Will we ever clone a mammoth?
By ED YONG - DISCOVER MAGAZINE
Added: Wed, 06 Jun 2012 21:55:47 UTC
Tens of thousands of years ago, woolly mammoths roamed the northern hemisphere. These giant beasts may now be extinct, but some of their bodies still remain in the frozen Arctic wilderness. Several dozen such carcasses have now been found, and some are in extremely good condition. Scientists have used these remains to discover much about how the mammoth lived and died, and even to sequence most of its genome. But can they also bring the animal back from the dead? Will the woolly mammoth walk again?
Akira Iritani certainly seems to think so. The 84-year-old reproductive biologist has been trying to clone a mammoth for at least a decade, with a team of Japanese and Russian scientists. They have tried to use tissues from several frozen Siberian specimens including, most recently, a well-preserved thighbone. Last year, Iritani told reporters, “I think we have a reasonable chance of success and a healthy mammoth could be born in four or five years.”
A few months ago, a second team led by Korean scientist Hwang Woo Suk also expressed interest in cloning a mammoth. While Iritani comes with impressive credentials, Hwang’s resume is less reassuring. He is perhaps best known for faking experiments in which he claimed to have cloned the first human embryo and produced stem cells from it. The fact that he has confessed to buying mammoth samples from the Russian mafia does not help to instil confidence.
Regardless of their pedigree, both teams have their work cut out. Any attempt to resurrect the mammoth faces an elephantine gauntlet of challenges, including the DNA-shattering effects of frost and time, and the rather unhelpful reproductive tract of the eventual surrogate parent—the elephant.
Siberian ice might preserve the bodies of mammoths, but it is not kind to them. Ice crystals puncture cells, spilling out their contents. Even if the DNA inside the cell is not exposed, it tends to break down over time. Stephan Schuster from Penn State University, who led the mammoth sequencing project, says, “Even the genomes from much younger organisms rapidly decay. It’s like smashing a mirror on the floor.” Schuster’s team compared the heavily fragmented DNA of a mammoth against the genome of an elephant. That approach allowed them to read the genome, but it cannot be used to reconstruct it.
Synthesising an animal genome from scratch is a massive challenge by today’s technological standards. It would require: a far more accurate draft than the one we have; knowledge of the number of chromosomes a mammoth had; the ability to stitch together such large stretches of DNA; ways of packaging that DNA into a nucleus; and hoping that all the DNA will still be in good working order.
There is another option. Rather than producing mammoth DNA from scratch, you could tweak DNA from an African elephant. The genomes of the two species differ by just 0.6 percent, half the difference between us and chimpanzees. By identifying and swapping the different sequences, you could potentially rewrite an elephant genome so that it reads like a mammoth one.
Palaeontologist Jack Horner is trying something similar by rolling back a chicken’s genes into a state more like its extinct dinosaur ancestors, and scientists like Harvard University’s George Church are developing techniques that can rewrite vast swathes of DNA at once. But even if the technology catches up with the ambition, Schuster says: “That’s not making a mammoth. It’s ‘mammothifying’ an elephant.” The resulting creature may be a more mammoth-like version of today’s pachyderms, but it won’t be the real deal.
These problems might be avoided if we could find intact nuclei from frozen mammoths, at least if experiments in other animals are anything to go by. In 2008, Sayaka Wakayama and colleagues from RIKEN, Japan cloned healthy mice from individuals that had been frozen for 16 years. They found intact nuclei in the chilled bodies, and fused them with empty eggs. By all accounts, Iritani is trying to do the same thing with frozen mammoth remains (he did not respond to a request for an interview). But Schuster does not mince words about the odds of finding intact mammoth nuclei. “It’s entirely impossible,” he says. Sixteen years in the freezer is one thing; 16,000 years is quite another.
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