Nov 21

Nov 21 Making a comeback - the science of de-extinction

Bucardo (Pyrenean Ibex) from the book 'Wild oxen, sheep & goats of all lands, living and extinct' (1898) by Richard Lydekker. Via Wikipedia, public domain

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Read more about the science of de-extinction in Helen Pilcher’s excellent book Bring Back the King.

Every day, everywhere, species are going extinct. The last organism of its kind finally dies, and a twig on the tree of life comes to an end.

While it’s hard to put a precise number on it, some experts think that there are between 20 and 150 plant and animal extinctions every single day.

But although the exact figures are contested – partly because it’s incredibly hard to figure out exactly how many species are out there in the world, and exactly when any one of them might have popped off this mortal coil for good – it’s generally held that current extinction rates are many times higher than what might be expected, and many of these vanishings are the result of human action.

One obvious solution is to invest in conservation – preserving precious habitats and protecting populations on the brink of death. But what about the ones that have already gone? Could we bring them back?

Many people will be familiar with the science of de-extinction from Jurassic Park – the infamous Steven Spielberg film franchise based on a novel by Michael Crichton. Alas, the fictional premise of resurrecting dinosaurs from DNA in blood cells preserved in mosquitoes trapped in amber is very unlikely to ever happen – not least because the oldest DNA ever found in around a million years old, and the youngest dinos date back 66 million.

Bring things closer to the present, however, and science fiction starts to become science fact.

Alberto Fernández-Arias has seen his favourite species – the bucardo - go extinct not once but twice. These large mountain goats inhabited the Pyrenees for thousands of years until hunting sent their numbers plummeting. And as head of the Hunting, Fishing and Wetland department in northern Spain, it fell to Fernández-Arias to protect them.

Despite his best efforts, by the year 2000 there was just one bucardo left – a female that he and his team named Celia. Her demise – and the extinction of her entire species - was announced by the sad beep from her radio collar as she was crushed by a falling tree.

But buried deep in their laboratory freezer was the chance for Celia to live again. Inspired by the recent successful birth of Dolly the sheep – the first mammal cloned from an adult cell - Fernández-Arias had gathered a sample of Celia’s cells nine months before her death, in the hope of resurrecting her species one day in the future.

Using a similar technique that Ian Wilmut and his team at the Roslin Institute in Scotland employed to make Dolly, which we talked about in episode 23, the Spanish team injected DNA from Celia’s cells into goat eggs that had been emptied of their own DNA, then kick-started them into dividing and starting the process of making an embryo.

The next step was to implant these tiny balls of cells into a surrogate mother animal. And it’s here that things got tricky.

Whereas Wilmut could use sheep as surrogate mothers for growing his cloned lambs, obviously, there are no more mums left for a species that has gone extinct. First, Fernández-Arias tried implanting his cloned bucardo embryos into domestic goats, but their wombs didn’t nourish the growing foetuses properly and every attempt resulted in a miscarriage.

Instead, he had to breed hybrid species by crossing goats with a close relative of the bucardo – the ibex – and then implanting the embryonic clones into them instead. But by 2003, everything was in place for the bucardo’s return.

After 57 egg implantations, seven pregnancies and six miscarriages, the first bucardo in three years came into the world by caesarean section and was quickly swept up into Fernández-Arias’ eager waiting arms. Tragically, his joy at seeing his beloved mountain goat brought back from extinction was short lived. Within a matter of minutes, the bucardo was extinct once more.

Science writer Carl Zimmer describes the painful scene in his feature in National Geographic:

“As Fernández-Arias held the newborn bucardo in his arms, he could see that she was struggling to take in air, her tongue jutting grotesquely out of her mouth. Despite the efforts to help her breathe, after a mere ten minutes Celia's clone died. A necropsy later revealed that one of her lungs had grown a gigantic extra lobe as solid as a piece of liver. There was nothing anyone could have done.”

Fernández-Arias is still trying to bring back his beloved mountain goats, and cloning techniques have come on leaps and bounds since he first started cloning Celia’s cells back in 2003. Even so, using cloning to resurrect extinct animals from frozen cells is fraught with difficulty.

Kickstarting cell division requires an electric shock, which doesn’t always work. There can be incompatibilities between egg and donor DNA, as well as difficulties with implantation and development in the womb, and even when everything works and a pregnancy goes to term, the resulting animals often have health problems.

One way round these problems is to use induced pluripotent stem cells, or iPS cells, which were first developed by Nobel prize-winning Japanese scientist Shinya Yamanaka in 2006.

Rather than going to all the trouble of generating embryonic cells by taking the DNA out of an adult cell and putting it into an egg, it’s now possible to turn an adult cell back into an embryonic one by adding a cocktail of special reprogramming molecules. These iPS cells can be used to generate an embryo, or even turned into eggs and sperm to create a new animal.

The technique hasn’t yet been used to resurrect an extinct species but it has been used to clone mice, and could one day be used to convert stored adult cells from extinct species into sperm, eggs or even embryos.

But while they’ve got a huge amount of potential, using cloning techniques and iPS cells to bring animals back from extinction relies on having a stash of intact frozen cells – something that simply doesn’t exist for most of the species we’ve lost from the world, from woolly mammoths to passenger pigeons, T-Rex to Elvis Presley. So, can we really bring back the King?

In 1914 the very last passenger pigeon, known as Martha, died in Cincinnati Zoo. This extinction event would have seemed inconceivable to American naturalist John James Audubon, who a century earlier had described a migrating flock of passenger pigeons joining him on his journey along the Ohio River to Louisville.

“The air was literally filled with Pigeons,” he writes. “The light of noon-day was obscured as by an eclipse, the dung fell in spots, not unlike melting flakes of snow; and the continued buzz of wings had a tendency to lull my senses to repose.”

The flock passed overhead for three whole days, rousing the good citizens of Louisville to arms to shoot as many of the birds as possible.

Yet this incredible flying bounty couldn’t last forever. Thanks to excessive hunting and shrinking of their natural forest habitats, by 1900 the last wild passenger pigeon met its maker at the hands of a young boy with a BB gun, with Martha’s death in captivity over a decade later marking the species’ final demise.

A century after that, the passenger pigeon is making a comeback – and not just because someone really loves birds. The dense, migratory flocks of Passenger Pigeons in the past are thought to have served a vital role in maintaining forest ecosystems by eating, pooping and leaving, so their restoration could help to stabilise and restore fragile woodlands.

Unfortunately, there are no samples of intact cells from Martha or any other passenger pigeon for cloning. Instead, the team working on bringing back her species are taking a different approach, cobbling together bits of available passenger pigeon DNA and DNA from living relatives to create a genome that represents the extinct species.

Currently, DNA has been sequenced from 37 different passenger pigeon samples, including two whole genomes. Work is now underway to create pigeons that carry genetic engineering tools in their DNA to carry out the cutting and pasting required to splice in this ancestral DNA into the modern pigeon genome, with the aim of hatching the first of a new generation of rebooted passenger pigeons in 2025.

Other scientists have set their sights on a much bigger prize- the woolly mammoth. Again, this isn’t just because mammoths are awesome (although they are…)

When mammoths last roamed the earth, they helped to maintain grasslands in the frozen North. Bringing them back to the arctic tundra could support biodiversity and allow deeper freezing during winter months and less melting during the summer. In turn, this would preserve the arctic habitat and reduce the release of greenhouse gases.

The mammoth has been extinct for around 3,600 years, and there are samples of mammoth DNA preserved in the natural deep freeze of its ancient homeland. It also has a very close living relative that shares around 99.96% of its DNA – the Asian Elephant.

Scientists at Harvard University, led by George Church, are attempting to use gene editing techniques to take elephant DNA and engineer in mammoth genetic traits like a woolly coat and the ability to live in a cold climate. This includes genetic variations for altered haemoglobin – the molecule that carries oxygen around in the bloodstream – along with extra hair and fat.

So far Church and his team have managed to engineer some of these mammoth genes into elephant cells growing in the lab, although we are still a long way from seeing these mighty beasts roaming the artic circle once more.

Scaling up further still, the ultimate prize is still resurrecting dinosaurs, a la Jurassic Park. But although scientists found what looks a lot like red blood cells in a fossilised dinosaur bone in 2015, there was no DNA.

And even if it did turn out to be possible to get hold of dinosaur DNA, de-extinction will be much more difficult as dinosaurs don’t have such close living relatives as the passenger pigeon or the woolly mammoth.

Reverse engineering 66 million years of evolution is probably almost impossible, and even if you did manage to assemble a full dinosaur genome, good luck finding a suitable surrogate mother!

Closer to home, George Church has also discussed bringing back our own human ancestors, the Neanderthals from extinction using this method. Parts of the Neanderthal genome exist in our genome, while other bits have been recovered from ancient bones. However, we don’t have anything resembling a full genome right now.

And that’s not really the biggest problem with this approach to bringing long-dead species back to life. As well as the technical issues surrounding de-extinction, there are also philosophical ones.

Does gluing bits of mammoth DNA into their modern-day relatives really recreate the species? Or are these creatures just hairy, fat, cold-resistant elephants? And what about the ethics of bringing back long-vanished species into a world that may have changed dramatically since they was last alive?

More broadly, we don’t fully understand the implications of de-extinction. Bringing these long-lost animals back doesn’t end when they’re born or hatched – they need an environment and ecosystem that can support them, which might be long gone in some cases.

They also need protecting from harm, whether from humans, habitat destruction or climate change. There’s also the issue of disease – for example, what happens when a woolly mammoth doesn’t have its native gut bacteria or the parasites that it had in prehistoric times?

So is de-extinction really worth it? Is there any point in bringing back animals just for them to quickly die out again? Listening to Alberto Fernández-Arias talk about his beloved bucardos, it’s undoubtedly worth all the effort to him to see these beautiful goats back in the wild.

Based on his experiences with cloning from frozen cells, it’s arguable that the main scientific focus should be on recently extinct creatures that are easier to bring back and could realistically recover in an environment that’s similar to the one they left behind.

It’s here where I have my doubts about the benefits of resurrecting Neanderthals. Most scientists agree that Neanderthals would not be well suited to surviving in the modern world, and I certainly would be ethically uncomfortable with the idea of experimenting on a hominin species so closely related to our own.

However, for the sake of the planet and our own survival as a species, it might be worth trying to bring back animals that can support ecosystems and perform functions that no other animal does, like the passenger pigeon or even the woolly mammoth.

Alternatively, rather than thinking about wholesale de-extinction, we could look into the genomes of ancestral species for specific genes and variants that might be useful for survival and conservation in the modern world.

And, of course, maybe we could put some more of that attention and effort towards stopping species going extinct in the first place.

References and further reading: