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The Man Who Saw the Pandemic Coming

Will the world now wake up to the global threat of zoonotic diseases?

Berger_HERO

Dennis Carroll doesn’t mean to sound callous when he says the coronavirus outbreak was predictable. And he doesn’t. He sounds sympathetic to people frightened by the outbreak. He has been an eyewitness to people around the world suffering from similar viruses. Most of all, Carroll sounds authoritative.

For decades, Carroll has been a leading voice about the threat of zoonotic spillover, the transmission of pathogens from nonhuman animals to us. Scientists are confident the current outbreak, which began in Wuhan, China, stemmed from a virus inherent in bats. In 2009, after years of studying infectious diseases at the Centers for Disease Control and Prevention, and the United States Agency for International Development (USAID), Carroll formed a USAID program called PREDICT, where he guided trailblazing research into viruses hiding, and waiting to emerge, in animals around the world.

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“Dennis is a visionary,” says Christine K. Johnson, an epidemiologist at the One Health Institute at the University of California, Davis, where she is a professor in the School of Veterinary Medicine. “He took the reactive approach to infectious diseases and turned it on its head. He said, ‘We’re going to work on a proactive approach to help countries prepare for the emergence of infectious diseases.’” Johnson, an investigator at PREDICT for 10 years, says Carroll was a pioneer in looking beyond livestock. “Dennis saw that emerging infectious diseases, far and wide, have mostly come from wildlife, and there needed to be investment in research in the wildlife sector.” For a decade, PREDICT received annual federal funding of $15 to $20 million. In 2019, its funding wasn’t renewed. Carroll left USAID and formed a new program, the Global Virome Project, “to build on PREDICT’s scientific insights and experience,” he says.

This is a global event. It is going to hit every community everywhere in the world.

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In conversation, scientific insights, based on his experience, emerge from Carroll with a sting, whether he’s talking about the biology of viruses or the stagnant response to the outbreak from the White House. I began by asking about the source of the outbreak.

on site: While in Vietnam being filmed for the recent Netflix documentary series, Pandemic, Dennis Carroll took a moment to pose with two members of the Vietnamese crew.Courtesy of Dennis Carroll

How did the current coronavirus pass from a bat to humans?

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We don’t know specifically, but presumably the virus was being shed by the animal in the market, and humans were proximal. Or it could have been that people were directly handling the animal. There may have been a secondary source. In the 2002 SARS outbreak in China, we didn’t see people’s direct exposure to bats as the source of infection. There was a secondary source, a wildlife animal, the civet cat.

Could the transmission have resulted from people eating the wildlife?

Typically the preparation of the animal is where you have exposure. By the time it’s cooked and prepared, the virus would have been dead. It’s more common that transmission is through the animal shedding or people slaughtering the animal, when they’re exposed to bodily fluids, blood, and secretions. With the avian influenza from poultry, a lot of the exposure and infections go back to the preparation of chicken for cooking. In Egypt, for instance, when you look at who was infected, more common than not it was a woman, directly responsible for slaughtering and preparing the animal.

We think of ourselves as special. But viruses are infecting us with the same purpose they infect a bat.

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In 2018, you and colleagues wrote in Science, “Our ability to mitigate disease emergence is undermined by our poor understanding of the diversity and ecology of viral threats.” What do we need to understand about the diversity and ecology of viral threats?

The first thing to understand is that whatever future threats we’re going to face already exist; they are currently circulating in wildlife. Think of it as viral dark matter. A large pool of viruses are circulating and we don’t become familiar with them until we see a spillover event and people getting ill.

Do bats have a particularly high potential for spillover?

Certainly. We’ve been able to identify bats as reservoirs for coronaviruses and documented specific bat populations as reservoirs for Ebola virus. We want to understand how each of these bats operate within an ecosystem. Do they have certain behaviors and practices that either keep them remote from or proximal to human populations? The bat population in which we isolated the Ebola virus in West Africa was a species of bat that also tends to co-roost within human housing, so it elevates the opportunity for spillover.

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Have there been disturbances in their environments that have brought bats closer to us?

The disturbances in their environments are us. We’ve penetrated deeper into ecozones we’ve not occupied before.

What’s a telling example of our incursion?

In Africa, we see a lot of incursion driven by oil or mineral extraction in areas that typically had few human populations. The problem is not only moving workers and establishing camps in these domains, but building roads that allow for even more movement of populations. Roads also allow for the movement of wildlife animals, which may be part of a food trade, to make their way into urban settlements. All these dramatic changes increase the potential spread of infection.

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Are spillover events more common now than 50 years ago?

Yes. EcoHealth Alliance, an NGO, and others, looked at all reported outbreaks since 1940. They came to a fairly solid conclusion that we’re looking at an elevation of spillover events two to three times more than what we saw 40 years earlier. That continues to increase, driven by the huge increase in the human population and our expansion into wildlife areas. The single biggest predictor of spillover events is land-use change—more land going to agriculture and more specifically to livestock production.

I’m stunned by the absolute absence of global dialogue for what is a global event.

Is there something specific about a virus that makes it zoonotic?

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You can argue viruses aren’t living organisms. They’re sheets of proteins encapsulating some DNA or RNA. Beyond that, they have no machinery to be able to live on their own. They’re looking for an ecosystem that has all of the other cellular machinery essential for replication. They can’t live outside another animal population. They need that animal to replicate. And we’re just one more animal. We think of ourselves as something special. But viruses are infecting us with exactly the same purpose they infect a bat or a civet cat.

Viruses live on a delicate balance, don’t they? They have to be able to thrive without killing their host.

Right. The ones that kill off their host quickly will disappear. With the SARS virus, it’s no surprise that killing 10 percent of its host, it wasn’t able to establish itself as a pandemic virus on this planet.

Are there any signs that this coronavirus will kill itself?

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This one has a lower pathogenicity. The lower its virulence, the more likely it’ll become part of an endemic, part of a seasonal event. That’s one of the big things that’s going to be a worry. If it does go quiet over the summer months, then the question’s going to be, “Is it still infecting people?” We could be walking around in the middle of summer with influenza viruses, but they’re not active. They’ve just gone quiet. When the right ecology comes into play, it starts getting cold, and damp, then it starts replicating like crazy. If it’s able to park itself, and not kill its host over the summer months, then we’ve got a virus that has all the telltale signatures of establishing itself as part of our normative landscape, much to our detriment.

Do you think the current outbreak was inevitable?

Oh, sure. It was predictable. It’s like if you had no traffic laws and were constantly finding pedestrians getting whacked by cars as they crossed the street. Is that surprising? No. All you need to do is to better manage how we set up crosswalks, how we establish traffic rules and regulations. We’re not doing that. We’re not establishing the kind of safe practices that will minimize the opportunity for spillover. If we better understood where these viruses are circulating and understood that ecology, we would have the potential to disrupt and minimize the risk of spillover.

Why aren’t we—governments and policymakers—doing that?

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First, this is an expanding problem driven by unprecedented population change. It’s only in the last 100 years that we’ve begun adding people at a rate that’s causing this incredible disruption of the larger ecosystem. If you and I were having this discussion 100 years ago, there were 6 billion fewer people on this planet. It took us the better part of our total existence of the species, 300,000 years, before we hit the 1 billion mark. But in 100 years we’ve added 6 billion people and we’ll add another 4 to 5 billion before the end of this century.

Second, governments and society by and large are governed by inertia. We don’t change and adapt and evolve very quickly. And we’re barely cognizant as a global society that the world we’re living in today is fundamentally different than the world our species has ever lived in. You know that old saw that if you drop a frog in a pot of boiling water, it will leap out. But if you take that same frog and put it in a pot of ambient water and slowly crank up the temperature, it will stay in that water and boil to death. It loses perspective on the changing environment around it. We’re that frog in the ambient water. We’re oblivious to the conditions that have enabled zoonotic viruses to become integrated into us.

There are things about this outbreak that are not being talked about. Those are the things that worry me the most.

What first really opened your eyes to the scale of the spillover problem?

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You mean my Saul on the road to Damascus moment?

Exactly.

It was avian influenza in the 2000s. What you saw with avian influenza was a direct consequence of how much poultry was being produced to feed people. If you look at China today, it produces something on the order of 15 to 20 billion poultry per year. But if you went back and you looked at the data from the 1960s, you see that, at best, only a few hundred million poultry were under production. When you look in Bangladesh, Vietnam, and elsewhere in Asia and Indonesia, you see that the amount of poultry that was being produced 50 years ago was orders of magnitude less than poultry being produced today. That’s a consequence of more people and more purchasing power. One of the things we know about household purchasing power is that when you have disposable income in your hands, you’re going to move from a root- or grain-based diet and try to get animal protein. And that’s what happened.

One statistic that jumps out of what you wrote in Science is there are 1.67 million viruses on Earth and an estimated 631,000 to 827,000 have the capacity to infect people. That’s pretty frightening, no?

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On one level it is pretty frightening. But on another level the potential to infect doesn’t necessarily correlate with illness and death. Some viruses may not have any consequence at all. And some may be involved in enhancing our own biology. They could become part of our microbiome. It’s nothing new in the course of evolution. We have to be open to the idea that viruses aren’t simply our enemies, that they may have an important and positive role to play for us. We found that out about bacteria. At the same time, we have to keep our eyes open and be cautious about the pharmaceuticals we take. If we’re taking broad-spectrum antivirals, they could be opening up other complications.

How would you describe the general attitude of the United States government toward the threat of zoonotic diseases?

It’s not just the U.S. government but governments at large and the private sector—we don’t invest in risk. Talking about zoonotic diseases is different than talking about tuberculosis or malaria. Those are tangible. They are clear and present problems. Zoonotic diseases are an emerging problem. But we as a society don’t invest in things that are not kicking our door down.

The coronavirus is kicking our door down now, don’t you think?

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Yes, it’s got everyone’s attention. But this coronavirus will fall off the headlines and when it does, you will see a contraction in the kind of investments that are made in it. We have war budgets and then no monies during peacetime. So part of the challenge—it’s a social engineering exercise—is getting lawmakers and investors to invest in risk. That’s really difficult.

The fact that your PREDICT program was not refunded has become a political rallying point against President Trump, who has shown an ignorance of science. Do you think there’s a connection between the end of PREDICT and what has happened with the coronavirus?

No, I don’t think so. PREDICT was a beautiful project. It was scientifically well executed. It was forward-leaning. But its scale was small. It discovered slightly more than 2,000 viruses. If you’re going to have a public health impact, finding 2,000 viruses out of a pool of 600,000, over 10 years, isn’t going to transform your ability to minimize public health risk. And PREDICT didn’t really navigate the second step in a critical equation—turning science into policy. We didn’t design it for that purpose. Also, even an annual budget of $20 million is not sufficient. You’d need about $100 million a year to carry out the kind of global program that would give us evidence to transform how we think about viral risk and how we should prepare for it. That’s what my new Global Virome Project aims to do.

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What worries you about this coronavirus?

There’s the obvious stuff that’s worrying everyone. But there are things not being talked about. Those are the things that worry me the most. This is a global event. It is going to hit every community everywhere in the world. And the impact will not be equally distributed because there are parts of the world that have health care systems that are far more fragile than ours or China’s or Europe’s. We know that when fragile healthcare systems have extraordinary new demands put on them, there’s an enormous risk those health systems will collapse. Specifically in the Africa region and regions where there’s civil disorder or war.

In 2014, when the Ebola virus swept across the three countries of West Africa, we saw that one of the immediate consequences of the virus was to essentially shut down health-service delivery. Health workers became exposed, sickened, and fearful. For five months, you did not have health services that were tending to people’s normative healthcare. Pregnant women didn’t have access to trained birth attendants. Kids didn’t have access to anti-malarials. Immunizations didn’t go on. You had an undocumented population of people whose lives were compromised because they couldn’t get routine health services. My fear is this will likely play itself out again. If the coronavirus continues to be as significant as it appears to be, we’re going to see health systems get overloaded and not be capable of responding to both the virus and normative health issues. No one in government seems to be talking about this.

In 2005, during the avian influenza, George W. Bush was on the phone routinely with leaders around the world about how to coordinate a global response. Barack Obama did the same in 2009 for the second H1N1 pandemic and in 2014 for the Ebola epidemic. You saw presidential leadership step up and act as a catalyst for forging a global way forward for a global problem. It has been absolute silence in this White House. I think the only reason the White House is even paying any lip service to this is because the stock market has gone into a free fall. So they’re trying to figure out what are the words they need to say to placate the stock market.

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Why do you think there’s been silence in this White House?

Because the Trump administration is only interested in America first. Populism here and across Europe and elsewhere has fragmented the global networks, which had been so instrumental in being able to bring together a global approach to problems like this. I’ve not seen any reports coming out of the White House that showed that as China was struggling to bring the virus under control, our president reached out to President Xi to talk about how to coordinate action. I’m stunned by the absolute absence of global dialogue for what is a global event. In Europe right now, you would never believe that there was a European Union. From where I sit, it looks like every country is making this up as they go along. Italy isn’t coordinating with Brussels. Brussels isn’t coordinating with Germany. There’s no coherent regional approach to this problem in Europe, even though they have a platform for doing it.

So what will it take to make people aware of the global threat of zoonotic diseases?

There’s nothing like a serial assault to heighten your awareness, and that’s what we’re looking at. We’re on a cycle of about every three years of getting something like this. And each time that happens, there’s more awareness that these investments need to be made and sustained. The problem is getting these monies as part of the annual regular non-emergency funding.

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There’s been exemplary sharing of data among scientists and geneticists, don’t you think?

Yes. But think of the syllogism from Socrates: right thinking leads to right action. We know that’s not the case. Your thoughts can be absolutely right on, but your practices can be completely divergent. What science allows us to do is understand, with greater granularity, what’s at risk. Science will give us insight. But we have to translate that insight into a sustained valuation of risk and move that forward.

How, ideally, should we move forward?

These viruses inherently have the ability to mutate. What we’re looking at today isn’t necessarily what we’ll be looking at in a few months. It could become more deadly or it could attenuate and disappear, like the common cold. The big issue is, Are we tracking that? Do we have enough data and transparency and the availability of samples? What’s showing up in Iran? What’s showing up in Israel? What’s showing up in Italy? What’s showing up in the United States? Is there enough open transparency in real time that allows us to keep our finger on the pulse? I’m an internationalist. Figure out how to care for our people. Pay attention to communities around the world that need assistance. We’re all part of the same ecosystem. This is a global issue. We either prepare for it and respond to it in the context of a global lens, or we don’t. If our preparations and responses are country-centric, we’re in for some serious trouble.

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Kevin Berger is the editor of Nautilus.

Lead image: Associated Press

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