Council membership and terms of reference ……………………………………………………………………….iii
Foreword…………………………………………………………………………………………………………………………….v
Acknowledgements…………………………………………………………………………………………………………….vi
Members of the Working Party …………………………………………………………………………………………viii
Working Party terms of reference ………………………………………………………………………………………xv
Summary and recommendations……………………………………………………………………………………….xvii
SECTION 1: INTRODUCTION AND CONTEXT . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
Chapter 1 – Introduction ……………………………………………………………………………………………..3
Research involving animals: outline of the controversy …………………………………………………………5
Types of research and numbers of animals used……………………………………………………………………6
Issues raised by specific types of animal research ………………………………………………………………….7
The context of the debate …………………………………………………………………………………………………..8
Structure of the Report ……………………………………………………………………………………………………….9
Chapter 2 – The context of animal research: past and present …………………….13
Introduction………………………………………………………………………………………………………………………15
Early forms of animal research in the biological and medical sciences………………………………….15
Scientific developments and public opinion in the 18th and 19th centuries………………………….16
Developments in policy and public opinion ………………………………………………………………………..19
The context of the current debate in the UK………………………………………………………………………28
Summary…………………………………………………………………………………………………………………………..29
Chapter 3 – Ethical issues raised by animal research……………………………………31
Introduction………………………………………………………………………………………………………………………33
Facts, values and the reflective equilibrium ……………………………………………………………….33
Provided there are substantial benefits associated with animal research, why should the ………..
use of animals require special justification?……………………………………………………………………..35
Is there an obligation to alleviate suffering?……………………………………………………………..35
Is all animal research aimed at developing treatment for severe human suffering ………….
that can only be alleviated through medicines? ……………………………………………………..36
‘Engaging in research is a part of human nature’ ………………………………………………………37
Why should the use of animals in research be acceptable in cases where it would be
unacceptable to use humans? ………………………………………………………………………………..37
Can any use of animals by humans be justified? Which specific issues need to be…………………….
considered in the case of research?………………………………………………………………………………….38
The moral status of different beings …………………………………………………………………………38
The relationship between moral status and morally relevant features ………………………..41
The functional role of morally relevant features: absolute constraints or factors to ………..
be balanced?………………………………………………………………………………………………………..48
Consequentialism……………………………………………………………………………………………………..49
Deontological/rights-based approaches……………………………………………………………………..51
Hybrid frameworks …………………………………………………………………………………………………..52
What role does the unavailability of alternatives play in the justification of research ………………
involving animals? ………………………………………………………………………………………………………….53
How does the justification of animal research relate to the justification of animals for……………
other uses? …………………………………………………………………………………………………………………….54
What is the appropriate role of regulation for research involving animals?………………………….55
Two views about moral agency …………………………………………………………………………………55
Should regulations be relaxed or tightened to achieve least risk and best moral practice?…55
Summary…………………………………………………………………………………………………………………………..57
Chapter 4 – The capacity of animals to experience pain, distress and suffering….59
Introduction………………………………………………………………………………………………………………………61
Philosophical problems with regard to assessing the welfare of animals………………………………62
The evolutionary continuum………………………………………………………………………………………………64
Pain, suffering and distress: meaning and function in animals and humans………………………….66
Subjective and objective elements of assessing welfare:
a correlative approach……………………………………………………………………………………………………….68
Summary of paragraphs 4.3–4.28 ……………………………………………………………………………………….72
Sources of harm for laboratory animals………………………………………………………………………………73
Summary…………………………………………………………………………………………………………………………..81
SECTION 2: USE OF ANIMALS IN SCIENTIFIC RESEARCH . . . . . . . . . . . . . . . . .83
Introduction to Section 2……………………………………………………………………………85
Chapter 5 – The use of animals in basic biological research ………………………..87
Introduction………………………………………………………………………………………………………………………89
Behavioural studies……………………………………………………………………………………………………………89
Physiological studies ………………………………………………………………………………………………………….90
Studies of animal development ………………………………………………………………………………………….95
Genetic studies ………………………………………………………………………………………………………………….96
Research tools and techniques………………………………………………………………………………………….100
Summary…………………………………………………………………………………………………………………………103
Chapter 6 – The use of animals in the study of human disease………………….105
Introduction…………………………………………………………………………………………………………………….107
The pathogenesis of disease …………………………………………………………………………………………….107
New therapeutic strategies for rheumatoid arthritis………………………………………………………….108
The transmissible spongiform encephalopathies ………………………………………………………………110
The discovery of the hepatitis C virus using the chimpanzee ……………………………………………..113
Study of polio and the development of polio vaccine………………………………………………………..114
Diseases for which treatments and cures have been difficult to develop…………………………….116
Summary…………………………………………………………………………………………………………………………118
Chapter 7 – Genetically modified animals in the study of human disease…..119
Introduction…………………………………………………………………………………………………………………….121
The mouse as a model for human disease…………………………………………………………………………122
Disease models in the mouse……………………………………………………………………………………………123
Zebrafish and rats as disease models ………………………………………………………………………………..128
Summary…………………………………………………………………………………………………………………………129
Chapter 8 – The use of animals for research in the pharmaceutical industry …131
Introduction…………………………………………………………………………………………………………………….133
The development of the pharmaceutical industry ……………………………………………………………..133
Use of animals in pharmaceutical research and development…………………………………………….134
Stages 1–2: discovery and selection of compounds that could be effective medicines…136
Stages 3–4: the characterisation of promising candidate medicines …………………………..137
Stage 5: selecting candidate medicines and ensuring their safety ……………………………..140
Stages 6–8: clinical studies on humans……………………………………………………………………..142
Support for the marketed medicine…………………………………………………………………………144
The validity of animal models used in pharmaceutical research………………………………………….146
Summary…………………………………………………………………………………………………………………………151
Chapter 9 – Animal use in toxicity studies ………………………………………………..153
Introduction…………………………………………………………………………………………………………………….155
The current approach ………………………………………………………………………………………………………155
Principal types of animal based toxicity tests …………………………………………………………………….158
Acute toxicity …………………………………………………………………………………………………………158
Repeated-dose toxicity studies ………………………………………………………………………………..160
Carcinogenicity……………………………………………………………………………………………………….160
Genotoxicity …………………………………………………………………………………………………………..160
Effects on reproduction and development……………………………………………………………….161
Safety pharmacology………………………………………………………………………………………………161
Ecotoxicity ……………………………………………………………………………………………………………..162
Issues concerning the welfare of laboratory animals in toxicity testing ………………………………163
Effects due to toxicity……………………………………………………………………………………………..164
General observations concerning the assessment of animal welfare in toxicity studies……165
Summary …………………………………………………………………………………………………………………………167
Chapter 10 – Summary of Section 2 ………………………………………………………….169
Basic research (Chapter 5) ………………………………………………………………………………………………..171
Animals in the study of human disease (Chapter 6) …………………………………………………………..173
GM disease models (Chapter 7) ………………………………………………………………………………………..174
Animal use by the pharmaceutical industry (Chapter 8)……………………………………………………..175
Animal use in toxicity testing (Chapter 9)………………………………………………………………………….176
Extrapolating the results of animal studies to humans: the scientific validity of animal research…..177
General arguments about scientific validity……………………………………………………………..177
All modelling approaches face limitations concerning transferability and predictability….179
Critical evaluation of scientific validity …………………………………………………………………….181
Summary …………………………………………………………………………………………………………………………184
SECTION 3: ALTERNATIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .185
Chapter 11 – Replacements ………………………………………………………………………187
Introduction…………………………………………………………………………………………………………………….189
The current debate ………………………………………………………………………………………………………….189
Use of the concepts ‘Alternatives’ and ‘Replacements’ ………………………………………………………190
The potential for Replacement of animals in different areas of research ……………………………194
Biomedical research …………………………………………………………………………………………………………195
Barriers to developing Replacements and how these could be overcome……………………………195
Making progress – some national and international activities ……………………………………………199
Summary …………………………………………………………………………………………………………………………200
Chapter 12 – Reduction and Refinement…………………………………………………..203
Introduction…………………………………………………………………………………………………………………….205
Applying Reduction and Refinement to research strategies ……………………………………………….205
Reduction………………………………………………………………………………………………………………………..206
Definition and scope ………………………………………………………………………………………………206
Harmonisation of international test guidelines ………………………………………………………..208
Refinement…………………………………………………………………………………………………………….209
Definition and scope ………………………………………………………………………………………………209
Potential for Refinement ………………………………………………………………………………………..210
Some specific examples of Refinement…………………………………………………………………….210
Barriers to implementing Refinement ……………………………………………………………………..214
Overcoming constraints…………………………………………………………………………………………..215
Summary …………………………………………………………………………………………………………………………216
SECTION 4: LEGAL, ETHICAL AND POLICY RELATED ISSUES . . . . . . . . . . . . . .217
Chapter 13 – Legislation, regulation and policy relating to scientific……………….
procedures on animals …………………………………………………………219
Introduction…………………………………………………………………………………………………………………….221
Historical background to the A(SP)A…………………………………………………………………………………221
The A(SP)A: general operational aspects …………………………………………………………………………..222
The A(SP)A in practice ……………………………………………………………………………………………………..223
Recent issues of public debate………………………………………………………………………………………….232
International regulation…………………………………………………………………………………………………..233
Regulations requiring the use of animals ………………………………………………………………………….236
Summary…………………………………………………………………………………………………………………………237
Chapter 14 – Discussion of ethical issues…………………………………………………..239
Introduction…………………………………………………………………………………………………………………….241
Summary: four stances on the ethics of animal research ……………………………………………………244
Discussion: four stances on animal research ………………………………………………………………………245
1. The ’anything goes’ view …………………………………………………………………………………….246
2. The ’on balance justification’ view……………………………………………………………………….247
3. The ‘moral dilemma’ view……………………………………………………………………………………249
4. The ‘abolitionist’ view …………………………………………………………………………………………252
Public policy in the context of moral disagreement …………………………………………………………..255
Chapter 15 – Discussion and recommendations…………………………………………259
Introduction…………………………………………………………………………………………………………………….261
Consensus statement by all members of the Working Party……………………………………………….261
Research involving animals and other uses of animals………………………………………………261
The benefits of research involving animals ………………………………………………………………262
Desirability of a world without animal research……………………………………………………….262
The ethical importance of the Three Rs……………………………………………………………………263
Regulation……………………………………………………………………………………………………………..263
Duplication of experiments on animals ……………………………………………………………………264
The context of the debate ………………………………………………………………………………………264
Conclusions and recommendations …………………………………………………………………………………..264
The context of the debate ………………………………………………………………………………………265
General observations…………………………………………………………………………………………..265
Provision of information by the Home Office……………………………………………………….266
Provision of information by campaigning organisations and researchers, and …………….
ways of improving the broader context of public debate…………………………………..269
The role of legislation and regulation ……………………………………………………………………..273
Cost-benefit assessment and moral agency…………………………………………………………..274
Development and implementation of the Three Rs ………………………………………………….275
Publishing information about the Three Rs ………………………………………………………….275
Coordination of effort between funding bodies and the NC3Rs ……………………………275
Enhancing the role of the ERP……………………………………………………………………………..276
Examination of new technologies for Three R potential: Chair of the Three Rs ……..276
Thorough analysis of scientific barriers to Replacements ………………………………………276
Other issues ……………………………………………………………………………………………………………277
Motivating and monitoring the reduction of research involving animals……………….277
Duplication…………………………………………………………………………………………………………279
The use of GM animals in basic research………………………………………………………………280
The scientific validity of animal research and the use of animals in the study of …………
human disease ………………………………………………………………………………………………..281
Testing for toxicity………………………………………………………………………………………………282
The international context of animal research……………………………………………………….283
Appendix 1: Statistics – Use of animals in the UK ……………………………………..289
Appendix 2: Statistics – Research involving animals in the UK, EU, USA ………….
and Japan ……………………………………………………………291
Appendix 3: Reports by other organisations……………………………………………..297
Appendix 4: Method of working………………………………………………………………299
Appendix 5: Consultation with the public …………………………………………………305
Glossary…………………………………………………………………………………………………..315
Glossary of abbreviations…………………………………………………………………………321
Index……………………………………………………………………………………………………….323
