The Woolly mammoth could be brought back from extinction in just four years

Woolly mammoth (Picture: Getty/iStockphoto)

The Woolly mammoth could roam the planet once again – in just four years.

Colossal Biosciences, a de-extinction company, has announced its dedicated team achieved a world-first breakthrough by successfully reprogramming pluripotent stem cells (iPSC) from elephants.

The stem cells are a single cell source, which can grow without limit, and create other cell types featured in a body.

It means if the team can edit the genes in the right way, they could bring back the Woolly mammoth 4,000 years after they went extinct.

The Texas-based experts already have a date in mind – 2028 – when they hope to create the first version of a mammoth – to be born to an elephant mother.

This was one of the early goals of the mammoth project and provides hope of creating an ex-utero mammoth gestation.

It is a process where the cells could potentially be modified and differentiated to create cold adaptation traits, like woolly hair growth and fat storage in cellular and organoid models.

‘In the past, a multitude of attempts to generate elephant iPSCs have not been fruitful. Elephants are a very special species, and we have only just begun to scratch the surface of their fundamental biology,’ said Dr Eriona Hysolli, head of biological sciences at Colossal Biosciences.

‘My early work in Dr. George Church’s laboratory had been partially successful with iPSC-like cells that led to the foundation of the cells we have currently developed.

‘And now, using a multi-pronged approach to reprogramming we have the most successful efforts to date. The Colossal Mammoth team persisted quite successfully as this progress is invaluable for the future of elephant-assisted reproductive technologies, as well as advanced cellular modelling of mammoth phenotypes.’

Asian elephant iPSC colonies stained for pluripotency factors (Picture: Colossal Biosciences/ George Church/ Eriona Hysolli)

In 2006, Dr Shinya Yamanaka pioneered mouse iPSCs that used a four-factor protocol to derive human, horse, pig, cattle, rabbit, monkey, ape, big cats, rhino and even avian species iPSCs, but elephant iPSCs remained elusive.

‘Elephants might get the “hardest to reprogram” prize, but learning how to do it anyway will help many other studies, especially on endangered species,’ said Colossal co-founder Dr. George Church.

‘This milestone gives us insights into developmental biology and the balance between senescence and cancer. It opens the door for obtaining gametes and other cell types without surgery on precious animals.

‘It opens the door to establishing connections between genes and traits for both modern and extinct relatives – including resistance to environmental extremes and pathogens.’

Now the team is focused on further maturing these cells, and once the iPSCs can be used to design a model for artificial elephant embryos, it will help provide an understanding of the long and complex elephant (and by association mammoth) development and gestation cycle.

‘We knew when we set out on the Woolly Mammoth de-extinction project that it would be challenging but we’ve always had the best team on the planet focused on the task at hand,’ said co-founder and CEO of Colossal, Ben Lamm.

‘This is a momentous step, with numerous applications, that we are proud to share with the scientific community. Each step brings us closer to our long-term goals of bringing back this iconic species.’

Any progress with elephant iPSCs could potentially be used to study cell development, cell therapy, drug screening, synthetic embryos, in vitro gametogenesis, and the use of iPSCs for nuclear transfer across all species.

The company also hopes to bring back the Tasmanian tiger and the dodo back from extinction.

Colossal’s paper is currently featured in Bioarxiv with a peer-reviewed article in a scientific journal in progress.