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Wednesday, October 24, 2012

"Where Will The Next Pandemic Come From?"

A horse dies mysteriously in Australia, and people around it fall sick. A chimpanzee carcass in Central Africa passes Ebola to the villagers who scavenge and eat it. A palm civet, served at a Wild Flavors restaurant in southern China, infects one diner with a new ailment, which spreads to Hong Kong, Toronto, Hanoi, and Singapore, eventually to be known as SARS. These cases and others, equally spooky, represent not isolated events but a pattern, a trend: the emergence of new human diseases from wildlife.

The experts call such diseases zoonoses, meaning animal infections that spill into people. About 60 percent of human infectious diseases are zoonoses. For the most part, they result from infection by one of six types of pathogen: viruses, bacteria, fungi, protists, prions, and worms. The most troublesome are viruses. They are abundant, adaptable, not subject to antibiotics, and only sometimes deterred by antiviral drugs. Within the viral category is one particularly worrisome subgroup, RNA viruses. AIDS is caused by a zoonotic RNA virus.
So was the 1918 influenza, which killed 50 million people. Ebola is an RNA virus, which emerged in Uganda this summer after four years of relative quiescence. Marburg, Lassa, West Nile, Nipah, dengue, rabies, yellow fever virus, and the SARS bug are too.
Over the last half dozen years, I have asked eminent disease scientists and public-health officials, including some of the world’s experts on Ebola, on SARS, on bat-borne viruses, on HIV-1 and HIV-2, and on viral evolution, the same two-part question: 1) Will a new disease emerge, in the near future, sufficiently virulent and transmissible to cause a pandemic capable of killing tens of millions of people? and 2) If so, what does it look like and from where does it come? Their answers to the first part have ranged from maybe to probably. Their answers to the second have focused on zoonoses, particularly RNA viruses. The prospect of a new viral pandemic, for these sober professionals, looms large. They talk about it; they think about it; they make contingency plans against it: the Next Big One. They say it might happen anytime.

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[There are] [t]wo reasons for that [the large number of RNA viruses], he explained. It’s not just the high mutation rates but also the fact that their population sizes are huge. “Those two things put together mean you’ll produce more adaptive change,” he said.

RNA viruses replicate quickly, generating big populations of viral particles within each host. Stated another way, they tend to produce acute infections, severe for a short time and then gone. Either they soon disappear or they kill you. Eddie called it “this kind of boom-bust thing.” Acute infection also means lots of viral shedding—by way of sneezing or coughing or vomiting or bleeding or diarrhea—which facilitates transmission to other victims. Such viruses try to outrace the immune system of each host, taking what they need and moving onward quickly, before a body’s defenses can defeat them. (The HIVs are an exception, using a slower strategy.) Their fast replication and high rates of mutation supply them with lots of genetic variation. Once an RNA virus has landed in another host—sometimes even another species of host—that abundant variation serves it well, giving it many chances to adapt to the new circumstances, whatever those circumstances might be.
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To put the matter in its starkest form: Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly. In other words, outbreaks of new zoonotic diseases, as well as the recurrence and spread of old ones, reflect things that we’re doing, rather than just being things that are happening to us.

We have increased our human population to the level of seven billion and beyond. We are well on our way toward nine billion before our growth trend is likely to flatten. We live at high densities in many cities. We have penetrated, and we continue to penetrate, the last great forests and other wild ecosystems of the planet, disrupting the physical structures and the ecological communities of such places. We cut our way through the Congo. We cut our way through the Amazon. We cut our way through Borneo. We cut our way through Madagascar. We cut our way through New Guinea and northeastern Australia. We shake the trees, figuratively and literally, and things fall out. We kill and butcher and eat many of the wild animals found there. We settle in those places, creating villages, work camps, towns, extractive industries, new cities. We bring in our domesticated animals, replacing the wild herbivores with livestock. We multiply our livestock as we’ve multiplied ourselves, establishing huge factory-scale operations that contain thousands of cattle, pigs, chickens, ducks, sheep, and goats. We export and import livestock, fed and fattened with prophylactic doses of antibiotics and other drugs, across great distances and at high speeds. We export and import wild animals as exotic pets. We export and import animal skins, contraband bushmeat, and plants, some of which carry hidden microbial passengers. We travel, moving between cities and continents even more quickly than our transported livestock. We visit monkey temples in Asia, live markets in India, picturesque villages in South America, dusty archaeological sites in New Mexico, dairy towns in the Netherlands, bat caves in East Africa, racetracks in Australia—breathing the air, feeding the animals, touching things, shaking hands with the locals—and then we jump on our planes and fly home. We provide an irresistible opportunity for enterprising microbes by the ubiquity and sheer volume and mass of our human bodies.

Everything just mentioned falls under this rubric: the ecology and evolutionary biology of zoonotic diseases. Ecological circumstance provides opportunity for spillover. Evolution seizes opportunity, explores possibilities, and helps convert spillovers to pandemics. But “ecology” and “evolutionary biology” sound like science, not medicine or public health. If zoonoses from wildlife represent such a significant threat to global security, then what’s to be done? Learn more. RNA viruses are everywhere, as Eddie Holmes has warned, and science has identified only a fraction of them. Fewer still have been traced to their reservoir hosts, isolated from the wild, grown in the lab, and systematically studied. Until those steps have been achieved, the viruses in question can’t be battled with vaccines and treatments. This is where the field and laboratory scientists—veterinary ecologists, epidemiologists, molecular phylogeneticists, lab virologists—come in. If we’re going to understand how zoonoses operate, we need to find these bugs in the world, grow them in cell cultures the old-fashioned way, look at them in the flesh, sequence their genomes, and place them within their family trees. It’s happening, in laboratories and at field sites all over the world; but it’s no simple task.
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