Colossal Biosciences, a pioneer in the field of de-extinction, recently announced a significant breakthrough in their efforts to bring back the woolly mammoth—or more accurately, to create a cold-resistant elephant with mammoth-like traits. Their team has successfully developed induced pluripotent stem cells (iPSCs) from Asian elephant skin cells. These are stem cells that can transform into any type of cell in the body.
The iPSCs created by the startup appear to have passed certain tests that show that they can, theoretically, be edited into sperm and egg cells of a mammoth-like creature, fertilized in vitro and injected into a surrogate to spawn an elephant with traits reminiscent of its ancient, now-extinct relative. In a recent paper posted to the preprint server bioRxiv, the team says that these stem cells can grow quickly without turning into other cell types unless directed, and they seem to be in a very versatile, youthful state compared to other similar stem cells.
A big piece of evidence from the paper that these iPSCs are going to play a significant role in de-extinction efforts is that the cells could form structures representing all the three germ layers—the endoderm, the ectoderm and the mesoderm—proving their ability to turn into a wide range of cells.
The paper, which hasn’t yet been peer-reviewed, also suggests that when implanted into mice, these cells could develop into tumors containing a mix of different cell types, further demonstrating their potential to turn into many kinds of cells.
Additionally, when comparing these elephant stem cells to those from other mammals, especially those with large body sizes, the scientists found that the elephant cells have similar characteristics to stem cells from other big mammals. This research could have significant implications for conservation, medical research and understanding how large animals develop and maintain their tissues.
Why Colossal’s Achievement Is So Noteworthy
Stem cells are the body’s raw materials, unique for their ability to transform into virtually any cell type—from bones and hair to skin and internal organs—when given the right signals. This process is called differentiation.
For a long time, scientists believed this was a one-way process, but groundbreaking work in the early 2000s led to the discovery of a specific mix of ingredients that could revert mature cells back into versatile stem cells.
This discovery was a game-changer, opening the door for biologists to create stem cells, known as induced pluripotent stem cells (iPSCs), from types of cells that were previously hard to obtain in a laboratory setting. This method of reverting cells to a stem cell state worked across many species, including humans, monkeys and even birds. However, elephant cells proved stubbornly immune to this process, a puzzle that intrigued scientists.
Recognizing the need for a tailored approach, Colossal’s team experimented with a variety of chemical formulations and genetic tools specifically designed for elephant cells. This required a deep understanding of elephant genetics, including the specific factors that contribute to their resistance to the standard iPSC reprogramming protocols used in other species.
The breakthrough came when the scientists developed a novel cocktail of chemicals and genetic factors that effectively induced the de-differentiation of mature Asian elephant cells back into iPSCs. This innovative mixture not only included standard ingredients known to initiate reprogramming in other species but also unique components that addressed the specific biological hurdles of elephant cells.
How Close Are We To Seeing Woolly Mammoths Roam The Earth Again?
The path to actual de-extinction is strewn with both scientific and ethical hurdles. Firstly, there’s ongoing debate among scientists outside of Colossal’s project regarding the true nature of these iPSCs. Some experts question whether these cells meet all criteria to be considered “true iPSCs,” indicating that further validation through rigorous experiments is needed to confirm their pluripotency. This skepticism underscores the complexity of replicating the exact conditions required for a cell to be considered fully pluripotent, capable of developing into any cell type.
Moreover, the introduction of mammoth-like traits into an Asian elephant raises broader ecological and ethical concerns. There’s the question of how a cold-resistant, hairy elephant would fit within current ecosystems, particularly given that the habitat of the Asiatic elephant is vastly different from the frozen, arctic environments once roamed by woolly mammoths. Adapting to these habitats involves a range of behavioral and survival skills that have evolved over millennia. Will a “woolly mammoth” born to a elephant learn the necessary skills to survive in cold environments from its surrogate mother?
The truth is there are many hurdles we are yet to cross when it comes to seeing this resurrection play out.