For more than 3 billion years since single-celled organisms first appeared on the planet, life has evolved in one direction only. When a plant or animal becomes extinct, there is no coming back. Or so we thought.
Two weeks ago Australian scientists revealed they had reversed natural selection. Not only had the aptly named Lazarus Project group revived the genome of an extinct species, the gastric-brooding frog, they had also grown embryos containing the bizarre amphibian's DNA - the crucial first step in their attempt to resurrect a dead species.
The head of the team, University of NSW palaeontologist Mike Archer, announced his team's milestone at the Tedx DeExtinction event in Washington in front of international peers pursuing the same goal with other long-dead creatures - the passenger pigeon, woolly mammoth and Spanish ibex.
What stands out about the Australian team, however, is the pace of their progress. While other groups are years, more likely decades, from achieving their goal, the Lazarus team could have a gastric-brooding frog hopping back to life in the next few years.
The precise motivation for reviving a species, a process some call de-extinction, differs among its revivors, but a central theme exists. Aside from the wow factor, Archer says, scientists hope their attempt to turn science fiction into reality will help conserve the world's ever diminishing biodiversity.
Cloning technology could not only bring back extinct species, especially those vanquished by humans, it could also play a vital role conserving critically threatened plants and animals living today.
"If it is clear that we exterminated these species, then I think we've got a moral imperative to try to do something if we can," Archer says.
As with all endeavours that challenge the natural order of things, de-extinction has critics. Some conservationists fear the ability to revive species will distract from current efforts to rescue the vast number of endangered, yet living, creatures.
Others wonder what environment revived species will be born into. If the reason they became extinct in the first place still exists, would we be resurrecting plants and animals only to watch them endure the same fate?
Mike Tyler's first encounter with the gastric-brooding frog came in 1974 when he received a call from a pair of Queensland schoolboys who had collected a frog with a bizarre method of gestating its young.
Female frogs swallowed their fertilised eggs and transformed their stomach into a uterus where the young would metamorphose from tadpoles into baby frogs. Close to bursting, the mother would then regurgitate her offspring one by one.
"My feeling was that we were looking at something remarkable," says Tyler, a herpetologist at the University of Adelaide.
Tales of the bizarre creature quickly sparked the interest of the medical fraternity, who looked to the species for insights into how to treat stomach disorders.
But, just as this interest piqued, the frog vanished from the wild in 1979, mostly likely a victim of habitat destruction and the human-spread chytrid fungus that continues to decimate global frog populations today.
When the last two adult frogs Tyler raised in his laboratory died in 1983, the species officially became extinct. Even though it would be years before scientists would attempt to clone a mammal, let alone an extinct species, Tyler had the foresight to preserve a gastric-brooding frog in his deep freezer. "I thought it was a very special creature. At least I'd have material other people could use in the future," he says. Years later Tyler told Mike Archer of his frozen specimen. Lazarus' resurrection could begin.
Over the past five years, the team's Monash University genetics specialists, Andrew French and Jitong Guo, have painstakingly inserted single cells containing the DNA of the frozen frog into hundreds of donor eggs from a distant relative, the great barred frog, whose own DNA had been deactivated by UV light. In the beginning, the single cell frog eggs "just sat there", Archer says.
"But then, all of a sudden, one of the cells divided, and then it divided again, and again ... There were a lot of high fives around the laboratory at that point," he says.
The cloning technique, known as somatic nuclear cell transfer, was used in 2003 by Spanish scientists to resurrect a recently extinct native goat - it survived for 10 days - and was similar to the process used to clone Dolly the sheep.
In the lab, the Lazarus cells continued to divide into three-day-old embryos. But then they died. Genetic tests revealed the embryos, known as blastulas, contained the DNA of the extinct frog, so the team is confident its extinct genome is functioning. "We know not all embryos survive," says French.
The quality of the donor egg, injecting the extinct DNA, even the jelly that cells are cultured in can influence their survival, he says. "The planets just have to align on the day."
While the team is yet to bring back the bizarre amphibian, the success so far can prevent other frogs becoming extinct. "The project is much bigger than the gastric-brooding frog," says Simon Clulow, the team's youngest member and expert frog wrangler from the University of Newcastle.
With each species that is extinguished from the planet, a little piece of diversity is lost forever. But the story need not end there, says Clulow. If the team succeeds in cloning a gastric-brooding frog using a close relative as a scaffold, it demonstrates cross-cloning one species with another is possible.
One of Clulow's greatest passions is advocating for a national gene bank, which stores the tissue of endangered species that could be used to prop up dwindling wild populations or, should the creature go the way of the dodo, allow it to be revived later. "This project provides irrefutable evidence that gene banking is valid," he says.
But for University of Adelaide ecologist Corey Bradshaw, attempts to resurrect extinct animals detracts from efforts to conserve critically endangered species because it fails to solve the drivers of extinction. Species revived from a few specimens would contain little genetic diversity, making them vulnerable to future threats and at risk of becoming extinct again.
"It's not solving the real problem," says Bradshaw. "If we encourage this sort of behaviour, it's a massive financial distraction."
Clulow disagrees, saying the Lazarus project was inexpensive compared with other scientific endeavours and the money was donated from entrepreneurs and philanthropists such as Dick Smith and geneticist John Shine. "We haven't touched a cent of public money," he says.
With thousands of species around the world under threat, mainly from habitat destruction and disease, Archer wants to assist attempts to save them, not sidetrack them.
"I'm exploring every conceivable initiative that's going to optimise conservation, not only for species that are struggling to survive today but potentially even some of the ones that are lost," he says.
What makes a species an ideal candidate for revival depends on who you ask. Most proponents agree the decision needs to consider whether it is technically feasible - is there functional and intact DNA, is there a close relative to donate an egg - and whether it would be practical to reintroduce the animal to the wild.
Given DNA decays over time, 65-million-year-dead dinosaurs will not make a return appearance. Jurassic Park remains science fiction.
Neither would it be sensible to resurrect species whose habitat has disappeared or changed dramatically, says Ryan Phelan, a founder of the Revive & Restore project, part of the not-for-profit Long Now Foundation.
The organisation has chosen the iconic passenger pigeon, which once flocked across North America in their hundreds of millions, as its keystone revival species.
The project's leader, Californian geneticist Ben Novak, says many factors make the passenger pigeon a perfect contender: its genome is shorter and more manageable than mammals, and it performed a vital "biological dance" within forest ecosystems before hunters blew them from the sky. "These dense flocks would come in to roost, depleting resources, fertilising the ground, letting sunlight in and allow many other animals to flourish," says Novak.
But unlike the Lazarus team, who recovered a complete sequence of intact DNA from frozen frog tissue, Novak has only fragments of the passenger pigeon's genetic blueprint. Other groups, including a South Korean team trying to revive the woolly mammoth, face similar problems.
Even with a full passenger pigeon genome, Novak's team would still face the bigger hurdle of how to insert its DNA into a donor embryo and implant that into a surrogate mother, given chicks develop inside hard-shelled eggs.
But the team, which includes world-leading Harvard geneticist George Church, sees these issues as workable challenges.
Their plan, broadly speaking, is to sequence many fragments of passenger pigeon DNA from museum specimens and compare them with the genome of the bird's closest living relative, the band-tailed pigeon, to reveal the extinct bird's most important traits.
This information is then fed into a specialised sequencing technology, developed by Church, which can manufacture part of the passenger pigeon's genome by rewriting sections of the band-tailed pigeon's DNA.
If they succeed, the edited sequence could be inserted into the genome of stem cells of another close relative, the common rock pigeon. These stem cells could then be coaxed to form germ cells - sperm or egg cells - that could then be inserted into the developing embryo of its cousin, in the hope the cells migrate to the chick's sex organs.
If this works, the chick would carry the doctored DNA of the passenger pigeon, and if bred with another such bird would create a chick with passenger pigeon traits.
The features could be selected for subsequent generations until the team produced a bird that is, to all intents and purposes, 99 per cent passenger pigeon.
"It's my job to bring the passenger pigeon back to life, not as a science novelty or a zoo attract, but back into the skies above," says Novak.
But reintroducing extinct species into the wild is a major concern for some conservationists, who say ecosystems transform, some to a greater extent than others, when species go extinct.
David Bowman, an ecology professor at the University of Tasmania, says bringing back an extinct species raises the same issues as introducing non-natives.
Bowman's not against the idea of introducing foreign species to perform critical roles within an ecosystem - last year he suggested Australia introduce large herbivores such as elephants to contain introduced grass species taking over the continent's centre - but bringing back species from the dead is expensive, and will likely face opposition from the public.
He cites the community angst surrounding the introduction of the beleaguered Tasmanian devil, which remains in the land of the living, but only just, onto Maria Island as an example. "People think the devil might endanger other animals because it's not native to the island," says Bowman.
Mike Archer, who has previously led an attempt to revive the Tasmanian tiger, has heard all these criticisms before, but he won't be deterred.
"It's the 'You can't do it' zone that attracts me," he says.
Waking the dead
Revival projects underway
Things to consider
Is there any preserved tissue of the species, does it have a manageable sized genome, does any of its habitat still exist, has the original cause of its extinction
Dodo, Chinese river dolphin, New Zealand giant moa, Cuban red macaw