A company that intends to bring back the woolly mammoth has taken a small, but significant step toward its massive de-extinction goal: it has created a woolly mouse. The company, Colossal Laboratories & Biosciences, used a variety of gene-editing techniques to create a number of tiny rodents with the massive, extinct species’ bushy hair. They reported their results in bioRxiv.org.
Making the Woolly Mouse
Their gene editing efforts focused on two general traits — both of which are associated with cold-weather survival. One, the mammoth’s curly textured hair, is quite visible. The other — altering a mouse’s metabolism to store, not burn fats — is less so.
To identify what genes they might target to achieve those features, they first compared the mammoth genome to that of the Asian elephant — the mammoth’s closest surviving relative. Then they examined the genomes of many mouse models to identify the best spots in their genomes to alter.
A mouse is the most genetically scrutinized mammal; it has been edited to study the traits of countless genes, sometimes by knocking out or removing them, then observing what physical characteristic or phenotype results.
Read More: Will Woolly Mammoths Ever Make a Comeback?
Genetic Editing Toolbox
The researchers altered a total of 10 genes — but not all in the same mouse. And not all mice had the same genes edited. The most heavily edited mouse had 7 genes altered with 8 different tweaks.
“The edits that we predicted resulted in what we wanted,” says Ben Lamm, co-founder and CEO of the company. “We got what we predicted.”
The group’s next step is to study how these edits help the mice adapt to colder climates. They are awaiting animal study permission before they proceed with those experiments.
Even though the company’s ultimate goal is to bring back the mammoth — as well as the dodo and an extinct tiger species — they say their work will help both human health and wildlife conservation along the way.
First, using their toolbox of editing techniques on animals could pave the way for similar work in people. The toolbox includes a host of methods, ranging from the ability to change a single genetic letter to replacing a fairly lengthy string of DNA.
“Different tools allow us to access different parts of the genomes,” says Beth Shapiro, the company’s chief scientific officer.
Next Stop, Bringing the Mammoth Back?
Although the group does intense computation analysis first, this “proof of principle” is necessary to show how effective are the edits and what physical differences arise from them. This is an important step before they make similar changes in much larger mammals.
“We want to really understand what the impacts of our edits are before we experiment with elephants,” Shapiro says.
They are now working on edits that would change an Asian elephants skull and face to more closely resemble a mammoth’s. They are experimenting with artificial wombs that could birth a de-extinct mammal. The company intends to bring back its version of a mammoth in 2028.
Read More: A Freeze-Dried Woolly Mammoth Yields 52,000-Year-Old Chromosomes
Potential Ethical Issues
However, some people have doubts that, even if it is scientifically possible to bring back a large mammal from extinction, is it a good idea? Arthur Caplan, a bioethicist at New York University, isn’t so sure.
“Is this somehow ethically pernicious? No,” Caplan says. “But I think it's overpromised, somewhat misdirected, and maybe over-hyped.”
Caplan points out that much simpler techniques — like human gene therapy and animal cloning (without unintended birth defects) have still not yet been perfected. The project's money and expertise would be better served with scientific goals that could improve human health sooner.
He agrees that the scientific pedigree of the project’s founder George Church, a key pioneer in genome sequencing, is impeccable. But Caplan is not sure “pushing the envelope” scientifically just for the sake of it is wise. Such approaches “wind up giving us ethics heartburn,” he says, pointing to proposals to bring back smallpox for study or to research — or even create — some deadly viral agent.
The company says that it has been checking all the necessary bioethics boxes and is adhering to animal research reviews policies. They first do computational models, then experiments in petri dishes, before moving on to edits in animals. The results in this first round of experiments yielded no surprises.
“The only unexpected consequence was overall cuteness,” says Lamm.
Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
bioRxiv Pre-Print. Multiplex-edited mice recapitulate woolly mammoth hair phenotypes
Before joining Discover Magazine, Paul Smaglik spent over 20 years as a science journalist, specializing in U.S. life science policy and global scientific career issues. He began his career in newspapers, but switched to scientific magazines. His work has appeared in publications including Science News, Science, Nature, and Scientific American.
