How Cannibalistic Tadpoles Could Curb Invasive Cane Toads

Scientists used gene-editing technology to create “Peter Pan” tadpoles that would eat the eggs of Australia’s cane toads—and never grow up.

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• 0:00Speaker 00

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• 0:14Flora Lichtman?

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• 1:01Flora Lichtman?

  Hey, this is Flora Lichtman, and you're listening to Science Friday.

• 1:07Flora Lichtman?

  Today in the show, engineering cannibalistic tadpoles to solve an invasive species problem.

• 1:14Speaker 02

  This is the first time that I've felt some optimism that we could actually do something about controlling cane toads.

• 1:25Flora Lichtman?

  Cane toads are one of Australia's most destructive invasive species. Picture a football-sized brown toad with poisoned skin. So animals like dogs, snakes, even crocodiles will die if they try to eat them. And scientists have been trying for decades to reduce their population. Now researchers have turned to the gene-editing technology CRISPR to create cannibalistic tadpoles that never grow up and eat their brethren's eggs. You heard that right. So how does this work? And could this be the solution to Australia's cane toad problem? Here to tell us more is Dr. Rick Shine, an evolutionary biologist at Macquarie University in Sydney, Australia, who's leading that effort. He's also the author of the book Cane Toad Wars.

• 2:10Flora Lichtman?

  Rick, welcome to Science Friday.

• 2:12Speaker 02

  Thank you.

• 2:13Flora Lichtman?

  Let's start with some history. How did cane toads end up in Australia in the first place?

• 2:18Speaker 02

  Well, cane toads are native to a big area in South America. And people had the brilliant idea that they might be great to control beetle pests in sugarcane plantations. So they were brought to islands in the Caribbean, then to Hawaii, where they were growing a lot of sugar. And in 1935, the Queensland government sent a chap called Reg Montgomery over to collect 101 cane toads, brought them back to Australia, and their offspring were released in the sugarcane fields of northeastern Queensland.

• 2:50Flora Lichtman?

  And what kind of damage have they done? And what makes them so destructive?

• 2:56Speaker 02

  The big problem we have is that Australia is so isolated from the rest of the world that we don't have any native toad species. You know, there are toads over most of the world, but Australia didn't have any native toads. And toads have got a really distinctive set of chemical defenses, poisons called bufa toxins. And if you haven't evolved side by side with toads, and you're a predator that eats frogs, you come along when you see this great big brown wartie new kind of frog that's turned up in your backyard, you eat it and you do have a heart attack almost instantly. So we've had massive mortality of some of the big apex predators in Australian tropical ecosystems.

• 3:38Speaker 02

  Creatures like our goannas, our big voranid lizards, some of the biggest lizards in the world, quolls that are a marsupial predator, the size of a cat, some of our big lizards and snakes as well, and crocodiles. So there's been devastating mortality of some of the apex predators.

• 3:57Flora Lichtman?

  And have cane toads themselves evolved since arriving in Australia?

• 4:02Speaker 02

  Yeah, look, it's a remarkable story of rapid evolution. We used to think that evolution was a slow process, but invasive species have shown us that, under the right conditions, with new kinds of evolutionary challenges, a species can change incredibly fast. So the cane toads at the invasion front in Western Australia are very different in their body shapes, their physiology, their reproductive biology, their behaviour.

• 4:29Flora Lichtman?

  Including cannibalism, am I right?

• 4:32Speaker 02

  Yeah, so remarkably, the cane toads within Australia display intense cannibalism when they're tadpoles. If a cane toad tadpole is sitting in a pond and it detects a female toad has come along and laid her eggs into that pond, then the toad tadpoles race across and they eat those eggs, they kill them. And so it's incredibly intense cannibalism. It can wipe out 99% of any newly laid eggs. They're very abundant in Australia and so cane toads have to compete with other cane toads for food. If you're a tadpole and there's 20,000 new eggs just been laid in your pond, you're going to be in big trouble in terms of food supply unless you get rid of the competitors.

• 5:14Speaker 02

  That's not true in the native range and so the toad tadpoles in South America and Hawaii really are not very cannibalistic at all.

• 5:22Flora Lichtman?

  So your team created something called a Peter Pan tadpole. What is that?

• 5:28Speaker 02

  Okay, so we named it after the fairy tale character who never grows up. And that's exactly what we're creating here. We've gone in using CRISPR, we just inject a newly laid toad egg and we knock out a genetic pathway that produces a hormone that a tadpole needs to turn into a baby toad. If it doesn't have that hormone, it simply can't make that transition. And as a result, those gene knockouts simply live in the pond forever. They never turn into a baby toad, they simply live there as tadpoles. And if any other toad comes along and lays her eggs in that pond, the Peter Pans are there ready to eat them all.

• 6:06Flora Lichtman?

  And so you've used CRISPR to make this genetic modification to the cane toad?

• 6:12Speaker 02

  Yeah, look, absolutely. I think it's really critical to point out that this is just a gene knockout. A lot of people are very concerned about using CRISPR for biocontrol. They worry about transgenics, where you take genetic material from one organism and you put it into a different organism. You create something that doesn't occur in nature. But this is a simple mutation. This is just like something that happens probably in every clutch of cane toads that's ever been produced in the last few million years. There's always a few sad little tadpoles that don't transform. We're just making that happen on a major scale now so that we have a whole lot of non-transforming tadpoles.

• 6:51Flora Lichtman?

  And then what's the ultimate goal? How do they help with this invasives problem?

• 6:55Speaker 02

  Well, the fundamental problem with cane toads is to stop them from recruiting from a pond, from reproducing. You can go out there and kill adult toads, but a single female can have 20,000, 30,000 eggs. So you really have to stop that breeding. And the Peter Pans can do that. If you've got a pond with Peter Pans in it, then there can be no toad breeding from that pond until the Peter Pans finally die of old age. And so it's a relatively efficient way to stop a pond being a source of new toads. You know, you can go in there and trap tadpoles and the like, but that takes a heck of a lot of work. The Peter Pans will do that work for you.

• 7:32Flora Lichtman?

  What does success look like?

• 7:35Speaker 02

  I think success will look like a pond with Peter Pans in not producing all those little recruiting metamorphs hopping around the water's edge. Whereas the pond next door, where we haven't deployed Peter Pans, will have several thousand metamorphs. So that'll be the first step.

• 7:53Flora Lichtman?

  And then where are the rest of the challenges? I mean, can you scale this up to put Peter Pans in every single pond in Australia? I mean, every puddle that a cane toad might reproduce in?

• 8:05Speaker 02

  At the moment, the plans are all about coming up with a system that will work in selected sites where you can put the effort in. And in particular, we'll be looking at the semi-desert regions where they're restricted to a very small number of artificial ponds. They're the only places the toads can breed. And so we can take them out of the equation. We may be able to eradicate cane toads from hundreds and hundreds of square miles. Similarly, on small islands where there's only a few ponds, we could get rid of toads there. That would create real sanctuaries for biodiversity. So I think we'll start out small. We'll pick the areas where the method is most likely to be powerful. And then we'll start looking and thinking and dreaming and hoping that we can find a way

• 8:49Speaker 02

  to scale it up to cover a much larger area.

• 8:53Flora Lichtman?

  Obviously, there's a history of humans intervening in the natural environment and things going wrong, like how cane toads got to Australia in the first place. What are the things that you're worried about, that you're sort of testing for, that you're on guard for with this?

• 9:09Speaker 02

  Yeah, look, I think there's a very long and humbling history of scientists who think they understand it all well enough and they go ahead and do something and it has unintended consequences. And the cane toads are the classic example of exactly that problem. So we're moving very slowly and carefully. We have an enormous amount of background information about the ecological functioning of cane toads and their impacts on native fauna. But what we'll do is continue to run a whole series of trials, beginning in the lab and moving out to outdoor enclosures and finally to isolated water bodies where we deploy Peter pans and we look very carefully at every imaginable variable that we can think of

• 9:51Speaker 02

  and make sure that we're not accidentally creating problems. So far, it's looking great. But we have to proceed slowly and carefully because clearly, you know, I don't want to go down in history as the person that repeated the folly from 1935.

• 10:06Flora Lichtman?

  You know, I read that you started out as a snake biologist and got dragged into this cane toad field because they were eating your study subject. Do you feel like Sisyphus with this?

• 10:22Speaker 02

  Yeah, look, people have been trying to control cane toads in Australia for a very long time and it's failed miserably. You know, the toads are doing very well and continuing to spread. They've gone almost the entire way across the continent. This is the first time that I've felt some optimism that we could actually do something about controlling cane toads. Clearly, you know, right from the outset, when I made the decision to expand the work to look at the toads that were about to massacre my beloved snakes, I was hoping we would find ways to buffer impact and we did that. We've shown that you can train predators and that enables them to survive despite the presence of toads.

• 11:07Speaker 02

  But I always hoped we'd have something that might contribute to toad control and I never thought it would happen. And it seems to be happening. So I'm not going to, you know, break out the champagne yet, but I think it's looking very encouraging.

• 11:22Flora Lichtman?

  Rick, thanks so much and good luck.

• 11:25Speaker 02

  Thank you.

• 11:27Flora Lichtman?

  Dr. Rick Shine is a professor of biology at Macquarie University in Sydney, Australia.

• 11:35Flora Lichtman?

  Don't go away. After the break, New Yorker writer Elizabeth Colbert is here to talk about other similar monumental efforts to control nature and what they tell us about ourselves.

• 11:46Speaker 03

  We want to think of some nice, easy fix that's going to get us out of it. And often that fix turns out to be either extremely elusive or even non-existent.

• 12:01Speaker 00

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• 12:36Speaker 04

  And from the Alfred P. Sloan Foundation, working to enhance public understanding of science, technology, and economics in the modern world.

• 12:49Flora Lichtman?

  Using CRISPR to genetically modify animals, to kill animals that we brought in to kill animals, obviously raises a lot of deep questions about our role in the environment, unintended consequences, rapidly changing technology. What should we make of all of it? To get some answers, we called up someone who's thought about these themes a lot. Elizabeth Colbert is a staff writer at The New Yorker. She's reported on CRISPR and cane toads and virtually every other giant environmental problem and our sometimes out there attempts to solve them. She's the author of "Under a White Sky: The Nature of the Future." Elizabeth, welcome back to Science Friday.

• 13:29Speaker 03

  Thanks so much for having me.

• 13:31Flora Lichtman?

  Can you put Rick's Peter Pan work in context? There's a history to this approach with cane toads, right?

• 13:39Speaker 03

  Well, I visited several years ago, a group also in Australia. And what they were trying to do was genetically engineer with CRISPR, a cane toad that would be less toxic. What cane toads do is they produce a toxin and then they produce an enzyme that really bumps up the toxicity of their toxin by many, many times. And that is what ends up being so dangerous for other animals. When they get agitated, they produce this enzyme. And enzymes are genetically encoded. And their feeling was if we can prevent them from doing that, we will produce a less toxic cane toad.

• 14:17Flora Lichtman?

  How successful were they?

• 14:19Speaker 03

  I think that they've managed to produce, you know, a couple of these less toxic toads, but I don't think it went farther than that.

• 14:27Flora Lichtman?

  Is there controversy around this? Like, how do other scientists or ecologists think about using CRISPR genetic modification to control invasive species?

• 14:37Speaker 03

  Well, there's a lot of interest in it, absolutely, because invasive species are a very significant source of extinction. And genetic engineering has many possible pathways that it could be helpful, as Rick's work shows. The problem that you encounter pretty quickly is, you know, you're dealing with huge, huge numbers. In the case of the cane toad, you know, probably hundreds of millions. And so to do something at that kind of scale becomes very difficult. And it takes you or drives you quickly to this idea of gene drive, which is not just genetically modifying an organism, but genetically modifying it in a way that you basically push

• 15:21Speaker 03

  this characteristic or this packet of genetic modifications into the next generation and into the next generation after that. And you sort of override the rules of evolution that way. And that raises a tremendous

• 15:36Speaker 03

  Concerns because you could, for example, there are gene drive mosquitoes out there. They've been engineered and the notion is you could put them out in the landscape and they could potentially make a big difference in places that suffer from a lot of malaria. But you could also potentially, you know, doing all the mosquitoes in the world or all the mosquitoes of that species because your gene drive is so powerful, but at least that's theoretically possible. So you do run into this question of in order to be effective, it has to be very powerful, it has to spread, but in order to engineer that spread, then you're engineering in something that is potentially very dangerous and quite controversial.

• 16:18Flora Lichtman?

  So you often write about these monumental efforts to correct something in nature, from eradicating invasive species to people working on geoengineering solutions to fight climate change. I mean, what is your point of view on these projects? Like, I guess I'm asking, how should I feel about them or how do you feel about them?

• 16:41Speaker 03

  Well, I think that's a very good question and a very hard question. And I guess I try to go into this as a reporter. I'm agnostic. I'm just interested. And I think that the point that people would make is, it's really, you know, compared to what? So we get a lot of concern about tweaking these organisms and putting them out on the landscape. But Mark Tizard, who was the geneticist who was working on this project, whom I interviewed several years ago, I remember very distinctly him saying to me, well, look, the cane toad itself, it's just a package of genes, but that whole genome shouldn't be there, right? So the question of whether you should tweak that one gene or whether you should have,

• 17:23Speaker 03

  you know, 200 million examples of this whole genome that doesn't belong in this landscape, you know, are we arguing about the wrong things? And those are, those are really interesting and tough questions.

• 17:33Flora Lichtman?

  And I'm sure they're different in every situation. You know, there's no one size fits all answer either.

• 17:39Speaker 03

  Yes, and I think one of the reasons that these efforts haven't really gotten off the ground yet is this scale problem. It's so huge. And if you think about this effort to, you know, introduce these sort of Peter Pan tadpoles to the landscape. In order to curb the cane toad population, you know, you're probably talking about releasing literally millions of these. So we're really talking about a monumental effort. And cane toads also have a way, as Rick Shine's group has, you know, demonstrated, of evolving very fast. They actually have undergone some really, really fascinating evolutionary changes, including this cannibalistic behavior. So there's this super interesting genetic experiment.

• 18:23Speaker 03

  They themselves are evolving and they can evolve potentially defenses against what you genetically engineer to try to get rid of them.

• 18:34Flora Lichtman?

  That's fascinating. One more question. What has reporting on these themes taught you about us?

• 18:42Speaker 03

  Well, I think that that is a, I guess ultimately that is the question, isn't it? What kind of creature are we? And I think what it teaches us is that these natural systems are incredibly complicated. And we intervene in them, often unconsciously. In the case of the cane toad, it was conscious, actually. It was just a huge blunder to introduce them, but they were purposefully introduced. But often invasive species are introduced, you know, in someone's luggage or on the sole of their shoe. And they have huge consequences that we can't anticipate. And then we have to try to sort of backfill. And that is very, very difficult because these systems are so complicated.

• 19:26Speaker 03

  And once we realize we have a problem, often, you know, it's a question of having, of the genie being way, way out of the bottle. And we'd want to think of some nice, neat fix that was as easy as bringing in this organism, which turned out to be super easy. And we want to think of some nice, easy fix that's going to get us out of it. And that, often, that fix is, turns out to be either extremely elusive or even nonexistent.

• 19:54Flora Lichtman?

  This is like the stuff of Greek myths.

• 19:56Speaker 03

  Exactly.

• 19:58Flora Lichtman?

  Thank you for all your work on this, Elizabeth.

• 20:00Speaker 03

  Oh, thanks for having me.

• 20:02Flora Lichtman?

  Elizabeth Colbert, staff writer at The New Yorker and author of Under a White Sky: The Nature of the Future.

• 20:11Flora Lichtman?

  And that is about all we have time for. Lots of folks helped make the show happen, including

• 20:17Speaker 05

  John Dinkowski.

• 20:18Flora Lichtman?

  Annie Nira.

• 20:19Speaker 05

  Jason Rosenberg.

• 20:21Flora Lichtman?

  Rasha Urdi. I'm Flora Lichtman. Thanks for listening.