Animals in Research Lecture KEC 2024 PDF

Animals in research Dr Kate Chapman PM-138, Skills for Medical Sciences Learning objectives History of animal experimentation Outline the regulatory framework for animal experimentation in the UK and discuss the ethical issues it raises Outline the regulatory procedures involv...

Animals in research Dr Kate Chapman PM-138, Skills for Medical Sciences Learning objectives History of animal experimentation Outline the regulatory framework for animal experimentation in the UK and discuss the ethical issues it raises Outline the regulatory procedures involved in obtaining permission to perform experiments on vertebrate species Explain what is meant by the ‘3Rs Principle’ Describe possible animal alternatives /nuffieldbioethics.org/ Public opinion on animal research “On balance the public is supportive of the use of animals in research; for example, almost two thirds (64%) ‘can accept animal experimentation so long as it is for medical research purposes’.” (Ipsos Mori) Source: Foundation for Biomedical Research How many animals are used in research? Based on Home Office Source: RSPCA Which species are used for medical research? Which species are most used? Based on Home Office statistics Major advances in basic research that depends on animal experimentation Medical breakthroughs following animal experiments Physiology of digestion Insulin Electrocardiogram (ECG) Penicillin Hepatitis B Yellow fever Polio vaccine Molecular structure of DNA Animals and the COVID-19 vaccine Mice, rats, monkeys Helped to test and validate New vaccines Antibody tests Safety and efficacy of COVID-19 treatments NEJM Advantages of animals in science Alternative to humans Genetic and systemic similarities between animals and humans (95% of our DNA shared with mice) Animals suffer from similar diseases to humans including cancer, TB, influenza and asthma Limitations of animals in science Ethical issues of animal use Expensive Time-consuming Humans are in some ways physiologically different to animal models, e.g., CYP enzyme expression, important for drug metabolism, varies among species Unrealistically high doses used What is The 3Rs Principle? The Reduction, Replacement and Refinement of animals in research Framework for humane animal research “The most humane science is also the best Integrated into national and science.” international legislation Russell and Burch, regulating the use of 1959 animals in scientific procedures The NC3Rs The National Centre for the Reduction, Replacement and Refinement of Animals in Research/Testing UK government funded Collaborate with universities, industry, research councils and regulatory authorities NC3Rs studentship review 2017, pp.38/9 https://tinyurl.com/y3vzmtkt The 3Rs Principle Source: NC3Rs website Replacement Replace or avoid the use of animals Human volunteers, tissues and cells (e.g., HeLa cells) Established animal cell lines Immature forms of vertebrates, or Nematode worm Drosophila melanogaster invertebrates, such as Drosophila and nematode worms to supplement research Mathematical and computer (in silico) models In collaboration with Innovate UK, NC3Rs are establishing a world- leading non-animal technologies (NATs) sector in the UK In silico drug screening/safety testing In vitro models as animal alternatives Nanofibres (scaffolds) “Mini-brains” Spheroids/organoids Human Organ-on-a-chip epidermis model (microchip) 3D human skin models: Animal alternative for cosmetics testing Culture well -As of 2013, a full ban on Tissue cup cosmetics testing on animals in the EU (7th Amendment to the Tissue Cosmetics Directive) Media -Skin model considers route of exposure H&E-stained sections of 3D skin models Chapman et al. (2014) Mutagenesis. 29 (3): 165-175 Can we What do you think? ever replace all animal What would need to testing? change in order to achieve this? Reduction Taking measures to use a smaller number of animals, to obtain information from fewer animals or more information from the same number of animals Power calculations Culture cells from a single animal Save all samples Reduction - example Easton et al., Durham University Multiple trials with single rat, no handling in between Reduced no. rats required Redesigned apparatus with GSK – no. mice reduced by 50% (8/expt) Multiple applications for models of cognitive decline – reduced variation, insights into age- related memory decline in TASTPM mouse model  Refinement Refinement: improving experiments, housing and care to reduce suffering throughout animals’ lives Example: Certain methods of handling can cause mice stress This may influence their behaviour and physiology, possibly leading to variability within/between studies Therefore, handling mice to Source: NC3Rs. Further reading: Gouveia and Hurst (2013) PloS One. minimise stress is not only beneficial 8:6 for experimental results but also animal welfare UK regulations on research using animals Animal research in the UK is strictly regulated The laws on research using animals are set out in the Animals (Scientific Procedures) Act 1986. Home Office - enforces the laws, including regulations on housing, environment, welfare, care, and health Permission to work with animals is granted by the Home Office by license only under very specific conditions Home Office’s inspection system ensures that rules are not violated Home office license Three licenses are required by the ASPA before testing on animals is permitted: personal license for each person carrying out procedures on animals project license for the programme of work establishment license for the place at which the work is carried out ARRIVE Guidelines Animal Research: Reporting of In Vivo Experiments Initiative to improve the design, analysis and reporting of animal research – maximising information published and minimising unnecessary studies Published in the online journal PLOS Biology in June 2010 Endorsed by scientific journals, major funding bodies and learned societies Lecture summary Animals in research and testing confers both advantages and limitations Scientists have a duty to avoid unnecessary animal experimentation New technologies are being applied to avoid animal use in research and testing Extra reading is available on Canvas