Colossal Biosciences, a US biotech start-up, has announced the birth of what it calls a “woolly mouse” – the world’s first animal genetically altered to express key genes from a woolly mammoth.
The company says the luxuriously haired rodents are living proof that it’s making progress in its mission to resurrect the woolly mammoth from extinction within a matter of years.
To make the mice, scientists used the latest genetic technologies to introduce eight simultaneous edits to the genomes of laboratory mice. These include the addition of genes that cause their fur to grow up to three times longer than normal, and others that make the hairs wavy and golden.
Other edits targeted genes associated with fat metabolism that are thought to have helped mammoths increase in size.
The mice are the result of years of painstaking work by scientists to reconstruct key parts of the mammoth genome. The last woolly mammoths are thought to have died around 3,000 years ago, and scientists have been piecing together bits of degraded mammoth DNA from remains between 3,500 and 1.2 million years old.
This is the first time that some of the key genes identified through that work have been expressed in a living animal.
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Mammoth 2.0
Colossal’s ambitious long-term plan is to add lots of these mammoth genes to embryos of modern-day elephants to create mammoth-like hybrids.
Despite its claims to be resurrecting the woolly mammoth, the original Mammuthus primigenius, with all its original genetic complexity and population diversity, isn’t being brought back to life. The creatures are more accurately described as “cold-resistant elephants”.
Announcements that the return of the mammoth is close have been made repeatedly by various groups, dating as far back as 2011. The groups are generally privately funded and the exact details of their work are often rather opaque.
But these living, breathing and rather cute woolly mice do show that scientists have made impressive progress in reconstructing some of the key genes that made mammoths unique. Colossal’s chief scientist Dr Beth Shapiro says the mice are “an important step toward validating our approach to resurrecting traits that have been lost to extinction".
A mammoth task
There’s still an awful lot of work to do before we see mammoth-like creatures stepping out across the tundra or walking around our zoos.
For a start, it’s much easier to create gene-edited mice than elephants. Mice have been a staple of genetic experiments for decades and can be bred in huge numbers, quickly.
Elephants, on the other hand, are rarely used in laboratory experiments and happen to have the longest gestation period of any living mammal – over 18 months.
Colossal has been making impressive progress in manipulating elephant cells into stem cells that could, one day, be used to create modified embryos.
But even if Colossal can create viable elephant-mammoth embryos, both Asian and African elephants are endangered, so can’t be used as surrogate mothers in any great numbers, if at all.
This means Colossal must also develop its own artificial wombs to develop the experimental embryos all the way to birth. This has never been done before: not only will such a system have to recreate all the complexities of a placenta, it’ll need to support a calf that weighs at least as much as an Asian elephant calf – that’s over 100kg (220lbs).
But perhaps the biggest question that remains is simply, why? Colossal says that resurrecting the mammoth – and other similar work to resurrect the dodo and thylacine – will lead to biotechnology that can help save other species from environmental change.
The company argues that starting with these iconic extinct creatures will inspire interest and investment like nothing else could.
It’s certainly true that the project generates lots of media attention, and has attracted over $200m dollars (£157m)of investment that probably wouldn’t have come to conventional conservation projects.
And there are examples already of this technology being used to help species facing extinction today. In Australia, for instance, gene-editing is being used to give Northern quolls – adorable and endangered marsupials – resistance to the poison of the cane toad, an invasive species that’s killing many animals in the region.
In the US, scientists have used similar biotechnology to boost the genetic diversity of black-footed ferrets, which had been reduced to such a tiny population size that they were essentially becoming inbred.
More broadly, Colossal’s work could help scientists produce eggs, sperm and embryos for a range of threatened species, including Asian and African elephants, to help boost their numbers.
The could we/should we question
But do these lofty ambitions justify the Jurassic Park-esque use of genetic engineering? Many people feel uneasy about the modification, let alone a complete overhaul, of genomes, especially in intelligent, social animals like elephants.
And what will life be like for the first man-made woolly elephants? Where will they live, and will they be introduced to a herd or family?
Will they be healthy or dogged by genetic problems? And shouldn’t we focus our efforts on saving habitats and ecosystems, not individual species?
In recent years, genetic engineering has gained greater acceptance among the public, and is generally seen as an important way of producing things like new medicines or disease-resistant crops.
Could the creation of a big, hairy elephant be the thing that makes people feel biotechnology has gone too far? Or, as Colossal hopes, might it serve as an inspiring symbol of how technology can save the thousands of species that become endangered each year?
It’s a question that biologists, ethicists and biotech regulators need to consider carefully, as work on scaling up from mouse to mammoth continues.
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