Animal models for biomedical research
What is an animal model?
The term animal model describes a living, non-human animal which is used during scientific research for the purposes of investigating human disease. The objectives of the research involving an animal model range from basic research to understand how normal biological processes become altered in disease, to studies where the effectiveness of a potential treatment is being tested. Most of the research carried out at the University of Bristol does not involve living animals and research that does use animal models involves studies investigating disease processes. The knowledge gained from this work is then used to identify new ways to treat the condition and some of our research then involves testing these potential new treatments.
Why do we use animal models?
There is a lot which is not known about human diseases and it is not possible to answer all the questions which scientists need to ask by studying human patients. There may be ethical, practical or scientific reasons why a scientific objective cannot be achieved using human subjects, and in these situations, an animal model may be appropriate. There are many different types of animal model used in research and they do not necessarily exactly mirror the human condition but can still provide important insights into relevant biology. For example, an animal model may be used to predict the likely effectiveness of a novel treatment before it progresses to studies in patients. In basic biology, an animal model may be used to gain insights into the mechanisms which are causing the disease to help identify new ways it might be treated in the future. However, it is important to recognise that all animal models have some limitations.
How do we review research involving animal models?
For most studies involving animal models the work will require a Home Office project licence because the experience of the animal exceeds the threshold in terms of its potential to cause pain, distress, suffering or lasting harm. It is also important that the potential benefits of the specific model and all the latest developments in the field have been considered when the experiments are planned. The choice of model and its justification is evaluated against the scientific questions and it is the responsibility of our scientists, the University’s Animal Welfare and Ethics Review Body (AWERB) and inspectors from the Animals in Science Regulation Unit (ASRU) on behalf of the Secretary of State for the Home Office to do this for any study involving animals. Under the Animals in Scientific Procedures Act (ASPA), our scientists must obtain authority from our AWERB and the Secretary of State for the Home Office to undertake regulated research before they can undertake any studies.
Responsibility of the scientist: To obtain authority, in the form of a project licence, our scientists provide a detailed justification of the validity of the methods they plan to use and explain how these will enable them to achieve their scientific objective. They must explain why the use of a living animal model is necessary and why the work could not be achieved using alternative, non-animal methods (replacement). They must explain how they have ensured that the numbers of animals they plan to use is the minimum required (reduction) and, why the chosen animal model involves the least suffering (refinement). The scientist is required to provide an up-to-date review of the latest literature for any animal model and explain both the benefits and potential limitations and how these are being addressed.
Responsibility of the AWERB: All studies involving animals are reviewed by our AWERB which has a membership of expert and lay members with expertise in biomedical science, animal welfare, the law, ethics and the 3Rs (replacing animals with non-animal alternatives, reducing the numbers of animals used and refining techniques that involve animals). In relation to animal models, the AWERB reviews all project licence applications and interviews each applicant so that details of the planned work can be explored. The AWERB review will look at any animal model which is proposed in a project and consider how well validated the method is, what are the potential limitations and whether there are any more refined models which should be considered. This may include an independent review of the literature and additional consultation if sufficient expertise is not available within the committee. The AWERB considers the experience of the individual animal against the potential benefits and whether there are further refinements which could be achieved.
Only once the AWERB is satisfied that the planned research meets all of the 3Rs and any proposed animal models are suitable for the scientific objectives will they recommend to the Establishment License Holder that the work should be approved and the licence submitted for Home Office Review.
Responsibility of the Establishment Licence Holder (ELH): The ELH takes overall responsibility for compliance with ASPA including ensuring that key roles are in place and appropriate processes followed to ensure that all work is ethically reviewed and conducted using procedures that comply fully with the requirements of the 3Rs, namely replacement, reduction and refinement.
Responsibility of the Home Office: Inspectors from the ASRU assess the application and then make a recommendation to the Secretary of State for the Home Office who makes the decision to approve the work and grant a project licence for a period of up to five years. They take into consideration the potential harms to the animal and potential benefits and only grant the licence where the requirements of ASPA have been met. The Home Office Inspector will also consider developments at a national level and consider the work alongside other approved programmes in the UK.
Once a project has been approved, our AWERB continue to monitor progress and evaluate the planned studies including any new developments in the field. For animal model-based research, this will include recommendations which have been introduced since the work was approved. The review process is ongoing and forums such as our annual 3Rs symposium, researcher continuing professional development (CPD) and NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) workshops provide resources which enable researchers to disseminate and hear about 3Rs developments. The AWERB also undertake two formal reviews of project licences which occur at the mid-term and end of the planned studies. The AWERB can also review any research project if there are new developments in a particular area or concerns have been raised about a particular model or procedure.
Openness and transparency
The University of Bristol is a signatory of the Concordat on Openness on Animal Research in the UK and is committed to enhancing our communications with the media and public about our research using animals.
Exemplar: The Forced Swim Test (FST)
There has been a lot of recent discussion about a test used in neuroscience called the forced swim test (FST). Originally conceived by Porsolt in the 1970s, the method was developed to predict if a drug would be antidepressant in people (Nature 1977). The test worked well for certain types of drug (antidepressants which target monoamine transmitters) and played an important role in the development of drugs such as fluoxetine (Prozac) and other second-generation antidepressants. Whilst not without their critics, these antidepressants are some of the most widely prescribed drugs in modern society. However, the use of this test expanded into testing animals for depression-like behaviour which is not what it was originally designed or validated to do and rightly, there has been criticism of this (Nature 2019).
What has also emerged over the last decade is that the forced swim test is a valid model to understand stress coping (Commons et al., 2017). Stress is known to contribute to depression but also many other illnesses and so understanding the biology of stress can help in the treatment of stress-related illnesses. As we emerge from the global COVID-19 pandemic, this is likely to become an even more important research area.
Following concerns about the FST, project licence applications (PPLs) using this procedure were reviewed and planned research using this model was discussed at the Animal Services Unit Management Board. The Board concluded that current or planned research using the FST were appropriate and justified by the scientific objectives and the University would continue to support research projects which included this method for appropriate studies.
Read our media statement on the Forced Swim Test.