supplies adequate to meet poor countries, rich countries, middle income, all of them, the supplies are being diluted and more adjuvant is being loaded in. It’s probably not helping us get to what we need.

What we really need, and everybody knows it, is a universal influenza vaccine with cross-reactivity that doesn’t have to be made freshly every single year against specific circulating strains. And I would add that—and John mentioned this—the pace of the emergence of strains is hastening. It’s not—you know, it’s a pure coincidence sometimes that the strain that happened to be included in the quadrivalent vaccine just happens to be the one that came to town, because we have so much going on out there. And it’s tough to say to manufacturers you have to somehow miraculously get the right combination and guess correctly so that whatever comes swooping into town is reflected in your vaccine.

BARRY: And I’d like to—this doesn’t relate directly to vaccines, but one of the thing—in terms of the ethics of who gets what, you know, there was a lot of planning among governments after—since 2004. And in 2009, many governments paid absolutely no attention to whatever plans had been laid, chiefly because, in most countries, the public-health officials do not have the juice to make sure that they’re listened to. They were—in Mexico, the World Health Organization had to intervene so that the head of their emergency health services was even allowed into meetings on handling—on the Mexican response.

And, you know, Mexico actually told the truth. They ended up getting punished for it. France, Britain, China, India, Egypt all—and other countries—all did totally irrational things or planned irrational things that bore no relationship to either the WHO recommendations or their own internal planning.

One of the reasons I accepted the invitation to come here is because of the audience and the hope that somebody in the audience has some influence on government and get them to listen, number one, to put some money, more money, into the universal vaccine research, which is ongoing; and the other, to get them to listen to the public-health professionals if a crisis does erupt.

GARRETT: And I would add to that. If you go to Donald Trump’s—don’t laugh; this is serious. If you go to Donald Trump’s tweet history, predating him becoming president of the United States, to see how he has responded to outbreaks around the world, in every case his reaction is let’s pull up the drawbridge, fill the moat, and here in our castle America we will be safe.

And there’s—the only evidence that quarantining a nation, blocking yourself off from the rest of the world, has any effect on influenza are the following. One, Tasmania had the lowest death toll in 1918. They did literally shut themselves down. But, then again, we’re not Tasmania.

Number two, our flu season was delayed by two weeks in 9/11 when all our airports were shut down, but we still got slammed eventually.

Number three, New Zealand has done its own analysis of what if that islands nation shut itself off to all travel, all trade. And they figured they would buy themselves 30 days. All right, the United States can never shut itself off to the rest of the world. Our economy, as you point out, would collapse very quickly. And it’s just not—it’s just not possible.

So our big challenge is a president and an administration that is mired in a kind of thinking about disease threats reflected in how they responded to Ebola, how he has responded to the threat of vaccine-associated side effects, and on and on and on. It’s an administration mired in a notion that imagines that America can cut itself off from immigrants, cut itself off from the world, and be safe.

FINK: Well, and clearly even under the previous administration there were some—you know, a nexus between politics and public health and, you know, when there’s a lot of political pressure to do something to stop something scary like Ebola, we saw some, you know, measures taken, like quarantines in certain situations, that were not recommended by public-health professionals.

I don’t know if, before we go to the next question, Dr. Schuchat wants to address the politics versus the public-health issue.

SCHUCHAT: I mean, we have many instances in history where, you know, we or others have reacted poorly to public-health emergencies. And I think there are now a couple of frameworks that help us. There’s international health regulations that got updated after the SARS outbreak that really tried to change the cultures in countries, including, you know, all over the world, to say that transparency mattered and that sharing information mattered because it was going to hurt you to cover things up the way that China did during SARS.

The global health security agenda now is a similar partnership of, you know, about 70 governments and private-sector partners trying to help make sure that every country has the ability to find, stop, and prevent outbreaks, and that the world as a community will surge rapidly and not, you know, let that particular area go. And it’s in everybody’s best interest to do it.

You know, the H1N1 pandemic obviously did start in North America. We were all focused on birds and we were all focused on Asia, and it was pigs in Mexico. And the first cases were literally detected in a research project in San Diego. It was because a new test was being tried out, and two out of the first 25 samples failed. And the people thought, well, this test is going nowhere. And then it turned out those two strains were the first detections of this novel strain that became a pandemic.

So we have frameworks, but I think the thing is how do we behave in the middle of a crisis. And many of the governments in public health, as well as other sectors, have been drilling, doing exercises, practicing. And I would say even with transitions of administrations, there are exercises so that new leaders learn, well, who does what when it comes to an emergency?

You know, we had these three simultaneous hurricanes. And so the administration is dealing with how does it work and what does FEMA do. What does—what do the other departments or agencies do in the middle of an emergency?

FINK: We’ve got a question over there.

Q: Hi. I’m Billy Karesh. I’m a member of the CFR. But for my day job, I do pandemic prevention preparedness work.

Earlier in your conversation, you were—I think all of you were alluding to the kind of external components, outside the medical world. So, Laurie, you were talking about live-bird markets and birds migrating. But then the conversation always seems to fall back to a better vaccine. So we kind of have this—I think society is all looking, well, the medical community is going to solve this. But these problems originate beyond that.

And so we have a term One Health, which is the health of the environment and the health of animals and the health of people, that are inextricably linked. But for some reason the burden—when people start dying, the burden is why didn’t the medical community do anything, when, in fact, the prevention, the risk reduction, is outside of the purview of the medical community.

FINK: The question?

Q: So the question is really where do you see those opportunities for engaging these other parts of society? How do we engage the environment sector and the animal sector to work with the health community and say we’re all in this together? Do we share money? Do you share budgets? You know, what are some of the ways to deal with that?

GARRETT: So one thing to think about right away is there was a really powerful paper published in Science Magazine early this summer; multiple authors from all over the world tracking how climate change is affecting the migratory routes of hundreds of different animal species and plant species. And the most dramatic shifts have been in fish populations.

So, you know, cod used to be the staple of Portugal, and now you have to go above Greenland to catch cod. When I was in Greenland, everybody was complaining, all we can find is this crummy mackerel. The patterns of fish shift. When the fish change, the birds change, and you go up the whole order of things.

China’s environment has been devastated by its pollution. And its air pollution is so acute that many migratory birds can’t actually find their routes and are going off in other routes. And the water supply for landing of birds has changed.

So one theory about why H5N1 mutated in 2005 into a form that then affected birds that did the East-West migration and took it into Europe and Northern Africa is that the migratory route for the birds coming from Indochina up to China had become so polluted and the water supply so devastated that more and more of those birds were all co-landing in one giant lake area. I think it’s pronounced Qinghai, Lake Qinghai. And there, there appears to have been a mixing of them—

FINK: So I think you’re saying that the—

GARRETT: —that allowed the mutation of the virus.

FINK: —premise of his question is correct. But his real question was, how do you get those sectors interested in investing—

GARRETT: Well, what I—no, I’m trying to get there if I could finish.

FINK: Please.

GARRETT: And that is that we, you know, we need to make the links with climate change, we need to make the links with the Anthropocene and planetary health movement. There needs to be a sense that all of this is a common struggle. And seeing each little piece of the influenza problem on its own is a valid thing for trying to address a specific flow of cash and a specific technological solution. But the real threat and why the threat parameter is getting greater for influenza has to do with the larger change in how we’re all living on this planet and what we’re doing to the planet.

BARRY: Basically, we need somebody to write another “Silent Spring.”

GARRETT: I’m working on it. (Laughter.)

FINK: Up here, please.

Q: Joelle Wyser Pratte, OCP Capital.

So one of the things I think has resonated, but maybe not—I have another question. And that is, if the drug companies aren’t keeping up with the rate that the viruses are changing—in part because they’re not being financially remunerated because they change so fast that the drugs they produce aren’t making enough money to keep producing, the R&D is the question—so what other sources of capital are available? How does this play into the universal vaccine that you’re talking about? If the drugs are between 10 percent and 60 percent effective and declining or maybe not, how does that all work?

GARRETT: Actually, the drug market is worth $4 billion for the vaccines.

SCHUCHAT: You know, one thing—yeah, yeah. I think the market is—it’s very unusual that—

GARETT: It’s robust.

SCHUCHAT: You know, the use of flu vaccine has pretty much doubled in the past decade. But there’s not much incentive—some would say, let me preface this—some would say that there’s not much incentive for companies that have a lot of the market to change their approach. If they, you know—if we’re reaching 70 percent of seniors every year with flu vaccines that they do make money off of with the egg-based approach, is there a market to change that completely when there’s going to be a development and risks and so forth?

The universal—you can think about it from the market terms. The universal vaccine, which we as doctors or community members may think is fantastic as an idea, might be something that you get a couple of times in your life, not every single year. And so the return on that may be different and the science is complex.

And so I know, you know, Tony Fauci wants to think of it as, like, our Manhattan Project like we did with the antiretrovirals. We put a lot of infusing money as well as getting the best scientists attracted to work on it so that we will get something better, but I don’t know that the vaccine industry itself has as much of an incentive to take it on.

GARRETT: But just to go to your point, the seasonal market, seasonal flu market, in just seven countries combined—U.S., France, Germany, Italy, Spain, U.K., and Japan—is $4 billion.

SCHUCHAT: Yeah, and let me just—

Q: (Off mic)—Viagra, though, isn’t it? (Laughter.)

SCHUCHAT: Yeah, but it’s still huge. No, but what vaccine companies would say is they’re, like, the bottom of the totem pole because you don’t—even a flu vaccine that you get every year you don’t get every day. You know, it’s not like the pills.

And the other thing is, you know, to just say something on the record about the vaccine companies. You can spend a lot of money and a lot of time developing a product that maybe works and then you can have an unexpected safety problem. You know, the Philippines has just suspended use of dengue vaccine. And that, you know—it was a lot of research to go and to try to get us a product that was at least partially protected and then to realize, well, maybe there’s some issues there. So it’s a complex market, I think.

FINK: OK. Boy, lots of questions. How about you, right in the center there.

Q: Hi. Jove Oliver, Oliver Global.

I’m wondering, like, how, when we’re looking at the sort of traditional infectious diseases, like tuberculosis or HIV that are with us, you know, how much does sort of investments globally in the infrastructure to fight those or the general infrastructure to support health systems pay dividends on flu? We hear a lot about vaccine, silver bullet, universal vaccine. How much does the sort of incremental, slow, grinding progress that we try to make on even noninfectious, noncommunicable diseases, like diabetes and cancer that are blowing up in the developing world, how much does that pay extra dividends?

SCHUCHAT: Yeah. You know, for sure, the global surveillance efforts have benefited from longer-term initiatives. You know, as we were in—2005 when the CDC started to get resources to expand global influenza surveillance and to help countries develop capacity, a lot of the sites that were developed were built on the polio laboratory network. You know, that had been a big eradication initiative and there was capacity that could be expanded and adapted.

I think that the surveillance is a little bit easier to translate—the rapid response, epidemic investigations, you know. Right now, there’s actually joint teams that go out. Animal health and human health will go out for unusual clusters to investigate. But I think the manufacturing and R&D doesn’t really build so easily.

GARRETT: And polio is a really good point which you bring up, because we have this vast polio surveillance network because we want to eradicate polio. We’re this close to achieving eradication. And then we go to the next stage, which is there will have to be massive environmental surveillance looking for any wild-type polio that shows up in sewer systems and water supplies, so that we can pounce quickly on it.

If we can do the smart play, we can build influenza on top of that existing infrastructure. And the danger is that everybody that’s funding polio eradication is going to say, oh, goody, it’s eradicated, I can move my cash somewhere else. That includes Bill Gates who is the number-one funder of that effort.

FINK: Interesting. OK, how about right there. Just wait for the mic, please, sir. Thank you.

Q: Michael Alderman.

Laurie, you made the point that in the 1918 epidemic, people died of the flue. Subsequent epidemics might involve older people and there might be secondary infection with pneumococcal disease and that might be an important cause of death. Do you think there’s any money in the idea of really pushing a pneumococcal vaccine as something that is ahead of the immediacy of the outbreak of an epidemic?

GARRETT: That’s already happening.

BARRY: Yeah.

GARRETT: Gavi is already doing that globally.

And you’re doing that at CDC.

BARRY: Anne was the head of the program.

SCHUCHAT: Yeah. And we definitely—you know, in 2009 when the influenza season came in the fall instead of the winter and spring, we did have a very early pneumococcal pneumonia season as well. But now we have, you know, two vaccines for adults: The polysaccharide vaccine we’ve had since the ’70s and a conjugate vaccine that’s been used in children since 2000, but the newer formulation is available now for adults as well, and it’s routinely recommended for people 65 and over.

We recommend you get one of each, you get a conjugate vaccine followed by a polysaccharide. But if you already had gotten the pneumococcal polysaccharide, we recommend you get one dose of the conjugate.

GARRETT: Tell them about the grandchildren.

SCHUCHAT: Oh, yeah. So the most amazing thing in the early 2000s, we started vaccinating kids under 2 against seven types of pneumococcal disease. And, you know, at the time, we were talking a lot about flu and we were trying to figure out, could we get a dose-sparing regimen for flue? You know, we were trying to make this H5N1 vaccine.

Well, with the pneumococcal vaccine, we got the ultimate dose-sparing vaccine because we had the seven types that the vaccine targeted in young children. We saw a 97 percent reduction in people over 65 getting bloodstream infections caused by those seven types, without a single dose being given to the seniors, just by vaccinating the children.

GARRETT: Especially the grandchildren.

SCHUCHAT: So, you know, and that actually may work for some influenza, you know, the issue of vaccinating school-age kids who are a big reservoir for spread to others.

BARRY: Yeah, I have a comment regarding who died of influenza, who died of secondary infections. Most of the scientists who look at that these days believe that the overwhelming number of deaths were secondary bacterial pneumonia.

FINK: In 1918.

BARRY: In 1918. Personally, I do not—I certainly think a majority, but I think there was a very significant minority of this that were caused by the virus, chiefly because, as an historian, I have maybe more respect for the work of the people whose papers I was reading. And pneumonia was the number-one cause of death back then. They were very familiar with what an autopsy looked like of someone who died of secondary bacterial pneumonia. They were all repeatedly amazed by what they found. But without a doubt, I think a majority.

However, even with antibiotics today, you still have a pretty high mortality rate from pneumonia following influenza, bacterial pneumonia following influenza.

Also, in 2009, you had almost two entirely different diseases. The overwhelming majority—and first, the worldwide death toll was probably around 300,000, about 12,000 in the United States, which is significantly less than seasonal influenza. But you had, as I said, almost two different diseases. The overwhelming majority of cases were very mild. But the people who did get sick, it was like 1918. And there were a lot of viral pneumonias, if not an overwhelming—and I don’t recall the exact numbers, but a tremendous number of viral pneumonias. And it was also a much younger population.

FINK: Pregnancy then and—I want to get one more question in—

BARRY: Sure.

FINK: —before we have to end. Please, sir.

Q: Hi, Gligor Tashkovich, AlphaSource Capital Securities.

Laurie, I think it was you who said that the effectiveness rate of H3N2 vaccine in Australia was 10 percent this year. Did we—if Australia is our canary in the coalmine, did we—do we have enough time to improve the effectiveness for our use when it hits us?

GARRETT: Well, you can answer that.

But let me just say one thing. The Australian—again, there’s a lot of parsing, trying to figure out what happened in Australia and there’s a lot of debate among Australians about what happened in Australia. But one suggestion they have made is that they think that the vaccine didn’t have staying power. And there are a lot of people who got vaccinated very early in the epidemic, got infected late in the epidemic. So they’re actually suggesting you get twice vaccinated.

SCHUCHAT: Yeah, there wasn’t time to change the formulation of vaccine for the Northern Hemisphere, but there has been a recommendation to change the composition of the vaccine for the Southern Hemisphere. So it’s just, you know, twice a year, the world powers, including us, decide what strains should go into the influenza vaccine. And because we have to count on it taking about six months, that decision is made, you know—we’ve moved it back from late February to early March to try to catch the late-season strain. But essentially, in early March the strains are selected that will be used in the summer/fall vaccination that hopefully many of you have already gotten.

FINK: I’d really like to thank our panelists for taking the time to inform us—(applause)—Anne Schuchat, Laurie Garrett, and John Barry.

And a cocktail reception will be following this meeting, and we hope you will join us. Thank you all for joining us tonight.

(END)

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