animal experiments

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The Implications of Microarray Technology for Animal Use in Scientific Research

Elizabeth S. Jenkins, Caren Broadhead and Robert D. Combes

Microarray technology has the potential to affect the number of laboratory animals used, the severity of animal experiments, and the development of non-animal alternatives in several areas of scientific research. Microarrays can contain hundreds or thousands of microscopic spots of DNA, immobilised on a solid support, and their use enables global patterns of gene expression to be determined in a single experiment. This technology is being used to improve our understanding of the operation of biological systems during health and disease, and their responses to chemical insults. Although it is impossible to predict with certainty any future trends regarding animal use, microarray technology might not initially reduce animal use, as is often claimed to be the case. The accelerated pace of research as a result of the use of microarrays could increase overall animal use in basic and applied biological research, by increasing the numbers of interesting genes identified for further analysis, and the number of potential targets for drug development. Each new lead will require further evaluation in studies that could involve animals. In toxicity testing, microarray studies could lead to increases in animal studies, if further confirmatory and other studies are performed. However, before such technology can be used more extensively, several technical problems need to be overcome, and the relevance of the data to biological processes needs to be assessed. Were microarray technology to be used in the manner envisaged by its protagonists, there need to be efforts to increase the likelihood that its application will create new opportunities for reducing, refining and replacing animal use. This comment is a critical assessment of the possible implications of the application of microarray technology on animal experimentation in various research areas, and makes some recommendations for maximising the application of the Three Rs.
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Report of a Meeting to Discuss a National Centre for the Replacement of Animals in Experiments

Christine Brock, Gill Langley and Carol Newman

Following the publication of their joint proposal for a National Centre for the Replacement of Animals in Experiments in 2002, the Dr Hadwen Trust and the Lord Dowding Fund organised a meeting, held on 18 November 2003 at Portcullis House, Westminster, in London, in order to discuss the concept further. A one-page summary of their proposal is attached as an appendix, and full copies are available from the Lord Dowding Fund and the Dr Hadwen Trust. The meeting aimed to discuss the need to stimulate and promote research to replace animal experiments by means of a National Centre (a coordinating body), and how this should be established and funded. Participants, numbering about 80 in total, included politicians (national and European), government officials, scientists, funding bodies and animal welfare representatives. This report is a summary of the issues raised by speakers and other participants at the meeting.
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Estimates for Worldwide Laboratory Animal Use in 2005

Katy Taylor, Nicky Gordon, Gill Langley and Wendy Higgins

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and
unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that publish national statistics, and standardised these against the definitions of ‘animals’, ‘purposes’ and ‘experiments’ used in European Union Directive 86/609/EEC. We developed and applied a statistical model, based on publication rates, for a further 142 countries. This yielded our most conservative estimate of global animal use: 58.3 million animals in 179 countries. However, this figure excludes several uses and forms of animals that are included in the statistics of some countries. With the data available, albeit for only a few countries, we also produced, by extrapolation, a more comprehensive global estimate that includes animals killed for the provision of tissues, animals used to maintain genetically-modified strains, and animals bred for laboratory use but killed as surplus to requirements. For a number of reasons that are explained, this more-comprehensive
figure of 115.3 million animals is still likely to be an underestimate.
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The FRAME Reduction Steering Committee: Reflections on a Decade Devoted to Reducing Animal Use in Biomedical Science

Michelle Hudson and Bryan Howard

Established in 1998, the FRAME Reduction Committee (FRC) (now the FRAME Reduction Steering Committee [FRSC]) has continued to pursue its aim of reducing the number of animals used in biomedical science. Through its expertise in statistics, experimental design, animal welfare and research on alternatives, it has contributed to raising awareness of the need for reduction and the means of achieving and demonstrating it. In recognising the need for training of scientists to appreciate and understand the concept of reduction, the FRSC has organised dedicated workshops and training schools. Some of the Committee’s major achievements are described, and, bearing in mind the current year-on-year increases in the number of scientific procedures on animals, its future activities are outlined.
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Computer Simulation Models are Implementable as Replacements for Animal Experiments

Dinesh K. Badyal, Vikas Modgill and Jasleen Kaur

It has become increasingly difficult to perform animal experiments, because of issues related to the procurement of animals, and strict regulations and ethical issues related to their use. As a result, it is felt that the teaching of pharmacology should be more clinically oriented and that unnecessary animal experimentation should be avoided. Although a number of computer simulation models (CSMs) are available, they are not being widely used. Interactive demonstrations were conducted to encourage the departmental faculty to use CSMs. Four different animal experiments were selected, that dealt with actions of autonomic drugs. The students observed demonstrations of animal experiments involving conventional methods and the use of CSMs. This was followed by hands-on experience of the same experiment, but using CSMs in small groups, instead of hands-on experience with the animal procedures. Test scores and feedback showed that there was better understanding of the mechanisms of action of the drugs, gained in a shorter time. The majority of the students found the teaching programme used to be good to excellent. CSMs can be used repeatedly and independently by students, and this avoids unnecessary experimentation and also causing pain and trauma to animals. The CSM programme can be implemented in existing teaching schedules for pharmacology undergraduate teaching with basic infrastructure support, and is readily adaptable for use by other institutes.
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Reflections on Dialogue Processes, FRAME and the Three Rs

Jane A. Smith

My contribution to FRAME’s 40th Anniversary meeting started by looking back: offering some reflections on the benefits and difficulties of engaging in wide-ranging dialogue on laboratory animal issues, largely based on experience with two forums — both of which have involved FRAME. Drawing on this discussion, I then looked forward: arguing that such dialogue now has an especially important role to play in developing strategies to replace (and reduce or avoid) the use of animals in research.
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Reporting the Implementation of the Three Rs in European Primate and Mouse Research Papers: Are We Making Progress?

Katy Taylor

It is now more than 20 years since both Council of Europe Convention ETS123 and EU Directive 86/609?EEC were introduced, to promote the implementation of the Three Rs in animal experimentation and to provide guidance on animal housing and care. It might therefore be expected that reports of the implementation of the Three Rs in animal research papers would have increased during this period. In order to test this hypothesis, a literature survey of animal-based research was conducted. A randomly- selected sample from 16 high-profile medical journals, of original research papers arising from European institutions that featured experiments which involved either mice or primates, were identified for the years 1986 and 2006 (Total sample = 250 papers). Each paper was scored out of 10 for the incidence of reporting on the implementation of Three Rs-related factors corresponding to Replacement (justification of non-use of non-animal methods), Reduction (statistical analysis of the number of animals needed) and Refinement (housing aspects, i.e. increased cage size, social housing, enrichment of cage environment and food; and procedural aspects, i.e. the use of anaesthesia, analgesia, humane endpoints, and training for procedures with positive reinforcement). There was no significant increase in overall reporting score over time, for either mouse or primate research. This review provides systematic evidence that animal research is still not properly reported, and supports the call within the scientific community for action to be taken
by journals to update their policies.
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Replacing Animal Use in Physiology and Pharmacology Teaching in Selected Universities in Eastern Europe — Charting a Way Forward

David G. Dewhurst and Zvezdana Z. Kojic

The aims of this study were to explore the use of animals in teaching and the implementation of innovative technology-based teaching practices across a small sample of universities in Eastern Europe. The research methods used were a questionnaire circulated four weeks before a workshop took place (in October 2009, in Belgrade, Serbia), as well as focused, face-to-face group discussions, led by one of the authors during the workshop. Twenty-two faculty (physiologists and pharmacologists), from 13 Eastern European countries, attended the meeting. Fourteen of the eighteen schools represented at the workshop were making use of animals, in some instances in quite large numbers, for their teaching. For example, a single department at a Romanian university used over 250 animals per annum, and at least 1130 animals were used, per annum, across all of the institutions. The species used in largest numbers were the rat (34%), frog/toad (29%), mouse (22%), rabbit (10%), guinea-pig (4%) and dog (1%). None of the universities sampled had implemented institution-wide virtual learning environments (VLEs), although there were isolated instances of local use of VLEs. There was relatively little current use of technology-based teaching and learning resources, but there was considerable enthusiasm to modernise teaching and to introduce innovative learning and teaching methods. The major perceived barrier to the introduction of replacement alternatives was the lack of versions in local languages. There was a consensus view that developing local language exemplars and evaluating their usefulness was likely to have the greatest impact on animal use, at least in the short-term.
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Guidelines for the Design and Statistical Analysis of Experiments in Papers Submitted to ATLA

Michael F.W. Festing

In vitro experiments need to be well designed and correctly analysed if they are to achieve their full potential to replace the use of animals in research. An “experiment” is a procedure for collecting scientific data in order to answer a hypothesis, or to provide material for generating new hypotheses, and differs from a survey because the scientist has control over the treatments that can be applied. Most experiments can be classified into one of a few formal designs, the most common being completely randomised, and randomised block designs. These are quite common with in vitro experiments, which are often replicated in time. Some experiments involve a single independent (treatment) variable, whereas other “factorial” designs simultaneously vary two or more independent variables, such as drug treatment and cell line. Factorial designs often provide additional information at little extra cost. Experiments need to be carefully planned to avoid bias, be powerful yet simple, provide for a valid statistical analysis and, in some cases, have a wide range of applicability. Virtually all experiments need some sort of statistical analysis in order to take account of biological variation among the experimental subjects. Parametric methods using the t test or analysis of variance are usually more powerful than non-parametric methods, provided the underlying assumptions of normality of the residuals and equal variances are approximately valid. The statistical analyses of data from a completely randomised design, and from a randomised-block design are demonstrated in Appendices 1 and 2, and methods of determining sample size are discussed in Appendix 3. Appendix 4 gives a checklist for authors submitting papers to ATLA.
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