Ethics of Research involving animals
Other issues - continuation I
Duplication
15.68 Another area where there may be potential for reduction concerns the avoidance of duplication of research or testing (see paragraphs 12.6 and 15.16). In some areas, this can be achieved simply by better coordination and dissemination of information. For example, a recent report by the European Commission on the Evaluation of the Active Substances of Plant Protection Products34 observed:
‘4.6 … multiple dossiers. Many different dossiers were submitted for the same substances, unnecessarily multiplying the number of evaluations required. While every effort was made to encourage notifiers to create taskforces and to submit a single dossier per substance, it was not always possible to achieve this. For example, there were 35 notifiers for the active substance glyphosate and 11 dossiers were submitted. This proved wasteful of resources, as the Rapporteur Member State (Germany) had to examine each one. In the event, only four dossiers were considered complete and could be assessed in detail.
Ideally, there would have been a single dossier. This would have saved resources both for the various notifiers and for the Rapporteur Member State. It would also have resulted in fewer laboratory animals being sacrificed in duplicated testing. While every effort is still being made to encourage notifiers to create taskforces and to submit a single dossier per substance, it is still not always possible to achieve this. A solution could be to introduce provision in the legislation to avoid duplicate testing e.g. action point 5F in the White Paper on a Chemicals Strategy35 proposes that any duplicate testing on vertebrate animals will not result in an exemption from the duty to reimburse the party that owns the property rights to the first test.’
15.69 While this is a clear and unfortunate example of duplication, it appears that the extent to which duplication occurs, whether internationally or nationally, is difficult to assess. Those suspecting that there is a substantial and avoidable amount of duplication are concerned that academic and commercial competition and the aim of protecting intellectual property rights frequently lead researchers to be reluctant to share data. They also assert that many more examples of insufficient coordination, similar to the one described above, could be given.36 Those who disagree consider that in general there are sufficient mechanisms in place to ensure the avoidance of duplication, such as the publication of peer-reviewed research in scientific journals and presentation at conferences. They take the view that duplication is unlikely to be a widespread phenomenon because funding bodies only support novel research and because both academic and commercial research institutes need to manage resources efficiently, usually implying that only original research is carried out.
15.70 We cannot explore the question of the extent to which duplication occurs, or the feasibility of devising mechanisms that help to avoid the duplication of research in this Report. But we are clear that, in principle, duplication is unacceptable (paragraph 15.16) and we therefore welcome the approach underlying the UK Government’s Inter-Departmental Data Sharing Concordat (paragraph 12.6). The Concordat has recently been reviewed by the Government who commented that the agreement had ensured that ‘regulators promote data sharing within the scientific community’, noting also that there was no evidence that duplication was ‘a significant problem in the UK.’37 The Working Party has not been able to study the review, and is hence not in a position to comment on the Government’s view.38 We note that the APC welcomed the Concordat in its 2003 Report Review of Cost Benefit Assessment in the Use of Animal Research39 but cautioned that it is not yet clear how effective it will be in preventing duplication of animal studies. In particular, the APC was concerned about the voluntary nature of the Concordat, and considered whether more binding measures, such as legislation, will be needed to achieve the Concordat’s aims. We endorse the APC’s conclusion that the operation and effectiveness of the Concordat should be monitored carefully and reports placed in the public domain. The Concordat will be reviewed again in 2006. Depending on the outcome of the review, Ministers should explore whether it would be useful to request the APC to undertake a systematic study addressing in more detail specific issues raised by the possible duplication of research. Such a study could complement and develop further the review of the Concordat, for example by assessing the extent of the problem and, where appropriate, identifying strategies for the avoidance of duplication nationally and internationally. Consideration could also be given to the question of whether duplication occurs because some kinds of data are not made publicly available when experiments fail. It would be especially undesirable if researchers wasted time and effort in duplicating experiments that have elsewhere been found to be unsuccessful. The study could also consider whether funding bodies would have a role in sharing or making available information about past or current research, in order to avoid duplication. We consider special issues with regard to avoiding duplication in the case of GM animals in the next section.
The use of GM animals in basic research
15.71 Specific problems in assessing welfare may be raised by relatively novel ways of producing animals, such as genetic modification or cloning. We take the view that the focus of any concern, in the case of all deliberate attempts to influence the genetic basis of animals, should be on the welfare implications in terms of the likely pain, suffering or distress.
15.72 Welfare implications that may be associated with specific ways of producing animals should be assessed as far as possible in advance. In some areas of basic research, such as forward or reverse genetics, welfare assessments are often not straightforward. If such research is deemed desirable, it is important to limit the number of animals produced as far as possible, for example by ensuring good coordination within and between different laboratories and countries. This is especially so in view of estimates that over the next two decades 300,000 new genetic lines of mice could be created, and expectations that the total number of mice that are expected to be used in mutagenesis and phenotyping studies are of the order of several million each year in the UK alone. We also observed that large numbers of animals are used to produce and maintain each line of GM animals (see paragraphs 5.22 and 7.5).
15.73 Documentation of the phenotypic outcomes of genetic modification (i.e. documentation about the way in which animals are affected) can facilitate the future monitoring and assessment of welfare implications experienced by animals produced in the context of forward or reverse genetics (paragraphs 5.18–5.21). A systematic approach to the description of GM phenotypes is crucial for assessing and monitoring welfare implications, and for undertaking thorough cost-benefit assessments. For this reason, we recommend that more efforts should be made to establish comprehensive ontologies40 in the form of databases for GM animals. These databases should not be restricted to the receipt and dissemination of phenotypic information relevant to the scientific objectives of the research, but should also provide detailed description of associated implications for welfare. Established central databases, such as the Mouse Genome Database (MGD) in the USA,41 should be used as the primary mechanism for archiving and distributing information on GM animals. The information should be made available on freely accessible websites for the use of the scientific community and interested lay people.
15.74 It is also important to continue to investigate and improve current methods for assessing the phenotypic and welfare status of GM animals. Any terminology and ontology for describing specific welfare implications should be integrated with the emerging phenotype ontologies. We note that current welfare assessment systems vary with regard to the amount of information and the degree of detail being made available.42We recommend that the NC3Rs should consider this variation with a view to advising on the rationalisation and development of phenotype and welfare ontologies and their interrelationships.
15.75 We also recommend that scientific journals require the submission of phenotype and associated data about welfare to databases as a condition of acceptance of submitted papers. Although scientists often routinely submit information about new phenotypes to databases such as MGD, a more systematic approach would be useful in promoting the availability of information about both the phenotype and the implications for welfare, which would help avoid duplication and improve welfare management. Data should be provided according to the requirements of the standardised transgenic mouse nomenclature.43
The scientific validity of animal research and the use of animals in the study of human disease
15.76 In Chapters 5-8 we gave a number of examples which illustrated the use of animals as models for human diseases, and for the assessment of effective and safe interventions. We also considered claims about the predictability and transferability of animal experimentation (paragraphs 8.37–8.41, 8.43 and 10.27–10.43) and concurred with the APC that, because of relevant similarities of anatomical, physiological and neurological structures the scientific validity of animal experiments is:
‘a condition capable of being fulfilled, but has to be judged case by case and subjected to detailed critical evaluation.’44
15.77 The question about the scientific validity of animal experimentation for medical purposes is often confused with questions about complex ethical issues. We emphasised in Chapter 3 that the separation of scientific and ethical questions is essential if greater clarity is to be achieved in the debate about research involving animals. We observed that there is a relatively limited number of useful reviews currently available (paragraph 10.46). In principle, it would therefore be desirable to undertake further systematic reviews and meta-analyses to evaluate more fully the predictability and transferability of animal models (see paragraph 10.39). We are aware that carrying out such reviews may be complicated by a number of problems.
15.78 First, it may be difficult to assess if an animal experiment failed to yield specific data because the wrong animal model was used or because the study design was flawed. Any proposed review should identify clearly whether there are areas of research in which scientific methodology (for example, statistical analysis) needs to be improved, or whether there is reason to question the scientific validity of using specific animals as models in particular areas of research.
15.79 Secondly, care should be taken when selecting the studies that are analysed in any review, and the reasons for selection must be made explicit to avoid misunderstandings. Problems could arise if, for example, a review focuses exclusively on an area where progress has been difficult, as the results might be interpreted by some as suggesting that animal research in general yields insufficiently transferable results. Similarly, reviews that focus exclusively on areas where progress has been relatively straightforward might be interpreted as proof that all animal research yields useful and directly applicable results. Clearly, such interpretations are not useful and contrary to the evidence presented in Chapters 5–9.
15.80 On balance, we consider that there is merit in undertaking appropriately designed and presented reviews on the scientific validity of animal research in specific areas. Since the scientific evaluation of animal research is fundamental to the cost-benefit assessment of any research, we recommend that the Home Office, in collaboration with major funders of research such as the Wellcome Trust, the MRC, the BBSRC, animal protection groups and industry associations such as the ABPI, should consider ways of funding and carrying out these reviews. In devising a strategy, priorities should be identified which, in order to respond to concerns of the public, consider, among other things, the validity of research that falls in the substantial category, and research that involves primates next page
Footnotes34 Services of the European Commission (2001) Technical Annex to Report from the Commission to the European Parliament and
the Council on the Evaluation of the active substances of plant protection products, SANCO/2692/2001 of 25 July 2001,
available at: http://europa.eu.int/comm/food/plant/protection/resources/ppp01_ann_en.pdf. Accessed on: 21 Apr 2005.
35 European Commission (2001) White Paper: Strategy for a future chemicals policy. COM (2001)88 final of 27.2.2001 (Brussels: EC).
36 See, for example: British Union for the Abolition of Vivisection (2004) Memorandum from the British Union for the Abolition of
Vivisection, submission to the Select Committee on Science and Technology, available at:
http://www.publications.parliament.uk/pa/cm200304/cmselect/cmsctech/172/172we20.htm. Accessed on 21 April 2005.
37 Home Office (2005) Ministerial Response on the Report by the Animals Procedures Committee – Review of Cost Benefit
Assessment in the use of animals in research, p10, available at:
http://www.homeoffice.gov.uk/docs4/jw280305flint_banner_report_by_the_animal_procedures_committee.pdf. Accessed on: 21
April 2005.
38 Parliamentary Under Secretary of State Caroline Flint commented in the Government’s response of 28 March 2005 to the APC’s
Report on the cost-benefit assessment that ‘the outcome of the review’ would be published as an Annex to the Minutes of the
Inter-Departmental Group on the Three Rs, see Home Office (2005) op. cit. However, the Working Party was not able to
consider this document before finalising this Report.
39 Animal Procedures Committee (2003) Review of cost-benefit assessment in the use of animals in research, p52, available at:
http://www.apc.gov.uk/reference/costbenefit.pdf. Accessed on: 4 April 2005.
40 An ‘ontology’ in this context is an explicit formal specification of terms and the relationships among them, used to underpin
the construction and querying of databases.
41 See Mouse Genome Informatics (MGI), available at: http://www.informatics.jax.org. Accessed on: 21 Apr 2005.
42 Jegstrup I, Thon R et al. (2004) Characterization of transgenic mice - a comparison of protocols for welfare evaluation and phenotype characterization of mice with a suggestion on a future certificate of instruction Lab Anim 37: p1-9.
43 See Mouse Nomenclature Home Page, available at: http://www.informatics.jax.org/mgihome//nomen/index.shtml. Accessed on
21 April 2005.
44 Animal Procedures Committee (2003) Review of cost-benefit assessment in the use of animals in research, p26, available at:
http://www.apc.gov.uk/reference/costbenefit.pdf. Accessed on: 4 April 2005.