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Anne Stone traces evolution of tuberculosis and its hosts

AAAS Fellow Anne Stone's research focuses on population history and in understanding how humans and other primates have adapted to their environments, including their disease environments. (Photo: Lara Herrington Watson)

Obsessed with the way species live and evolve together, anthropological geneticist Anne Stone wants to know "How close are we to our closest relative?" and "Are we a reservoir for pathogens?"

To illustrate the interconnectedness of all species in the modern world, the Arizona State University associate professor and AAAS member climbs Tempe Butte, known locally as "A" Mountain, on the edge of campus, which lies along the flight path of the nearby Phoenix Sky Harbor airport. As planes whiz past, she discusses the nature of contagion within today's global infrastructure. She wants to know more about how pathogens spread thousands of years ago.

Her research on ancient diseases focuses on tuberculosis in human and non-human populations in the Americas and elsewhere. Specifically, Stone wants to better understand its evolution and how it has moved between species and continents, both before and after European contact and colonization. Tracing its footprint will shed more light on its current behavior and may prevent some tuberculosis cases, she says.

Scientists used to think humans contracted tuberculosis from cattle, and that Europeans brought it to the Americas. "However, evidence of ancient bone lesions has shown the presence of tuberculosis prior to European contact, before cows were here. So, actually, we may have given tuberculosis to them," Stone says.

In other words, a separate, non-European strain of tuberculosis made its way to the Americas before Columbus. Since European contact, more virulent European tuberculosis strains have outcompeted and replaced all active American strains, except in large cities, where immigrants inadvertently bring non-European strains.

Though she is working on at least six research projects at once, "the current work on ancient tuberculosis is really fascinating and surprising," Stone says. "We're not curing cancer here, but it's a public health and conservation concern. It's also very interesting to find more about our history."

Her research compares modern DNA samples of Old World non-human primates, some of whom are infected with tuberculosis, to the DNA of New World pre-contact humans infected with tuberculosis.  Stone collaborates with behavioral primatologists and bioarchaeologists to get cheek swabs and other DNA samples from primates and bone samples from museums.

"It's exciting, because the research we're doing wouldn't have been possible two years ago," Stone says.

Extracting pathogen DNA from ancient human remains used to be much more difficult. This is because ancient human DNA samples have spent thousands of years underground, breaking down and decaying, and accumulating a lot of fresh microbial and soil DNA.

"The pieces of DNA needed for this research were often too small to be extracted and then sequenced successfully," Stone said. "It was like looking for a needle in a haystack."

Thanks to new DNA extraction techniques, which Stone compares to a smaller strainer, her lab can search through this "haystack" faster to capture, then sequence, the elusive tuberculosis DNA.

Stone, who recently submitted the lab's findings for publication, says her research will help scientists understand how pathogens have changed over time and which pathogens are circulating in non-human primates.

Stone has worked across disciplines and departments her whole career. She double majored in biology and archaeology at the University of Virginia, and again as a Ph.D. student at Pennsylvania State University, choosing a geneticist and an archaeologist as her mentors.

Currently she teaches molecular biology courses while conducting research out of her lab housed in the anthropology department.

"My tradition is to have one foot in each field," Stone says.

Fueled by coffee and curiosity, Stone oversees multiple research projects and mentors a dozen undergraduate and graduate students.

One current project focuses on the presence of L-gulonolactone oxidase in primates, a gene that is associated with the production of Vitamin C. It became ineffective in most primates at some point in their evolution, probably when they began eating food high in Vitamin C, Stone says. To learn how and when this occurred, her lab is researching the gene in strepsirrhine primates, including lemurs, which still carry the effective gene.

Stone is eager to learn more about tuberculosis and leprosy. She plans to gather analyze more samples from primates in the wild and ancient samples from North America, which should continued insights into primates carrying different strains of tuberculosis and leprosy that are not yet sequenced. Tracking a variety of existing strains will clarify how they relate across species. It will also give her specific answers about how pathogens have adapted over time. She may also explore human and non-human variation in susceptibility to infectious disease.