A Review of the Contributions of Cross-discipline Collaborative European IMI/EFPIA Research Projects to the Development of Replacement, Reductionand Refinement Strategies

Sarah Wolfensohn

The objective of this review is to report on whether, and if so, how, scientific research projects organised and managed within collaborative consortia across academia and industry are contributing to the Three Rs (i.e. reduction, replacement and refinement of the use of animals in research). A number of major technological developments have recently opened up possibilities for more direct, human-based approaches leading to a reassessment of the role and use of experimental animals in pharmacological research and biomedicine. This report reviews how projects funded by one of the research funding streams, the Innovative Medicines Initiative (IMI), are contributing to a better understanding of the challenges faced in using animal models. It also looks how the results from these various projects are impacting on the continued use of laboratory animals in research and development. From the progress identified, it is apparent that the approach of private–public partnership has demonstrated the value of multicentre studies, and how the spirit of collaboration and sharing of information can help address human health challenges. In so doing, this approach can reduce the dependence on animal use in areas where it has normally been viewed as necessary. The use of a collaborative platform enables the Three Rs to be addressed on multiple different levels, such that the selection of models to be tested, the protocols to be followed, and the interpretation of results generated, can all be optimised. This will, in turn, lead to an overall reduction in the use of laboratory animals.

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To Be Credible, Success in “Reducing the Use of Animals in Scientific Research” Must Involve the Use of Fewer Animals

Michael Balls

Much worthy effort on the Three Rs is under way in the UK, but its promise of a reduction in laboratory animal use will only be credible and laudable when the number of procedures and animals are progressively and permanently reduced.
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A ‘Road Map’ Toward Ending Severe Suffering of Animals Used in Research and Testing

Elliot Lilley, Penny Hawkins and Maggy Jennings

Ending severe suffering is a desirable goal for both ethical and scientific reasons. The RSPCA has pledged to work toward the end of such suffering for laboratory animals, and in this article we outline a practical approach that establishments can follow to achieve this aim.
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Comment: Every Silver Lining has a Cloud

Robert D. Combes and Michael Balls

The Scientific and Animal Welfare Issues Surrounding a New Approach to the Production of Transgenic Animals

The scientific basis and advantages of using recently developed CRISPR/Cas-9 technology for transgenesis have been assessed with respect to other production methods, laboratory animal welfare, and the scientific relevance of transgenic models of human diseases in general. As the new technology is straightforward, causes targeted DNA double strand breaks and can result in homozygous changes in a single step, it is more accurate and more efficient  than other production methods and speeds up transgenesis. CRISPR/Cas-9 also obviates the use of embryonic stem cells, and is being used to generate transgenic non-human primates (NHPs). While the use of this method reduces the level of animal wastage resulting from the production of each new strain, any long-term contribution to reduction will be offset by the overall increase in the numbers of transgenic animals likely to result from its widespread usage. Likewise, the contribution to refinement of using a more-precise technique, thereby minimising the occurrence  of unwanted genetic effects, will be countered by a probable substantial increase in the production of transgenic strains of increasingly sentient species. For ethical and welfare reasons, we believe that the generation of transgenic NHPs should be allowed only in extremely exceptional circumstances. In addition, we present information, which, on both welfare and scientific grounds, leads us to question the current policy of generating ever-more new transgenic models in light of the general failure of many of them, after over two decades of ubiquitous use, to result in significant advances in the understanding and treatment of many key human diseases. Because this unsatisfactory situation is likely to be due to inherent, as well as possibly avoidable, limitations in the transgenic approach to studying disease, which are briefly reviewed, it is  concluded that a thorough reappraisal of the rationale for using genetically-altered animals in fundamental research and by the pharmaceutical industry, and for its support by funding bodies, should be undertaken. In the meantime, the use of CRISPR/Cas-9 to generate new transgenic cells in culture is to be guardedly encouraged.

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