Photo credit: www.sciencenews.org
Recent advancements in the field of de-extinction have highlighted a significant milestone: scientists have successfully developed transgenic mice with long, golden fur reminiscent of woolly mammoths. These mice, dubbed “Colossal woolly mice,” not only showcase a novel genetic engineering achievement but also captivate with their adorable appearance.
Transgenic mice are not a new phenomenon; however, the innovative aspect of this project lies in the ability to make multiple genetic modifications across several genes concurrently. Researchers conducted three distinct experiments, each employing various combinations of genetic edits, achieving a high success rate in creating living animals that exhibit the desired traits.
“Our achievement isn’t just in producing woolly mice; it also underscores a crucial step in genetic engineering that has been underappreciated,” states Beth Shapiro, chief science officer at Colossal Biosciences. She and her colleagues detailed their findings in a paper released on March 4 via bioRxiv.org.
In total, the research team has bred 32 woolly mice, each presenting slight variations but all embodying the predicted characteristics. Shapiro remarked on their success, noting, “There were no misfires or surprises; they’re just absurdly adorable.”
However, the connection between these genetically altered mice and the potential to bring back woolly mammoths is more complex and has led to various misunderstandings. For example, some reports misleadingly described the woolly mouse as a new species or suggested that scientists had “spliced mammoth genes into mice,” which they did not do. “Our goal was never to transfer elephant genes into a mouse,” Shapiro clarifies, explaining the rationale behind their approach.
What Defines a Woolly Mouse?
To engineer the woolly mouse, researchers examined the genetic sequences of 121 samples from mammoths and elephants to identify genes responsible for various mammoth traits, such as their thick fur and adaptations for cold weather. This analysis allows them to compare differences and similarities in genomes, crucial for distinguishing mammoth genes from those of their elephant relatives.
Shapiro explains, “With the mammoth genomes at our disposal, we can compare them to those of elephants and pinpoint what makes each unique.” This investigation aims to identify specific traits that could be replicated in mice, who are simpler to manipulate genetically than elephants. Mice require less space, breed faster, and have been extensively studied in genetic contexts. For instance, altering the FGF5 gene has been shown to produce longer hair in mice, while other genes like Mc1r and Frzd6 influence hair color and texture.
The culmination of this research involved converting edited embryos into living, furry mice. Despite critiques regarding the disparity between mice and elephants, Shapiro emphasizes that the woolly mice are a pivotal step within the broader context of de-extinction efforts. Colossal Biosciences is concurrently experimenting with Asian elephant cells, given their close evolutionary affinity to now-extinct woolly mammoths.
Additionally, the organization is researching reproductive technologies that would facilitate implanting a genetically modified elephant embryo into a living host. This goal is part of a larger initiative, including projects focused on reviving the dodo and the thylacine, or Tasmanian tiger.
Challenges to Cloning Woolly Mammoths
Jacquelyn Gill, an ice age ecologist at the University of Maine, expresses enthusiasm over the potential of witnessing a woolly mammoth one day. She acknowledges the appeal for many researchers who long for a glimpse into a world long past. Nevertheless, Gill harbors skepticism regarding the current methods employed by Colossal Biosciences to achieve de-extinction.
Despite numerous well-preserved mammoth finds in permafrost, the degradation of cellular structures over thousands of years precludes cloning, an avenue that has been successfully executed in other species, like sheep. Gill affirms, “We can’t pursue that path with mammoths.”
While gene editing might enable researchers to modify an Asian elephant in ways that mimic woolly mammoths externally, it is challenging to replicate the complex genetic makeup that characterized mammoths as a distinct species. “A mammoth is not just an elephant with fur,” warns Tori Herridge, an evolutionary biologist at the University of Sheffield.
Skepticism Surrounding De-Extinction
Herridge finds the study of candidate genes for mammoth adaptations intriguing but underscores the complexity of genetics, emphasizing the many interlinked factors that govern traits like fur type. She notes that the actual impact of genes identified in mice may differ when applied to Asian elephants.
Colossal Biology is investigating how elephant cells behave in lab cultures, allowing them to learn more about the appropriate genetic targets for their experiments. Moreover, they have created elephant pluripotent stem cells, which could lead to various cell types necessary for reproductive endeavors.
A significant complication arises from the lengthy gestation period of Asian elephants, lasting up to 22 months, compared to the mere three weeks for woolly mice. This extended timeframe poses additional hurdles in the development of a transgenic elephant. Furthermore, as Asian elephants are classified as endangered, regulatory frameworks will likely impact the feasibility of such endeavors.
Even if cloning or gene editing can yield a viable population of mammoth-like elephants, important social and ecological questions linger. Modern elephants exhibit intricate social structures evolved over generations, and transplanted traits will not impart the knowledge needed for survival in the wild. Gill remarks, “You can’t teach a transgenic elephant how to be a woolly mammoth.”
Moreover, the environments suitable for mammoths have altered drastically since their extinction, creating new ecological challenges. Gill notes that the mammoth steppe, a once-diverse biome, has transformed significantly. Some scientists speculate that mammoths played a fundamental role in shaping this ecosystem. If restored, mammoths might help revitalize ecosystems and manage permafrost, thus combating climate change—a critical long-term goal of Colossal Biosciences.
The Future of Woolly Mammoths
Shapiro remains cautiously optimistic about the company’s ambitions, acknowledging critiques while believing in the potential for success. In fact, she surmises that the project to resurrect the dodo might be more achievable in the near term given its reproductive requirements. “While our timelines are ambitious, the hard biological challenges still need addressing,” she acknowledges.
Looking forward, Shapiro notes that the edited elephant cells will be prepared by early 2027, paving the way for possible results by 2028. “However, significant biological and technical hurdles still lie ahead,” she concludes.
Source
www.sciencenews.org