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The Threat of Global Pandemics

Speakers: Michael Osterholm, director, Center for Infectious Disease Research and Policy, University of Minnesota; associate director, National Center for Food Protection, Department of Homeland Security; professor, University of Minnesota School of Public Health, Rita Colwell, chair, Royal Institution World Science Assembly's Pandemic Preparedness Project, Laurie Garrett, senior fellow for global health, Council on Foreign Relations, and Anthony S. Fauci, director, National Institute for Allergy and Infectious Diseases, National Institutes of Health
Presider: James F. Hoge, Peter G. Peterson chair, editor, Foreign Affairs
Introductory Speaker: Nancy E. Roman, vice president and director, Washington Program, Council on Foreign Relations
June 16, 2005
Council on Foreign Relations

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Washington, DC


NANCY ROMAN: I will leave the introductions, of course, to Jim Hoge. But I do want to say what a treat it is to have him here. Many of you know him. He is the editor of Foreign Affairs. His impressive journalism career is detailed in the bio that you have, but for the last 12 years we've been fortunate to have him running the magazine, which is, one, making money, two, really impressive. We now have 140,000 readers of any given issue, and it is really first-rate. And it's a treat to have him here, because he's very much a New York kind of guy.

JAMES HOGE: Thank you, Nancy, very much— although I did spend about eight years here once. I loved it.

Why are we here today? Let me set this in a little bit of context before we get to our panelists, but I'll keep it brief. If we take the outside concentric circle, history tells us that we are doomed for a major pandemic. There were three in the last century. Time is up, so to speak. A closer concentric circle is that there is one influenza or avian flu that is out there now and operating that presents a particular prospective danger. And you all have been reading about it. Lots of people are now covering this story about the avian flu in Southeast Asia, which is known as H5N1. It is particularly lethal for animals, and unless it was to mutate into a milder form, it would be terribly lethal to human beings, on the scale of the influenza of 1918. And of course, given the much larger population today, and the mobility of populations, the impact of that would be enormous. We'll get to that in a moment.

But still, why are we here, if everybody else is covering it? It was our feeling at Foreign Affairs, at Nature magazine, and at the Royal Institution World Science Assembly [RiSci] that a catalytic push was needed in addition to coverage that might help inform the public to a problem out there that needs to be addressed. A catalytic push was needed to the agents of change, so to speak, whether they be international organizations, national, or to borrow a phrase from homeland defense, the first-line responders in communities around the world. So we have done a special section in Foreign Affairs. Nature has done special coverage in its May issue, and more follow-up to come. And the two of us were brought together, so to speak, by the Royal Institution. And they are going to follow up as well, and we'll hear about that before we're finished.

Now with that as prologue, let's get to today's discussion. And we have up here Anthony Fauci, who is director of the National Institute of Allergy and Infectious Diseases at the National Institute of Health. And on my immediate left is Laurie Garrett, who is the senior fellow for global health, Council on Foreign Relations. And next to her is Michael Osterholm, who is director of the Center for Infectious Disease Research and Policy, University of Minnesota; also, associate director, National Center for Food Protection and Defense, Department of Homeland Defense; also a professor at the University of Minnesota School of Public Health. He brings a lot of credentials.

We're going to discuss it up here for about 20-25 minutes, and then I'm going to ask Rita [Colwell] to explain the ongoing role that RiSci is playing, and then we'll go to you for questions. So let me just start with— as I say, there's been a lot of coverage, but what is— Laurie, what is the danger? This is a highly lethal flu virus for animals. Why should we as human beings be so concerned at this time?

LAURIE GARRETT: Well, the major thing to remember is that influenza is an animal virus, a bird virus. So we always see it in birds, and we always need to be watching what is going on with the flu virus in any given season, how it's mutating, how it's changing, in the bird population, particularly in aquatic migratory birds in the Asia flyway, a flyway that extends from southern Indonesia all the way up to southern Siberia.

We always see flu emerge from that setting, and we always have to be nervous and anxious about what sorts of strains may be emerging, what may be coming. What we're very nervous about this year is that particular strain that seems to be emerging as this H5N1, which is 100 percent lethal to chickens, and appears now in a fashion that may be unprecedented. We don't really know ancient history, but it's certainly unprecedented in the timeframe in which people have been observing it. It's also lethal to the usual host species, meaning the very migratory birds that carry it, and to a whole range of ducks and geese and so on. So this is really very, very troubling, and very concerning.

Now why this year or next year, why this particular timeframe in history, should be of special concern, beyond the nature of this H5N1 is that we have— as you said, we are overdue. We also have a whole set of circumstances changing in that ecology, that ecological setting.

First of all, we have far more domestic birds. We have a huge amount of poultry production going on, as the GDPs [gross domestic product] of China in particular and many of its neighbor countries rise. So as Asians become wealthier, they're able to eat more chicken. And as a result, we have statistical odds that you're going to have a greater likelihood of transmission from the migratory birds to the chickens, to the humans.

The second problem is that the flyway itself has become severely polluted, severely damaged, so that the migratory animals are forced to land on farms, land near industrial areas, land therefore in greater proximity to our species and to species very close to us, so the odds of any given flu jumping species closer and closer to our level in the pecking order, to use a bad pun, are increasing steadily.

HOGE: Michael, it's primarily an animal community now. Why are we concerned that it may be mutating, if that's the proper way to look at it? And if it does, give us sort of an overview of what the consequences will be, how it rolls out.

MICHAEL OSTERHOLM: Well, first of all, thank you for the opportunity to be here. I think that probably if I had to summarize my 30-year career in public health dating back to antibiotic resistance to HIV/AIDS, et cetera, and put it altogether, none of it equals, combined, the potential impact that this will have on society.

First of all, just to follow up, as you laid out, Laurie and Jim, the terms of your question, make no mistake about it, of all the infectious diseases ever in humankind, influenza is the lion king. And we forget that, and that's been one of the important concerns that in modern medical science today we somehow think that we can either forget about the past, or that we've taken care of that past, and we haven't.

We really have no armamentarium today that is any different on a whole than what we had 100 years ago, at least in terms of what's available to the world's population. We have vaccines, we have some antivirals, but they will be in such insufficient quantities as to be what we like to say, "Filling Lake Superior with a garden hose," in overall impact.

The question you're asking is, remember that pandemics have been happening dating back to antiquity. This virus emerges out of birds, it goes through genetic changes which then allows it to infect humans. And it takes that right lock-and-key mutation to occur. Typically in the past what's happened is, the bird virus and a human virus will get together in the same cell. This particular virus is a very promiscuous, very indiscrete, and a very careless virus that will allow it to genetically combine with other genetic material from other influenza viruses. When a human strain and a bird strain get together, they make a third strain, which has many times the principles and properties that are bad for humans, but now also can be transmitted between humans.

That has gone back to antiquity. In 1918, we all know about that particular pandemic. If you look today at the best data we have, based on recent historical review of country-by-country mortality, it's clear that that virus killed between 50 to 100 million people in 1918 and ‘19, in a world population that was only 1.8 billion in size. We've had several subsequent pandemics of much lesser impact. But if you go back in history, 1830 to 1832, the mortality in the world was just as bad as it was in 1918. So what we found is that some pandemics are worse than others, and it depends on the virus that infects the human population.

The difference with this situation is, unlike 1957 and ‘68 where, yes, we had thousands and thousands of deaths, even in a place like the United States, this virus has the characteristics of killing like 1918 did, or 1830, where it actually turns your immune system on its head, and it causes that part to be the thing that kills you.

In 1830— or excuse me, in 1918, the vast majority of deaths were healthy people between 20 and 40 years of age whose own immune system killed them. And it wasn't the very young and the very old. Today we don't have much better tools to handle that situation than we did in 1918. As I noted in my article, in this country today we have 105,000 mechanical ventilators. On any one given day, 70-80,000 are in use, just with routine medical care, and during just a mild flu season we get right up to the 105,000, and we're moving ventilators around like we do donated organs, to make sure that they're there. We have no capacity. So what we're worried about is that this virus is due to spin out again of this bird population, as Laurie pointed out. This time, if it is the H5, it has all the bad characteristics of causing this kind of severe problem.

If you were going to extrapolate 1918 to the United States today in terms of mortality, and with the world population change, today you would expect to see about 1.7 million deaths. And that is unfathomable when you think on a worldwide basis, that's 360 million deaths. And I think that when you think about HIV/AIDS having killed about 28 million people from the beginning of the pandemic in the early 1980s to now, it gives you a relative perspective, particularly when you think about how these are going to be very healthy people. And we have every reason to believe that the H5 situation in Southeast Asia very much could be just that kind of situation.

HOGE: One follow-up question, quickly. There have been in the neighborhood of about 60 human deaths because of this so far.

OSTERHOLM: Right.

HOGE: Describe them, because that's hardly a pandemic. So what has not yet happened, and what is about to happen?

OSTERHOLM: First of all, the virus to date has made its way in isolated situations from birds to humans, where basically— and I, too, don't mean to make a pun; this is actually a real term in public-health epidemiology— they have been what we call "dead end" hosts, meaning that the virus ends there because they're not able to continue to transmit the virus. Not enough genetic changes have occurred. These deaths largely have been, as I said, in previously healthy people, in that age group that we talked about of the 1918 kind of situation. And they died deaths very similar to that of 1918.

Even though these patients have been in Southeast Asia, and you think of a very different healthcare delivery system, let me remind you that there are some outstanding healthcare delivery systems in those areas, and many of these patients received what we would consider in this country high-level tertiary care, and died anyway. And again, the— all the data we have from the virus, from the host, autopsy, and so forth, supports this 1918-like picture.

If I could just add one piece to that, quickly, it used to be— I mentioned— we thought of virus re-assorting, the fact that you had to get these two promiscuous viruses together to recombine. One of the things we're very worried about in today's situation versus 1918 is that, in fact, we have so many new hosts available, that virus can transmit between those billions and billions of chickens in one year more so today than it used to be able to do in a whole century.

So each time that that virus moves from one infected bird to another— or to a non-infected bird, that's one more chance for a mutation, that's one more chance for slow gradual changes. And what we have seen since the 1997 introduction of this virus into Hong Kong is a very rapid change in this virus. Today, the H5N1 in Southeast Asia is not the same one that was in Hong Kong, and everything about it has mutated towards getting close to this human-transmitted virus that may never need a re-assortment. It may get there on its own, because we've given it so many ample opportunities at the crap table to basically just throw it and come up with the right set of mutations. And that's where it's moving, and that's why we're so concerned.

GARRETT: Can I just make a real quick point of clarification, so everybody— we're all on the same table. We first observed— we, the world community— first observed this virus and recognized that something new was happening in 1997 when a little boy became ill with what was determined to be a super-virulent chicken flu in Hong Kong.

So when we talk about an arc, we're talking about a time period that starts in 1997, roughly. Where did that virus come from? Best evidence is it came from the province immediately to the north of Hong Kong known as Guangdong Province, China, which seems to be a real cauldron for the emergence of flu viruses, and frankly, was also the cauldron for the emergence of SARS [Severe Acute Respiratory Syndrome].

And the other thing is, a lot of the data points you will hear, and when you— any of the journalists in the audience that may be thinking of writing stories, it may get confusing. You may hear somebody say, "There were 100 cases," or, "There were 50 cases," or what have you. It depends on whether the observer is taking their demarcation point from 2003 when this virus made another evolutionary shift and emerged in Vietnam, or are they taking it from 1997, when it first emerged in Hong Kong. Just wanted to make that clarification.

HOGE: Thank you. In a moment, we're going to talk about the state of preparations and planning, and what has been done and what needs to be done. But before we get there, Tony, I want to address what idealistically would be the best answer, which is, to contain this at its source at the time it is beginning to occur, rather than once it's going around the globe as a pandemic. What is the likelihood, what are the problems of trying to deal with this particular flu, or any other one, I suppose, but this one at its source, which is primarily in Southeast Asia?

ANTHONY FAUCI: That really is one of the real major problems, is that if you look at what has evolved over the past few years, given the relationship between economies of the countries involved and the relationship between flocks of chickens, the cross-contamination with migratory fowl, and the dependence of individual countries on these chicken flocks, it would have to be almost an economic revolution in the countries to be able to address it in a way that would essentially put a major block in the way of the ultimate progression.

I think the things that people don't understand, and we were just discussing this outside, we may well— in fact, it is highly likely— that we'll get away this year without there being a pandemic flu. But then what people will say is, "Well, OK, we've dodged that bullet. Let's move on to the next problem, whatever the next problem is, and likely not influenza." But the ingredients that have gone into the situation where we are right now, where we have over 100 documented infections, 54-plus deaths, is not going to go away, because the chickens are still infected, the customs and practices of the interaction between fowl, pigs, and humans in these Asian countries is not changing. So that the ingredients that gave us the issue that we have now are going to reappear next year. It may still be H5N1 or it may be H9N2 or it may be something else.

So unless we, as a global effort, get the countries involved to take a look at the conditions in those countries, and how we can alleviate them without destroying the economy of those countries, this problem is not going to go away. So that's the point source. And then there is a number of other layers of prevention that we— I'm sure we'll get to talk about.

HOGE: I want to take you back to the source. You described quite ominously what the problem is, which is the nature of farming there, the number of animals, and so on. But, practically, is there anything we can do about that at this stage, since we know that that is at the core of the problem? Are there steps that can be taken? Are there funds that can be invested, and if so, what should they be invested in?

FAUCI: Well, yes, but it has to be not just funds from the Western world to the Asian countries. It has to be a partnership among the countries. And there are enlightened people and organizations and nations there, so it isn't as if it's them against us.

But we really need to continue to get the global public spotlight on that, so that transparency is absolutely essential. We cannot have, for example, what we had in the early months of the SARS epidemic in China, and only when it got to Hong Kong was there a degree of transparency.

We can't have cases in Vietnam or even in China, be they human cases— or even in China, be they human cases or bird cases, without there being a total transparency of what's going on, transparency not only in the local and then, ultimately, global public health area, but also exchange of isolates. For example, if there is H5N1 now that is percolating in China, we need to know how that relates molecularly to what we know is now in Vietnam, because if it's drifting a bit to the point where it's different enough from the H5N1 that's in Vietnam, those of us like our organization and others that are developing a vaccine, that are looking for resistance or not to Tamiflu and other antivirals, we need to know that. So there needs to be transparency and cooperation, and maybe even economic help. I'm sure that's part of the equation.

OSTERHOLM: Jim, if I could just add a piece to that. Because I think the question you're asking is, what can we do right now? And the bottom line message is, almost nothing. Understand that there are 12 billion to 13 billion chickens in China. A chicken basically has a life of about six months before they're harvested. So even though we talk about having killed off 300 million chickens in trying to reduce it, we turn over billions of chickens a year in China just for food supply. Each one of those that are born and hatched are brand new incubators for the virus, too, so we keep re-supplying this susceptible population, we keep allowing this.

The only thing that will work is one day to have an effective vaccine that is cost effective and effective scientifically. Now first of all, finding something cost effective, it would have to cost pennies at the most in American dollars to be able to be used over there, otherwise it won't be cost effective and won't be used.

Second of all, we're nowhere close to an effective vaccine for birds that will interrupt this wild bird/domestic bird-to-human potential. So what we have to understand is that we've got ourselves in this fix. We've known for decades that this was going to be a potential. And we didn't do the research. We didn't invest in this area. Think about even a human vaccine. Today we're using a human vaccine with one slight change to it, and an important change, but it's basically the same basic vaccine we used in the 1950s, 1960s, a vaccine that was common when we used a slide rule as the state of the art for mathematical calculations, and today we use the computer.

Where has the comparable increase in technical ability been? And so, until we make that jump in technical ability for animals or for humans, we are stuck with this immediate situation without an apparent real, just, "Come in, we'll solve it," kind of situation.

HOGE: I just want to summarize a point here, because I think it's important. But I wanted to jump from the moment to, OK, a pandemic starts, what is the state of our preparations and so on? But I think this point is so important I just want to underscore it with a quick summary, and that is the timeline question. As Michael said, if a pandemic involving this particular virus was to start this summer or fall, we are totally unprepared and there is very little we can do about it. If it starts two years from now and we do the right things now, it'll be bad, but it'll be— we can at least contain it at some point. If we start preparing now and it doesn't happen until five years from now, we may be in reasonably good shape. Now, why even think about five years? Because as Tony pointed out, and I've read in all the literature, H5N1 and variants thereof are not this season's dilemma. It will be with us for many years. Now let's go to the broader questions of preparation in there. Laurie, maybe we can deal with the issue of, why pharmaceuticals have not been doing more than they've done? But why don't you pick up where you wanted to start?

GARRETT: Well, I wanted to just say, I think that the foreign-policy picture here, we could lose a lot of what's going on if we don't pay attention to a few key details. First is that, just to underscore something on the scientific level, and that is that this constellation of hemagglutinin type-five and neuroaminidase type one, which is why we say H5N1 flu, these are markers on the flu virus, this particular constellation as far as we know has never ever circulated in the human population before. So there are no naturally immune humans walking around. None of you are immune to this virus. That is a marked difference from anything we've dealt with historically, because in the past, there's always been a reservoir of immune human beings to whatever was circulating around, at least in the past that we know.

UNKNOWN: Not 1918.

GARRETT: Well, why do you say that?

UNKNOWN: Because it was the first explosion of H1N1 in 1918.

GARRETT: But I thought that in the 1880s there had been a similar outbreak among the elderly population.

UNKNOWN: But it's unlikely it was H1N1, that's the point. H1N1 was the first— it's the same thing, you're experiencing something that just as you said, nobody has experienced.

GARRETT: So you don't have an immune system that is going to say, "Ah, I recognize this one." And that is one of the reasons, by the way, that the immune response is so severe. Because if you have a very, very healthy, strong immune system, you're a young adult, you're taking good care of yourself, and you have a strong immune system, your immune system will see this extremely foreign thing and actually overreact. You'll actually have an astonishing response to it, which can lead to this thing called ARDS [acute respiratory distress syndrome], a syndrome in the lungs that is overwhelming.

And it is why for many, many years, skeptics argued— and I know Michael and Tony and I were all in these meetings— in the early days of people warning that flu might be a problem, skeptics said, "Ah, 1918 they didn't have antibiotics, and that's why so many people died. But now we have antibiotics, and it won't be a problem." Wrong, antibiotics probably would not have made a big difference in 1918, because those young adults that were dying, it was their immune system going bananas, having seen something that their body had never seen before. So I just want to make that side point.

Going into the foreign-policy things, I think there are a number of things that we can look at that are short term, long term, and longer term, foreign-policy interventions that we could be thinking about right now. The ecology is changing rapidly in the fly zone that we're working about, in that ecological setting in Asia. It's not just, as Michael points out, this astounding increase in chicken production and the turnover, but it's how chickens are being raised. It's the nature of how people are coexisting with their poultry and other farm animals.

It used to be that the paradigm we worried about was the small farmer who lives on the edge of a rice paddy and has a couple of ducks, a pig, and maybe a couple of chickens, and the flying aquatic bird would land in such a setting. Increasingly, of course, we're seeing poultry operations that rival Purdue in Arkansas, massive-scale poultry operations in Thailand in particular, and southern China, and parts of Singapore, Hong Kong, and Taiwan. And the question is whether those people running those operations have any concept of appropriate hygienic conditions or any attempts to try and create appropriate settings for growing massive amounts of poultry.

These are the sorts of things that one would like to see our USDA [U.S. Department of Agriculture] and counterpart agencies from other advanced industrialized societies, working closely through the Food and Agriculture Organization and OIE [World Organization for Animal Health] to try and facilitate improvements in the nature of how that poultry is being raised. That's the kinds of interventions that could be going on right now, but they need a lot of support, a great deal of financial support and political support to be executed properly.

And I think the other thing is that the huge ecological difference is that, in Asia, people prefer to buy a live chicken, take it home and slaughter it. We buy chicken meat already chopped up in the market. The difference is huge in terms of human exposure. And any of you who have traveled in Asia have seen the old ladies that think that the right way to tell if a chicken is perky and young is to pick it up and sniff the rear end and check it out— a lot of exposure going on there.

In incredibly densely populated settings like Hong Kong, one would like to see centralized slaughtering going on. One would like to see a discouraging of the live market sales and the stacks and stacks and stacks of chickens in cages right in densely populated walkways. And these are things that the international community in a collegial atmosphere, in a non-judgmental, non-punitive atmosphere could, over time, be encouraging key Asian nations to be thinking about and addressing.

These are cultural issues, though, that are very, very deep, and they're not going to change just because a lot of Americans are suddenly very nervous. They're going to change in a concerted process. It's going to have to engage APEC [Asia-Pacific Economic Cooperation] and other major international institutions in Asia, and there is going to have to be a sense that we're all in this together. And on the transparency question, that is something that is changing. And China experienced great shame in having been caught in a lie— in a massive lie that killed people outside of its own borders.

HOGE: You're talking about SARS?

GARRETT: I'm talking about SARS. And we are witnessing a real shift in transparency in China about disease, a shift that I believe is headed in a good direction.

But there has to be some payback for engaging appropriately, for being transparent, for slaughtering chickens, and so on. If you're looking at an agrarian society like Vietnam, like Cambodia, like Laos, if each one of those individual farmers who may have a chicken flock with bird flu is compelled to or ordered to destroy all those chickens and there is no reimbursement, there is no payback of any kind, all you're going to see is a steady increase in resentment against those outside powers that be, whoever they may be out there, that— us, America, somebody— angry at them and worried about flu.

There have to be mechanisms in place that do not penalize nations for their openness, and do not penalize at the local level those farmers who willingly are slaughtering infected animals.

HOGE: OK, before we go to the audience, I want to call on Rita Colwell, who is the chairman of the Royal Institution World Science Assembly's Pandemic Preparedness Project. There are several aspects of this subject we can get into during the Q&A period that we haven't had time to touch on. One is the wider economic and social concerns that one would have, and the other would be, what are some of the very specific obstacles to getting better preparation? And, what are some of the centers that could be offered up?

Now RiSci, who brought us all together, has these kinds of concerns very much in mind. And Rita, you might explain where we go from here.

RITA COLWELL: Thank you very much, Jim. The RiSci is a 200-year-old institution that is based in Britain but has offices in New York and London. It's really focused on the highest levels of global leadership, mainly to bridge the gap between policy and science.

Now back in 2004, there was a concern amongst those of us involved with RiSci that this pandemic was going to happen. I was asked to chair. Why did I choose to chair? Well, I worked with cholera my whole career, and there the epidemics, if I may, are puny compared to the description that I'm hearing here today. Having worked in epidemics where we may see 100,000 people in a country like Bangladesh, here we're talking about millions of people globally. So it became very obvious that we needed to bring the top scientists and politicians and industry leaders together.

Being a private institution, that was possible. So we've assembled a steering committee with officials from the WHO [World Health Organization], the U.N., the European Commission, the Chinese, Canadian, South African health ministries, executives from pharmaceutical and biotech corporations, and very importantly, the editor of Foreign Affairs and the editor of Nature, as well as the senior scientists who are expert in influenza, SARS, and HIV viruses. Now we have the issue of Foreign Affairs which has appeared, and to which reference has been made. And the issue that appeared recently by Nature, focused on influenza. Now where do we go from here? The desired outcome really for us is to be able to align the plans of all the countries for the pandemic.

At the moment, the coordination seems to be rudimentary at best. And we would also like to do the cost-benefit analyses that would perhaps be more persuasive to the policy-makers to invest in the preparedness measures that we have been discussing. And then reference materials being made available, and then possibly to force the increased production of Tamiflu— and maybe Tony and Michael and Laurie might want to address that as well— but to build capacity regionally around the world to address this pandemic.

I would point that, as Tony has mentioned, that perhaps we may not have the pandemic this year. It might be next year. But in any case, for any pandemic, we should have a global capacity. So this is an opportunity to do that.

Now the next steps: On July 6th, we'll have a videoconferencing between Washington, New York, and London, and with Asian current leaders as well, involved as a kind of virtual workshop to address the— to operationalize the actions that we can take to address this pandemic. Now there are websites for all three partners— the Foreign Affairs, Nature and RiSci, which are available and cross-linked, which is very important. I think this is the first time that policy-makers and scientists have been brought together in such a forceful way. And I would just finally just mention that also in the audience are [RiSci President] Dan Sharp, [RiSci representative] Nelson Gonzalez, and [head of the nonprofit consultancy firm, the Ulanov Partnership] Nicholas Ulanov, if you want to speak to them after the meeting.

But this is an opportunity, I think— unprecedented— to work with global leaders and with powerful opinion-makers to address a problem that I think is incredibly difficult and important. Thank you.

HOGE: Thank you, Rita. Raise your hand if you have a question, identify yourself, and wait for the mike. Yes, sir, we'll start back— yes, ma'am, excuse me.

QUESTIONER: I'm Anne Solomon from the Center for Strategic and International Studies [CSIS]. I'm interested in the question of the role of the private sector and the involvement of the private sector in this problem, in terms of product development, manufacture, and also stockpiling, and the issues in terms of getting the private sector involved not only in this problem, but also in bioterrorism, the development of bioterrorism countermeasures. I'd like to have the panel members make any comments on this, and especially the question of whether or not the government should take over some of the responsibilities for the manufacture of biologics, for which we have a dearth of manufacturing capability globally, and certainly in this country.

HOGE: OK, a big subject, and I think you're all probably going to want to— let's start with Tony.

FAUCI: You put up a very good point, the analogy between the incentivization of industry and partnering with industry in the arena of biodefense countermeasures is strikingly analogous to the problem we face with vaccines in general, and much, much more emphatically on influenza vaccines, because of the risks involved on the part of industry, because of the tenuousness of demand and the market, and the fact that industry and the ones that want to get involved could do much better from a profit margin to look at something else other than a countermeasure for a disease that may or may not happen.

So I think that that's the core of the entire issue. The government cannot do it alone. The government is not going to be a vaccine-manufacturing corporation or a drug-manufacturing corporation. It must, by definition, partner with industry, but industry will not partner unless there are some incentives.

Let's just take influenza in general, with a subset of a potential for pandemic flu as a specific. We have a problem every year with influenza vaccines, and I think unless we solve that yearly problem, we're going to be still behind the eight-ball when we need to ratchet up for a pandemic problem. For example, if you look at the number of people that we would ultimately want to get vaccinated on seasonal or what we call inter-pandemic flu, it's a crazy game that goes on each year. How many vaccine doses are going to be made? How many are going to be used? Will the company know? What happens when they make too much and they don't sell 10 [million] or 20 million?

They play that minuet every single year. We've got to eliminate that. We've got to ultimately get a solid market, not of 60 [million], 70 [million], 80 [million], but 180 [million] and maybe 200 million people who would get vaccinated in this country each year, so that the market for influenza vaccine is solid on a yearly basis. Then you have the capacity, at least in this country, to be able to make enough vaccine to really provide protection. And I emphasize this country, because as Laurie and Michael pointed out, if you look at the global capacity and the global need, it's a drop in the bucket.

But if you just want to address it in this country, we've got to push the relationship between industry and the government to its max on a yearly basis, and I think we'll be able to better tackle pandemic flu if and when it occurs— and get rid of the "if" because it is going to occur.

GARRETT: Three key things: No. 1, even if we could ratchet up our vaccine-production capacity, identify the antigen in time, and make enough so that we actually could vaccinate the American people, we would face the foreign-policy outcome in a truly virulent pandemic of, after the pandemic had passed, the rest of the world saying, "You know, we don't really love you. You didn't share vaccine with us. Our people died in huge numbers while yours survived." We have desperate, unbelievably enormous foreign-policy issues to consider.

The second is that, increasingly when we look around the world right now, we can see that a lot of the industrial sector, the major globalized corporations, are already making plans of their own for pandemic flu. Especially in key industries that were hard-hit by SARS— the hotel industries, the airline industries, those businesses that have highly globalized and dispersed operations, particularly in Asia. There is a little concern on my part that, in a way, we're creating a kind of privatized infrastructure for response that is not directly linked in any way to WHO or to any government institutions of any kind, and that we're already seeing a lot of concern from the corporate sector about where do we call, what's the phone number that says, "Here's how your company should respond, and now you should be alerted, or you shouldn't be." We're also seeing that a lot of companies are beginning to purchase their own stockpiles for their own employees of Tamiflu. And that leads to the third issue, which is Tamiflu itself.

Tamiflu is a drug which, if taken appropriately, in the first roughly 36 hours of infection, can greatly alter the course of the disease and increase your chance of survival. We don't know how well it'll work against H5N1 or its permutation, when whatever the big megillah is, actually comes into the human population on a large scale. But in general, it's about 84 percent effective if taken properly under the right circumstances. So obviously, if you thought pandemic flu was coming, and you're a major multinational investment bank with offices all over Asia, you might be right now trying to buy up a lot of Tamiflu and stockpile in key locations for your employees.

But there is a problem. Tamiflu is only made by one company. It's a patented product. There are significant production problems for that company in terms of its ability to ratchet up on a massive scale production. That leads to an issue that was brought up at the World Health Assembly in May in Geneva. This is the governing body of WHO. It meets once a year in Geneva. And they had passed an massive resolution on pandemic influenza at the meeting. But what I heard in the days and days of debate there in Geneva was all the developing countries and the middle income countries saying, "Yeah, hello, what about us? Anybody buying Tamiflu for us? All your multinational corporations, all your rich countries, are going to buy up all the Tamiflu, and what happens to us?" "And can we not," said South Africa, "do compulsory licensing, and mandate that Roche yield their patent, and our local generic manufacturers be allowed to try to have their hand at making Tamiflu?" This could turn into a big, bloody mess.

HOGE: Michael.

OSTERHOLM: Well, let me take a step back first, because I think your question on the private sector has to be expanded, in a sense. And frankly, I think pandemic influenza is— to use a very overused term— the absolute perfect storm for our world economy. We live in a just-in-time global economy today, where in this country we depend on the rest of the world for many of the goods and services that we use everyday. Many of them are life-saving services.

So it's not just the fact that we have to worry about this vaccine capacity, which on a worldwide basis today all the pipes, all the building, all the blocks, could only put out about a billion single doses of vaccine a year, if we stretched it to its max. And even then, if you take two doses or more before you're vaccinated, that's 500 million people that would get— of the immunizations— six to 12 months after the pandemic begins, because it takes six months to make the vaccine. That is a drop in the bucket, if 14 percent of the world's population would have access to vaccine, and that's only basically made in 12 different countries in the world. I don't see any increase in capacity there right now, short of a major three, five, to seven year effort. It would take that long.

Tamiflu is the same thing. Tamiflu has been, I think, an unfortunate part of this discussion, because it has been so misunderstood. It may work. We don't know against the cytokine storm phenomena, the thing where the virus elicits an immune response. It works against garden-variety flu. We hope it will, we think it will, but right now the company makes about 100 million treatment doses a year. They have a plant in Switzerland with a precursor chemical that is critical to this coming from China, that if we shut down world travel and trade, which I think many of us believe we will, and watch the whole global economy sink, all these things, all bets are off.

When you think about today, we actually have many drugs in this country that come from a foreign country. Even though we have this debate about importing, because this was a vaccine from England, for flu, is not going to show up in the way we would like it again this year. If you look today, we have a just-in-time economy in the pharmaceutical industry. We actually have pediatric cancer drugs right now that are in such short supply that patients are actually being given only partial treatments because there is not enough of that drug right now.

If you look on the websites for the American College of Healthcare Pharmacists today, there are eight antibiotics in this country that are in major shortage status because of a single-plant, just-in-time delivery problem. You put flu on top of this, you shut down international travel and trade, and many of the things that we take for granted, light bulbs, everything that you think about, your food supply, will end.

Today, in this country, when you even think about something as simple as, how are we going to take care of the dead? In 1969 in the last pandemic, the average time from the time that a casket was constructed until it was in the ground was almost six months. Today it's two-and-a-half weeks. Today we have no excess capacity. We [inaudible] caskets overnight. Well, then you move to crematoriums. We don't have crematorium space, because again, everything is just-in-time delivery. We have food supplies today, where we have two to three days' supply in our warehouses; that's it. Even a bad blizzard day causes us to have real problems on a regional basis.

So one of the things I think that's critical is to take your question one step further, the private sector has to be involved in this in a lot of ways. Because the collateral damage that will occur with the pandemic, and I do have— I have no doubts we will shut down international trade and travel. Just as we saw with SARS regionally, and I talk about that in the article that I wrote, what will happen, overnight we will shut down all these other things.

We won't have many of the life-saving drugs. We won't have the antibiotics, we won't have the food supply, we won't have the parts of the water pumps that runs our city water supply. Those are all overnight FedEx kind of pieces today, in this just-in-time economy, that won't exist. So I think the private sector has a much, much larger role to play than even just the discussion of drugs.

Let me just conclude with one last thing: If we protect ourselves in this country, and if some miracle comes about where we could have a vaccine quickly that could protect 300 million people, we would still experience tremendous collateral damage with a lot of people dying. Because those products that we assume that will be there everyday for many of our life-saving kinds of things, many of the chronic disease drugs et cetera, won't be there. They will stop, because the rest of the world's economy will tank. And no one has ever figured out how to [inaudible] a just-in-time global economy when there is no electricity for the pump. And so I think this is going to be a critical piece of this discussion.

GARRETT: Let me just— I want to make a point off that, because I think what Michael's saying is incredibly important. And it almost goes beyond the sort of imagination capacity of all of us here in this room.

Let's just step back for a second and imagine that in 1918, the influenza that spread had a less than 3 percent mortality rate in human beings. So— and it killed probably up to about 100 million people in the world. This H5N1 that we're looking at in the people who have acquired it so far, it's been a 55 percent mortality rate. So we are way out of the ballpark here on mortality.

Let us assume that in order for it to be made— whatever that little genetic change is that it needs to make to become a highly human-to-human transmissible virus, and we don't know what that change is, but let's assume that that forces the virus to lose some of its virulence and come down, oh, say only 10 percent from 55. That still is fantastically more virulent than what we saw in 1918.

What would a 10 percent virulence influenza mean to Washington, DC? First of all, think about how you get flu. Most people think, incorrectly, that you get flu because somebody coughed on you. That sort of comes down to our sort of social judgment ways that we deal with disease. But actually, the flu virus is a very, very hardy environmental virus. It loves door knobs. It loves the poles in the Metro. It loves every entrance, every common surface that we touch. And the virus is persistent on those surfaces for hours, even days, depending on the environmental conditions.

So all of Washington, DC, is full of commonly touched surfaces, and all of a sudden, you would see this city utterly paralyzed. Government would stop. You could not imagine, anyway, that people would feel safe commuting in and out of the District, going to government offices, getting on the Metro, all the things that are of the essence of how you keep this place moving around. If you added to it the notion that young people would somehow be particularly vulnerable because they would have these stronger immune systems that would result in this ARDS cytokine storm, this incredibe intensity in response, think about how much this city rests on vast pools of interns that are the essence of how we run this government, right?

UNKNOWN: Right. [Inaudible] feels good. You [inaudible] this point.

GARRETT: All right. All I'm saying is that if you amplify your imagination of what this would mean to Washington, to all the most important hubs of the global economy, you easily can see the impact this would have on the global economy.

HOGE: OK. Given the topic, I don't think it's surprising that we're going to run out of time before I can get to all of you, and I apologize for that. But, in the interest of getting in as much as possible, I'm going to take three questions at a time and rely on the brilliant memories of our panelists. We're going to start in the back on the right.

QUESTIONER: My name is Steve Hofman. I'm not an expert in this, and after hearing all of this, I think I'm going to get in my car and go move to Montana or something like that.

GARRETT: It won't help.

QUESTIONER: That's what my imagination is [inaudible]. But the one thing I do think I know about is how we as a government and other governments respond to these kinds of things. And what they are really not very good at is being proactive. So let's assume for a second that everything you've just said here has absolutely no affect in the short run, including, say, getting 180 million Americans to get proactively vaccinated, which you can produce 180 million vaccine doses, but to get people vaccinated proactively on the idea. Anyway, tell us what are the firewalls, assuming that we will not proactively be effective as a nation in the United States and globally?

HOGE: What exactly do you mean by firewalls?

QUESTIONER: What can we do if we don't have—

HOGE: What can we do under that set of circumstances? [Inaudible] All right. So if we haven't prepared adequately, what still can we do? Terry.

QUESTIONER: Terry Schaffer from CSIS. The previous discussion of the private sector leaves me wondering, don't we have to reevaluate also the role of government? The U.S. has a particularly small model of what the role of government should be. Is that still appropriate and should one also be thinking in larger terms about reevaluating what international organizations, like the WHO and perhaps others, ought to be doing?

HOGE: I have a question right here. Did you have a question? Yes, right here. Second row.

GARRETT: All the way up front, speaking of the young people of Washington.

QUESTIONER: Without whom, we wouldn't even have mikes in a meeting. Peter Zimmerman, King's College, London. I'm a physicist and some of this went by me, leaving me a little puzzled and wanting to ask you a less foreign policy, and more technical questions so that I would understand when I read— Laurie, what you write when I read things in the papers, what I should really gather out of it. You answered very quickly my first question, which was what exactly does H5N1 mean. But Tony mentioned something about, well maybe next year it will be H9, this or that. How many of these markers in each series, and perhaps how many series of markers are there? And how precisely does saying H5N1 pin down the organism itself? It clearly doesn't get all the way down to the DNA level for the whole structure.

GARRETT: It does.

FAUCI: It does.

GARRETT: It's RNA, but, yes, it goes done to the nucleic-acid level.

QUESTIONER: But not for the totality, only for a couple of markers.

GARRETT: No, no—

FAUCI: Yes, he's right, if the hemagglutinin and the neuraminidase are the two major markers for influenza. There are a bunch of other genes. They generally are constant and don't change as much as the hemagglutinin. The hemagglutinin is the protein on the surface that would designate the difference between what we're experiencing now in our own country, the H3N2, compared to an H5N1. So both the hemagglutinin and the neuraminidase are different. And the answer to your question, there's about 16 to 18 variations of it. The humans generally experience H3s, H2s, and H1s. When you get to the fives, sixes, sevens, eights, nines, those are generally more animal, predominately bird flus.

HOGE: OK. We've got two other questions. One on government role and the other one, the firewall. Let's—

OSTERHOLM: Well, I think, to start out with the first question back there, let me just say in my most scientific Iowa farm boy way, describing it to you, I don't know what we can do right now other than say we're screwed.

GARRETT: That's scientific.

OSTERHOLM: And I mean that in a very honest way in the sense that, right now, if it happens tonight, we don't have the ability to suddenly gear up capacity. For example, the two major companies in the world that make the masks that would protect us, have 80 percent of the market share. They're running at 95 percent capacity right now for everyday goods. The masks are made overseas, largely. Many of the component pieces come from another third, foreign country. It would take them three to five years to build another plant just to produce more masks.

And I could go through every one of the commodities that we would need tonight. So this idea of stockpiling, in part, is a figment of imagination. When these companies say they have all these Tamiflu, many of these have delivery dates of 2007 and 2008, OK. So don't let a country off by saying, "We're covered by having so much Tamiflu." It hasn't been delivered yet. And I think that part of it is, we would just have to figure how to get through the panic and fear.

We saw this with SARS in a very limited way. How would we bury the dead? How would we get food to the people? How would we maintain some semblance of order? Not just domestically, but worldwide. We worry greatly what would happen in terms of international security, opportunities for international unrest as might not otherwise occur. So, in essence— but each day we get out farther if we could get planning in place where we could get decisions made.

Are we going to close schools in this country? If we do, how will they handle that? Are we going to go to work? Are we going to have people riding airplanes, subways? Are we going to have goods delivered? We need to start working through that kind of thing now. That's the best hope we have, is to get through. But it's not going to change the number.

We will provide healthcare in gymnasiums and schools. Our hospitals right now are down to the bone. Even in this country, when we actually get just a slight increase in influenza every winter, we go on what's called on-diversion status. Seventeen of the 20 major metropolitan areas last winter were on-diversion status for their emergency rooms, where they're legally able to close their emergency room, which right now you can't do without getting permission to do that from a civil authority because of the laws. They're full. We have no excess capacity. So we're going to have to figure out how to do that. We don't have those plans in place. We need that kind of granularity right now.

Finally, on a worldwide basis, this isn't a WHO issue. The WHO and groups like that are, at best, very, very limited partners for what this is needing. This is a G-8 [Group of Eight] issue that is all about, "Are we going to make a decision that we're going to invest a tremendous amount of money and resources well beyond what the United States can do to actually create a world capacity for a new vaccine, build it, and then make it available and knowing that it's going to cost a lot of money?"

The single— just one last point. In Minnesota, one of the very best well-funded fire departments in our entire state is the Minneapolis-St. Paul International fire department. There has never been a major plane crash at that airport since it's inception over 80 years ago. We pay for that every day because, if there ever is one, we've got to have it there. We made a decision that's an investment we're willing to make for that very, very remote chance something will happen. Today we have to do that for vaccine. I appreciate what Tony said. I agree with him. I think we need to have the capacity to make 6.5 billion doses or treatments for people around the world just so we don't have this world economy collapse issue.

FAUCI: Can I just very briefly expand on the firewall issue, because it really relates to the nature of this virus and how it compares to other perceived, frightening public-health threats. Generally, there's a public-health firewall: identification, isolation, quarantine, things like that. That could be helpful, but the reason why it's not the answer with influenza is the nature of how influenza spreads.

You take something like Marburg or Ebola; it's only spread in very, very, very close contact. So identifying, isolating, quarantining, is very good for that. It was even recently good for SARS because of the fact that it's droplet-transmitted. When you have something like influenza, almost from the get-go, once the virus assumes the capability of efficient spread from human to human, the horse is out of the barn almost immediately, because the kind of public-health measures that would isolate and contain are very inefficient because of what Laurie said about how the virus is there and how it spreads.

Influenza is spread very easily. That's the combination that is the real killer for us: A, it is a potentially deadly virus, and B, it is very, very rapidly spread, historically over centuries. We know that. That makes a difference from a lot of other killers that are frightening, but are not as readily spread. So firewalls become less effective when you're talking about public-health firewalls.

GARRETT: I just want to say a couple of things about governance. We've spent somewhere in the neighborhood of 3.7 to 5 point something or other billion dollars in the United States since 9/11 bolstering our public-health infrastructure with a heavy eye towards how you would respond to smallpox, how you would respond to bioterrorism issues. And a lot of it has been sold to the American people, in part, as that there's dual use. That money spent preparing us for smallpox equals money generally spent to bolster our capacity to respond to a range on infectious disease threats and epidemics and so on.

But the truth of the matter is, if you go down the list, smallpox is a whole lot easier to deal with than influenza. And the kind of preparation that was put in place is not necessarily going to be particularly helpful in the case of influenza. Governance is what really matters. It's hard to think of anything more important than governance at this time, but we haven't really prepared government. We haven't prepared our local government institutions. We haven't prepared internationally. We have no agreed-upon mechanisms of any kind.

And Mike is absolutely right about the limitations of WHO, the idea that somehow we're going to have sat down and made decisions. No, it won't work to quarantine off huge populations. No, it won't be effective to shut your borders. No, you can't stop this kind of a pandemic by ordering all plane flights and paralyzing the global economy. We've not had that decision process. We've not had those discussions. They have to take place at all tiers of government, and there's been no incentive whatsoever to get government moving to have that discussion.

HOGE: I'm sorry to say that we are officially out of time, and I lose a ribbon or two on my lapel if I keep us going. So I'm going to have to call a halt, but I think our panelists have a few moments to continue afterwards for those of you who can hang around, but it is 9:30 and so the meeting has officially got to come to an end. And Rita Colwell will close us out. Thank you.

COLWELL: I think it's perfectly clear why the Royal Institution has settled on the pandemic project. This is not a trivial action, and the discussions, the interactions, the continuation of this project will be very important in the months to come. And there'll be additional dialogues, and I really appreciate the opportunity that we've had to partner with the Foreign Affairs journal, with Nature, and with the scientists and government workers around the world. Thank you.

HOGE: Thank you all very much.

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