The Mystery of How Tuberculosis Got to the Americas

Back in the 1990s, Felipe Cárdenas-Arroyo came across a collection of human vertebrae, excavated near Bogotá, Colombia, that were pockmarked with tiny holes. To him, this looked like tuberculosis, which can in rare cases spread from the lungs to infect the adjacent bones of the rib cage and spine. So Cárdenas-Arroyo, an anthropologist at the Colombian Institute of Anthropology and History, sent them along to a colleague, Jane Buikstra, who had long been interested in the mystery of tuberculosis’s presence in the Americas. Twenty years passed and nothing much happened with these bones until 2018, when Buikstra realized that they might in fact hold some of the answers.

The conundrum that Buikstra and others had been puzzling through was this: In North and South America today, the tuberculosis that sickens people tends to match the lineage that circulates in Europe, suggesting that colonists brought the disease with them some 500 years ago. But bones with signs of tuberculosis in the Americas actually go back thousands of years—long before the arrival of Europeans. “The history of medicine books just sort of ignored it,” Buikstra, a bioarchaeologist now at Arizona State University, told me.

She thought, instead, that the first humans in the Americas might have brought tuberculosis across the Bering Land Bridge and then south through the two continents. But this theory, too, ran up against some inconvenient evidence. The oldest bones with signs of TB were found in Peru and Chile and the more recent ones in North America, as if the disease had spread south to north rather than north to south. Were the bioarchaeologists who saw TB in the bones mistaken? Or did this pattern simply reflect which bones had been preserved and excavated? Then in 2014, a stunning finding turned the mystery on its head: Tuberculosis DNA extracted from 1,000-year-old pockmarked bones from coastal Peru did not match the modern European lineage of TB, nor did it match any lineages that infect humans. It instead matched a lineage of tuberculosis bacteria that infects seals. Seals.

“We were all absolutely shocked,” Buikstra said. Naturally, the finding raised more questions. It was plausible enough that coastal people who hunted seals could get infected with tuberculosis from the animals, but was this more than an occasional fluke? Did that seal-associated bacteria ever become adapted to humans? Could seals actually explain all those mysterious old cases of TB found all over the Americas? Buikstra thought of the pockmarked vertebrae that Cárdenas-Arroyo had noticed some 20 years ago, which came from sites in the highlands, hundreds of miles from the ocean.

Seal-associated tuberculosis, it turned out, was present in bones from those sites too. A recent study analyzing three ancient TB genomes—two from the plateau that surrounds Bogotá and a third from inland Peru—suggests that the seal-associated tuberculosis really did spread through the Americas. “The transmission of TB was a lot more complex than was ever thought beforehand,” says Helen Donoghue, who has studied ancient TB at University College London and was not involved in the study.

These three genomes, when compared with those of related tuberculosis lineages, together weave a tale of an ancient pathogen jumping from species to species. The bacteria that causes TB seems to have first begun infecting humans in Africa some thousands or tens of thousands of years ago—the exact date is still controversial—before it likely spread to animals living nearby. From there, tuberculosis somehow made its way to seals, who took it across the ocean. On the west coast of South America, the seals were hunted by humans, the distant relatives of the humans in Africa in whom tuberculosis likely first originated. In this process, the seals gave tuberculosis back to humans. This now seal-adapted tuberculosis called Mycobacterium pinnipedii spread through South America, either through another animal intermediary or from human to human along trade routes that connected the coasts to the mountains. The Muisca people who lived in the plateau near modern-day Bogota, says Cárdenas-Arroyo, traded salt, emeralds, and cotton with those from the coast. There is no archaeological evidence of seals at the Muisca sites, though, and isotope data suggest that the people’s diet did not include the animals either. “They would not have had direct contact with marine mammals. But they all have M. pinnipedii,” says Tanvi Honap, an anthropologist at the University of Oklahoma who was part of the study team. So whatever path the seal TB took there, it must have been indirect.

From there, the seal-associated TB might have then spread even farther north to modern-day Mexico, where archaeological evidence of the disease is more recent than that in South America. M. pinnipedii was at some point completely replaced by the European tuberculosis brought by colonists. Today, it’s not known to infect humans except in isolated cases, such as among zoo staff.

All of this suggests an origin and spread for TB that is more complicated than once thought. But this tangled story is perhaps not hard to believe now that we’ve watched a novel pathogen—the coronavirus—make many of the same moves, if on a much more accelerated timeline. The coronavirus, too, has jumped from species to species; scientists think it most likely began in a bat that transmitted the virus to an unconfirmed animal intermediary and then to humans, who gave it to yet other animals, including mink, deer, even tigers—which in turn have sometimes given the virus back to humans. And the virus has pulled off evolutionary sweeps, in which a fitter variant completely replaces a previous one.

To nail down how M. pinnipedii spread through the Americas, Åshild Vågene, a study author who specializes in ancient DNA at the University of Copenhagen, suggests investigating ancient animal remains for TB. If other animals carried the seal-associated lineage inland, then that might show up in the archaeological record. More human evidence could also fill in the path tuberculosis took through the Americas. For example, Tiffiny Tung, an anthropologist at Vanderbilt University who studies the collapse of the Wari empire, has collaborated with some of the scientists behind this study on an analysis of ancient tuberculosis DNA from about 1000 to 1400 A.D. in the Andes of Peru. She told me she couldn’t share the sequencing results, but the team is very interested to see if these are also seal-associated lineages.

Moreover, Tung is interested in how tuberculosis prevalence changed as the Wari empire collapsed, wreaking violence in the region and changing diets. Most people who encounter tuberculosis bacteria do not become sick, and even fewer get sick enough to develop the bone lesions so obvious in the archaeological record. “TB is a disease that’s very tightly linked to overall health status,” says Tung. “If you already have a weakened immune system or you’re suffering from malnutrition … you’re going to be more susceptible to TB.” This is why tuberculosis remains deadly in developing countries, despite being considered a bygone of the Victorian era for most of the developed world. It still kills 1.5 million people a year worldwide, making it the deadliest infectious disease outside of the coronavirus pandemic.

Ancient DNA can uncover extraordinary genetic details about pathogens from long ago. But in all of human history, how that pathogen then manifested as disease—who it killed and how many—has always depended on the social and political context in which it spread. And this pattern, too, has continued well into our modern times.

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