Implementing

Implementing the 3Rs (refinement, reduction and replacement) is a legal requirement under the Animals (Scientific Procedures) Act 1986 as amended in 2012. (ASPA). Before a project licence is granted, the Secretary of State (advised by an inspector) must weigh the likely benefits from the programme of work against the likely harms to the animals involved. They must be satisfied that there are no alternatives to using the animals, and that the procedures will use minimal numbers and cause the least suffering.

All breeding, supply or scientific procedure establishments must have an Animal welfare and ethical review body (AWERB). The AWERB promotes awareness of animal welfare and the 3Rs. It replaces the local Ethical Review Process and advises the establishment licence holder whether to support project proposals in relation to the 3Rs. They will ask for justification for the use of the animals and discuss ways to reduce the numbers used. They will also make retrospective reviews of the projects completed to identify anything that could be learnt that would contribute to the 3Rs.

The technicians working with the animals are important to implementing the 3Rs and their training should reflect this. Organisations such as the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) work with establishments to train staff in the use of the 3Rs.

Describe examples of the 3Rs in practice

Reduction:

Reduction means methods which reduce the amount of animals used in each experiment, either by enabling the same amount of information to be obtained from less animals or more information obtained from each animal. Improved experimental design can achieve a reduction in the amount of animals required. For example the use of cross over studies in rats implanted with cannulas for blood sampling means the same animals can be used for the IV and Oral phases of the study where in the past different animals had to be used because of the invasive blood sampling techniques.

Pilot studies using a small number of animals can be used to determine the feasibility, time, cost and toxicological effects of a substance before commencing a full study to try to improve the study design.

The Home office and AWERB require full justification of the numbers of animals required for each study proir to the relevant licences and permissions being granted for each project.

Refinement:

Refinement is methods that minimise the pain, distress and lasting harm experienced by the animals. Refinements can be made in all the aspects of animal use.

A research environment can be a very stressful place for animals and it is a very unnatural setting. Therefore enrichment should be provided so that the animals can display as much natural behaviour as possible. Therefore group housing of animals is important for social species. For example the use of hides and bedding for rodents reduces stress. The use of enrichment to make animals work for food can be useful to keep the animals busy for example feed balls for mini-pigs, increases the time the animals spend eating.

Refinements in pre and post-operative care and use of anaesthesia and analgesia should be used when surgical procedures are carried out. The use of non-invasive procedures should be used instead of invasive procedures where possible.

Where possible animals should be acclimatised to handling, this reduces stress when they are handled for procedures. Training animals to voluntarily accept procedures such as primates offering an arm for blood sampling is an example of a refinement that reduces stress.

Technicians should be well trained and competent in handling the species correctly to reduce stress on the animal as well as competent in any procedures they are performing to ensure they are completed with the least pain and stress to the animal as possible.

The correct equipment should always be used for the procedure taking place. Using the wrong equipment can be detrimental for the animal’s welfare.

All technicians should be encouraged to come up with new ideas for improving the welfare of the animals they work with. This includes the housing, the equipment and methods that they use.

Replacement:

Replacement is methods that replace the use of a protected animal, where they would normally have been used. There are many methods that have been developed to help replace the need for some testing on animals. There are the use of mathematical or computer modules which are being developed to predict what a compound will do within the body. Pre-screening of compounds is commonly used to select suitable candidates to go into animal testing, replacing the need to test all the compounds in animals.

Ex vivo studies can replace the use of live animals. This is where some tissue or organ is removed from the animal or human and the compounds are tested on these in a lab environment. This can for example involve the use of tissue slices or perfused organs. This removes the need to perform licenced procedures on live animals. In vitro methods can be used that include tissue cultures.

The use of invertebrates, micro-organisms and even the use of human volunteers can be used to replace the need for testing in animals.

Describe how the implementation of the 3Rs is encouraged

Standard operating procedures (SOPs) are the most basic way to encourage the implementation of the 3Rs. These are instructions of how to carry out tasks and procedures; they will explain the technique that should be used to prevent any unnecessary pain or discomfort. They will also describe husbandry procedures and techniques to ensure that the animals are always provided with the correct enrichment.

Implementation of the 3Rs is encouraged in research establishments mainly by the AWERB. They provide a forum for discussion and development of ethical advice about the 3Rs and promote a culture of care in the establishment. This culture of care should aim to ensure that all technicians are aware of their individual responsibilities in implementing the 3Rs in their daily work. The AWERB organises training and workshops for technicians to attend to learn best practice. They also liaise with the Named Training and Competence Officer (NTCO) and the Named Information Officer (NIO) who ensure that the technicians are fully trained and competent to carry out their procedures and that they have access to all the information they need. The AWERB runs competitions to encourage the development of new 3Rs projects with prizes for the best. They also encourage the sharing of best practice through poster workshops and presentations. In my workplace Technicians are encouraged to come up with proposals for the 3Rs and to run projects on these ideas in their Objectives, and are rewarded in their end of year appraisals for successfully completing these. Technicians are also encouraged to attend national and international meetings and forums of organisations such as for example the Infusion Technology Organisation and RSPCA/UFAW Rodent Welfare Group where presentations are often given detailing good practice and refinements to procedures etc. The technicians then have to report back what they learnt and encouraged to run projects to try to implement the latest knowledge into their establishment.

The sharing of good practice is crucial throughout the industry to ensure the advancement of the 3Rs. The AWERB should provide examples of good practice in relation to the national Animals in Science Committee (ASC) who then pass on this information to national welfare bodies within the UK and other national committees in the EU.

Learning Outcome 2

Understand that there is a broad range of ethical, welfare and scientific perspectives on the use of animals in scientific procedures, and that thinking of all these matters evolves over time and is influenced by culture and context.

Discuss different arguments for and against the use of animals as research models.

An argument against animal testing is that is cruel and inhumane and that the animals have no cannot consent to the experiments. The introduction of ASPA and the promotion of the 3Rs make the UK one of the most regulated countries when it comes to using animals in research, there are not such strict regulations in other parts of the world. Different cultures have different attitudes when it comes to animals, for example the Buddhist doctrine of right livelihood dissuades Buddhists from doing any harm to animals.

Animal testing is expensive and some would argue that the money would be better spent on continuing to develop alternatives to using animals. The percentage of money spent on animal modules within the UK research and development spend continues to shrink indicating that this is taking place.

There is an argument that animal tests do not reliably predict results in humans. According to Professor Robin Lovell-Badge (2013) 94% of drugs that pass animal tests fail in human clinical trials. This in itself seems a considerably good argument for not using animals as a drug testing model, but when put into context with the fact 86% fail in human pre-clinical trials, the use of animal experiments remove 36% of the potentially toxic drugs from moving onto the next stage and being given to humans. Over 200 Phase I clinical trials are carried out in the UK each year and there has not been one death in Phase 1 clinical trials in the UK in over 30 years and the last major incident was in 2006 (Lovell-Badge, 2013).

Animal research has played a vital role in nearly every major medical advance of the last century in human health. If it wasn’t for animal testing there would be less antibiotics, vaccinations, chemotherapy and even major heart surgery has all been tested in animals. This of course has also resulted in major advances in veterinary health such as tetanus vaccines for horses. The respiratory disease Pasteurellosis used to affect 1 in 5 cattle. The vaccine since development had prevented around 20 million calves getting the disease, and was only tested on 450 calves.

The argument that alternative methods such as mathematical and computer modules along with in vitro studies is justified to some extent but it probably can’t completely eliminate the need to use animals to test exactly how the compound will react within the live body. Also just because the compound is active on the requires site, would the compound be able to get to the relevant site within the body or would if for example get removed from the system by the liver before it could reach its target tissue or will it be broken down into something that was toxic. It will probably be a long time until this can be modelled by computers accurately. However these methods provide a great opportunity to reduce the use of animals.

Describe how ethical standards have changed animal welfare over time.

Ethic standard have changed dramatically over time originally no thought was given to the ethics of doing anything to animals as they were seen as less superior to humans and it was thought that animals couldn’t feel pain. The UK was the first country in the world to implement laws protecting animals. The first one was the 1822 Act to Prevent the Cruel and Improper Treatment of Cattle. Over time the government has responded to the change in the moral climate within the UK. Once people realised that animals were capable of feeling pain and being stressed new legislation was introduced to guard animals from abuse. The last legislation relating to animals used in experiments was introduced in 1986 and amended in 2012. These regulations ensure that any regulated procedures cause as little pain, stress and discomfort as possible. According to a Mori opinion poll in 2005 the percentage of people in the UK that were willing to accept the use of animals for serious medical purposes if suffering is minimised and the alternatives were fully investigated was 89%. However most people were unaware that legislation exists which actually makes this the law.

As more information has been collected about the natural behaviours of species used in research, more emphasis has been placed on making sure that they can perform as much of these behaviours as possible in the laboratory environment. This is included in ASPA in the implementation of the 3Rs. With primates for example a lot of effort is now put into work out the social interactions and hierarchy within a group to make sure that none are bullied or there are not two dominant animals fighting. Essentially the less stressed the animals are the

better the experimental results will be. Also having less stressed animals that are more willing to accept procedures is good for health and safety for the technicians as there are less chance of animal bites and scratches is the animals are calm. This will also reduce the chance of a needle stick injuries which may occur if the animal is struggling.

It is good to have pressure groups that are against the use of animals in science as they make us question what we are doing and strive to make things better. There is currently a mood of openness within the research community which will hopefully develop the general public a better understanding of what goes on. This is resulting in a better quality of life for the animals we use. Apply relevant theory to a work based example.

Traditionally cannulated rats are attached to a tethering system to protect the cannula from damage. This is designed so that the animal can still move around in its cage. This means that the animal can continue to do its normal activities while it is being dosed. There are different methods of doing this one is the harness and another is the tail cuff which is what we use. This is a refinement of the method which keeps rats restrained in a device such as a tube for example for however many hours the dose is needed. After cannulation surgery the animals are singly housed as it would be impossible for them to be housed in groups with the tethers on. This is obviously detrimental to the animal’s welfare as they are usually housed in pairs or groups. They also can’t have hides in their cages as these would become tangled with the tether.

Our new method is to use the pinport in tail cuff method which means that the animals only need to be tethered during dosing and acclimatisation periods. The rest of the time the tether can be disconnected and the animals just have the tail cuff attached. The animal can the n be housed in groups as normal and carry on its normal activities. This is a big improvement in the welfare of these animals. The most obvious measurement is the bodyweight gain. Previously it could have taken up to a week after surgery for the rat to gain the weight it had lost just after surgery, with this new method within a couple of days the animals have exceeded their pre-surgery weigh and they are much more active in their cages. We are also working on the same model for mice.