A Tissue Sample From 1966 Held Traces of Early HIV

In 1966, a 38-year-old man visited a hospital in what is now the Democratic Republic of Congo. His name, his symptoms, and everything about him beyond his age and gender have been lost to history. But a piece of one of his lymph nodes was collected and preserved. By analyzing it, a team of researchers led by Michael Worobey from the University of Arizona have shown that the man was infected by HIV, the virus that causes AIDS. He wouldn’t have known it, though, and nor would his doctors. HIV was formally discovered 17 years later.

By wresting tiny genetic fragments from that tissue sample, Worobey’s team has almost completely reconstructed HIV’s genome from a time before anyone even knew it existed. And that work helps to flesh out the origin story of what would become one of the most important pandemics in human history. “There’s no other way to test these important inferences about the origins of one of the most important infectious diseases to ever hit humans,” says Worobey, who spent about five years trying to piece together that one tiny genome. “In retrospect, we’d probably do it again, but it’s crazy how much work it was.”

HIV was identified only in the 1980s, after a mysterious new syndrome began affecting men in United States. It seemed to come out of nowhere, but it had actually originated decades earlier and a continent away. We know this because as the virus spreads, its genes change. By comparing those changes and estimating how quickly they happen, scientists can backtrack their way through HIV’s evolutionary history to its very beginning.

The place, most likely: southern Cameroon. The estimated time: the 1920s. There and then, a chimpanzee virus hopped into some unlucky person, before making its way to the city now known as Kinshasa. In a populous and growing hub with a multitude of hosts, the new virus gained ground, eventually spawning lineages that spread around the world.

“Why are we interested in fossils? Because they tell a story,” says Beatrice Hahn, from the Perelman School of Medicine, who studies the evolution of HIV. “This HIV ‘fossil’ is no different. It’s an important piece in the evolutionary puzzle.”

The team also used the 1966 sample to check the history of HIV that they and others had gleaned by looking at modern viruses. Happily, that narrative turns out to be mostly right. The team estimates that the virus first arose sometime between 1896 and 1905—a little earlier than what others have calculated, but within the right ballpark. HIV’s present, it seems, is a good indicator of its past.

That’s not always the case with viruses. When researchers found traces of hepatitis B from the Bronze Age, they learned that the virus evolved 100 times more slowly than anyone had thought, which radically revised estimates of its origins. Even SIV, HIV’s chimp-infecting cousin, evolved at different rates in the distant past and in recent history, making it hard to work out when it arose. HIV, by contrast, has been more consistent. “It’s very reassuring,” Worobey said.

It might seem unexciting to spend a lot of time to learn that everything you knew was more or less right, but science depends upon such work. Without it, entire edifices of research can be constructed on shaky or nonexistent foundations.

The study is “admirable,” says Bette Korber from Los Alamos National Laboratory, and “the reconstruction of HIV’s emergence and spread is very important.” Korber pioneered such reconstructions: She created the first decent estimate of HIV’s date of origin, using a genetic database that she and others (including Worobey’s team) have repeatedly turned to. She notes that 60 million to 100 million people have been infected with HIV, and 25 million to 50 million have died—a scale of suffering comparable to past world wars. “HIV has left a wound of deepest sorrow across humanity,” she says. “It is part of the human experience. We need to understand it.”

That wouldn’t be possible, Worobey added, without the work of the Congolese pathologists who collected the relevant tissue samples decades ago. Their names are unknown too, and even their modern-day counterparts can go unnoticed. “They’re often unappreciated,” Worobey said. “They not only help the doctors you interact with directly but also play a crucial role in preserving these collections of tissues, which are now helping us to figure out the true history of this important virus.”

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