Woolly Mouse Takes a Step Toward Resurrecting the Mammoth

The quest to bring the woolly mammoth back to life has taken another significant, albeit small, step with the creation of the Colossal Woolly Mouse. These lab-engineered rodents have been modified with seven genes, imparting them with “core traits” of the long-extinct mammoth.

Colossal Biosciences and its Mammoth Mission

Many may be familiar with Colossal Biosciences, a U.S.-based startup that has garnered attention in recent years for its work on mammoth-related genetic research. In 2021, the company revealed its ambitious plan to “de-extinct” the mammoth, a species that disappeared around 4,000 years ago. Almost a year ago, the team made significant progress in deciphering the mammoth’s genes, largely due to the close genetic relationship with the Asian elephant (Elephas maximus). The research team has also expressed interest in resurrecting other extinct species, such as the thylacine and the dodo.

While it’s important to acknowledge the difference in size between tiny mice and the massive mammoths that once roamed the Earth, the woolly mouse is much more than just a rodent dressed for winter.

Ben Lamm, Co-Founder and CEO of Colossal Biosciences, emphasized, “The Colossal Woolly Mouse represents a pivotal moment in our de-extinction journey. By incorporating multiple cold-tolerant traits from mammoth evolutionary pathways into a living species, we’ve demonstrated our ability to recreate complex genetic combinations that took nature millions of years to evolve. This success brings us closer to bringing back the woolly mammoth.”

To make this leap, the team studied the genomes of 121 mammoths (Mammuthus primigenius) and elephants, identifying genes that influenced hair and other characteristics, which enabled the extinct animals to survive in cold climates. By using CRISPR/Cas9 ribonucleoprotein (RNP) technology to edit seven genes in single-cell zygotes of lab mice, they modified the mice’s fur length, color, texture, thickness, and even added a distinctive mammoth-like “curl.” Further edits affected their fat tissue, making them better suited to cold environments.

A Foundation for Further Mammoth Traits

“The multiplexed editing strategies and mouse models created here provide a foundation for evaluating complex genetic combinations that lead to the mammoth phenotype,” the researchers noted in their preprint paper. “Future work will explore additional mammoth-specific variants tied to other cold-adaptive traits.”

While the woolly mouse represents progress, it’s clear that significant differences remain between small rodents with short lifespans and massive, long-lived mammals. Thus, while bringing back a woolly mammoth might seem far off, it is clear that genetic engineering has come a long way.

Professor Merlin Crossley, a molecular biologist at the University of New South Wales (UNSW), commented, “We won’t see a woolly mammoth, a dodo, or a thylacine for decades. It’s not just about changing seven genes – we would need to alter thousands and address reproductive biology too. It’s a huge challenge, but this group of scientists is pushing the boundaries of genetic modification.”

Genetic Engineering for Climate Adaptation

Many experts share this view, while also acknowledging that, despite the long road ahead, precise genetic modifications could revolutionize the way species adapt to a warming planet. However, phenotype expression is highly complex, as it is influenced by genetic interactions, environmental factors, and more.

Associate Professor Damien Fordham from the University of Adelaide’s Environment Institute added, “The engineering of cold-tolerant traits from woolly mammoths into a living species is an exciting scientific breakthrough, showcasing the advancement of gene editing in recent years. However, the threats that led to the woolly mammoth’s extinction have worsened. It seems unlikely we will ever have self-sustaining mammoth populations again.”

Despite this, Fordham believes the technology could play a role in saving species at risk of extinction due to climate change by engineering traits that could help them adapt to changing environments.

Colossal researchers, however, remain optimistic. They believe that with time, large-scale genetic editing will make it possible to bring iconic animals like the mammoth back into existence.

Beyond De-Extinction: A Bigger Vision

“Beyond de-extinction, this research deepens our understanding of evolutionary biology, genetic adaptation, and conservation genetics,” said Andrew Pask, a Genetics & Developmental Biology professor at the University of Melbourne, who has worked with Colossal on thylacine research. “The ability to reintroduce lost traits could contribute to biodiversity restoration and climate resilience efforts. The Colossal Woolly Mouse is a milestone moving us closer to our ultimate goal.”

In the end, the woolly mouse – though undeniably adorable – represents years of research and breakthroughs that have allowed scientists to pinpoint genes and predict the outcomes of their modifications. Reaching this point in just a few short years is a monumental achievement.

Dr. Beth Shapiro, Chief Science Officer at Colossal, concluded, “The Colossal Woolly Mouse demonstrates our ability to use cutting-edge genome editing tools to produce predictable phenotypes. This is a crucial step toward restoring traits lost to extinction, and our ultimate goal is to bring them back.”

Read the original article on: New Atlas

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