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 Non-animal methods as adjuncts 11.13 Non-animal methods may act as an adjunct to animal experiments rather than replace them, but in so doing, they may serve to reduce the total number <strong>of</strong> <strong>animals</strong> used in a programme <strong>of</strong> work. A classic example is the screening <strong>of</strong> anti-cancer drugs in nude 9 mice with human tumours. An initial screen using cell cultures can be used to demonstrate basic tumour cytotoxicity, and only the active toxins are tested in vivo. <strong>The</strong> same principle is used in high-throughput screening <strong>of</strong> potential medicines (see paragraph 8.6). This approach involves testing a large range <strong>of</strong> potentially useful candidate chemicals for a particular purpose in non-animal systems (especially computer prediction studies and in vitro tissue culture) using techniques that can be carried out very rapidly. Those chemicals with desirable biological activity (efficacy) and devoid <strong>of</strong> undesirable activity (toxicity) can then be selected for further study. In this way, it is possible to reduce the numbers <strong>of</strong> animal tests required to assess a given number <strong>of</strong> chemicals. <strong>The</strong> severity <strong>of</strong> animal tests can be minimised by screening out substances that are likely to be toxic at an early stage. In recent years, high-throughput screening has become widely adopted by the pharmaceutical industry (see paragraphs 8.4–8.6). Alternative approaches 11.14 Another equally important concept is the use <strong>of</strong> an alternative approach to an experimental goal enabling the avoidance <strong>of</strong> animal use. Even where there are no obvious alternatives, any proposed scientific study should consider at an early stage not only whether the animal experiment is the most appropriate and only method <strong>of</strong> addressing each <strong>research</strong> question, but also whether the question is worth asking, and whether it justifies causing pain and suffering to a sentient animal. In other words, the first alternative to consider is the option not to carry out the experiment at all. For example, within the REACH testing programme (see Box 9.2) the first consideration might be whether a particular test is actually necessary, regardless <strong>of</strong> whether there are, for example, adjunct Replacement methods that could be used in <strong>research</strong>. <strong>The</strong> potential for Replacement <strong>of</strong> <strong>animals</strong> in different areas <strong>of</strong> <strong>research</strong> Toxicity testing required by regulation as a special case 11.15 <strong>The</strong>re is a tendency for discussion on the potential for replacing <strong>animals</strong> to focus solely on toxicity testing required by regulation and efficacy testing (which comprises around 16 percent <strong>of</strong> all animal use in science). Tests for regulatory purposes have received the most obvious and specific attention with respect to the development <strong>of</strong> Replacements. 10 Two factors have been influential in this respect: first, over the past 30 years public concern about the types <strong>of</strong> substances tested, such as cosmetics, household products and chemicals, and the type <strong>of</strong> tests carried out has increased (for example, the LD 50 and Draize tests; see paragraph 9.14 and Box 9 ‘Nude mice’ are mice born without any T lymphocytes, which means that they effectively have no immune responses. 10 <strong>The</strong> British Toxicology Society (BTS) produced a report on the use <strong>of</strong> in vitro methods for toxicity testing in 1997, see Fielder R, Atterwill CK, Anderson D et al. (1997) British Toxicology Society (BTS) Working Party Report on in vitro toxicology Hum Exp Toxicol 16: S1–40. <strong>The</strong> Third FRAME Toxicity Committee has also published a comprehensive discussion on the development <strong>of</strong> replacement methods for toxicity testing over the last decade, see Combes R, Schechtman L, Stokes WS and Blakey D (2002) <strong>The</strong> international symposium on regulatory testing and animal welfare: recommendations on best scientific practices for subchronic/chronic toxicity and carcinogenicity testing ILAR J 43, Supplement: S112–17; see also Salem H and Katz SA (1999) Toxicity Assessment Alternatives – Methods, issues, opportunities (Totowa, NJ: Humana Press); Castell JV and Gómez-Lechón MJ (Editors) (1997) In vitro Methods in Pharmaceutical Research (London: Academic Press); Knight DJ and Breheny D (2002) Alternatives to animal testing in the safety evaluation <strong>of</strong> products Alternat Lab Anim 30: 7–22; Combes RD (2002) <strong>The</strong> ECVAM workshops: a critical assessment <strong>of</strong> their impact on the development, validation and acceptance <strong>of</strong> alternative methods ATLA 30, Supplement 2: 151–65. 194
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 11.2) 11 . Secondly, the nature <strong>of</strong> these tests suggests that it is easier to make progress in this field, as toxicity testing required by regulation asks defined questions and tends to involve a limited number <strong>of</strong> standardised tests, which are repeated (on different chemicals) many times. <strong>The</strong>re is also an established institutional structure for the validation <strong>of</strong> alternatives (see paragraph 11.32). 11.16 Most toxicity testing required by regulation is carried out by industry which has devoted considerable resources and managed effort to the development and implementation <strong>of</strong> Replacements. <strong>The</strong>se developments have occurred partly in response to activities by animal protection organisations, and partly because many alternative approaches are developed as ‘advanced methods’ to solve specific problems (paragraph 8.42). Added impetus has recently been given by the amendment <strong>of</strong> the EU Cosmetics Directive 12 to impose a marketing ban on cosmetics that have been tested or have had any <strong>of</strong> their ingredients newly tested on <strong>animals</strong>. 11.17 Standard test methods are also used in the safety and efficacy assessment <strong>of</strong> biologicals, including vaccines. <strong>The</strong> technical problems in replacing these tests are quite different from those encountered in the testing <strong>of</strong> chemicals. Further efforts are required to develop and validate methods that allow replacement <strong>of</strong> the use <strong>of</strong> <strong>animals</strong>, particularly in highly distressful challenge tests (see paragraph 8.24 and Box 8.5). 13 CHAPTER 11 REPLACEMENTS Biomedical <strong>research</strong> 11.18 In contrast to tests for safety and efficacy, the development <strong>of</strong> Replacements to current uses <strong>of</strong> <strong>animals</strong> in biomedical <strong>research</strong> is generally perceived as more difficult. <strong>The</strong> scientific questions that are addressed in biomedical <strong>research</strong> are more diverse and open-ended, with less-predictable outcomes. Moreover, the animal model itself is <strong>of</strong>ten the focus <strong>of</strong> the <strong>research</strong> (see Chapters 6 and 7). <strong>The</strong> objectives and designs <strong>of</strong> biomedical <strong>research</strong> projects are extremely diverse. It may sometimes be possible to identify certain basic, widely used techniques that would be amenable to replacement <strong>of</strong> <strong>animals</strong>. <strong>The</strong> replacement <strong>of</strong> the ascites method <strong>of</strong> production <strong>of</strong> monoclonal antibodies is one such example (see paragraph 5.26). In general, however, opportunities for replacement or avoidance <strong>of</strong> animal use in every project need to be explored on a case by case basis, with due regard to the specific objectives and the scientific barriers to the use <strong>of</strong> non-animal methods. Barriers to developing Replacements and how these could be overcome 11.19 <strong>The</strong>re are some general principles regarding the constraints on the development <strong>of</strong> Replacements. <strong>The</strong>se are well documented in the case <strong>of</strong> toxicity testing required by regulation 14 but many <strong>of</strong> the same principles apply to biomedical <strong>research</strong>. We now consider some general features <strong>of</strong> scientific and non-scientific barriers to developing Replacements. In Chapter 15 (paragraphs 15.61–15.67) we set out recommendations about how they might be overcome. 11 See <strong>The</strong> Boyd Group (1998) <strong>The</strong> use <strong>of</strong> <strong>animals</strong> for testing cosmetics: A discussion paper from the Boyd Group, available at: http://www.boyd-group.demon.co.uk/cosmetics.htm. Accessed on: 29 Apr 2005; <strong>The</strong> Boyd Group (2002) <strong>The</strong> use <strong>of</strong> <strong>animals</strong> in testing household products: A discussion paper and statement <strong>of</strong> principle, available at http://www.boydgroup.demon.co.uk/householdproducts.pdf. Accessed on: 29 Apr 2005. 12 European Commission (2003) Directive 2003/15/EC <strong>of</strong> the European Parliament and the <strong>Council</strong> Official Journal <strong>of</strong> the European Union 11 March 2003. 13 See Hendriksen CFM, Spires J-M, Akkermans A et al. (1998) Validation <strong>of</strong> Alternative Methods for the Potency Testing <strong>of</strong> Vaccines: ECVAM Workshop Report 31, ATLA 26: 747–61, and Weissler K and Hechler U (1997) Animal Welfare Aspects in the Quality Control <strong>of</strong> Immunobiologicals: A critical evaluation <strong>of</strong> the animal tests in Pharmacopoeial Monographs (London: FRAME). 14 European Commission (2004) Opinion <strong>of</strong> the Scientific Committee on Toxicity, Ecotoxicity and the Environment on <strong>The</strong> BUAV- European Coalition to End Animal Experiments Report: <strong>The</strong> Way Forward – Action to End Animal Toxicity Testing, available at: http://europa.eu.int/comm/health/ph_risk/committees/sct/documents/out217_en.pdf. Accessed: 26 Apr 2005. 195
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The ethics
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The ethics
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Foreword The issue
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Table of contents
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Stages 1-2: discovery and selection
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Conclusions and recommendations ...
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Terms of reference
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T h e e t h i c s o f r e s e a r c
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Chapter 1 Introduction
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Chapter 2 The cont
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Chapter 3 Ethical issues raised by
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Chapter 4 The capa
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Section 2 Use of <
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Chapter 5 The use
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Chapter 6 The use
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Appendices
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Genetic screening: ethical issues P
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