Throughout 2017 the NC3Rs launched a number of initiatives and funded work addressing the welfare of rats and mice used in research as part of our "Year of Laboratory Rodent Welfare". This theme was chosen to highlight the welfare needs of the most commonly and widely used laboratory animals and demonstrate how improvements in welfare can also improve the quality of scientific outputs.
We have produced the following timeline to document these activities and showcase the exciting work that was completed during 2017. You can learn more, including how to order our free resources, on our dedicated rodent welfare hub, or subscribe to our monthly newsletter for future updates.
Prize-winning research into improving laboratory rat housing
This year's 3Rs Prize, sponsored by GSK, was awarded to Dr Joanna Makowska of the University of British Columbia for a paper co-authored with Dr Daniel Weary. The paper provides evidence that natural behaviours such as burrowing and standing upright are important for the welfare of laboratory rats. This work provides a scientific basis for a change in guidelines on laboratory rat housing, including increasing cage height and providing burrowing materials. A number of laboratories have already modified their rat housing to accommodate some of the features described in the paper.
Playtime for Rats at the 2017 IAT Congress
The NC3Rs, in collaboration with AstraZeneca, organised two workshops at the 2017 Institute of Animal Technology (IAT) Congress. The aims of the workshops were to explore practical approaches to providing laboratory rats with increased opportunities to exercise and to perform natural behaviours in a more complex, enriched environment than is often provided for them. The workshops highlighted that there is significant interest from technicians to improve the complexity of the environment for laboratory rats within their care. While barriers to adoption were identified, ways in which these could be overcome were also discussed.
Optimising mouse embryo manipulation and transfer
Dr Virginia Pensabene, University of Leeds, was awarded £100,000 through the NC3Rs open innovation competition CRACK IT Challenges for EASE, 'EliminAting Surgical Embryo transfer in mice'. Genetically altered mice are used extensively to study the function and regulation of genes and their role in human development and disease. Current embryo transfer techniques require surgery and are inefficient, necessitating the use of large numbers of mice. Sponsored by MRC Harwell, the EASE Challenge aims to explore improved implantation rates focusing on the use of a non-surgical embryo transfer (NSET) technique, potentially refining studies and reducing the use of animals.
How serious are we about asepsis for rodent surgery?
Professor Paul Flecknell, Newcastle University, is a world renowned laboratory animal veterinarian who specialises in anaesthesia and analgesia. In this guest blog post he discusses aseptic surgery and the need to maintain good asepsis for the benefit of rodent welfare as well as improving the scientific outcomes of research. He explores various techniques for maintaining asepsis and advocates for more widespread implementation of the current recommended standards.
Maximising the success of bile duct cannulation studies
The NC3Rs brought together a working group of contract research organisations that routinely carry out bile duct cannulation (BDC) studies to share their experiences and identify opportunities for best practice across various aspects of the studies. Their recommendations aim to support all staff involved in conducting BDC studies to maximise the amount of useful data generated using the fewest animals possible, whilst ensuring the highest possible standards of animal welfare, A paper summarising these recommendations was published in Laboratory Animals.
Applying home cage monitoring systems in rodent preclinical safety studies
The Home Cage Analyser (HCA) is a rodent home cage behavioural monitoring system developed by Actual Analytics through the Rodent Big Brother CRACK IT Challenge. The HCA provides continual, minimally-invasive, 24/7 automated monitoring of individual rats' behaviour and temperature while group-housed in a standard, unmodified home cage. Benefits of the system include improved animal welfare and improved data quality. The NC3Rs, in collaboration with AstraZeneca and Actual Analytics, hosted a one-day workshop to showcase the HCA, identify opportunities and barriers to using home cage monitoring systems in preclinical safety studies and agree a strategy for facilitating uptake.
New project grants address rodent welfare issues
Nine new project grants totalling £2.7m were awarded, including two with direct applications to rodent welfare. One of these projects will investigate the enhanced-welfare technology for wild small mammal research, while the other will identify whether pain perception differs between mouse strains and establish more effective analgesic regimens for laboratory mice. Three other projects aim to reduce or replace the use of rodents – reducing the animal cost of CRISPR/Cas9 mutagenesis by eliminating mosaicism, modeling liver cancer in vitro using human cells, and using computational models to measure spatio-temporal changes of bone tissue in mouse models of osteoporosis and osteoarthritis.
New device for refined neural recording in mice
A new device funded by a CRACK IT Challenge allows the neural activity of mice to be studied in more detail whilst avoiding many of the welfare concerns associated with existing approaches. The device, referred to as TaiNi, was developed by engineers at Imperial College London in collaboration with pharmaceutical company Lilly’s UK research labs. It is wireless, lightweight and can record for up to 72 hours continuously with a high signal bandwidth. This system could prove transformative both in pharmaceutical and academic research for the study of neural networks, including brain diseases such as dementia.
IMPROVE-ing animal welfare in experimental stroke research
The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments) are the result of a collaboration led by the NC3Rs and involving representatives from the UK’s stroke research community. They aim to improve the welfare and increase the scientific value of rodent models of stroke. The guidelines, which were published in the Journal of Cerebral Blood Flow and Metabolism, set out 43 recommendations for best practice for the most commonly used mouse and rat stroke models. While the focus is on refinement, the guidelines highlight many sources of variability commonly present in experimental stroke studies.
Resources for refined mouse handling techniques
Research by Professor Jane Hurst and her team at the University of Liverpool has shown that picking up laboratory mice by the tail leads to aversion and high anxiety. They found that methods such as tunnel handling and cupping led to higher welfare and improved performance in behavioural tests. The NC3Rs has worked with the team to develop a series of resources to help raise awareness about non-aversive mouse handling methods and train handlers in their use. These include posters for display in animal facilities, video tutorials providing practical instruction on the refined techniques, and FAQs addressing common misconceptions. We also hosted a free workshop in September 2017.
Rodent Big Brother: we CRACK-ed it
In 2011, Dr Will Redfern from AstraZeneca set the Rodent Big Brother CRACK IT Challenge to develop a home cage monitoring system that could be used in studies involving the analysis of rat behaviour. Actual Analytics Ltd, a spin-out company from the University of Edinburgh, were awarded £500,000 to deliver the product. The system allows, for the first time, the recording and analysis of the behaviour of individual rats whilst socially housed in their familiar home cage, which offers major animal welfare as well as scientific benefits. A paper describing the system was published in PLOS ONE.
A new test guideline for refined acute inhalation studies
Work carried out by the NC3Rs has resulted in the approval of a new and refined OECD test guideline for acute inhalation studies, which are conducted in animals as part of chemical hazard identification and characterisation. The Fixed Concentration Procedure (FCP) uses fewer animals than currently accepted methods and does not require death as an endpoint. This test guideline was officially adopted by the OECD on 9 October 2017. The NC3Rs has been leading efforts to have the FCP accepted internationally for almost a decade.
The NC3Rs goes to Austin for the AALAS National Meeting
The AALAS National Meeting is the largest gathering in the world of professionals concerned with the production, care, and use of laboratory animals. This year's event took place in Austin, Texas, and NC3Rs staff and grant holders were in attendance. As well as co-sponsoring a workshop on the use of positive reinforcement training with non-human primates and showcasing the NC3Rs' activities and free resources on our exhibition booth, we ran a seminar on improving rodent welfare featuring talks about Rodent Big Brother, mouse handling, a new mouse model of pulmonary embolism and opportunities to improve welfare in rodent models of epilepsy.
Laboratory mouse aggression study
The NC3Rs led a data crowdsourcing project for animal technicians to collect data on the prevalence and potential triggers of cage aggression in group-housed male mice. The project was open to all technicians working within licensed facilities across the world and the deadline for data submission was November 2017. The outcomes of this study will be published in 2018 and could have a big welfare impact on a significant number of laboratory animals.
Re-use of needles: is this an indicator of a culture of care?
While it’s essential that there is an overall structure and leadership of culture of care, it’s often the apparently small things that demonstrate the actual quality of the institute’s culture within the animal unit. In this guest blog, Dr Lucy Whitfield from the Royal Veterinary College and Dr Sally Robinson from AstraZeneca examine the issue of re-using hypodermic needles in day-to-day practice. They question whether this common practice is compatible with the commitment to a culture of care. They list the risks associated with re-using hypodermic needles and offer practical solutions on how to overcome potential concerns around the issue.
Using microsampling to further refine a model of mouse thrombosis
With further funding from the NC3Rs, Dr Mike Emerson from Imperial College London has made his refined mouse model of thrombosis, which avoids the use of paralysis and death as an endpoint, more accessible to labs that do not have the specialist expertise and facilities to use radioisotopes. Based on measuring platelets from microsamples of blood, the new method has been correlated with data obtained from real-time monitoring using radiolabelled platelets in mice and validated with the standard anti-thrombotic drug, aspirin.
Tickling rats: a social enrichment to improve rodent welfare
It has been almost 20 years since rat tickling was first demonstrated by the late Jan Panskepp as a method of improving rat welfare. Designed to mimic the play activity of juvenile rats, tickling has been shown to increase approach behaviour, decrease anxiety measures and improve handling. In this story rounding off our Year of Laboratory Rodent Welfare we highlight the technique and its benefits, applications and challenges, as well as resources developed by Megan LaFollette and Dr Brianna Gaskill at Purdue University to help you introduce it in your lab.