by Nathan Wolfe
Category Four agents represent the final step on the journey to become a human-specific microbe. They also present particular problems for public health. When scientists finally succeed at generating a vaccine for dengue, it will help countless people. But vaccination alone does not mean that we can eradicate dengue. Even if every single human were vaccinated, the fact that the virus can persist among monkeys in forests in Asia and Africa means that it will always have the potential to reenter human populations.
Monkeypox still ranks as a Category Three agent, but that could certainly change. Since our work in 2007, we’ve shown that the cases of monkeypox continue to grow in the DRC. Part of the explanation for this is that after smallpox was eradicated in 1979 the smallpox immunization program was stopped. As more and more nonimmunized, and therefore susceptible, children have been born into the population, the number of cases has steadily risen. And each additional case represents an opportunity for a unique monkeypox virus to jump or mutate. One of these may have the potential to spread and push monkeypox to the next level, which is why we keep tabs on this particular virus.
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Only a handful of the microbes that have started on the path toward becoming exclusive human microbes have succeeded. The examples that have made it represent the mainstay of contemporary disease control. Viruses like HIV are generally considered to be present exclusively in humans, as are bacterial microbes like tuberculosis and parasites like malaria.5 Yet it’s often difficult to make the human-exclusivity call. Unless we have comprehensive data about the diseases of wildlife, it’s hard to know if there may be a hidden reservoir of a supposedly exclusive human agent that could reenter human populations. And our understanding of the diversity of microbes in wild animals is still in its infancy. We know very little about what’s out there.
Agents like human papilloma virus and herpes simplex virus almost certainly reside exclusively in humans, but they have likely been with us for millions of years. With an agent like HIV, we get into a gray area. Could the virus that seeded HIV a hundred or so years ago continue to live on in chimpanzees? Viruses very close to HIV have been found in chimpanzees, but we haven’t sampled every chimpanzee in nature, so even closer relatives might still be out there. Similarly, given the diversity of malaria parasites we’ve seen in some of the African apes during recent studies, the possibility remains that some population of ape in some forest shares “human” malaria.
The question of reservoirs is an important one. We celebrated with great fanfare the eradication of smallpox in 1979. Eliminating that scourge from the human population was probably the greatest feat in public health history. Yet much remains unknown about how smallpox originated.
Smallpox appears to have first emerged during the domestication revolution. Evidence points to an origin in camels, which are infected with the closest known viral relative to smallpox, camelpox. Yet camels may very well have been a bridge host permitting the virus to jump from rodents, where most of the viruses like smallpox reside. If so, could there be a virus out there living in some North African, Middle Eastern, or central Asian rodent that’s too close for comfort? A virus close enough to smallpox to reemerge and spread in humans? If so it might look a lot like monkeypox, and, like monkeypox, it might be largely missed.
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For our purposes we should certainly consider smallpox to be one of our Category Five agents—a virus that made it to the point where it could live and survive exclusively in humans. And we should be proud of the herculean and successful effort to wipe it out.
Smallpox certainly had the right stuff. It probably killed more humans than any virus that has ever infected our species. Following the domestication revolution, the growing human populations and domestic animal populations (like camels) set the stage for the virus to gain a true foothold in our species.
We’ll probably never know definitively what the first real pandemic was, but smallpox is a good candidate. It spread throughout the Old World after its likely camel origins but never made it to indigenous human populations in the New World on its own. When the Old World and New World collided at the onset of global travel some five hundred years ago, smallpox had the chance to make the jump, killing millions of the completely susceptible inhabitants of the Americas. That jump across continents positions it as the most likely candidate for the first real pandemic.
By the middle of the eighteenth century, smallpox had not only spread to every part of the world but had established itself just about everywhere, save for some island nations. And it killed. During the eighteenth century, it’s estimated that smallpox killed around four hundred thousand people a year in Europe. The death rates elsewhere may have been even higher.
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The human tendency to travel, to explore, and to conquer would accelerate dramatically over the five hundred years that would follow the discovery of the New World—and the coinciding smallpox pandemic. Global transportation networks would tie humans and animals together in a way that would accelerate the emergence of new viruses. These connections would result in a single, interconnected world—a world vulnerable to plague.
6
ONE WORLD
In 1998 scientists working independently in Australia and Central America announced that they were finding massive numbers of dead frogs in the forests where they worked. The large-scale die-off was especially dramatic. Global amphibian populations had been declining for some time, but these mounting frog deaths occurred in pristine habitats—places far less likely to have been exposed to toxic by-products of human cities or other man-made environmental threats. Field biologists and tourists alike witnessed the large numbers of dead frogs scattered about the forest floor. This was rare indeed since scavengers quickly eat dead animals. To see so many indicated that the predators already had their fill of free frogs and these were the leftovers. In fact, it was just the tip of the iceberg. A massive and unprecedented amphibian carnage was under way.
The expiring frogs all displayed similar and worrying symptoms. They became lethargic, their skin sloughed off, and they often lost their ability to right themselves if turned over. In the months that followed the first announcements, a number of possible explanations came forth—pollution, ultraviolet light, and disease among them. Yet the particular pattern of death was most consistent with an infectious agent. Animal deaths spread in wavelike patterns from one location to the next suggesting the spread of a microbe, a contagion sweeping through the Central American and Australian frog world.
Frogs killed by the amphibian chytrid fungus. (Joel Sartore / National Geographic / Getty Images)
The solution to the mystery came in July 1998, when an international team of scientists reported the source of the frog disease. The team found evidence that a majority of the frog species succumbing to the die-offs were infected with a particular species of fungus. The fungus they identified was Batrachochytrium dendrobatidis, known more simply as the chytrid fungus (pronounced KIT-rid). They found evidence of chytrid, which had previously been seen exclusively in insects and on decaying vegetation, on a number of dead frogs. Tellingly, when they scraped the fungus from the dead and infected healthy laboratory tadpoles with it, they were able to re-create the fatal symptoms. The fungus was to blame.
Since the 1998 report, this fungus is now documented on all continents that have frog populations. It can survive at sea level but also wreaks havoc at altitudes up to twenty thousand feet. And it’s a killer. In Latin America alone, chytrid fungus has been linked to extinction in 30 of the 113 species of the strikingly beautiful harlequin toads. Thirty species forever removed from the biological diversity of our planet.
While the spread and devastation of chytrid has now been well documented, much about it remains unknown. The large-scale declines in amphibian populations predated the emergence of the fungus, so it is not the only problem that is devastating global frog populations, but it’s definitely among them. Another key factor is the steady decline in available frog ha
bitat as the human footprint has increased over the last hundred years.
The questions of where the fungus originated and how it spreads are largely outstanding. Work done on archived specimens from South Africa shows that the fungus has infected African frogs since at least the 1930s, decades before it hit any other continent. This points to an African origin. Yet at some time, the fungus spread and did so quite effectively. How did it manage to get so cosmopolitan so quickly?
One possibility is the exportation of frogs. The researchers who discovered the early evidence of chytrid in South Africa also noted that some of the species of the frogs infected were commonly used in human pregnancy tests. When injected by lab technicians with urine from pregnant women, African clawed frogs (Xenopus laevis) ovulate—which made for an early, if significantly more cumbersome, version of the common pregnancy dipsticks used today! Following the discovery of this human pregnancy test in the early 1930s, thousands of these frogs were transported internationally for this purpose. Perhaps they took chytrid fungus with them.
But Xenopus was likely not alone in causing the global spread; since one stage of the fungus’s life cycle actively spread in water, that was also a probable factor. Human movement almost certainly played a role as well. Our shoes and boots are at least partially to blame. This small fungus, wanted in the deaths of frogs worldwide, hijacked us.
The chytrid fungus has resulted in global frog deaths and in some cases extinction of entire frog species, a tragic loss for wildlife on our planet. In a 2007 paper, Lee Berger, one of the researchers who first identified the chytrid fungus, used language uncommon in conservative scientific journal articles when he wrote, “The impact of [chytrid fungus] on frogs is the most spectacular loss of vertebrate biodiversity due to disease in recorded history.”
What happened with the chytrid fungus also gives us important clues to a larger phenomenon that affects much more than just amphibians. Over the past few hundred years, humans have constructed a radically interconnected world—a world in which frogs living in one place are shipped to locations where they’ve never previously existed, and one where humans can literally have their boots in the mud of Australia one day and in the rivers of the Amazon the next. This radically mobile world gives infectious agents like chytrid a truly global stage on which to act. We no longer live on a planet where pockets of life persist for centuries without contact with others. We now live on a microbially unified planet. For better or worse, it’s one world.
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How did we get to this point? For the vast majority of our history as living organisms on this planet, we had incredibly limited capacity to move. Many organisms can move themselves over short distances. Single-celled organisms like bacteria have small whiplike tails, or flagella, that allow them to move, but despite their molecular-scale efficiency, flagella will never push their owners far. Plants and fungi have the potential to move passively by creating seeds or spores blown by the wind. They also have adopted methods that co-opt animals to help them move, which explains the existence of fruit and the spores of fungi like chytrid. Nevertheless, precious few forms of terrestrial life regularly travel more than a few miles in the course of their lives.
Among the wonderful exceptions to the largely static life on Earth is the coconut palm. The seeds of the coconut palm (i.e., coconuts), like a number of other drift seeds, evolved buoyancy and water resistance, permitting them to travel vast distances through ocean currents. Among animals, some species of bats and birds are masters of space. The best example might be the Arctic tern, perhaps the most mobile species on Earth outside of our own. The tern flies from its breeding grounds in the Arctic to the Antarctic and then back again each and every year of its life. A famous tern chick was tagged on the Farne Islands in the UK near the time it was born in the summer of 1982. When it was found in Melbourne, Australia, in October of the same year, it had managed a twelve-thousand-mile journey in the first few months of life! It’s been estimated that these amazing birds, which can live over twenty years, will travel about one and a half million miles in their lifetimes. It would take a full-time commercial jet pilot, flying at the maximum FAA permitted effort, nearly five years to cover the same distance.
Yet despite their wings, most bird and bat species actually live their lives quite close to where they’re born. Only a few, like the Arctic tern, have evolved to regularly move great distances. Highly mobile species, whether bird, bat, or human, particularly the ones that live in large colonies, are of particular interest for the maintenance and spread of microbes. Among primates, only humans have the potential to move themselves great distances during a single lifetime, let alone in a few days. That’s not to say that other primates simply stay put. Almost all species of primates move every day in their search for food, and young adults routinely move from one area to another before mating. Yet whether primate or bird, nothing on the planet—certainly nothing outside of the sea—matches humans in our capacity to move long distances quickly. The human potential to move, which now includes traveling to the moon, is unique and unprecedented in the history of life on our planet. But it comes with consequences.
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Humans started globetrotting in earnest millions of years ago using our own two feet. Bipedalism gave us an advantage over our ape cousins in terms of our capacity to wander. And, as discussed in chapter 3, it had consequences for how we interact with the microbes in our environment. Yet our capacity to negotiate the globe in the amazing way we do now started with our use of boats.
The earliest clear archaeological evidence of boats dates to around ten thousand years ago. Found in the Netherlands and France, these boats (which might be better called rafts since they were made by binding logs together) were probably used primarily in fresh water. The first evidence of sea-going boats comes from a group of British and Kuwaiti archaeologists, who in 2002 reported finding a seven-thousand-year-old vessel that undoubtedly was used at sea. The archaeologists made their discovery at the Neolithic site of Subiya in Kuwait. Stored in the remnants of a stone building, the boat consisted of reeds and tar. Most strikingly, the bits of boat had barnacles attached to the tar, indicating that it was definitely used in the sea.
Employing genetics and geography, we can get a much earlier estimate for the first use of seafaring boats. The indigenous people of Australia and Papua New Guinea provide perhaps the best case for this. By comparing the genes of the Australasian people with other humans throughout the world, we can conclude that people reached Australia at least fifty thousand years ago.
During this time, our planet was a relatively cold place—it was the peak of an ice age. Since more of the Earth’s water was locked up in ice, the sea level was lower, revealing pieces of land that connected what are currently islands. Many of the islands in the Indonesian archipelago were joined by these so-called land bridges.
Despite the land bridges that ice ages expose, we know that no one walked all the way to Australia. In particular, the deep-water channel between Bali and Lombok in present-day Indonesia, a channel around thirty-five kilometers long, would have required boats to navigate. So we can infer that these early populations also used at least some form of sea transport.
We know very little about these early Australian settlers, although we know that they traveled at a time before animal domestication so certainly didn’t move with animals in tow. Nevertheless, their movements impacted how they related with microbes. When they first crossed from Bali to Lombok, they encountered a completely novel set of animals.
The channel between Bali and Lombok lies squarely on Wallace’s Line, the famous geographic divide named after the nineteenth-century British biologist Alfred Russel Wallace who, along with Charles Darwin, codiscovered natural selection.1 While the distance between Bali and Lombok was no greater than that between many of the waterways separating the hundreds of islands along the Indonesian archipelago, Wallace noted that animal populations on either side of the channel differed extensively. And while h
e didn’t have the precise models for ice age water levels that we have today, he surmised that this biological divide existed because Bali and Lombok were never connected by a land bridge, something we now know to be true.
Like humans, other animals take advantage of land bridges, but unlike these earlier settlers who had boats, the animal populations that couldn’t fly long distances were largely stuck on one or another side of this deep-water barrier. When the first explorers left Asia for the Australasian continent, making the thirty-five-kilometer hop from Bali to Lombok, they took a fairly short trip by boat but a huge leap for primates. When they crossed this divide, these early explorers entered a world that had never seen monkeys or apes before. They also encountered completely new microbes.
Wallace’s Line, and the landbridges that once connected the islands on either side of it. (Dusty Deyo)
These early settlers would have been hit with novel diseases from Australasian animals and their microbes, infectious agents that had never seen a primate before. Yet the impact of these agents for the human populations as a whole was likely limited, since the small population sizes of the settlers wouldn’t have been able to sustain many kinds of agents.
It’s hard to know exactly what the first trips across Wallace’s Line were like. They may have been colonization events with small groups that were then completely cut off. Perhaps more likely they were short initial forays into new lands, followed by the establishment of temporary outposts, much as we consider colonizing the moon. The actual way in which the new lands were colonized would have played an important role in determining the flow of microbes in either direction. And while these first Australasian humans almost certainly had some connections to the “mainlanders” they left behind on Bali, that contact may have been very infrequent. Yet some new Australasian infections that had the potential for long-lasting human infection could very well have made their first forays into human populations on the Asian side of the divide.