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The ethics of research involving animals - Nuffield Council on ...

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T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />

be used to define humane endpoints include flank twitching (paragraph 12.19) and<br />

chemical and haematological changes in the blood. 28<br />

12.22 But in some cases the <strong>on</strong>ly way to determine the clinical signs indicating that <str<strong>on</strong>g>animals</str<strong>on</strong>g> should<br />

be euthanised may be to allow some <str<strong>on</strong>g>animals</str<strong>on</strong>g> to suffer c<strong>on</strong>siderably or even die, carefully<br />

recording the clinical signs throughout their lives so that a retrospective analysis can be<br />

undertaken. This approach has been used successfully to refine some <str<strong>on</strong>g>of</str<strong>on</strong>g> the protocols<br />

required for toxicity testing <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccines. 29 Humane endpoints should generally be easier to<br />

define within safety-assessment programmes because routine procedures are used and the<br />

<strong>on</strong>ly variable is, for example, the batch <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccine. 30<br />

Barriers to implementing Refinement<br />

12.23 We have observed above that implementati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinements is usually more<br />

straightforward than Reducti<strong>on</strong> and Replacement and that many Refinements have been<br />

developed by scientists during the normal course <str<strong>on</strong>g>of</str<strong>on</strong>g> their work. <str<strong>on</strong>g>The</str<strong>on</strong>g>re should in fact be<br />

fewer scientific barriers to Refinement. Where they do occur, it can be difficult to determine<br />

whether they are real or perceived and exactly what the nature <str<strong>on</strong>g>of</str<strong>on</strong>g> the barrier is. One<br />

comm<strong>on</strong> c<strong>on</strong>cern is that the provisi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinement in the form <str<strong>on</strong>g>of</str<strong>on</strong>g> envir<strong>on</strong>mental<br />

enrichment may add unwanted variables that may reduce the validity <str<strong>on</strong>g>of</str<strong>on</strong>g> experimental data.<br />

For example, in toxicology it might be argued that giving wooden chews to <str<strong>on</strong>g>animals</str<strong>on</strong>g> affects<br />

their metabolism and interfers with the results. This may mean that more <str<strong>on</strong>g>animals</str<strong>on</strong>g> have to<br />

be used to generate statistically significant results. However, there are usually ways around<br />

such problems, for example, by using commercially available enrichments that have been<br />

fully characterised and standardised.<br />

12.24 Other, n<strong>on</strong>-scientific, barriers to the applicati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinement can result from:<br />

■ limited understanding <str<strong>on</strong>g>of</str<strong>on</strong>g> the c<strong>on</strong>cept <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinement, why it is important and when and<br />

how to apply it;<br />

■ limited understanding <str<strong>on</strong>g>of</str<strong>on</strong>g> the species-specific needs <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g>, causes <str<strong>on</strong>g>of</str<strong>on</strong>g> suffering and the<br />

impact <str<strong>on</strong>g>of</str<strong>on</strong>g> laboratory <str<strong>on</strong>g>research</str<strong>on</strong>g> and housing <strong>on</strong> the full lifetime experience <str<strong>on</strong>g>of</str<strong>on</strong>g> an animal;<br />

■ lack <str<strong>on</strong>g>of</str<strong>on</strong>g> specific informati<strong>on</strong> and guidance <strong>on</strong> practical Refinements, relating to what to<br />

do and how to do it;<br />

■ lack <str<strong>on</strong>g>of</str<strong>on</strong>g> resources, including time and funds; and<br />

■ lack <str<strong>on</strong>g>of</str<strong>on</strong>g> motivati<strong>on</strong> and training.<br />

12.25 All <str<strong>on</strong>g>of</str<strong>on</strong>g> these factors can significantly limit the implementati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinement, which, in view<br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> its relative ease <str<strong>on</strong>g>of</str<strong>on</strong>g> applicati<strong>on</strong> and its great potential for reducing suffering, is<br />

regrettable. Nevertheless, many establishments in the UK are very proactive with regard to<br />

Refinement and, taking animal husbandry as an example, have good, innovative<br />

envir<strong>on</strong>mental enrichment programmes. But there is also anecdotal evidence that some<br />

<str<strong>on</strong>g>research</str<strong>on</strong>g>ers argue that <str<strong>on</strong>g>animals</str<strong>on</strong>g> ‘do not do anything’, and therefore do not need anything<br />

28 See Hendriksen CFM and Mort<strong>on</strong> DB (Editors) (1999) Humane Endpoints in Animal Experiments for Biomedical Research.<br />

Proceedings <str<strong>on</strong>g>of</str<strong>on</strong>g> the Int C<strong>on</strong>ference, 22–5 Nov 1998, Zeist, <str<strong>on</strong>g>The</str<strong>on</strong>g> Netherlands. (L<strong>on</strong>d<strong>on</strong>: Royal Society <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicine).<br />

29 Johannes S, Rosskopf-Streicher U, Hausleithner D et al. (1999) Use <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical signs in efficacy testing <str<strong>on</strong>g>of</str<strong>on</strong>g> erysipelas vaccines, in<br />

Humane Endpoints in Animal Experiments for Biomedical Research. Proceedings <str<strong>on</strong>g>of</str<strong>on</strong>g> the Int C<strong>on</strong>ference, 22–5 Nov 1998, Zeist,<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> Netherlands, Hendriksen CFM and Mort<strong>on</strong> DB (Editors) (L<strong>on</strong>d<strong>on</strong>: Royal Society <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicine), pp102-105; Krug M and<br />

Cussler K (1999) Endotoxin in porcine vaccines: clinical signs and safety aspects, in Humane Endpoints in Animal Experiments<br />

for Biomedical Research Proceedings <str<strong>on</strong>g>of</str<strong>on</strong>g> the Int C<strong>on</strong>ference, 22–5 Nov 1998, Zeist, <str<strong>on</strong>g>The</str<strong>on</strong>g> Netherlands, Hendriksen CFM and<br />

Mort<strong>on</strong> DB (Editors) (L<strong>on</strong>d<strong>on</strong>: Royal Society <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicine), pp114–17.<br />

30 See also: Hendriksen CFM and Mort<strong>on</strong> DB (Editors) (1999) Humane Endpoints in Animal Experiments for Biomedical<br />

Research. Proceedings <str<strong>on</strong>g>of</str<strong>on</strong>g> the Int C<strong>on</strong>ference, 22–5 Nov 1998, Zeist, <str<strong>on</strong>g>The</str<strong>on</strong>g> Netherlands. (L<strong>on</strong>d<strong>on</strong>: Royal Society <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicine).<br />

214

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