The Ethics of Research involving Animals
Workshop: Ethics and research involving animals (7)
Appendix:
The use of genetically modified animals
Although there has been a downward trend in the number of ‘genetically normal’ animals used in research, the use of genetically modified (GM) animals in research has increased tenfold in the last decade. In 2000, the total number of GM animals registered in the UK was 575,000, although only 46,000 of these were actually used in experiments[1]. The remainder are ‘breeding stock’ used to maintain GM lines, and are not actually used in research or testing procedures. However, by the terms of the 1986 Animals (Scientific Procedures) Act, all GM animals must be registered [2]. This is because the Act specifies that any scientific procedure applied to a protected animal which may cause pain, suffering, distress or lasting harm must be regulated. It is very difficult to predict accurately whether a genetic modification will lead to harm, and so as a precaution all GM animals, even those used only for breeding, must be regulated [3].
Whether or not an animal is categorised as a ‘genetically modified’ animal is therefore not necessarily an indicator of the harm that an animal may suffer. Non-GM animals can be bred to possess genetic defects that are harmful to them [4], whereas some GM animals may not suffer in any way. The Home Office is currently considering whether to alter the way in which genetically ‘normal’ and genetically ‘modified’ animals are defined.
The legal definition of a ‘genetically modified organism’ applies to ‘an organism whose genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination of its genes.’[5] There are a number of techniques used in order to produce genetic changes in animals; the four types of mouse model increasingly in use are:
i) transgenic mice – adding genes
ii) knockout mice – deleting existing genes
iii) ENU mutagenesis – generating specific point mutations in genes using a chemical (ethylnitrosourea)
iv) Inbred strains – breeding mice to exhibit particular genetic effects
However, only the first two methods are currently classed as genetic modification (and therefore must always be regulated). This leads to discrepancies: it is not always necessary to obtain a project license for work with inbred (non-GM) strains, for example a C3H mouse which is blind is classed as ‘non-harmful’. However, if the same mouse was created with genetic modification techniques, it would be classed as potentially ‘harmful’ and would have to be registered.
It was suggested that when considering the acceptability of a particular experiment, the technique used should be less important than the end result. For example when considering the harm suffered by an albino mouse, the fact that it is albino should be assessed, rather than whether it was created by genetic modification or selective breeding. Additionally, the environmental context will affect whether a genetic change is expressed - a genetic mutation might therefore be harmful in some contexts but not in others - but this is not clarified in the regulations.
ENU mutagenesis is currently the preferred technique of researchers and its use is likely to increase dramatically in the near future. It does not require previous knowledge about the underlying gene pathways involved in a particular phenotype and requires substantially fewer mice to generate a model.
Concerns about genetically modified animals can be broadly placed in two categories: extrinsic concerns and intrinsic concerns.
• Extrinsic concerns
Extrinsic concerns are about the consequences of genetic modification for the animal and wider environment. They include the welfare of the animals created, the likely benefits of the research and the scale of use and the corresponding change in attitudes towards laboratory animals and time available to care for them. With regard to welfare, it could be argued that genetic modification could have a more serious and more direct negative effect on animals, and there are considerable problems with assessing welfare. Currently assessments of welfare tend to focus on that part of the animal that the research is based around, whereas a wider examination might be required. It is often difficult to predict accurately the likely harm to an animal. However, it was proposed that in this respect, genetic modification is more accurate than selective breeding.
• Intrinsic concerns
Intrinsic concerns are about the nature of the act of genetic modification, including broad issues such as genetic integrity, the idea of ‘unnatural’ intervention in the natural world and the commodification of animals. It could be argued that genetic modification is no different than selective breeding in these ways – and as such both are either equally unacceptable or equally permissible. Other concerns include the speed of developments in genetic modification and the crossing of species and kingdom boundaries.
1 Rodents are used in the majority of procedures (82%), although the use of zebrafish has significantly increased in the last few years.
2 Section 2(3) of the Act states that anything done for the purpose of, or liable to result in, the birth or hatching of a protected animal is also a regulated procedure if it may have the effect of causing pain, suffering, distress or lasting harm. Initial production of GM animals is therefore regarded as a regulated procedure and must be carried out with appropriate licenses.
3 GM animals that can be demonstrated not to be prone to pain, suffering, distress or lasting harm may be discharged from the controls of the 1986 Act, but decisions are taken on a case-by-case basis.
4 These are categorised as ‘harmful mutants’ by the Home Office
5 This definition draws a sharp distinction between artificial and natural processes, but mutation of specific genes can occur spontaneously under natural conditions.
Last Updated Thu, 10 June 2004