Spillover: Animal Infections and the Next Human Pandemic (51 page)

Worobey amplified fragments of the viral genome, pieced the fragments together, recognized them as an early version of HIV-1, and named the sequence DRC60. Comparing his sequence with ZR59, the other earliest known strain, he reached a dramatic conclusion: that the AIDS virus has been present in humans for decades longer than anyone thought. The pandemic may have gotten its start with a spillover as early as 1908.

To appreciate Worobey’s discovery and how it splashed down amid previous ideas, you’ll need to know a little context. That context involved a heated dispute over just how HIV-1 entered the human population. The prevailing notion as of the early 1990s, based on what had been learned about HIV-2 and the sooty mangabey, among other factors, was that HIV-1 also came from an African primate, and that it had probably gotten into humans by way of two separate instances (for groups M and O, the ones then recognized) of butchering bushmeat. This became known as the cut-hunter hypothesis. In each instance, a man or a woman had presumably butchered the carcass of an SIV-positive primate and suffered exposure through an open wound—maybe a cut on the hand, or a scratch on the arm, or a raw spot on any skin surface that got smeared with the animal’s blood. A wound on the back might have sufficed, if the carcass were draped over shoulders for carrying home. A wound in the mouth, if some of the meat were consumed raw. All that mattered was blood-to-blood contact. The cut-hunter hypothesis was speculative but plausible. It was parsimonious, requiring few complications and no unlikelihoods. It fit the known facts, though the known facts were fragmentary. And then in 1992 a contrary theory arose.

This one was heterodox and highly controversial: that HIV-1 first got into humans by way of a contaminated polio vaccine tested on a million unsuspecting Africans. The vaccine itself, by this theory, had been an unintended delivery system for AIDS. Someone, according to the theory, had monumentally goofed. Someone was culpable. Scientific hubris had overridden caution, with catastrophic results. The scariest thing about the polio-vaccine theory was that it
also
seemed plausible.

Viruses are subtle, as you’ve seen. They get in where they shouldn’t. Laboratory contaminations occur. Even viral or bacterial contamination of a vaccine at the production level—it has happened. Back in 1861, a group of Italian children vaccinated against smallpox,
with material direct from a “vaccinal sore,”
came down with syphilis. Smallpox vaccine administered to kids in Camden, New Jersey, at the start of the twentieth century, seems to have been contaminated with tetanus bacillus, resulting in the death of nine vaccinated children from tetanus. Around the same time, a batch of diphtheria antitoxin prepared in St. Louis, using blood serum from a horse, also turned out to carry tetanus, which killed another seven children. Producers then began filtering vaccines, an effective precaution against bacterial contamination; but viruses passed through the filters. Formaldehyde was sometimes added to inactivate a target virus, and that supposedly killed unwanted viruses too, but the supposition wasn’t always correct. As late as midcentury, some of the early batches of the Salk polio vaccine were contaminated with a virus known as SV40, endemic in rhesus macaques. SV40 in vaccine became a hot issue, several years later, when suspicions arose that this virus causes cancer.

Whether vaccine contamination happened with HIV-1, and far more consequentially, is another matter. That the vaccine in question had been given to Africans was not in dispute. Between 1957 and 1960, a Polish-born American researcher named Hilary Koprowski—a lesser-known competitor in the same vaccine-development race that engaged Salk and Sabin—arranged for his candidate vaccine to be widely administered in areas of the eastern Belgian Congo and adjacent colonial holdings. These were parts of what would eventually be DRC, Rwanda, and Burundi. Koprowski himself visited Stanleyville, in 1957, and made contacts who later oversaw the trials. Children and adults lined up trustingly, in places like the Ruzizi Valley north of Lake Tanganyika, to receive oral doses of liquid vaccine from a tablespoon or a squirting pipette. Spritz, you’re good. Next! The numbers are uncertain. By one account, roughly seventy-five thousand kids were vaccinated just in Léopoldville. The heterodox theory argued two additional points about this enterprise: First, that Koprowski’s vaccine was produced by growing the virus in chimpanzee kidney cells (rather than in monkey kidney cells, the standard technique); second, that at least some batches of that vaccine were produced from chimpanzee kidneys drawn from animals infected with SIV
cpz
.

The result of that flawed vaccinating, certain people have argued, was iatrogenic infection (disease caused by medical treatment) of an unknown number of Central Africans with what later became recognized as HIV-1. By this notion, known for short as the OPV (oral polio vaccine) theory, a single reckless researcher had seeded the continent—and the world—with AIDS.

The OPV theory has been around and notorious since 1992, when a freelance journalist named Tom Curtis described it in a long article for
Rolling Stone.
Curtis’s piece ran under the headline:
THE ORIGIN OF AIDS: A STARTLING NEW THEORY ATTEMPTS TO ANSWER THE QUESTION, ‘WAS IT AN ACT OF GOD OR AN ACT OF MAN?’
Several other researchers had mooted the idea earlier, more obscurely, and one of them had put Tom Curtis onto the story. When Curtis started looking into it, some eminent scientists responded with defensive dismissals, which served only to suggest that maybe the theory did merit consideration. Curtis even drew a brusque comment from the head of research for WHO’s Global Programme on AIDS, Dr. David Heymann: “
The origin of the AIDS virus is of no importance
to science today.” He quoted another expert, William Haseltine of Harvard, as saying: “
It’s distracting, it’s nonproductive, it’s confusing
to the public, and I think it’s grossly misleading in terms of getting to the solution of the problem.” After publication of the piece, lawyers for Hilary Koprowski filed a lawsuit against Curtis and
Rolling Stone,
charging defamation, and the magazine ran a “clarification,” admitting that the OPV theory and Koprowski’s role represented just an unsupported hypothesis. But as the dust settled at
Rolling Stone,
an English journalist named Edward Hooper took hold of the OPV theory as a personal obsession and an investigative crusade, giving it a second life.

Hooper spent years researching the subject with formidable tenaciousness (though not always critical good sense) and in 1999 made his case in a thousand-page book titled
The River: A Journey to the Source of HIV and AIDS.
Hooper’s river was a metaphorical one: the flow of history, the stream of cause-and-effect, from a very small beginning to an ocean of consequences. In the book’s prologue, he alluded to the quest by Victorian explorers for the source of the Nile. Does that river begin from Lake Victoria, pouring out at Ripon Falls, or is there another and more obscure source upstream from the lake? “
The controversy surrounding the source of the Nile
,” Hooper wrote, “is strangely echoed by another controversy of a century and a half later, the long-running debate about the origins of AIDS.” The Victorian explorers had been wrong about the Nile and, according to Hooper, so were the modern experts wrong about the starting point of the AIDS pandemic.

Hooper’s book was massive, overwhelmingly detailed, seemingly reasonable, exhausting to plod through but mesmerizing in its claims, and successful at bringing the OPV theory to broader public attention. Some AIDS researchers (including Phyllis Kanki and Max Essex) had long been aware that vaccine contamination, with SIV from monkey cells, was at least a theoretical possibility; they had even conducted screening efforts on vaccine lines, and found no evidence of such a problem. Hooper, following Tom Curtis, raised the idea from a concern to an accusation. His vast river of information and his steamboat of argument didn’t prove the essential thesis—that Koprowski’s vaccine had been made from chimp cells contaminated with HIV. But his work did seem to raise the possibility that the vaccine
could
have been made from chimp cells that
might
have been contaminated.

The issue of possibility then gave way to the issue of fact. What had actually happened? Where was the evidence? At the urging of an eminent evolutionary biologist named William Hamilton, who believed that the OPV theory deserved investigation, the Royal Society convened a special meeting in September 2000 to discuss the subject within its broader context. Hamilton was a senior figure, liked and respected, whose early work in evolutionary theory helped inform Edward O. Wilson’s
Sociobiology
and Richard Dawkins’s
The Selfish Gene
. He swung the Royal Society into giving the OPV theory a fair hearing. Edward Hooper, though not a scientist himself, was invited to speak. Hilary Koprowski also came, as well as a roster of leading AIDS researchers. By the time that meeting convened, though, William Hamilton was dead.

He died suddenly in March 2000, of intestinal bleeding, after an attack of malaria contracted during a research trip to DRC. In his absence, his colleagues at the Royal Society discussed a wide range of matters related to the origins of HIV and AIDS. The OPV theory was just one topic among many, though implicitly it drove the agenda of the whole meeting. Did the available data from molecular biology and epidemiology tend to support, or to refute, the vaccine-contamination scenario? A corollary to that question was: When had HIV-1 first entered the human population? If the earliest infections occurred before 1957, those infections couldn’t have resulted from Koprowski’s OPV trials. Archival HIV-positives might be decisive.

This is the context that brought DRC60 out of Kinshasa. After the Royal Society meeting, a Belgian physician named Dirk Teuwen, who had taken part, recollected some references to early pathology work in the Congo that he had seen in archival reports of the colonial medical laboratories. Teuwen conceived the idea—and raised it with other attendees—that HIV-1 might be detected in some of the tissues preserved within those old paraffin blocks. He met skepticism; the others doubted that any useful traces of virus could have survived through the decades—decades of tropical heat, simple storage, administrative upheaval, and revolution. But Teuwen was stubborn. He enlisted an ally, a senior Congolese bacteriologist named Jean-Jacques Muyembe, and, with approval from the Ministry of Health, Muyembe started looking. He went up to the University of Kinshasa, rifled through the pantry behind the blue curtain, packed 813 paraffin-embedded specimens into an ordinary suitcase, and carried it with him on his next professional visit to Belgium. There he handed the trove to Dirk Teuwen. Teuwen, in accord with a prior agreement for collaborative study, sent the samples to Michael Worobey in Tucson.

These two lines of narrative fold back into each other. Worobey, as a grad student, knew both Bill Hamilton at Oxford and some of the disease biologists in Belgium. Impelled by his own interest in the origins of HIV, Worobey accompanied Hamilton to DRC on that last fatal fieldtrip. They went in January 2000, during the chaotic aftermath of the civil war, which had replaced President Mobutu Sese Seko with President Laurent Kabila. Hamilton wanted to collect fecal and urine samples from wild chimpanzees; those specimens, he hoped, might help confirm or refute the OPV theory. Worobey, for his part, put little stock in the OPV theory but wanted more data from which to chart the origin and evolution of HIV. It was a crazy time in DRC, more crazy than usual, because two rebel armies opposed to Laurent Kabila still controlled much of the eastern half of the country. Hamilton and Worobey flew into Kisangani (formerly Stanleyville), a regional capital along the upper Congo River, the same city where Koprowski had begun his vaccinating enterprise. Now it was occupied by Rwanda-backed forces on one riverbank and Uganda-backed forces on the other. Commercial airlines weren’t flying, because of the war, so the two biologists shared a small, chartered plane with a diamond dealer. In Kisangani they paid their respects to the Rwanda-backed commander, whose ambit included most of the city, and as quickly as possible got out into the forest, where they would be safer among the leopards and snakes. They spent a month collecting fecal and urine samples from wild chimpanzees, with help from local guides, and by the time they left, Hamilton was sick.

Neither he nor Worobey knew
how
sick, but they caught the next exit flight they could, which took them to Rwanda. From there they bounced to Entebbe in Uganda, where Hamilton got a confirmed diagnosis of falciparum
malaria and some treatment, then onward to Nairobi, and from Nairobi up to London Heathrow. By now Hamilton seemed past the worst of his illness; he was feeling much better. They had accomplished their mission and life was good. An American field biologist once expressed to me how he felt in such moments. “That’s the name of the game: getting home with the data.” This man’s research too involved dangers—shipwreck, starvation, drowning, snakebite, though not malaria and AK rifles. “If you take too many risks, you don’t get home,” he said. “If you take too few, you don’t get the data.” Hamilton and Worobey got the data, got home, and then learned that the ice cooler containing their precious chimp specimens had gone astray in luggage handling somewhere between Nairobi and London.

I visited Michael Worobey in Tucson to hear about all this. “Everything was fine,” he told me, “except we checked six bags, including the cooler that had samples, and five of our bags came through the carousel and the one with the samples disappeared.” His friend Hamilton, feeling ill again the next morning, went to a hospital—and hemorrhaged catastrophically, perhaps due to anti-inflammatory drugs he’d been taking against the malarial fever. Worobey phoned and got the news from Hamilton’s sister:
Who are you why are you calling Bill is in extremis
. Worobey meanwhile had been hassling by long-distance phone with a luggage handler in Nairobi, who assured him that the cooler had been found and would arrive on the next flight. What arrived was someone else’s cooler, full of sandwiches. “So that was an extra bit of drama that unfolded as Bill was dying in the hospital,” Worobey told me. The correct cooler arrived two days later but Hamilton was in no shape to celebrate. He went through a series of surgeries and transfusions and then, after weeks of struggle, he died.