Bringing Woolly back to life

The woolly mammoth had a two-layer coat of wool topped by long, coarse fur and a layer of fat under its skin up to 10cm thick.
PHOTO: Wikimedia Commons

The last of the woolly mammoths died about 3,500 years ago, when the Egyptians were still building their pyramids.

Although the giant animals once roamed the vast, frozen landscapes of northern Asia, Europe and North America, they likely became extinct due to climate change and being hunted by people.

But now, a team of scientists from Singapore and the United States has published research that is a step towards resurrecting the prehistoric creature.

They have sequenced, for the first time, a highly detailed and complete genome or genetic blueprint of the woolly mammoth, which researchers could use to start recreating the animal. The team believes that its work will lead to a "mammothified" Asian elephant before long and, eventually, the resurrection of the mammoth.

Said Nanyang Technological University's (NTU) Dr Stephan Schuster, who was part of the effort: "In the series of steps that needs to be done to bring the mammoth back to life - and there are many - having its genetic blueprint, which we have now released, is the very first step."

The team's research could also benefit the mammoth's surviving relatives, the Asian and African elephants.

The genes that might have helped the mammoth to survive in the Arctic's extreme cold, for example, could be inserted into Asian elephants to help the endangered species tolerate colder temperatures, expanding its range.

Already, scientists at Harvard University in the US have claimed to have successfully recreated mammoth genes and inserted them into lab-grown live cells of an elephant, although the work has yet to be published in scientific journals or reviewed by peers.

In the Singapore-US effort, researchers from NTU, Penn State University and the University of Chicago used next-generation sequencing, a technology that has become cheaper and more powerful only in recent years, to delve into the preserved hair of two woolly mammoths - one which died about 60,000 years ago, the other 20,000 years ago.

The team also broke scientific ground by sequencing the complete genomes of three living Indian elephants - the mammoth's closest living relative - for the first time. By comparing the genomes of the woolly mammoth and the Asian and African elephants, the scientists discovered the differences that made the mammoth unique.

They identified about 1.4 million genetic variants unique to the mammoths. These caused changes to the proteins produced by about 1,600 genes, and are likely linked to the warm-blooded animals' evolution to survive in the frigid Arctic as the climate changed.

Unlike other elephants, the mammoths had a two-layer coat of wool topped by long, coarse fur, "almost like you would make a down jacket today", said Dr Schuster, a research director and professor of environmental genomics at NTU.

They also had a layer of fat under the skin up to 10cm thick to keep warm, and small ears and tails to reduce heat loss and frostbite, while long curved tusks probably came in handy to move snow out of their way.

So far, the Singapore-US team has definitively uncovered the work of just one of the 1,600 genes.

The scientists referred to databases of known gene functions and looked at earlier mice studies to infer how the genetic changes might have affected the mammoths.

In mice, changes in the same genes had an impact on circadian clocks, temperature sensation and skin, hair and fat deposits - traits linked to cold weather adaptation.

But the scientists also went one step further by "resurrecting" one of the genes, called TRPV3. In every other sequenced mammalian genome, the gene did the same thing - but not in the mammoths.

The team produced synthetic copies of the gene from a mammoth and an Asian elephant and put them into separate cell lines or colonies, which then produced different proteins.

When the scientists compared the proteins, they found that those from the elephant TRPV3 gene were more active than those from the mammoth gene.

"Luckily for us, we knew that there were mice that also did not have an active TRPV3 gene," said Dr Schuster. "We might have hit the jackpot with this gene, because those mice had much more curly hair and looked much more woolly compared to other mice."

He added that when the team gave the TRPV3-inactive mice a choice between going to a cold area and going to a warm area in their cages, they invariably chose the cold area.

"This gene very likely not only affects their coat, but also makes them more accepting of cold."

The team studied hair samples from eight other mammoths to make sure the TRPV3 gene mutation existed in all of them and was not a freak change in the two mammoths it had sequenced.

Now that the scientists have the list of 1,600 genes, they can test each of them in the same way to determine their specific functions.

Some researchers are very keen for this to happen so that the genes' work can be linked to more unique traits. They include Dr George Church, a professor of genetics at Harvard Medical School, who has been studying how to create hybrids of Asian elephants and woolly mammoths that can survive in the Arctic's freezing temperatures.

Expanding the Asian elephants' range, especially into areas that are unsuitable for human habitation, could save them from extinction due to negative interactions with people, said Dr Church, who was part of the team that says it has spliced mammoth and elephant DNA.

"In theory, Asian elephants could adapt evolutionarily, but this would take a million years... Occasionally, species need some help," he said.

The hybrid elephants could also reduce climate change, partly by stomping on snow and soil and packing the ground tighter, thus preventing trapped greenhouse gases in the soil from escaping, said Dr Church.

But obstacles remain. Scientists have said, for instance, that to recreate the mammoths' DNA, researchers would need to know the chromosome and genetic changes to the mammoths in the 7.6 million years since they diverged from their African ancestors. And even if a single mammoth was created artificially, others would have to follow for the species' continuation.

The animals' genomes would also need to be tweaked to ensure diversity so they would not be wiped out by disease, for example.

Other scientists have raised ethical concerns and worries that "de-extinction" success would blunt the urgency of animal conservation. They point out that research money would be better spent on saving the vulnerable African and endangered Asian elephants.

Professor Alex Greenwood from the German Leibniz Institute for Zoo and Wildlife Research told reporters earlier this year: "Why bring back another elephantid when we cannot even keep the ones that are not extinct around?"

Dr Schuster agreed. "I think the biggest concern we should have, especially with global climate change, is to preserve species that are at the brink of extinction."

But he added: "Still, if you ask me will there eventually be a resurrected mammoth, the answer is clearly yes. If it can be done, somebody will do it."

Resurrecting extinct species

The world of Jurassic Park is no longer a complete fantasy. In 2003, scientists briefly brought a wild goat of an extinct species back to life, although the clone died 10 minutes after birth.

Dinosaurs are off the table as DNA decays and they have been extinct for too long to be cloned, but researchers are trying to revive species like the passenger pigeon, once the most abundant bird in North America.

Here are some projects.

PASSENGER PIGEON

WHAT: The passenger pigeons were so abundant in North America in the 19th century that their flocks were said to darken the sky for hours as they passed.

EXTINCTION: By the late 1800s, however, their numbers had plummeted due to habitat loss and hunting. On Sept 1, 1914, the last-known passenger pigeon, a female named Martha, died in the Cincinnati Zoo at the age of 29.

REVIVAL: In 2012, the US-based Revive and Restore Project, which aims to resurrect extinct animals, chose the passenger pigeon as its flagship effort. It hopes to take passenger pigeon DNA from museum specimens and fill in the blanks with DNA from its close surviving relative, the band-tailed pigeon. The team is still studying how to engineer the birds. Some scientists, however, are sceptical about whether today's forests can support a revived population.

AUROCHS

WHAT: Giant cows called aurochs once roamed Europe. They weighed nearly 1,000kg, were about 2m tall, and were dangerous. Some were domesticated about 8,000 years ago, but others remained in the wild. Most were killed by the 15th century due to overhunting and habitat loss.

EXTINCTION: The last survivor died in a nature reserve in Poland in 1627, where it had "the dubious honour of being the first documented case of extinction".

REVIVAL

• In the 1930s, the Nazis produced a breed of aggressive cattle that was genetically different from the aurochs.

• Private Dutch organisation Stichting Taurus is leading an effort to scour museums for auroch bone and teeth fragments, in the hope of gleaning enough genetic material to recreate its DNA. The researchers will then compare it with modern cattle to see which breed has the aurochs' genes, and try to reverse thousands of years of evolution through selective breeding. The project is seeking funding.

TASMANIAN TIGER (THYLACINE)

WHAT: The wolf-like marsupial was once found throughout mainland Australia and New Guinea.

EXTINCTION: When humans introduced dingoes to the area about 4,000 years ago, the thylacines were probably out-competed for food. Eventually, the species remained only on the dingo-free island of Tasmania.

It was blamed for killing livestock and was hunted to extinction by the early 1900s. The last thylacine, in Tasmania's Beaumaris Zoo, died on Sept 7, 1936.

REVIVAL: The Australian Museum announced plans in 1999 to reconstruct the animal from the DNA of a pup preserved in ethanol in 1866. But in February 2005, it said it was thwarted by poor DNA samples and a lack of technology. Later that year, the University of New South Wales said it would pick up the work with other partners, but nothing has come out of it so far.

PYRENEAN IBEX

WHAT: Once common in northern Spain and the French Pyrenees, the species was reduced to fewer than 100 in numbers because of extensive hunting in the 19th century. It is the only animal that scientists have brought back from extinction, but only for 10 minutes.

EXTINCTION: In 2000, the last of the wild goats, a female nicknamed Celia, was killed when a tree toppled and crushed it.

REVIVAL: In 2003, French and Spanish scientists delivered a newborn clone after 57 tries but it died after 10 minutes, due to a lung defect. The project was mothballed shortly after that. In November 2013, the scientists received new funding, and are still trying to clone Celia.

 

 

This article was first published on July 31, 2015. Get a copy of The Straits Times or go to straitstimes.com for more stories.