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By Owain Edwards, Peter Brown, Mark Tizard, Tanja Strive, Andy Sheppard Owain Edwards, Peter Brown, Mark Tizard, Tanja Strive, Andy Sheppard Owain Edwards, Peter Brown, Mark Tizard, Tanja Strive, Andy Sheppard Owain Edwards, Peter Brown, Mark Tizard, Tanja Strive, Andy Sheppard Owain Edwards, Peter Brown, Mark Tizard, Tanja Strive, Andy Sheppard 7 December 2017 9 min read

Bird in flight
The Tristan albatross breeds almost exclusively on Gough Island, where it is under threat from non-native mice predation. Image: Flickr/Cláudio Dias Timm ©  Claudio Dias Timm

GOUGH Island—a remote island in the Atlantic Ocean, 2,700 km off the coast of South Africa and 3,200 km from the nearest point of South America—is a UNESCO World Heritage Site that is home to one of the largest seabird nesting colonies in the world. But something disturbing is playing out there—almost 1 million newly hatched chicks are being devoured every year by non-native mice. The rodents established themselves after stowing away on seal-hunting ships in the 19th Century and are now driving the island’s Atlantic Petrels and Tristan Albatrosses, which breed there almost exclusively, towards extinction.

And this problem is not isolated to Gough, rodents are one of the major threats to species on thousands of islands right around the world, including Australian islands. On Lord Howe Island, for example, ship rats have caused the extinction of a number of birds, insects and plants. In fact, the majority of recorded extinctions have occurred on islands, and invasive species are implicated in most of those. As we know here in Australia, invasive species have an enormous impact on the biodiversity of continental mainlands also.

Green cliffs and beach
Remote islands, like Australia's Macquarie Island, are important nesting sites for sea birds. Image: Wikipedia/M. Murphy

There is an ambitious poison baiting campaign currently being planned for Gough in an attempt to control rodent numbers and give the birds a chance to recover. While this form of control proved successful on Macquarie Island—a sub-Antarctic island located 1500 kilometres southeast of Hobart—it is extremely costly, can have indiscriminate impacts for other species on the island, and eradication success is not guaranteed.

With scientists and environmental managers being confronted with such complex and urgent problems, attention is now turning to new technologies that could offer more targeted solutions. Recent advances in genetic technologies, such as discovery of the CRISPR/Cas9 system as a tool for precision gene editing are leading to revolutionary applications in health, agriculture, manufacturing, environmental remediation, and other industries. One derivative system, synthetic RNA guided gene drives (gene drive), which is based on CRISPR/Cas9, has provided new hope of delivering much needed solutions for threatened species conservation.

Since breakthrough CRISPR advances were published in 2012, there has been a lot of information published explaining the CRISPR/Cas9 system and gene drive, like this overview from the Office of the Chief Scientist and this gene drive explainer. Essentially, gene drives are systems that can bias genetic inheritance via sexual reproduction and allow a particular genetic trait to be passed on from a parent organism to all offspring, and therefore the ability of that trait to disperse through a population is greatly enhanced.

Gene drives occur in nature, and so the potential for these naturally occurring gene drives to be used to introduce engineered genes to a genome have been studied for quite some time by molecular biologists. The CRISPR/Cas9 system has vastly accelerated this process by providing a simple, flexible and precise way of editing DNA, making it much more efficient and effective than previous methods. So, using the specificity of CRISPR gene editing to direct gene drives, it is now hypothetically possible to rapidly disperse a genetic trait that has been engineered for a specific outcome through a target population. Potentially, the system can be designed to function in any species that relies on sexual reproduction, animals and plants alike.

For example, researchers have successfully used this artificial gene drive technology in the lab to disperse a trait through a group of mosquitoes that made them no longer able to carry the malaria parasite. Theoretically, this raises the possibility of eliminating malaria altogether, demonstrating the remarkable power of the technology. Indeed, this approach now has the support of the Bill & Melinda Gates Foundation and the Open Philanthropy Project Fund through the Target Malaria initiative.

The promise and the risk

In the case of the rodent problem on Gough Island, gene drives might provide an avenue for eliminating the mouse population from the island. For example, if a gene drive that increased the likelihood of all offspring being male was introduced into the mice and then released on the island, the mice could breed themselves into being an all-male population, eventually leading to population collapse.

While the possibilities for such applications seem endless, the excitement generated by these technologies is tempered by the need to consider the associated risks. Development of genomic biocontrol strategies will need broad public acceptance, including a full assessment of potential risks to ensure that all reasonable mitigation measures are put in place before any release of a gene drive system occurs.

For example, the advantage of trialling the technology on remote, oceanic islands is that there would be a high degree of geographic containment that reduces risks and increases the chance of success. But if such mice were released, can we be sure that they won’t escape the island and breed with mice in their native range? And if they did, what would be the likely consequences? Would the gene drives even work as theorised? What level of risk are we and any affected communities willing (and permitted) to work with and how can the risks be effectively mitigated?

Cane toad
Scientists have learnt much about the ecological impacts of invasive introduced species, which informs present-day biosecurity and risk management. Image: Liz Poon

These questions are not new. Lessons learnt from the unintended impacts of biocontrol interventions in the past, such as the cane toad in Australia, as well as the disastrous impacts from species like rabbits and foxes having been introduced from Europe for sport and 'acclimatisation', have driven the development of a stringent risk management framework and, importantly, have spurred scientists at the frontiers of their disciplines to give careful consideration to the ramifications of potential breakthrough technologies. The risk management framework that has developed around traditional biocontrol is now being applied in genomic biocontrol research and makes us well equipped to consider the associated risks. Already there is promising research about the factors that need to be understood to deliver low-risk gene drives with high probabilities of success, as well as techniques for designing gene drive systems with controls built in at several levels—from genetic controls to environmental controls—so they can be more locally contained, reducing risks of non-local transfer and unmitigated, invasive spread.

In considering risks, it’s important to view the broader context in which these sorts of technologies are being considered. In the case of the mice on the island, if traditional methods are not feasible, such as the use of poison baits, are we willing to risk extinction of the seabirds? On the Australian mainland, there are currently no effective controls for some invasive species that are impacting native species, such as cane toads and feral cats. Feral cats have been found to kill up to 1 million native animals every day across Australia, contributing to the increasing extinction risk for some of these species.

Proceeding responsibly

The urgency of these situations will force us to operate with some degree of risk. We will face risks whether we pursue gene drive solutions or not, and the only way to manage them is to have more information, more research and more evidence with which to better understand and mitigate those risks and proceed responsibly.

For these reasons CSIRO has endorsed the ‘Guiding principles for the sponsors and supporters of gene drive research’ recently published in Science, along with a growing consortium of research institutions and funders from around the world that are active in the gene technology research space. This signifies our continuing commitment to responsible gene technology research and a strong community engagement agenda. We’ve been actively contributing to the public discussion about these technologies, such as our contributions to the Australian Academy of Science report, Synthetic gene drives in Australia: implications of emerging technologies.

The cautious and responsible approach to working with these new technologies, outlined in these publications, will categorise our ongoing work in this area. Last year, we launched the Synthetic Biology Future Science Platform (SynBio FSP), one of several Future Science Platforms working in scientific disciplines that look set to shape the future. Synthetic Biology, which gene editing technologies like CRISPR and gene drive form a part of, is one of the fastest growing areas of modern science. By being active in this field and developing a collaborative community of researchers around Australia, we will be in a better position to understand global developments in synthetic biology and what they may mean for Australia. The SynBio FSP is also coordinating a risk analysis and social science program that aims to ensure ethical, socially responsible development of new technologies like gene drive, and to engage the public with our research.

In the environment and biosecurity space, we are currently investigating the potential for novel genetic technologies (including but not limited to gene drive approaches) to be used to control a range of invasive species, including cane toads, rodents, carp and fruit flies. We’ve joined a project led by Island Conservation, Genetic Biocontrol of Invasive Rodents (GBIRd for short), and in collaboration with an international consortium, we will help determine whether gene drive is a safe and viable solution for invasive rodents on islands like Gough, and others with similar problems—including some Australian islands. It’s an ambitious project that will engage the community in making decisions about the conservation of the native species under threat and the tools that are used in managing the threats. And recently, we formed an agreement with the Australian Wildlife Conservancy to explore whether genetic technologies may eventually play a role in controlling the extensive impact feral cats are having on native biodiversity in Australia.

We’re also involved in another international collaboration, the Debug Project, exploring the use of these technologies to tackle mosquito-borne diseases like Dengue and Zika. An important part of our role in this project, as well as in the GBIRd project, is to contribute our expertise in risk analysis. CSIRO has many years of expertise in quantitative risk analysis of biocontrols and in the development of the very latest approaches to effectively assess and mitigate risks.

One thing is clear, we will never get closer to answering the questions raised by gene drive without undertaking fundamental research in this area of science. Without developing our understanding of gene drive technologies in the lab, we won’t know if they are a viable solution or not. And without developing our technical knowledge and capability for utilising gene drive, we wouldn’t be in a position to implement a gene drive solution in time to deliver the critical conservation outcome we hope to achieve—even if the risks were appropriately mitigated and we had local community and international support to proceed.

Our ongoing research is essential for providing much-needed knowledge to navigate the risks and to develop the appropriate new tools that will be required, as well as providing hope for the future of the seabirds under threat, like those on Gough Island, and our native animals here in Australia.

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