Statement on the use of animals in research in the University of Dundee
Updated on 17 May 2023
Statement covering why the University uses animals in research and how this is regulated.
1. Why use animals at all?
1.1. Models of human normality and disease
Animals are used in research when the biological systems being studied are too complex to be modelled in any other way. For example, our immune systems are composed of very many different cell types, located in different parts of our bodies. We can study some of the properties of each of these individual cells in isolation, having harvested them from a dead animal, and this is indeed a very informative approach. However, at present, we can only see how they work together to produce a reaction, for example to a vaccine, by studying the immune system in an intact organism. Likewise, the control of blood glucose levels (which goes wrong in diabetes), involves not only the pancreas (where the hormone insulin is made) but also our muscles, fat stores and the brain.
More and more complex biological systems are being modelled successfully, so the range of non-animal subjects for productive research will continue to grow. It is a central ethical principle, also enshrined in UK law, that, when such opportunities to replace animals with other equally informative experimental systems arise, then these must be taken.
There is another important ethical principle embedded in the law, that research carried out using animals must have a foreseeable benefit and not be driven by curiosity alone.
1.2. Use in the University of Dundee
Animals are used in research in the University in two connected ways:
- As examples of normal physiological systems. How are these controlled (down to the molecular level)? How do they respond to changes in the environment? In what ways can these control mechanisms become disrupted and how does this lead to disease?
- As models of diseased or abnormal states. Can these be reversed, or at least slowed, by interventions that might form the basis of new treatments?
While the number of medical treatment and prevention options to improve human health have increased dramatically over the last few decades, there remain a number of very challenging areas, such as:
- degenerative diseases of the nervous system (e.g., Alzheimer's disease and Parkinson's disease)
- diseases associated with the global obesity epidemic (e.g., diabetes and cardiovascular disease)
- "neglected diseases" (often involving parasitic infections and prevalent in some of the poorest countries in the world)
- diseases involving imbalances in the immune system (e.g., asthma, and severe combined immunodeficiencies)
The University has important research programmes in all these areas. We need to have much better understanding of how the conditions first arise if new methods for prevention, early detection and treatment are to be developed. The initial "benefits" are therefore in terms of enhanced knowledge, with the expectation that this will become the basis of improvements in human health. For example, if we understand the molecular details of how certain parasites survive, reproduce and associate with their "host" organisms, we can then identify targets for the development of entirely new drugs that will disrupt these processes, while having only minor and acceptable effects on the human or animal host. This onward development might also occur in the University or almost anywhere else in the world, spurred on by the basic findings coming out of Dundee and collaborating institutes.
2. The 3Rs
The University constantly strives to improve animal welfare and to minimise animal suffering through implementation of the "3Rs". These are:
- The REPLACEMENT of animals, wherever possible, with alternative systems with which to conduct research.
- The REDUCTION of the number of animals used to the minimum consistent with the desired outcome, e.g., by detailed review of the existing scientific literature to avoid unnecessary repetition and by careful design of new experiments and rigorous statistical treatment of their results;
- The REFINEMENT of procedures so that the least possible harm is done in collecting the scientific information;
The ethical review process acts as a central hub for the dissemination of best practice in the 3Rs within the University, so that an advance made by one individual or group can be swiftly adopted by as many others as possible. It also connects with similar processes in other establishments, to allow even wider sharing of best practice.
There is a National Centre for the 3Rs which exists to drive progress in all three of these principles across the UK. Some research projects in the University are aimed specifically at enhancing the 3Rs and others have been recognised (in one case by the award of a prize from the National Centre) as having made significant contributions in this area as well.
3. What do we mean by "animal"?
To a biologist, the animal kingdom encompasses a huge range of organisms, from singlecelled microbes to humans. A more restricted definition is used in UK law, which defines an "animal" to be any vertebrate (i.e. with a backbone) except humans, and any cephalopod species (octopus, squid, cuttlefish and nautilus). The reasoning behind this choice is largely based on "sentience", i.e. our expectation that an animal can perceive events as being unpleasant, distressing and/or painful. This is, of course, a subjective judgement and, while "lower" species such as worms and insects should be used wherever possible instead, there may still be ethical questions that need to be addressed as to their welfare, and whether they in turn can be replaced in future by even less sentient systems.
The UK law provides additional protection to non-human primates (monkeys, apes, etc.) and to species commonly thought of as companion animals, i.e. cats, dogs and horses. In other words, having made a case why the use of animals in research is necessary, someone must then have further justification why only members of these species are suitable.
4. Species in use in the University
The University currently has facilities for the housing of mice, rats and amphibia. It currently has no facilities suitable for housing other legally recognised "animal species", though some research is done on insects (fruit flies) and on nematode worms. At present, there is little, or no field research carried out on wild animals or birds.
5. Legal regulation
In the UK, the use of animals for scientific and education purposes is regulated under the Animals (Scientific Procedures) Act 1986 (ASPA). The law was modified slightly in 2012 to bring it into complete compliance with updated EU legislation. Although the UK has now left the European Union, no significant changes to the national legislation have occurred or are expected as a result.
5.1. Regulated Procedure
ASPA controls the performance of regulated procedures on protected animals (see above). A regulated procedure is defined in the Animals (Scientific Procedures) Act 1986 as any experimental or other scientific procedure applied to a protected animal which may cause pain, suffering, distress, or lasting harm equivalent to, or higher than, that caused by the introduction of a needle in accordance with good veterinary practice.
The University breeds and uses genetically altered mice, as these are invaluable tools for studying the effects of individual genes or groups of genes on normal physiology and on the development and treatment of disease. These animals, however normal their welfare and behaviour appear to be, are regarded simply by existing as being on a regulated procedure. In other words, the benefit of the doubt is given to the animal.
While the law allows for the performance of regulated procedures on living animals for education purposes, no such procedures are currently carried out at the University. The only use of regulated procedures here is therefore for a scientific purpose.
5.2. Non-regulated procedures
There are some procedures on living animals that are not regulated. These include:
- procedures which cause less pain, suffering, distress or lasting harm than the threshold. Examples include observational or behavioural studies;
- Certain methods for the humane killing of animals, listed in Schedule 1 to ASPA. These might be used, for example, to kill animals prior to harvesting tissues or cells for detailed laboratory study.
5.3. Licence authority
Legal regulation is by the granting of licences by the Home Office and by the scrutiny of our facilities by the Home Office inspectors. There is an Establishment Licence, whose holder accepts overall responsibility for the University's compliance with the law. Project licences are issued to senior researchers and describe the regulated procedures to be performed, the scientific necessity for those procedures, their expected effects on animal welfare and the steps that will be taken to reduce these effects to a minimum. Personal licences are granted to individuals who perform the regulated procedures. There are approximately 40 project licence-holders and about 80 personal licence-holders in the University.
6. Ethical review
The ethical issues arising from the use of animals in scientific research can usefully be debated in terms of the balance between harms and benefits. Harms in this context relate to the deviations from normal welfare experienced by the animals undergoing regulated procedures. Benefits, as described above, relate to the potential for better human or animal health in the future.
The harm / benefit analysis is carried out in the University's ethical review process. This involves a detailed analysis of research proposals by a welfare and ethical use of animals committee, which comprises a mixture of scientists and non-scientists and includes people with specific animal welfare expertise (e.g., a veterinary surgeon). As well as the consideration of applications for projects to use animals, there are processes for monitoring progress and compliance of on-going research programmes, overseeing the training and competence of University members who work with animals and maintaining the standards of housing in which animals are kept.
7. What actually happens to the animals
Every experimental protocol listed in a project licence has a severity category attached to it (mild, moderate, severe, or non-recovery), representing the greatest deviation from normal welfare that is expected, even in only one animal.
When a procedure has been completed, then the actual lifetime experience of the animal must be assessed and assigned a severity, which may be less than, equal to, or more than the category that was applied prospectively to the experimental protocol. For the reporting of actual severity, an additional category, sub-threshold is included.
All procedures are defined by the Home Office using different severity classifications detailed below.
- Sub-threshold. These procedures may result in below threshold severity. For example, the procedure was expected to cause pain or suffering equal to, or higher than, that caused by inserting a hypodermic needle, but the actual experience was in fact less than this, e.g., the breeding of genetically altered animals under project licence authority but without a harmful phenotype
- Mild. These procedures may cause short-term mild pain, suffering or distress and/or minor changes in well-being or condition e.g., taking a blood sample.
- Moderate. These procedures may cause short-term moderate pain, long-lasting mild pain, suffering or distress, e.g., surgery under general anaesthetic.
- Severe. These procedures are where it is likely that the animal will experience severe pain, long-lasting moderate pain, suffering or distress and severe impairments to its well-being or general condition, e.g., breeding animals with genetic disorders that are expected to result in severe and persistent impairment of general condition.
- Non-recovery. Where the animal is placed under general anaesthetic before the start of a procedure and is humanely killed without ever regaining consciousness
It is important to note that there must never be any unnecessary pain or distress, whether it be moderate or even mild. Experimental procedures must always be refined to cause the least deviation from normal welfare, regardless of the limits set on severity in the protocols. It should therefore be the case that the great majority of animals on which a particular procedure is carried out will experience much less deviation from normal welfare than that defined by the severity category.
In the University of Dundee at the present time, there are no experimental protocols with a category of severe. Most project licences have a mixture of protocols in the mild and moderate categories, and few have one or more non-recovery protocols as well. Most research at the University of Dundee is either mild or sub-threshold (Figure 1B).
It is important to understand that the aim of the severity classification is to assess the harm caused by the scientific intervention only. As background sickness is very rare in modern high-health rodent colonies, it is usually safe to assume that any deviation from normal welfare during a scientific procedure (or in the maintenance of a line of genetically altered animals) is related to the scientific intent and must therefore be included in the assessment.
A particular difficulty, however, arises when animals that appeared to have been in good health all their lives are unexpectedly found dead. Background mortality is never zero in large colonies of mice or rats so, if an animal is found dead, one cannot be certain that the event was related to the scientific procedure or the genetic makeup. Background deaths are often associated with giving birth, the early days of post-natal life, or old age (much as in humans), but can occur at any stage of an animal's life.
The law gives us some helpful guidance on how to assign severity to these events. If it seems that animals are found dead more often in genetically altered colonies than in normal animals, then these events are associated with the genetic alteration and must therefore be included in our assessment of severity. However, such events are always rare, so the colonies may have to be quite large before we can be reasonably sure of this. In the meantime, we will usually give the benefit of the doubt to the animals; if they were genetically altered, then we assume that the events were associated with that. As we gather more data, we may find that there is no evidence for such a link, in which case we no longer consider the events in our assessment of actual severity.
Then we must consider the severity of the event itself. Competent humane killing of an animal is not assigned a severity, so the question is the extent of any pain or distress the animal may have experienced since last being observed as being in apparent good health. If we know or can show from post mortem analysis that death was relatively quick, then we may not have to consider it as particularly severe. However, most often we do not know this for sure, in which case we again give the animal the benefit of the doubt and assign a severe category to the event.
7.2. What if something unexpected happens?
Science is all about investigating the unknown and therefore the results of experiments cannot be predicted accurately in advance. We make our best assessments as to what we expect the welfare effects of a scientific intervention will be, but sometimes we are confronted by unexpected events. These may be of a different nature to the expected ones, e.g., we observe a mobility problem, as well as or instead of, an expected weight loss. Or they may be of an increased magnitude or speed, e.g., we observe a weight loss of greater than 20% when we expected a lesser one. Either type of unexpected event can result in an assignment of an actual severity greater than that originally predicted.
All such expected events must be dealt with in the best interests of the animal and then reported to the Home Office, who will determine which of the following options should apply:
- This particular type of experiment should be stopped (most likely because the event jeopardises the scientific validity and therefore there is no longer a justification to proceed);
- If the effect can now be managed and minimised within the original severity category (i.e., it now becomes an expected one), then work may be allowed to proceed. Again a Home Office inspector has to be convinced that, while the animal may experience no greater harm, the scientific justification is still strong enough to out-weigh it;
- If the work is considered of sufficient scientific value, then the inspector may allow a temporary or permanent increase in the severity category of the protocol. This is never a decision taken lightly; all steps to avoid or minimise the effect must still be taken.
8. Annual Statistics 2022
8.1. Total Numbers of Regulated Procedures
The numbers of regulated procedures carried out in the University over the last few years are shown in Figure 1A. In 2022, the University carried out 43,567 scientific procedures involving animals. Most of these involved mice (99%), with rats and frogs also being used.
Figure 1A. Tabular representation of total animal number and species used in regulated procedures between 2015-2022.
Breeding: The University makes extensive use of genetically altered mice in its research programmes, primarily to develop our understanding of how certain genes affect the development of disease and the response to therapies. While the great majority of these animals apparently experience completely normal welfare throughout their lives, the law requires us to view their maintenance and breeding as being, in themselves, regulated procedures. In 2022, a total of 25,295 mice were recorded as being used for the maintenance of established breeding colonies of genetically altered mice, and a further 124 mice for the generation of new colonies. These animals had no procedures performed on them when they were alive, but, whilst some will have been used as part of the breeding programme only, many will have had tissues taken from them after they were humanely killed to answer research questions.
Experimental: Some research programmes require interventions to happen in living animals rather than in tissues. Any intervention, or series of interventions in the same animal, that crosses the threshold for regulation outlined above, is a regulated procedure. The number of mice that received one or more regulated procedures in that year, so excluding those in breeding programmes, was 17,745.
There had been a substantial fall in the number of animals used in 2020/2021, due to the general restrictions on research activity in the University as part of its response to the Covid-19 pandemic. The numbers of animals used in 2022 is higher than the numbers used in 2016-2019 before the pandemic and it is likely that this was because of worked delayed from the restrictions during 2020 and 2021.
8.2. Severity of Regulated Procedures
Figure 1B shows the actual severity of the 43,164 procedures carried out on mice in 2022.
30,482 (70.6%) were assigned an actual severity of below threshold. As above, most of these were genetically altered animals in breeding programmes, where there was no evidence at all of anything other than normal welfare. Some animals assigned sub-threshold will have had experimental procedures performed but where the effects didn’t cause effects as uncomfortable as a single injection, for example where they were fed an altered diet that had the possibility to change their welfare (increase or decrease in body weight) but where there were no detectable effects.
A mild actual severity applied to a further 8,952 mice (20.7%) and a moderate severity to 2,895 mice (6.7%). These experiments did involve deviations from normal welfare which were either expected and authorised in the relevant project licence (the vast majority) or will have been unexpected (very rarely). Where unexpected events happen, these are reported to the regulator and details provided to them of how such events will be avoided in the future. A total of 728 mice (1.7%) underwent procedures conducted entirely under irreversible anaesthesia, formally classified as non-recovery.
In the mouse breeding programmes, 74 animals were found dead: 0.3% of the 25,419 animals in those programmes. For some of these animals, there appeared to be a clear genetic link. In other cases, we could not be certain that the events were not related to the genetic alteration, so based on Home Office guidelines, all these events were assigned to an actual severe category. However, this percentage of animals found dead unexpected is at the lowest end of the range expected for any rodent breeding colony and are almost certainly related to sudden deaths seen in any population.
In the mice used for scientific interventions, 33 events (0.2% of the 17,745 animals used) were assigned to an actual severe category. None of these were expected and all were investigated and reported to the Home Office at the time. While the severe events constituted only 0.2% of the total number of procedures and may have been over, rather than under-reported, it was very important to investigate each one to ensure that, if it could be avoided in future, it would be.
In rats, 142 procedures were assigned a mild actual severity, and 54 a moderate one. There were 162 non-recovery procedures. All 45 procedures carried out on frogs were assigned an actual severity of mild.
The percentages for 2022 were very similar to those in pre-pandemic years.
8.3. Non-regulated Procedures
The University also uses some animals for scientific purposes where licences are not required because the Home Office do not consider that there is any chance of animals experiencing any pain or distress above the threshold. In 2022, 2,877 mice and 889 rats were used in this manner. All the animals were genetically normal. Some of these animals will have been used to understand behaviour, so they will have been observed only, e.g., investigating their surroundings in a novel area. Some of the mice and all the rats were killed humanely to provide tissues and cells for detailed laboratory study. The remaining mice were genetically normal animals that were generated in the breeding of genetically altered mice.
9. Relevant websites
- The Institute of Animal Technology. This is the professional body for animal care staff working in the scientific domain. The University is a corporate member.
- The Concordat on Openness on Animal Research. The University is a signatory to this important agreement.
- The University has endorsed the ARRIVE guidelines, which are intended to improve the reporting of experiments involving animals in academic publications.
- The Home Office.