More than 120 million laboratory rats and mice are used worldwide each year. Many are accustomed to studying distressing conditions like cancer, arthritis and chronic pain, and almost all spend their lives in small, empty box-like cages: a kind of permanent confinement.
Our new analysis shows that this restrictive artificial housing causes chronic stress in rats and mice, altering their biology. This raises disturbing questions about their well-being – and how they represent typical human patients.
We identified this impact of housing by extracting data from over 200 studies investigating the effects of cage design on health outcomes known to be stress-sensitive in humans, such as mortality rates and severity. diseases such as cardiovascular disease, cancer and stroke.
The importance of housing
The studies we synthesized compared all conventional “shoeboxes” – the small, sterile cages typical of laboratories – with better equipped housings containing wheels, nesting boxes, extra space or other elements allowing natural behaviors like digging, climbing, exploring and hiding.
Overall, animals in conventional cages became sicker than those in better equipped housing. For example, if they received cancer, they developed larger tumors.
Conventionally housed animals were also at greater risk of dying, with their average lifespan reduced by around 9%. Scientists have known for decades that rats and mice want more comfort, exercise and stimulation than is normally provided, and therefore conventional cages induce abnormal behavior and anxiety.
But this is the first evidence that they also cause chronic distress severe enough to compromise animal health.
Our study – like many before us – also found evidence of methodological problems and poor reporting of experimental details. For example, the rodents used were male biased, with few studies using female animals.
Additionally, despite investigating the effects of housing, two-thirds of the studies in our analysis did not fully describe the animals’ living conditions. Our results support many previous suggestions that rats and mice living in sterile cages devoid of stimulation may not be suitable models, for several reasons. Research animals are usually males, often overweight, sometimes chronically cold and cognitively impaired.
We suspect that a reliance on “TABLET” animals – cold, plump, abnormal, male-biased, locked up and distressed – could help explain the current low success rates in biomedical research. There are already examples of research studies generating quite different conclusions depending on how their animals are kept, and we are now looking to assess the extent to which this is happening.
The fact that housing is critical to rodent biology, but often poorly described in papers, could also help explain the “replicability crisis”: that at least 50% of preclinical research results cannot be replicated when other scientists relaunch a study.
Only 1-2% of the world’s research animals live in Canada, so why should Canadians care? On the one hand, because it still means that 1.5 to 2 million animals are unintentionally stressed: something that anyone who cares about animals will find worrying.
But if animal housing does change research conclusions, it also has financial implications. Canada spends about C$4 billion a year on health research.
According to US estimates, if half of these studies are animal-based, of which only 50% are reproducible, Canada could be spending around C$1 billion per year on non-reproducible animal studies.
And even when studies are reproducible, far less than 5% of them provide usable medical benefits for humans. This stands in stark contrast to the expectation of the Canadian public that approximately 60% of work on animals leads to new drugs for humans.
Canadian standards require that mice be given nesting materials that can keep them warm, but is it time to improve them further?
The “shoeboxes” in which rats and mice currently live should stop being ignored as if they were a neutral backdrop, and instead be seen as a determinant of health: the one we can modify, improve and study. This would allow us to better model the various social determinants of human health and improve animal welfare at the same time.
Georgia Mason, Professor, Integrative Biology, University of Guelph and Jessica Cait, PhD Student, Integrative Biology, University of Guelph.
This article is republished from The Conversation under a Creative Commons license. Read the original article.