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Race to modify the DNA of endangered animals and resurrect extinct ones

By Steve Connor

Published 14/04/2015

It is without irony that some scientists are seriously raising the possibility of bringing back the mammoth from extinction to help prevent our own demise
It is without irony that some scientists are seriously raising the possibility of bringing back the mammoth from extinction to help prevent our own demise

De-extinction, or the idea of bringing extinct species back from the dead, has come a long way over the quarter century since Jurassic Park was first published. It has now matured into a quasi-serious science and has even been the subject of its own TEDx conference.

Of course, no-one is talking about bringing back dinosaurs – their DNA is lost for good – but some scientists are proposing to resurrect a range of other, more-recently extinct species such as the passenger pigeon and the gastric-brooding frog, both lost within living memory.

There are quite a few animals that have become extinct relatively recently that are potential candidates for de-extinction. They include the thylacine, or Tasmanian tiger, a large marsupial carnivore wiped out by sheep ranchers a century ago, the Pyrenean ibex which was hunted for sport until the last one fell dead in 2000, and the Steller’s sea cow, a gentle giant annihilated by hungry sailors in the 18th century.

Perhaps the most emblematic of them all is the woolly mammoth. There are few animals that better represent the lost world of the Pleistocene than these huge, shaggy relatives of the modern elephant. Woolly mammoths roamed the vast grassy steppe of Eurasia and North America for hundreds of millennia. The very last individuals were an isolated population of pygmy woolly mammoths that lived on Wrangel Island off northern Russia about 4,500 years ago.

There is no shortage of woolly mammoth tissue, some of it remarkably well preserved in the permafrost of Siberia and some scientists are confident that they can extract its DNA to bring the species back to life, either as clones or as a kind of mammoth-elephant hybrid.

Scientists in South Korea and Russia are collaborating on a project to clone a woolly mammoth by extracting a cell nucleus from frozen mammoth tissue and inserting its entire genetic material into the enucleated egg cell of an Asian elephant, which would also act as a surrogate mother.

It’s the same basic cloning technique that led to the birth of Dolly the cloned sheep in 1996, except this time two species are involved rather than one – and one of them has been extinct for thousands of years.

The difficulties facing this particular de-extinction project are immense and few expect it to succeed. For a start, finding a good enough mammoth cell nucleus in preserved tissue is a tall order. Getting it to spark into life as a cloned embryo developing from the egg of another species is even more problematic – and that’s before the difficulties of pregnancy and birth.

At present, the oldest frozen material used to create a cloned mammal has been laboratory-stored cells of mice kept in a fridge for 16 years. Being able to clone a mammoth from tissue cells that have been frozen for thousands of years in less than ideal conditions presents a far more formidable set of obstacles.

Another de-extinction approach is to cut and paste large fragments of mammoth DNA into the chromosomes of an Asian elephant, thereby creating a genetically-engineered mammoth-elephant “hybrid”. Scientists involved in this project prefer to think about it as a way of making a cold-adapted Asian elephant with mammoth-like traits, such as hairy skin and layers of subcutaneous fat for good thermal insulation.

Scientists have already managed to sequence about half of the mammoth genome from the many small fragments of DNA isolated from frozen remnants of biological material, such as skin, hair, bone, teeth and even dung.

They believe it is only a question of time before they achieve their ultimate de-extinction aim: a living hybrid. “We’re preparing to make a hybrid elephant that would have the best features of modern elephants and the best features of mammoths,” George Church, professor of genetics at Harvard Medical School, told the TEDx conference on de-extinction, held in Washington two years ago.

Since then, Professor Church has applied a sophisticated and revolutionary “gene editing” technique known as Crispr and has managed to get it working in elephant cells to carry out 14 precise changes to its genome. “We are now working on in vitro organogenesis [organ formation] and embryogenesis [embryo formation],” he told The Independent in an email.

Put to one side for the moment the question of “why would anyone want to do this?” and ask “can Professor Church and his colleagues be serious?” Would it really be possible to bring back mammoths, or at least a creatures resembling and behaving as them, using the synthetic life technology of molecular genetics and cloning?

Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz and expert on the ancient DNA of the Arctic, is something of a sceptic – despite writing a book called How to Clone a Mammoth: The Science of De-extinction. She points out the immense technical problems with this kind of work, mostly connected to the degradation of the DNA molecule after thousands of years.

She says there are seven steps needed to clone a mammoth, starting with the DNA sequencing of the full mammoth genome, and ending with the birth and rearing of the mammoth hybrid or clone, and we haven’t yet cracked problem number one.

“It’s a hard problem and a problem that probably won’t be solved without new and different biotechnology to what’s available today. But if it’s what we want to do we will eventually learn how to sequence the complete genome of an extinct animal. And then we will have completed step one,” she says.

“While it’s not clear to me that there are compelling reasons to bring exact replicas of extinct species back to life, there may be compelling reasons to develop the technology to genetically manipulate living species. For example, this technology might be useful to provide a genetic “booster” shot for species that are critically endangered. So, instead of using this technology to bring extinct species back to life, we could use this technology to aid in the conservation of living and endangered species or ecosystems,” she says.

Hendrik Poinar, principal investigator at the ancient DNA centre at Canada’s McMaster University in Hamilton, Ontario, is more optimistic. Like Professor Church, he is excited by the idea of de-extinction. He believes the technical barriers are not necessarily insurmountable. “The revival of an extinct species is actually within reach,” he says. “I do believe it is.

How you define ‘extinct’ may be at question. But I have no doubt that at some point we will be very close to having an organism that looks, feels and maybe even at some point behaves as its extinct ancestors did. ”

Which brings us back to the question: why? Even if it were possible to generate enough individuals to produce a viable, breeding population of mammoths or mammoth-elephant hybrids, what would be the point? Some conservationists believe that the entire enterprise is a potentially dangerous distraction from the main job of preserving the many thousands of threatened species we still have left in the world. For years they have argued that “extinction is forever” but if governments and corporations believe that it’s not, then this could fatally undermine efforts to preserve and protect what we have.

Stanley Temple, emeritus professor University of Wisconsin-Madison, believes that even if it works, the de-extinction approach could end up with a net loss of biodiversity, with less charismatic species in particular losing out. “Conservation biologists worry about de-extinction having a destabilising effect. If extinction is not forever, a lot changes... de-extinction might undermine conservation efforts. It could reduce concern over threats to biodiversity by giving us an unfortunate ‘out’,” he says.

Professor Church argues the opposite. He says that creating a cold-adapted Asian elephant would mean that the species could roam further north than its existing, threatened habitat. “Elephants are currently in danger as they overlap with human populations. If they could be readapted to places of minus 50C, where there is low human density, they would stand a higher chance of survival,” he says.

Both have suggested that the present-day tundra landscape of Canada or Siberia could accommodate a latter-day population of mammoths. It would be an extreme version of the idea of re-introducing lost species into an ecosystem where they were once expelled, only this time set in the Pleistocene and not in the present.

“This landscape would easily be able to house the mammoth and I have to admit that there is a part of me, the child or boy in me, that would love to see these majestic creatures walk across the permafrost once again, but I do have to admit that part of me, the adult in me, sometimes wonders whether or not we should,” Poinar says.

Back for good? ‘Jurassic Park’ popularised the idea of de-extinction, which could potentially be used on other species, including mammoths
Back for good? ‘Jurassic Park’ popularised the idea of de-extinction, which could potentially be used on other species, including mammoths

By knowing about the mammoth-elephant genes for oxygen transport in the blood, the genes for body fat and hair growth, and other genes needed for survival, it might be possible to recreate a hybrid elephant-mammoth that is well suited for the conditions of the subarctic tundra, Professor Church believes. Furthermore, the reintroductions of this extinct species could have wider benefits for the Siberian wilderness, he argues, citing the work of Russian scientists who are already trying to recreate the sub-arctic habitat of the Pleistocene.

One such researcher is Sergey Zimov, director of the Northeast Science Station in Cherkii, in the Russian republic of Sakha. Zimov has long had an ambition of bringing back ice-age species and letting them loose in an area of Siberia he has named Pleistocene Park – a vast nature reserve on the Kolyma river in the Russian Far East that aims to recreate the subarctic steppe grassland that was replaced by mossy tundra when the mammoths became extinct.

Zimov articulated his vision 10 years ago in the American journal Science. He argued that recreating the lost Pleistocene habitat could be possible by re-introducing the right combination of animals that helped to shape these landscapes. “If we accept the argument that the pasture landscapes were destroyed because herbivore populations were decimated by human hunting, then it stands to reason that those landscapes can be reconstituted by the judicious return of appropriate herbivore communities,” Zimov wrote.

His vision is to have reindeer, moose, Yakutian horses, musk oxen, hares, marmots and squirrels feeding on the vegetation of Pleistocene Park. These could be kept in check by predators such as wolves, bears, lynxes, wolverines, foxes, polar foxes and sables. Bison could eventually be re-introduced from Canada and even the Amur tiger could be brought in as a predator, once animal densities increase to levels that would sustain such a carnivore, he explained.

If mammoths existed, they would play a role in maintaining the grassy vegetation of the mammoth steppe, which turned from relatively lush grass steppe to mossy tundra once they went extinct. By constantly churning the ground and spreading their manure, mammoths would be the key species that would keep the grassy steppe from being smothered again by mossy tundra. Some experiments have even indicated that a mammoth-trampled tundra would keep the ground colder and prevent it from thawing in a warmer climate.

In Zimov’s vision, returning the tundra to mammoth steppe would help to keep the vast stores of carbon locked away in the Siberian permafrost from escaping as the world gets warmer. “At present, the frozen soils lock up a vast store of organic carbon. With an average carbon content of 2.5 per cent, the soil of the mammoth ecosystem harbours about 500 gigatons of carbon, 2.5 times that of all rainforests combined,” Zimov argues.

“Preventing this scenario from happening could be facilitated by restoring Pleistocene-like conditions in which grasses and their root systems stabilise the soil. The albedo – or ability to reflect incoming sunlight skyward – of such ecosystems is high, so warming from solar radiation also is reduced,” he explains. “And with lots of herbivores present, much of the wintertime snow would be trampled, exposing the ground to colder temperatures that prevent ice from melting. All of this suggests that reconstructed grassland ecosystems... could prevent permafrost from thawing and mitigate some negative consequences of climate warming.”

It is without irony that some scientists are seriously raising the possibility of bringing back the mammoth from extinction to help prevent our own demise. But not everyone is happy with the idea of de-extinction. Some conservationists see it as a distraction from the battle to preserve species teetering on the brink.

“If it works, de-extinction will only target a few species and it’s very expensive. Will it divert conservation dollars from true conservation measures that already work, which are already short of funds?” asks David Ehrenfeld, professor of biology at Rutgers University in New Brunswick, New Jersey. “At this moment brave conservationists are already risking their lives to protect dwindling groups of African forest elephants from heavily-armed poachers, and here we are talking about bringing back the woolly mammoth. Think about it.”

Source: Independent

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