The most expensive rat on the menu at the Animal Resources Centre (ARC), in Western Australia, costs $872.13. The priciest mouse is $421.70. Both are pregnant “mutants” – that’s the technical term – which have been bred to a specific genetic design for biomedical research.
But in 12–18 months, access to either will be strictly curtailed, because even at those prices Australia’s largest supplier of common mice and rats for research seldom makes a profit, and is being shut down, after the WA Government announced it would close the quasi-government facility in Canning Vale, south-east of central Perth, after having to kick in $4.5 million over the last five years.
The news has shocked Australia’s research community, which has come to depend on the ARC for easy access to a wide range of mouse and rat strains necessary for both exploratory research and the preclinical studies required by law before a drug can be given to a human being.
No more WA subsidy
The ARC was established with a law in 1981 to supply pedigreed, pathogen-free mice and rats, and associated support services, to mainly Western Australia research institutions. Legally, it’s supposed to at least break even.
But the majority of mice and rats sold are not the extravagant designer models mentioned earlier, but common breeds that are the stock-in-trade for basic research. These are mainly sold interstate and overseas for medical research; only about 16% of animals are bought by WA organisations, says Kym Coolhaas, a media advisor with the WA government.
In 2020, the ARC made a $1.2m loss, chasing a $118,939 loss the year before.
With profits realised in only two of the last eight years and irked by the fact that it’s “effectively” subsidising research activities in other states, the WA Government used the impending 2023 expiry of the ARC’s lease with Murdoch University to spur a review. The government decided the cost of setting up a new purpose-built facility for research animal breeding wasn’t commercially viable, Coolhaas says.
The money in mice
If you perform a bit of basic arithmetic on the ARC’s 2021 price list, the average price for a mouse works out at $60–70, and $100–130 for a rat.
That’s factoring in higher prices across the board for female mice and rats – which are preferred over males, as the latter must be kept in separate cages to avoid vicious fights – and excluding the significantly higher rates for a specifically timed pregnant female.
“[Breeding research mice and rats is] not profitable. It’s a very labour- and capital-intensive process,” says Dr Malcolm France, a consultant veterinarian specialising in the care of laboratory animals and the inaugural president of the Australian and New Zealand Laboratory Animal Association.
Facilities are expensive to build, because they require complex air conditioning, air filtration and other barriers to prevent animals, particularly those bred to be immunodeficient, from infection. And it’s labour intensive to operate: the ARC had 43 full-time staff last year to keep cages clean, animals healthy, and genetics on track.
“The other thing that ARC does better than what smaller institutions could do is the genetic monitoring of their animals,” France says. “This is crucial, because most laboratory rats and mice all look the same. If you see a black mouse in a lab you have no idea what it is.
“And then add to that the broad diversity of different strains you need to maintain, many of which [there] might only be low demand for, but might be very important for research. So you’re maintaining a large number of breeding populations but you might only see a small number of progeny.”
Increasingly, ARC’s revenue is coming from “new models”, such as that $872.13 rat (admittedly cheaper when not pregnant), which is extremely immunodeficient: two genes – the Rag2 and Il2rgamma – are “knocked out” or inactivated to make it ideal for cancer research.
Researchers are worried about the lack of alternatives.
Australia’s second largest supplier, Australian BioResources, an outpost of the Sydney-based Garvan Institute of Medical Research, only grows mice and is set up for researchers who want unusual and highly specialised strains. The Australian Phenomics Facility, at ANU’s John Curtin School of Medical Research, specialises in “reanimating” cryogenically stored designer genetics.
Dr Paul Callaghan, an imaging neurophysiologist with national research institution ANSTO (the Australian Nuclear Science and Technology Organisation), says small, local, university-based facilities don’t have the capacity to replace the ARC in either quantity or in terms of diversity of strains.
Budgeting for rodents
The vagaries of national public funding for biomedical research are also writ large on the ARC’s fate.
The federal government launched the $500m Biomedical Translation Fund in 2016, and $1.9bn over 12 years from 2017–18 to implement the Research Infrastructure Investment Plan.
At a mouse level, this led to a turnaround in sales for the ARC in 2019, but even with a 7% price increase in 2020 those rising sales weren’t enough to cover costs.
Asked why the ARC couldn’t balance its books in a newly hot market, Coolhaas says only that ARC’s operating losses “are due to a combination of factors, including a sustained decline in sales dating back to 2014–15”.
The ARC declined to answer questions, directing all queries to the Western Australia Government.
But its 2020 annual accounts indicate it was hoping for a financial revival on the back of increased long-term government support for biomedical research – until the 2019–20 bushfires killed off the rat trade in NSW. The ARC accounts don’t specify why bushfires had such a negative impact on rat studies.
Finally, the onset of the pandemic in February 2020 stalled all research, as lockdowns cut exports from WA to the rest of the world by 50%, and both lockdowns and drastic cuts to research budgets affected demand from Australia.
The implications of the ARC’s closure for Australia’s medical research are “huge”, according to France.
Not only will breeding skills be lost, but France says the ARC has been the centralised hub supplier for most of Australia’s universities and medical research institutes looking for specialised strains of lab mice and rats for more than 30 years.
Subbing in wild mice from NSW’s mouse plague isn’t a solution: they’ve got no pedigree and are likely to be riddled with diseases, which can affect research data.
The disappearance of the country’s main mouse and rat supplier could also put a wrecking ball through budgets and research output.
“If we can’t get animals to complete milestones that will lead to an inability to deliver research outcomes,” says ANSTO’s Callaghan.
“Because of the diminishing funding opportunities in Australia, if there is a significant shift in the cost of supply and no proportional increase in the degree of funding, then you would likely see a decrease in research output.”
Part of the ARC’s attraction is it can quickly supply a range of rats as well.
Physicist Dr Mitra Safavi-Naeini, also with ANSTO, says mice are just too small to study different treatments in the brain, for example.
“It will impact the whole lot of fields, from cancer research to behavioural science to looking at neurophysiological pathways that are triggered or suppressed by diet,” she says, adding that a shortage of mice and rats will reduce the amount of early-stage exploratory research that leads to discovery.
But the biggest impact could be that research institutions will now need to pay a lot more attention to the real cost of the animals they use.
“Maybe the research community does need to pay more attention to the real costs of breeding mice and rats for research,” France says.
“The broader community obviously has mixed feelings about the use of animals for medical research. Most people probably accept that it’s acceptable up to a point, but a lot of people think we should be [trying] much harder to look for alternatives.”
And what will happen to the animals?
The wind-up will take 12–18 months and the number of mice and rats “will gradually reduce”, Coolhaas says.
With the news still fresh and researchers in shock it’s not yet clear who or what will step into the mousetrap. The coming months are going to be uncomfortable for Australian biomedical research.