Refining weaning age in macaques destined for neuroscience research

Rhesus macaques (Macaca mulatta) are an important animal model in neuroscience research and there is no immediate prospect of their replacement with less sentient species or in vitro models. The long-term, invasive nature of neuroscience research places substantial demands on macaques, raising valid concerns about cumulative severity. For these reasons, refinements to macaque husbandry that improve tolerance of laboratory housing, improve compliance with experimental procedures and/or reduce infection rates could have a significant positive impact on the welfare of macaques involved in neuroscience research.

The age at which juvenile macaques are permanently separated from their mothers (henceforth weaned) is a promising candidate for refinement in macaques bred for use in laboratory research. There have been many studies showing that both the age and method of weaning can have long-lasting negative impacts on behaviour (increased neophobia and stereotypies), general health (reduced weight and increased enteropathies) and immune competence (lower proportion of CD8plus cells and natural killer cell activity). Following from these data, current guidelines for macaque husbandry (e.g. NC3Rs) suggest macaques should be left in their natal groups for as long as possible. However, these guidelines are not currently implemented in UK breeding centres, where perceived costs of later weaning arising from increased aggression within the breeding colony are used to justify earlier weaning (albeit after the recommended minimum age of 10-14 months).

We hypothesise that there are likely to be significant long-term health and welfare benefits associated with weaning beyond the current recommended minimum age of 10-14 months. Furthermore, the assumed costs of delaying weaning, namely decreased colony productivity and the increased incidence of fight injuries in both natal and juvenile groups, could have been overestimated and may be small compared to the benefits. To test these hypotheses, well-designed studies in UK breeding centres, are needed to compare the immediate and long-term consequences of weaning macaques at ages between 12 and 30 months.

Data collection will take place at the MRC breeding colony (Centre for Macaques, CFM). We will take advantage of past and current variation in weaning age within the colony. The project will involve both analysis of historical data held in the CFM database as well as the collection of new data (~120 monkeys from across 3 year groups) at CFM. We will also use historical data from the neighbouring macaque colonies at Public Health England. We will use a comprehensive range of behavioural and health measures to assess the impact of different weaning ages on the immediate welfare of macaques at CFM and their likely future welfare in neuroscience laboratories. These include measures of temperament, general health and immune function. Given the constraints of the studentship, measurements will be made in the period up to 36 months of age before the monkeys are supplied to laboratories. We will also measure potential costs of later weaning at the breeding colony, including reduced productivity and increased aggression and consequent fight injuries.

Finally, we will work with the four UK laboratories that use macaques in neuroscience research (Cambridge, Newcastle, Oxford and UCL) to develop and put in place unified welfare monitoring protocols. These will be used to collect data on the long-term welfare of macaques with different weaning histories for future analysis.

• Early Career Engagement Award: Inaugural award scheme supports NC3Rs-funded junior researchers