What Makes Us Human?

UO researchers use molecular methods—like those used by crime-scene investigators—to merge anthropology and biology and explore far-reaching questions

Teetering on the cusp of extinction, African red colobus monkeys have long eluded all efforts to pin them down.

Spotting them is easy enough. Ranging up to twenty-six pounds, these tree-dwellers have dark, seemingly aged faces and fur that features black and white markings across the chest and shoulders and an orange blaze down the back. More challenging, though, is identifying the distinct ancestral lines within this simian’s family tree—it’s one of the longest-running unresolved issues in the classification of African primates.

As a result, conservation efforts are stymied: Given limited resources, which red colobus monkeys should be protected?

NelsonTingUO anthropologist Nelson Ting (right) turned to the monkey’s molecules. Then a doctoral candidate at the City University of New York, Ting isolated and unwrapped the monkey’s DNA, comparing one red colobus to another at the most fundamental level. Among eighteen family lines, he found specific strains extending back as far as three million years; the extinction of these distinct-but-related lineages in western Africa would be a major loss of the monkey’s evolutionary history, he argued.

The work is part biology, part anthropology. Those in the know call it “bioanth.” Today, Ting, Kirstin Sterner and Josh Snodgrass compose a trio of young faculty members at the UO who pursue their research with detective methods straight from CBS’s “CSI: Crime Scene Investigation.” Their fascination with the largest anthropological questions—what makes a human a human?—inspires an exploration of life at its most reductionist level: the cell.

Anthropologist or Molecular Biologist?

The two-inch-tall test tube between Ting’s thumb and forefinger is half-filled with a clear liquid. The liquid suspends precious cargo that is invisible to the human eye, but tells Ting everything he wants to know about the monkey in question.

Working in a lab, Ting has isolated from a feces sample the monkey’s DNA, the molecule that dictates how organisms develop and function. He effectively dissects this complex double helix in a series of chemical reactions that play off the nature of DNA’s four building blocks to bind to one another—adenine to thymine, guanine to cytosine. Using a computer, Ting can read the sequence of a particular fragment—AGTCTTG, for example—and compare it to samples from other monkeys to answer questions about the ecology and evolution of a species.

So is Ting a biologist who studies anthropology or an anthropologist who uses biology?

“That’s a good question,” Ting said. He acknowledges that the lines are blurring. “Many U.S. biologists these days aren’t as interested in organisms as they are in biological processes.” This is the deciding factor for Ting, in terms of defining himself as an anthropologist. Unlike biologists, “I’ve always been more interested in organisms,” he said, “and anthropologists are, by definition, organismal—they study humans and our closest relatives.”

Ting’s interest in human evolution led to a fascination with primates and conservation. Genetics is a popular approach for addressing conservation questions, Ting said, because it can identify crucial lineages or populations within a species, as with the red colobus monkey.

“We can’t save everything, unfortunately, and when you say one species is endangered you’re saying it has a higher conservation priority than something else,” Ting said. “How do you end up making that decision? People can use molecular methods to get the answer.”

The biological method complements the other approaches of colleagues in the UO anthropology department, Ting says. Faculty members and students in the department also study humans through archaeology and cultural anthropology; areas of focus include ecology and the environment, gender and sexuality, indigenous groups, health and globalization.

Molecular methods can be especially useful in situations where an incomplete fossil record hinders discovery. Perhaps the watershed moment for molecular anthropologists came in 2010. Using the genetic code extracted from 40,000-year-old Neanderthal fossils found in Europe, researchers proposed that there was once breeding between Neanderthals and modern humans, a highly contentious point of debate in the history of anthropology.

How Pathogens Are Transmitted

Of late, Ting has turned his gaze to Uganda. He’s taking part in a five-year project funded by the National Institutes of Health to determine how pathogens are transmitted within and among primate species in a community, including humans.

In one study, Ting was part of a team that identified two new strains of simian hemorrhagic fever virus, a lethal disease for captive macaques. In another, this group screened blood specimens from nine black-and-white colobus monkeys in Kibale National Park; they found new versions of simian immunodeficiency virus, the transmission of which led to the emergence of HIV, which subsequently jumped to humans. In that study, the group used an innovative approach called “deep-sequencing,” whereby a computer reads the genetic code of a monkey hundreds of times over to improve the accuracy of results.

That’s not to say there aren’t limitations—or occasional headaches—with the biological approach to anthropology.

On an afternoon earlier this spring, Ting’s phone rang: an urgent caller explained that a shipment of preservatives necessary for a new batch of fecal samples was unlikely to reach Uganda on schedule, and could prove much more expensive than originally expected.

After finishing the call, Ting leaned back in his chair and rubbed his forehead. “These are the kinds of logistics I deal with all the time,” he said, a tired smile breaking across his face.

Understanding Our Susceptibility to AIDS

KristinSternerIt’s a vexing question: HIV—predecessor to AIDS, a potentially lethal breakdown of the immune system in humans—came from the simian version, SIV. But many monkeys with SIV never even get sick.

Finding an explanation for that, Kirstin Sterner says, will help scientists understand our own susceptibility to AIDS and may lead to new treatments.

For many anthropologists, the allure is fieldwork in the farthest reaches of the globe. Sterner considers the laboratory her field—that’s where she can explore how life functions at what she calls “the nitty-gritty” level.

Under a microscope, we have a lot in common with other primates, Sterner says; the sequence of molecules in one species is very similar to that in the other. Yet we look nothing like apes—understanding how so few genetic changes can produce such differences between humans and other primates can provide insight into human evolution and public health questions.

“I love the idea of mixing big questions about human evolution with how it all works at the molecular level,” Sterner said. “It’s those subtle differences in how and when genes are actually used that may explain why some primates have one reaction to a virus and humans have another.”

When an immune cell detects a virus, the response is like runners in a relay race, passing a baton to the finish line. Proteins sitting on top of the cell are constantly scanning the environment for intruders; when they spot one, they pass a message to other proteins. This “baton” is passed from protein to protein until it arrives in the center of the cell—its nucleus—where a specific response is generated.

Like a Track Coach

The nuances of this process make a big impact in how the body responds to a virus; there may be subtle differences between some monkeys and humans. Sterner, who teams up with Ting and Snodgrass on some projects, is like a track coach: She knows the precise path these molecules run to deliver their message.

Among her colleagues, “I have more of an interest in exploring these cellular pathways and how they work,” Sterner said. “I enjoy studying how evolution has shaped different pathways so the outcome is slightly different in this species versus that species.”

Consider the sooty mangabey, a monkey found in the forests of West Africa. When infected with SIV, the monkey at first shows a surge in the virus throughout its body, similar to that seen in humans who have HIV. In both species, this “viral load” eventually drops and stabilizes. But in most humans, the virus will surge again, years later, as the immune system crashes; these mangabeys can carry the infection indefinitely without that breakdown.

Sterner’s approach, like Ting’s, relies primarily on breaking DNA into smaller sequences of molecules that can be read by a computer and compared against other samples. But she also wants to take the work an important—and demanding—step further.

Thanks to technological advances, biological anthropologists today can test whether slight differences in genetic sequences observed on a computer screen actually amount to anything in cells.

The anthropology department is developing a laboratory that will enable Sterner and others to manipulate DNA, using methods from molecular biology. She’ll be able to custom-design cells that have been modified with a particular sliver of DNA; how—or whether—the cell responds will tell Sterner if the test sample actually plays a role in a particular question.

“The process is technically difficult, but it gets you closer to inferring function from DNA,” Sterner said. “The differences in DNA sequences don’t always lead to something. You need to test them to see whether they actually result in a different outcome.”

A Drop of Blood

JoshSnodgrassA drop of blood can tell Josh Snodgrass a lot about the health of a community.

A DBS or “dried blood spot” sample is a simple finger prick that releases a drop of blood onto a piece of paper the size of a business card. Working closely with scientists, medical professionals and locals in the communities under study, anthropologists can quickly and painlessly (relatively speaking) collect scores of samples; the blood spots are later reconstituted in a solution.

Snodgrass can then measure the concentration in the blood of an antibody such as immunoglobulin E, which is a telltale sign that the body is defending itself against parasitic worms. With that, Snodgrass has what he needs to pursue questions about the differences in how human immune systems have developed in response to the environment in different regions; he can also share important public health information with the people he studies.

That second piece is especially important to Snodgrass. Biological anthropology, as he practices it, is not solely an investigation of human evolution in service to his personal curiosities; it’s an opportunity to partner with local scientists and communities to improve the health of remote, often disadvantaged groups across the globe.

In Siberia, Snodgrass is studying the health ramifications for indigenous peoples adjusting to a post-Soviet world. He’s found that economic turmoil and marginalization have caused an overall spike in blood pressure, and obesity is rising as groups that long survived on physically demanding subsistence means—reindeer-herding, fishing, hunting—move to villages and towns and assume sedentary, wage-based jobs.

In Ecuador, he’s examining how economic development and its suite of social and cultural changes affect the health of the Shuar, an indigenous group of 50,000 to 100,000. Working with UO colleagues and Thomas McDade of Northwestern University, Snodgrass learned that the Shuar have a different immune response from those of people in industrialized nations; he credits the group’s high exposure to parasites and viruses, bolstering arguments that early exposure to pathogens (despite their risks) is good for long-term health.

Snodgrass is also part of a World Health Organization initiative to address the gap in reliable data on aging and health in low- and middle-income countries. Under the effort, called SAGE (Study on global AGEing), scientists are studying the factors that influence aging and why they’re different between China and Ghana and the U.S. or western Europe.

“The SAGE project is really exciting,” Snodgrass said. “It has a lot of potential because it’s such an untapped, untouched area—this issue of aging and what it looks like cross-culturally.”

A ‘Human Biologist’

Snodgrass liked biology as an undergraduate, but it was his experience in an anthropology class that he found, in his words, “mind-blowing.” The discipline’s wide-ranging reliance on environment and evolution in explaining the human condition resonated with Snodgrass’ desire not to be pigeonholed in one field.

As an undergraduate at the University of California at Santa Cruz, he worked in conjunction with medical examiner’s offices, using his knowledge of skeletal anatomy to create biological profiles of unidentified corpses. At the graduate level, Snodgrass discovered wide gaps in our understanding of the fossil record, based on what he calls “imperfect knowledge of the present.” Snodgrass saw an opportunity to contribute by learning how human metabolism, immune systems and body sizes differ around the world.

Today, he calls himself a “human biologist”—someone straddling the line between biology and anthropology to better understand humans.

“Over my career, I’ve gone back and forth—‘oh, I see myself as a biologist, I just wish I could be in a biology department, my anthropology colleagues don’t understand me,’” Snodgrass said. Then he laughed: “The problem with that is that the biologists don’t understand me, either.”

— Matt Cooper

Photo Of Monkey By Olivier Lejade From France (P8200006.Jpg) [Cc-By-Sa-2.0 (Http://Creativecommons.Org/Licenses/By-Sa/2.0)], Via Wikimedia Commons