In the early 1980s, a mysterious new disease called AIDS started appearing in the United States. Suddenly and simultaneously, people in several major cities—gay men in particular—started developing immune problems, opportunistic infections, and skin cancers. Starting in California, researchers at the Centers for Disease Control (CDC) interviewed several patients, and eventually constructed a network of 40 infected men who were all connected through sexual encounters. It was a clear sign that AIDS was caused by some kind of sexually-transmitted infection.
One of those 40 cases was a Canadian flight attendant named Gaëtan Dugas. Having had sex with patients from both California and New York, he seemed to connect the epidemic from coast to coast. As the 57th AIDS patient to reach the CDC team’s attention, Dugas was originally billed as Case 057. But since he came from outside California, and wasn’t even a U.S. resident, the investigators started referring to him offhandedly as the “Out-of-California patient”—or “Patient O” for short.
That was an unfortunate move. “When the study got written up and was circulated beyond the immediate team to other people within the CDC, that ambiguous oval got interpreted by some as a zero,” says Richard McKay, a medical historian at the University of Cambridge, who recently tracked down the details of the case. By the time the CDC study was published in 1984, Patient O had become Patient 0. In the paper’s sole diagram, Dugas sits at the center, like the spider in a web of disease.
Labels have power. As “Patient Zero,” with its connotations of ground zero, Dugas came across as not just the center of that particular AIDS cluster, but as the source of the entire U.S. epidemic. The CDC team did their best to naysay this misconception, but it gained steam globally in 1987, after the journalist Randy Shilts published his bestselling book And The Band Played On. Shilts identified Dugas by name, and while he never specifically claimed that the man was the source of the U.S. AIDS epidemic, reviewers and media commentators weren’t so restrained.
The idea fit with the prejudices of the day: Here was a modern Typhoid Mary, whose homosexuality and irresponsible promiscuity had brought a plague to American shores. “Whether it’s explicit or not, there’s always a focus on the potential moral failings of the first recognized individual,” says McKay. But the concept of Patient Zero has been weakening for years, with several lines of evidence showing that HIV—the virus behind AIDS—likely arrived in the U.S. well before Dugas was ever infected.
Now, a new study exonerates Dugas once and for all. It combines McKay’s historical detective work with genetic evidence compiled by Michael Worobey, an evolutionary biologist at the University of Arizona. He sequenced the complete genomes of HIV taken from U.S. samples collected in the late 1970s, and showed that Dugas could not possibly have been the first AIDS patient in the U.S. Indeed, the disease likely entered the country from Haiti in 1971, flying under the radar for a decade before anyone realized what was happening.
HIV first started infecting humans somewhere in West Africa, having jumped into us from chimpanzees. From there it spread around the world, and as it did so, its genes changed. By sequencing those genes and comparing those changes, scientists can reconstruct a family tree of HIV—a phylogeny—and work out which strains are descended from which.
Worobey did this in 2007 using archival blood samples from five Haitian immigrants, who were among the first AIDS patients in the U.S. He showed that these Haitian strains most likely gave rise to those that later swept the country, implying that virus stopped in the Caribbean on its way from Africa to America. He also concluded that the virus must have arrived in the U.S. around 12 years before AIDS was formally recognized in 1981.
But when he tried to publish his results, “one reviewer said: There’s no way the virus was circulating in the U.S. for that long under the radar; I don’t believe it,” Worobey recalls. It was hard to convince the doubters because the Haitian samples were all collected in the 1980s, after the epidemic’s supposed start. He was looking further back in time by analyzing the virus’s genes, and skeptics either didn’t understand or didn’t buy that approach.
So Worobey started looking for older samples. He found several that had been collected from gay men in New York and San Francisco in 1978 and 1979, for studying hepatitis B. He and his colleagues tested thousands of these, and a few yielded enough genetic material for him to sequence the complete HIV genome.
These sequences bolstered his earlier conclusions, and added some new ones. They reveal that HIV had spread from Africa to the Caribbean by around 1967, and had jumped into the U.S. by around 1971. It landed in New York City and began diversifying rapidly. From there, it spread to San Francisco in 1976, creating more clusters of infection. By the time anyone noticed the first sign of AIDS in 1981, the virus had already hopped from coast to coast, and become genetically diverse.
“Some people may say that we knew this already, and in broad strokes, that’s true,” says Beatrice Hahn, from the Perelman School of Medicine, who studies the evolution of HIV. “But all the other stuff was inferences, using samples collected after the outbreak, and not everyone is comfortable with phylogenetic reasoning. When a tube shows up that has 1978 on it, that means something.”
It certainly means something for the reputation of Gaëtan Dugas. Worobey sequenced the virus that infected Dugas and found that it was typical of the U.S. strains at the time. It wasn’t the ancestor of the strains that ravaged America, and it wasn’t any more closely related to the West Coast strains than those on the East. This means that not only did Dugas not bring AIDS to America, but he didn’t spread it west either. He was a totally mundane part of a very unusual epidemic.
The sexual network constructed by the CDC team—one of whom is a co-author on the new study—“almost certainly was not the true network that the virus had moved through,” says Worobey. Rather than showing chains of transmission, it simply showed sexual contact between 40 men years after they had contracted the virus. “Their conclusion that HIV spreads via sexual contact was correct, but the thinking that got there was not,” Worobey says.
The study shows how powerful genetics can be in reconstructing the path of an outbreak—and it’s far from the only one. In 2010, evolutionary biologists used gene trees to prove that a man named Anthony Eugene Whitfield had knowingly infected many women with HIV. More recently, biologists used a pocket-sized DNA sequencer to track the evolution of Ebola in real-time, providing details about routes of transmission that helped to curtail the recent west African outbreak. The same techniques that help us peer into the deep past can help us protect our future.
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