Standard operating procedures in experimental liver research: time to achieve uniformity.

Abstract

In the last two years the European Parliament and the Council of the European Union (EU) have implemented the EU Directive 2010/63 in their Member States. This legislation regulates the protection of animals used for scientific or educational purposes. The Directive was adopted on 22 September 2010 and is based mainly on the execution of the 3R principle first proposed in 1959 by William Russell and Rex L Burch as an ethical framework for conducting scientific experiments with animals that encourages the replacement, reduction and refinement of animals used for scientific purposes and testing. In the 66 Articles of Directive 2010/63, strict rules for breeding, marking, and care including the accommodation and killing of animals as well as the evaluation and authorization of projects involving the use of animals in so-called ‘procedures’ are laid down. The term ‘procedure’ in this revised regulation is defined as any intervention that may cause pain, suffering, distress or lasting harm to an animal. A report published at the end of 2007 covering statistical data that was collected in the former 25 EU Members States in 2005 revealed that about 12.1 million animals were used for experimental and other scientific purposes in the EU, of which mice (53%) and rats (19%) were by far the most used species. In addition, this report further emphasized that 57.5% of the total animals used for experimental purposes in the EU were used for studies analysing both animal and human diseases. On the basis of these facts, it is surprising that in many research fields that conduct ‘translational medicine’ there is no comprehensive consensus on how to execute, evaluate, or characterize potential animal models and ‘procedures’. Unfortunately, this makes the direct comparison of experimental results and the effective exchange of data between different research groups difficult or even impossible. Of course this precludes the realization of the 3R principle and further generates conflicting data that needs to be verified by additional animal experimentation. Therefore, considerable effort is presently being expended in developing novel alternative replacement strategies and also to provide detailed and standardized operating procedures (SOPs) for the conducting of the different ‘procedures’ in biomedical research that employ animals. In hepatological research, animal models are still the gold standard for analysing complex disease-associated cellular reactions, signalling pathways and networks, or testing the efficacy of candidate drugs. Most of these studies are carried out in laboratory mice. However, a recent literature review that highlights the reporting of details related to mouse welfare in 119 studies which involved, for example, bile duct ligation in mice as a model for hepatic fibrosis and cholestasis, has shown that there is a fundamental failure to report details that may be sources of considerable experimental variability. This example indicates that the specific SOPs (including information starting from the animal’s caging, housing, care, feeding and bedding up to anaesthetic regimen, surgical procedure, and post-operative monitoring, also specifying details about nursing care and humane endpoints) are still necessary. It is the scope of Laboratory Animals to publish papers dealing with all aspects of the use of animals