
Photo: S.C. Schuster
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?”