Awarding best ethical practice in animal research

Within the last hundred years, science has made remarkable breakthroughs in human health. Some diseases like smallpox and polio have been nearly eradicated. Continual breakthroughs in research mean that cancer-survival rates have continued to rise. And the development of antiretroviral drugs means that AIDS is no longer the death sentence it was 30 years ago.

These medical breakthroughs have been accelerated to a great extent thanks to the use of animals in research.

Humans share 95% of their genes with mice, which makes mice a very appropriate model for the human body. As animals also suffer from similar diseases, including cancer and asthma, if we can treat those diseases in animals, this will help us to treat them in humans.

While the use of animals in research is unavoidable, such research is carried out ethically and only after independent approval. Taking into account research animal welfare invariably leads to better science. To achieve this, the University of Cape Town (UCT) has committed to four guiding principles in its use of animals in research. These are:

• replacement with a non-animal model wherever possible

• reduction in the number of animals used

• refinement in the way they are used, which means the animals are treated humanely, with every attempt made to enrich their lives

• responsibility in all aspects of research using animals.

These guiding principles are known as the 4Rs.

In 2020, for the first time, UCT has awarded a prize to researchers and facility staff who were exemplary in their implementation of the 4Rs. This prize was awarded to two individuals: Associate Professor William Horsnell from the Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, for the exemplary use of technologies to reduce and refine the use of animals in research; and to Sister Janet McCallum, UCT Faculty of Health Sciences Animal Welfare Manager, Manager: Para-veterinary clinical services and UCT-Research Animal Facility (RAF) Conventional Unit Manager, for innovation and achievements in improving the housing and quality of life for the animals used in research at UCT.

Non-invasive use of mice to prevent cervical cancer

Human papillomavirus (HPV) is a common sexually transmitted infection. So common in fact that according to the US Centers for Disease Control and Prevention, most sexually active people will at some point, contract some variety of the infection, even if they have few sexual partners. While there are often no symptoms or health problems, HPV can cause cervical cancer, which is the fourth most common cancer in women. Even though there is now a vaccine for HPV, each year, thousands of women, particularly in low-and middle-income countries, still die of cervical cancer.

In 2020, for the first time, UCT has awarded a prize to researchers and facility staff who were exemplary in their implementation of the 4Rs.

Horsnell’s research has shown that infection by a parasitic worm (Nippostrongylus brasiliensis) decreased HPV infection. The work was undertaken using an in vivo optical imaging system (IVIS) to help researchers non-invasively study molecular and biological processes of disease in mice.

During the procedure, the mice are anaesthetised and recover with minimal after-effects. The procedure using the IVIS is completely non-invasive and is thus a very refined method of experimental animal-data collection.

Importantly, the mice do not have to be euthanised (as would have been the case in the past), and therefore data can be collected multiple times from the same animals to establish a timeline of infection or disease progression. This allows for a reduction in the number of animals needed to generate reliable, good quality and insightful data for preclinical studies.

This IVIS equipment was acquired with grant support from the National Research Foundation and UCT in which the awardee was a co-applicant. The IVIS  is now available to all UCT researchers to obtain comparable levels of information from fewer animals. This allows all UCT researchers to implement the 4Rs more effectively and to enhance animal welfare for all research animals.

Animal-husbandry refinements in the UCT Research Animal Facility

There are a number of animals permanently housed at the UCT - RAF (UCT-RAF) and all efforts are made to ensure their optimal well-being. McCallum was awarded the prize for excellent work in implementing a range of refinements, aligned with the growing evidence base of emerging animal-welfare science, including addressing the mental well-being of the animals.

 These refinements include:

• Provision of gnawing blocks for rodents: this provides an activity for the rodents where they can express their natural behaviour of gnawing and serves as a positive welfare indicator.

• Introduction of food treats for the animals: beyond nutritional benefits, this simulates the natural behaviour of foraging in rats, mice, guinea pigs and rabbits as well as rooting in pigs. It also encourages natural stretching behaviour in rodents. In addition, the treats create a positive association with experimental procedures for the animals and promote a social bond between animals and humans.

• Provision of additional toys and bedding for pigs: these help to create a stimulating environment for the pigs. Additional bedding and oat hay add complexity to the pens and ensure a suitable rooting substrate.

• Increased human-animal interaction programmes for animals: this leads to a reduction in animal stress and anxiety during procedures and overall positive animal welfare.

• Refinements to the rat metabolic cage: rat cages were made larger to create a complex and interesting space where they can express their natural behaviours of climbing, stretching and exploring.

In addition to these refinements, McCallum consults with the research community and prospective applicants in the Faculty of Health Science during the pre-submission phase of ethics applications. This is to make sure researchers and postgraduate students are mindful of possible animal welfare issues that may arise when performing animal procedures. The 4Rs is an integral part of these consultation sessions.

Greater transparency, responsibility and a higher ethical standard

These awards are part of a broader commitment by UCT, in line with international animal-welfare trends, to transparency to ensure the use of responsible, ethical practices in the use of animals in research. This move towards transparency has been supported by animal-welfare groups in countries such as Australia and the United Kingdom.

UCT will be the first African university to make this move in our use of animals in research, opening our work to public scrutiny and working with animal-rights groups to ensure the highest ethical standards.