How scientists tracked down the origin of Aids

WHEN Aids first struck an unsuspecting American population in 1981, no-one had a clue what caused this lethal new disease, or where it came from.

As the disease spread at an alarming rate, scientists hurried to identify the cause. Two years later, French scientists Françoise Barré-Sinoussi and Luc Montagnier from the Pasteur Institute in Paris, isolated a virus, later called the human immunodeficiency virus – HIV – that proved to be the cause of Aids. And just last month, more than 20 years after the event, they were awarded the Nobel Prize for Medicine for their monumental discovery.

By the time the French scientists identified HIV, thousands were suffering from Aids and, we now know, an epidemic of unprecedented magnitude was already under way in sub-Saharan Africa. But where did the virus come from? And when did it first infect humans?

HIV is very prone to mutation, meaning that it evolves rapidly – up to a million times faster than animal DNA. This allows the virus to foil attempts by the body's immune system to eliminate it. It also allows the virus to develop drug resistance, and has so far prevented us making an effective vaccine. But the mutations are useful for tracking the virus back to its roots. By following the trail of genetic changes HIV has accumulated over time, molecular detectives traced it to west-central Africa, pinning down its launch pad to Kinshasa (previously Léopoldville), capital of the Democratic Republic of Congo, where they found viruses with the greatest genetic diversity. Just one of these HIVs, carried by a single individual, jumped from Kinshasa to Haiti, and from there to the United States, thus spawning the pandemic in the US and Europe.

But where did the ancestral virus originally come from? For several years scientists searched for HIV-like viruses among captive African primates without success, but then a team headed by Beatrice Hahn at Alabama University found a chimpanzee (called Marilyn and trained for space flight by the US air force) of one particular subspecies, Pan troglodytes, the common chimpanzee, which carried a virus similar to HIV.

They suggested that HIV jumped from chimps to humans in Africa, perhaps during the bloody process of killing and butchering chimps for bush meat. To prove this they needed to isolate viruses from wild chimps, but these animals are reclusive, endangered and live in remote jungle areas, so taking blood samples was out of the question. Instead, scientists resorted to collecting chimp faeces from the forest floor at ten sites in south-east Cameroon known to be chimpanzee territory. After air-lifting some 600 samples to the US and analysing them for chimp subspecies as well as viruses, they pointed the finger unequivocally at chimpanzees in Cameroon as the origin of HIV.

Another part of HIV's complex history fell into place last month when a group of US scientists compared the genetic material of two HIVs rescued from human samples taken in Léopoldville and stored since 1959.

The differences between them showed that even 50 years ago, HIV had been around long enough to accumulate a substantial number of mutations, and dated HIV's transfer to humans to the beginning of the 20th century.

Now two questions remain: why did a chimp virus from Cameroon first appear in Léopoldville, 700km to the south-east, about 100 years ago? And if HIV first infected humans in the early 1900s, why did it go global only in the 1970s?

Firstly, in the early 1900s, rivers were the main thoroughfare out of the Cameroon forests, and since rivers in south-east Cameroon form part of the Congo River basin, all eventually lead to Kinshasa. So, spread by sexual contact, the virus must have travelled down-river, perhaps painstakingly slowly, from one village to the next, before it finally reached the city. Secondly, HIV spreads rapidly only in concentrated city populations. Thus the growth of Léopoldville in early 20th century colonial Africa was the key to its dissemination, giving the virus the opportunity to transform from a local to a global player that still kills 10,000 people every day.

• Dorothy H Crawford is professor of medical microbiology at Edinburgh University