Animals in research

The Institute’s mission is to make a vital contribution to understanding and treating major human health problems including cancer, heart disease, diabetes and mental illness. We also seek to increase the understanding of animal disease. In order to do this research, we must use animals for some of our research.

Our researchers and technicians work hard to ensure we are always applying and developing the highest welfare standards for the animals we use, and we always seek alternatives to the use of animals in research. Research using animals is never undertaken without due consideration and justification.

All research using animals must have approval from the Institute’s Animal Welfare and Ethics Review Body. When planning research using animals all our researchers must fully explain the purpose of the research, justify the use of animals in that research and demonstrate they have applied the principles of the 3Rs – Reducing the number of animals we use, Refining experiments to improve the quality of animals’ lives and Replacing the use of animals through the use of alternative techniques.

As signatories to the Concordat on Openness on Animal Research in the UK, we are working hard to engage with interested groups on all our science, and our participation in the Concordat strengthens this approach on a topic which can elicit wide debate and strong opinions.

If you would like ask us about our research using animals you can contact us animalsinresearch@sanger.ac.uk

Animals (Scientific Procedures) Act

The Sanger Institute uses animals in some of its research. All research using animals must comply with the Animals (Scientific Procedures) Act 1986 Amendment Regulations (2012), also known as ASPA.

Any procedure covered by ASPA can only be undertaken by a researcher holding a Personal Licence (PIL), as part of a programme of work covered by a Project Licence (PPL) in an institution with an Establishment Licence (PEL). To handle or work with animals, researchers are required to attend courses, including those accredited by the Home Office and sign a Code of Conduct detailing expected behaviour and responsibilities to the animals in their care. The Institute will also assess researchers’ competency in all procedures they intend to undertake using animals.

The Animal Facility

Our animal facility is state of the art and animal welfare takes priority over any other considerations.

We use the highest standard of caging and husbandry and the facility is subject to regular visits by Home Office inspectors, whose roles are to ensure all our work is in compliance with the Act. The staff who work in the facility work hard to continually improve standards and we have regular open meetings to discuss issues and to develop strategies that will enhance our care of, and provision for, our animals and the quality of our science.

The Institute’s animal facility operates 24 hours a day, 365 days a year. Trained and qualified staff, supported by the Institute’s Named Veterinary Surgeon, carry out animal health monitoring day and night and all staff who care for or work with the animals are responsible for promoting a culture of care. We respect and protect the animals entrusted to us and do not inflict unnecessary pain, suffering or harm on them.

All research programmes are regularly reviewed to consider the value of the science we do and whether it justifies the use of animals. In addition, we regularly audit our facilities and working practices, and have a continuous program of training and assessment of the competency of our staff.

We actively encourage collaboration and the sharing and archiving of animal types (such as a particular group of animals carrying a unique genetic modification) to avoid repetition of animal experiments, thereby reducing the number of animals used around the world.

Concordat on Openness on Animal Research

The Institute is a signatory to the Concordat on Openness on Animal Research in the UK, which has been developed by Understanding Animal Research in collaboration with leading research institutes. The Concordat aims to broaden understanding and acceptance of humane animal use in biomedical research, and calls for research institutes to be transparent with the public about all aspects of research conducted using animals.

The Concordat consists of four commitments:

We will be clear about when, how and why we use animals in research
We will enhance our communications with the media and the public about our research using animals
We will be proactive in providing opportunities for the public to find out about research using animals;
We will report on progress annually and share our experiences.

We have a series of actions that we will take under each of the commitments and will report back to Understanding Animal Research. Our activities include:

Explaining our work with animals through our media work, including being clear where animal or human cells are being studied
Welcoming journalists to the Institute animal facilities
Working on student activities in the UK and abroad
Providing training and support to spokespersons
Providing images and other resources to enquirers.

Governance

The use of animals in research is monitored by independent inspectors from the Home Office, who routinely come to the Institute to inspect our facilities, the condition of the animals and the work being undertaken. In addition, the Institute has policies and guidelines monitoring all its research and a public statement of what it expects from any member of staff working with animals.

In compliance with the law, the Institute holds a Home Office Establishment Licence, each research project is covered by a Project Licence and the researcher carrying out the research holds a Personal Licence. Each licence comes with statutory obligations which must be fulfilled. In addition, all researchers using animals at the Sanger Institute must sign the Institute’s code of conduct, which is strictly enforced.

Before a researcher can start a new research project using animals they must write an application for a 5 year project license which describes their research, the benefits of the research, the number of animals they plan to use, the procedures they will use on the animals and how they have applied the 3Rs to the design of their research. Each proposed procedure must be classified as mild, moderate or severe depending on how they are expected to impact on the animal’s welfare and must be justified. These classifications are strictly defined by the Home Office, and the Institute and the researcher are legally bound to observe these classifications. The result of procedures must not exceed the severity limit outlined in the research proposals. At the Sanger Institute, over 80% of our procedures are classified as mild and less than 0.5% are severe.

All applications are reviewed by the Institute’s Animal Welfare and Ethical Review Body (AWERB) which is made up of scientists, statisticians, the Establishment Licence Holder, staff who work in the animal facility, a veterinarian, and internal and independent external lay members. The applicant must present their work to the AWERB and answer their questions. The AWERB’s priority is the ethics of the research and the welfare of the animals rather than the science and they may turn down an application, ask for revisions to improve welfare, or approve the research.

The researcher must report back to the AWERB on the progress of the project during year 3 and at the end of the fifth year. Failure to adhere to the conditions of the licence or major deviation from the numbers used or the severity listed can result in cancellation of a licence and sanctions from the Home Office, which can include criminal prosecution where appropriate.

The 3Rs

The principles of Replacement, Reduction and Refinement (the 3Rs) are embedded in European and UK law. The 3Rs are not simply a way of using fewer animals in an experiment or using animals less often, they are a driver for innovations and developing new tools.

It is a key requirement that all applications for Project Licenses show how the 3Rs have been applied to the experimental design. Researchers at the Sanger Institute not only do this, but have been very active in developing the 3Rs. They have taken a variety of approaches including developing new non-animal systems and models, refining experimental techniques, developing new technologies that reduce the number of animals needed for breeding and through developing tools to help researchers design their experiments more effectively and ensure that they use the right number of animals to ensure statistical significance whilst minimising the number of animals used.

The Institute has been particularly active in the design and implementation of an Experimental Design Assistant (EDA) whose development was led by the NC3Rs. This freely-available, online tool guides researchers through the design of experiments that use animals and ensures that they use exactly the right number of animals so that results are statistically significant without using more than is necessary. A critical problem with implementation of the 3Rs in recent years has arisen with well-intentioned scientists using too few animals in experiments. The outcome has been that the results obtained fro

Alternatives

Although it is not possible to completely remove the need for animal models altogether, the Sanger Institute has developed a number of alternatives to the use of animals in some areas. These alternatives are able to significantly reduce the number of animals needed, or are able to replace animals in one step of the scientific and translation process.

Open Targets

Open Targets is an innovative collaboration between EMBL-EBI, the Wellcome Sanger Institute, GSK and Biogen, which seeks to accelerate drug discovery using genome-scale experiments and analyses. Drug discovery is a highly challenging process and with a relatively low success rate. Traditionally, animal models have played a key role in the process of validating possible drug targets. The goal of the CTTV is to transform the drug discovery process by predicting whether a drug acting on a particular target is likely to provide therapeutic benefit, more effectively and much earlier in the drug discovery process than is currently possible.

The Open Targets have developed an open-access informatics platform (www.targetvalidation.org) that allows users to start from the standpoint of the disease or the target. Users can ask what might be likely targets for a certain disease, or what diseases might be associated with a particular target. The platform works by combining information from a range of biological data sources which are then scored to reflect the strength of an association between a target and a disease.

In order for drugs to be approved and licensed for use in humans, their safety and efficacy must still be tested in animals; however the Open Targets programme allows researchers to validate targets using information from existing biological data and human disease models thereby reducing the need for data from animal models in the earlier stages of drug development.

Organoids

Before any research is ever carried out in animals preliminary data must be gathered in order to provide evidence and justification for moving into animal models. For many researchers much of this evidence is gathered using cell-lines. Cell-lines are cultures of individual cell types such as white blood cells or liver cells, for example. They are cheap and easy to grow and use, however they often contain large genetic differences from cells found in the body and they also only grow in 2D layers. This means they are poor models of the three dimensional organs they are derived from.

The Sanger Institute has been heavily involved in the development of organoids – small clusters of cells that grow in 3D so they more accurately mimic the behaviour of human tissue than traditional cell-lines.

Many of the organoids created at the Sanger Institute have been created from tumours of patients with cancer. This means they carry all the genetic mutations which are unique to the individual tumour making them identical to the tumour. By building up a collection of organoids it will be possible to test a range of existing and new therapies on multiple tumours from the same cancer type and connect drug efficacy with the mutations present in the tumour, offering the potential for more tailored treatment in the future.

Although unable to replace the use of animals, organoids provide an additional screening step between cell-lines and animal models meaning fewer potential therapies and interventions will move on to testing in animal models and a higher rate of success in those animals.

This research was awarded a prestigous 3Rs Prize by the National Centre for 3Rs. The international NC3Rs Prize is awarded to highlight an outstanding original contribution to scientific and technological advances in the 3Rs in medical, biological or veterinary sciences published within the last three years. The prize is part of our commitment to recognise and reward high quality research which has an impact on the use of animals in the life sciences.

Genome Editing in induced Pluripotent Stem cells

Researchers at the Sanger Institute have traditionally used mouse models in order to understand which genes are required for development of the embryo into the adult. By “knocking out” different genes they have been able to determine which genes are required for the development of stem cells all the way into tissues in the adult mouse. This has helped researchers understand which genes in humans are vital for human development as mice and humans share many genes. However, the methods for deleting genes or turning them off in mice are difficult, expensive and each gene can take months, making such a project hugely expensive and time-consuming.The development of the CRISPR-Cas9 technology, which allows precisely targeted changes to be made easily and cheaply to genomes of many species, has allowed our researchers to make genetic changes to human induced Pluripotent Stem (iPS) cells grown in culture. When grown in the right conditions iPS cells can develop into different human tissues. CRISPR-Cas9 allows researchers to switch off specific genes, in a way that previously wasn’t possible at the scale we work at. The development of a large-scale, high-throughput approach means some research programs no longer use animals.

Scientists' views on using animals in research

The decision to use animals in research is not an easy one for researchers to make. When asked about their work with animals in research, Institute researchers and technicians talked about the importance of their work developing the standards of care and their refinement of techniques and experiments to minimise suffering. They also expressed pride in their work and the value of their research which contributes to the Institute’s mission of improving health worldwide.

“I have the privilege of supporting the research staff who carry out the experiments and who strive for cures and further understanding of diseases that affect many people worldwide. It is good to see that the research is well planned and considers the 3Rs, in regard to animal use. I also work with the Animal Technicians who are advocates for the animals and can honestly say that that they are true professionals – ensuring that the animals are very well cared for.”

Animal Facility Operational Manager

Every research project using animals must have a licence and licence holder. Only senior members of Institute staff are able to hold these licences and they are legally responsible for all research that happens under that licence. Obtaining a licence is a serious undertaking that requires time and commitment from researchers. Most researchers find the process of applying for a Project Licence challenging but they recognise the rigour of the application process and the level of responsibility that holding a Project Licence brings. Researchers are frequently confronted by the ethical implications of the work they do and the Project Licence application process gives them the opportunity to consider these issues and decide how and when to use animals.

“Running research programs which work with animals is more complicated than most people think, and I’ve found that often includes the scientists that don’t use them. At every stage, there are checks and balances to make sure that the work to be carried out meets the criteria for being able to perform any study. From ethical reviews, to ensuring staff competency, making sure that the legal, regulatory and welfare requirements are in place as well as correctly designing and implementing the study, all these things need to be in place even before any animal is touched.”

“Some people may consider that the barriers to being able to work with animals are too high and that science is inhibited by regulations and bureaucracy. My view is that these safeguards have an essential role to play. Appropriate barriers should be there to prompt the simple question, do you really need to use animals? The people I know that work with animals all want what is best for the animal but balanced with the scientific value that can be derived from the study. That tension between the value of using the animals and the welfare consequences for it runs to the heart of whether it is ethical to perform animal experimentation and is something that we should continuously evaluate when working with animals.”

Project Licence Holder

All research using animals must be approved by the Animal Welfare Ethical Review Body (AWERB). The AWERB committee is made up of Faculty, the Establishment Licence Holder, a statistician, internal and external lay members, ethical and regulatory advisers, and staff from the animal facility. The committee reviews all applications for new Project Licences and they review the progress of Project Licences already underway. Project Licence holders are expected to present their applications or progress reports in person to the AWERB and will take into consideration all comments and recommendations made by AWERB.

“Sitting on the Institute’s Animal Welfare Ethical Review Body (AWERB) has allowed me to see how hard researchers work when designing their experiments and how dedicated the technicians are to the care of the mice and zebrafish. Not only do researchers design experiments that answer important research questions but they also include implementation of the 3Rs, consider the welfare of the animals and decide whether the research is good enough to justify using animals.”

“All researchers applying for a project licence come in front of the AWERB committee and are questioned on their entire proposal by statisticians, other researchers and by the animal facility staff who care for the animals. It’s a long and exacting process but the researchers are held to account and it means better care for our animals and improved science. There have been times when we have said no to researchers and I’m proud of the fact that the AWERB holds everyone accountable for their work.”

Animal Welfare Ethical Review Body Lay Member