The Chimp and the River: How AIDS Emerged from an African Forest (3 page)

Taking blood samples from macaques, they did find a new retrovirus, and saw that it was closely related to the AIDS virus. Because this was 1985, they used Gallo’s slightly misleading label (HTLV-III) for what would soon be renamed HIV. Their monkey virus would be renamed too and become, by analogy, simian immunodeficiency virus: SIV. The group published a pair of papers in
Science
, which had grown hungry for AIDS breakthroughs. This discovery, they wrote, could help illuminate the pathology of the disease, maybe even advance efforts to develop a vaccine, by providing an animal model for research. Only a single sentence at the end of one of the papers, a modest but pertinent comment dropped in like an afterthought, noted that SIV might also be a clue toward the
origin
of HIV.

It was. Phyllis Kanki performed the lab analysis of samples
from the captive macaques and then made it her business to wonder whether the same virus might exist in the wild. Kanki and Essex looked at other Asian macaques, testing blood samples from wild-caught animals. They found no trace of SIV. They tested still other kinds of wild Asian monkey. Again, no SIV. This led them to surmise that the macaques at Southborough had picked up their SIV in captivity by exposure to animals of another species. It was a reasonable guess, given that the primate center at one point had a monkey playpen in its lobby, where Asian and African infant monkeys were sometimes allowed to mingle. But then which kind of African monkey was the reservoir? Where exactly had the virus come from? And how might it be related to the emergence of HIV?

“In 1985, the highest rates of HIV were reported in the U.S. and Europe,” Essex and Kanki wrote later, “but disturbing reports from central Africa indicated that high rates of HIV infection and of AIDS prevailed there, at least in some urban centers.” The focus of suspicion was shifting: not Asia, not Europe, not the United States, but
Africa
might be the point of origin. Central Africa also harbored a rich fauna of nonhuman primates. So the Harvard group got hold of blood from some wild-caught African simians, including chimpanzees, baboons, and African green monkeys. None of the chimps or the baboons showed any sign of SIV infection. Some of the African green monkeys did. It was an epiphany. More than two dozen of the monkeys carried antibodies to SIV, and Kanki grew isolates of live virus from seven. That finding too went straight into
Science,
and the search continued. Kanki and Essex eventually screened thousands of African green monkeys, caught in various regions of sub-Saharan Africa or held captive in research centers around the world. Depending on the population, between 30 and 70 percent of those animals tested SIV-positive.

But the monkeys weren’t sick. They didn’t seem to be suffering from immunodeficiency. Unlike the Asian macaques, the African green monkeys “must have evolved mechanisms that kept a potentially lethal pathogen from causing disease,” Essex and Kanki wrote. Maybe the virus had changed too. “Indeed, some SIV strains might also have evolved toward coexistence with their monkey hosts.” The monkeys evolving toward greater resistance, the virus evolving toward lesser virulence—this sort of mutual adaptation would suggest that SIV had been in them a long time.

The new virus, SIV as found in African green monkeys, became the closest known relative of HIV. But it wasn’t
that
close; many differences distinguished the two at the level of genetic coding. The resemblance, according to Essex and Kanki, was “not close enough to make it likely that SIV was an immediate precursor of HIV in people.” More likely, those two viruses represented neighboring twigs on a single phylogenetic branch, separated by lots of evolutionary time and probably some extant intermediate forms. Where might the missing cousins be? “Perhaps, we thought, one could find such a virus—an intermediate between SIV and HIV—in human beings.” They decided to look in West Africa.

With help from an international team of collaborators, Kanki and Essex gathered blood samples from Senegal and elsewhere. The samples arrived with coded labeling, for blind testing in the laboratory, so that Kanki herself didn’t know their country of origin, nor even whether they derived from humans or monkeys. She screened them using tests for both SIV and HIV. Despite one possible misstep involving a lab contamination, her team found what they had thought they might: a virus intermediate between HIV and SIV. With the code unblinded, Kanki learned that the positive results came from Senegalese prostitutes. In
retrospect it made sense. Prostitutes are at high risk for any sexually transmitted virus, including a new one recently spilled into humans. And the density of the rural human population in Senegal, where African green monkeys are native, makes monkey-human interactions (crop-raiding by monkeys, hunting by humans) relatively frequent.

Furthermore, the new bug from Senegalese prostitutes wasn’t just halfway between HIV and SIV. It more closely resembled SIV strains from African green monkeys than it did the Montagnier-Gallo version of HIV. That was important but puzzling. Were there two distinct kinds of HIV?

Luc Montagnier now reenters the story. Having tussled with Gallo over the first HIV discovery, he converged more amicably with Essex and Kanki on this one. Using assay tools provided by the Harvard group, Montagnier and his colleagues screened the blood of a twenty-nine-year-old man from Guinea-Bissau, a tiny country, formerly a Portuguese colony, along the south border of Senegal. This man showed symptoms of AIDS (diarrhea, weight loss, swollen lymph nodes) but tested negative for HIV. He was hospitalized in Portugal, and his blood sample was hand-delivered to Montagnier by a visiting Portuguese biologist. In Montagnier’s lab, the man’s serum again tested negative for antibodies to HIV. But from a culture of his white blood cells Montagnier’s group isolated a new human retrovirus, which looked very similar to what Essex and Kanki had found. In another patient, hospitalized in Paris but originally from Cape Verde, an island nation off the west coast of Senegal, the French team found more virus of the same type. Montagnier called the new thing LAV-2. Eventually, when all parties embraced the label HIV instead, it would be HIV-2. The original became HIV-1.

The paths of discovery may be sinuous, the labels may seem
many, and maybe you can’t tell the players without a scorecard; but these details aren’t trivial. The difference between HIV-2 and HIV-1 is the difference between a nasty little West African disease and a global pandemic.

4

D
uring the late 1980s, as Phyllis Kanki and Max Essex and other scientists studied HIV-2, a flurry of uncertainty arose about its provenance. Some challenged the idea that it was closely related to (and recently derived from) a retrovirus that infects African monkeys. An alternative view was that such a retrovirus had been present in the human lineage for as long as—or longer than—we have existed as a species. Possibly it was already with us, a passenger riding the slow channels of evolution, when we diverged from our primate cousins. But that view left an unresolved conundrum: If the virus was an ancient parasite upon humans, unnoticed for millennia, how had it suddenly become so pathogenic?

Recent spillover seemed more likely. Still, the case
against
that idea got a boost in 1988, when a group of Japanese researchers sequenced the complete genome of SIV from an African green monkey. That is, they detected and assembled the linear message of nucleotide bases—represented by the letters A, T, C, and G—comprising that SIV’s genetic inscription. The host animal came from Kenya. The nucleotide sequence of its retrovirus proved to be substantially different from the sequence for HIV-1, and different in roughly the same degree from HIV-2. So the monkey
virus seemed no more closely related to the one human virus than to the other. That contradicted the notion that HIV-2 had lately emerged from an African green monkey. A commentary in the journal
Nature
, published to accompany the Japanese paper, celebrated this finding beneath a dogmatic headline:
HUMAN AIDS VIRUS NOT FROM MONKEYS.
But the headline was misleading to the point of falsity.
Not from monkeys
? Well, don’t be so sure. It turned out that researchers were just looking at the wrong kind of monkey.

Confusion came from two sources. For starters, the label “African green monkey” is a little vague. It encompasses a diversity of forms, sometimes also known as savannah monkeys, that occupy adjacent geographical ranges spread across sub-Saharan Africa, from Senegal in the west to Ethiopia in the east and down into South Africa. At one time those forms were considered a “superspecies” under the name
Cercopithecus aethiops
. Nowadays, their differences having been more acutely gauged, they are classified as six distinct species within the genus
Chlorocebus.
The “African green monkey” sampled by the Japanese team, because it was “of Kenyan origin,” probably belonged to the species
Chlorocebus pygerythrus.
The species native to Senegal, on the other hand, is
Chlorocebus sabaeus.
Now that you’ve seen those two names you can forget them. The difference between one African green monkey and another is not what accounts for the genetic disjunction between SIV and HIV-2.

The trail backward from HIV-2 led to another monkey entirely: the sooty mangabey. This is not one of the six
Chlorocebus
species, not even close. It belongs to a different genus.

The sooty mangabey (
Cercocebus atys
) is a smoky-gray creature with a dark face and hands, white eyebrows, and flaring white muttonchops, not nearly so decorative as many monkeys on the continent but arresting in its way, like an elderly chimney sweep
of dapper tonsorial habits. It lives in coastal West Africa, from Senegal to Ghana, favoring swamps and palm forests, where it eats fruit, nuts, seeds, leaves, shoots, and roots—an eclectic vegetarian—and spends much of its time on the ground, moving quadrupedally in search of fallen tidbits. Sometimes it ventures out of the bottomlands to raid farms and rice paddies. The sooty mangabey is hard to hunt within the swampy forests but, because of its terrestrial foraging habits and its taste for crops, easy to trap. Local people treat it as an annoying but edible sort of vermin. Sometimes also, if they’re not too hungry, they adopt an orphan juvenile as a pet.

What brought the sooty mangabey to the attention of AIDS researchers was coincidence and an experiment on leprosy. It was an instance of the old scientific verity that sometimes you find much more than you’re looking for.

Back in September 1979, scientists at a primate research center in New Iberia, Louisiana, south of Lafayette, had noticed a leprosy-like infection in one of their captive monkeys. This seemed odd, because leprosy is a human disease caused by a bacterium (
Mycobacterium leprae
) not known to be transmissible from people to other primates. But here was a leprous monkey. The animal in question, a sooty mangabey, female, about five years old, had been imported from West Africa. The researchers called her Louise. Apart from her skin condition, Louise was healthy. She hadn’t, so far as the records showed, yet been subjected to any experimental infection. They were using her in a study of diet and cholesterol. The New Iberia facility didn’t happen to work on leprosy infections, so once Louise’s condition had been recognized she was transferred to a place, also in Louisiana, that did: the Delta Regional Primate Research Center, north of Lake Pontchartrain. The researchers at Delta were glad to get her, for one very practical reason. If Louise had acquired her leprosy naturally, then (contrary to previous suppositions
) the disease might be transmissible in populations of sooty mangabey. And if that were true, then the sooty mangabey could prove valuable as an experimental model for studies of human leprosy. This is how human medical research works: at the expense of other creatures.

So the Delta team injected some infectious material from Louise into another sooty mangabey. This one was a male. Unlike Louise, he is nameless in the scientific record, remembered only by a code: A022. He became the first in a chain of experimentally infected monkeys that turned out to carry more than leprosy. The scientists at Delta had no idea, not at first, that A022 was SIV-positive.

The leprosy from Louise took hold easily in A022, which was notable, given that earlier attempts to infect monkeys with human leprosy had failed. Was this strain of
Mycobacterium leprae
a peculiarly monkey-adapted variant? If so, might it succeed in rhesus macaques too? That would be convenient for experimental purposes, because rhesus macaques were cheaper and more available, in the medical-research chain of supply, than sooty mangabeys. So the Delta team injected four rhesus macaques with infectious gunk from A022. All four developed leprosy. For three of the four, that proved to be the least of their troubles. The unlucky three also developed simian AIDS. Suffering chronic diarrhea and weight loss, they wasted away and died.

Screening for virus, the researchers found SIV. How had their three macaques become SIV-positive? Evidently by way of the leprous inoculum from the sooty mangabey, A022. Was he unique? No. Tests of other sooty mangabeys at Delta revealed that the virus was quite prevalent among them. Other investigators soon found it too, not just among captive sooty mangabeys but also in the wild. Yet the sooty mangabeys (native to Africa),
unlike the Asian macaques, showed no symptoms of simian AIDS. They were infected but healthy, which suggested that the virus had a long history in their kind. The same virus made the macaques sick, presumably because it was new to them.

The roster of simian immunodeficiency viruses was growing more crowded and complex. Now there were three known variants: one from African green monkeys, one from rhesus macaques (which they probably acquired in captivity), and one from sooty mangabeys. Needing a way to identify and distinguish them, someone hit upon the expedient of adding tiny subscripts to the acronym. Simian immunodeficiency virus as found in sooty mangabeys became SIV
_sm
. The other two were labeled SIV
_agm
(for African green monkeys) and SIV
_mac
(for Asian macaques)
_.
This little convention may seem esoteric, not to mention hard on the eyes, but it will be essential and luminous when I discuss the fateful significance of a variant that came to be known as SIV
_cpz
.