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But Colossal is forging ahead and cleared one of the many hurdles it faces: It created the first induced stem cells from elephants and will be placing a draft manuscript describing the process on a public repository on Wednesday. (Colossal provided Ars with an advanced version of the draft that, outside of a few editing errors, appears largely complete.) Beyond providing the technical details of how the process works, the manuscript describes a long, failure-ridden route to eventual success. Several methods have been developed to allow us to induce stem cells from the cells of an adult organism. The original Nobel-winning process developed by Shinya Yamanaka involved inserting the genes that encode four key embryonic regulatory genes into adult cells and allowing them to reprogram the adult cell into an embryonic state. That has proven effective in a variety of species but has a couple of drawbacks due to the fact that the four genes can potentially stick around, interfering with later development steps. Although there are ways around that, others have developed a cocktail of chemicals that perform a similar function by activating signaling pathways that, collectively, can also reprogram adult cells. When it works, this simplifies matters, as you only have to remove the chemicals to allow the stem cells to adopt other fates. Colossal tried both of these. Neither worked with elephant cells: “Multiple attempts with current standard reprogramming methods were tried, and failed, and resulted in no, or incomplete, reprogramming.” Apparently, lots of additional trial and error ensued. The eventual solution ended up being based in part on combining the two primary options: Cells were first exposed to a chemical reprogramming cocktail and then given the four genes used in the alternative reprogramming method. On its own, however, that wasn’t enough. The researchers also had to address a quirk of elephant biology.

Obviously, for Colossal, this is a means to an end: the mammoth. But that’s remarkably underplayed in the manuscript. Instead, its emphasis is on the technology’s use in the conservation of existing species. [T]he researchers note that studying things like elephant development and metabolism in actual elephants is not especially realistic. But we can potentially induce the stem cells developed here into any cell we’d want to study — nerve, liver, heart, and so on. So, the stem cells described here could be a useful tool for research. So, these cells are being presented as a valuable tool for the research community. Still, you can expect the people behind the de-extinction project to be getting to work on some of the easier things: showing that the genome in the cells can be edited and that they can be induced to start the process of embryogenesis. Separately, some unfortunate individuals will need to be working on the hard problems we mentioned earlier.