TalkScience@BL: Replace, Reduce, Refine: Animals in Research
As part of the Royal Society of Biology’s Biology Week 2016 and in collaboration with the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) the British Library presented the panel discussion TalkScience@BL: Replace, Reduce, Refine: Animals in Research. Professor Stephen Holgate CBE, Clinical Professor of Medicine at the University of Southampton and NC3Rs Board Chair, presided over the sold out event showcasing how the principles of the 3Rs are ingrained and implemented within British research.
Focusing on replacement, Professor Robin Williams, Head of the Biomedical Sciences Centre at Royal Holloway, University of London discussed his research into epilepsy using social amoebae. To demonstrate just how easy social amoebae are to keep and observe, Professor Williams brought along some study subjects in petri dishes for the audience to observe. These eukaryotes are an excellent model for his genetic research because their entire genome has been identified and can be easily edited. Unlike humans, each amoeba carries only a single copy of their genome, making it much simpler to knock-out, or delete, specific genes. Researchers then observe the altered amoebae to find out what these genes do.
Professor Williams and his team used social amoeba to understand the cellular pathways impacted by common epilepsy medication sodium valproate and the ketogenic diet prescribed for one third of patients resistant to anti-epileptic drugs. By understanding how the mechanisms of epilepsy medications and diet manage seizures on a molecular level, they were able to develop potential new treatments for patients who did not respond to standard medication.
Dr Sally Robinson, Head of Laboratory Animal Science (UK) at AstraZeneca, explained the role of animal research in the development of new drugs. Consumers have high expectations of medications. We expect them to be safe, effective and have minimal side effects, but this can take 6-10 years, or more, for the pharmaceutical industry to achieve. First, researchers need to identify a target, such as a protein that controls a process within the body on a cellular level. Usually these targets function in combination, making the development of new medications that impact all the targets much more difficult.
Once a substance has been identified researchers then need to understand the pharmacokinetics, how a drug moves into, through and out of the body. Does it have the desired effect? How much does the patient need? At this stage in vivo modelling, the use of living animals, is required on two species by UK law to ensure drug safety before new medications can be trialled on people. Dr Robinson emphasised that this research is tightly controlled and that relatively few animals are used in toxicology studies. She further championed the work within the industry to continue to reduce the number of animals used for the betterment of both animal welfare and scientific data. As part of a collaboration of 18 pharmaceutical companies from across Europe Dr Robinson demonstrated that data from acute toxicity testing, administering a lethal dose of a new drug to animals, could be gained from other tests with lower costs to animals. She estimated that this change cut animal use by 15,000 animals each year.
Dr Robinson closed with her refinement work with the Refining Dog Care Project (image showing positive welfare indicators from http://www.refiningdogcare.com/resources/multimedia/WelfareAssessment/photoguides/index.php). By applying scientific study to the housing and care of lab dogs they developed a guide to best practice and a welfare assessment tool combining behavioural and medical measures to evaluate animal welfare of research dogs. Creating a common language and precise method of evaluating the physical and emotional well-being of research dogs has improved both the welfare of the animals and the quality of research data.
Professor Robin Lovell-Badge, Head of the Division of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute, concluded the presentations with an overview of animal use and the importance of openness. As a Council Member of Understanding Animal Research, he championed the Concordat on Openness on Animal Research with 107 UK signatory organisations dedicated to being more open about their use of animals in research. Publishing data and annual statistics enables the public to see what research is being done. Many organisations go a step farther inviting journalists and schools to visit their facilities. This high level of public and professional scrutiny raises the bar on science, keeping the quality of research produced to a high standard. Professor Lovell-Badge spoke eloquently of the transformation of animal research from an unspoken topic to something to be quite proud of within his wide experience in the sector.
So what animals are used in medical research? In the UK mice are the most commonly used animal model. (Image above created from Great Britain 2015 Annual Statistics) Mice are well-understood as well as affordable and easy to keep. However it is important to use the best model, animal or alternative, to answer each research question. Translucent zebrafish are ideal for many in vivo studies and ferrets are used to develop flu vaccines as they develop the same symptoms and respond to treatment in a way that is similarl to humans. With the power of new gene editing technology, genetically altered animals are increasingly developed and used to create more accurate disease models. Creating and breeding genetically altered animals made up nearly half of all procedures in 2015.
Opening to the audience for questions, the lively discussion explored potential alternatives to the use of animals in research. Researchers spoke positively of the potential to use anonymised human tissue (with donor consent) and engineered tissues to replicate organs for study, but cautioned that such models were not always suitable. There was wide support of the need for more biostatisticians to refine and build computational models, and ensure that the minimum number of animals are used in experimentation to achieve significant results. The panel was supportive of the development and need for funding of alternatives to the use of animals in research, but confirmed that animals are currently still necessary for research and unlikely to be completely replaced in the near future.