Ethics of Research involving animals
Genetically modified animals in the study of human disease
Introduction
7.1 In Chapter 5 we gave an overview of the many ways in which animals are used for basic research, including genetic modification (see paragraphs 5.16–5.23). In Chapter 6 we focused on their use as disease models. We now consider an area which brings together GM animals and the study of human disease. In this chapter we first explain the general relevance of drawing on genetic data for the purposes of both improving our understanding about disease processes, and devising ways of preventing and treating them. We then describe commonly used disease models and explain how and why mice, zebrafish and rats are used in this type of research. We also give a range of examples that illustrate the scientific benefits and welfare implications for GM animals involved in research.
7.2 The pathology of all diseases, be they infectious, inherited or environmentally induced, is affected either directly or indirectly by an individual’s genome. The study of genetics can help us to understand these fundamental interactions. The recent sequencing of the human and mouse genomes has revealed remarkable similarities. Ninety-nine percent of the genes in these two genomes have direct counterparts in the two species, although they have slightly different structures and functions, and are in some cases regulated differently. Because of these similarities and because of practical considerations (mice breed rapidly, and methods of genetic modification are more effective, when compared with other mammals) the mouse is used as a model for research on human diseases in a range of different types of studies.
| Comments on the use of GM animals in the study of human disease from respondents to the Consultation ‘The use of genetically modified animal models has allowed researchers to generate more accurate and appropriate models of human diseases. This has facilitated progress and makes it more likely that research will transfer to human subjects more quickly.’ Genetic Interest Group ‘One viewpoint is that the use of transgenic animals will result in a reduction of the use of larger animals…as rodent models for disease are now available.’ Sarah Johnson, member of the ethical review panel at the MRC NIMR ‘Many GM animals have normal lifespans and suffer no ill effects as a result of the presence of a transgene. Some GM animals do suffer as a result of their genetic modification but…in many cases this is less than the alternative methods of generating a similar ‘model’ through surgery or chemical treatment.’ Anonymous ‘The number of GM animals we use is rising fast. This process is best described as commodification. The moral problem is that animals are not computers or areas of land or other "resources".’ Shaun Carey ‘Even when scientists think they have a "good model" it is difficult to determine how much its attributes are due to its genes or to environmental factors. Wildly differing results have been found to occur in different laboratories using the same strains of animal in the same procedures.’ Animal Aid ‘GeneWatch believes that an unjustified emphasis is being placed on the potential for GM animals to help understand and treat disease. This is driven by a lack of recognition of the complex nature of most diseases and the failings of laboratory research to mimic environmental, social and economic factors in disease.’ GeneWatch UK |
7.3 Naturally occurring animal models of human genetic diseases are rare, probably because such animals fail to survive in the wild. In GM models, detailed analyses of the development, physiology and biochemistry of a particular disease can be related to a specific gene or group of genes. It then becomes possible to understand the often complex relationship between the gene(s) and the disease process. Furthermore, comprehensive genomic analysis can improve not only our understanding of basic biological processes but also help us appreciate the potential of genes to affect disease processes. It is also possible to insert human genes into the genome of mice to study, for example, their physiological role. Researchers working in the field believe that, in some cases, such experiments may yield more accurate animal models of human disease (see paragraph 6.35).
7.4 The animals that are used most frequently to model the genetics of human disease are the mouse, rat and zebrafish. Virtually all of the GM animals used in experimental procedures in the UK during 2003 were from this group (see Appendix 2).1 As we explain in more detail below, these three organisms have been chosen for a variety of reasons.