In the early 1980s, when AIDS deaths began to ripple across the U.S. in force, most people—including healthcare professionals—had never even heard of the virus behind the outbreak. It was a distant infection on African continent. Few predicted it would explode into a pandemic that would baffle scientists into the 21st century.

Now, researchers are piecing together HIV's full origin story: how it went from a simian virus in chimps to a human one that has infected an estimated 75 million people worldwide. In a paper published today in the journal Science, researchers follow the first reported cases of HIV from Cameroon (which previous studies had suggested as the likely place that the virus jumped from chimps to humans) down the Sangha River to Kinshasa, now the capital city of the Democratic Republic of the Congo.

"Léopoldville (now Kinshasa) was at the very heart of the development of the pandemic," says Jacques Pépin, an epidemiologist at the University of Sherbrooke in Canada and coauthor on the paper. "That is where the virus was amplified to the extent that it eventually spread from there to the rest of the world."

Modern Genetics, Colonial Puzzles

Pépin and his colleagues analyzed more than 800 HIV samples, using modern molecular biology to scour hundred-year-old viruses for genetic similarities. They organized the DNA sequences of each sample into a viral family tree, ultimately tracing the viruses back to one common ancestor that originated in the year 1920.

One big mystery this team hoped to solve was how different strains of HIV separated over time. The predominant strain, called HIV-1, is generally broken down into groups. The M group is the major strain that now infects patients in the United States and Europe while the O group remains largely in central-west Africa.

Both strains surfaced in Kinshasa at around the same time, the researchers say. But by 1944, the M group had tripled its growth rate relative to the O group and quickly outpaced human population growth in the city. The reason for the surge is unclear, though the researchers speculate that sexual activities and unclean needles played a major role.

Another question is exactly how the virus first spread across Africa. Although prior studies had pointed to riverboats that ferried passengers—and their diseases—between African nations, the authors of this study suggest that the bustling African railroad was the more likely culprit. Many of the early sites of the outbreak were major coal mining centers connected by rail lines. At the height of the coal mining economy, these trains transported thousands of passengers every year. The authors suspect that HIV hitched a ride on the rails to gain a foothold in many African cities.

The Mysteries

This study may paint the clearest picture yet of the early days of HIV and its spread across Africa. But it remains unclear just what happened in Kinshasa. We know that this is where HIV gained the traction that would propel it into full-blown pandemic status. The question is, how?

"We are working on this—to what extent what happened in Léopoldville in the mid 20th century was the result of iatrogenic transmission [contaminated needles] versus sexual transmission," Pépin says.

Spread of HIV, 1920 to 1961.

And the specifics of the initial infection, including the identity of HIV patient zero, remain elusive. "Where did the very first patient, the one who got it from a chimp, live?" Pépin says. "I don't know whether anybody has any plan to investigate this now."

Why Study the History of HIV?

"The methodology is good, and the results are convincing," says Demetre Daskalakis, an infectious disease physician and head of New York City's Bureau of HIV/AIDS Prevention and Control, who was not involved in the study. It's important to remember, he says, that the findings, probably will not impact the treatment or prevention of HIV. "This is more of a viral archaeology paper," he says.

While Pépin acknowledges this, he is quick to add that a real understanding of the factors that caused the emergence of HIV could help us prevent similar disasters in the future. And besides, he argues, there is value in memorializing the dead by studying the origins of an infection that has taken so many lives.

"At least 35 million people have died from this virus so far," he says. "I think we owe it to them to try to understand how it happened."

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