Company That Plans To Bring Back the Mammoth Takes a Key Step (arstechnica.com) 29
John Timmer reports via Ars Technica: A company called Colossal plans to pioneer the de-extinction business, taking species that have died within the past few thousand years and restoring them through the use of DNA editing and stem cells. It's grabbed headlines recently by announcing some compelling targets: the thylacine, an extinct marsupial predator, and an icon of human carelessness, the dodo. But the company was formed to tackle an even more audacious target: the mammoth, which hasn't roamed the Northern Hemisphere for thousands of years. Obviously, there are a host of ethical and conservation issues that would need to be worked out before Colossal's plans go forward. But there are some major practical hurdles as well, most of them the product of the distinct and extremely slow reproductive biology of the mammoth's closest living relatives, the elephants. At least one of those has now been cleared, as the company is announcing the production of the first elephant stem cells. The process turned out to be extremely difficult, suggesting that the company still has a long road ahead of it. [...] Overall, it's a project that has a high probability of failure and may ultimately require generations of scientists. If we do successfully de-extinct a species, the first example will probably be a different species, even though the projects launched later.
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.
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.
we will start with raptors as they are smaller! (Score:2)
we will start with raptors as they are smaller!
What about the mitochondria? (Score:2)
Re:What about the mitochondria? (Score:4, Interesting)
Good question, but it's important to note that they don't have to perfectly recreate a genetically authentic mammoth descendant to accomplish the primary goal here, (which if you'll remember previous articles is actually about naturally terraforming Siberia to be human-habitable again) they really just have to make an elephant that's hairy and fat enough to thrive in the cold.
Re: (Score:2)
I'm not even being sarcastic or ironic - I would love to understand step 2.
Re:What about the mitochondria? (Score:4, Interesting)
There's a nature documentary series ("Nature," on PBS I actually think) that had a whole episode recently of how critical elephants are to the environment in Africa, through how they actually literally irrigate and spread seeds around while eating and playing. There's corroborating evidence of what happened to the local plant life in Siberia after the mammoths went extinct that strongly suggests they were serving the same purpose there. Recently some people have talked about a pie-in-the-sky plan to try to repair Siberia's ecology by re-introducing mammoths. There's good science behind the plan, and it has actually been discussed on Slashdot before.
Re: (Score:1)
... it might have actually been something on BBCA now that I think of it. Just find an episode about how the mud ponds they create and the paths they track between them turned out to actually be critical to the plant life and in turn the weather, average temperatures, and overall biodiversity.
A Statue for Father (Score:2)
Yabba dabba doo!
Re:What about the mitochondria? (Score:4, Informative)
If we find intact frozen cells with viable nuclear DNA, they'll likely also have viable mitochondrial DNA.
Mammoths and Asian elephants diverged about 4 million years ago. Their mtDNA is likely compatible.
They diverged from African elephants about 6 million years ago.
Re:What about the mitochondria? (Score:5, Interesting)
Sixteen months ago they found a frozen, baby woolly mammoth in Canada. It is 30,000 years old and might have samples of mammoth DNA that can be sequenced and used for the revival project.
Well-Preserved, 30,000-Year-Old Baby Woolly Mammoth Emerges From Yukon Permafrost [smithsonianmag.com]
Re: (Score:2)
I was going to eat that mummy!
https://www.youtube.com/watch?... [youtube.com]
Mammoth burgers (Score:3)
That's what I'm looking forward to.
Re: (Score:2)
I'm holding out for a Brontoburger.
https://i.pinimg.com/236x/ae/2... [pinimg.com]
Re: (Score:2)
Too gamy! For me, it's glypodont ribeyes, and plenty of them!
Re: (Score:2)
Even the smallest ones were 30 kg and their DNA ought to be available.
Re: (Score:2)
Nature finds a way
Mammoth burgers for me too
But who will eat who?
I call this one, "McJurassic".
Re: (Score:2)
Since it's going to be close to a elephant, here are some insights that could be valid for both:
"the flavor is described as being very gamey with a strong red meat taste. It is considered to taste similar to venison. Generally, onions and garlic are used to mask some of the strong flavor."
"elephants are not farmed and cannot be due to the long time needed for them to reproduce. Moreover, wild elephants are more valuable as tourist attractions than they are as meat." -- Mike Ruder, Foodlve https://foodlve.co [foodlve.com]
Re: (Score:1)
People actually ate frozen Mammoth in Siberia. Perhaps we can find articles about it?
Re: (Score:2)
Birdseye, the scientist, did a lot of work on this.
It led to his technology which led to his frozen-vegetable company.
A good example of pure science leading to remarkable benefits
Jasper Fforde? (Score:3)
This is straight out of Jasper Fforde's books with their re-engineered fauna [jasperfforde.com].
And the big evil corporation in his Thursday Next books [jasperfforde.com] is Goliath, which is also the branding for his merch store [myshopify.com].
Strangely, the story has no mention of toast [jasperfforde.com].
Re: (Score:2)
£219.99 for a toaster? It had better talk.
https://www.youtube.com/watch?... [youtube.com]
Re: (Score:2)
Invasive species (Score:1)
The woolly mammoth has been extinct so long it would be a "non-native" species if it's release into the wild.
When it comes to disrupting its new home's ecosystem, "what could possibly go wrong?" is an important question to ask.
Re: (Score:2)
Not even extinct. But the same thing could be said about cutting back on cattle raising and turning the prairies back over to the buffalo.
Re:Invasive species (Score:5, Informative)
The woolly mammoth has been extinct so long it would be a "non-native" species if it's release into the wild.
The last mammoths died out about 3700 years ago when the pyramids were already a thousand years old.
Maybe re-create politicians worth a damn (Score:3)
Meh (Score:2)
I'm waiting for the saber-toothed squirrel.
ice age adapted mammal? hello? (Score:2)
Issues (Score:1)