Presider:	Ray Suarez, Senior correspondent, NewsHour with Jim Lehrer
Speakers:	Amin Soebandrio, Assistant deputy, medical and health sciences, Ministry of Research and Technology, Indonesia
	Robert G. Webster, Professor, Division of Virology, Department of Infectious Diseases, St. Jude Children’s Research Hospital
	Steven Wolinsky, Chief, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University
Introductory Speaker:	Richard N. Haass, President, Council on Foreign Relations

November 16, 2005

Council on Foreign Relations

Audio

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Council on Foreign Relations

New York, NY

RICHARD HAASS (President, Council on Foreign Relations):  Good morning.  We're just getting some Evian for our panelists.  That is my last joke of the day -- or attempted one. 

My name is Richard Haass, and I'm lucky enough to the president of the Council on Foreign Relations. 

And I want to begin the day by issuing a warm welcome to all of you to this conference on the global threat of pandemic influenza. 

In order to do some of my own homework for today, I turned to my friend Bill Sapphire, who informed us all several weeks ago that pandemic is an adjective that derives from the Greek word pandemos -- 'of all the people' -- and becomes a noun now to mean, quote, "the outbreak of a disease spreading over a large geographic area; epidemic, disease visit on a large segment of a population is now considered regional rather than global."  So what we're talking about today is global. 

The word influenza -- maybe all of you knew this; I didn't -- comes from the Italian word for influence, and it was adopted in the English language several hundred years ago, based on the widespread belief that epidemics were caused by the influence of the stars. 

Well, we've come some ways since then.  And what we're grappling with this morning to me is a classic public policy problem.  It's a problem for policy practitioners, and it's a policy -- a problem for policy intellectuals because it deals with the age-old trade-off between probabilities and consequences.  And all of us who have grappled with these issues know that to deal with high-probability, high-consequence challenges is relatively straightforward, as is low-probability, low-consequence, as is high-probability, low-consequence. 

But when it comes to low or unknown probabilities and possible or likely high consequences, then we're up against the classic insurance dilemma, which is what should we do and how much should we be prepared to invest and spend, in every sense of the word spend, to deal with a situation that could have enormous consequences, but we simply don't know how likely it is to actually happen. 

This also seems to me to be classic in another way.  In some ways this is one of the poster children issues of globalization.  It's a challenge for the United States for the American people, but it's not a challenge for the United States or the American people alone.  What happens everywhere else will matter to us in this.  Or to put it another way, the world is not Las Vegas.  What happens there will not stay there.  And the United States, to use another metaphor, cannot become a large dated community.  We cannot find ways to shut ourselves off from this.  So this is globalization. 

It's also a classic problem in another way because it deals with all sorts of trade-offs and all sorts of inevitable partnerships, like it or not, between federal, state, local government, between civil and military authorities, between public and private.  This is not something that fits easily into a box. 

And then it's a classic problem in still yet another way, and here I could be talking the language of dealing of any global issue, from disease to terrorism.  We have to look at questions of prevention.  We've got to look at questions of protection.  We've got to look at questions of consequence management.  We've got to figure out where we go on the offense, where we play defense. 

Clearly, we've got our work cut out for us today.  The good news is we've got an incredible array of experts here, practitioners and policy makers from around this country and from around the world. 

Our decision to convene all of you this morning was driven in part by the enormous feedback that we received to (adhere ?) to the work we're doing at the council on global health following the release of the summer issue of the magazine Foreign Affairs, where a big chunk of the issue, as I think most or all of you know, was devoted to the question of the next pandemic.  And there was so much reaction to that issue from people who wanted to know more, and also we saw how it became a central part of the debate in the United States Congress that we felt compelled to go on from there. 

What we've done today, as you see from your program, is divided it up into five separate but related panels.  We've also, though, tried to leave you ample time to talk with one another during breaks and over the lunch hour. 

We're also joined here -- besides all of us in this room, we are actually, in some ways -- as is fitting with a challenge that is truly global, we're joined by people from all over the world.  In particular, in our Washington office, in the council's Washington office, we've got people who are linked with us, as you can see, by video-conference, where Susan Dentzer, who's the health correspondent for the NewsHour with Jim Lehrer.  She'll basically be facilitating the conversation from there. 

This conference is also being webcast to the council's national members across the country.  More than one-third of our members are located neither in Greater New York nor Greater Washington, so they're a part of this meeting, as are students at universities and colleges across the United States.  Several other organizations are linking to the webcast, making it available to their constituents -- for example, the American Public Health Association, the Public Health Preparedness for the City of Houston, the Bill and Melinda Gates Foundation, PATH, the Program for Appropriate Technology in Health, Carnegie Mellon University and -- (inaudible) -- the Virginia Department of Public Health, and several other student health and wellness centers across the country.           

I would be remiss if I didn't express my personal gratitude but also the gratitude of this organization to the Leonard and Evelyn Lauder Foundation.  In part, this meeting is the result of Leonard's own personal interest in these issues.  But again, it would not have been possible without the generosity of the foundation and to Evelyn and Leonard personally, and I want to thank him and them personally here this morning.  (Applause.)

I want to thank as well Chris Derry (sp), a council term member, and his colleagues at Edelman (sp) for all of their work in assisting with our putting this on this morning.  And when I get to thanks, I've really got to first and foremost thank Laurie Garrett.  Laurie Garrett is our own walking, talking, writing, thinking resource on this, and she's essentially my tutor on this subject.  And to the extent I've come some ways, and Lord knows I have a long ways to go in this, it's because of Laurie's endeavor.  She really has been an inspiration and a sparkplug inside the council and beyond at raising knowledge of and awareness of this issue and what to do about it.

Let me also just thank everybody associated with the council, from Nancy Bodurtha and our meetings people for putting together such a large undertaking in a relatively small amount of time.    

Just one piece of housekeeping:  I would ask you all to turn off your cell phones, your beepers, your BlackBerrys -- indeed, just about anything except hearing aids and pacemakers.  So if you could do that, it would facilitate our ability to concentrate on the day. 

Let me also remind everyone that everything today is on the record.  What you say can and will be used against you. 

With that, let me turn it to someone who has been one of the people who has literally and figuratively talked to this nation day in, day out in raising public awareness and public understanding of a range of issues, including those related to health, Ray Suarez.  (Applause.)

RAY SUAREZ:  Thank you, Mr. Haass.

The function of this first session of the day is literally to set the table for our conversations throughout the day -- session one, literally, "Where do we stand?"  And I have assembled with me here a terrific panel to sort of fill in the crosshatching, the gradual way that a public impression of the nature of a challenge is understood. 

Avian flu hasn't landed in the public's lap in one coherent, contiguous chunk.  It gets signaled -- a little two-column-inch brief on an inside page, in the front page of your newspaper, a 30-second story at the end of a radio newscast, the report of someone who is reportedly dead from the disease but we're not sure, someone who's newly sick in a new country from the disease but we haven't checked yet whether it's true that they've got it.  Birds have moved from here to there.  China reports that it's vaccinating -- vaccinating -- 5 billion birds.  The president discusses openly using the United States Army to support a quarantine and mentions it almost casually in the context of a news conference from the White House.  Taiwanese birds being shipped to Britain die in quarantine -- dozens of them, and it's not quite understood how they got there, how they were quarantined, just exactly what the state of play is as this disease either gets ready to break wide or ready to be met by a coherent and well-thought-out world strategy.

To the left is Amin Soebandrio; he's the assistant deputy for Medical and Health Sciences at the Ministry of Research and Technology of Indonesia.  To the far right, Steven Wolinsky, chief of the Division of Infectious Diseases at Northwestern University Feinberg School of Medicine.  And sitting right next to me is Dr. Robert Webster, professor in the Division of Virology in the Department of Infectious Diseases at St. Jude's children's hospital. 

Later on, we'll include your questions and get some answers to things that may have been bugging you all along, and we'll try to get them settled today. 

Dr. Webster, where do we stand?  As people try to form some sort of understanding of what's moving where, what's percolating in the bloodstreams of animals large and small through the world's time zones, where do we stand?

DR. ROBERT WEBSTER:  We're sitting on the knife-edge right now.  The virus has spread across most -- from Asia to Central Asia to Europe.  It's sitting on the knife-edge for spreading to Africa and next season probably to the U.S.  And the situation in humans is growing by the day.  The number of human cases keeps creeping.  And the situation is extremely serious. 

SUAREZ:  What is the bio-break point, the threshold that gets crossed in the change in the virus itself that moves this from something that only affects a small number of humans, and a large number of birds, to something that really can be a worldwide problem?

WEBSTER:  The answer to that is unknown.  We are not there yet in terms of our understanding of transmissibility.  The key question is sustained transmission between people.  We've had small clusters of humans infected in different countries, but there's no -- so far, thank God -- no sustained transmission from person to person.  What is the basis of transmissibility, we don't know. 

SUAREZ:  When there is a human-to-human confirmed case, will that tell us something about the underlying health status of the humans involved, or will it tell us something that's changed fundamentally about the virus itself?

WEBSTER:  One human-to-human won't tell us very much.  And unfortunately, we don't get enough information from humans in Asia on what has happened to humans.  The number of postmortems done is extremely small.  The number of viruses we get to examine is extraordinarily small.  And we will not know from one or two passages the molecular basis.  We have to take this back into the laboratory to really understand this, and we will know when we have sustained transmissibility; that's the breakpoint. 

SUAREZ:  Dr. Wolinsky, is there a situation that's created by human activity or a situation that's created by bird activity, which is something sort of beyond our reach, that can make this a greater or lesser danger?

DR. STEVEN WOLINSKY:  Well, certainly when, during the course of human events when we're put in greater proximity to animals that have other viruses, they do have a propensity to leap from their animal host to humans.  This has gone on in many situations.  HIV/AIDS is a perfect example of a virus that existed within a primate host for a long period of time until it actually was successful in its jump to humans.  But that leap was preceded by many sort of tentative steps, as we're seeing now where it sort of makes a little dance forward; maybe there's a one or two person spread.  It doesn't quite make it.  And again, I would emphasize that we really do need to know what is going on at the molecular level.  What really characterizes the virus that makes that leap?  What are the underlying genetic factors that both the virus, the host and its immune response that makes this happen? 

SUAREZ:  Are there changes that happen in the virus that blunt any attempts to defend against it? 

WOLINSKY:  Well, in respect that the virus can have enhanced pathogenicity -- its ability to actually do greater damage to the host -- there may be aspects of the virus, per se.  Witness the 1918 influenza virus.  There's properties that we've seen in the animal models where it really has shown an enhanced ability to kill in a situation where other viruses, other influenza viruses did not -- its ability to incite an immune response that far outweighs what is needed for the host to be protected, and in fact, ravages the host, ravages the animal model.  So there are some genetic variants that exist in particular and have been transmitted.  What are the actual particular pathogenic factors that mediate this are still really not known.

SUAREZ:  We tend to talk about mutation as if it's a discrete event which gets you from one place to a single new place.  Could five or six or 10 or 100 variants be cooking right now in animal host bloodstreams and some just end up being mutational dead ends because they kill too quickly or don't kill at all or don't spread easily, and, in fact, it's only the one that's successful that catches our attention? 

WOLINSKY:  Well, certainly -- we can just go back to Darwin on this -- (inaudible) -- we're looking at dissent with modification. 

SUAREZ:  You can do that because we're in New York State. Okay?  (Laughter.) 

WOLINSKY:  That's right.  We're not in Kansas anymore.  (Laughter.)  And like other RNA viruses, flu is highly mutable, highly adaptable and capable of rapid evolution.  And within the host, it's not a single virus that you have but actually a swarm of viruses.  And they're all genetically related but yet distinctive.  The virus is constantly mutating.  And it's on a cycle that's akin to other RNA viruses that every time it replicates, it makes a mistake.  And so basically you're left with this viral swarm.  And how the swarm actually adapts to the host, how the immune system actually manages that is really up to an individual basis as well.  And there are individual differences in terms of how people respond to infectious diseases, and there are differences because of their genetic makeup, because of their immune response, their underlying difficulties with immune response, how the virus is able to exploit these and the fact that certain ones become adapted, better able to grow in a certain environment. 

SUAREZ:  Dr. Soebandrio, what do we know about the situation, the state of Avian flu in Indonesia? 

DR. AMIN SOEBANDRIO:  Yes, as you are already aware that the first outbreak in Indonesia among birds was announced by the government in the middle of 2003 and the number of bird deaths increasing.  But actually, we could control until the beginning of 2004; the number of bird death is decreasing very much.  But a few months after that increase, again we have a small peak.  But what makes us so scared -- in end of June this year, we have the first human case.  A small child was hospitalized with the symptoms fever and problem with the respiratory track, and when she was hospitalized, her sister also then developed same symptom, and also their father.  They all died.  That was the first cluster.  But unfortunately, we couldn't find any source of contact because they don't live in area where close to poultry farm or something like this.  It was the fist cluster. 

A few weeks later appeared some other cases.  And so far, we have nine confirmed human cases, five of them dead.  And by virus isolation, helped by a Hong Kong laboratory, we then identified already now four clusters.  The first cluster has three members, one family; second cluster, one young lady and then her nephew, a boy; and then third cluster, also a young lady and also one of her family; and then coming the fourth cluster.  The other three -- the last three cluster only consist of two family members.  But the last -- (inaudible) -- cluster we could identify the source, really.  They have clear contact with birds.  But still, for the first cluster, it's unclear. 

So with that situation, we realized that -- already a very serious situation happened in Indonesia especially -- (inaudible) -- Jakarta.  As you know that most of the cases -- (inaudible) -- in Indonesia is in surrounding area of Jakarta, in outskirts of Jakarta -- only one-hour drive from center of Jakarta.  Why it happened in the area, one of the most important hypotheses -- dense human population and also dense chicken population.  Human population is up to 12,000 per square kilometers, and chicken population up 5,000 head per square kilometers.  And they are all in the same vicinity.  So -- and also one more thing:  yeah, we have to admit that the bio-security of most of the farm is still very low.  So that's the situation -- current situation in Indonesia.

Of course, probably the nine confirmed cases just the tip of the iceberg, because we do receive reports from other parts of Indonesia.  People develop similar clinical symptom, but the laboratory, unconfirmed.  That is the situation with the human influenza situation.  I meant human cases. 

If you are talking about the situation in birds, so far we have already 10 million birds already killed or died.  As a comparison, in Indonesia we have 1.4 billion population of bird, compared to China about 4 billion birds.  So quite a lot.  And another interesting situation is after last year, we have the bird confirmed to be infected by Avian influenza virus, just localized in the western part of Indonesia -- Java, Sumatra, Borneo, not in the eastern part of Indonesia.  But from this year, we could identify many places in eastern part of Indonesia already infected by Avian influenza.                   

SUAREZ:  You've mentioned the number of birds killed.  How do you know whether that really works?  One of the most common features of the news stories concerning how governments respond to bird flu involve huge culls in Thailand, in Vietnam, in China; you mentioned Indonesia.  We've been killing birds by the tens of millions, yet Dr. Webster talked about the virus now spreading to all points on the globe. 

SOEBANDRIO:  Actually, if we follow the procedure, the OEI procedure, we should have killed more than 10 million.  But the problem is the government has not enough resources to pay the compensation to the farmer, because this time we have to kill birds or pigs or ducks.  We have to give compensation to the farmer.  That's the problem.  Compared to other countries, if we find a case of bird -- a flock of birds infected by Avian influenza, we have to kill in the area of up to three kilometers from the farmer, from the farm.  But in fact, we didn't do that.  Only we killed the bird in the same farm. 

SUAREZ:  Dr. Webster, do culls work?  And in the case of limited culls like Dr. Soebandio just described, is sort of doing it halfway almost as good as doing nothing? 

WEBSTER:  Culling does work.  The documentation -- the H5N2 outbreak in the United States in the early 1980s, that virus is gone.  Japan got rid of H5N2.  Korea got rid of it by culling.  On the other hand, if you turn to other countries where the virus was widespread before culling began, as in Mexico in the early '90s, H5N2 was widespread before culling began, and then culling doesn't work.  In China, in Indonesia, where the virus was widespread before it was recognized, then culling does not work.  It is not possible to cull in China at this time and cull in some countries.  So yes, culling does work in some countries if you act quickly but not after it has become widespread.    

SUAREZ:  But here's a case where we have a mixture of very biologically similar bird types -- domestic and wild fowl among ducks and geese, both large-hold farms, where you're supplying protein to market, and small-hold farms, where you're feeding a family.  So you've got stratification of all kinds and, now, passage to migratory populations of non-domesticated species.  I mean, can you kill everything? 

WEBSTER:  You raise an extremely important point.  This virus is now endemic.  H5N1 is now endemic in the wild birds in Asia.  And if we take the case in Thailand, Thailand killed and killed and killed, and they had nearly a year almost free of bird flu, but it's back.  There are human cases.  The virus is spreading again.  And that virus is being spread, presumably, again by wild birds.  So at this point, we're beyond the point where culling will work.  We really have to think in terms of culling.  Tough vaccination is the only way forward at the agricultural level. 

SUAREZ:  Is it important to know, Dr. Wolinsky, how we got here, whether there was a change in conditions that suddenly lit a match to the tinder?  People have been farming birds in very close quarters in Southeast Asia for a long time.  They've been living in close quarters.  If you look at, you know, temple paintings and ancient carvings, there are domesticated birds, birds tied to each other by the ankle that are held by people's houses.  Was there something qualitatively different about this last decade that made it possible for this disease to do something that it either hasn't done before or only done cyclically?

WOLINSKY:  Interesting question.  We've basically been faced with influenza pandemics, at least three, four a century, so that there seems to be some juxtaposition of when the virus actually makes a leap into the human population and when the population has not really contained its spread.  And part of that is because we have not had an immunological memory to that specific type.  No one, really, has seen H5N1 before.  So if the fact is -- if that virus actually takes hold and is sustained transmission, so there's person-to-person spread, what we had is a situation whereby it goes through a population bottleneck.  We have not really seen this virus before. And even though these viruses are highly mutable and can change rapidly, there's no reason for it to change once it hits a population that has never been exposed to it before, and it can ravage through a population.  That's really what makes this such a difficult disease and why we have to really put everything at the forefront to try and contain it. 

Again, what is the particular event that leads to one particular case of transmission that leads to it?  I would defer to the person on my right who studied that the most in terms of how that occurred.

WEBSTER:  I would answer that in a slightly different way in what is different from what we've been -- what's happened before is globalization.  And farming practices have changed.  Previously, we had backyard poultry.  I grew up on a farm in New Zealand.  We had a few backyard chickens and ducks.  The next-door neighbor was so far away it didn't matter.  Now we put millions of chickens into a chicken factory next door to a pig factory, and this virus has the opportunity to get into one of these chicken factories and make billions and billions of these mutations continuously.  And so what we've changed is the way we raise animals and our interaction with those animals.  And so the virus is changing in those animals and now finding its way back out of those animals into the wild birds.  That's what's changed. 

SUAREZ:  Is that the case in Indonesia?  And if you know, tell us about other places in Southeast Asia as well.

SOEBANDRIO:  Yeah -- (inaudible) -- in Thailand.  They have succeeded in controlling the Avian influenza, but they have the problem, as hypothesized by -- wild bird population coming into that area.  The same thing happened also in Indonesia, because if we look at most of the small farms, they don't have, say, bird nets to protect their chicken from contact with wild birds.  So that means that the chance of heavy contact with wild bird is very, very big.  That's why it's very difficult to control.

In this case, I think vaccination will be one of the most important steps to stop the propagation of the disease.  However, the problem is when we were in (chaotic ?) condition in Indonesia, many people was trying to import vaccine from many countries without confirming the quality of the vaccine itself.  That's why if I was asked how many doses already given to the birds, I cannot give a real answer because if we say one million, is it (real ?) 1 million effective dose or only one-half or one-third probably? 

So our concentration now is to try to find much better vaccine with its (effectiveness ?) hopefully close to 100 percent, of course, to protect all the birds in the farm from getting infected by the virus because if we have to say -- if the government has to prepare some of -- money to give compensation to the farmer, if we have to kill the birds, probably the amount of money will be very, very huge.  If we could use some of the money to prepare vaccines at the same time, probably it will be much, much better. 

In this case, I think international collaboration will be very, very important because, as we know from -- (inaudible) -- wild bird play a very important role in this case.  So Avian influenza is a disease without border.  It's impossible to stop the disease only in one country or two countries, but the whole countries should have good collaboration.  Of course, in the United States, we don't have the case yet.  But yeah, I (learned ?) from Dr. Webster that this season -- November, December, January -- usually there will be a lot of -- high incidents of human influenza.  If at the same time that people -- the person is infected by bird influenza virus, what will happen?  The possibility of -- (inaudible) -- will be very, very high.  And then the virus will become human virus.  And the chance of developing human-to-human transmission is much, much higher.  So it could happen at any time and anywhere, not only in Indonesia or neighboring countries.

SUAREZ:  Well, Dr. Soebandrio just described his country embarking on a vaccination program, and then, in the next breath, he says he has no idea how many effective doses is given out.  Talk a little bit about the usefulness as a weapon of a vaccine and vaccinating birds.

WEBSTER:  This is an extremely important topic that hasn't received anything like enough attention.  Let's go to where vaccines are being used effectively in poultry.  If we go to Hong Kong, where this event first emerged in '97, Hong Kong's been dealing with this problem for many years.  And they have solved the problem and demonstrated to the world that if you use vaccine, an approved vaccine, have all of the poultry vaccinated with H5N1 vaccine that are imported into Hong Kong, there was no H5N1 either in the poultry or in the humans in 2003 and 2004 in Hong Kong when it was ravaging China and the surrounding countries.  Vaccines -- poultry vaccines are the key.  They're still the key to determining whether this virus becomes a pandemic, and it hasn't received enough attention.  And this is -- I can become very passionate about this question because there are good agricultural vaccines and bad agricultural vaccines.  The good vaccines protect disease (signs ?) in the chicken, stop virus shedding, reduce the virus (load ?) so the virus doesn't spread chicken to chicken.  The bad vaccines protect the disease, but the chickens and the ducks keep popping out virus; they don't die.  And so they continue to spread virus. 

So I argue that in Asia, we've got both of these things going on now, and it's been acknowledged in China.  Some of the vaccines were -- actually contained little more than water.  And so this is the key question.  There are good vaccines available.  The technology is there.  We have produced vaccines by the current reverse genetic technology where we can inoculate one dose of vaccine into a duck, totally protected.  The technology is available in the world.  We have to use this technology globally. 

SUAREZ:  Dr. Wolinsky, in China there are approaching four domesticated birds for every human being.  Why does it make more sense to vaccinate 5 billion birds than 1.25 billion humans?

WOLINSKY:  Well, right now if we contain it at the source, it's probably the best approach we can have to public health, is basically to contain what is going on in chickens right now.  Our human vaccines right now haven't really been to any extent as good as we would like.  Certainly the agricultural vaccines have.  Right now in humans, we have had some tests with some vaccine.  They've ordered approximately 20 million doses.  But usually with vaccines, it takes about 15 micrograms for protection, but with the current vaccines that we have for the H5N1, it takes about 180.  So basically, the 20 million doses that we have already ordered are really going to only protect about 3.3 million people.  There's a little disconnect there with the human vaccine.  The agricultural vaccine works quite well, and it makes a lot of sense to really target primary source and to decrease the potential out of that primary source.

SUAREZ:  A lot of people, if they can get their hands on it, are stockpiling their own Tamiflu.  Now does this confer any kind of protection in human populations, or is this almost like a modern chemical fetish object -- (laughter) -- to have in your medicine chest?

WOLINSKY:  I don't have mine here.  You have to -- like any of the antibiotics or any viral agents, you have to use them in the appropriate circumstance.  Certainly, we've seen that some of the farmers have used amantadine-like agents, which are ones that prevent virus entry into the cell.  In the bird population, we've had resistance to the virus by using it indiscriminately in that case.  Oseltamivir and the other neuraminidase inhibitors basically prevent the virus from being released from the cell.  So basically you want to use it in a situation where you want to reduce the potential for spread and reduce the disease.  It has been shown to reduce severity of symptoms by a day, half a day in terms of treatment, but more importantly, it's really shown that it's been a protective effect -- (inaudible) -- have actually been exposed to the virus. 

(Audio break.)

SUAREZ:  Is there a scenario where you can actually make things work by self-prescribing and self-medicating with preparations like that?

WOLINSKY:  Absolutely.  When we have family clusters, if the -- if one member of the family is actually infected, and we have a number of family members that we want to protect against infection, we don't want to give the drug to the person who's actually infected, believe it or not.  We give it to the other family members.  If we give it to the person who's infected, it has a high amount of virus replication, and a lot of virus is being put out by -- through respiratory secretions.  The chance of getting resistance in that person is very high, and then we lose the protective effect in the other family members.

SUAREZ:  In a few minutes, we'll go to questions from the floor. 

There is just one more theme I want to make sure we introduce during this session.

Dr. Soebandrio, if you locate through your public health service a case of flu in a rural area, how long does it take before you know whether it's H5N1?

SOEBANDRIO:  It's a very good question. 

That's why I wanted to make sure I answered it. 

Yes, we do have the capacity -- I mean we do have the human resources, the -- (inaudible) -- and the laboratories to go from our -- (inaudible).  But first, based on the regulation, we have to send a specimen to WHO (cooperative ?) reference laboratory to confirm the test.

So before we do have the confirmation, we have to wait that result before we make a decision.  That usually -- that takes about six to seven days. 

That was one thing I can -- (inaudible) -- Health.  Why should we wait until seven days before we take important steps to control the surrounding areas?  That's why I recommended very much the minister of health to have one or two laboratories in Indonesia having enough capacity to give a confirmation on the test.

Of course, we still have to send a specimen to the reference laboratory.  But we don't need to wait that long until we make the decision.

I think now the government is preparing some laboratories, supervised by -- (inaudible) -- from Hong Kong.  Probably next year we will have two or three laboratories.

Of course, if we are talking about the biosafety level three laboratories, the operation of the laboratories are so expensive.  That's why we have to limit the number of laboratories only in big cities,  probably only in Jakarta and one in Surabaya, East Java.

So in that case, a specimen from -- (inaudible) -- sent to Surabaya -- (inaudible) -- sent to Jakarta. 

So we have -- we can -- we could make it shorter.  So hopefully within three to four days, we have already found the result.  

SUAREZ:  But now, seven days?

SOEBANDRIO:  Now, seven days.  Actually, the local laboratory could give the preliminary result in two days, but still, we'd have to wait for confirmation from Hong Kong.

SUAREZ:  Dr. Webster, if we put enough emphasis on diagnostics, and if we haven't, what do we do to change that?

WEBSTER:  We need a immediate test for H5N1 -- a dipstick test.  But the technology at the moment is quite good.  We can get an answer in a matter of hours in the most sophisticated labs in the world.

The problems are that there aren't enough sophisticated labs, and it takes time to get the samples from Indonesia to a sophisticated lab in Hong Kong. 

That's the big problem.  Until we get the technology to the point where we can have such a dipstick, give it to Indonesia so they can put the dipstick in the sample and it turns red it's flu -- bird flu.

We're not there yet, so there is more research to do.  But in the sophisticated labs it can be done quickly.

SUAREZ:  For our first questions, let's go to Washington, D.C., where my colleague Susan Dentzer is standing by.

Susan, how are we going to do this?  Who is asking your questions from Washington?

SUSAN DENTZER (Correspondent, Newshour with Jim Lehrer):  Ray, I'll take the moderator's prerogative here and ask the first one, and then I'll invite my Washington colleagues to join in.

I want to follow up on something Dr. Webster said, which was that by next flu season we would expect to see the avian flu, the H5N1 virus, here in the  United States.  And I take it by that he meant in birds.

Recognizing that this would be an educated guess at best, what hallmarks of either point mutations or signs of reassortment or whatever changes in the virus should we be on alert for over the next year that would heighten our concerns that sustained human transmissibility would be a reality by the time the avian flu shows up here in the United States?

WEBSTER:  The point mutations that we're watching for I think have been identified by the group working on the 1918 influenza virus and by the mutations that are seen in a few of the strains that are transmitted human to human.

The residue -- there's a residue, if I can become technical for a moment, in the PB2 gene residue 627.  If that change occurs in conjunction with other sets of changes, then we have to become extremely worried.

So there are some point mutations that we are watching for, and when they all line up, then the danger increases.  At this time those point mutations are not all in the same virus, so we know some of them; we don't know all of them.

DENTZER:  And in terms of signs of reassortment?

WEBSTER:  Whether or not reassortment -- there are two possibilities as everyone knows -- the accumulation of point mutations or reassortment.  Which way will it go, we don't know.

At the moment, the virus has much more chance to accumulate these point mutations, and we have to think, again, to 1918, Spanish influenza. We know from the studies, from Jeffrey Taubenberg (ph) and others, that this was an avian virus that transmitted directly from some avian species to humans, accumulated the necessary point mutations.

This virus is tending to mimic that.  The other strains -- pandemic strains -- they reassorted.

So the option is there for the virus to do either of those.  At the moment I am worried -- most worried -- about the accumulation of point mutations that will allow sustained human to human.

DENTZER:  Okay, thank you.  Others in Washington who want to ask questions, please identify yourself by name and affiliation briefly.

Go ahead.

QUESTIONER:  Hi, I'm Elizabeth Prescott (ph), with Eurasia Group. 

I have a question, what do you think, in the communities where we are seeing disease emerging into humans, do you think there's an underlying immunity that may exist in populations and countries that have been experiencing this pandemic -- this disease -- in birds for some time?  And do you have any idea how we might be able to gauge that from current data that we may have available?

WEBSTER:   Right now, when we're looking at H5N1.  We really have not seen this virus before.  This is a totally unique virus strain that is being let go, so that, as far as any underlying immunity, no, the population has not seen this before.  So there is no underlying immunity to this particular virus.

QUESTIONER:  Even in Indonesia, Thailand, Vietnam, at this point, after several years of dealing with the virus?

WEBSTER:  No.

SUAREZ:  Why is that?  Why, if there is sort of ambient presence of this virus in a population that lives in close proximity to where it's bred and cultivated, is immunity not conferred in a population?

WEBSTER:  Well, basically, the virus hasn't infected a large enough population or a great number of people to actually induce the immune response at all.  So no, we haven't really seen it yet.

That's not to say that this is one of the primary worries, is the fact that we have had no immune response to a related to the viruses.  And the fact is is that once it does take hold, it will rapidly spread through the population, because this doesn't exist at this time.

SUAREZ:  Susan, let's take one more from Washington, then we've got some questions here in New York.

QUESTIONER:  Sean Pike (ph) with Globalsecurity.org. 

Genetically, is there -- what is the linkage between factors that you would be looking to change -- alter the transmissibility of the virus -- versus changes in its pathogenicity -- that is to say, is there any particular reason for believing that if it becomes readily transmissible between humans that it's going to become substantially less lethal?

WEBSTER:  That is a very interesting question of whether or not once the virus does become transmitted human to human will it become less pathogenic?  There is absolutely no way to tell.  If I was the virus, I would become less pathogenic, because I don't want to kill off all my hosts.  But I would guess the scenario would be that the -- this thing will occur probably in multiple waves.

The first wave will be disastrous.  Whether it's 50 percent, 10 percent, or 5 percent, that's disastrous for the world population.  But if it does go human to human, we will have a wave of enormous pathogenicity.   And the virus will rapidly revert to less pathogenicity, so we will have a lethal wave, a less lethal wave and then benign.

And that's the way the virus will happen.  That's what happened in 1918.

SUAREZ:  Granted the sample was tiny, but do recall that Dr. Soebandrio mentioned that out of his eight cases, five have died.

Let me remind you to say where you're from and who you are and say your question in a big loud voice.

QUESTIONER:  Paul Marx from Memorial Sloan-Kettering. 

Has there been any effort to determine whether antibody to the virus forms on any of the infected animals or infected humans that are on record?

SUAREZ:  Dr. Soebandrio?

SOEBANDRIO:  Yes, you get antibody in humans, yes.  It's a little bit of a long story.

Among the poultry workers, we -- so far we (found it ?) in one person -- positive.  And so far no other poultry worker was found positive for antibodies against H5N1.

And that person, when he was then isolated from the poultry, the antibody titer decreased and disappeared after a few weeks.

And among the patients, nine confirmed cases -- not the whole cases -- showed positive with PCR and antibody at the same time.  For the example, the first three cases -- deadly cases -- in -- (inaudible) -- Jakarta, the father shows positive for PCR, but negative for antibody.

Conversely, the daughter, positive with -- (inaudible) -- but negative with RT PCR.

SUAREZ:  What about non-human animals that live in close proximity to humans and the bird?

SOEBANDRIO:  Human animal?

SUAREZ:  Non-human animals that are also on the farm -- beasts of burden?

SOEBANDRIO:  Ah, yes.  For example, in the zoo, we found 30 percent of birds in the Jakarta zoo was positive -- (inaudible).  Then the zoo was closed for public for one month.  And then what they did with those birds, because they are fairly exotic birds, they tried to treat the birds with antiviral drugs.  And after a few weeks, they found negative -- the test.  And the put the birds back in the zoo, and they reopened the zoo now, already.

That's an example.  And in some other animal they found positive result in some pet birds.  For example, in Surabaya, they found positive results in doves, also in some (cat ?), I guess.

SUAREZ:  Could we get the microphone around to the aisle here?  This lady right here.

QUESTIONER:  Betty Washoe (ph). 

What about eggs -- chicken eggs, duck eggs, geese eggs?  Would that be a way to transmit the virus to humans?

WEBSTER:  The eggs -- the problem with eggs is that fecal contamination -- these viruses are transmitted in feces.  If the egg is contaminated on the outside by feces, that is a problem.

The very last egg that the chicken lays before it dies has the potential to have virus within the egg.  But prior to that, the information is that the virus is not incorporated into the egg.  But regardless, in this situation, eggs are a potential way of spreading it.

On the other hand, if you cook the eggs, there is no problem. 

QUESTIONER:  Bob Dreswitz (ph), Wellington Management Company. 

Recognizing that the H5 antigen might still drift, what would -- what's  the argument for not instituting a broad human vaccination program now, at least to begin to deliver some kind of a herd immunity, even if, you know, at the end of the day it might be slightly different, but at least we will have seen it?

SUAREZ:  Dr. Wolinsky?

WOLINSKY:  Yeah, this -- most of the antibodies that -- most of the immunogens that we're looking at in terms of flu are really looking at conformational epitopes, in other words, ones that are existing in, say, in space as far as a structure that actually changes and moves frequently.

So there is no real way -- good way -- to tell what the common antigen would be that would confer immunity.  We already know that on an annual basis that we have to change our flu vaccine each year, and that's because of the fact that these epitopes change so readily and can escape immune recognition so that, even though there is some baseline immunity that may exist from a larger vaccine, we really need to tailor it to the exact variant that exists within the population.  The better that we can get the match to what's actually circulating with the vaccine, the better the efficacy is of the vaccine.

Is it 30 percent better than nothing?  Probably.  And that is some of the thinking that we're looking at now with using some reverse genetics based on what's out there to get some sort of a basis to a vaccine.

But it's a difficult question to answer.  We don't really know what's going to do it.  The antibody response really provides more of a protection than the cell-mediated immune response or the cells that actually attack the virus.  We haven't really, you know, seen it.  Off years, there's been some minimal protection with vaccines that don't match with circulating or not.  I think the idea is, the better the match, the better we're going to do.

SUAREZ:  In the back there. 

QUESTIONER:  James Kynge (ph), Eye on Asia. 

My question is for Dr. Soebandrio.  (Indonesia phrase ?) -- and welcome to New York.

You in Indonesia have seen difficulties in overcoming vested interests such as local agricultural businesses and local farmers and difficulties, as well, in educating the population.

I'm wondering if you could offer your opinion on what policy approaches you think would best work in these types of situations, either for Indonesia or for other countries in a similar predicament? 

Thank you.

SOEBANDRIO:  Yes, -- (inaudible) -- if could divide the poultry farm into three main groups.  One is the large farm -- (inaudible).  We have no problem, because they have the resources.  They have the money to vaccinate their poultry.  But the second and the third -- the second is moderate size farm, and the third is small farm and backyard farm.

The most difficult task is when we have to educate the backyard farmer and the small farmer, because they have very limited resources, and they don't have systematic way to distribute or to sell the chicken. 

For example, in Jakarta itself it has been identified, there are 200 collection centers for chicken.  They receive chicken from small farms; they collect in the center.  Each center has capability of collecting up to 2,000 chickens, and, of course, they don't have biosecurity processes at all.

Another example is in -- (inaudible).  The government educate the farmer not to move the product from one area to the other area.  It works.  But they forget to educate the farmer not to move the feces of the -- they use this as the fertilizer.  So they send the fertilizer to other area.  That's why the virus spread to other area.

So what we are trying to do is to educate them through the local leader, because if the government send an official to the village, usually they'll run away.  They don't like to hear from official -- I mean, from the -- say, from the Ministry of Agriculture official or Minister of Health. 

So we have to first educate the local leader, and then ask him to educate the farmer -- the small farmer.

Usually it works better than if we directly go to the village and tell everything to the farmer. 

I think that's the best way so far.  And the second thing is, we have to provide everything for free for the small farmer.

SUAREZ:  Yeah, thank you.

Yes?

QUESTIONER:  Laurie Garrett, Council on Foreign Relations.

Dr. Webster, you're really the godfather of flu research.  Among flu scientists you wear the crown.  So I had the question for you. 

And, Steve, since you are, also -- your other hat is HIV research, I'd ask you the same question -- does the section of the migratory bird flyway that's likely to fill in in the next few weeks, is that which heads to Africa.  And in Africa we have an unprecedented problem.  They have a massive population of people infected with HIV.

Would you please speculate on what you think would happen when an individual who is HIV positive becomes exposed to a bird or in some other way acquires an infection of H5N1?

WEBSTER:  Well, thank you for the crown.  I'm not sure that I wear it comfortably at the moment -- not at all.

My great concern I think I'm sharing with you is that if this virus and when this virus gets into Africa into the HIV-positive people, who are immunosuppressed, what happens in an immunosuppressed person we know with influenza in cancer patients, the virus is shed for an extended period of time, and it gives the virus the chance to accumulate the mutations of adaptation to humans.

And so this -- you put your finger on the great worry that we all have for this virus getting into Africa along with HIV.

WOLINSKY:  I agree it's -- in one respect, and then give you an alternative.

Certainly it's been a changed world.  We now have, not only in Africa, but HIV infection is worldwide.  We have cancer patients that didn't exist in previous epidemics -- solid organ transplant patients, bone marrow transplant patients.

And certainly if we saw a -- an influenza problem like we saw in 1957 or 1968, that's indeed true.  We would see prolonged shedding; it's a definite problem there.

But let's go back to another era, 1918, where really influenza caused what we could call a storm of cytokines, that the immune system would be so far revved up that we would see primary infections from the virus itself and not the secondary bacterial infections that we usually see.

In that case, we don't know if these people would actually -- who would have some underlying immunodeficiency would not be able to mount this kind of immune response with some respect, they may be actually saved by the fact that they have some underlying immune deficiency.

I mean these are clearly experiments that need to be done in nonhuman primate models or such so that we can determine the effect, because we do have large numbers of people that will be infected and will certainly impact on how we manage and treat them in terms of antivirals.

SUAREZ:  As Laurie mentioned, you're talking about very atypical populations, with 30 and 40 percent HIV-positive among adults. 

WOLINSKY:  Well, we're looking at that, and if we're looking at a flu epidemic that is coming through that would be similar to what we've seen, let's say, in 1957 or 1968, where there has been a significant impact on patients that have immune deficiency.  We haven't seen HIV per se, unless we look in our usual annual epidemics that we're seeing, that it could be devastating and incredibly so.  And you're in populations that don't have access to physicians, that they don't have access to hospitals, that they -- it's -- it can be quite staggering in terms of the potential for death toll and disability, the impact that it'll have on those populations.

SUAREZ:  Okay, yes, in the back on the left.  That guy, keep your hand up until they find you.  There you go.

QUESTIONER:  Hi, I'm that guy.  I'm  Richard Werlin (ph). 

I write books.  What about the role of our close human relative, the pig?  Does he figure in this potential devastation?

SUAREZ:  (Inaudible) -- Indonesia.

SOEBANDRIO:  The only example of close human relation is the first cluster of other animals to young children, because -- (inaudible) -- one young lady and her nephew, who not directly one family, only they live in the same area.

SUAREZ:  No, but our questioner, Doctor, was asking about pigs.  Do pigs, because they live so close to human beings and also live close to these domesticated populations, play a role in the disease?

SOEBANDRIO:  Yes.  We, in Indonesia, we don't have epidemics that pig has transferred the virus from the pig to human.  But we did control the case -- for example, in the first case -- there is -- there are some pig farm in that area, and because at the time the government was also a little bit -- (inaudible) -- condition.  So they kill all the pigs in that area, because they found also some pigs positive -- (inaudible). 

But so far we don't have any evidence that pigs was a source of infections that family.

SUAREZ:  Any observations?

WEBSTER:  Yes, let me comment on pigs.  This virus has been isolated from pigs in China on a number of occasions.  And experimentally, we can infect pigs in containment facilities.

Why do we worry about the pig?  The pig has been proposed as an intermediate host between the bird and humans.  The pig has receptors for both the avian flu and the human flu, and it's been described as the mixing vessel.

Therefore, we give particular attention to the pig.  But the message that we had is that this virus can go into pigs.  It has not established itself in pigs in any country that we know of, and experimentally, this virus in pigs behaves like in humans.  If we infect pigs -- put another pig in the same cage -- the virus doesn't transmit pig to pig.  The pig gets sick, doesn't transmit.

So it behaves as a model -- a great model -- for studying transmissibility.

SUAREZ:  One of the primary duties of Council on Foreign Relations moderators is that they get off on time. 

So I want to thank you for being with us.  This break is 15 minutes.  Please be back in your seats at 10:00 o'clock to start the next panel.  And please thank our guests. 

(Applause.)

 

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