In Search of the Origin of AIDS

No one knows if drug cocktails will ever become a truly practical cure for AIDS. At best, they only keep the virus in check, and they cost tens of thousands of dollars every year, which puts them beyond the reach of the vast majority of AIDS victims. In the hopes of finding new treatments, other researchers are studying the history of the virus. Hidden in its past they may uncover a cure that they would not otherwise find.

When AIDS was first recognized as a disease of its own, it seemed to come out of nowhere. In the early 1980s American gay men started coming down with bizarre diseases that a healthy immune system could easily suppress. Their immune systems had collapsed, and soon researchers in France and the United States discovered that HIV was responsible. It was a dangerous virus, they found, but a fragile one. A cold virus can travel through the air and cling to fingers and lips. But HIV needs to be helped from the bloodstream of an old host to a new one, through sex, shared hypodermic needles, or contaminated blood transfusions.

By the end of the 1980s, researchers recognized that they had a global plague on their hands. But AIDS is like no other epidemic. During the Black Death of the 1600s, for example, Europeans who came down with bubonic plague usually were dead in a few days; HIV can take 10 or 15 years to do its damage. Because of its slow, masked course, HIV spread quietly during much of the 1980s, slipping from one unsuspecting victim to the next. By 2000, 36 million people were suffering from AIDS, and 21.8 million people had already died of the disease. Sub‑Saharan Africa has suffered the heaviest blow, with 25.3 million people now infected with AIDS.

Where did HIV come from? There are hardly any clues from before the virus became epidemic in the 1980s. (The oldest known sample of HIV comes from the blood of a patient in Zaire in 1959.) But scientists can go back in time by looking at the genetic code of today’s HIV and building an evolutionary tree for the virus.

HIV belongs to a class of slow‑breeding viruses known as lentiviruses (lentos is the Latin word for “slow”). Cats, both wild and domesticated, get feline immunodeficiency virus; cows get bovine immunodeficiency virus. And most significantly, primates get simian immunodeficiency viruses (SIVs), which resemble HIV. Unlike humans, though, most primates never seem to get sick from their infections. The viruses may have once been as lethal to them as HIV is to humans now, but natural selection has preserved only the resistant primates.

Scientists have found evidence that the HIV epidemic is the result of SIVs jumping from primates into humans several times. HIV exists in many different strains, which are classed as either HIV‑1, the form found in most parts of the world, or HIV‑2, which is limited to West Africa. In 1989 virologist Vanessa Hirsch of Georgetown University and her colleagues found that HIV‑2 is more similar to SIV from the sooty mangabey, a monkey from West Africa, than it is to HIV‑1. Likewise, the SIV of the sooty mangabey is more like HIV‑2 than the SIV of other monkeys. Sooty mangabeys are kept as pets in West Africa and hunted for food; Hirsch suggested that HIV‑2 originated as people were scratched by the monkeys and picked up infected mangabey blood through open wounds.

Although HIV‑1 is much more common, it wasn’t until 1999 that a clear picture of its history emerged. Beatrice Hahn of the University of Alabama in Birmingham and her colleagues discovered that SIVs found in chimpanzees were the closest known relatives of HIV‑1. And not just any chimps–the viruses most like HIV‑1 all came from a single subspecies of chimpanzee: Pan troglodytes troglodytes, which lives in Gabon, Cameroon, and surrounding countries in equatorial West Africa. From this one subspecies of chimp, Hahn concluded, strains of HIV‑1 had evolved at least three separate times.

Hahn and her colleagues are now putting together a picture of how HIV got its start. It’s only a hypothesis, certainly, but one that has been bolstered as more evidence has come to light. The ancestors of sooty mangabeys and chimpanzees carried the ancestors of HIV for hundreds of thousands of years. Hunters sometimes contracted these viruses–along with many others–when they killed and butchered monkeys and chimps. But the ancestors of HIV, poorly adapted for life in humans, had little chance of establishing themselves in a new host. Even if they could survive in the body of a single hunter, they couldn’t spread very far. They only rarely came into contact with hunters, and the hunters themselves lived in remote villages without much contact with the outside world. The virus was likely to die off before it could be transmitted to other hosts.

The dramatic changes that came to West Africa in the twentieth century finally unleashed HIV on our species. Cities sprang up; railroads were built into the interior; loggers moved deeper into the forests; people were forced to move to plantations to work. The market for bush meat grew, and with it the contact between hunters and primate blood. With people moving quickly across the countryside on buses and trains, a virus could easily spread from its first human contacts to new hosts.

The diversity of HIV in the people of equatorial West Africa is immense compared to the rest of the world, and that, Hahn argues, is the result of many separate leaps the virus has made from primates into humans there. HIV‑2 has jumped from sooty mangabeys to humans as many as six times, and HIV‑1 has crossed from Pan t. troglodytes at least three times. Most of these leaps were dead ends. Only two of the six HIV‑2 strains have made any headway in humans, while the global AIDS epidemic is due mainly to a single strain of HIV‑1. As West Africa came into closer contact with the rest of the world, the virus spread to Europe, the United States, and elsewhere.

For now, this hypothesis awaits more tests. Hahn’s tree of HIV is based on viruses from only six chimps; as more data comes in, researchers may have to rearrange the branches of the tree. But it is no easy task finding viruses in wild chimps, and the job gets harder every day: the trade in chimpanzee meat that may have triggered the AIDS epidemie is driving Pan t. troglodytes rapidly toward extinction.

These endangered chimpanzees may carry the first chapters of the biography of AIDS inside them. They are infected with the closest known relatives of HIV‑1, and yet their immune systems are able to hold the viruses in check. Because their virus is so closely related to HIV, the adaptations they have evolved against it may be the secret to a human cure. If they should disappear, clues to a cure may disappear with them.

“Our hospitals are filled with incurable infectious diseases such as AIDS–well, these same diseases have affected animals, but they haven’t had the benefit of an emergency room,” says Stephen O’Brien, a virologist at the National Cancer Institute. “All they’ve had is natural selection. If we look through their genomes and discover how they deal with these same onslaughts, we’ll be much better equipped to come up with therapies for humans.”