THE GREAT MICROBE BOTTLENECK
The oysters were excellent, but the company was even more striking. As I sat in the
small Parisian bistro with a tray of fresh shellfish, I savored the taste of the ocean.
But the more powerful memory of that day was of another patron of the restaurant.
At the table next to me sat an impeccably put together Frenchwoman. Her bag,
skirt, and socks all matched—not exactly, but just enough to notice. Her dining
companion sat to her right—a miniature poodle, sitting on the chair and drinking
water from a bowl on the table. Pieces of his meal—chicken I think—fell over the
side of his plate, mingling with the crumbs from his owner’s bread.
Dogs play an important role in the lives of many people around the world. I had
stopped only briefly in Paris on the way home from a month-long trip conducting
research in Asia and Africa. It might have been the jet lag, but my recollection of
the event could only be described as surreal. During my trip I’d spent time in a part
of Borneo where people eat dog, including on at least one occasion my unsus-
pecting self. I’d also visited Muslim areas of the Malay Peninsula, where devout
people won’t even touch dogs because of religious beliefs. And I’d spent time in
central Africa, where I’d seen local hunters work with their small, silent basenji
hunting dogs—dogs that lived on their own but in exchange for scraps followed
hunters into the forests, helping them catch their prey. In the United States, many
people treat dogs as members of their families, paying large fees for medical ex-
penses and mourning for them when they die. Sitting on the beach near my home
in San Francisco, it would be hard for me to spend an hour without seeing some-
one kiss his or her pet dog on the mouth. Watching that woman in Paris sharing a
meal with her dog solidified just how linked we are to these animals.
The close relationships we have with dogs, whether as companions, work animals,
dinner guests, or a source of food, should not surprise us. Dogs play a special role
in human history. If we were to compile the “greatest hits” of human evolution,
hunting and cooking would certainly make the cut. Language and the capacity to
walk on two feet would also be on the list. But central among our species’ critical
historical events is domestication—and dogs were the first in a long line of plants
and animals that our ancestors tamed.
The capacity to domesticate plants and animals underlies much of what we now
think of as being human. To imagine a world without domestication, we’d have to
spend time with one of the few dozen human populations on the planet that still
practice hunting and gathering lifestyles, groups like the Baka and Bakoli, the so-
called pygmies, living in central Africa that I have worked with for years, or the Aché
that live in South America. For these groups of people, there is no bread, no rice,
no cheese. There is no agriculture, and therefore the many rituals of our planet’s
major traditions, including the harvest and planting pilgrimages and their asso-
ciated festivals, are entirely absent—no holidays such as Ramadan, Easter, or
Thanksgiving. There is no wool, no cotton, only textiles made from wild tree bark
or grasses and the skins from hunted animals.
These hunter-gatherer populations have complex histories, and many of them
lived at some point with some form of agriculture before returning to a foraging
lifestyle. Yet they provide us with interesting clues on what the lives of our ances-
tors looked like before the advent of widespread domestication.¹ Among the traits
hunter-gatherer populations share are small population sizes and a nomadic life-
style. As we’ll see, these traits have an important impact on keeping the microbial
repertoires of these populations at low levels.
The first human foray into domestication came with modification of wolves into
the canines we know today. Archaeological and DNA evidence suggests that pop-
ulations in the Middle East and east Asia began domesticating gray wolves as early
as thirty thousand years ago, turning them into guard dogs and work animals as
well as using them for food and fur. The early history of dog domestication is still
unclear. One hypothesis is that wolves followed humans, scavenging off of their
kills, and over time became dependent on humans, a dependency that set the stage
for their later domestication. But no matter how it began, by fourteen thousand
years ago dogs played an integral role in human life and culture. In some archaeo-
logical sites in Israel, humans and dogs were even buried together. These early
dogs would have resembled modern-day basenjis, the silent hunting dogs pre-
ferred by the central African hunters with whom I work.
Occurring around twelve thousand years before we would domesticate anything
else, the domestication of the dog was an early precursor to what would follow.
Around ten to twelve thousand years ago, a domestication revolution occurred in
earnest, starting with sheep and rye and then followed by a diverse group of other
plants and animals.
The consequences and opportunities of the domestication revolution were pro-
found. Prior to domestication, human populations were limited by the food avail-
able in wild environments. Wild animals migrate, which forced our ancestors, who
were dependent on the hunting of these wild animals, to do the same. The wild
fruits and other plant foods present in the local habitat were spread out, which
again forced seasonal movement. Wild environments, with a few minor
exceptions,² lacked the capacity to sustain large populations of people. As a conse-
quence, human population sizes were small, probably numbering no more than
fifty to a hundred people in a group, and mobile.
Human population through history. (Dusty Deyo)
As domestication truly kicked in around five to ten thousand years ago, this
would all change. With a combination of domesticated plants and animals, hu-
mans gained the capacity to have sustained sources of calories year-round. Agri-
culture (i.e., the domestication of plants) made it possible for human populations
to stay in one place and avoid the constant movement that characterizes hunting-
and-gathering populations as well as populations with only domesticated animals,
which need to move in order to find feed for their herds. A sedentary lifestyle and
the capacity for food surplus radically increased the potential for populations to
grow, leading to the first real towns and cities. The particular combination of larger
population sizes, sedentary groups of humans, and the growing populations of
domestic animals would play a central role in transforming the relationship be-
tween humans and microbes. But humans aren’t the only animals that tame the
wild.
Despite conventional wisdom, the capacity for domestication is not unique to hu-
mans. The most striking example of domestication in the animal kingdom comes
not from primates, dolphins, or elephants—in fact, not from a vertebrate species
of any type—but from ants. Far from simple-minded insects, ants are part of
unique and complex colonies, each of which is perhaps better imagined not as a
group of individual ants but rather as a collective ant “superorganism.”³
Leaf-cutter ant colonies exist in most tropical American habitats. Known to
schoolchildren worldwide for their incredible strength, the workers march through
the jungle carrying pieces of green leaves many times their own size back to the
nest. Yet the leaf-cutter’s strength is not its most interesting feature. This amazing
group of ants has mastered the art of domestication. Rather than eat those massive
leaves, the workers chew them up into a fertilizer. The colony uses the fertilizer in
order to support their gardens—for leaf-cutter ants, made up of the Atta and
Acromyrmex groups, cultivate a fungus-based crop and have spent millions of years
living off it. These ants are farmers.
Domestication of fungus has helped leaf-cutter ants become one of the most
successful species on our planet. Mature leaf-cutter colonies, measuring fifteen
meters across and five meters deep, can house upward of eight million ants. The
massive underground colonies are sedentary, sometimes lasting for more than
twenty years in the same location.
These remarkable ants have attracted a number of scientists, including a Cana-
dian researcher named Cameron Currie. Dr. Currie has used molecular tools to
examine the genetics of the ants, their fungus, and the other members of this in-
credible community. His research has shown the evolutionary links between the
ants and their fungus crop. The colonies and their crop species have lived together
for tens of millions of years, a much more mature farmer-crop relationship than
that seen in humans.
Like human farmers, the ants have agricultural pests, including a specialized
fungal parasite that spoils the farms. Dr. Currie has shown that not only have the
ants and their crops lived together for millennia; the parasitic fungus has been
along for the ride since the beginning. Another amazing twist to this elegant sys-
tem is that, like human farmers, the ants utilize a pesticide. They cultivate a species
of bacteria that produces fungicidal chemicals that help the ants control their ver-
min. Some people think of ants as pests, but these ants have their own pest prob-
lems.
Humans began domesticating other species merely thousands of years ago,
rather than millions, as with the leaf-cutters. Like the ants, we’ve found that one of
the consequences of high crop densities is parasites. The fungus species that the
ants cultivate almost certainly had pests tens of millions of years ago, before they
were cultivated by the leaf-cutters. But when the leaf-cutters accumulated the fun-
gus and added fertilizer, it allowed more fungus to live closer together than re-
sources would have permitted without active farming. Cultivation leads to concen-
trated populations, and concentrated populations have higher burdens of para-
sites, whether fungus or virus.
While the leaf-cutters focus exclusively on farming fungus, humans have taken
agriculture and livestock to entirely new levels. Rather than cultivate a species or
two over the course of a few millennia—lightning speed in evolutionary terms—
humans domesticated a vast range of plant and animal species.
We take it for granted, but the diversity of living things that our species culti-
vates boggles the mind. In an average day, we might wake up in sheets (cotton)
and wool blankets (sheep); put on leather shoes (cow) and perhaps a cashmere
sweater (goat); eat a breakfast of eggs (chicken) and bacon (pig); bid farewell to
our pets (dog, cat) on the way to work; for lunch we might eat a salad (lettuce, cel-
ery, beets, cucumber, garbanzo beans, sunflower seeds) with dressing (oil from
olives); for a snack we might eat a fruit salad (pineapple, peaches, cherries, pas-
sionfruit) or mixed nuts (cashews, almonds, peanuts, actually a legume); for din-
ner a caprese salad (tomato, buffalo mozzarella) and pasta (wheat) with peas and
smoked farmed salmon with fresh basil (all domesticated). It would be an uncom-
mon day for many of us not to interact with at least three domesticated animals
and a dozen or so domesticated plants. We are truly masters of domestication.
Consumption of wild foods, the source of calories for virtually all other organ-
isms on our planet, now represents an almost quaint luxury for most humans. My
friends Noele and Giovanni make a delicious wild asparagus pate from plants gath-
ered in woods outside their small hillside village near Reggio, Italy. But using wild
vegetables is now the exception rather than the rule. Wild salmon costs signif-
icantly more than farmed salmon in the vast majority of the world. Eating wild veni-
son, something my friends Mimi and Chris like to do each year in their Massa-
chusetts cabin, represents a challenging “return to nature” rather than a regular
source of calories.
The transition from a species primarily dependent on wild sources of nutrients
to a species that cultivates most of its food means that we don’t need to depend on
the fluctuating food availability in uncultivated habitats. It also allows for the con-
centration of these activities, with a few individuals focused on developing food
while the rest of us have time to pursue other objectives, like, say, virology. We are
freed from the daily foraging required of our ancestors before domestication. For
our purposes here, it also radically changed the way that we related to the microbes
in our world.
In the field sites where I work throughout the world, my collaborators and I work
closely with hunters and monitor for new microbes that cross into them as they
catch, prepare, and consume wild animals. Yet the hunters are not our only focus.
Among the things we study in rural villages are the domestic animals—the dogs,
goats, pigs, and other species that surround these people. Each animal, wild and
domestic, has their own microbial repertoire, and when concentrated on a farm or
in a house or herd, these microbes thrive.
Domestic animals have contributed novel microbes to humans in different
ways. Since these species each had their own predomestication microbial reper-
toires, the initial close contact of farming led to an early exchange of their microbes
to humans. My colleague Jared Diamond has provided detailed evidence for this
exchange and its consequences for human history in his excellent book Guns,
Germs, and Steel. Among other things, Jared showed that the preponderance of
domestic animals in temperate regions contributed to a higher diversity of mi-
crobes among temperate populations. For example, measles descends from rinder-
pest, a virus of cows that entered into humans, a domestication-associated virus
that continues to plague us.
Humans have close interactions with domesticated animals, whether for com-
panionship, protection, or food. These interactions reach fascinating extremes. In
Papua New Guinea, women in some ethnic groups actually suckle their pigs, pro-
viding human breast milk to ensure the survival of these valuable animals. This
level of close connection has obvious implications for the movement of infectious
agents.
Of the microbes that originated in our domesticated animals, many entered into
humans thousands of years ago, at or near the time that we first domesticated
them. Acquiring the microbes that belonged to our domestic animals played an
important role in enhancing the microbial repertoire of our ancestors during the
climax of domestication five to ten thousand years ago. Over time, this has
changed. In the case of dogs, for example, most of the microbes that they had to
contribute to humanity have already crossed over. In some ways, the microbial
repertoire of our species has merged with that of dogs and the other animals we’ve
domesticated. Even without breastfeeding our domestic animals, we often cuddle
with them for warmth or play. We almost always have closer connections to them
than we would to wild animals.
The historical “predomestication” dog microbes that had the potential to cross
into humans have largely done so, and the human microbes that could survive in
dogs have also crossed. The ones that haven’t crossed successfully likely don’t
have the potential to, and while they may lead to occasional infections in one or
two individuals, they won’t have the capacity to spread—the critical trait required
for something to have true impact.
Over the thousands of years of interaction, we have reached a sort of microbial
equilibrium with domestic animals. But this doesn’t mean that these animals don’t
still contribute to our microbial repertoire; quite the contrary. Domestic animals
continue to feed new microbes into the human species. These bugs derive not
from the animals themselves, but from wild animal species that they are exposed
to. Our domestic animals act as microbial bridges, permitting new agents from
wild animals to make the jump into us.
There are numerous examples of domestic animals bridging the microbial di-
vide between humans and wild animals. Perhaps the best documented of these is
the case of Nipah virus, a fascinating bug whose emergence has been studied in
detail by my collaborators Peter Daszak and Hume Field and their colleagues.
Through years of viral sleuthing, they have shown in exquisite detail exactly how
the virus negotiates the complex world of humans and our farms.
Nipah virus was first detected in Malaysia, in the village that gave it its name.
This virus kills. Of the 257 cases of infection seen during 1999 in Malaysia and
Singapore, 100 people died, a startlingly high mortality rate. Among the survivors,
more than 50 percent were left with serious brain damage.
The first clues to the origin of the virus were the patterns of human cases. The
vast majority occurred among workers in piggeries. At first, the investigators
thought the virus causing the illness was Japanese encephalitis virus, a mosquito-
borne virus present throughout tropical Asia. Yet menacing and distinct symptoms
led the investigating teams to determine that it must be a new and still unidentified
agent.
Early symptoms of Nipah virus include those common in viral infections—
fever, decreased appetite, vomiting, and flu-like systems. But after three to four
days, more serious nervous system manifestations appear. The exact impact that
the virus has differs from person to person. Some individuals experience paralysis
and coma, while others have hallucinations. One of the first documented patients
reported seeing pigs running around his hospital bed.
MRI scans show serious damage to patches of the brain, and the patients who
die usually do so within a few days of the onset of brain damage. Among the indi-
viduals infected in Malaysia and Singapore in 1999, none appeared to seed addi-
tional human infections, yet cases in subsequent years in Bangladesh provide evi-
dence that the virus has the potential to spread from human to human under at
least some circumstances.
When scientists discover a new virus, a mad rush often ensues to identify the reser-
voir of the virus—the animal that maintains it. While certainly useful, the concept
of a reservoir also has limitations. Scientists often see stark divisions between
species. We neatly divide up the world of animals into families, genera, and
species, but we often forget that these divisions are based on our own conven-
tions. A taxonomist can clearly sort out the difference between a colobus monkey,
a baboon, a chimpanzee, a gorilla, and a human, yet the traits that permit us to
classify these animals as distinct are, as I’ve mentioned, often irrelevant for a mi-
crobe. From the perspective of a virus, if cells from distinct species share the
appropriate receptors, and ecological connections provide the appropriate op-
portunities to make a jump, the fur of a baboon or the upright status of a human
does not matter at all.
Some viruses persist permanently and simultaneously in multiple hosts.
Dengue virus, a viral infection originally called breakbone fever because of the in-
tense pain it causes, appears largely in human cities. Yet dengue also lives in wild
primates in tropical forests, where it is referred to as sylvatic dengue.⁴ Sylvatic
dengue simultaneously infects multiple species of primates and does not discrim-
inate. It has a wide host range.
Among the numerous dry technical scientific papers that I digested as a doc-
toral student, few are indelibly etched on my brain. One that I remember in detail
was a report describing experiments to determine the host range of sylvatic
dengue.
In the study, which used outdated methods now considered unethical, scien-
tists put various species of primate into cages and used ropes to lift the cages high
into the canopy where dengue’s forest mosquitoes feed. There they gathered sam-
ples of viruses to determine which species had the potential for infection. The
study largely worked—except in one case where they brought the cage down only
to find a massive python with a very badly distended abdomen. The large snake
had entered the cage to consume the trapped and no doubt terrified monkey. Hav-
ing miscalculated, the satiated snake could not squeeze through the bars to escape
and found itself in the same trapped predicament as its monkey prey. Most likely
the snake didn’t get infected with the virus; few viruses infect both reptiles and
mammals. It did, however, make for a memorable photo in an otherwise dry tech-
nical journal.
The capacity for sylvatic dengue to thrive in multiple species presumably helps
the virus persist in regions where the population density of any single primate
species would not be sufficient to protect the virus from extinction. And the mech-
anism dengue uses to move from one animal to another—mosquitoes—helps
make this movement seamless.
For dengue, the notion of a single reservoir does not, strictly speaking, make
sense, but when Nipah was discovered in 1999, that was still unclear. Scientists
then asked themselves: what local animal or animals, wild or domestic, were Ni-
pah’s reservoir? Knowing what animal or animals a virus lives in prior to infecting
humans helps us respond to it. Depending on the reservoir, we may have the
potential to simply change farming practices or modify human behavior to avoid
the critical contact that leads to viral exchanges, effectively cutting off the virus’s
ability to enter humans.
Knowing that a microbe has the capacity to maintain itself in an animal reservoir
also changes the way that we think about public health strategies. Microbes can
jump in both directions, so while novel human microbes like Nipah originate in
animals, established microbes also have the potential to cross back into animals.
Animal reservoirs for established human bugs can potentially derail control efforts.
In effect, if we eliminate a bug in humans in a particular region, but it lives on in
animals, the microbe may have the potential to reemerge with deadly conse-
quences. In order to truly eradicate a human pathogen, we must know if it can also
live outside of humans.
When Nipah emerged in 1999, the scientists studying it moved quickly to home
in on its reservoir. Over the years that followed, an intricate relationship among
wild animals, domesticated animals, and plants revealed itself, a story that empha-
sizes the complex ways that domestication can provide new avenues for bugs to
pass into people.
The Malaysian piggeries that Nipah entered are not small-scale affairs. They
house thousands of pigs at very high densities, creating a ripe environment for
viral spread. The farmers who raise the pigs work hard to maximize their income
both from the pigs themselves, but also from the surrounding land. One of the
practices in this area of southern Malaysia is to grow mango trees in and around
piggeries, providing a second source of income to increase the viability of the
farming enterprise.
In addition to producing delicious fruit for the farmers to sell, the mango trees
attract the flying fox, a large and appropriately named bat with the scientific name
Pteropus. This bat was the unexpected Nipah reservoir, the virus’s link to the wild.
Remarkably, it now appears that the Pteropus bats, while consuming their mango
suppers, urinate and drop partially eaten mango into the pig pens. The omnivorous
pigs consume the Nipah-infected bat saliva and urine as they eat the mango. The
virus then spreads quickly in the dense pig populations, which, because the ani-
mals are sometimes shipped from place to place, infect new piggeries and occa-
sionally infect their human handlers.⁵
Emerging thousands of years after the advent of domestication, Nipah illus-
trates the impact that domestication had on our relationship with microbes. The
larger and more sedentary populations of humans that emerged following the do-
mestication revolution were susceptible to outbreaks in ways that our predomestic
ancestors never were. In the small mobile communities that dominated human life
prior to agriculture, novel microbes that entered these communities from animals
would often sweep through, killing certain individuals and leaving the rest of the
small populations immune. At that point the viruses would effectively die out; a
virus without a susceptible host is unable to survive.
As villages and towns formed around agricultural centers, they did not do so in
isolation. Communities were connected, at first with footpaths, then roads. While
we might think that these towns were separate functional entities, from the per-
spective of a microbe, they represented a single larger community. As this inter-
connected community of towns grew, it provided the first opportunity in human
history for an acute virus to persist permanently in the human species.
Chronic viruses that live permanently within their hosts, like hepatitis B, do not
necessarily require large populations because they can continue to pass on their
progeny for many years. These viruses have the potential to persist in very small
communities, taking a long-term strategy—he who fights and hides away lives to
fight another day. On the other hand, acute viruses, such as measles, do not re-
main in a single individual for long and require a constant supply of susceptible
hosts. As they burn through populations, they kill some and make the rest im-
mune, often leaving no one to perpetuate the infection.
Therefore, within the small, mobile hunter-gatherer lifestyle that our ancestors
led prior to domestication, acute viruses could not survive for long unless they
were microbes that we shared with other species. In the same way, chimpanzee
populations, including those that were studied by the pioneering primatologist
Jane Goodall, have sometimes been hit with polio. The virus that causes polio nor-
mally requires large populations of contemporary humans to sustain itself. Never-
theless, in 1966 Dr. Goodall and her colleagues saw that the wild chimpanzees they
studied had come down with something that looked very much like human polio,
including symptoms of flaccid paralysis. The outbreak was devastating for the
chimpanzee community in Tanzania, killing a number of animals.
The virus that caused chimpanzee polio was in fact the same virus that caused
polio in humans. It had jumped over from nearby humans who were experiencing
an outbreak at the same time. Dr. Goodall and her colleagues administered vaccine
to the chimpanzees, which no doubt limited the harm to the community. Chim-
panzees, like our early human ancestors prior to domestication, would not have
had the population sizes to maintain such a virus—current estimates suggest that
communities of over 250,000 people are necessary to sustain it. In small commu-
nities, the virus would simply have swept through, harming some and creating
immunity in the others, before dying out.
But when our ancestors, with their farms and domestic animals, began to have
interconnected towns, viruses like polio gained the ability both to infect us and to
be maintained within our species. As more and more towns appeared and the
connections between them improved, the number of people in contact with each
other increased. From the perspective of a microbe, the physical separation of
these towns didn’t matter if there were enough people moving between the towns.
Hundreds, and later thousands, of interconnected towns effectively became a sin-
gle megatown for microbes. Eventually, the number of interconnected people
would become so large that viruses could maintain themselves permanently. As
long as new people entered into the populations through birth or migration, and
did so with enough frequency, there would always be a new person for the microbe
to try.
In effect, domestication provided a triple hit to our ancestors when it came to mi-
crobes. It provided sufficiently close contact with a small set of domesticated ani-
mals, allowing their microbes to cross over into us. At the same time, domestic
animals provided a regular and reliable bridge to wild animals, giving their
microbes increased opportunities to cross into us. Finally, and perhaps most cru-
cially, it permitted us to have large and sedentary communities that could sustain
microbes that previously would have been a flash in the pan. Together, this viral
hat trick put us in a new microbial world—one that would lead, as we’ll see in the
next chapter, to the first pandemic.
