Ethics of Research involving animals
Animals in the study of human disease (Chapter 6)
10.10 Animals are used for the study of diseases affecting animals and humans to learn about causal factors, development and infectivity, and to explore therapeutic and preventative strategies. Many diseases induce complex and dynamic interactions between molecular, cellular and organ systems. Although in vitro experiments form an important part of research on diseases, scientists whose work involves animals emphasise that their work is crucial in understanding the interactions of these complex processes. Disease models can be obtained by discovery of spontaneous mutations, by selective breeding or by means of more targeted interventions such as genetic modification (paragraphs 10.16-10.18). If animals are to provide useful models, it is only important that relevant elements of their bodily processes are similar to those of humans. In some cases this may mean that although animals can be useful models for the study of diseases that cause great suffering in humans, the animals used may not experience the same level of discomfort. In others, animals may spend much (or all) their lives suffering from the animal form of the disease under study.
10.11 We described two recently developed disease models for rheumatoid arthritis (RA) and transmissible spongiform encephalopathies (TSEs). RA is one of the most common human autoimmune diseases. It is a crippling disease resulting in chronic inflammation of the joints, the cause of which remains unknown. In the last ten years there have been major advances in the understanding of the disease process. Both animal and non-animal approaches to research have been pursued simultaneously and often by the same researchers (paragraph 6.5). Study of rodent models with induced arthritis helped to contribute to the discovery that an immune molecule called TNF plays a crucial role in the inflammatory process. The animals experienced a painful swelling of the paws, and damage to the cartilage which would have affected the animals’ welfare since rodents use their front feet extensively for grooming, holding food, eating and moving around. Various interventions were tested on the models, aimed at neutralising the inflammatory reactions by blocking the molecule through administration of antibodies. This strategy had dramatic effects on reducing the inflammation and damage caused by the disease in mice. In the early 1990s, clinical trials were carried out in humans and proved successful (see paragraphs 6.9-6.10). Some 200,000 people have since been treated effectively with the antibody therapy.
10.12 When BSE emerged in cattle in the mid-1980s little was known about its causes and infectivity (paragraph 6.12). Experimental animals were used to test the novel hypothesis that the disease was caused by abnormal forms of a protein, called prions. Transmission of BSE to monkeys by injecting bovine prions into their brains was the first demonstration that the disease was able to cross the species barrier to primates, and ultimately also to humans. In 1996, the first cases of vCJD occurred in people in the UK who had been exposed to the BSE agent. Experiments using mice were used to define important stages in the development of spongiform encephalopathies. The mice typically experienced progressive neurological dysfunction, behavioural and gait abnormalities as well as weight loss. Researchers aimed to limit suffering by euthanising animals when they were unable to eat or drink without assistance or when they reached certain stages that were known to precede the experimentally induced terminal disease.
10.13 The scientific research that was carried out on BSE strongly influenced public health policy and led to the introduction of control methods in cattle and sheep. Animal tests showed that pigs and chickens were not susceptible to BSE when fed with infected tissue, which meant that the same control measures were not necessary for these species. Other research helped to identify further measures to protect humans from infective TSE agents. These included the removal of brain and spinal cord material from meat destined for public consumption and the implementation of the Over Thirty Month Scheme (paragraph 6.22). BSE pathogenesis studies in sheep also showed that blood can be a source of infection. In response to the hypothesis that two people who died of vCJD had been infected by a blood transfusion, the Department of Health announced in 2004 that anyone who had received a blood transfusion in the UK since 1980 would no longer be able to donate blood (paragraph 6.24).
10.14 Animal disease models were also used for research on hepatitis C, and polio. The hepatitis C virus worldwide affects 170 million people, many of whom develop cirrhosis and liver cancer. Polio is estimated to be responsible for causing disability in more than half a million people around the world per year in the late 1950s and early 1960s. There are hopes that the virus will soon be eliminated. The hepatitis C virus was found to infect only primates and early research involved chimpanzees and monkeys. With regard to welfare implications, if the animals develop hepatitis C, they are likely to experience similar physiological symptoms to humans. These may range from malaise to paralysis. The symptoms associated with polio affect a whole range of behaviours including ambulation, climbing, social interactions, grooming and foraging. Affected animals are likely to be aware of their deficiencies and so may experience distress at not being able to carry out normal behaviours. In long-term research animals have to be isolated as they will be infectious to other animals and humans, and their welfare may be negatively affected.
10.15 We described two areas of research where progress continues to be difficult. Despite the use of animal research to improve understanding about the biological processes underlying diseases such as HIV/AIDS and various forms of cancers, fully effective cures or vaccines have not yet been developed. Due to the complex pathogenesis of these diseases which have many different sub-types in humans and animals there are inherent difficulties in studying them and developing successful animal models. However, effective treatment has been developed for some types of cancer, such as breast or prostate cancer. Scientists involved in this type of research believe that refined models (especially primate models) may accelerate scientific progress. Transgenic mice have also been developed which express human receptors on their cells and may be used as replacements for primates in certain experiments (paragraph 6.35).