The 3Rs today event at the House of Lords
On Wednesday 25 March 2009, the NC3Rs held an event in the Cholmondeley Room at the House of Lords to highlight the latest 3Rs research to an invited audience of MPs, Peers and other key stakeholders. The event was sponsored by Lord Sainsbury, former Minister of State for Science and Innovation, and was held as part of the NC3Rs' activities to mark the 50th anniversary of the 3Rs.
Forty-three posters were presented by scientists from academia and industry, communicating work across all three 'R's. The posters were judged on the quality of the science, the impact on the 3Rs and, most importantly, the ability of the poster presenters to communicate their research to a non-specialist audience. A judging panel of nine assessed the entries and awarded three prizes of £3k, one each for Replacement, Refinement and Reduction.
The prizes were presented by Lord Drayson, Minister of State for Science and Innovation. In addition, to the three winning posters, recognition was also given to six highly commended posters. A press release was issued to highlight the event and an abstract booklet (PDF, 4.1 MB) was produced which briefly describes the work that was presented, in the words of the researchers involved. Below are details of the winning posters.
Winner of the Replacement prize
A 3D model of breast cancer: towards replacing the need for animal experiments (PDF, 278KB)
Deborah Holliday, University of Leeds and Kellie Brouilette, Anja Markert, Linda Gordon and Louise Jones, Barts and The London School of Medicine and Dentistry
Breast cancer is the commonest female cancer in the UK with over 45,000 new cases diagnosed and more than 12,000 women dying of the disease every year. Whilst the events leading to breast cancer development are not fully understood, a pre-invasive lesion is recognised as the main precursor of invasive disease. Understanding how pre-invasive lesions develop into invasive breast cancer is critical as currently there is no way of knowing which tumours are likely to progress, which can lead to unnecessary surgical intervention or unpleasant chemotherapy.
We have developed a three-dimensional (3D) laboratory model of pre-invasive breast cancer. Our model is the first of its kind to grow the three major cellular components of the breast: luminal epithelial cells, myoepithelial cells and fibroblasts in one system. Using this model we have shown that fibroblasts play a major role in the development of invasive breast cancer.
Currently we are manipulating our 3D model to closely reflect the many different types of breast cancer. In doing this we hope to replace animal models of breast cancer, such as mouse xenograft models which commonly use over 100 mice per experiment. Our model is likely to be advantageous over animal models because it more closely represents human disease and allows us to mimic the complex cellular interactions occurring in breast cancer; an essential step in understanding breast cancer behaviour.
Winner of the Reduction prize
Refinement and reduction in an animal model used in obesity research (PDF, 980KB)
Steven Wang, AstraZeneca
Obesity is an important global health problem, resulting in a strong emphasis on R&D in this area and its related illnesses, such as Type 2 diabetes. Uncontrolled obesity and diabetes can also increase the risk of stroke, impotency, blindness and kidney failure. One approach to tackling this problem is to search for proteins in the body which control the biology of these diseases. By manipulating these proteins, scientists aspire to develop new medicines.
One of the proteins identified is diacylglycerol acyltransferase-1 (DGAT1), an enzyme which converts excess circulating fat into fatty tissue for storage. By blocking the activity of this enzyme, scientists hope to reduce the build up of excess fatty tissue. To test this concept, we developed a method to quantify the activity of this enzyme in the rat. Historically, we used an anaesthetised rat, which required invasive surgery to infuse radiolabelled fatty acid into the vein. The rats were then euthanased and a sample of the fatty tissue analysed. This method was laborious, surgically invasive and time consuming.
In line with 3Rs principles, we replaced the use of live rats with an ex vivo model involving a simple incubation of a small sample of the rat adipose tissue with radiolabelled fatty acid. This reduced the number of animals required to achieve statistically valid results (the old method used 10-12 per group and the new method uses only five per group). The new methodology also meant that there was no need for animals to undergo surgical procedures. The new method generated very robust and reproducible data, and could also be directly applicable to humans to help in conducting clinical trials.
Winner of the Refinement prize
Opportunities for refinement and reduction: use of dried blood spots for generation of toxicokinetic data (PDF, 124KB)
Cerys Lovatt, Sue Sparrow, Neil Spooner, Matthew Barfield and Susan Fowles, GlaxoSmithKline
Before a new medicine is given to people, an assessment of its safety in animals must be made to meet international and national regulations; any harmful effects (toxicity) are evaluated and related to the amount of medicine circulating in the blood of the animal (toxicokinetics). A safety margin can then be estimated by comparing circulating blood concentrations of medicine in the animal at doses causing adverse effects with concentrations predicted to be effective in treating disease in humans.
Traditionally, toxicokinetics has been performed using plasma due to the ease of handling and transport, compared to whole blood; technology is now available to enable the use of dried blood spots (DBS) instead. DBS requires much smaller volumes of blood than traditional plasma analysis (potentially up to around 85% less) and offers exciting opportunities for the 3Rs in safety studies, particularly refinement and reduction.
Use of smaller volumes offers opportunities for refinement, by decreasing the amount of blood sampled from animals and by reducing or removing the need for pre-warming the animal (considered stressful) prior to blood sample collection. Furthermore, the lower blood volumes required leads to the most exciting opportunity the potential reduction in animal numbers by up to 36%, through eliminating the need to include additional animals for toxicokinetic assessment. As part of sharing good practice, we are working collaboratively with other pharmaceutical companies to promote the use of DBS.
Highly commended prizes
Development of a cell-based diabetic wound bioassay
Matthew Peake, Stuart Jones, Matthew Caley, Peter Giles, Lindsay Davies, David Kipling, David Thomas and Phil Stephens, Cardiff University
Caterpillars as a model to replace mammals used to study fungal infections
Joanne Slater and Peter Warn, University of Manchester
Lighting the way to reduced animal use
Siouxsie Wiles, Imperial College London
An improved technique which has reduced the number of dogs used in the discovery of new inhaled medicines
Karen Wright, Tim Davies and Balaji Agoram, Pfizer
Refinement of a standard gastrointestinal (charcoal meal) study
Helen Prior, Patricia Pimlott, Liz Fantham, Lorna Ewart, Guy Healing and Jean-Pierre Valentin, AstraZeneca
Refinement and reduction of animal use for routine pharmacokinetic experiments using surgically modified animals
Ruth Storer, AstraZeneca