Extended Interviews

Dr. Stuart Nichol

Interview with Dr. Stuart Nichol

Dr. Stuart Nichol is chief of the Molecular Biology Section, Special Pathogens Branch, at the Centers for Disease Control (CDC) in Atlanta, Georgia. He is also a professor of microbiology and immunology at Emory University. He spoke with FRONTLINE/World’s Serene Fang from the CDC headquarters in Atlanta about what we can learn from the origins and history of zoonotic diseases as well as new approaches the CDC is taking to combat them.

FRONTLINE/World: Can you tell us what led the CDC toward the One Health concept?

Dr. Stuart Nichol: If you look where emerging diseases are coming from, the vast majority of those are coming from animals. Viruses are jumping over from natural animal reservoir hosts into the human population, and they're causing these large emerging disease problems. As an agency like CDC, you can't just focus on the human disease problem. You have to think more holistically and think about what's going on in animals and where these viruses are coming from. How are they being maintained in these animals? How are the animals getting exposed to them, and how are they making that jump from their natural animal hosts to the human population? So you've got to start taking a much broader look at emerging disease problems.

"Clearly, trying to merge the programs and the expertise and the knowledge from both the animal side and from the human health side makes for a much more effective strategy in detecting these emerging disease problems."

I think, in a way, there's a very different culture associated with the health sciences and with the veterinary and livestock communities. They're living in very different professional organizations, and they're living in different institutions. Clearly, trying to merge the programs and the expertise and the knowledge from both the animal side and from the human health side makes for a much more effective strategy in detecting these emerging disease problems -- how to respond to them very effectively and how to try to start predicting where these emerging diseases are going to come from, which areas of the world, which types of communities, and so forth. Working closely with the public health officials, veterinary authorities, agricultural people, wildlife specialists -- pulling in all those kinds of institutions and different expertise -- makes you much much more effective in dealing with emerging disease problems.

What are some examples of why this is such an important issue?

A good example would be the discovery of hantavirus pulmonary syndrome (HPS) in the United States in 1993, a very severe pulmonary disease in people that caused many deaths. That was associated with a virus normally seen in deer mice populations throughout the southwest of the United States, which spilled over into humans. Obviously, understanding what's going on in the deer mice gives you the ability to predict when we might see more HPS cases and where might we see them. Looking at examples like Ebola or Marburg hemorrhagic fevers, we now have good evidence that these viruses are normally in bat populations. We're getting a spillover of the virus from the bat populations into humans. To put in place risk reduction measures to try to prevent or reduce the numbers of human infections, you have to understand what is going on in bats.

Another example would be Nipah, a disease that emerged in Malaysia in the mid-90s. This was a disease first seen in pigs. We realized that pig farmers and people coming in close contact with those pigs were also getting a severe disease. It turned out, actually, that the virus tracked back again to Lyle’s flying foxes [a species of bat]. So you had spillover of the virus from the foxes to the pigs, from the pigs into the humans. As you can imagine, in that kind of outbreak investigation and response, eliminating the virus from the pig population took very close coordination between the public health authorities and the agricultural authorities and then, for the bat part, with the wildlife authorities as well. Coordinating those efforts and communicating well across a spectrum of agencies really gives you the most effective way of dealing with emerging disease problems.

So I think this whole One Health approach to emerging diseases is really trying to merge these links between different agencies and people working with infectious disease. And, actually, even spilling over into the environmental and ecological fields as well. For example, increased, abnormal rainfall in East Africa causes large mosquito populations. And mosquitoes carry Rift Valley fever virus, which causes huge, high-mortality disease outbreaks in livestock in East Africa. And then, as it becomes amplified in livestock populations, you see very large outbreaks in humans, too, as they deal with very infectious animal products and blood.

So there you have a good example of an emerging disease problem that takes in satellite data, such as looking at rainfall patterns. So you really have to take this holistic approach to the emerging disease problem, and that’s what CDC is trying to promote very strongly at the moment.

How did we first come to know about these diseases, like Ebola and Marburg, and what can be learned from those examples?

For Marburg virus, this is really a story that goes back to the 1960s. That virus was actually discovered by an outbreak of hemorrhagic fever in facilities in Europe, in Germany and Yugoslavia. These facilities were importing African green monkeys from Uganda and then using the tissues of these animals as part of vaccine production. What happened was, they got a batch of African green monkeys with a high mortality rate, which was unusual. Then, several people who were working with these materials became infected with a very severe hemorrhagic disease, and about a quarter of those people died very rapidly with this massive hemorrhaging, which was very, very graphic. So it really captured the imagination of the authorities and of the public at that time. A lot of work went into it and showed that this was a new family of viruses -- not just a new species of virus, but a completely new virus that was previously unknown in science.

It became known as Marburg virus because of the town in Germany where this facility was. Then, the virus activity kind of dropped off the radar screen. We saw one or two very small cases in various parts of East Africa and down as far south as Zimbabwe, but no major outbreaks. And we had no idea how people had acquired the virus in those cases.

And then, the first large outbreak that we saw in Africa was in Derber in the Democratic Republic of Congo in 1998. So you had almost a 30-year gap without the virus, and then we saw a very large outbreak -- more than 150 cases. About nine out of ten people who got infected died very rapidly with this virus. And the epidemiological data, and eventually the genetic data, tracked the virus back to an illegal gold mine outside the town of Derber.

People were mining in very poor conditions in this old abandoned gold mine, and it turned out there was a large population of bats in that mine. And eventually, we found the actual virus, the Marburg virus, in the bats in that mine. That's clearly where the people had got infected.

And then, skipping forward, there have been very recent, high-profile infections that have happened to a couple of tourists in East Africa. A Dutch woman who went as a tourist to a python cave in Uganda contracted a hemorrhagic fever, which eventually was identified as Marburg. Unfortunately, that woman died.

But the publicity surrounding that case was picked up by folks in the United States, and it turns out there had been a woman from Colorado who had also gone to that same cave in Uganda several months earlier. And she had come back and was quite sick with a hemorrhagic disease, but was never diagnosed. So retrospectively, we went back and looked at her specimens and found that, yes, indeed, she'd also been infected with Marburg virus at this cave. This was the first imported case of Marburg hemorrhagic fever in the United States.

Since then, we've looked really carefully at the bats in that cave and have shown that, yes, the Marburg-virus-infected bats reside in that cave, and it's actually a specific species called Rosset Aegyptiacus or the tomb bat.

"I think we all agree that we're probably at a unique place in human history in terms of the size of the human population and the amount of global travel that is going on."

So, over the decades, we've slowly pieced together that Marburg, this nasty hemorrhagic disease, is acquired either directly or indirectly from the bat reservoir. And that shows that you're linking the public health program to wildlife. We now need to understand where this virus is in bats and what’s the mechanism of transmission from the bats to the people. Then put in place the risk reduction measures so that we can try to prevent people from getting these infections.

Working very closely with the Uganda wildlife authorities, we've limited tourists going into the cave, and we're hoping to fund the Ugandan wildlife authority to build a viewing platform that is a safe distance from the mouth of the cave but has telescopes on it so that people can see this massive concentration of bats as they fly out of the cave. So the tourist attraction stays in place for the national park, which is good for the Ugandan economy, but we've now got the safety measure built in, so people can see it in a very safe way.

In looking at these cases, particularly of the woman from Colorado, does it tell you anything about the vulnerability of our country to virus?

I think we all agree that we're probably at a unique place in human history in terms of the size of the human population and the amount of global travel that is going on. This is the time when we're most at risk for viruses coming over from wildlife populations or coming from livestock, and getting introduced at a local level into the human population. Then, from that local level, very rapidly being able to go global, due to the amount of movement that we have with people. So I think from a U.S. perspective, this is a time when we're highly vulnerable to emerging diseases; so we really need to take the problem very seriously and put a lot of resources into being prepared for it.

And I think that the most recent example of H1N1, or “swine flu,” shows that kind of vulnerability, where things can pop up in a very localized way and then very quickly turn into a pandemic because of the rapid movement of people around the globe.

What about Ebola? Where and how did that start?

Ebola actually was discovered after the Marburg viruses. It was discovered in 1976, as part of a large hemorrhagic fever outbreak in what was then Zaire, northern Zaire, which is now the Democratic Republic of Congo. At first, people thought maybe this was Marburg virus again. Things were very confusing because, at the same time this outbreak was being reported in northern Zaire, there were similar reports starting to come in from southern Sudan. It turned out that a hemorrhagic fever outbreak was going on in that area, too.

And, to make a long story short, basically we found that it wasn't Marburg virus in either of these locations; it was a new genus of virus, the Ebola virus. And it turns out that the two outbreaks were two different viruses, two different Ebola viruses. It wasn't the same virus in both locations. One became known as the Zaire Ebola virus, and the other became known as the Sudan Ebola virus. It was just a parallel kind of eruption of these two outbreaks, but actually there wasn’t a direct epidemiological link.

We're still trying to figure out -- again working with the wildlife authorities, working with the agricultural people -- trying to figure out where Ebola Zaire and Ebola Sudan are in nature. What is the role of bats? How are bats potentially moving the virus around? How much do environmental factors -- changing rainfall patterns, changing temperature patterns, how much deforestation is going on, changes in land use issues -- how do they affect why things pop up in different areas? You have to take a very holistic view of the virus and the disease problem and try to get this bigger picture that could improve your ability to  predict and respond to these sorts of outbreaks, and see if you can prevent people from getting infected with these viruses.

Why are zoonotic diseases so difficult to control?

Zoonotic diseases are difficult to control because you can't eliminate animals from the planet. A good example would be when we discovered HPS. We quickly identified the deer mouse as the reservoir for that virus. That's where the virus was coming from. That's where the people were acquiring their infections, from deer mice. But deer mice are the most common mammal in North America. There are probably more deer mice than anything else. So obviously you can't eliminate the source of the virus from the environment. You can't eliminate deer mice, because it would have a negative impact on the ecosystem in these areas. That's just one example. With the Ebola and Marburg viruses, which are hosted by bats, the response to those disease problems cannot be to eradicate all bats. They serve a very important role in the ecosystem. So, dealing with zoonotic diseases is a very complex and difficult problem because the source of this is not going to go away. This very large reservoir of mammalian species across our planet is always going to be there. We're always going to be getting viruses popping over these species barriers.

So what we have to work very hard on is understanding where viruses are in the animal populations. Which are the ones that may have pathogenic potential for humans? Where are those spillover events occurring most frequently? Then try to build programs so we can predict what might be the next emerging diseases. We can design better surveillance mechanisms and better response mechanisms.

But the basic problem is that, you know, we can't make it go away. There are lots and lots of viruses out there in animals. And, really, what we know today -- we know only the tip of the iceberg, if you think about how many different mammalian species there are across the planet. You think every one of these mammalian species carries at least ten viruses. You're looking at 10s, 100s of millions of viruses out there. So it's a huge problem. It's not going to go away anytime soon. We have to figure out how to make the resources to best protect the public from these emerging threats.