Key points
- European rabbits cause significant environmental and agricultural damage in Australia.
- Biological control agents such as viruses have reduced rabbit populations, but evolving resistance demands new virus strains.
- Our improved organoid cell cultures enable faster, more efficient virus testing and could help future-proof biocontrol strategies.
European rabbits have plagued the Australian environment since 1859, when they were introduced to Australia near Geelong in Victoria .
The spread of rabbits over Britain took 700 years. However, in less than 70 years rabbits had colonised 70 per cent of Australia, an area 25 times the size of Britain. This was the fastest ever recorded invasion of a mammalian pest anywhere in the world.
Introduction of biological control
Rabbits remain one of Australia's most destructive pests today. They compete with native animals for food and shelter, their burrows cause erosion and even extremely low densities of rabbits can prevent tree and shrub regeneration, leading to long-term species loss.
It is estimated that rabbits cost around 200 million dollars a year in agricultural loss, and before any biocontrol methods were introduced this figure was closer to two billion dollars a year . They also negatively impact 322 nationally threatened species , more than those under threat from feral cats and foxes combined.
Biological control has proven to be the most effective solution against rabbits. The myxoma virus and the rabbit calicivirus both significantly reduce rabbit numbers, and continue triggering outbreaks in the smaller, residual rabbit populations.
This means the viruses suppress rabbits without a person having to go and re-apply the virus each year. Even better, both viruses are spread by insects feeding on dead rabbits, which means they effectively transmit the viruses across larger distances and between rabbit populations that are not in direct contact.
A need for new virus strains
Whilst these viruses have been incredibly effective , saving Australian agriculture more than 70 billion dollars, with more than 90 per cent population reduction in some areas, they are not an eradication tool.
The viruses and their hosts evolve together, and over time rabbits can become resistant and populations bounce back. This is why we need to be ahead of the curve, developing new biocontrol tools and strategies to continue to control rabbit populations, and protect the gains made by past biocontrol initiatives.
A new development in testing
Until recently, studying rabbit caliciviruses has been difficult due to the lack of a reliable cell culture system to use in testing. 
In 2023, CSIRO succeeded in demonstrating for the first time in more than 40 years the growth of these viruses outside rabbits, in organoids . Organoids are tiny 3D cellular structures derived from stem cells that mimic the organ they come from.
This organoid-derived cell culture system has now undergone a major upgrade and is now able to effectively support virus testing.
In a recently published paper in Journal of Virology , CSIRO's rabbit biocontrol researchers demonstrated how they have now released the cell culture's 'hand break' that was holding back effective virus production, making it healthy and robust enough to allow for high level virus replication, serial passaging and in-depth testing.
This breakthrough presents a game changer in working towards the next successful virus strain targeting rabbits.
Dr Michael Frese is a virologist working with our rabbit biocontrol research group and the University of Canberra . He explained how pivotal these new and improved organoids are in the ongoing rabbit biocontrol research.
"Essentially you are saving time and resources with this new and improved cell culture system," Michael said.
"In testing a virus, we need to determine the concentration of infectious virus particles, and in the past, this required the infection of many rabbits.
"With the cell culture system, this can be done in a cell culture plate, and the need to infect laboratory rabbits is significantly reduced.
"This system will allow our researchers to work faster and more efficiently in delivering new virus strains," he said. 
Additional benefits of cell culture testing
Dr Tanja Strive is our senior principal research scientist in rabbit biocontrol. She has worked at CSIRO on a series of projects investigating biocontrol options for a range of invasive animal species, including European foxes, mice, cane toads and for last 18 years, rabbits.
The immediate purpose of this research is clear to Dr Strive.
"The goal is to greatly reduce the number of animals needed for virus testing and to increase the speed of biocontrol research," she said.
However, Tanja also acknowledged that the establishment of this culture system for rabbits can have further benefits.
"It will allow scientists to study the viruses in a controlled environment. This could help further our understanding of the diseases they cause and develop further calicivirus-based biocontrol strategies," Tanja said.
"The benefits of this research aren't limited to virus testing and production.
"For example, we can explore its suitability for producing vaccines for rabbits we want to protect from caliciviruses, like pet rabbits or rabbits bred for the meat industry.
"And it finally allows us to get a much deeper understand of the biology of these viruses, that play a vital role in current and potentially future biocontrol strategies," she said.
Staying ahead of the virus cycle
Dr Strive explained the current state of play of CSIRO's rabbit biocontrol work, and the long-term commitment required to secure the pipeline of research, develop new virus strains and ultimately successfully suppress invasive rabbit numbers.
"Identifying, developing and rolling out an effective viral rabbit biocontrol is a long process," Tanja said.
"We have previously observed that the effectiveness of rabbit biocontrols starts to wane after approximately 10-15 years. Given the exotic RHDV2 (Calicivirus) arrived in Australia around 2014, we are at the point in the cycle where we can expect to see increases in numbers again now.
"So, we are currently at the point of selecting new variants, a panel of which will then need to be tested for virulence in rabbits and species specificity," Tanja said.
"Once a suitable candidate is found, it will need to undergo thorough testing to prove its safety and efficacy before it can be registered as a biocontrol agent through the appropriate regulatory processes and released. All in all, this is a long process, taking around 8-10 years."
The development of this organoid culture system is one component of delivering against Australia's Rabbit Biocontrol Pipeline Strategy . This strategy outlines short, medium and long-term actions that will put us in the best place to be able to stay on top of rabbits. These will hopefully give Australia more control in the biocontrol pipeline.
Ultimately, there is a need to keep developing tools and strategies to roll out every 15 or so years, to prevent rabbit numbers from building up again, and losing all the gains that have been made over the last decades.
"Our researchers are also beginning to explore novel genetic control technologies as an alternative long-term strategy for rabbit control," Tanja said.
"This could be the future of rabbit control, however, in the meantime, we may need several new viruses to stay on top of rabbit numbers while this long-term solution is developed."
CSIRO continues to actively look to partner with government and industry to ensure rabbit biocontrol research continues to hop in the right direction.
The recent advances in calicivirus and organoid research is the result of a collaboration between CSIRO and University of Canberra with the support of Meat & Livestock Australia (MLA) and the Commonwealth Department of Agriculture, Fisheries and Forestry (DAFF) .
