The Plague Fighters: Stopping the Next Pandemic Before It Begins
Pastor Dale Morgan
The Plague Fighters: Stopping the Next Pandemic Before It Begins*
Evan Ratliff
Wired News
HIV, Ebola, SARS — any of the world's most horrifying diseases are
caused by animal viruses that made the jump to humans. Now a UCLA
scientist thinks he can stop the next pandemic before it even starts.
Array Sampson slings a makeshift shotgun over his shoulder and sets off
down a footpath leading away from Okoroba, a remote village in
Cameroon's Southwest Province. The lanky 36-year-old hunter is wearing
ankle-length pants and slotted plastic shoes. He has a shaved head and a
thin mustache, and his long strides carry him quickly past small stands
of cacao trees and into the thick forest that blankets the surrounding
hills. Expecting a half-day's hunt, he travels light: In addition to the
shotgun, he carries only two shells, a small cane backpack, and a
machete that hangs in a sheath from his neck. Fleetness could make the
difference between a feast of monkey or antelope — bushmeat, as such
forest quarry is known in central Africa — and a meager dinner for his
family.
Trailing behind Sampson, in slacks and an untucked polo shirt, is Efuet
Simon Akem, a graduate anthropology student at the University of Yaound
in Cameroon. Akem, who grew up in a village in a region south of
Okoroba, is here to record how and what Sampson hunts. Every now and
then, he fishes a notebook out of a ratty backpack hanging across his chest.
A mile into the trek, Sampson turns off the main path and plunges into
the underbrush. Soon the three of us are picking our way through termite
mounds the size of fire hydrants and slogging across muddy, waist-high
streams. Although the canopy shields us from direct sunlight, the forest
air is hot and thick with humidity. The murmur of insects is broken by
the sound of stork-sized birds flying above the trees, like the beat of
distant helicopter blades. As Sampson hurries along, pausing to check
buried snares or to examine low- hanging leaves for the recent brush of
an animal, he breaks off tiny stems and branches, creating a trail he
can use to trace his way home. "It's like his own GPS," Akem says.
Most villagers in Okoroba, which lies at the end of a dirt road near the
Nigerian border, subsist either by selling cacao or, like Sampson,
hunting bushmeat. Lately, logging has thinned the forest, and the locals
have had to settle for lean fare: wild birds and rodents. But every hunt
brings new possibility, and other villagers' recent monkey kills have
made Sampson optimistic. He seems further buoyed by the fresh rut of a
bush pig, and as we splash through a creek, he catches the ooh-ooh sound
of a monkey. The ensuing chase is unsuccessful, and Akem records what
Sampson points out as the missed prey — a red-capped monkey — on a
collection of photocopied pictures the researcher keeps stuffed in his
backpack. A half hour later, Sampson stops short again, this time at the
sound of a squirrel's warning. "Sometimes a squirrel call means there's
a viper nearby," Sampson says, warily scanning the brush for the deadly
but prized snake. "If you shoot one, you share it with the whole village
— after you remove the poison."
We press on, dripping sweat and nursing bites from the ant swarms we
periodically wade into, which send us into mad sprints through the
forest. Then Sampson spots movement through a gap in the trees, motions
us to stop, and shoulders his shotgun. He squints for a moment and
fires, the kick of the gun shoving him backward. Catching his balance,
he plunges into the jungle after his wounded prey.
Photograph by Joe Toreno
Sometime around the 1930s, epidemiologists theorize, a hunter much like
Sampson walked into a forest a few hundred miles southeast of Okoroba,
killed a chimpanzee carrying a then-unknown virus, and became an
unwitting driver of human fate. Perhaps blood — infected with simian
immuno deficiency virus — dripped down his back into an open wound as he
hauled the catch home. Or perhaps he cut his hand while butchering the
chimp. But somehow, his own blood came into contact with another
primate's blood, and the pathogen changed into a form well built to
spread from one human to the next. The hunter then passed the virus, now
known as human immuno deficiency virus-1 group M, or HIV, to a fellow
villager, and it began its slow leach into the surrounding human population.
Today it may seem like the only opportunity to contain HIV came after
its discovery in the 1980s. But what if the disease, which has infected
or killed an estimated 63 million people, could have been stopped
decades earlier? What if that hunter had carried the chimpanzee more
carefully that day? For Nathan Wolfe, a biologist at UCLA and head of
the project sponsoring Akem's data-gathering, those are the kinds of
questions to build a career upon. "Very few people ask whether we could
have prevented HIV," Wolfe told me over beers one night last fall in
Yaound , the capital of Cameroon. "That's what I encourage people in my
lab to think about."
Launched in 1999, Wolfe's Cameroon project aims to discover viruses
that, like HIV, originate in wild animals and then cross over to infect
humans. Known as zoonoses, such pathogens constitute an estimated three-
quarters of all emerging human diseases. The list of animal-to-human
invaders includes malaria, smallpox, West Nile, Ebola, SARS, and — the
threat of the moment — avian influenza. Despite these killers and the
near- certainty that new devastating zoonoses will emerge, little is
understood about either the range of potential pathogens in the animal
kingdom or the way they enter and spread among humans. "We are at the
absolute infancy" of understanding the origins of viruses like HIV, says
Beatrice Hahn, a professor of medicine at the University of Alabama at
Birmingham who last year led the team that traced the origin of HIV to
Cameroon.
We do know that it takes three steps for a zoonotic agent to become an
HIV or a smallpox. First, a human must be exposed to the virus. Then,
the virus must either be virulent or become so through mutation. Finally
the virus must be able to move from human to human and not kill its host
so quickly that it doesn't have time to spread. Each of these steps is a
complex biological process, and each presents opportunities to ward off
a pandemic. Traditionally, however, the study of infectious disease has
focused on containing and tracing outbreaks — say, Ebola in Africa, or
HIV around the globe — after a zoonosis has started spreading.
(Occasionally, as with avian flu, scientists have identified a
potentially dangerous virus one stage before human-to-human
transmission.) When it comes to searching for new or unknown viruses
among wild animals — and discovering the process through which they
cross to humans — few scientists have ventured into the forest.
That's what Wolfe hopes to change. His group is organizing a vast range
of field research in Cameroon: collecting blood from hunters and their
kills, testing wild and domestic birds for avian flu, conducting
anthropological surveys of hunters' habits, and investigating sudden
die-offs of primates in the jungle. The combined effort is a year-round
operation, employing more than 30 full-time scientists, technicians,
veteri narians, and IT specialists. Wolfe's group collaborates with
dozens more worldwide, from the US Centers for Disease Control and
Prevention to the virology lab at France's University of Montpellier.
The early results have been promising. The Cameroon project recently
discovered at least three unexpected or unknown viruses — all in the
same family of RNA retroviruses as HIV — by collecting and analyzing the
blood of bushmeat hunters like Sampson. The findings cemented Wolfe's
reputation in the world of viral discovery and were dramatic in their
own right. But to him, what they really represent is a proof of concept.
Now, using $2.5 million he received in 2004 from a National Institutes
of Health Pioneer Award as seed money, he's building a network of
virus-discovery projects, using Cameroon as the prototype. By monitoring
hunters and wild-game markets in a dozen hard-to-reach potential sites
in places like the Democratic Republic of Congo, Malaysia, Laos,
Madagascar, Para guay, and China, he plans to build a taxonomy of what's
called "viral chatter": the regular transmission of viruses from wild
animals to humans, often without any further spread among humans or
consequences for the infected. It's the epidemiological equivalent of
information blips on a CIA analyst's screen. "In the intelligence
community, you have people monitoring intelligence and looking for
keywords," Wolfe says. "Every time a keyword comes up, it's not going to
signal a terrorist threat. But by studying the patterns, you can begin
to understand what you might be looking for. I study some agents that
are very unlikely to be pandemic. But we are asking, where did they die
out? What are their features?"
The answers — assuming Wolfe can find them hidden in the world's
tropical forests — will do more than give us a better basic
understanding of how viruses work. They will help fine-tune disease
models that forecast where the next zoonoses will emerge and potentially
allow us to contain a disease through targeted education, economic
development, and blood-supply testing. This type of analysis could
transform the public health model — from reactive to predictive — giving
us a chance we didn't have with HIV.
Wolfe, 36, lived full-time in Cameroon for six years before returning to
the US last October. He has a bearded, cherubic face and dark curls that
cascade to his shoulders. Around the project's headquarters in Yaound ,
he is simply referred to as The Doctor, and he projects an easygoing
demeanor — favoring flip-flops and T-shirts in the field and the office.
When he arrived in Cameroon in 1999, Wolfe had a single contact and
spoke no French, the country's principal language. Raised in Detroit, he
had studied human biology at Stanford and Oxford before starting a
doctoral degree in immunology and infectious diseases at Harvard. For
his dissertation, he researched orangutans in a remote part of Borneo,
only to venture into town one day and find a scolding email from his
mother. "I'm not sure what kind of trouble you are in," she wrote, "but
there's a general trying to reach you from the US military." The general
turned out to be a colonel named Donald Burke, then head of the Army's
AIDS research program at Walter Reed Army Institute of Research. Burke
had met Wolfe at a conference and was calling to see whether he would
take a post-doc fellowship in Cameroon.
Burke had been researching the evolution of HIV and had discovered
several new variants of the virus in different parts of the globe. In
1996, he traveled to Cameroon on the invitation of Mpoudi Ngole Eitel,
the imposing, mustachioed colonel who headed the country's national AIDS
control program. At the time, bushmeat wasn't considered the source of
HIV, Burke says. But "just in traveling around the country with Mpoudi,
it jumped out at me as a possible route of infection." Together they
came up with the idea of screening hunters in remote villages to
investigate the diversity of HIV strains. Bushmeat hunters are the
perfect "viral interface" because of their close contact with wildlife —
particularly primates, whose genetic similarity to humans makes them
especially dangerous.
Burke asked Wolfe to run that project. It was, at first, a lean
operation: In 2001, Wolfe's group relied on a single vehicle — a
dilapidated red Toyota Prado — to visit 17 villages and collect blood
samples from 4,000 hunters. Mat LeBreton, head of Wolfe's ecology team,
recalls using a backpack strap to refasten the car's fuel tank after it
fell off. Samples occasionally had to be transported miles by foot or
public bus over Cameroon's notoriously impassable roads in a race to
process the blood in the 48 hours before it spoiled. From bribe- seeking
highway patrols to intransigent tribal chiefs, Wolfe was unfazed by the
obstacles. "Nathan seemed to thrive on working in that very difficult,
complicated environment," Burke says. "He was an absolute genius."
Wolfe would ship the blood samples to the CDC in Atlanta and then fly
there himself, spending months at a time examining the viruses in the
lab alongside his associates at the center. They decided to look first
for simian foamy virus, a primate retrovirus. Foamy virus, so named
because of how infected cells look under the microscope, had been found
in a handful of laboratory and zoo workers but had never been traced to
contact with wild animals. The results of Wolfe's research, published in
The Lancet in 2004, showed that 1 percent of hunters were infected with
SFV. Whether SFV actually causes symptoms in humans remains unknown, but
fears over the disease prompted the Canadian government to begin
screening out blood donors who'd had close contact with primates.
Wolfe and his colleagues, meanwhile, were also busy screening the same
batch of samples for variants of a virus called HTLV. More than 20
million people globally are infected with HTLV-1, a virus that sometimes
leads to adult T-cell leukemia, or HTLV-2, a potential source of
neurological disease. These are among the six viruses that US blood
banks screen every blood donation for. Analy sis of the hunters' blood
samples, however, uncovered not only the known HTLV variants but also
two entirely new viruses, which the researchers named HTLV-3 and HTLV-4
and whose dangers remain unknown.
The implications of those results, published in the Proceedings of the
National Academy of Science in 2005, were astounding: Retroviruses
similar to HIV were crossing from primates to hunters far more
frequently than anyone had expected. The long-ago Cameroonian hunter who
acquired SIV was no freak occurrence. Viruses, it turns out, are
constantly spilling over from animals to humans. The only reason we
don't have frequent pandemics is that most of those viruses have a hard
time establishing themselves and then spreading. "There were already
some hints of viruses emerging this way," says Burke, who coined the
term viral chatter. "What I wasn't ready for was finding them on the
order of 1 in 100 people. That means there are literally tens of
thousands of people walking around in equatorial Africa harboring
viruses in this state."
When Sampson tromps back through the undergrowth, he's gripping a large,
bony bird with indigo-lidded eyes. "Harnbeel," he says — the local
pronunciation. He drops it to the ground and finishes it off with his
machete, then pulls out a piece of plastic and carefully folds the bird
into it, placing the bundle in his backpack. "See how he wraps it?" Akem
says. "That's to avoid getting the blood on him. They used to just carry
them, but this is after our education program."
Explaining to the hunters how to avoid blood contact is a major line of
defense against animal viruses. For his early research, Wolfe and his
team traveled to remote towns and collected from locals not only blood
samples but also questionnaires about the villagers' contact with bush
animals. Gradually, he expanded his scope. The program now uses hunter
volunteers like Sampson to collect blood samples from the animals they
kill onto small filter papers that can preserve dried blood spots
unrefrigerated for months. A researcher returns periodically to each
village and collects the papers, which are cataloged at Wolfe's lab in
Yaound and shipped to other labs in the US, Europe, and Africa. Then one
of Wolfe's graduate students screens them for known viruses,
particularly primate-related pathogens.
To expand his network, Wolfe has sought out collaborators working in
similar environments. Ann Rimoin, for example, runs a parallel project
designed to detect the emergence of monkeypox, a relative of smallpox,
in the Democratic Republic of Congo. Wolfe's team is developing
universal protocols for gathering blood and anthropological information.
The samples will be held in a central repository at UCLA and then sent
to experts around the globe. "I think of it almost like being a
curator," Wolfe says.
Being a curator, though, involves politics as well as science, which for
Wolfe means everything from filing the proper inter national
blood-shipping permits to convincing the hunters that he and his crew
mean well. In the past decade, bushmeat has become a controversial
environmental issue across central Africa, as the growing commercial
hunting trade supplies more and more food for the continent's swelling
cities, threatening the survival of species like chimpanzees and
gorillas. Such markets have been found in Europe and the US, too, where
several thousand tons of bushmeat are illegally imported each year.
Because of the crisis, villagers who subsist on bushmeat are often
suspicious of outsiders who come to talk about the practice. For Wolfe
and his field teams — relying on unpaid volunteers for their samples —
that means a great deal of time spent consulting with village elders,
making donations to local schools, and developing the stomach for palm wine.
The night after Sampson's hunt, a Cameroonian project leader named
Joseph Le Doux Diffo convenes a village-wide meeting in Okoroba to
explain the goals of Wolfe's research and provide lessons on how to
avoid blood contact during hunting and butchering. "Even a small child
in your house can accidentally catch a disease if you have bushmeat
there," he tells the assembled villagers. "We are not telling you not to
eat meat, but bad diseases are out there now."
That evening I sit down outside Sampson's house to watch him butcher the
hornbill. He cleans it deftly with his machete, preserving every part of
the bird for the evening's meal except the beak, which he sets aside to
sell to local Nigerian healers. He explains why he volunteers for the
research program: "I am a hunter, and this is my own way of assisting.
If it happens that we kill an animal and they discover some drug from
this, that would be a good thing."
As he finishes carving up the last parts of the bird, I ask him whether
he considers that afternoon's hunt successful. "Not a good day, no," he
says. "But if I hadn't gone out today, my family would not have eaten."
In a lab at the Blood Systems Research Institute, perched on a hilltop
in a San Francisco residential neighborhood, some of the blood samples
taken from hunters like Sampson are stashed in Eric Delwart's freezer.
Delwart is a professor at UC San Francisco and direc tor of molecular
virology at the institute — the disease-research arm of the nation's
second-largest blood bank. A few years ago, he stumbled across a paper
by a National Institutes of Health researcher describing a new method of
identifying unknown viruses. Delwart was so intrigued that he began
cold-calling labs in places as far away as Egypt in search of blood
samples to scan for undiscovered pathogens. "My hunch," he says, "was
that there were a lot of viruses yet to be found."
When Delwart heard about Wolfe's sample collection in the forests of
Africa, he knew he wanted to get his hands on that blood. And Wolfe was
only too happy to send some. One of the potential breakthroughs of
Wolfe's work, after all, is the discovery of previously unknown viruses.
But doing that requires over coming the same dilemma faced by
intelligence analysts: How do you find something you don't know you're
looking for?
Delwart's method does just that, scanning the blood for any virus, known
or unknown. "The key," he says, "is what we call a random PCR." Short
for polymerase chain reaction, PCR is a standard lab technique used in
everything from paternity tests to criminal DNA analysis. It allows you
to amplify a sequence of DNA, creating enough copies to analyze the
strand. Typical PCR, however, requires that you know the nucleic acid
sequence that makes up the DNA you're looking for. But we obviously
don't know that for an undiscovered virus. So, after removing the large
human cells and bacteria from a sample, Delwart chops all the remaining
genetic material into little pieces and looks at every possible
sequence. Then he uses specially designed bioinformatics software to
check them against Blast, an NIH database of all known viruses, and
identify any that match even remotely. Sequences that repeatedly turn up
in the blood but show no similarity to anything in the database could
represent new discoveries.
Delwart's work is at the forefront of the new science of viral
metagenomics, and scientists employ the same technique to look for
unknown microbes in everything from seawater and mud to lung fluid.
"There could be a new golden age of virology based on this brute-force
genomic approach," he says. "The next human epidemic may come from a
sick person; it may not. We may find somebody in whom the virus is in
the process of adapting. It may never adapt enough to cause an epidemic.
But the earlier the warning, the better. That's why the wildlife and the
bush hunters are so essential."
In the near future, Nathan Wolfe expects, a hunter in a remote forest
will carry home an ape for dinner, primate blood dripping down his back.
Perhaps a researcher like Efuet Simon Akem will pass through the village
soon after and collect that hunter's blood, or take a sample from the
ape meat in a nearby market. The researcher will package it up and ship
it to UCLA, where it will be rerouted to labs like Delwart's and scanned
for viruses, both known and unknown. But then what? What happens when
Wolfe and his collaborators are staring down a microscope at an unknown
animal disease swimming in human plasma? Just as eavesdropping
intelligence agents know that not every mention of airplanes and bombs
constitutes a terrorist plot, an episode of viral chatter alone could
seem like a threat but never amount to anything.
Wolfe knows that his discoveries have already hinted at the huge number
of viruses yet to be discovered, and that most of them will be harmless.
Some, though, will be dangerous, possible forerunners of truly deadly
diseases. HIV, after all, is thought to have made as many as 10 forays
into humanity (in addition to changing into the form that caused the
pandemic). But if his network is successful — if hunters like Sampson
wrap kills in plastic or if Delwart's lab detects a blood-borne virus
and takes steps to protect the blood supply or develop treatments — it
will help prevent the truly deadly viruses from becoming pandemics. The
trick is to stop things before they start. "Once things are in flames,"
Wolfe says, "it's hard to figure out what caused the fire."
At the moment, Wolfe's main goal is to get a clear understanding of
viral chatter in locations where diseases are most likely to enter human
populations. The probable next step, which he and his colleagues are
just beginning in Cameroon with SFV and HTLV, is to look more closely at
infected people to determine what symptoms, if any, the viruses produce
and whether any of the infections can be traced to human transmission.
That process will include research like finding and testing blood from
rural cases of undiagnosed fever. Such rapidly mutating RNA viruses have
the potential to become pandemics. But to find out if they will requires
the sustained effort of old-fashioned epidemiology. "The genomics," says
Andrew Dobson, a disease ecologist at Princeton University, "tell you
nothing about questions like: What makes a virus infectious? What makes
you get sick from it? What makes it spread? Anything we really want to
measure, we are going to have to measure in the field."
Wolfe has been in constant motion in recent months, checking in on the
Cameroon project and working to develop other sites for the network in
remote areas chock-full of bio diversity and where humans interact with
wild animals. In Malaysia, he is working with a researcher studying the
Nipah virus. First identified in 1999, it originated in fruit bats and
causes a highly fatal and untreatable disease. In Laos, Wolfe is in
discussions with a scientist who's following tropical rickettsial
diseases. In China, he's in preliminary talks with researchers who
traced the origin of SARS. In Para guay, Mada gascar, and several other
places, he is investigating sites and laying the groundwork with local
scientists to establish a new network that will send blood samples
streaming into UCLA, full of unknown microbes. It's equivalent to
building a roster of spies in potential hot spots around the world who
will eventually feed top-quality intel back to HQ.
Wolfe's brand of globe-trotting, open-ended viral discovery echoes an
almost Victorian scientific ethic, an expedition to catalog the unseen
menagerie of the world. In the end, Wolfe says, as long as one is
willing to plunge deep into the jungle, the concepts behind his research
are "phenomenally" simple. "Someone should have done it already," he
told me in his whitewashed Yaound office one afternoon, the rain beating
down and his voice tinged with exhaustion. He admits that no
surveillance effort is comprehensive. The next HIV might emerge from
somewhere other than the deep forest, or it might elude surveillance
until it has already spread. But Wolfe insists there is a basic human
imperative to illuminate the viruses that lurk where the road ends — and
to improve our odds of containing them there. "It's really a 100-year
thing," he says. "Will people look back and say you did a good job
responding to epidemics but you didn't do anything to prevent them?"