De-extinction of the woolly mammoth takes a major step forwards: Scientists successfully reprogramme elephant stem cells

  • Colossal Biosciences has made induced pluripotent stem cells from elephants
  • These cells could be used to make elephant-mammoth hybrids in the future 



It has been more than 4,000 years since the woolly mammoth last walked the Earth, but these extinct giants might not be gone for good. 

Researchers have made a major breakthrough that could see woolly mammoths returning to life before 2028. 

Scientists from Colossal Biosciences have successfully created elephant ‘pluripotent’ stem cells which can grow into any cell in the body.

Dr George Church, co-founder and lead geneticist of Colossal, told MailOnline that the creation of these cells ‘opens the door’ to the de-extinction of the mammoth. 

‘It’s not a huge extrapolation to think that we’ll be able to synthesise on a large scale in the future,’ he said. 

Scientists have made a breakthrough that allows them to make pluripotent stem cells out of elephant cells. By combining these with genes taken from a frozen woolly mammoth they hope to one day create hybrid eggs that can be grown into embryos in an artificial womb
Colossal Biosciences has made a major breakthrough that could lead to the wooly mammoth returning to Earth before 2028

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The key to this development is the ability to induce elephant cells to become pluripotent stem cells. 

In 2006, a scientist named Shinya Yamanaka discovered a way to use a chemical cocktail to trigger cells from adult animals to turn into stem cells – those with the unique ability to grow into any other type of cell.

While this has already been done successfully in humans, rabbits, big cats, and even the northern white rhino, until now, it had never been done before with an elephant. 

To go from these cells to a living breathing mammoth, the scientists hope to edit them with genes taken from a frozen woolly mammoth corpse.

The cells could then be induced to grow into an egg which could be fertilised and grown in an artificial womb. 

While the de-extinction of the woolly mammoth might be the ultimate goal, Dr Church says that the first step is to create an elephant-mammoth hybrid.

This image shows the colonies of induced pluripotent stem cells derived from elephants. These cells have the unique ability to grow into any other cell in the body, making them a perfect base to test and grow mammoth-elephant hybrids from
Using pluripotent stem cells, the scientists hope to create gametes – eggs and sperm – and tissue like structures called organoids which they can use for testing

What is Crispr-Cas9? 

CRISPR-Cas9 is a tool for making precise edits in DNA. 

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut.

By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes — effectively switching them off.

However, the system can also be used to add in new genetic code at precise locations along the genome.

Dr Church told MailOnline: ‘What we’re doing is making a particular hybrid that will both enrich the Asian elephant and bring back the diversity of the mammoth.’

Colossal hopes that the resulting hybrid will help elephants thrive and repair damaged Arctic ecosystems.   

Asian elephants are currently ‘stuck’ in areas with high human population densities, which causes issues for both elephants and humans. 

But if they could be bred to withstand more extreme conditions, they could potentially thrive in areas away from humans where the woolly mammoth once roamed. 

‘We hope to use the diversity that comes from their not-so-long-ago ancient relatives to help them cope with new environments that might be needed for their thriving,’ Dr Church said. 

However, without the development of induced pluripotent stem cells, none of this would be possible.

This hasn’t been straightforward, according to Eriona Hysoll, head of biological sciences at Colossal Biosciences, who revealed that it has taken years to develop the techniques to produce these cells from elephants.

Most mammals have a set of genes called TP53 retrogenes that are involved in suppressing tumour growth. 

While a human only has two copies, an elephant has almost 40.

By using a set of processes that represses the action of these genes, the researchers finally overcame this barrier and managed to create induced pluripotent stem cells. 

Dr George Church says that creating elephant-mammoth hybrids will help conserve the elephant by letting it extend its range and help repair damaged arctic ecosystems

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Since different animals have this gene but in varying amounts, it might go some of the way to explaining why some species are more prone to cancer.

Dr Church said: ‘It could help us understand why mice almost always die of cancer while elephants almost never do.’

Colossal Biosciences hopes that these cells will provide a boost to their efforts in testing cold resistant genes in elephants and conserving existing populations. 

Scientists are able to edit the genes of living animals through a technique called CRISPR, but this is too slow to do testing at scale. 

Dr Church explains that by using stem cells, scientists can see whether their genetic changes have been successful within a couple of weeks rather than waiting for elephants’ almost two-year gestation period. 

Best of all, induced pluripotent stem cells are ‘immortal’, which means scientists will be able to create thousands of tests at the same time on a much smaller time frame.

The team now plans to continue testing cold resistant genes in elephants and working towards growing eggs and sperm cells for use in conservation and study. 

And Colossal Biosciences isn’t stopping there – it also wants to bring back the extinct woolly mammoth and the dodo. 

Reference

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