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How To Clone A Mammoth

Beth Shapiro

(London Times)

SCIENTISTS have taken a major step towards recreating the woolly mammoth after inserting 14 of the extinct animal's genes into the live DNA of an elephant.

In the research the scientists analysed DNA from mammoths preserved in Arctic permafrost to find its structure, then used the results to reproduce exact copies of 14 mammoth genes. These were integrated into the elephant genome, where they functioned as normal DNA.

George Church, professor of genetics at Harvard University, used a new technique known as Crispr that allows scientists to make precision edits to DNA, replacing sections of elephant DNA with the mammoth genes.

'We prioritised genes associated with cold resistance including hairiness, ear size, subcutaneous fat and, especially, haemoglobin [the blood molecule that carries oxygen around the body],' said Church.

'We now have functioning elephant cells with mammoth DNA in them. We have not published it in a scientific journal because there is more work to do, but we plan to do so.'

Mammoths are close relatives of Asian elephants, arising from a common ancestor that lived 2-5m years ago, and they played a dominant role in the ecosystems of colder regions of the northern hemisphere. They largely died out in the last Ice Age, possibly because of human hunting.

The last few survived on Wrangel Island in the Arctic Ocean until about 3,300 years ago, where their carcasses provided the DNA used as a template by Church and his colleagues.

But deciphering and recreating individual genes is just a start. Other researchers are trying to reconstruct the whole mammoth genome, with at least three teams in the race.

What excites some scientists, and disturbs others, is that the genome could one day become a template to recreate real mammoths - or something like them.

In her new book, How To Clone a Mammoth, Beth Shapiro of the University of California, an expert on ancient DNA, said: 'If we really want to bring mammoths back to life, then we're in luck, as far as DNA preservation goes. Some mammoths lived in places where their bones and carcasses were buried in permafrost, like being stuck in a freezer for 30,000-plus years. 'It's in pretty shoddy condition, so hard to piece together, but if we sort through these tiny pieces, finding where they fit along the elephant genome, then we can slowly build a lot of the mammoth genome.'

Working out how the full mammoth genome fitted together is the first step. The next is to recreate that DNA within the cells of a living relative - the closest being the Asian elephant.

Shapiro, who will give a talk on resurrecting mammoths at London's Royal Institution on May 21, said advances in synthetic biology such as those of Craig Venter, who built DNA from chemicals and then put it into a bacterium where it functioned like its natural counterpart, showed the potential.

'If we identify part of the mammoth genome that looks distinct from elephant DNA and which might make a mammoth look and act like a mammoth, then we can synthesise it in the lab,' she said.

'Then we could use technologies like Crispr to cut an elephant gene out of an elephant genome and replace it with a synthetic mammoth version.'

Shapiro acknowledges that the resulting animal would not be an actual mammoth but an approximation. So why do it? Church, an enthusiast for 'de-extinction', as the science of reviving lost species is now known, said genetic purity was not the issue but that the real aim was to restore ecosystems.

'The Siberian permafrost is melting with climate change, but research suggests large mammals could stabilise it,' he said. Others disagree. Professor Alex Greenwood, an expert on ancient DNA, said: 'We face the potential extinction of African and Asian elephants. Why bring back another elephantid from extinction when we cannot even keep the ones that are not extinct around?'

'What is the message? We can be as irresponsible with the environment as we want. Then we'll just clone things back?

'Money would be better spent focusing on conserving what we do have than spending it on an animal that has been extinct for thousands of years.'

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(New Scientist)

When Beth Shapiro started writing How to Clone a Mammoth a few years ago, she could have had little idea how timely her “how-to” manual would be. Now, with a flurry of headlines in recent months about the “imminent” resurrection of the woolly mammoth, her timing looks impeccable. Already, news of mammoth genes cloned in living elephant cells has emerged from two research groups this year.

“De-extinction”, the preserve of proleptic fiction like Jurassic Park, and coined from that genre, is becoming real. Shapiro, a biologist who researches the mammoth and the passenger pigeon, gives us a clear and fascinating update.

For some, de-extinction means the literal resurrection of long-lost species through whole-genome cloning, while for others it’s about conferring the traits of extinct animals on closely related living species to create approximations.

Shapiro is in the second camp. As she says, we are never going to get back the woolly mammoth our forebears hunted, but science may help us build a proxy. The Herculean hurdles involved provide much of the book’s focus.

So how do you do it? First, there’s old-school, Dolly-the-sheep cloning, which involves taking a whole genome from the DNA of your target species and injecting it into an egg of a closely related species that is minus its nucleus, and coaxing it to develop. Ice is far better at preserving DNA than the amber of Jurassic Park, but only bits of the genetic sequence are likely to survive.

Then there is back-breeding, where you select the closest descendants to your desired creation and breed for traits most like those of the extinct animal. Clearly, having the right genes in the first place is crucial here.

Then there’s the deluxe version, with new gene-editing techniques like CRISPR, currently a hot topic. Harness these, and you no longer need a full ancient genome – just an idea of which genes confer what trait and where they sit. Cut and paste mammoth genes into the genome of its closest relative, the Asian elephant, and voilà.

So much for the how-to. A sceptical proponent, Shapiro poses other big questions. Why do it at all? Once done, what next? Where will the new beasts live? Are they endangered species or genetically modified organisms? Could they upset our ecosystems?

Researchers are working on these issues. A mammoth, for example, would already have a home – Pleistocene Park in Siberia, tundra turned to fertile grassland by Sergey Zimov of the Russian Academy of Science.

De-extinction is an exciting topic, but the book can be a little academic, although Shapiro explains complex molecular biology clearly. It really comes alive, though, when she describes her own expeditions, for example, hunting mammoth bones across Arctic tundra in rickety Russian helicopters – minus window glass, for smokers.

Shapiro handles the debates well, although I’d have liked more about the “benefits” of de-extinction. For example, some experts say repopulating Siberia with mammoth-alikes would refill a niche that would make the ecosystem flourish, and have a positive effect on global warming.

Who knows? Some of us just have a soft spot for mammoths. Mine dates to 2014 when Lyuba, a baby mammoth, visited London’s Natural History Museum from the Shemanovsky Museum, Siberia. Sadly, says Shapiro, the baby did not yield usable DNA.

Public appetite for mammoths – and de-extinction – is clearly immense, and Shapiro has received both fan and hate mail. Her book can only prove a great aid to informed debate.

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