In the ten years since the NC3Rs began, we have proved that cutting edge science and 3Rs advances go hand-in-hand. The environment has changed significantly and many scientists are now far more engaged with the 3Rs agenda; recognising the benefits of minimising animal numbers, improving welfare and searching for alternative approaches. This year’s annual report describes our various strategic approaches for driving change, including;
Our biggest milestone this year was the launch of ‘Our Vision 2015-2025’, which sets out our future plans around five ‘Ps’; Practice, Procedures, People, Places and Policy. Other highlights include the launch of our new website, an increased focus on public engagement activities, and our collaboration in a new national programme to drive business creation in the area of non-animal technologies.
Dr Vicky Robinson CBE, Chief Executive
Professor Stephen Holgate CBE, Board Chair
Vicky Robinson talks about this year's annual report
The ARRIVE guidelines are intended to improve the reporting of research using animals - maximising information published and minimising unnecessary studies. We are working with journals that have signed up to ARRIVE to encourage better enforcement of the guidelines' use by providing a checklist for authors, reviewers and editors.
We support research funders committed to high standards in animal studies by providing expert advice on the 3Rs. This mainly involves reviewing grant, fellowship and studentship proposals, prioritising those which involve non-human primates, cats, dogs or equines.
In 2014, we reviewed over 60 research proposals submitted to the MRC, BBSRC and Wellcome Trust. Working with the AMRC, we held a second workshop on incorporating the 3Rs in the peer review process.
We began reviewing research proposals for AMRC charities in 2014. The EPSRC also joined our peer review service in 2014.
As part of our programme on experimental design we have worked with the MRC to strengthen the information on animal numbers that is required in grant applications. The revised guidance has been adopted by other Research Councils.
* Wellcome Trust includes joint initiatives with Indian Department of Biotechnology (DBT) and Kenyan Consortium for National Health Research (CNHR) ** Other includes the Royal Society and AMRC member charities
We have increased our focus on public engagement activities in 2014.
We introduced the Public Engagement Awards to support NC3Rs grant holders with outreach activities. We made seven awards for a range of activities, including events held at science museums and schools, as well as laboratory visits.
We also sponsored three Pint of Science events, with our researchers giving informal talks in pubs in London, Oxford and York. We held a public lecture entitled “Keeping a watchful eye on animal behaviour” at the British Science Festival, where three NC3Rs grant holders spoke about using the latest video technologies to monitor animal welfare.
Our public engagement events were attended by over 2,300 people.
New analytical techniques and methods for taking small blood samples, or 'microsampling', provide the opportunity to assess both exposure to a drug and related adverse effects in the same animals, rather than requiring a separate 'satellite' group of rats or mice for toxicokinetics.
We have shown that microsampling can reduce the number of rats used from 200 to 140 per study and the number of mice from 158 to 80 by minimising the need for satellite animals. The smaller blood volumes also mean that sampling can be refined.
Widespread uptake of microsampling has been limited by concerns among pharmaceutical companies about regulatory acceptance and practical challenges around implementing new techniques.
We are working with 25 companies and international regulators to address these concerns. In 2014 we published a paper in Drug Discovery Today and a commentary piece in Bioanalysis, both with industry collaborators, on the barriers to microsampling and the importance of collaboration between toxicologists, pathologists and bioanalysts.
To increase uptake we are developing an online portal, providing practical advice for microsampling.
Environmental safety testing of chemicals is a legal requirement, and represents a significant driver of animal use. This is an important area for the NC3Rs, since increasing societal concerns over how chemicals affect the environment will impact on animal testing. Working with agrochemical and industrial chemical industries, we have carried out a number of data analysis projects on fish acute and chronic toxicity tests, and bioaccumulation studies.
In 2014, we published a paper on our analysis of 236 general chemicals, which demonstrated that only one concentration of a chemical needs to be used in bioaccumulation studies – saving approximately 50 fish per chemical tested. The paper published in Regulatory Toxicology and Pharmacology, was viewed over 1,200 times in the first three months after publication.
In 2014, we worked with experts to map a ten year vision for future work in ecotoxicology; highlighting global harmonisation of test requirements as a priority area.
Our work on applying the 3Rs to asthma research is the most advanced of our disease-related scientific programmes. In 2014, we continued to work with the respiratory biology community on the utility of non-animal approaches.
We carried out a survey to better understand how human lung tissue is currently used in asthma research, and to identify potential barriers to wider adoption. The survey was conducted in collaboration with Asthma UK, the UK Respiratory Research Collaborative and the UK Human Tissue Authority, and the results have been published in Thorax.
We awarded four strategic grants, totalling £400k, to explore the use of non-mammalian model organisms for asthma research, based on the premise that they may be appropriate for studying conserved biological pathways related to inflammation.
The awards were for new collaborations between asthma researchers and experts in the use of zebrafish, Drosophila and Dictyostelium models.
Our portfolio also includes other disease-related programmes on epilepsy, stroke, pain and cancer. The areas selected are based on a number of criteria, including questions about the validity of current animal models and their human relevance, increasing demand for animal use in particular areas, concerns about the severity of the procedures involved and the opportunities arising from emerging technologies.
The Rodent Big Brother CRACK IT Challenge, developed with AstraZeneca, was the first to produce a marketable product. Winning company Actual Analytics launched their rodent behaviour tracking system in September 2014. The system provides continual monitoring, identification of specific behaviours and comprehensive data collection. The technology also improves rat welfare by allowing the animals to be socially housed in their home cage.
Winning the Rodent Big Brother Challenge has provided new and exciting opportunities for our company. The monitoring system that we have developed for assessing the behaviour and welfare of rats used in safety pharmacology and toxicity studies has the potential to have a global impact. We estimate that there are around 2.5 million rat procedures carried out each year in our target users. With a 5% market penetration we estimate $60 million of sales.
David Craig, Chief Executive Officer
Using our technology partnering hub, CRACK IT Solutions, Dr Colin Brown, from Newcastle University, has partnered with SOLVO Biotechnology and secured substantial investment to make his aProximateTM proximal tubule cell model commercially available.
Many drugs fail before they reach the clinic owing to nephrotoxicity not identified earlier in drug development. Most toxic and drug-induced injuries in the kidney occur in the proximal tubules. There is a need for more predictive models to assess nephrotoxicity. Dr Brown’s model offers a solution to this problem.
SOLVO Biotechnology now includes the aProximateTM model in it's portfolio of renal transporter assays, making the technology available to a global customer base and maximising the potential 3Rs and drug development benefits.
We have demonstrated the commercial potential of the 3Rs through our CRACK IT programme. This has led to a new collaboration with Innovate UK, and a new national programme to drive business creation in this area, specifically focusing on non-animal technologies such as stem cells, tissue engineering technologies and computational modelling.
With Innovate UK, BBSRC and EPSRC, we have co-funded fifteen business-led feasibility studies to explore the commercial viability of non-animal technologies. The awards totalled approximately £4 million and the winning teams included 25 SMEs, 12 academics and five major companies, including Unilever and GlaxoSmithKline.
We are leading, in partnership with Innovate UK, the development of a roadmap on non-animal technologies, which will be published in 2015. The roadmap will set out the market opportunities, the areas for science and technology investment, and the infrastructure that will be necessary to establish the UK as a world leader in the non-animal technologies industry.
Total committed by NC3Rs in 2014* = £5,580,777
*Research funding only.
We support our early-career researchers with a number of development opportunities, including targeted training on the 3Rs.
We hosted our second PhD student summer school in Cambridge in June, and in July we held our first fellowship meeting in London. One of the goals of these events is to build relationships and establish career-long networks. Our first cohort of five students has now graduated, and four have secured post-doctoral positions.
In 2014, we committed almost £600k to fund three David Sainsbury Fellows, and a further £900k to support ten studentship projects at eight institutions across the UK.
NC3Rs student summer school attendees 2014
We have a dedicated 3Rs evaluation framework for measuring our impact to ensure that our strategy is effective, the projects we fund provide value for money and are on track, and that there is a benchmark for progress on the 3Rs.
To support the framework, we joined Researchfish in 2014, an online self-reporting system used by more than 80 research organisations and funding bodies. There is an annual data collection period, where information on a range of outputs including publications, collaborations established and research materials developed, are submitted by grant holders.
Tracking the impacts of our funded research is a useful tool for assessing progress, although it is important to note that it can take a number of years for the full 3Rs benefits of the awards to be realised.
Outcomes of interest*
of completed grants
have reported a 3Rs impact
publications have resulted
from NC3RS awards since 2004
of awards developed new
research materials, such as models,
products have been reported,
two patents and two trademarks
*Data collected in 2014, although not relating to 2014 exclusively
Our strategic award scheme allows us to target funding to areas of key importance, for example, where animal use is increasing or where there are new technological opportunities to exploit.
In April 2014, we awarded £1.5 million in a strategic call to develop preclinical imaging technologies and approaches. Imaging technologies have significant 3Rs potential, for example, allowing earlier humane endpoints to be used and longitudinal studies on the same animals to be conducted.
The funding supported five projects to increase the utility of a broad spectrum of imaging techniques, including bioluminescence, radiolabelling and implantable technologies. The EPSRC contributed £500k to this call.
This annual report describes the NC3Rs activities for the calendar year 2014. The financial information provided covers the period 1 April 2013 to 31 March 2014 and has been compiled using data from UK Shared Business Services Ltd (UK SBS).
The UK SBS provides the NC3Rs with accounting and budget management services with additional support from the MRC.
Total income for this financial period was £7.74 million. The income from ‘Government’ comes from the Department for Business, Innovation and Skills (via the Research Councils and Innovate UK), Defra and the Home Office.
Total expenditure in 2013/14 was £7.74 million. Awards typically commit expenditure over a three year period with payments spread over four financial years. Award costs in 2013/14 are related to funding awarded between 2009 and 2013.
Programme costs cover science initiatives led by the NC3Rs staff and include staff salaries and costs for working groups, workshops and events.
Operating costs include staff salaries for core administrative duties, staff travel and training, and rental charges.
1 Includes £3.6 million deferred income from previous financial years. Government contribution in 2012/13 totalled £8.19 million.
2 Includes planned spend of deferred income from previous financial years.
The NC3Rs receives funding from the public, commercial and charitable sectors. A list of funders is provided below.
Association of the British Pharmaceutical Industry1
Alzheimer’s Research UK
Biotechnology and Biological Sciences Research Council
Department for Environment, Food and Rural Affairs
Engineering and Physical Sciences Research Council
Medical Research Council
The Dow Chemical Company
1 In accordance with the ABPI’s Code of Practice regulating the pharmaceutical industry, the following companies have provided funding to the NC3Rs as part of the ABPI-NC3Rs collaboration: AstraZeneca, Covance, Eli Lily & Company Limited, GlaxoSmithKline, Huntingdon Life Sciences, Novartis, Pfizer, Shire, Takeda and UCB.