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Belesarius

I'm feeling like Disney just might want in on this one... How about Jurassic Park for real?

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Living mammoths would be rad as hell, have there been any similar efforts for other ice age megafauna?

I'm not aware, though it would make sense if there are DNA samples of stuff like the Woolly Rhino or an American Lion for a project to be attempted. I'm just hoping the Pleistocene Park in Russia is turned into a reality. 

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There is something primeval and RIGHT about seeing Wooly Mammoth herds again. I hope to see the day.

Also, one of the things bush pilots in Alaska do is fly low and "slow" along the beaches looking for mammoth and walrus tusks that have eroded or washed up on the shore.

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I'm not sure if we've fully examined the potential military benefits of cloning dinosaurs.

 

 

Whereas there is a moral dilemma bringing back to life sentient Woolly Mammoths who must live with the knowledge that everyone whom they knew and loved have died 10,000 years ago. While being stuck in the 1990s...

 

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Part of the issue with cloning mammoths is that your surrogates are going to be elephants, and elephants tend to have ridiculously long pregnancies (edging up to two years). Meaning that you'll be spending an enormous amount of money and will only get the payoff decades down the line (if at all*).

 

Anyway, here is the program I worked out for the project. Note that this assumes a stepwise germline-transformation approach (rather than a one-shot attempt at full genome synthesis) piggybacking off of a standard cloning study:

  • Phase 1a: elephant cloning program. Expected timeline: 5-10 years.
  • Phase 1b: elephant/mammoth genome comparison and transgenic strategy study. Expected timeline: 2-5 years. Runs in parallel with 1a.
  • Phase 1c: elephant/mammoth hybrid cell line transformation and culture. Expected timeline: 2-5 years. Runs after 1b.
  • Phase 2: round 1 elephant/mammoth hybrid nuclear transfer/IVF experiment. Expected timeline: 2-5 years. Hybrids would include partially and fully-transformed cell lines.
  • Interphase: follow-up rounds of nuclear transfer and IVF, growth and maturation of F1 generation (if any). Expected timeline: 9-14 years.
  • Phase 3 (optional): follow-up hybrid nuclear transfer and IVF on F1 generation. Expected timeline: 2-5 years. hybrids would all be from fully-transformed cell lines.
  • Phase 4: beginning of conventional breeding program.

Total time: 16 - 35 years.

 

The budget would be in the billions of dollars, and would include things like a large molecular genetics lab, clean lab for cell line propagation and transfer, stable and paddock facilities for elephants, elephant-capable theatre facilities and a number of park areas for the parent population and hybrids.

 

A one-shot approach would, of course, be cheaper and quicker. But it would also have a much lower chance of success. On the other end of the spectrum; an incremental breeding/transformation program would be very likely to succeed on some level (and might also be cheaper), but would take something like 50-100 years to complete.

 

* One of the biggest issues with interspecies surrogates is that we just don't have a clear handle on what might cause rejection. As an example, there are two closely-related rat species that have been tested for surrogacy using lab rats. One works fine, the other doesn't work at all and there is nothing much that points to why. Worse, we still don't have a strong handle on why cloning fails either. So most of the interspecies surrogacy experiments end with the foetus being rejected or the animal dying a short while after birth.

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So with that said Toxn, would it be easier to start with a critter in an egg like a passenger pigeon, dodo or some such thing? Or even a lowly amphibian while we are at it?

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Part of the issue with cloning mammoths is that your surrogates are going to be elephants, and elephants tend to have ridiculously long pregnancies (edging up to two years). Meaning that you'll be spending an enormous amount of money and will only get the payoff decades down the line (if at all*).

 

Anyway, here is the program I worked out for the project. Note that this assumes a stepwise germline-transformation approach (rather than a one-shot attempt at full genome synthesis) piggybacking off of a standard cloning study:

  • Phase 1a: elephant cloning program. Expected timeline: 5-10 years.
  • Phase 1b: elephant/mammoth genome comparison and transgenic strategy study. Expected timeline: 2-5 years. Runs in parallel with 1a.
  • Phase 1c: elephant/mammoth hybrid cell line transformation and culture. Expected timeline: 2-5 years. Runs after 1b.
  • Phase 2: round 1 elephant/mammoth hybrid nuclear transfer/IVF experiment. Expected timeline: 2-5 years. Hybrids would include partially and fully-transformed cell lines.
  • Interphase: follow-up rounds of nuclear transfer and IVF, growth and maturation of F1 generation (if any). Expected timeline: 9-14 years.
  • Phase 3 (optional): follow-up hybrid nuclear transfer and IVF on F1 generation. Expected timeline: 2-5 years. hybrids would all be from fully-transformed cell lines.
  • Phase 4: beginning of conventional breeding program.

Total time: 16 - 35 years.

 

The budget would be in the billions of dollars, and would include things like a large molecular genetics lab, clean lab for cell line propagation and transfer, stable and paddock facilities for elephants, elephant-capable theatre facilities and a number of park areas for the parent population and hybrids.

 

A one-shot approach would, of course, be cheaper and quicker. But it would also have a much lower chance of success. On the other end of the spectrum; an incremental breeding/transformation program would be very likely to succeed on some level (and might also be cheaper), but would take something like 50-100 years to complete.

 

* One of the biggest issues with interspecies surrogates is that we just don't have a clear handle on what might cause rejection. As an example, there are two closely-related rat species that have been tested for surrogacy using lab rats. One works fine, the other doesn't work at all and there is nothing much that points to why. Worse, we still don't have a strong handle on why cloning fails either. So most of the interspecies surrogacy experiments end with the foetus being rejected or the animal dying a short while after birth.

 

Tox just said a bunch of stuff that makes me feel good but that I don't understand. Tox for poaster of the yeer.

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So with that said Toxn, would it be easier to start with a critter in an egg like a passenger pigeon, dodo or some such thing? Or even a lowly amphibian while we are at it?

I know there is a plan to bring back the passenger pigeon using an approach like the one I outlined, but I honestly don't know enough about eggs to give a good answer to this question. My gut instinct is that, so long as there is a way to get a viable egg (cell) into an environment where it can develop, the same general rules will apply.

 

Here is an article on nuclear transfer, which is one of the techniques this whole thing would hinge on. In a recurring theme; it's interesting to note how the guy who cracked the problem had endless issues with obtaining funding. Truly, good science and fundable science are two completely separate beasts.

 

 

Tox just said a bunch of stuff that makes me feel good but that I don't understand. Tox for poaster of the yeer.

Come on guys, I even put up an ask-a-geneticist post  :)

 

Are there any specific things I can help with in terms of understanding?

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Come on guys, I even put up an ask-a-geneticist post  :)

 

Are there any specific things I can help with in terms of understanding?

"Comprehend" would be a more accurate term. I understood what you were saying just fine, and have no way of knowing whether it represents a well-informed opinion.

But see, if you replace "understand" with "comprehend" in that sentence, it sounds like I'm saying you're some sort of higher life form with a consciousness that expands into multi-dimensional space, whereas with "understand" it can almost be interpreted as a jab at your expository abilities.

My smug-yet-gentle sense of superiority demands the latter.

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"Comprehend" would be a more accurate term. I understood what you were saying just fine, and have no way of knowing whether it represents a well-informed opinion.

Hmmm, that's a tough one. My opinion is relatively well-informed, but I would certainly bow to the experience of someone working directly in the field.

 

 

But see, if you replace "understand" with "comprehend" in that sentence, it sounds like I'm saying you're some sort of higher life form with a consciousness that expands into multi-dimensional space, whereas with "understand" it can almost be interpreted as a jab at your expository abilities.

I can explain things all day like the giant pedant I am, I just need to know what needs to be explained.

My smug-yet-gentle sense of superiority demands the latter.

"yet-gentle", oh you card.

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"Comprehend" would be a more accurate term. I understood what you were saying just fine, and have no way of knowing whether it represents a well-informed opinion.

Hmmm, that's a tough one. My opinion is relatively well-informed, but I would certainly bow to the experience of someone working directly in the field.

 

 

But see, if you replace "understand" with "comprehend" in that sentence, it sounds like I'm saying you're some sort of higher life form with a consciousness that expands into multi-dimensional space, whereas with "understand" it can almost be interpreted as a jab at your expository abilities.

I can explain things all day like the giant pedant I am, I just need to know what needs to be explained.

My smug-yet-gentle sense of superiority demands the latter.

"yet-gentle", oh you card.

 

 

:D

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The core problem with the whole endeavour is that, as I explained earlier (somewhat badly, apparently) cloning is a big issue all by itself. We're talking a sub-1% success rate here. And, as I also mentioned, interspecies surrogacy is also incredibly hit-and-miss.

 

The end result is that, if you use the approach I outlined, you're going to go through a lot failed elephant pregnancies (each taking close to two years to come to term) before you get your first viable baby mammoth.

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The core problem with the whole endeavour is that, as I explained earlier (somewhat badly, apparently) cloning is a big issue all by itself. We're talking a sub-1% success rate here. And, as I also mentioned, interspecies surrogacy is also incredibly hit-and-miss.

 

The end result is that, if you use the approach I outlined, you're going to go through a lot failed elephant pregnancies (each taking close to two years to come to term) before you get your first viable baby mammoth.

 

Yeah, I think Steve was being a bit optimistic. But when you're him, I think you get license to, no?

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On approaches, I neglected to explain in much detail the hows and whys. Looming over all of these is the decision whether to bring back a genetically-identical creature, a phenotypically-identical creature or simply settle for something good enough.

 

For the first, the only thing that would work is somehow find a viable mammoth cell and go from there. For the last, you could simply do what they did for the quagga project and breed hairy elephants.

For the middle option, you have to decide what makes a mammoth a mammoth and roll with that.

 

My approach, which seems to be pretty popular, would be to forget about mitochondrial genetics and whole-genome transfer, and use an elephant donor egg. Then, I would compare the elephant and mammoth genomes to see where they are alike and where they differ. Having done so, I would decide on the most important differences and work to transform my donor eggs using something nifty like Crispr/Cas-9. The result would be a series of donor cells, with each being closer and closer to the original mammoth genome.

 

Once I had my donors ready, I would do the whole cloning thing (which I would have tried out on elephants already, just to make sure it is possible) using my pseudo-mammoth genomes. I'd be careful to include a few attempts using donors intermediate between my elephant and mammoth genomes as well - in case there is some weird interspecies block which would fuck up the process.

Finally, after going through what would probably be hundreds of induced elephant pregnancies, I'd end up with a small pool of pseudo-mammoths to breed with.

 

With careful and thorough breeding, you could get a decent founder population of pseudo-mammoths going, then go from there.

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Yeah, I think Steve was being a bit optimistic. But when you're him, I think you get license to, no?

I don't know him from a bar of soap, so as far as I'm concerned he can be as optimistic as he wants.

 

Moving on to the big confounder in my little estimate; there is plenty of time in that one to three decade-long process for the technology to improve. If cloning technologies improves along with our understanding of the genetic causes of rejection, there is a possibility that you could do a one-shot program. That would involve going directly to the full mammoth genome (properly methylated and all the rest) and shoving it straight into the donor. That would cut the timeline down to 5-10 years.

However, considering the slow pace of improvements on our existing cloning process, I feel that being a pessimist is warranted here.

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I was planning to do more effort poasting but have prior commitments. 

 

But here is an article on what mammoths may have eaten. The description seems a bit different than the tundra plants that I'm used to dealing with up north.

 

http://www.cbc.ca/news/technology/woolly-mammoth-diet-mystery-solved-by-dna-analysis-1.2524015

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More news about mammoths.

 

Researchers map genomes of woolly mammoths, raising possibility of bringing them back

 

 

“With a complete genome and this kind of data, we can now begin to understand what made a mammoth a mammoth—when compared to an elephant—and some of the underlying causes of their extinction which is an exceptionally difficult and complex puzzle to solve,” he says.

 

While scientists have long argued that climate change and human hunting were major factors behind the mammoth’s extinction, the new data suggests multiple factors were at play over their long evolutionary history.

 

“We found that the genome from one of the world’s last mammoths displayed low genetic variation and a signature consistent with inbreeding, likely due to the small number of mammoths that managed to survive on Wrangel Island during the last 5,000 years of the species’ existence,” says Love Dalén, an associate professor of Bioinformatics and Genetics at the Swedish Museum of Natural History

 

“The dates on these current samples suggest that when Egyptians were building pyramids, there were still mammoths living on these islands,” says Poinar. “Having this quality of data can help with our understanding of the evolutionary dynamics of elephants in general and possible efforts at de-extinction”.

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