National Geographic

Resurrecting the Extinct Frog with a Stomach for a Womb

Two years ago, Mike Archer from the University of New South Wales looked down a microscope and saw that a single fertilised frog egg had divided in two. Then, it did it again. And again. Eventually, the egg produced an embryo containing hundreds of cells.

“There were a lot of hi-fives going around the laboratory,” says Archer.

This might seem like an over-reaction. After all, millions of frog eggs divide into embryos every day, as they have done since before dinosaurs walked the earth. But this egg was special. Archer’s team of scientists had loaded it with the DNA of the southern gastric brooding frog—a bizarre creature that has been extinct for almost 30 years.

The fact that it started to grow into an embryo was a big deal. The fact that it never went further was disappointing, but not unexpected. This is cutting-edge science—cloning techniques put to the purpose of resurrection.

Archer’s goal is simple: To bring the extinct gastric brooding frog back from oblivion and, in doing so, provide hope for the hundreds of other frogs that are heading that way. Getting the embryo was a milestone and Archer is buoyantly optimistic that he’ll cross the finish line soon. Lazarus, he says, will rise again.

Frozen southern gastric brooding frog. Photo by Bob Beale

Frozen southern gastric brooding frog. Photo by Bob Beale

Stomach for a womb

The southern gastric brooding frog (Rheobatrachus silus) was discovered in 1972 in the mountains of Queensland, Australia. But the world only took notice of it in 1974 when Mike Tyler discovered how it reproduced.

Simply put, the mother frog converts her stomachs into a womb. She swallows her own eggs and stops making hydrochloric acid in her stomach to avoid digesting her own young. Around 20 to 25 tadpoles hatch inside her and the mucus from their gills continues to keep the acid at bay. While the tadpoles grow over the next six weeks, mum never eats. Her stomach bloats so much that her lungs collapse, forcing her to breathe through her skin. Eventually, she gives birth to her brood through “propulsive vomiting”, spewing them into the world as fully-formed froglets.

When news broke about this weird strategy, other scientists were incredulous. Tyler provided vivid accounts of a young frog poking its head out of mum’s mouth like an amphibian Russian doll, but even these were insufficient. “It just seemed to many zoologists absolutely impossible,” he later wrote in a book. “There were frequently insinuations that somehow we were wrong.”

It took many years, field surveys and photographs to persuade the naysayers. Tyler eventually published a full description of the frog and its behaviour in 1981. (Nature rejected the paper because they—wrongly—deemed it uninteresting.) The medical community took notice. If this creature could deliberately stop making acid in its stomach, it might provide new ways of treating stomach ulcers or helping people who go through stomach surgeries to heal more quickly. Several teams started studying the frog.

They didn’t have long. “There was intense interest and all of a sudden it was gone,” says Archer. The last specimen was seen in the wild in either 1979 or 1981 and despite extensive field surveys, none was ever found again. The last captive individual died in 1983, and the species was no more.

Then, good news! A second species—the northern gastric brooding frog (Rheobatrachus vitellinus)—was discovered in 1984 in Queensland’s Eungella National Park. But a year later, almost before anyone could uncork the celebratory champagne, it too went extinct.

Archer, however, is in the business of de-extinction. He’s going to clone the southern gastric brooding frog back into life.

A barred frog provides surrogate eggs for cloning the southern gastric brooding frog. Photo by Bob Beale

A barred frog provides surrogate eggs for cloning the southern gastric brooding frog. Photo by Bob Beale

Cloning Lazarus

Archer has several reasons for trying. There’s the medical potential. There’s the unusual nature of the frog’s life cycle, which no other animal shares. But really, it’s a more “transcendent reason” that drives him. “If we were responsible for the extinction of the species, deliberately or inadvertently, we have a moral responsibility or imperative to undo that if we can,” he says.

But hang on–no one really knows why the frogs disappeared or if we played any role. Human forestry might have contributed. Alternatively, the lethal chytrid fungus that’s currently triggering a global frog apocalypse might have claimed the gastric brooders as early victims. But Archer still holds to his “moral imperative” argument. He also figures that restoring the frogs might help to inform his other efforts, like a project to resurrect the thylacine—Australia’s charismatic “Tasmanian tiger”. “Maybe it would be easier to get something like the frog across the finish line,” he says. “And then people who were so negative might take a deep breath and back off.”

To clone the gastric brooding frog, the team first needed its DNA. Archer called up Mike Tyler, who rummaged through his freezers and found some old tissue samples. They were in shoddy condition—just bits of frog dropped in a container, without any antifreeze to protect them. The cells should have been useless, ruptured sacks but they had somehow stayed intact. “We thought it was worth a try,” Archer says.

The team then needed something to put the DNA into—the egg of another frog. He chose a barred frog—a reasonably close relative that produces large eggs of the right size. The downside—and it’s a big one—is that barred frogs only lay eggs once a year. “We had a few times when we went in and the frogs weren’t laying, and that was that for the year,” says Archer.

Once the team had their surrogate egg, they had to destroy the native nucleus so they could insert one from the frozen gastric brooding frog tissues. They either did the job manually with a very fine instrument, or bombarded the egg with ultraviolet (UV) radiation. They tried both techniques on hundreds of eggs and one of these eventually divided into an early embryo with hundreds of cells.

Every time the team has done this, the ball of cells starts to turn inwards on itself—a crucial moment called gastrulation—and stops. That’s where they are for now. They have the beginnings of a gastric brooding frog, but are a long way from even a simple tadpole.

Still, Archer is hopeful.  Whenever he has gone through the same technical motions with a living frog, and inserted the species’ nucleus into its own egg, the resulting embryo also paused at the same point. This suggests that there’s something wrong with the team’s techniques, rather than with Tyler’s frozen gastric brooding frog tissues. Busted tissues would be a deal breaker but technological problems can be fixed, and Archer has brought in stem cell expert Robert Lanza to help him do so. “We retain our vibrant optimism,” he says.

Southern gastric brooding frog, by Peter Schouten

Southern gastric brooding frog, by Peter Schouten

Is it worth it?

Archer has faced his share of naysayers, from those who think that the technological hurdles are too great to others who believe that restoring the dead is a vanity project. “If you were thin-skinned, you’d race to the corner and give up,” he says.

Some of the arguments against de-extinction don’t apply to the gastric brooding frog. Unlike the woolly mammoth or passenger pigeon, the frog isn’t a social creature that would need companions to learn from or travel among.  Unlike the mammoth, which would need to be born inside an elephant, the frog doesn’t need a complicated surrogate parent.  And unlike many of the candidates for de-extinction, like the moa or saber-toothed cat, the frog is small and can be reared in a laboratory. Archer has so much frozen tissue that once he successfully clones one frog, he could make a practically infinite supply of them.

“It seems like a good choice as a test case for many reasons, and I think is very defendable choice from scientific and ethical viewpoints,” says Karen Lips from the University of Maryland, who works on conserving living amphibians.

Archer believes that the project is not just defensible, but necessary. Frogs are in such a bad way that some conservationists are already trying to preserve tissue samples in a genetic ark, with a view to cloning these species should they ever disappear completely. “Everyone blissfully takes for granted that we’ll be able to do this down the line but no one has shown that you can,” says Archer. “This work will be relevant to the rest of the frogs around the world and possibly to animals of all kinds.”

Let’s assume Archer succeeds. Where would the new generation gastric brooding frogs live? Their habitat in the Queensland mountains is being threatened by feral pigs, invasive weeds and polluted or diverted waters. And then there’s the chytrid fungus, which has spread to almost every part of the world. It would be like releasing Lazarus into an ecological dystopia.

Archer is unfazed. “We can ultimately fix the wild,” he says. “Even if we had to maintain most of the world’s wildlife in artificial environments, that would be a thousand times better than to let them slide off the brink.” The frogs can wait until their homes are ready for them. In the meantime, scientists could perhaps engineer or breed them to be resistant to the chytrid fungus, or carry out experimental releases to see whether they would actually find a niche in this brave, new world.

But Lips argues that this is impractical. “Zoos are extremely limited in space,” she says, and the resurrected frogs would have to compete with the thousands of other amphibian species that are facing extinction—around 40 percent of the 7,000 or so that we know of. “We can’t keep them all in captivity at sufficient numbers to maintain genetic diversity.”

Lips has another concern: Resurrection projects take up a lot of money. Archer concedes that cloning research is initially expensive, but he says that costs will eventually fall. “I can’t think of what cloning Dolly must have cost and now it’s a routine technique,” he says.

Still, funding is a zero-sum game. There’s only so much cash to go around and conservationists need it to monitor animals that are still alive, work out why they are disappearing, and develop ways of saving them. There are plenty of cases where we know how to save a species, but can’t afford to do so. “I can’t help but think that we can’t even take care of what we’ve got, and now we’re going to invest in very expensive techniques to recover a handful of special-interest species that may or may not be able to survive in the wild on their own,” says Lips. As a best-case scenario, she hopes that these high-profile projects will help to drum up interest in saving a broader swathe of imperilled wildlife.

Archer sees it slightly differently—the plight of living species gives him even more recourse to bring back extinct ones. “No matter how many resources we put into looking after the environment, wildlife is no longer safe in the wild,” he says. “If we accept that maintaining biodiversity is important, we can’t assume that if you whack a fence up, everything’s going to be okay. You need to explore lots of parallel strategies.”

There are 31 Comments. Add Yours.

  1. Noumenon72
    March 15, 2013

    I really like how you present the two sides of this one! It’s kind of a problem with government funding, that everyone thinks they’re competing with everyone else. People who get money from customers are using resources other people want too, but it doesn’t feel as zero-sum.

  2. Tom
    March 15, 2013

    This frog does seem like an ideal candidate for all the reasons stated in the story. Should they do it? Absolutely! Should we do a better job protecting species that are still around? Absolutely! Should we also invest in better human contraception? Absolutely!

  3. John
    March 15, 2013

    Just by bringing back one species you could save lots more. If that one species was to take root establish a breeding population and multiply it could provide food for other species that might have otherwise died off cause of their food source going extinct. If it was a eucalyptus tree going extinct and you manage to save it in doing so would also save the koalas.

  4. Scott
    March 15, 2013

    I had an old highschool textbook that had some information on the gastric brooding frog, saying that it was only endangered, not extinct!!! Came as a surprise that this was so… If they ARE gonna start bringing these neat lil creatures back, maybe the scientific community out to figure out what’s made the chytrid fungus so prolific, and mitigate that, before anything else is done. Amphibians are biosphere health indicators, and when they’re in trouble, everything is.

  5. Angie Biotech
    March 15, 2013

    What a fantastic project, if for better reason than to stretch the limits of our technology and see where they can go. Does anyone, perchance, have links to the publications of these experiments? I’d be very interested int eh exact cloning methods being used, and whether manual insertion or UV produced better results.

    [They're not published yet - Ed]

  6. David
    March 15, 2013

    I don’t know much about it, but maybe the frog egg needs something special for his development and that’s why it only lays eggs once every year, perhaps its a certain climatological emboirement, or some sort of fungus or other chemical released by some other thing…

  7. Julie
    March 15, 2013

    Please give us an address where we can donate to this wonderful experiment! I would hate to see if fail for lack of funding.

  8. Jonathan So
    March 15, 2013

    funding is a problem? well, I suppose they can always try Kickstarter. There may be enough interest.

  9. Alene
    March 15, 2013

    Doesn’t anyone wonder that technology is being relied on too heavily? He nonchalantly points out they can save all manner of frogs heading for extinction – but should we? Will the, oh, don’t worry, we’ll cook up more in the lab state of science make us put less emphasis on protecting our environment? I’m seriously troubled that science is taking us in this direction. At least, in some arenas.

  10. Lee Richards
    March 16, 2013

    I am a raging ranophile, so I am all for the preservation and resurrection of any frog. I believe learning the procedure is important, even if the environment is unavailable. Quite frankly, the frog is photogenic and its reproductive cycle is memorable, which draws attention to both the science (funding) and the threats to amphibians (conservation).
    My thought on the egg growth is that some environmental stimulus is lacking; the eggs develop in a stomach of a frog that goes without eating, probably while in a state of hibernation. The purpose of gastric brooding is to ensure the development of tadpoles into froglets in a very dry environment. There are probably some very specific biochemical cues that stimulate egg development that come from the female (I had always thought it was the male that swallowed the eggs).

  11. James IV
    March 16, 2013

    Am I the only one here who’s having doubts. Like maybe these extinctions have or will happen for a reason.

    Never the less this is fascinating (and now I get flashbacks to Jurassic Park)

  12. Chi
    March 16, 2013

    They might need to be incubated in an artificial stomach.

  13. Roland Harding
    March 16, 2013

    I grew up in rural Rhodesia (Zimbabwe) as I read this article clearly remember frogs becoming really large then baby’s in their mouth thought it was a way to protect them like crocodiles may be not – possibly there is another frog you need to find

  14. Amy
    March 16, 2013

    I like the idea of bring back extinct species, I also I the idea of reverse evolution in egineering species. However, I do share some of the fears voiced by Alene. But my premise in being weary of such manipulation is Should we do it? Is thinking such as ““We can ultimately fix the wild,” he says.“Even if we had to maintain most of the world’s wildlife in artificial environments, that would be a thousand times better than to let them slide off the brink.” The frogs can wait until their homes are ready for them.” really a valid approach to nature? Can the frogs really wait? can we really fix the wild? This statment particularily scares me because we somehow think nature can be controlled. Point is nature is random for a reason, species die out so others may evolve. and nature/’the wild’ fights back when assualted by something that does not belong. So while I like the idea and approve of the work for the purposes to learn and understand how such a cloning process will be accomplished successfully. I do not think this should be the norm by any means, as in we do not and should not try to maintain populations of these newly recreated species, please tell me what would be the purpose of that especially if there is no where for them to go!!

  15. Cameron Turner
    March 16, 2013

    Similar to the post by Noumenon72, I think it’s important to point out that new and unusual research like this can actually be the exact reason why funding is NOT a strictly zero-sum game. The post by Julie (asking how to donate money) reiterates this: sometimes new and unusual research draws in new funding sources that weren’t already in the game. Thereby enlarging the cake rather than slicing it more thinly. I think amphibian conservationists can be hopeful that this research will attract some new funding to our efforts rather than increasing competition for existing funds. And what a weirdly cool species to try resurrecting.

  16. Lil’
    March 16, 2013

    Very interested in this as a fan of amphibians, but also an avid fish hobbyist. Some cichlids and other fish are extinct or heading fast down the path and this could save so many wonderful creatures, such as the Australian Hand Fish. Gosh I love science :)

  17. Donna
    March 16, 2013

    Zoos out of space? Give them to hobbyists. WE will take care of them, and in sufficient numbers to ensure their survival into the future. Set up genetic records from the start, and with careful instruction, we’ll keep them. Private citizens can and do contribute to conservation.

  18. chascpeterson
    March 16, 2013

    While the tadpoles grow over the next six weeks, mum never eats.

    In case this seemed contradictory to anybody else: the eggs are apparently supplied with sufficient yolk to support the entire process of development through metamorphosis.

  19. Choti Singh
    March 16, 2013

    for all you ‘ranophiles’ out there go to savethefrogs.com to see what you can do to keep amphibians alive!!!

  20. Richard Pearse
    March 17, 2013

    I’d like to emphasize Chi’s previous comment for the researchers in case they missed it. most frog embryos developed great ex vivo, but this one would almost certainly require a modified frog stomach environment.

  21. Fang Ewe
    March 18, 2013

    Maybe the problem is not with the technique but the environment, since the eggs are in the stomach, maybe the mother releases something that induces the embryos to develop further. A simple test using other species but identical methods for cloning would identify whether it is a technological problem.

  22. Liath
    March 19, 2013

    Thank you Choti Singh. And thank you Ed. Your articles are always appreciated.

  23. Evan
    March 19, 2013

    I didnt know that ther can be frogs like this I love science

  24. MJ
    March 19, 2013

    next topic: should we clone and resurrect the mummies…

  25. Jasmin
    March 22, 2013

    At the point when it stops suddenly,I think that is the point when it should be inside the frog’s stomach or an artificial frog stomach for it to grow. Otherwise it will just stop there.It needs the correct environment for it to grow.Maybe that will help.The artificial frog stomach must also have what the embryos need to continue developing, like what Fang Ewe said. Maybe you should find out what that is,then introduce that substance to the embryos either in an artificial stomach or an environment that it can survive.

  26. Fish
    March 22, 2013

    Everyone’s comments here, regardless of perspective, are unrealistically civil.

    I think that the research should be done and funded, as far as it can be taken. Scientists notes are often catalysts for tomorrow’s discoveries, be then next year or decades, or centuries from today. There are no dead ends in science, perhaps to individual hypothesizes, but the scientific community can learn so much from others “failures”, incomplete works, progress,,, and if this man never succeeds at all, he could be the precursor to legitimate species management, resurrection, and fortification. So the frog has no home. The frog is only inspiration, and you must take into account all of God’s creatures, and our outsized responsibility to the world we exploit, rightly. I lost my train of thought, this widow is so small, but also, ulcers, must be stopped.

  27. Buyun
    March 22, 2013

    Have you tried serial nuclear transplantations? Have you sequenced the cells in the gastrula? Have the gastric brooding frog eggs ever been shown to develop outside the mother? If not, it might not be this might not be the wisest venture…

  28. Zeegert
    March 24, 2013

    Archer is right. If it is possible to try, try it. If you succeed a species, or at least it’s unique DNA is saved. If you don’t succeed humanity will have learned more.

  29. Karyn
    April 12, 2013

    I think you should try. After all, we are guilty of killing them so we should bring them back.

  30. shanny thomson
    April 21, 2013

    this is so cool!! i love frogs

  31. Michelle Davila
    July 9, 2014

    As a biologist, I don’t think it’s realistic or wise to bring back a species. Will enough genetic variety be available to prevent a bottleneck effect on the population you’re producing? How will the new frog populations interact with the environment, will they be able to adapt and reproduce successfully? How will they find and capture prey? While a lack of parental care may signal that these behaviors are largely instinctive, the environment they were adapted to has changed. If they went extinct in the early 80s, the environment they once called home will likely be unrecognizable–what I mean by this, is that there may not be adequate stimulus from the environment to trigger the “appropriate” instinctive responses. Perhaps the niche that these frogs filled has been taken by another organism and they will no longer have the genetic diversity to adapt to another niche or compete/share the niche. While there may be several samples of frog tissue, what is known about the relatedness of the individuals the tissue comes from? It would be impossible to replicate the original genetic diversity, and very difficult to approximate it–what was the original population like and how genetically variable was it?

    Additionally, we don’t know what caused their extinction. While all organisms are valuable in their own right, regardless of medical or miscellaneous knowledge we can gain, every organism is tested by the process of evolution. It is selfish and arrogant to decide, and think we can/should decide, which species should be brought back and which deserve our interference. If they went extinct, it’s likely due to several reasons working together. Without knowing any of the causes for extinction, we can’t discern the proximate or distal/ultimate causes. Without knowing any of these causes, how could we possibly prevent their extinction after cloning a population? If we were to clone and produce a population, only to have it go extinct, what would we learn? When do we stop bringing back a species or population?

    If the point of reinstating a species isn’t to bring it back to the wild, but to use them for research purposes, that would be another matter. A very different matter, with its own issues. Additionally, if the goal is to engineer or genetically manipulate the species to better suit the environment–this too has serious ramifications. I feel this takes evolution and its intricacies too lightly. Will these frogs be tomatoes, bred for certain environments and traits? Evolution is a process with no end. If we were to invest in a species or population and attempt to help it adapt to its environment, this would be a never ending battle. Again, agricultural examples (as well as ornamental) come to mind. Such tactics would likely further reduce their genetic diversity, the major issue I would take with such a feat, as I mention earlier.

    I think that such research may come from a good place; there are many endangered species that would be amazing to save and potentially “keep safe” through genetic means. My personal favorites, the big cats, are surely headed for extinction. Cheetahs, as part of their natural history, have already gone through a population depleting event and so already exhibit some of the detrimental traits of a population affected by a bottleneck event. While we may be able to slow their extinction, preventing it would be much more difficult. It is also questionable whether or not we should. As a person, I would definitely try to prevent their extinction. As a scientist, I don’t know that it’s a good idea.

    I simply do not think we should act as if we can master and control evolution.

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