Impact case study database

Prior to Prof Hurst’s research, grasping the tail between fingers or by forceps was the method universally used to pick up laboratory mice worldwide and recommended in all guidelines. Refined handling methods that she developed were not in use in other laboratories. After initial publication in 2010, uptake of the refined methods was low and tail handling continued as the global standard. To promote impact, Hurst gained a BBSRC Sparking Impact award to create training resources (2013-2014) and partnered with UK National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) to establish a freely available online training hub on mouse handling (live since September 2016). Hurst’s team have also delivered more than 80 invited presentations and/or tutorial demonstrations across 12 countries to widen awareness.

External recognition confirming high level of impact:

The substantial impact of this research on laboratory rodent welfare and improving scientific reliability of animal models has been recognized through several prestigious national and international awards. Prof Hurst was awarded the NC3Rs 2010 international prize for the most significant 3Rs advance in medical, biological or veterinary sciences; the Swiss Laboratory Science Association 2019 international prize for Refinement; and an OBE (2020 New Years Honours) for services to animal welfare [5.1]. Working with Hurst at UoL, animal care technician John Waters has provided practical advice and training resources to animal caretakers to encourage implementation in animal facilities. His highly effective role in promoting uptake has been recognized through the Andrew Blake Tribute Award 2017, the AAALAC International Fellowship 2019, and the Times Higher Education Outstanding Technician of the Year 2020 award (for contribution in 2018-2019) [5.1].

Impact on policy and animal welfare:

Research from UoL and subsequently from other laboratories has confirmed that replacement of tail handling with the UoL refined handling methods substantially reduces aversion, stress and anxiety in laboratory mice, with additional benefits for physiological health, avoidance of depression-like behaviour and improved reliability of scientific data in mouse models influenced by background stress [5.2, 5.6]. The UoL refined handling methods are now strongly promoted as best practice for mouse handling by the NC3Rs, the UK authority for providing guidance on design and implementation of animal research to industry and academia nationally and internationally. This has been widely advertised to users (scientists, veterinary and other care staff, policy makers, students) through NC3Rs Newsletters, meetings and the NC3Rs website since 2016, with online advice accessed by users in 107 countries [5.2, 5.6]. NC3Rs Chief Executive states that Prof Hurst’s research “has led to the largest improvement in laboratory mouse welfare in a decade” [5.6]. She confirms that the research findings both “have welfare implications for millions of mice worldwide” and “can affect the reliability and therefore quality of animal research” in this most commonly used species. Major 3Rs centres in other countries also promote the use of Hurst’s refined handling methods in place of tail handling, referring users to her scientific evidence and online NC3Rs mouse handling hub for training resources. This includes the influential North American 3Rs Collaborative (NA3RsC), Norecopa (Norway’s 3Rs centre accessed by countries across Europe), the Danish 3R-Center, the Swiss 3R Competence Centre, and Charité 3R [5.2]. An independent online survey of those working with laboratory mice in Sep 2018 – Jan 2019 (390 respondents from 27 countries) found that >80% of respondents were convinced that tunnel handling improves animal welfare, and >70% were convinced it improves scientific outcomes [5.4]. In an independent survey of 107 participants on three courses on mouse handling in Berlin in Nov-Dec 2019, almost every respondent agreed that tunnel and cup handling improve mouse well-being (99%) and the human-animal relationship (96%) [5.4].

To promote rapid uptake of Hurst’s refined methods to replace tail handling and ensure staff were given appropriate support to achieve this, the UK Home Office Animals in Science Regulation Unit (ASRU) implemented a formal review on mouse handling across all licensed establishments in the UK using laboratory mice in early 2019 [5.3].

Impact on uptake of refined methods:

An independent online survey in Sep 2018 – Jan 2019 (390 respondents from 27 countries, 30% from UK, 30% non-academic) found that 61% of respondents working with mice were using Hurst’s refined methods by the survey date [5.4]. This survey also indicated that >80% of respondents who had heard of the methods were using them.

A UK Home Office ASRU survey of all UK licensed establishments using mice (industry, academia) in the first half of 2019 found that 68% of UK establishments were using the new handling methods, with 59% using these methods exclusively, completely replacing picking up mice by the tail. Those still using tail handling were in the process of introducing refined handling methods [5.3]. Interviews with animal care staff and training officers (conducted independently by NC3Rs) confirm that mice are “less anxious” and “more calm and relaxed” during procedures, “aggressive mice are a lot calmer” and “non-aversive handling methods are essential for jumpy strains”. Users state “I can spot health issues earlier because [animals] display more natural behaviours”, “you don’t get bitten as often”, “you can much easilier get mice out of the cage with a tunnel”, “it creates that connection between the human and the animal” and “it only took me a week to learn how to do the tube handling and cupping, and now it's as fast as tail handling” [5.5]. The very rapid increase in uptake from 2016 to early 2019 combined with user satisfaction with the refined methods predict an even higher uptake by July 2020.

The biopharmaceuticals industry is a major user of laboratory mice, sensitive to the economic value of gaining reliable data from animal models and the ethical requirement to ensure the highest standards of animal welfare. For example, the multinational Novo Nordisk replaced tail handling with Hurst’s refined methods across all their animal facilities globally (Denmark, China, USA) in 2018-2019. Not only has this improved welfare for approximately 37,000 mice used per year, but it has also led to a noted improvement in job satisfaction among animal caretakers and wider improvements in handling other species. The Novo Nordisk Vice President of Laboratory Animal Science states “This change would not have happened without the research that Professor Jane Hurst published from 2010 onwards. Her persistence, offers of help, and partnering with NC3Rs to provide training resources, have been instrumental in driving this important refinement” [5.7]. AstraZeneca plc rolled out the refined methods simultaneously across all five of their internal animal facilities in the UK, Sweden and USA. Hurst presented current scientific evidence and a Q&A session to all sites at the launch of this major initiative (May 2018), with Hurst and Waters visiting UK and USA facilities to provide advice. Implementation has benefited approximately 121,000 mice used per year. The Director of Animal Science and Technologies at AstraZeneca confirms that without Professor Hurst’s research and a robust evidence base for the new methods “we would have been unaware of the aversion caused to mice by picking them up by the tail”. This has provided benefits for animal welfare, efficiency, staff satisfaction and reduced variability in scientific testing. For example, at the Swedish site, “tube handling and cupping have improved behavioural tests that are part of the phenotyping screens we conduct”. They report that “the methods do not take any extra time and reduce signs of stress (such as defaecation)”, “mice are easier to handle”, “staff enjoy the methods for handling”, and “having mice that are less anxious and therefore more consistently calm means that there is less variability in the scientific output” [5.8].

Impact on training:

NC3Rs’ website provides the main source of 3Rs information in the UK, with a strong global reach. A resource hub on best practice in mouse handling based on Hurst’s refined methods has been one of the ‘top level’ hubs under 3Rs resources since 2016 [5.2]. This hub features a video tutorial (14,390 views) and short training clips (17,565 views, 871 downloads) produced by Hurst’s team, a webinar by Hurst (5,453 views) and short video interview, a summary of the evidence base, FAQs and tips for implementation. The hub landing page is the 13th most popular page on NC3Rs website since initiation, receiving 35,290 unique views (62,449 unique views totalled across mouse handling pages); users are from 107 countries (22.3% UK, 20.4% USA). NC3Rs have sent out 4,015 instructional posters for animal facilities to 415 institutions in 56 countries, now translated into Chinese, French and German [5.2,5.6].

NC3Rs workshops for institutional trainers and Named Training & Competence Officers (NTCOs) were attended by 80 delegates each in 2017 and 2018, both featuring plenary presentations from UoL’s Hurst and Waters. Many institutions now provide their own internal training [5.5], with training also given in UK modular training courses required to gain personal and project licences e.g. The Learning Curve have trained 180-250 students per annum in these methods since 2017; Red Kite Veterinary Consultants trained 246 candidates March 2017- Nov 2019 [5.9]. Refined mouse handling was a central topic for the Sixth UK-China Seminar on Animal Welfare and Ethics in May 2019 to promote China’s alignment with international standards. The Swiss Laboratory Animal Science Association provides training in the refined methods in CPD training courses, and Hurst’s team have delivered over 80 presentations and tutorials across 12 countries.

Impact on provision of new commercial products:

The new cupping method does not require any equipment, as tunnel handling can use cardboard tubes already available as enrichment resources. However, purpose-designed clear autoclavable handling tubes provide a new product supplied by Datesand Ltd (UK), LBS Biotechnology (UK), Braintree Scientific Inc (USA) and SerLab (France) from 2016 onwards. Datesand Ltd have sold 84,993 tunnels from 2018-2020 (60% UK, 40% international). Customers were from 15 countries (54% industry, 46% academic sector) [5.10].