ETech Preview: On The Front Lines of the Next Pandemic

With all of the stress and anxiety that humanity deals with on a daily basis–confronting the dangers of global warming, the perils of a financial system in meltdown and the ever-present threat of terrorism–the fact that there’s yet another danger lurking out there ready to destroy mankind: the threat of a global pandemic, may be easy to forget. But although you and I may have driven thoughts of Ebola and the like from our minds, Dr. Nathan Wolfe worries about them every day. Dr. Wolfe founded and directs the Global Viral Forecasting Initiative which monitors the transfer of new diseases from animals to humans.

He received his Bachelor’s degree at Stanford in 1993 and his Doctorate in Immunology and Infectious Diseases from Harvard in 1998. Dr. Wolfe was awarded the National Institute of Health International Research Scientist Development Award in 1999 and a prestigious NIH Directors Pioneer Award in 2005. He’ll be speaking at the O’Reilly Emerging Technology Conference in March. His session is entitled, “Viral Forecasting.” Thank you for joining us.

Dr. Nathan Wolfe: My pleasure.

James Turner: So why don’t we start by talking about the Global Viral Forecasting Initiative. How is it different from the work that the CDC and the WHO and similar organizations do monitoring disease spread?

NW: Well, what we do is we actually focus on the interface between humans and animal populations. When we looked back and investigated the ways in which disease got started, the ways that pandemics really originated, what we found is that really the vast majority of these things are animal diseases. So rather than monitoring for illness, at which point it could potentially be too late, we’ve taken it one step backward. We actually focus on people who have high levels of contact with animals. And we set up large groups of these individuals and monitor the diseases that they have, as well as the diseases in the animal population. So the idea is to be able to catch these things a little bit earlier.

JT: The last disease that really made a big splash with the media was Ebola, earlier in this decade. But we really haven’t heard much recently. Have things calmed down as far as new and novel diseases? Or are we just hearing less about outbreaks these days?

NW: Well, I mean I think we’ve had really substantive important pandemics. If you take a look at SARS, for example. SARS really only infected about 1,200 individuals, but its impact was tremendous. It was billions of dollars of economic impact all throughout the world. Even in a place like Singapore, where you had a small number of cases, you had an incredibly substantive financial impact. And then, of course, right now we have H5N1 which is — they call it the bird flu. Actually, most influenzas are bird influenzas, so it’s a little bit of a misnomer. But H5N1 is a virus which is spreading around the world in birds. And if it does make a transition into humans, which some bird flu will over the next 20 to 30 years, it could be incredibly devastating. So I think that these are kind of constant and present dangers. They’re things that are increasing over time simply because of the way that we’re connected as a human population.

JT: Let me ask you about influenza because one of the things I’ve heard is that if we could just get the Chinese to stop putting their pigs and their poultry together, a lot of this would go away. Is that actually accurate? Is that how a lot of the new strains come out?

NW: Well, you know, what’s interesting about this current spread of this particular virus, H5N1–which is, again, this is a virus which is spreading around the world in bird populations, both domestic and wild populations–what’s interesting about it is it seems to be able to jump directly from birds into human populations. And so that’s a little bit different from the way that we’ve traditionally thought about the flu, which is that it did kind of have to make this jump over into a mammal like a pig before it could effectively jump into human populations. But we’re seeing that that might not always be the case.

JT: You’ve spent many years in the field; what is that experience like on a day-to-day basis? I mean the vision that we get of people working with these kind of problems in the field is they’re wearing spacesuits and they’re walking into villages of dying people. But I suspect that’s mainly just Hollywood.

NW: Well, look, we do do some outbreak investigation. And outbreak investigation really does sometimes involve just what you’ve described. But our day-to-day work is actually long-term monitoring of individuals in these rural villages, so it’s very much going in with local teams of scientists. We’re doing a project in Cameroon for example. And we work in countries throughout the world, but let’s say just as an example, Cameroon.

We have an entire team of Cameroonian scientists and field biologists. And we select the right villages. We go into the villages. We do spend a lot of time talking with leaders in those villages, and to individuals, explaining what it is we do. We spend a lot of time doing public health activities; for example, trying to help increase preventative activities for HIV as well as some conservation, some wildlife conservation. So there’s a lot of elements to the work. But some of the work is, in fact, bleeding individuals and getting samples from animals and things like that, so we can actually monitor this portal of entry for these viruses that are jumping from animals into human population.

JT: What is the experience of going into those types of situations?

NW: You know, often what I’ve found, and it depends on where you are in the world, but most often as you get into some of these rural areas, and we work in regions that have a lot of biodiversity because we’re looking for regions that are viral hotspots. And often that has to do with the diversity of animals that underlies them. So these are very rural regions, and one of the things you do find about rural regions pretty much all over the world is, while there definitely can be some questions about people that are coming into these locations, once they’ve gone through some of those questions, and often people are very welcoming, very hospitable, very interested in what we’re doing. In some of these places, we’re a little bit like the traveling circus, because we come in and people haven’t had the action and excitement in some of these locations. So often, we provide a little bit of entertainment, believe it or not.

JT: How do you actually do the tracking? Are you taking blood samples from animals and blood samples from humans and seeing what seems to be moving or —

NW: That’s right. What we do is, we have populations that have heavy exposure. So for example, hunters or people who are working in live animal markets or even, say, wildlife veterinarians. And then we follow these individuals over long periods of time. We collect various kinds of specimens from them. Blood specimens are typical. But, for example, if they would have a respiratory illness, then we would take specimens throat swabs and things like that. We also take specimens from the animals that they have exposure to. So, for example, if it’s somebody who’s butchering animals, then we have them collect blood from the animals that they’ve butchered, or at least a sample of those animals.

When they’re sick, we try to get additional specimens, so that we can actually try to catch things that are short-term diseases, because some things are acute diseases. Like for example, flu, where it comes in and causes someone to be sick and then they get better. But we also do the long-term specimen collection for viruses more like HIV or Hepatitis C, which are things that are long-term infections in individuals. And then, of course, once we find interesting new viruses, then we want to go back and monitor, to see if and how these things are spread from person-to-person. So that might involve going back and looking at households, looking at the children of infected individuals, looking at sexual partners. Because really, for us, what we want to do is identify viruses and other infectious diseases, but once we identify them, we really want to ask if these are just infections that came directly from an animal or if they’re things that have the capacity to spread and cause disease in humans. Because ultimately, our real interest is those things that have the capacity to spread and cause disease.

JT: We’ve heard a lot about the potential for shifting climate zones to place humans in greater contact with animal vectors if you’re seeing animals in areas that you didn’t see them before.

NW: You know, not really. I mean personally, I have not noted major differences in terms of climate change. I mean one of the things that obviously we do notice is that the roads, for example, logging roads and other roads, there’s more of these. And what that means is that there’s more connectedness between rural villages and urban centers. And what that means from our perspective is that things that previously might’ve gone extinct in rural villages where the virus would enter into a person from, say, an animal and may infect one or two people and would go extinct, all of the sudden, now there’s lots of ways for people to move back and forth and get to urban areas. And then, of course, the availability and movement of human populations through airplanes means that some of these very, very remote locations are very, very close to urban centers everywhere whether it be New York or Tokyo. So something that enters into one of our hunters in the middle of Congo previously would’ve been completely isolated now can move its way around the world very quickly.

JT: That kind of leads into the other question I had, which is the conventional wisdom has always been that because there’s so much easier access to global travel now, especially air travel, that we’re ripe for this horrible pandemic that’s going to wipe us out. And as you mentioned, even something like SARS which did start to spread more widely than a lot of these very isolated viral outbreaks we see, only infected under 2,000 people. Why do you think we’ve avoided, so far, one of these real pandemic in the sense of large percentages of the population being affected?

NW: Well, I mean I guess it depends on what you mean when you say avoided. I mean from my perspective, HIV was like a full — that was a full on hit. Now we’re talking about something like 35, 40 million people globally are infected with the virus. This is an animal virus that entered into people who were hunting and butchering chimpanzees. And it’s a virus that spread really globally just through these kinds of mechanisms. It’s a virus that we estimate probably entered into human populations quite early, perhaps late 19th century, even early 20th century. So before the Great Depression, there were a number of individuals in Central Africa who were infected with this virus, but it really only was with the contemporary air travel which occurred later in the 20th Century that this virus was capable of really becoming a pandemic. So I think there certainly are examples out there of how these things move.

And something like SARS, yes, the number of individuals it infected was very small relative to what it’s damage could’ve been. But the impact of that virus was huge economically. I mean, it really for some time was a local devastating point for some of these Southeast Asian economies. So if you imagine something like Ebola, while we’re not necessarily afraid of Ebola wiping out massive percentages of the human population because we can see it moving because there’s a really short amount of time between when people get infected and when they get sick and the symptoms are very obvious. So it’s not something which will spread without us noticing it.

But if you see really even three or four cases of Ebola in a place like Paris, that’s going to be something which will have tremendous economic long-term consequences. And I mean obviously, we know this from something like 9/11 where it was as devastating as it was, I mean we are talking a couple thousand individuals, but the long-term ramification of those deaths were incredibly substantive. And I think the same would be the case for certain kinds of diseases in certain locations. And SARS was a perfect illustration of that.

JT: Now, we’ve been talking mainly about viruses, but I’m just curious, the other big infectious agent that got a lot of attention in this decade was prions, specifically the ones colloquially known as Mad Cow disease. Have we seen more of these? Was that like a one off? Or are there more of those lurking out there to worry about?

NW: You know, I think that a variety of infectious agents have the potential to cause impact whether it be economic impact or health impact. And so prions are certainly one of those but also bacteria and parasites and, of course, viruses. Viruses have played probably the most important role in the major pandemics. But you have to remember something like malaria, which is a parasite, is an absolutely devastating thing. With regards to prions, I think, again, some of the factors associated with contemporary human lifestyles.

You know, for example, kind of industrial animal production does change the way that things work, right? If you think about a traditional setting where an individual kills an animal and then disburses that animal to however many people in the village, say 10, 20 people. So there’s going to be connections, say 20 connections between humans and animals. But if you talk about industrial animal production where you take, for example, making sausage or something like that, you may have a single meat product could’ve come from hundreds of animals. And that single product may be distributed to thousands of people. So the number of interconnections there increases very, very dramatically.

And so even if the probability of a jump over of one of these viruses or prions in this case, but you could have viruses jumping there as well, even if the per contact probability of transmission is low, you’ve so much increased the number of animal-human contact points that actually, the probabilities become more reasonable than they would’ve been in traditional settings.

JT: Right. I’ve heard a saying that when you eat a commercial hamburger, you’re actually eating a thousand cows.

NW: Yeah. I haven’t actually done the calculations myself, but that’s not surprising.

JT: Another question I had was we tend to be, as a race, very focused on the crisis du jour and I’d say probably right at the moment, the crisis du jour is the fact that no one has any money. How does that affect our focus on these more serious long-term problems, but ones that are easy to forget when you’ve got a hungry kid?

NW: I think just like in any area of work, what a group of people are doing sometimes will be the subject of attention and discussion and sometimes won’t. But in our case, we just plow ahead doing what we’re doing. People become very excited about the disease du jour. Say it’s bird flu and they get very excited about it one minute. And perhaps at that moment, their fear of a pandemic or of a major disaster is higher than say the people who have studied that phenomenon. But then later on, they focus on other things and they think the risk has gone away. And then their perception of the risk is lower.

And I think for those of us whose job it is to monitor these things on a day-to-day basis, our objective is just to keep steady and solid and not necessarily be too confused about whether people are focusing too much on it or not focusing on it and really just try to assess the risks. And that’s obviously what we do. But I do think it’s the kind of thing that in the long haul we don’t want to be distracted from this from a policy perspective, from a funding perspective. We need to keep on these things because their impact on economies is absolutely massive. So our own project, we’ve recently been awarded $11 million from a gift from and the Skoll Foundation. And we partner with those organizations in some of the work that we do. But we estimate that probably we need somewhere on the order of 30 to 50 million additional dollars to deploy this system, these early monitoring sites all throughout the world.

But if you think about that, even let’s say we really get what we need and we’re talking about somewhere between a $50 and $100 million investment, if we are successful over the next 30 years at early identification of a single pandemic, not to say even all of the information we’re going to find about all of these viruses, maybe we’ll find new things like human papillomavirus, other viruses that cause cancers which will have huge benefits, but all we have to do is not even prevent the pandemic but provide early warning for a single pandemic and the investment will have been one of the better investments ever in the history of human health. So I think we should be careful about being penny-wise, pound foolish when it comes to health, both for reasons of the importance of saving lives and preventing illness but even just from the perspective of cold hard economic realities.

JT: You obviously see a lot of things that we never hear about. What are the things right now that kind of would keep you awake at night if you were awake at night?

NW: I sleep really well, so staying up at night doesn’t tend to be my problem. But I mean I do — like just to give you a sense of it, for example, HIV, one of the consequences of HIV is that it causes immunosuppression. So people who have AIDS don’t have intact immune systems. But these individuals continue to have contact with say animals in different parts of the world. So that does represent a weakness that we have. So sometimes one disease can actually increase the probability that other things will enter into human population. So I am very concerned with people who are highly exposed to all of the animals and who are immunocompromised because of disease like AIDS.

I would definitely say influenza’s something we need to attend to. The history of influenza suggests that there will be a pandemic. It’s not to say that it occurs in a clockwise way, but certainly, every century we can expect at least two to three major flu pandemics. And when those happen, they definitely are devastating for human populations. And whether or not this circulating H5N1, what people call the bird flu, ends up being one of those or not is unclear. But we do need to certainly pay attention to it. And from my perspective, I think that when we know that certain diseases have pandemic potential, like for example, retroviruses or malaria parasites, we definitely need to focus at least some of our energy on understanding the unknown parasites or viruses in those known groups.

So the way I think about it is you have known galaxies and unknown galaxies of say viruses or infectious diseases. So we know about retro viruses, but there’s many unknown stars in the retro virus galaxy and we need to chart all of those unknown stars out and have a sense of which ones of them are entering into human populations. And so, for example, in our work we’ve demonstrated that there are a lot of retroviruses in humans that we’re not aware of and we should be aware of those things. But then also, part of our job is to identify completely unknown galaxies, groups of viruses that we simply are completely unaware of. And there will be many of those because our understanding of this really rich, diverse world of microorganisms is pretty limited. I would say that we’re probably in the stone age when it comes to our understanding of the microorganisms on our planet.

And that’s important for human health, but it’s important for everything because these are arguably some of the most dominant organisms on our planet, both in terms of their diversity as well as in terms of their mass and their ability to impact health and disease both with ourselves and our planet.

JT: You’re going to be speaking at the O’Reilly Emerging Technology Conference in March. Can you give us a feel for what you’re going to be speaking about there?

NW: Sure. I’m going to be talking about the importance of viruses and other what I call the micro cosmos, the viruses and bacteria on our planet and their importance both for human health and disease as well as the importance of these organisms for the health of our planet overall. But then I’m going to be talking about some ways that studying these, the micro cosmos if you will, can help us. So for example, I’ll be talking about our own network to study pandemics, but I’ll also be talking about ways that exploring this invisible diversity of organisms on our planet can help us in a range of different ways, both in terms of, for example, in changing our ability to alter our metabolism, helping us to come up with vaccines for cancers but also understanding some basic features about the nature of life both on our planet and elsewhere.

JT: Well, thank you. I’ve been talking to Dr. Nathan Wolfe who is the Founder and Director of the Global Viral Forecasting Initiative. He’ll be speaking at the O’Reilly Emerging Technology Conference in March. Thank you for taking the time to speak to us.

NW: My pleasure. Thank you.

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