The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
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 />
Vaccines and veterinary medicines<br />
8.18 Characterisati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccines and other biological products during stages 3 and 4 has a<br />
number <str<strong>on</strong>g>of</str<strong>on</strong>g> special features. First, the product may require modificati<strong>on</strong> so that it can be<br />
administered and remain effective as it is absorbed and transported around the body.<br />
Sec<strong>on</strong>dly, vaccines comm<strong>on</strong>ly c<strong>on</strong>tain an adjuvant (e.g. aluminium hydroxide) which is used<br />
to increase the effectiveness <str<strong>on</strong>g>of</str<strong>on</strong>g> the immune resp<strong>on</strong>se. Both vaccine modificati<strong>on</strong> and testing<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> adjuvants involve the use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g>. <str<strong>on</strong>g>The</str<strong>on</strong>g> product is <str<strong>on</strong>g>of</str<strong>on</strong>g>ten administered to <str<strong>on</strong>g>animals</str<strong>on</strong>g> and<br />
their immune resp<strong>on</strong>ses are measured by sampling blood and tissue. 23 For example, vaccines<br />
against tetanus are tested for potency in mice or guinea pigs. Animals are given the tetanus<br />
vaccine (which should c<strong>on</strong>fer protecti<strong>on</strong>) and later receive what would be expected to be a<br />
lethal or paralytic dose <str<strong>on</strong>g>of</str<strong>on</strong>g> tetanus toxin. If the vaccine has the required potency, the toxin<br />
will cause no adverse effects for the <str<strong>on</strong>g>animals</str<strong>on</strong>g> (see also Box 8.5). 24 In the past, many more tests<br />
were required during which the <str<strong>on</strong>g>animals</str<strong>on</strong>g> showed symptoms <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease, which could be<br />
severe and even lead to death. This methodology has been replaced in many cases by earlier,<br />
more humane, experimental endpoints (see paragraph 5.22), such as changes in weight,<br />
body temperature or behaviour. 25 In additi<strong>on</strong>, blood and tissue markers <str<strong>on</strong>g>of</str<strong>on</strong>g> infecti<strong>on</strong> are<br />
increasingly used. 26<br />
8.19 <str<strong>on</strong>g>The</str<strong>on</strong>g> development <str<strong>on</strong>g>of</str<strong>on</strong>g> new veterinary medicines <str<strong>on</strong>g>of</str<strong>on</strong>g>ten involves studies that use the same<br />
species for which the medicine is intended. Usually, <str<strong>on</strong>g>animals</str<strong>on</strong>g> with specific diseases are used as<br />
models, although <str<strong>on</strong>g>animals</str<strong>on</strong>g> sp<strong>on</strong>taneously affected by the disease or c<strong>on</strong>diti<strong>on</strong> are also used<br />
in field studies. 27 <str<strong>on</strong>g>The</str<strong>on</strong>g> effect <strong>on</strong> the <str<strong>on</strong>g>animals</str<strong>on</strong>g> is specific to the area <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g>, and may<br />
depend also <strong>on</strong> the state <str<strong>on</strong>g>of</str<strong>on</strong>g> their health. For example, in the case <str<strong>on</strong>g>of</str<strong>on</strong>g> the severe respiratory<br />
disease pasteurellosis, which affects cattle, 450 calves were used in a programme to develop<br />
a vaccine and a significant proporti<strong>on</strong> suffered from the disease. 28 <str<strong>on</strong>g>The</str<strong>on</strong>g> vaccine that was<br />
developed has now been used successfully to bring the disease under c<strong>on</strong>trol. 29 In field trials<br />
potential suffering is usually avoided by comparing the new vaccine to existing treatments<br />
(if available) rather than using placebos as a comparis<strong>on</strong>.<br />
Stage 5: selecting candidate medicines and ensuring their safety<br />
8.20 <str<strong>on</strong>g>The</str<strong>on</strong>g> aim <str<strong>on</strong>g>of</str<strong>on</strong>g> stage 5 is to decide whether promising compounds could be tested in trials<br />
<str<strong>on</strong>g>involving</str<strong>on</strong>g> human volunteers. Questi<strong>on</strong>s that need to be addressed include:<br />
■ Do particular compounds meet the quality threshold to be a successful medicine?<br />
■ Would the medicine be safe and effective for humans?<br />
■ How best could the medicine be administered?<br />
23 Leenaars PPAM, Hendriksen CFM, de Leeuw WA et al. (1999) <str<strong>on</strong>g>The</str<strong>on</strong>g> producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> polycl<strong>on</strong>al antibodies in laboratory <str<strong>on</strong>g>animals</str<strong>on</strong>g><br />
ECVAM Workshop Report 35 ATLA 27: 79–102.<br />
24 See Weisser K and Hechler U (1997) Animal Welfare Aspects in the Quality C<strong>on</strong>trol <str<strong>on</strong>g>of</str<strong>on</strong>g> Immunobiologicals: A critical<br />
evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> animal tests in pharmacopoeial m<strong>on</strong>ographs (Nottingham: FRAME, ECVAM and the Paul Ehrlich Institut).<br />
25 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 Internati<strong>on</strong>al C<strong>on</strong>ference, 22–25 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 />
available at: http://www.lal.org.uk/endpoints1.html. Accessed <strong>on</strong>: 26 Apr 2005.<br />
26 Griffin JF (2002) A strategic approach to vaccine development: animal models, m<strong>on</strong>itoring vaccine efficacy, formulati<strong>on</strong> and<br />
delivery Adv Drug Deliv Rev 54: 851–61.<br />
27 This is regulated under the authority <str<strong>on</strong>g>of</str<strong>on</strong>g> Animal Test Certificates (ATC). See Veterinary Medicines Directorate (2004) Animal<br />
Test Certificates, available at: http://www.vmd.gov.uk/lu/amelia/amelia13n.pdf. Accessed <strong>on</strong>: 26 Apr 2005.<br />
28 This would have included the <str<strong>on</strong>g>animals</str<strong>on</strong>g> used as the positive c<strong>on</strong>trols (to prove the bacteria could cause the disease) and<br />
unprotected <str<strong>on</strong>g>animals</str<strong>on</strong>g> that had been administered trial vaccines that proved ineffective.<br />
29 Nati<strong>on</strong>al Office <str<strong>on</strong>g>of</str<strong>on</strong>g> Animal Health (2002) Vaccinati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> farm <str<strong>on</strong>g>animals</str<strong>on</strong>g>, available at:<br />
http://www.noah.co.uk/issues/briefingdoc/22-vaccfarm<str<strong>on</strong>g>animals</str<strong>on</strong>g>.htm. Accessed <strong>on</strong>: 3 May 2005.<br />
140