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		<title>The 3Rs</title>
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							<p>As a way to bring some unity to discussions of the ethics of animal research, the animal research community and regulators generally also follow three fundamental principles. These principles were formed over 50 years ago, and are known as the "3Rs" (Russell and Burch, 1959).</p>

							<h3>Definitions and examples</h3>

							<p>The 3Rs provide a set of standards for judging whether a researcher has made a sincere effort to minimise the impact of their research on the animals they are studying. The responsibility for this rests with the researcher, who must explain what has been done to meet each of the 3Rs.</p>

							<instructional-text><p>Read the summaries of the 3Rs on the cards below, and then flip the cards to read some examples of how these principles might be put into action.</p></instructional-text>
							<accessible-text><p>Continue on for a summary of the 3Rs and for some examples of how these principles might be put into action.</p></accessible-text>

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										<p><strong>Replacement</strong>
											<br>Using non-animal models or species lower on the phylogenetic scale.</p> 
										</flashcard-front>
									<flashcard-back variant="text"> 
										<p>Replacement could involve using:</p>
										<ul>
											<li>Mathematical or computer models</li>
											<li>Physical or chemical analysis</li>
											<li>In vitro systems</li>
											<li>The substitution of higher species (e.g. mice) with lower species (e.g. non-vertebrate), such as fruit flies</li>
											<li>Human volunteers.</li>
										</ul>
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										<p><strong>Reduction</strong>
										<br>Using methods aimed at reducing the number of animals used.</p>
									</flashcard-front>
								  	<flashcard-back variant="text">
										<p>Reduction can be achieved by:</p>
										<ul>
											<li>Avoiding duplication of prior efforts</li>
											<li>Efficiently using experimental design</li>
											<li>Using appropriate animal models</li>
											<li>Employing proper statistical analysis</li>
											<li>Exploring data sharing</li>
											<li>Minimising animal loss</li>
											<li>Reusing animals.</li>
										</ul>
									</flashcard-back>
								</flashcard>
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									<flashcard-front variant="text"> 
										<p><strong>Refinement</strong>
										<br>Eliminating or reducing unnecessary pain and discomfort.</p>
									</flashcard-front>
								  	<flashcard-back variant="text">
										<p>Refinement could involve:</p>
										<ul>
											<li>Using imaging in place of invasive measurement</li>
											<li>Employing appropriate anaesthetics and analgesics</li>
											<li>Reducing stress</li>
											<li>Providing appropriate housing.</li>
										</ul>
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								<h4>Replacement</h4>
								<p><strong>Using non-animal models or species lower on the phylogenetic scale.</strong></p>
								<p>Replacement could involve using:</p>
								<ul>
									<li>Mathematical or computer models</li>
									<li>Physical or chemical analysis</li>
									<li>In vitro systems</li>
									<li>The substitution of higher species (e.g. mice) with lower species (e.g. non-vertebrate), such as fruit flies</li>
									<li>Human volunteers.</li>
								</ul>
								<hr>
								<h4>Reduction</h4>
								<p><strong>Using methods aimed at reducing the number of animals used.</strong></p>
								<p>Reduction can be achieved by:</p>
								<ul>
									<li>Avoiding duplication of prior efforts</li>
									<li>Efficiently using experimental design</li>
									<li>Using appropriate animal models</li>
									<li>Employing proper statistical analysis</li>
									<li>Exploring data sharing</li>
									<li>Minimising animal loss</li>
									<li>Reusing animals.</li>
								</ul>
								<hr>
								<h4>Refinement</h4>
								<p><strong>Eliminating or reducing unnecessary pain and discomfort.</strong></p>
								<p>Refinement could involve:</p>
								<ul>
									<li>Using imaging in place of invasive measurement</li>
									<li>Employing appropriate anaesthetics and analgesics</li>
									<li>Reducing stress</li>
									<li>Providing appropriate housing.</li>
								</ul>
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							<p>Adherence to the 3Rs allows researchers to enhance the benefits of their research while minimising the detrimental effects.</p>

							<h3>Case studies</h3>

							<p>How have the 3Rs been applied in practice?</p>

							<instructional-text><p>Click through the activity below to read about how application of each of the 3Rs has yielded benefits in practice.</p></instructional-text>

							<accessible-text><p>Continue on to learn about how application of each of the 3Rs has yielded benefits in practice.</p></accessible-text>

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									<h4>Replacement &ndash; Human organs 'on a chip' technologies</h4>
									<p>Scientists at Harvard developed technology that eliminated the need to use animals for the testing of drugs and toxins. This was achieved by developing an <em>in vitro</em> model of human lung tissue on an individual microdevice (microchip), which comprised a chamber surrounded by living human cells (Huh <em>et al.</em>, 2012).</p>
								</process-page>
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									<h4>Refinement &ndash; Alleviating anxiety in mice</h4>
									<p>Scientists at the University of Liverpool found that a very simple modification in the way that mice are handled in the laboratory reduced anxiety in the animals, and improved the reliability of research outcomes. The refinement involved researchers picking mice up within a tube that was in the mouse's cage, rather than lifting it by the tail (Hurst and West, 2010).</p>
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									<h4>Reduction &ndash; Identifying problems with design to reduce excess animal usage</h4>
									<p>One of the main problems that the 3Rs try to address is the wastage or unnecessary usage of research animals; for example, in situations where experiments lead to null, unpublishable or unusable results. There have been many examples of where animal research can be reduced, but one important example of this is by using systematic review and meta-analysis to help reduce the need for unnecessary or unfruitful animal experiments.</p>
									<p>An example of this is a systematic review carried out on animal models of neuropathic pain following chemotherapy carried out by scientists at the University of Edinburgh. The team identified specific problems with experimental design that will help researchers in the future to design their experiments more effectively, thus ultimately reducing excess animal usage (Currie <em>et al.</em>, 2019).</p>
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							<h3>Summary</h3>

							<p>It is important to measure your work against these principles carefully. The fact that you have always used a particular animal model, or that others use it, is no reason to use the same model in your next experiment. Widely used animal models have, in some cases, been shown to be misguided, and they can be changed.</p>
							<p>If there are good reasons why you are continuing with the same model or why you cannot reduce the number of animals, you should explain these reasons. If some pain or anxiety cannot be avoided, you should provide a full explanation of the design that you need to use, and the lengths that you will go to in order to minimise the suffering of the animals.</p>

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