Tiny primates provide a closer match to human DNA and yield more accurate data.
They’re tiny, adorable, and quite possibly the answer to medical researchers’ dreams.
The big-eyed mouse lemur, the world’s smallest primate, may soon replace fruit flies, worms, and even mice as the primary lab animal for scientific research.
For decades, these three animals were the prototypical lab specimen because they were inexpensive to maintain, easy to study, and reproduced quickly enough to offer researchers a constant stream of samples.
But their genetic makeup hasn’t been a close enough match to humans to work well for the studies today’s researchers need to conduct, said Mark Krasnow, MD, PhD, a professor of biochemistry at Stanford University.
“Many aspects of primate biology, behavior, health, and ecology cannot be modeled in those simpler genetic model organisms,” Krasnow said.
That’s why, in 2009, Krasnow challenged three of his lab’s high school interns to find a replacement for the mice, rats, flies, and worms. Krasnow, whose primary field of study is lung disease, needed this new creature to meet certain criteria. The potential replacement had to be easy to manage, reproduce rapidly, and yield many offspring.
A few months later, the interns came back with an answer: Madagascar’s mouse lemur.
A mouse lemur, unlike its larger cousin the ring-tailed lemur, is quite small. The average mouse lemur is about two times the size of a mouse, which, along with their small-sized diets, makes maintaining and managing a lab of mouse lemurs inexpensive.
Their gestation is fast — just 60 days. Another 60 days after birth, the tiny primates can be independent of their mothers. Most pregnant lemurs produce two offspring, and within a year, young mouse lemurs can begin to reproduce.
For Krasnow, however, it’s the lemur’s natural home that makes studying them so spectacular.
Mouse lemurs are found on Madagascar. The island nation is home to 24 million people and 20 million mouse lemurs.
“It [a mouse lemur] reproduces quickly, and there are millions of mouse lemurs in Madagascar, perfect for systematic genetic studies to identify the genes underlying individual traits,” Krasnow said.
Also, unlike the ring-tailed lemurs, mouse lemurs are not endangered. Many of the natural habitats for ring-tailed lemurs are threatened as farming, mining, and logging operations sweep the island. Despite the shifting landscape, mouse lemurs are prolific and run freely across Madagascar.
Genetically, they’re closer to humans than any of the other creatures researchers have used previously. Lemurs are about midway between mice and humans, according to Krasnow.
The researchers hope that means primate-specific studies that would have failed in mice may now succeed in lemurs. Their biology can mimic many aspects of human biology, and Krasnow and his colleagues have found that the creature naturally has many of the same diseases that humans develop.
Unlike mice that often must be injected or bred with genetic mutations, lemurs already have them, “including genes that influence movement, obesity, hypercholesterolemia, prediabetes, cardiac arrhythmias, and speciation,” Krasnow explained. So far, the researchers working on the project have identified 20 genetic mutations in lemurs that match mutations humans have.
For example, aging lemurs develop a form of dementia that other species don’t. Studying the reasons for this cognitive disorder isn’t possible in many other creatures.
Likewise, mouse lemurs accumulate plaque on their brains — just like humans with Alzheimer’s disease. Until now, dementia researchers had few options for studying this condition.
Advancements in understanding and treating diseases in mouse lemurs can lead to similar developments for humans.
Stanford University is nearly 11,000 miles or 17,000 kilometers from Madagascar. That makes studying lemurs from Krasnow’s California laboratories difficult.
When they first started the mouse lemur research, Krasnow and his colleagues joined forces with Centre ValBio, a research facility near the Ranomafana National Park in Madagascar. Then, in 2013, Stanford built a genetic lab within the complex for their faculty.
Krasnow said leaving mouse lemurs in their natural habitat is ideal. That way, researchers can understand more about the impact of the environment on these animals’ health and genes.
“One can study the relationship between genes and the natural environment, and how they interact to influence specific traits such as health and survival in native settings,” Krasnow said.
But sequencing genomes of lemurs is a big project, and it’s ongoing. The researchers need more hands to trap, tag, test, and release the lemurs for their study.
That’s why Stanford, in coordination with several research facilities and schools in Madagascar, helped launch a citizen science project. The mission is twofold.
First, Stanford professors are helping high schools in Madagascar develop a science curriculum in hopes of sparking in the students an interest in science. They’re using inexpensive tools to let kids explore the diverse and rich environment right outside their classrooms.
Then, after the students complete high school, the researchers hope they’ll return as university students to help screen mouse lemurs and contribute to the research. For those who don’t make it to the lab, the researchers hope to encourage appreciation of the vital work that’s being done with the island’s smallest primate inhabitants.
“The students are eager to learn, and love getting out of the classroom to explore their environment, equipped with simple but powerful science tools like $1 paper microscopes created by our Stanford colleague Manu Prakash,” said Krasnow. “And we love helping in their discoveries, all new to them and many new to us — and even science too.”