Can Duke Lemur Center primates point the way to more humane research?

Randy the ring-tailed lemur is an enthusiastic, if slightly fussy, research subject.

Splay-legged and wide-eyed, he buried his snout in a purple plastic cup last week and began his experimental task of the day — to eat a mash of dragon fruit, bell peppers, squash and blackberries.

Then, with two long bulbous fingers, Randy reached into his plastic cup, plucked a chunk of bell pepper out, and threw it to the side.

Bell peppers are an important data point for Duke Lemur Center researchers: they are studying how different types of seeds grow after passing through a lemur’s digestive tract.

But ultimately, Randy has a lot of control over whether — and how — he chooses to participate in scientific studies at the DLC.

“We do research through voluntary participation,” said Erin Ehmke, director of research. “We’re not forcing them to do anything.”

For decades, non-human primates — with whom we share more than 95% of our DNA sequence— have offered scientists a window into complex human diseases.

Studying their brains and bodies, which closely resemble human anatomy, has produced numerous medical advances, like HIV treatments, the COVID-19 vaccines and chemotherapy.

But what makes them such good models for studying human problems, namely their human-ness, is also what has thrown the future of primate research into uncertainty.

In the last decade, mounting ethical concerns about whether intelligent animals should be subject to invasive experiments have pushed federal agencies to scale back funding and some of the country’s largest primate research centers to shutter.

The Duke Lemur Center leaders see an alternative approach to primate research, where research questions can be studied non-invasively and even with the primate’s cooperation.

“It’s a way of changing the paradigm of research: it can be humane and there’s still a lot of great work that comes out of it,” said Greg Dye, executive director of the center.

Tiny hats and computer games

On the center’s 100 acres of enclosed forest, lemurs spend most of their days napping in trees and foraging for wild fruits and leaves. For nearly 60 years, the institution has housed generations of lemurs, our most distant primate cousins, whom Ehmke likes to call “living fossils.”

When lemurs living there are used in research, Ehmke said they’re treated as “willing participants,” giving lemurs like Randy the latitude to turn up their noses at unappetizing peppers.

At a minimum, experiments conducted at the DLC cannot cause harm to the lemurs, many of whom belong to critically endangered species.

The board responsible for vetting research proposals asks a simple question when judging whether to approve the experiment: “Would we do this study on ourselves?”

But Ehmke thinks some of the best research proposals go a step further, to think up experiments the lemurs actually enjoy.

One study, for example, provided lemurs with blankets and memory foam mattresses to study their nesting behavior. In her office Ehmke keeps a photo of one of the study participants, peering out contently from a cocoon of blankets.

Another research project used a touch-screen computer to study color blindness in ruffed lemurs. In exchange for raisins and dried cranberries, they were trained to tap a red square when it popped up on the monitor.

Some lemurs liked playing the computer game so much that the scientists had to bribe them with treats to stop playing, said Raymond Vagell, a Texas State University Ph.D. candidate, who has centered his research around primates at the DLC.

“The lemurs do not want to leave,” Vagell told the Lemur Conservation Network. “It’s like a child that can’t get enough of their video games or TV.”

A scientific opportunity

Vagell said non-invasive research is not just an ethical perk— it can also produce better scientific research.

“Depending on what questions you’re asking, a stressed animal will give you different data than an animal that’s not stressed,” he said.

These harmless research techniques, when applied creatively, can also be used to study trickier biomedical topics, like brain diseases, Ehmke said.

DLC researchers plan to use computer games to track cognitive decline in mouse lemurs, who, like humans with Alzheimer’s disease, experience brain shrinkage and a build-up of amyloid plaques as they age.

Ehmke said many primate researchers have been challenged to find new, non-invasive methods to collect primate data thanks to the DLC’s policies.

It could be something as simple as swapping a blood test for a saliva sample, which DLC researchers collect by letting lemurs chew banana-flavored cotton swabs.

One visiting scientist who had previously bolted a camera into lemurs’ skulls to study their eye movement was pushed to redesign their entire experiment, Ehmke said.

At the DLC, the scientist discovered it was possible to collect similar data by conditioning the lemurs to wear Velcro camera hats and tiny vests to hold the battery packs.

One lemur, so taken with the training, began to happily put the hat atop his own little head, Ehmke said.

Teddy Rosenbluth covers science and health care for The News & Observer in a position funded by Duke Health and the Burroughs Wellcome Fund. The N&O maintains full editorial control of the work.