Transparency in science: Talking about the potential of gene editing for conservation
THEVENARD Island, part of the Mackerel Island group, is located 22 kilometres off the coastal Pilbara town of Onslow in Western Australia.
The 550-hectare island is just six kilometres long, flat and relatively featureless, dominated by stunted acacia scrub and the ever-present buffel grass that infiltrates Australia’s semi-arid landscapes. The region averages 300mm annual rainfall most of which falls after cyclones or tropical lows over a few days a year.
Ordinarily, Thevenard Island caters for those chasing the Indian Ocean’s big game fish or the more intrepid eco tourists seeking the remote and unusual off-grid experience. And remote it is at 1,400 kilometres north of Perth. In November, it was not big game fish or marine turtles that attracted an eclectic group of national and international scientists but Mus musculus domesticus – the common house mouse.
Genetic biologists, ecologists, social scientists, computer modellers, invasive species experts and island conservationists are part of an international multidisciplinary team that seeks to better understand the intractable problem of invasive rodents on island flora and fauna. The primary purpose of the field trip is to collect data and samples of house mice, following an annual GBIRd (Genetic Biocontrol of Invasive Rodent) meeting, a consortium of seven research and conservation organisations from the USA, New Zealand and Australia.
And Thevenard Island could just be an example of a model island for a bold new concept in rodent management.
Tiny mice, big impact
At just five per cent of the planet’s land area, islands are home to more than 40 per cent of all endangered animals, and a staggering 86 per cent of all recorded extinctions on islands are linked to invasive species. In Australia alone, some 25 per cent of land mammal extinctions have occurred on islands.
Dr Aaron Shiels, research biologist with the US Department of Agriculture’s National Wildlife Research Centre in Fort Collins, Colorado explains:
“Rodents, particularly invasive rats and mice, are on almost all parts of the world.
“Over 80 per cent of the islands have been established by invasive rodent species. And they’re the animal that’s caused the most plant and animal extinctions. So, it’s a really big problem.
“I do a lot of work in Hawaii and other Pacific islands, as well as the Caribbean, and they’re so destructive because they have such a broad diet. They eat plants, seeds, invertebrates, and also birds, eggs, and chicks.”
Dr Dorian Moro, Senior Research Scientist at the Western Australian Department of Biodiversity, Conservation and Attractions, has been researching and managing island environments, including invasive rodents, for more than 20 years.
“We know rodents are problems on islands, particularly mice because of their high densities,” says Dorian.
In tropical and sub-tropical areas mice can breed year-round with each female having four to six litters a year with up to 10 offspring in each litter. Once established, mice numbers can grow exponentially.
“Getting rid of 90 per cent of introduced animals in a population is relatively easy. It’s the last 10 per cent that’s hard,” says Dorian.
“Our only effective way of control is to use rodenticides. We know these kill rats and mice. But they also have non-target impacts, as baits can be ingested directly by many native species, or can bioaccumulate and lead to secondary poisoning in higher-order predators and cause what we call ‘off-target’ effects.”
For the GBIRd group, the end point is the managed eradication of introduced rodents from islands because there is good evidence that native species such as sea birds return when rodents such as mice and rats are removed.
Synthetic biology, an interdisciplinary area that applies engineering principles to biology, is an emerging technology that could hold the answer to rodent management.
Dr Owain Edwards, who leads CSIRO’s Synthetic Biology Environment & Biocontrol Application Domain, describes synthetic biology as a step forward from traditional molecular biology.
“From a mechanistic point of view, it’s not all that different. The biggest difference is more philosophical in terms of what you’re trying to do with it. Because generally for something to be considered to be synthetic biology, you’re basically trying to figure out ways to get an organism to do something it doesn’t normally do.
“It’s principally around modifying the genetic code in some shape or form, which leads to a novel phenotype in an organism.
“We’re converting an organism that would normally be out there trying to propagate itself, we’re turning it into an organism that actually interferes with the reproductive success of populations. So it’s not something that you’d find would happen naturally.”
There have been big advances in recent times. Gene drive molecular biology – one tool of synthetic biology – aims to bias inheritance of particular gene(s) to result in the proliferation of a particular trait throughout an entire population. Gene drives have been effectively demonstrated in mosquitoes and fruit flies; however, application in mammals is a whole new ball game and the challenges stretch far beyond the technical hurdles of the laboratory.
Introducing ‘Ecomouse’ – a potential game changer in invasive species management
The concept GBIRd is exploring is whether invasive species on islands can be managed by introducing a strain of house mouse with edited DNA that results in an inheritance bias towards male offspring. The theory is that over four or five generations (the bias removes itself after this point) numbers of the target mice are reduced significantly and on an island, possibly eliminated.
Dr Andy Sheppard, who leads the CSIRO Health & Biosecurity Managing Invasive Species & Diseases Program, says the concept has potential to make a profound impact on island conservation that is cheaper, scalable and more humane.
“The approach to be able to not control species by introducing their natural enemies, but controlling them by using their genetic code against them – this is the really novel approach and allows us, for the first time, to potentially eradicate species that are already widely established which is a game changer.”
John Godwin, Professor of Biological Sciences at North Carolina State University, considers the mouse as the genetic model organism.
“We understand their genome better than any other mammal, including probably our own.
“They’re far more manipulable, so to do experimental manipulations is possible in a way with mice that isn’t possible yet with other mammals. We can look at the consequences of that, because they’ve been such an important bio-medical research organism for so long. One of the important things you’d like to ask when you make a GM edit, is have you affected the site that you’ve targeted, or other sites? And we have very powerful ability to look for those changes through the laboratory.
“What we are doing is scientifically difficult and so you want to start with a species that gives you the best chance at actually being successful in investigating this. And so the house mouse is the organism of choice for genetic experiments in mammals.”
Synthetic biology is not without controversy. The public cares about the ethics of this science, evident not least in news coverage dedicated to the recent claim by a Chinese researcher who claimed to have gene edited the embryos of twin girls.
“It’s primarily controversial because we’re manipulating genes,” says Andy Sheppard.
“Using gene drive and genetic technologies more generally to manage threatened species are theoretically pretty well understood.
“We’ve made huge steps forward for the discovery of the CRISPR/Cas 9 gene scissors that are so easy to use to precisely cut genomes where you want to, which gives us some really novel tools. The problem is that, clearly, when you try and develop these tools in the context of a specific situation it’s – surprise, surprise – turning out to be not quite as easy as we thought. The theory is still there but the challenge of making manipulations and field applications generate the outcome you want, but are also genetic manipulations that can provide the change you want in a safe way, are harder than we first thought.”
Many of the world’s leading scientific bodies and academies, including the Australian Academy of Sciences and Australian Council Learned Academies, acknowledge synthetic biology as a new field of science that promises great potential across a broad range of applications. There is an equally shared view that the discipline’s prosperity will hinge on the scientific community’s ability to undertake vigilant engagement with all the interests around a particular application of the technology.
At the heart of this are the socio-economic, cultural, moral or ethical considerations that define the benefits and risks with each case of the technology’s application. To some extent this is where the challenge lies.
Understanding community values
Dr Jason Delborne, Associate Professor of Science, Policy and Society at North Carolina State University, dislikes the term ‘social license to operate’.
“It has some assumptions built in that are problematic.
“It invokes the metaphor of a government licence, which is like a one-time permit. It suggests that once you get it, you’re off and running. And what I’m interested in is the kind of engagement that’s ongoing. There is no particular moment in time when you achieve social licence.
“Too often we see technology developed but behind closed doors in spaces that are private and not public.
“But when we see those technologies mature and all of a sudden the innovators realise people might have a concern about this, or raise questions, or we have to get regulatory approval and there’s a public component, then there’s this scramble to figure out how do we convince everyone that this is okay and they shouldn’t put any roadblocks in our way?”
Delborne brings a new perspective to the science of synthetic biology. In doing so, he challenges his research peers across other disciplines to think beyond the remit of the laboratory. He believes the social scientists’ role is not to figure out who is right and whose perspective makes more sense but for a scientist to know that other perspectives exist.
“People are used to being marketed to for commercial products. We know when we’re being persuaded and nudged to change our behaviour or our attitudes. And, so, when people are presented with a final version and final plan of a technology in its deployment they may or may not agree.
“The role of social scientists is to help create constructive dialogue and connect decision makers, and the public and communities and experts in conversation that is meaningful.
“One of the lessons is for experts and those who are in favour of this technology to keep talking about the non-technical issues that drive this.”
Andy Sheppard agrees: “In a sense, we’ve been here before with biological control. At CSIRO we have a huge experience in trialling new technologies in this space. We know it’s hard, we know there are pitfalls, and we also recognise we can’t undertake these kind of approaches without broad public acceptance but the benefits are potentially huge. So, we have to be very transparent in what we do. And we also have to be cognisant and consultative as much as possible with the community around what we’re trying to do. Recognising that there will always be those people who think it’s amazing and we should just go out and apply it, on the one hand. And on the other, there are those saying we shouldn’t touch it with a barge pole.”
Dorian Moro puts it another way: “I think that it’s important to have a visible and carefully managed team who can communicate their work to a lay audience in a non-scientific format. We should not be shy about the work we are pursuing and recognise that the work is conducted with sensible science and stakeholder engagement. This is not some random, ad-hoc research but is actually being processed within a risk management framework, and there is good science to guide our thinking.”
As a reproductive biologist John Godwin agrees: “I think there have been mistakes in the past, so I think it’s very reasonable for people to ensure a careful approach. And I think it’s really important that we be completely open about what we’re doing. If people really don’t want it then you know, there has to be that path to ‘no’.”
Why Thevenard Island?
Western Australia has about 21 islands with house mice. Thevenard is touted as a model island: while it has a native mouse population, its real advantage is a well understood system in terms of mice. Dorian Moro and his team have conducted studies here since the 1990s; they have a good baseline dataset on the dynamics of both house mice and the native mice, the only two mammal species on this island.
“Having good baseline data is critical in the event that there is any future release on an island.”
Agreeing on island criteria is just one part of the broader risk management and compliance obligations that will be needed for the safe and responsible deployment of this technology. Owain Edwards says the consortium has always accepted it will take time to develop the technology however, once developed, that technology would be ready to deploy.
“The World Health Organisation has established a process for vector and disease control done in field conditions which it has developed over decades that most regulators follow.
“This process essentially goes from lab work, to lab cage, population cages in the lab to enclosures in the field to sort of small contained releases,” says Edwards.
The regulatory approval for these sorts of technologies is understandably stringent. One of the founding principles of GBIRd includes only working in jurisdictions that have substantial regulatory frameworks – hence targeting Australia, United States and New Zealand.
Andy Sheppard believes the Australian regulatory system is robust with adequate requirements around these technologies.
“Should we go down the gene drive path, and it’s classified genetically modified, it will be fully regulated under the Office of the Gene Technology Regulator. And the moment we start talking about an application, that will invoke other legislation. And if we want to introduce something into the environment, further legislation is enacted so there are a number of parallel regulatory processes that need to be complied with.”
One novel approach to risk management being considered is to apply the risk management framework used in the aeronautical industry to invasive species management. Regardless of what form the risk management takes, it will need to be robust given the debate over synthetic biology continues. The Convention on Biological Diversity— the global framework that governs the protection of biodiversity — held its 14th Conference of the Parties in Egypt in November , exploring how to manage research into the application of such technologies for conservation.
Sheppard believes the horse has bolted: “In some ways, this is naive because you can actually do this kind of technology ‘in your garden shed’, so if you don’t regulate it properly and you don’t manage it properly it will happen anyway, in an unregulated way.”
Irrespective of the outcome, there is optimism for the potential of synthetic biology.
Andy Sheppard again: “The potential opportunities synthetic biology presents to us are huge in terms of being able to protect threatened species and manage over-abundant species. And therefore we can’t ignore the technology that already is starting to show major benefits in the context of areas like human health. We have to proceed with caution but we can’t ignore the fact that it can allow us to really redress some of the imbalances that we’ve created in nature through our activities as a species.”
“Synthetic biology won’t go away. And we cannot ignore it as a national science agency and the potential it offers. The SynBio people come up with a range of scientific approaches that have the potential to offer valuable solutions for the country. It’ll be up to the country to decide which ones it wants.”
Owain Edwards adds: “Within the agricultural context, I don’t think there’s another country in the world that would benefit more from mouse control than here in Australia.
“GBIRd has as its primary focus the base of rodents on islands but it’s already accepted within the consortium that if we were to achieve that aim we could expand not only in terms of mice in other situations but to start looking at other invasive animal pests.”
The use of EcoMouse is likely to be some years away – it is generally accepted by scientists that a mouse with edited DNA is five to 10 years away.
The scientists see this technology’s potential, however they are quick to check this enthusiasm. Says Owain Edwards. “Scientists shouldn’t be an advocate for a particular product, and especially if we’re delivering a particular product into a particular system. We should only advocate the science that underpins it.”