Replacing, reducing and refining animal use (the 3Rs)

The principles of the 3Rs (replacement, reduction and refinement) were created over 50 years ago to guide the humane use of animals in research. They underpin regulations on using animals and help guarantee that scientists actively look to replace, reduce and refine their use.

We are committed to ensuring our research follows the 3Rs that aim to:

• Replace the use of animals, or avoid the use of animals altogether by using alternative models and tools, such as cells or computer models
• Reduce the number of animals by using methods that minimise the number of animals used for an experiment
• Refine aspects of animal use, from housing and care to procedures, to minimise suffering and improve animal welfare

We’re a global leader in developing alternatives to replace, reduce and refine the use of animals in research. Read more about our work towards the 3Rs below.

Testing toxins
New ways to test vaccines
Protecting against polio
Improving welfare
Making safe meningitis vaccines

Testing toxins

Some bacteria produce substances, known as toxins, that can cause disease. Whilst they’re often thought to be harmful, certain bacterial toxins can also be used as treatments when given in small doses.

Botulinum toxin is used to manage muscle and nerve disorders, and even migraine. Whilst the dose used in patients is very low, the toxin is extremely powerful so each batch needs to be carefully tested to check the activity of the toxin before it’s used. Traditionally this testing was performed in mice. 

With funding from the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), NIBSC scientists developed an effective non-animal method that can be used to measure activity of botulinum toxin products. This technique has now completely replaced the use of animals for this type of testing at NIBSC.

Find out more about this research on the NC3Rs website.

New ways to test vaccines

Vaccines encourage our immune systems to fight off disease without actually ever infecting us. They normally work by introducing safe forms of the virus, or bacteria, that have been killed or inactivated, into the body. These medicines need to be strictly regulated to make sure that every batch of vaccine is safe and effective.  If public confidence in vaccines were to fall, the number of people who receive the vaccine could also drop, making it possible for diseases currently controlled by immunisation programmes to re-emerge.

Tetanus and Diphtheria are infections caused by bacteria. We have vaccines to protect people from these serious diseases, which work by targeting harmful chemicals, known as toxins, that are produced by the bacteria.  Historically, these vaccines were tested by giving vaccinated animals the toxin and seeing how they respond, so scientists could understand the level of protection the vaccine provides. However, working with other key European organisations, we’ve developed a new testing method that instead just looks at an animal’s immune system after vaccination.

This refined test means that animals no longer need to be given the toxin as part of the study, keeping the level of suffering experienced by the animal to a minimum. Scientists can also test both Diphtheria and Tetanus vaccines in the same group of animals, helping to reduce the total number of animals used for this procedure.

Protecting against polio

A few small changes to the genetics of a polio vaccine can turn it from a safe virus to one that’s able to paralyse. For many years, the best method for testing vaccines was to use non-human primates as they were the only animal, other than humans, that were affected by polio.

In the 1990s, a transgenic mouse that could be infected by polio was developed. With the World Health Organisation (WHO) and other regulatory laboratories, we collected evidence to prove that this new type of mouse could be used to test polio vaccines. These studies eventually led to the adoption of this mouse model meaning that hundreds of primates were no longer needed to test polio vaccines each year.

But we didn’t stop there. We helped develop a simple non-animal method that uses genetic changes, known as mutations, to check the safety of polio vaccines. This means that now, certain stages of polio vaccine testing can be done without using animals at all. 

As one of the only institutions capable of providing support and training for these alternative techniques we play a critical role in making sure they are adopted by laboratories throughout the world.

Find out more about our polio work

Improving welfare

Despite our best efforts, for some types of medicines testing, animals unfortunately still provide the only option. In these situations, our animal care staff work hard to provide animals with the highest standards of care and research news ways to improve housing or refine tests to minimise suffering.

For example, we designed a new caging system for rats to provide them with more space and the opportunity to practise natural behaviours. This housing is over 4 times the volume of the legal minimum cage size and provides the animals with different forms of environmental and dietary enrichments such as wall-mounted tunnels. We’ve observed that rats are more active when housed in these systems and show more natural behaviours, such as foraging and climbing.  

Our staff are constantly looking to improve life for our animals and are committed to sharing our advances in husbandry and care with other organisations to promote better animal welfare on a larger scale.

Making safe meningitis vaccines

Vaccines are often made using inactive parts of the virus or bacteria they are designed to protect us against. Some meningitis vaccines are made using specific parts of the bacteria that contain pyrogens (substances that cause fever). So, these vaccines need to be carefully tested before use to make sure that each batch contains a safe level of pyrogens. 

Rabbits were traditionally used in these tests as they respond to pyrogens in a similar way to humans. However, the Rabbit Pyrogen Test (RPT) was originally designed to uncover contamination of medicines and blood products by pyrogens, not to test their levels in vaccines.

In the 1980’s, we developed a Monocyte Activation Test (MAT), a non-animal alternative to the RPT, which uses a type of cell called a monocyte, to detect and measure pyrogens.

When a new vaccine for meningitis B, Bexsero, was developed in 2015, we worked alongside the manufacturers to quality test the vaccine. Our scientists adopted the MAT method to test pyrogens, believing it would not only provide better results but also supported the 3Rs principles.  The MAT method is now routinely used to test pyrogen levels in batches of Bexsero vaccines before they are used in global vaccination programmes.  This has prevented over 1000 rabbits from being used to perform pyrogen testing for this vaccine.

It has taken over 20 years to fully develop and validate the MAT, but the test is now included in European guidelines as an alternative to the RPT. However, there’s still work to be done to encourage wider use of this technique, so our scientists continue to promote its’ benefits and produce guidance for manufacturers and regulators to support its adoption worldwide.