Paul Hoffman: We are here now for our second panel, which we’ve called “Swine Flu and the Next Pandemic.”

Back in the Middle Ages, there were probably infectious diseases that hit a village and wiped everybody out. And then there were no humans near enough for the virus to jump to, so it’d just die out.

Now in this day and age, where the earth is much more populated than it was in the Middle Ages, where we have jet travel, where we’ve moved into areas like the rain forest, where there is a lot of species of microbes and things that we come in contact with that we didn’t in the Middle Ages, there is much more likelihood that new diseases will spring up.

We saw this even before jet travel really took off, and that was in 1918 where we had the influenza epidemic, where 50 to a 100 million people was the estimate that died. That’s a third of the population of Europe at the time. And 500 million people were infected, that’s the third of the population of the world; the population was 1.6 billion back in 1918.

The reason we are here today is of course to discuss swine flu, and understand what the latest thinking is about whether it’s a threat to public health, to understand what we learned from it, meaning what medical scientists have learned from it, what our public health system has learned from it. So we will ever be more prepared when we have the next public health crisis.

*****

Paul Hoffman: I’d like to introduce our first presenter. He’s going to talk about influenza and swine flu. Peter Palese. He is the chairman and a professor of the department of microbiology at Mt. Sinai Medical Center, here in New York. Please welcome Peter Palese.

Peter Palese: I would like to discuss briefly influenza viruses and the disease which is caused by these viruses.

So the viruses are in RNA [ribonucleic acid] containing virus. So it has this genetic information RNA. And if you look at this particle, it has eight RNA segments so they are one in the center and one, two, three, four, five, six, seven RNA. These are like mini chromosomes which are the genetic information of the virus.

This virus also has a very important characteristic and that is, on the surface, it has spikes. And one can see this in the electron micrograph. They are spikes associated with this various on the surface, and that’s actually what the immune system when we get infected, sees. So these surface proteins are called the hemagglutinin and neuraminidase, so these are two proteins which are on the outside.

We should also understand that the virus is very, very small. A cell which is infected by this virus is much, much larger. Not only larger than this room but it’s probably as large as the Empire State Building. So we are really dealing here with a very small virus which can within 8 hours, infect us all and kill this Empire State Building and make about a hundred thousand new virus particles. So this is a virus which can cause a disease.

In humans, we know that there is influenza every season in the Northern Hemisphere from November to March. And also many people know that a hallmark of the virus is that it changes. And if you look here at the different influenza viruses which have circulated in the last century, we know about the 1918 virus, which was, in terms of number of deaths, a very important historic event because within probably three month period, from November 1918 to about February of 1919, in the US alone, about three quarter of a million people died. So this virus, 1918, belongs to what we call the H1 sub-type. It means that it has a hemagglutinin of this H1 sub-type.

And this virus was also replaced in 1957 by a separate virus, a different virus which has a hemagglutinin II sub-type and that sub-type was prevalent for about 11 years.

And then in 1968, a new sub-type emerged, an H3 virus which, is actually still with us in 2009.

In addition to this there was also, in 1977, another H1 virus reappearing, and it turned out that it was very similar to a 1950 strand.

So in 2009, we have H1 viruses, we have H3 viruses circulating, and then in also an influenza virus. So the complexity of influenza is quite impressive that we have this co-circulating strand. And that explains why, for example, vaccines, which are very helpful, they are not perfect but they are very important way of preventing influenza, why vaccines have to have three different components. So for the last season, that means 2008 to 2009, we had in the vaccine formulation, three different influenza virus components; we had the H1 component, and this was an isolate from Brisbane, isolate number 59 and isolate in 2007; an H3 component; and an influenza B virus component, isolated in 2006.

Now that would be all very good if we could use these vaccines for several years. But unfortunately influenza also changes within, not only this major changes from 1918 to 1957 to 1968, but also within one of these H1 or H2 or H3; there are constantly changes going on. And that means, that the vaccines has to be changed as well.

For the 2009/2010 season, we have a vaccine formulation now which is being produced by manufacturers and there is actually a new strand and new influenza B virus. So for the season which will start in November of 2009, this is the new vaccine formulation.

So if we would only expect this three variance, we would be all happy. But what happened actually, in the end of March, April of this year [2009], was a new virus emerged and that was a virus which actually belongs to this H1 group, and is known as either the new swine virus, or the Mexican virus, or as the Mexicans call it, the American virus, the California virus. So clearly this is a new virus and I think the CDC [Centers for Disease Control] decided to just call it a new H1N1, H1 sub-type of the hemagglutinin and the N1 of the neuraminidase, the other surface protein.

And then very briefly, in the end of April [2009] morecases were confirmed in the US, and then we also found different countries. Five countries end of April. And we have several countries beginning of May. And then the World Health Organization (WHO), decided to call this a pandemic. The definition of a pandemic is a global epidemic. And as you can see here, we have several countries at the end of April and then in more countries in May. And then, about a month ago this was called a pandemic because it was found actually in many different countries.

Now, what is this virus? And why is it called, basically, a swine virus? It is a swine virus because most of its genes, most of these eight RNA segments actually are derived from a swine influenza viruses. In addition, we have also the yellow genes here, which is the PB1 which is one of the RNAs, one of the mini chromosomes that was actually derived from a human strain, two other genes that were derived from an avian influenza virus. And then five genes (four, five, six, seven, eight) were actually derived from different swine influenza viruses.

So it’s a very complex chimera and was very, very unusual. If someone would have asked me, and I think most of my colleagues in the fields, what would be the next pandemic virus? We would never have guessed it would be an H1N1 virus and one with this curious origin, curious derivation, one gene from human influenza virus, two genes from an avian influenza virus and the remaining genes from a swine virus. So this is a sort of a very unusual. Nevertheless, this virus has a sort of hit hard.

This shows us of the influenza cases in the US. Without going into detail, this is the peak of doing the January/February where B viruses are the green ones, the yellow ones are A viruses and then we have these different H1 or H3. And then, very suddenly in April and May, we get suddenly this new H1N1 viruses. Usually, we do not have the second peak. It’s a virus which is unusually in every respect that it is an H1 virus and then it is also occurs so late in the season in terms of isolates.

And the virus is actually quite active. This is a couple of weeks ago, 105 countries have already have confirmed this novel H1N1 virus. And the numbers here of total cases is probably not a very good estimate, but clearly in terms of the total deaths number, this is not probably much higher than we would see with regular season influenza, but nevertheless this is something to be concerned about.

What is also quite unusual is that the immunity, namely that micro neutralization tests showed that for those 24 years and under, the seasonal vaccination does not produce cross reactivity. In other words, people who are young actually, and had been vaccinated, they have very little protection against this. On the other hand, people over the age of 60 has shown to have some pre-existing immunity which is able to neutralize this virus. So this is one of the few things where old age is really good, in terms of this H1N1 virus. So the older ones sitting around here and standing around here are much more protected.

And the reason for that is that virus, H1N1 virus is actually derived from the 1918 virus. So this is a 1918 virus, which gave rise to, on one hand, the swine virus, because the virus really vent into the swine population and changed here. And this is a 90% change in the hemagglutinin in the H1 sub-unit. And on the other hand, it also went into humans and we still have H1 virus, as you remember from one of the first sites. And here we were able to make this comparison and this shows us that this new swine virus, which is a particular one is the California virus, is actually fairly closely related to this 1918 virus.

And so if you look at the genetic distance going from here, let’s say 1940, you can see that this is much more closely related than to a virus which was in 2007, if the lengths here indicate genetic distance.

So that explains, because the origin of both of these viruses, swine virus, as well as the pure H1 virus, is a 1918 virus and that it was closer if people like me who had been infected in 1945, 1948. So we have more immunity against this new swine virus which has jumped into humans.

So that is basically what is happening. There are a lot of studies that are going on right now. But I want to leave you with three interesting characteristics.

The first one is that indeed this new pandemic swine H1N1 virus is an H1 virus. Meaning that we all have some cross protection, of course the older ones more, but there are still some of what we refer to as herd immunity. So we all have some kind of protection. So it is not like an H15, or an H9 or an H5, whereas none of us have any protective immunity against such a virus. In the case of this H1N1, there is some evidence that there is some cross protection.

There is also very interesting thing, I mention this PB1 gene, one of this 8 RNAs, is missing, in terms of one of the protein at PB1F2, and it is present in the 1918, 1957, and 1968 virus. But it is not present in the 2009 swine virus. That I think, is very good news.

The last point is that it is also sensitive to FDA approved drugs. So, I think, yes it is a pandemic virus which we should all be concerned about. But on the other hand, it is not something which has all the virulence change which we seen in other pandemic strands, and we all have some herd immunity against this virus.

Paul Hoffman: Thank you very much.

*****

Our next presenter is Michael Worobey. He’s an ecologist and an evolutionary biologist at the University of Arizona. He is part of a team of researchers that have a very important paper published just last month in “Nature,” about the evolution of the swine flu virus. And what he basically found was that it has circulated undetected in swine for perhaps up to a decade. Michael Worobey.

Michael Worobey: Thanks, Paul.

I’m going to talk about the emergence of the swine flu epidemic. But I thought first I put it in the bigger context of the emergence of influenza virus in general.

So here is the kind of tool that I used. It’s an evolutionary tree and all I want you to notice is for this H1 variant here, there is a nice human lineage, the Spanish flu is on that. There is a swine lineage, and there is a bird lineage. And these are the major players in the emergence of human influenza.

And most of the genes, as Peter [Palese] said, of this new variant come from pigs.

So here is a picture from the paper that we published. And just in case this doesn’t mean much to you, all these lines and dots, I want to take you through what we found here.

So coming from British Columbia, I’d like to use the saguaro as the teaching tool. I actually work in Arizona now, so it makes some sense.

With viruses, they evolve so quickly that you can actually see evolution happen, not just on the time frame of years, but in this instance, in the time frame of weeks. And this was a bit of surprise with just a few weeks of sequences that were produced as this pandemic was unfolding, we were able to calibrate the molecular clock.

So let me just use this analogy, if you want to find out how old your saguaro was, you might not be able to do it just by counting tree rings or something. But if you have a photo from 1999 of this cactus in your yard, and you were able to compare it to how much it has grown in the ten years since that time. You start to have a grasp on how quickly this thing grows. And you can make some estimates from the different branches of the percent of that centimeter per year of growth rate, and that can allow you to work back to when the thing originated.

So we do the same thing with viruses. If you have a small observation window like this, you can often make really robust differences about things much deeper in time. Okay now as an analogy, I just want to show you an evolution tree that you are more probably familiar with here. So we do the same sort of things for primates, and if you did an evolutionary tree of primates, you will have a human branch on the tree, or more closely related species, or chimpanzees and bonobos, and then you have the more distantly related species here.

And you can place the date on the most recent common ancestors of all humans and that might be around a hundred years ago. You could also ask, what’s the most recent common ancestor of humans? And whatever is most closely related to them, and that’s all the way back here, around 5 million years ago. So for this swine origin flu pandemic we did exactly the same thing.

So two questions: What is the timing on that ancestor of the virus once it jumped into humans? So when that jumped take place and if you go gene by gene and asked what’s the most closely related species for each gene? It’s actually a pig virus. So we also ask for each gene, when that broke off from the rest of the sample of pig viruses. Okay, so now we’re back to this, and what you see for each gene is the human sequences go less quite recently in time, but nowhere near the March and April [2009] timeline that this thing first emerged, to our knowledge. And for each of the genes, the most closely related sequences are from pigs. Now Peter [Palese] mentioned that some of them ultimately are of avian origin, and some are human origin. What you see when you go gene by gene is that, even for the ones that are ultimately an avian or human origin, they traveled through pigs. And in each case, we find that there’s been a timeline of about 10 years where this virus has been in pigs but has gone totally unnoticed--which says something about our surveillance.

And for the human outbreak, what you see is a timeline of about somewhere around October to December of last year [2008] that the virus was probably in humans. So it took several months to actually spread to the point where the tip of the iceberg became apparent to us.

And here is a rather complicated looking slide that shows while you have genes from an avian pool, and from a human pool, each one of those actually travel through a pig before it got into this new swine origin influenza virus.

One other interesting detail when you look gene by gene and Peter showed a nice picture of the individual segments. So these are actual physically separated chromosomes. You can actually place a date for each one of those as to when it got to humans. When you do that, and you line it up against the answer you get if you take all of the genes together, you get a little bit of a discrepancy. And this discrepancy, it turns out, you get an earlier date with each gene than you do with the entire genome. And we think what’s going on there is once this virus jumps into humans, it actually started evolving at a more rapid phase, and it looks like it goes at about 1.5 times the rate that it evolves in pigs.

And there is some interesting reason why that might be. If you take that into account, and do a little correction for the rate of change, these gene by gene estimates actually starts to overlap the entire genome estimate, and they kind of converge on this timeline of the late autumn, possibly into the very first few weeks of January [2009] that this virus in humans is spreading.

So aside from the actual findings, I just want to spend a couple of moments talking about how this happens. So when the sequences first came out, they were published by places like NCBI [National Center for Biotechnology Information] and GISAID [Global Initiative on Sharing Avian Influenza Data]. And what was great about this situation was that information was made publicly available by pretty much all the parties in real time. So as soon as sequences are available, I started analyzing them, I started firing off emails to colleagues around the world who are doing the same sort of thing. And we set up a Wiki where we can all post our results and critic them, and people that are in competing groups worked together around the clock. We have some people n Arizona, people in the UK, people in Hong Kong.

So for a period of couple of weeks, we were working 16 hours a day and when you fell asleep, you knew that when you woke up in the morning, the research would be advanced another 8 hours, and pretty quickly came to grips with the timeline of this thing.

That kind of open access mentality flowed right through the publication in “Nature.” So “Nature” published this even though we’ve had some press coverage. They also made the paper open access so anyone can download it and look at it.

And I think it’s probably time to open up to the rest of the discussion and I’ll leave the rest of it for them. Thank you very much.

*****

Panel Participants:

Michael Worobey - Ecologist and Evolutionary Biologist, University of Arizona

Barry Bloom - Professor of Public Health, Harvard University

Jeff Koplan - Vice President for Global Health, Emory University

Peter Palese - Chairman, Dept. of Microbiology, Mt. Sinai Medical Center

Paul Hoffman - - Editorial Chairman, Big Think.com

*****

Paul Hoffman: I’d like to introduce our panelists now.

Seated right next to me is Barry Bloom. He’s from the Harvard School of Public Health. He’s a professor there and a former Dean. He’s advised the World Health Organization on malaria. He was one of the world’s leading experts on tuberculosis.

Next to him we welcome Jeff Koplan. He’s here from the University of Emory, where he is Vice President for Global Health. In an earlier life, he was the head of the Center for Disease Control during the anthrax years, and he began his career in public health in the 1970s. He’s one of the celebrated disease detectives of the CDC, which meant he would investigate HIV outbreaks, even environmental calamities like the Bhopal chemical disaster.

Peter Palese has returned to the stage.

And Michael Worobey.

Let me start by reading an account of swine flu that recently ran in “Seed Magazine”:

In March, the President of the United States appeared before reporters, discussed the reappearance of swine flu. Worried about a pandemic he announced that the appropriation of funds sufficient to inoculate every man, woman and child in the United States, amounting to nothing short of the largest public health campaign in the US history. What the New York Times call, quote, the virus that caused the great world epidemic of influenza in modern history has returned, and so the cost of inaction, the president argued was too great to countenance.

That was 1976, and Gerald Ford was president, and it was an outbreak of swine flu in 76. So immediately we started inoculating everybody. I think 25% of the population was inoculated. It didn’t amount to much. In fact, more people died from a rare syndrome from the vaccine. So the question is, are we overreacting this time around? Would you want to take a shot at this?

Jeff Koplan: I’m not sure we overreacted the first time around. It’s easy in retrospect to say that was an overreaction. But in fact the threat of the 1918 outbreak is such that it would be, were people to take it seriously, and after an expenditure of whatever it was to vaccinate people, was worth it.

You’re damned if you do, and damned if you don’t. You don’t do anything and that disease occurs and it kills a similar number of people as it occurred in 1918, you’re a fool and irresponsible in public health. If you try to prepare as best you can for something, and then it doesn’t occur, you are subject to criticism. But given those two options, I’d rather be prepared and be criticized.

Barry Bloom: Yes. I would just say that because of the anthrax outbreak in 2001, concern about bio-terrorism which maybe the public doesn’t see so much, has really strengthened tremendously the public health services within the States. So then I believe that we are a great deal more prepared even without a manufactured vaccine. To know what to look for, emergency rooms, hospitals, know how to keep score on this disease, so that if there were a serious pandemic with high fatalities, it would be a huge problem but were much further along now than we were in 2001.

Paul Hoffman: Are we out of the woods yet? In the 1918 pandemic, it was mild at first and then it struck with great virulence. What do we think it’s now? Michael?

Michael Worobey: Let me address that. So that’s something that has been repeated quite a few times since the swine flu outbreak originated, and there’s not a good scientific argument that that actually happened. Basically we know very little about what happened before the Fall of 1918. One of our colleagues Jeffrey Taubenberger has done fantastic work resurrecting the virus from the Fall of 1918 and after. But we don’t even know if the mild Spring wave was the same virus, or a totally different virus.

And I would just want to point out that there’s no particular scientific reason to expect that the virulence of this swine flu is going to increase. Now there are other concerns involving the numbers of people infected, but the virulence on a per case basis, we don’t expect it to increase.

Paul Hoffman: Here’s a very basic question. How can a virus that affects us have genes from birds in it, and genes from pigs in it? Could one of you explain?

Barry Bloom: It’s genes from viruses, not from pigs and birds.

Paul Hoffman: I understand.

Peter Palese: Basically it just tells us that we are also in a way, I trust, a different species, but we all belong to the animal kingdom. I didn’t say we’re animals.

Jeff Koplan: We are animals.

Barry Bloom: The biological big picture is this is really a bird virus. It’s something that probably existed in birds for thousands and thousands of years, and that’s where the greatest genetic diversity is. There are all sorts of different subtypes that circulate in wild birds around the world. And the viruses in humans and pigs are kind of a one-off advance. Every once and a while one of these bird viruses is able to replicate in a new host, and then it takes hold and spreads, and it’s a rare event. We can list or we can number these events on a single hand from 1918 onward, but they do happen every several decades.

Paul Hoffman: When do we think there will be a vaccine available for this [swine virus]?

Peter Palese: As Dr. Bloom said, we are much better prepared now than just five years ago. And companies are, as we speak, preparing new vaccines against this swine virus. So we have the regular formulation for the seasonal influenza, and those vaccines have been prepared. In additional, the companies prepare a forced strain, which will be a separate vaccine strain against the swine virus.

Because the swine virus is very similar to other H1 viruses which are circulating, there are no real technical challenges to make a vaccine, and companies are really able to make large quantities of this new vaccine.

Paul Hoffman: Jeff, in terms of the public health response to swine flu, what have we learned from this? What might we do differently if, say, a year from now another virus pops up?

Jeff Koplan: It think, as was indicated earlier, we’ve learned a lot year after year in a number of different episodes such as this. We’ve learned that the importance of the linkage of laboratory and epidemiologic information. We are learning but have much further goal in learning, something that Michael [Worobey] pointed out, which is that animal disease, and what goes on in veterinary medicine, and either will we commonly think of as agriculture, is extremely important to indicate upcoming risks for human populations. And that interplay, over and over again over the last several decades, has brought us disease after new disease. And that’s something we still have to do a better job of in the future, of getting a handle on animal infections as they apply to human population.

We talk about preparation. And that’s always one of the first questions asked: Are we prepared? And the answer is: Prepared for what? Prepared for an anthrax attack that involves ten thousand letters, and is mailed from forty different sites around the world? Prepared for ten thousand cases of a new illness, or a million cases?

So preparation is very relative, and we are better prepared scientifically, in terms of vaccine production and gearing up quickly, and probably recognition of new diseases, but it’s maybe very difficult to be adequately prepared for the clinical sequela of a serious case, because the number of respirators you’d need for a hospital, isolation rooms, protective equipment, is such that given our healthcare system, we can’t afford buying all that you would need for the worst case scenario, or even a medium case scenario.

So it is unlikely we will ever be prepared in the way people that people would say, that’s great, we’re really prepared for that. Nor would you want us to try to be because the expenditure in the healthcare sector would be so great, we wouldn’t be spending it on things you wanted now.

Paul Hoffman: What about world cooperation? We had another guest at Big Think, Laurie Garret, who’s the global health analyst at the Council for Foreign Relations, and she observed that Indonesia has not been releasing certain avian flu samples for a few years now, on the grounds that they believe that their own people, or poor people around the world, won’t benefit if any vaccine is created.

How do we address problems like this so we can have greater global cooperation, Barry?

Barry Bloom: It’s a big problem, and it has to do with the law of intellectual property. The perception that I have is that the rich countries are scientifically advanced. They invest in technology and they control most of the intellectual property and patents for things. And I think the cry from Indonesia, which is burst forth more quietly from other places, is that they want some share in any rights and royalties for discoveries made with materials, diseases, or viruses discovered in their countries.

That’s a radical change from the passivity of saying it’s the rich countries’ responsibility to take care of the poor countries. But it’s not putting tremendous, and I think appropriate demands, for just what you’ve said, is how do we share intellectual property? How do we make expensive vaccines available at low cost? As we are for AIDS drugs to people in Africa.

I would point out, when this played out with antiretroviral drugs; there was much screaming, particularly in countries in Africa, about intellectual property being monopolized by the rich countries. Turns out that the twenty-five sub-Saharan African countries with AIDS only one of them is a signatory to the intellectual property agreements at WIPO [World Intellectual Property Organization], and consequently, the rest of them were free to manufacture anything they wanted, because they were not bound by that. They simply didn’t have the technical capacity to do that.

I think the world has evolved. A lawsuit in South Africa was withdrawn. The companies have decided to reduce the price and say, we will share the technology that we have to help prevent death and save lives, when the case is really serious. And I would hope that Indonesia and other countries that are providing viruses for study, that get turned into vaccines, will be similarly cooperative.

Paul Hoffman: Michael, since your paper was published last month, have you seen any movement to try to monitor viruses in livestock more closely?

Michael Worobey: I have not any seen any movement of that sort yet. I’m not aware of everything that has happened, but I’m pretty optimistic that that’s the way things are going to go.

And to get back to your question about how we can be better prepared, I think this epidemic has taught us that we could do a lot more for surveillance, not only in humans but also in animals. And just being aware that there is a new subtype of virus circulating somewhere in the world, four months earlier than we were in this case, would set us up so much better to try that, isolate it, or at very least prepare a vaccine for it.

And I think that the convergence of that kind of thinking, with technology that’s out there, for sequencing these days, you can take a single sample from someone and produce amounts of data on the order of what the complete genome project produced over a several years, in a few hours now, for not very many dollars. And I think it’s reasonable to look into the future and see a time when doctors routinely take swabs from patients who might have influenza, when abattoir semblance samples, from a large sample of animals, and they go to somewhere, or multiple places, and if there’s any virus, we will detect it before it gets to the stage it is now.

Paul Hoffman: Barry, I know that we’ve been talking about infectious disease. Would you believe that there are other public health hazards that maybe claim more lives than what we’re talking about here?

Barry Bloom: The thinking that you hear about, that has been working out so beautifully with communicable diseases, I think, has much more general relevance just infectious diseases. And it gives me tremendous pleasure to show some slides that were put together by CDC [Centers for Disease Control] when Dr. Koplan was the director of CDC.

To try to convince you that the epidemic for example, of chronic disease of obesity, is not an epidemic of the press, but is much an epidemic in terms of transmissibility and across the globe as any communicable disease.

This is a map showing the body mass index, an index of weight over height. Anything over 30 is considered obese, anything over 25 is overweight.

This is the US 1985, 1988, 1991, 1994, 2000, 2001, 2002, 2003, 2004, 2005. If that doesn’t look like an epidemic, I don’t know what is, and it’s a very serious one.

If you say what are the consequences of this obesity epidemic, and how do we think about it in the same way we think about an infectious disease, how do we think about preventing it? We know that it’s a going to affect 20 million people in the US, 200 million worldwide. It’s costing us now 10% of the healthcare expenditures, some type 2 diabetes. It’s a major problem in this country and around the world. It leads to cardiovascular disease.

And I think it’s of interest that that is equally spread around the world, that it is not just a disease of rich countries. And so the tools of epidemiology have helped us follow the trends in disease and suggest to us the things that we must intervene in, or the cost of these diseases are going to be as great and greater than communicable diseases.

Paul Hoffman: Well Barry, we have vaccines that we can use to fight infectious diseases. Is there something in the wings that would work for this?

Barry Bloom: I’m very optimistic that there is a very exciting new development, one month old, in terms of the literature, there are three other studies that are similar.

We know that different heart diseases have dropped in the US since 1980, by at lest 50%, and deaths from stroke by 70%; 25% is that change in behavior, diet, and exercise. The majority of that is because we have medicines designed by scientists and the pharmaceutical industry that deal with the major risks involved. As you see here, cholesterol, blood pressure and platelet function.

How do you expect that to work in a poor country where we would give vaccines in and out quickly? And they have been combined into a single pill called the polypill; the first data in India have now appeared, and people just have to take one pill a day, that have a risk for heart disease, and what the results are quite spectacular, that the effects are about 62% prevention of all the symptoms that would lead to death from heart disease.

So this isn’t quite a vaccine but a one a day pill that we guess would cost maybe $30 a year, per patient, would save maybe million and a half lives in India and a million and a half in China. That’s as good as any vaccine that I know of.

Paul Hoffman: Jeff, one last comment and then we’re going to turn it over to question and answers from the audience.

Jeff Koplan: You refer to vaccines in the wings; well there is the equivalent of a vaccine on stage when it comes to tobacco. There are more people who quit smoking than are currently smoking in the country. It’s the largest preventable type of cancer in the world. It will kill a billion people before this century is over if we don’t make efforts to curtail it. And so, along with other plagues that we’ve been talking about, now the plague of tobacco smoking, that along with problems of diet, problems of physical activity, what I refer to as communicative diseases, as opposed to communicable diseases; we communicate them from one culture to another with disastrous effects.

Paul Hoffman: I’d like to take questions from the audience.

Audience member: Someone put up a slide that showed the mortality of this flu is around ½ or 1%. It sounds like that probably is overstated because of undiagnosed diseases and it just anecdotally appears that many people who died have had other immune compromises. What’s the likelihood of the virulence gene, the PB1F2, becomes part of this going forward, such that anyone would recommend an intentional exposure to the gene now, to the virus today?

Peter Palese: Okay so, you pointed out something very important. We don’t know the denominator, we don’t know how many people have been infected with the new swine virus, a-clinically or sub-clinically. So that’s one of the problems. We don’t know how many deaths or how many people got infected, so that’s one unknown at this point still.

The second question is, this virus, could it sort of change that it actually expresses its virulence gene and it turns out that actually three point mutations, which would make it possible that the virus would express as PB1F2, this virulence gene and that is sort of a fairly large number of mutations which would have to appear almost simultaneously. So yes it is possible. I don’t think it is very likely.

Paul Hoffman: Let me rephrase the question.

When I was a child, if you’ve had chicken pox there was a practice that many parents adopted, and that is they would take your siblings and have them sleep in the same room, such as you were exposed to chicken pox. The idea was that if you caught it as an adult, it would be much more serious, so you should get over it while you’re a child. I heard some suggestions that people wanted to do this in terms of swine flu. Is that a horrible thing to do?

Peter Palese: I think we have arrived a little bit further along. We don’t have chicken pox problems anymore, we fortunately have a vaccine, and I think we also have a vaccine come October of this year. So I think the answer is vaccination, not chicken pox stories.

Michael Worobey: There’s one other component. When you get chicken pox, then you’re immune for life. When you get measles, you’re immune for life. When you get the flu, you’re immune probably till next year, maybe two years down the road--because the flu is constantly changing.

So it’s one of the worst viruses that you could conceive of, having a pox party for, because the immunity doesn’t last like it does. What you’re doing is, you’re creating a scenario where the people at the pox party are probably going to infect other people who weren’t interested in having a pox party, who will infect other people. And when you take that into account, to me, it seems irresponsible.

Audience member: Professor Palese talked about how surprising the configuration of this flu is. The different genetic structure of it. What is the upshot of that? Do you think about that now, going forward, in terms of what flus we might see in the future, does that indicate that sort of what we thought about the flu genes was wrong? Or does it indicate that maybe the flu is evolving faster?

The avian flu scare was quite recent and now the swine flu pandemic. Is there more recombination that’s happening, or is this just happenstance or are we catching more of it? What does this mean for the future?

Peter Palese: Let me try to give it a shot and then maybe we can expand on it. As I’ve said, I think we all in the field, would not have expected this swine virus to emerge as a new pandemic strain. And I think it’s really not predictable that it was a swine virus and I don’t think it was predictable, the kind of re-assortment, the kind of origin these different genes have.

I think it’s really, I don’t know how to say this, it’s a winner, a lottery winner. In a way, I think it is a sort of unpredictable and I don’t think we really understand what happened in a way, I think it was just by chance.

I think these re-assortments do happen, and quite frequently, but only one out of that many really will cause a disease inherence. That will be my interpretation.

Michael Worobey: I agree with that, and especially with what you said about, it’s one in a million that actually work in humans and for every one that does jump, there must have been lots that tried to.

And in effect we noticed that if you look at veterinarians who work with pigs in the States, about 25% of them have antibodies to some kind of swine flu virus. So it’s a process that probably is happening all the time, but it dead ends. One person gets infected, maybe infects one other person but it goes extinct.

This one, for whatever reason, works well in humans. And although we didn’t predict it, and we don’t know why, I think it’s possible that we’ll now be able to go back and say, ok, well this thing has a matrix gene from ultimately that avian source.

Maybe its something about that combination, we may be able to learn something from this that will help predict it, but we’re still at a very primitive stage of being able to understand why these things happen.

Paul Hoffman: We have time for one more question.

Audience member: One of you mentioned some of the clinical challenges of pandemics, and about how the healthcare system isn’t quite ready to handle a huge pandemic. How might the current healthcare reform present challenges and opportunities for pandemics in the future?

Jeff Koplan: Oh you’ve hit the nail right on the head. When we talk about being prepared, that area we are least prepared with, is taking care of people at the early stages of their illness, because of the large number of people who won’t come in because they’re uninsured or under-insured.

And people tend not to think of the healthcare system as an element of this problem in being prepared. But the speed with which we recognize new cases in any outbreak, not just influenza, but an anthrax attack, bio-terrorism event, SARS [severe acute respiratory syndrome], it’s extremely important in control measures. And the longer you get significant pockets of population not coming for care when they become ill is a serious problem for these type of pandemics.

So I think healthcare reform that provides some level of universal coverage with people, and encourages them to come in when they’re sick at early stages, is extremely important in these control areas.

Paul Hoffman: We’d like to thank all our panelists. We’d like to thank you, the audience for coming out tonight. We’d like to thank Pfizer for making this all possible, and Big Think for making it possible, and the Rubin Museum which has lent us this wonderful space. If you didn’t have a chance to glance at the art on the way out, you still have a few minutes where you can do that. Thank you very much.

Recorded on: July 14, 2009.