Ethics of Research involving animals
Sources of harm for laboratory animals - continuation I
Housing/Husbandry and care/Handling and restraint
4.37 Breeding, stock and experimental animals spend most of their lives in cages or pens, not actually undergoing procedures. The size and quality of the housing environment therefore has a highly significant impact on their well-being. Current knowledge of animal behaviour and welfare makes clear that captive animals need adequate space for a range of natural behaviours including: appropriate social behaviour, exercise, foraging and play, solid floors of appropriate material and group housing for social species.
4.38 Where animals are housed in small and barren cages, they cannot perform their full range of species-specific behaviours. Housing conditions may thus prevent certain social behaviours such as the maintenance of appropriate distances between individuals. Research has demonstrated that inadequate environments have been the direct cause of a range of adverse physiological and psychological effects, for example the increased likelihood of active animals to suffer from osteoporosis when they are kept in small cages. Many animals, especially dogs, experience welfare improvements when enrichments such as refuges or viewing platforms are provided, which can assist in their perception of an environment as ‘secure’. Not providing for these needs can cause stress to the animals.
4.39 In their natural environment, all of the commonly used laboratory rodents, apart from guinea pigs, will dig tunnels or chambers in order to create refuges. Even animals from inbred strains will create such structures, which can be highly complex, if they are given the opportunity to do so. However, usually, few if any laboratory rodents have the opportunity to burrow and some experimental protocols may require animals to be kept in environments without enrichments such as artificial tunnels or refuges.
4.40 Some species, such as rats, experience better welfare if nesting material is provided. For example, female rats housed without a refuge will nurse their pups in the ‘cover’ position in an attempt to protect them, rather than the ‘half-moon’ position of a more ‘relaxed’ mother rat that feels safe within her nest. Nesting material is not only important for nursing mother rats. Its availability improves welfare for both sexes and throughout all stages of life.34
4.41 The type of food, and the way it is presented, also influences animal well-being. In their natural environment, most rodents are omnivores and visit many different feeding sites in a day whereas laboratory rodents are generally fed on standardised diets from fixed food dispensers. Many animals are highly motivated to explore relatively large areas and to forage even when food is freely available, a phenomenon known as contrafreeloading. It has been suggested that evolutionary pressures have led to animals being adapted to contrafreeload in order to find out more about their environment, helping them to prepare for possible food shortages. Thus thwarting such behaviour by housing the animals in small cages can be stressful.
4.42 Appropriate social contact and interaction has been demonstrated to be vital for the wellbeing of most commonly used laboratory species. Animals such as primates or dogs have evolved to form social groups with defined compositions and hierarchies. In their natural environment these animals usually have sufficient space to perform their social behaviours and maintain appropriate social distances. However, in the laboratory they find themselves in artificially composed groups and the cage or pen size that is provided in research facilities differs significantly from the space available in their natural habitats. The single housing of such animals requires special consideration.
Husbandry and care
4.43 Many different aspects of routine husbandry and care can adversely affect the welfare of laboratory animals. Three important examples concern the effects of cage cleaning, lighting and sound.
Cage cleaning
In contrast to humans, laboratory rodents are highly dependent on olfactory cues and communication, since they recognise their cage mates, social hierarchies and territories largely by smell (see paragraph 4.16). Routine changing of their bedding and sterilisation of cages, which removes their olfactory landmarks, can cause significant disorientation. The frequency of cage cleaning therefore requires careful consideration to strike a balance between the needs for hygiene, minimal disturbance and maintenance of habituation to humans, but the optimum frequency is not currently known.35
Light
Other sources of harm can result from lack of attention to species-specific features such as biorhythms. Rodents are nocturnal and are most active in twilight, yet they are often housed in bright light and used in procedures during what would be their sleep phase.
Sound
Rodents are sensitive to ultrasound. Although ultrasound is a normal part of the environment for rodents, exposure to sources of ultrasound produced by some electrical equipment, such as oscilloscopes and monitors, may be a source of stress.
Handling and restraint
4.44 The way that animals are approached and handled has the potential to cause fear and distress, particularly in prey species or if the animal has had a previous adverse experience. Capture and holding is commonly stressful for rats, even when they have been habituated to handling.36 In many cases, they have been shown to be able to anticipate what is about to happen to them if there are appropriate cues. It is plausible to assume that they can foresee the consequences of the administration of a substance if this has happened to them before.
4.45 Methods of restraint can also cause distress. For example, during toxicological testing, rats may be placed in polycarbonate tubes so that their snouts protrude from a hole at one end. A test substance might be delivered over the nose of the animals for periods of up to an hour, sometimes up to five times a day for several weeks or months. A recent report has indicated that a session of tube restraint is usually a stressful procedure.37
4.46 Close contact with humans can both improve and impair the welfare of laboratory animals. Social animals such as dogs or primates can benefit from establishing a relationship with staff at research facilities. Establishing appropriate relationships is of special relevance to many types of primate research, where the researchers depend on the cooperation of the animal to perform certain tasks (see Box 5.4). Problems may arise if there is a frequent change in personnel. Appropriate handling of animals is also required when animals are removed and re-introduced to and from their social groups, which can cause fear and distress. Reintroducing animals may result in increased aggressive behaviour, as hierarchies are re-established.
4.47 Restraint for primates is another cause for concern. This is particularly so when animals have not experienced adequate habituation and socialisation to humans, and when those interacting with the animals are not sufficiently familiar with the species-specific behaviour. A number of restraint methods are used for different purposes. For example, restraint chairs are used to support primates in a stable sitting position when the experiment requires that they sit still for a prolonged period of time.38 If the chair is incorrectly designed it could have an adverse effect on the animal’s physiology,39 and its welfare,40 as well as on the validity of the scientific study being undertaken. Training the animal with positive reinforcement so that it cooperates during the procedure is important to minimise negative welfare effects next page
Footnotes34 See Smith AL and Corrow DJ (2005) Modifications to husbandry and housing conditions of laboratory rodents for improved
well-being J Inst Lab Anim Res 46: 140–7.
35 Some research has been carried out in this area. See, for example, Reeb-Whitaker CK, Paigen B, Beamer WG et al. (2001) The
impact of reduced frequency of cage changes on the health of mice housed in ventilated cages Lab Anim 35: 58–73.
36 Meaney MJ, Mitchell JB, Aitken DH et al. (1991) The effects of neonatal handling on the development of the adrenocortical
response to stress: implications for neuropathology and cognitive deficits in later life Psychoneuroendocrinology 16: 85–103.
37 The method can also pose problems if the tubes are of the wrong size and shape for the animal. The animal could try to turn
around, become stuck, distressed and, at worst, die if the researcher selects the wrong size and if the animals are left
unobserved. See Jennings M, Batchelor GR and Brain PF (1998) Report of the Rodent Refinement Working Party: Refining
rodent husbandry: the mouse Lab Anim 32: 233–59.
38 The duration of such restraint varies. A recent paper reported a device suitable for restraining marmosets for up to three days
continuously, which would be an unusually long period of time. See Schultz-Darken NJ, Pape RM, Tannenbaum PL, Saltzman W
and Abbott DH (2004) Novel restraint system for neuroendocrine studies of socially living common marmoset monkeys Lab
Anim 38: 393–405. More commonly, primates experience between three- and five-hour-long sessions several times per week,
over a period of months. See, for example Box 5.4.
39 Norman RL and Smith CJ (1992) Restraint inhibits luteinizing hormone and testosterone secretion in intact male rhesus
macaques: effects of concurrent naloxone administration Neuroendocrinology 55: 405–15.
40 Klein HJ and Murray KA (1995) Restraint, in Nonhuman Primates in Biomedical Research: Biology and Management, Bennett
BT, Abee CR and Henrickson R (Editors) (New York: Academic Press), pp286–97.
41 See May RM (2004) Ethics and amphibians Nature 431: 403.