De-extinction through incremental genetic editing?

In My Humble Opinion
1

So I’m sure I’m not the first to think of this. But I was reading about how frozen woolly mammoths have been found. If you were to sequence the DNA of a large chunk of frozen mammoth-tissue, it should be possible to arrive at a complete and error free copy of the animal’s genome.

So, ok, you can’t just synthesize the genome, stick it in an active elephant egg, and hope for the best. Probably. The elephant mother is too genetically different, there’s probably too many incompatibilities.

But what you probably could do is first calculate the delta between the elephant and the mammoths’ genomes. Ignore any alleles in common. Then, randomly grab a sample of the differences, and make a hybrid embryo. Say the hybrid is 10% mammoth, 90% elephant. Do the hybridization process many times, and implant the hybrids that seem viable.

Then, grow a female hybrid elephant mammoth. Now, starting with that female’s eggs, do the process again…

It should be possible to eventually reach 100% pure mammoths doing this a little bit at a time. That’s how evolution got from mammoths to elephants in the first place, (well, ok, it might have gone through a common ancestor) so it should be possible to go in reverse like this.

Would this work? Can we de-extinct anything we have a complete genome for this way?

It has occurred to me that if you can do fancier editing, you could block certain mammoth genes from being expressed until birth, and thus get around obstacles that would otherwise prevent the hybrids from being viable as well.

In theory, if you started with a chicken, you could get to a T-rex the same way. You would need the complete genome (might be impossible to get), but if you had it, you could eventually get there. You can’t patch missing pieces with frog DNA like in the script for the movie, but you could in fact use chicken or frog DNA as bootstrap components temporarily while you breed your way to the goal.

2

A random hybridization approach might conceivably work for something like Drosophila, but it is not practical with a large (and itself endangered) mammal. In other words, even if it were ethical, it’s not practical to just breed hundreds of baby elephant-mammoth hybrids and discard the deformed or non-viable ones.

But the Church lab in Harvard is working on a project to selectively introduce segments of mammoth DNA that code for key evolutionary differences, with the ultimate goal of breeding something somewhat similar to a mammoth, and perhaps even reintroducing it to the wild.

3

Given a high enough technology, you could theoretically recreate any extinct species–or at least build something that looks and behaves like you suspect the original to look and behave. But you would be recreating phenotype, not genotype. Your faux T-rex or trilobite would seem T-rexy or trilobity enough as far as you know, but if you could pull a real one out of the past, there is almost zero chance they would be interfertile with the reproduction because there is almost zero chance the same suite of genes would have been black-boxed. (Little Jack Horner sat in a corner and wrote a book about this.)

4

This thread is about re-creating genotype correctly and exactly. It assumes you have a big enough sample of the extinct animal to get enough fragments of DNA to correct for any degradation or errors. Obviously, unless we find a frozen T-rex, it’s going to be hard to accomplish that. I just mentioned it at the end because while making a mammoth from an elephant sounds only modestly hard, a T-rex from a chicken (using hundreds of intermediates) sounds near impossible.