Resurrecting Mammoths Gets One Step Closer

If only Michael Crichton had lived to see this: scientists are announcing today that they have sequenced the genome of the woolly mammoth, which has been extinct for about 10,000 years. That makes it the first extinct genome to be sequenced, raising the tantalizing possibility that what Crichton envisioned for dinosaurs in Jurassic Park might come true for mammoths.

As scientists led by Stephan C. Schuster of Pennsylvania State University describe today in the journal Nature, they extracted DNA from the hair of several mammoths preserved in permafrost. The scientists estimate that entire mammoth genome is 4.7 billion nucleotides long (humans’ is 3 billion nucleotides; a nucleotide is one of the four chemical “letters,” designated A, C, T or G, that constitute the coding part of DNA), and they figure they’ve sequenced around 80% of it. All told, 28 vertebrate species have had their genomes sequenced, including humans, chimps, mice and dogs, but this is the first extinct animal to join the club (though the extinct cave bear and Neanderthals have been partially sequenced).

In their paper, the scientists emphasize the value of the study for understanding the evolution of elephant species (by comparing the mammoth DNA to that of living African pachyderms), but let’s face it: what we want to know is whether the genome sequence can be used to resurrect mammoths.

Nature writer Henry Nicholls lays out what would be required. “If you want to bring a species back to life,” he notes, “the mammoth would be almost as dramatic as a dinosaur. And unlike Tyrannosaurus rex, the mammoth has close living relatives to lend a hand. It is a fair bet that a complete genome and closely related species would make it easier to pull a Crichton on a mammoth than on a dinosaur.”

“Easier” does not mean “easy,” of course. To go from the genome being announced today to a living, breathing mammoth would require synthesizing a full set of chromosomes from the DNA, packaging them in a nucleus, transferring that nucleus into an egg, and implanting that egg into the womb of a surrogate mother (presumably an elephant). Although none of this has been done—Nature says there are “all but-insurmountable obstacles at every stage, and no evidence that anyone is going to work very hard to solve them”—none are scientifically impossible.

For instance, making a complete, error-free mammoth genome is almost surely in the cards. Figuring out how Mother Nature apportioned the 4.7-billion-nucleotide sequence into chromosomes, which is biologically necessary, is a challenge, but presumably studying how she did it in elephants (which have 56 chromosomes, compared to humans’ 23) would provide clues. Then you’d need the actual DNA—that is, take the known sequence and make all of those 4.7 billion chemicals in test tubes, link them up and actually package them in chromosomes. The largest such “synthetic genome” yet synthesized is the measly 582,970 nucleotide one of the bacterium Mycoplasma genitalium. For mammoths, you’d need to string the 4.7 billion onto 56 chromosomes, each averaging 160 million long. Tough? Sure, but as Nature says, “It is worth remembering that genome synthesis is further developed today, in terms of the maximum lengths achieved, than genome sequencing was when Crichton wrote Jurassic Park. And look how sequencing has progressed since then.”

Once you have your mammoth chromosomes, you have to pack them into a nucleus and then an elephant egg. Elephant eggs are not easy to come by, but it may be possible to harvest a steady supply by collecting tissue from the ovary of a recently deceased elephant and grafting it into a lab mouse or rat—something that has been done: frozen samples of ovarian tissue from African elephants have been transplanted into mice, where egg-making follicles developed.

Finally, you’d have to transfer the mammoth nucleus-encased DNA into the egg, fertilize it, and transfer the four-cell embryo into a surrogate mom (never been done). “Most evidence indicates that newborn woolly mammoths were about the same size as newborn elephants,” Nature notes, so size should not be a problem for the surrogate mom.

So, how feasible is all this? “The fact that just 15 years ago cloning mammals was confidently ruled out by many as being impractical should give people pause before saying any such thing is impossible," Nature concludes. "By 2059, who knows what [extinct species] may have returned, rebooted, to walk the Earth?”

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