Molecular Anthropologist Sarah Tishkoff

Geneticists do tricky work, but ordinarily it does not threaten their lives. Keep your hands out of the centrifuge. Don’t add water to acid. Wear gloves. The life sciences aren’t risk-free, but they usually can’t kill you.

Sarah Tishkoff might beg to differ. In her quest to collect DNA samples from thousands of men and women in Africa, she has beat her way through the kinds of bushlands that keep infectious-disease specialists in business. Tsetse flies, one learns in this kind of workplace environment, are not thwarted by bug spray. Animals really do attack. Soon after arriving in her empty new lab in the Clinical Research Building in March—an upright suitcase still unpacked in an office corner—she opened her laptop and pulled up a picture snapped in Cameroon. In it, Tishkoff’s sunglasses are pushed back over her shoulder-length auburn hair and she is gripping an eight-foot-long, freshly beheaded black mamba snake, which is thought to be one of the fastest on earth and carries enough venom to put 20 men in their graves.

A David and Lyn Silfen University Associate Professor with appointments in the School of Medicine’s genetics department and the biology department in the School of Arts and Sciences, Penn’s sixth PIK professor places herself in the way of such occupational hazards in the service of a third discipline: anthropology. Using present-day gene markers in place of fossilized bones, she is trying to unravel the deep history of humanity’s beginnings.

Where did our species originate? How did human populations spread and differentiate? What can genetic mutations tell us about the evolution of diet, culture, and disease? Those are some of the questions Tishkoff is addressing. Her work has taken her from South Africa to Sudan, and has led Popular Science magazine to name her in its annual roundup of scientists dubbed the “Brilliant Ten.”

“Within Africa,” she says, “there’s a lot of linguistic diversity, a lot of ethnic diversity, a lot of morphological variation—you have short-statured Pygmies and really tall Maasai—and people have very diverse diets: hunter-gatherers, pastoralists, agriculturalists.” That makes the continent a rich ground for exploring the genetic basis of human variation, a project many expect will dovetail with next-generation medical research.

“A lot of normal variability, whether it be height, skin color, resistance to infectious disease—these are traits that likely were adaptive in past environments,” Tishkoff explains. “So we’re looking at the evolutionary history of these genes that play a role in environmental response, with a major emphasis on infectious disease.”

To answer questions about how entire populations are related to one another, her research team focuses on random bits of the human genome to measure the degree of drift between, say, the Maasai in Tanzania and the bushmen of Botswana. This has allowed Tishkoff to demonstrate, for example, the common ancestry of geographically separated click-language speakers whose dialects are “as different as English and Chinese.” It has also contributed substantially to our understanding of population movements within Africa and emerging from Africa, from prehistoric times to the present day.  

Another element of her work involves zeroing in on specific genetic mutations that may predispose people to particular diseases, or shed light on why a diet that makes one person healthy can make another sick.

“One of the ones we started with is looking at lactase persistence, or the ability to drink milk,” the professor says. Most West Africans are lactose intolerant, as are, typically, East Asians and Middle Easterners. Most Northern Europeans and some East Africans, on the other hand, can drink milk without a problem. Tishkoff tried to examine this phenomenon by gathering DNA samples from East African pastoralists and then measuring how well they could metabolize the sugar in milk.

The mutation that allows Northern Europeans to do this is thought to have occurred about 8,000 or 9,000 years ago, which lines up with the archeological evidence for the origins of the domestication of cattle. “But cows didn’t make it past the Sahara desert—for climatic reasons or perhaps because of tsetse flies and things like that—until about 5,000 years ago,” Tishkoff says. Her DNA samples suggested that the East African mutation arose and swept speedily through pastoralist groups sometime between 7,000 and 3,000 years ago.

“So this is a great example—one of the few examples—of gene-culture co-evolution!” she says. “You’ve got the development of this new technology, which is the domestication of cattle, and then you have this mutation that happened to be around in the population that was beneficial, and it rapidly increased in frequency.”

The actual work of turning her field samples into scientific papers was even more challenging than that tidy result might lead one to believe—and not just because it involved dodging the occasional pair of venomous fangs.

“When I started to do this, I had never done field work before. I had no idea what to expect. I literally had to bring everything from sleeping bags to all of my lab equipment. I had to figure out, how am I going to isolate DNA with no electricity, in remote regions?” And how could she keep those samples from deteriorating without having access to refrigeration? And what were the odds any of that could happen when her first question upon finding a rural clinic in which to set up shop was typically, “Do you have a table?”

“They say yes, hopefully,” Tishkoff laughs.

Starting with blood samples instead of the more common (but more fragile) cheek swabs, she is able to spin down white blood cells with a centrifuge hooked up to a portable generator. Next, she adds a buffering agent that stabilizes the cells to withstand whatever passes for room temperature in Tanzania or Sudan. Back home, the DNA is extracted. So far, her samples have held up far better than she or anyone else expected. She hopes to continue using them for the rest of her career.

“In the future we want to start looking at the genetic basis of carbohydrate and lipid metabolism in some of the Africans with very distinct diets,” she says. “I want to understand, how are they adapted to these different diets? And how has that affected their metabolism of fat and protein and sugar? That could give us a clue maybe about diabetes, and why it is that diabetes is so prevalent in people of recent African descent in the United States.”

Now that she has landed on campus, Tishkoff is looking forward to joining in programs like Penn Medicine’s partnership with Princess Marina Hospital in Botswana [“Prognosis Botswana,” March|April 2007]. “If you speak to people who do fieldwork in that area, it’s almost an addiction,” she says. “I want to go back so bad. I can hardly wait.”

Assuming that she’s found time to furnish her lab and unpack that suitcase, the molecular anthropologist should be ready to get back to work.

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