These expeditions will return after a chosen length of time, with options of 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours before any speed modifiers. The Three Rs (3Rs) in relation to science are guiding principles for more ethical use of animals in testing. Institute of Laboratory Animal Resources. However, a substantial number of animals used in research and testing experience unrelieved pain and distress. invertebrates are not considered suitable replacements for vertebrates. Curzer HJ, Perry G, Wallace MC, Perry D. The three Rs of animal research: what they mean for the institutional animal care and use committee and why. In the original book, the 3Rs were restricted, arbitrarily, to vertebrates. For many years The European Centre for the Validation of Alternative Methods (ECVAM) established by the European Commission in 1991 to promote the scientific and regulatory acceptance of alternative methods, recently sponsored a workshop to discuss the current status of the Three Rs and to make recommendations aimed at achieving greater acceptance of the concept of humane experimental technique. Many journals now require authors to comply with the ARRIVE guidelines in the preparation of manuscripts. Organoids are also used in modeling genetic diseases such as cystic fibrosis,[8] neurodegenerative diseases such as Alzheimer's and Parkinson's, infectious diseases such as MERS-CoV and norovirus, and parasitic infections such as Toxoplasma gondii. Details of refinement and animal welfare considerations should routinely be included in scientific papers and publications. There should be international discussion and agreement on what levels of animal suffering should not be permitted in any circumstances, regardless of any likely or potential benefits. All rights reserved.Web policies, 615 N. Wolfe Street, Baltimore, MD 21205. , Johns Hopkins University. The use of the term alternatives to encompass all of the Three Rs is now widely accepted in many countries, enshrined in legislation, and incorporated into the names of various centers throughout the world. Who we are. the culture of human invertebrate cells and tissues. The Three Rs (3Rs) in relation to science are guiding principles for more ethical use of animals in testing. The Three Rs principle was launched in the early 1960s by two English biologists, Russel and Burch in their book “The Principle of Humane Experimental Technique”. The ARRIVE guidelines present a 20-point list of items which must be reported in publications which have used animals in scientific research, including sample size calculations, explicit descriptions of the environmental enrichment employed and welfare-related assessments made during the study. All countries should have a legal framework that actively incorporates the Three Rs into all animal-based research, testing, and education. Replacement refers to technologies or approaches which directly replace or avoid the use of animals in experiments where they would otherwise have been used. Scientists should be better informed about the Three Rs concept and should be encouraged to see it as an opportunity for reaping benefits of every kind--scientific, economic, and humanitarian. In "relative replacement", animals are still required, though during an experiment they are exposed, probably or certainly, to no distress at all. The Home Office (UK) led the Inter-Departmental Group on Reduction, Refinement and Replacement, which aims to improve the application of the 3Rs and promote research into alternatives, reducing the need for toxicity testing through better sharing of data, and encouraging the validation and acceptance of alternatives. Reports and resources. The Three Rs - replacement, reduction, and refinement – are a harm mitigation strategy and form the cornerstone of the CCAC programs. Existing laboratory animal protection laws should be fully implemented. It is unacceptable to export scientific work involving laboratory animals to avoid scientifically realistic, but more stringent, animal welfare codes. The project was managed by a committee under the chairmanship of Sir Peter Medawar, the Nobel prize-winning immunologist, with William Lane-Petter, Secretary of the Research Defense Society of Great Britain, among its members. In many countries, these 3Rs are now explicit in legislation governing animal use. Returns stem from customer dissatisfaction, a damaged product or poor product evaluation either during or post-purchase. Over the past 50 years, the Three Rs have become widely accepted ethical decision-making principles, and are now embedded in the conduct of animal-based science in Canada and internationally. A second method is by controlling variation amongst the animals used in studies, and a third method is careful design and analysis of studies. However, some scientists see its use as being driven by political and social forces rather than by scientific issues. For investigators with no previous training in statistics, this level of expertise can probably be obtained from an introductory course. The NC3Rs was set up to help scientists replace their use of animals and, where this is not possible, reduce the number of animals used and refine the care of the animals to keep pain and suffering to We hope that others will follow up the lead it has given, and that a generalized study of humane technique, as a systematic component of the methodology of research, will come to be considered essential to the training of a biologist.". The 3Rs concept was developed over 50 years ago by two scientists, Drs. 2016;22:549–65. [1] The 3Rs are: The 3Rs have a broader scope than simply encouraging alternatives to animal testing, but aim to improve animal welfare and scientific quality where the use of animals cannot be avoided. Altman DG (1982). They were first described by W. M. S. Russell and R. L. Burch in 1959. [14] Refinement encompasses not only the direct harms associated with animal use, but the indirect, or contingent harms associated with breeding, transportation, housing and husbandry. [11][12], Refinement: The Three Rs are basic principles of humane experimental technique that were first set out by Russell and Burch* in 1959. (2). Ethical review. [4] Therefore, the term 'Replacement' can refer to the use of a supposedly less sentient species,[5] as in "relative replacement". For example, the Animal Welfare Act in 1966 outlined the minimum standards for the treatment of animals both during and after any research study. The range of replacement alternative methods and approaches includes the improved storage, exchange, and use of information about previous animal experiments to avoid unnecessary repetition of animal procedures; use of physical and chemical techniques and predictions based upon the physical and chemical properties in molecules; use of mathematical and computer models; use of organisms with limited sentience such as invertebrates, plants and microorganisms; use of in vitro methods including subcellular fractions, tissue slices, cell suspensions, and perfused organs; and human studies including use of human volunteers, postmarketing surveillance, and epidemiology. With the advent, development and availability of computers since the original 3Rs, large data-sets can be used in statistical analysis, thereby reducing the numbers of animals used. Over much of the period they worked with a special Consultative Committee, chaired by Professor P.B. Animal Welfare Information Center Newsletter, 2(2): 1-2, CS1 maint: bot: original URL status unknown (, Universities Federation for Animal Welfare, National Centre for Replacement, Refinement and Reduction of Animals in Research, Animals (Scientific Procedures) Act (1986), The Principles of Humane Experimental Technique, 3Rs Alternatives: Technologies and Approaches, https://www.wellbeingintlstudiesrepository.org/cgi/viewcontent.cgi?article=1225&context=animsent, "Use and application of 3D-organoid technology", "iPS, organoids and 3D models as advanced tools for in vitro toxicology", "Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine", "National Centre for the Replacement, Reduction and Refinement of Animals in Research", "Harmonising the definition of Refinement", "The 3Rs Principle – Mind the Ethical Gap! They acknowledged that the arbitrary exclusion of invertebrates meant that in several contexts, these species could be considered as possible replacements for vertebrate subjects; they termed this "comparative substitution". [6] Human- and animal-cell-derived organoids are also used extensively in pharmacological and toxicological research. “3Rs alternatives” refers to the Reduction, Refinement, and Replacement of animals used in research, testing, and education. The 3Rs: Replacement, Reduction, and Refinement, are important from a legal, ethical and scientific standpoint. They are now widely accepted within the international scientific community and in associated legislation and guidelines, as a means of avoiding or reducing animal use and suffering and helping to improve the quality of science. In 1954, the Universities Federation for Animal Welfare (UFAW) decided to sponsor systematic research on the progress of humane techniques in the laboratory. The 3 “Rs” of Marketing consist of basic strategies used in developing an effective marketing plan. animal experimenters, institutional figures, policy makers, activists and the public) may interpret the Three Rs differently. More recent interpretations of the replacement principle suggest the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aims, i.e. Replacement: Johns Hopkins Bloomberg School of Public Health, Animals and Alternatives in Testing: History, Science, and Ethics, "This deserves to become a classic for all time and we have great hope that it will inaugurate a new field of systematic study. A CIOMS ethical code for animal experimentation. A key aspect of animal welfare is covered by what the biomedical community refers to as the three Rs (3Rs). Furthermore, there is no readily available up-to-date knowledge base on refinement. [15][16] The 3Rs principles do not address some issues, such as the ethics of using animals in research and focus instead on improving the humane use of animals which are used. However, at the present time, a thorough working knowledge and acceptance of the principles of humane experimental technique among scientists in general remains at best elusive and at worse ignored. Washington, D.C: National Academy Press, 1991. The Three R's originated in a proposal made in 1954 by Charles Hume, founder of the Universities Federation for Animal Welfare (UFAW) that the UFAW should undertake a scientific study of humane technique in laboratory animal experiments. ", "New techniques for producing transgenic animals - a mixed blessing from both the scientific and animal welfare perspectives", "Getting the measure of replacement, reduction and refinement - NC3Rs", "Prolonged pain research in mice: trends in reference to the 3Rs", "Survey of the quality of experimental design, statistical analysis and reporting of research using animals", "Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research", "The role of journals in implementing the 3Rs: ARRIVE and beyond - NC3Rs", "Two years later: journals are not yet enforcing the ARRIVE guidelines on reporting standards for pre-clinical animal studies", "Scientists and the 3Rs: attitudes to animal use in biomedical research and the effect of mandatory training in laboratory animal science", "Animal welfare: Inter-departmental group on reduction, refinement and replacement", "Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes", https://en.wikipedia.org/w/index.php?title=The_Three_Rs_(animals)&oldid=1022320141, CS1 maint: bot: original URL status unknown, Creative Commons Attribution-ShareAlike License, Appropriate anaesthetic and analgesic regimes for pain relief, Training animals to voluntarily co-operate with procedures (e.g. Our researchers make every effort to replace research animals with inanimate systems or non-animal models, reduce the number of animals involved, and refine husbandry and experimental procedures to minimize pain and … At present, we do not have a convenient and standardized way of objectively assessing animal pain and distress. One of these technologies, 3D cell cultures, also known as organoids or mini-organs, have replaced animal models for some types of research. [9][10], Reduction: Reduction refers to methods which minimise the number of animals used per study. Russell WMS, Burch RL. It is first described in their published book, Principles of Humane Experimental Technique The concept of recognizing, minimizing, and eliminating pain and distress in laboratory animals should be included in training programs for all persons involved in the care and use of laboratory animals. As a result, the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed[22] and published in 2010. The 3 Rs - Replacement, … Festing MFW (1992). Russell and Burch warned of the high-fidelity fallacy and of the danger of expecting discrimination in particular circumstances from models that show high fidelity in other, more general terms--a prediction illustrated by other more recent analyses of the differing molecular responses to certain chemicals by the rat, the mouse, and the human. Balls M, Goldberg AM, Fentem JH, Broadhead CL, Burch RL, Resting MFW, Frazier JM, Hendriksen CFM, Jennings M, van der Kamp MDO (1995). Veterinary health planning. As a contribution to the centenary of The Origin of Species, the quotations at the head of each chapter are all from the works of Charles Darwin. At the time of the book's publication, Charles Hume said: Hume's predictions regarding the book's impact have been realized as the concepts of replacement alternatives, reduction alternatives, and refinement alternatives have become established in law. Recognition and alleviation of pain and distress in laboratory animals. Training is defined as the acquisition of practical knowledge and skill directly associated with animal handling and procedures. Arising from the Government response to the report of the House of Lords Select Committee on animals in scientific procedures, the Group was asked to explore the scope for a UK centre for research into the 3Rs. Christine Stevens, founder of the Animal Welfare Institute (AWI) in the U.S., provided financial support for the project. Focus on severe suffering. Stokes WS, Jensen DJB (1995). Replacement refers to the preferred use of non-animal methods over animal use methods in the attainment of a similar level of results. Article Google Scholar 4. In the European Union, basic and applied research accounts for about two-thirds of the animals used in science. Refinement of animal use--assessment and alleviation of pain and distress. Russell and Burch writing six decades ago could not have anticipated some of the technologies that have emerged today. These principles are now standard in many regulatory institutions on both national and international scales. Joanne Zurlo, Deborah Rudacille, and Alan M. Goldberg Article reprinted from "Environmental Health Perspectives," August 1996, vol. Amsterdam: Elsevier, 1993. A common misconception of the 3Rs is that they refer only to replacement;[3] however, their scope is much broader. Tumoroids—3D cell cultures derived from cells biopsied from human patients—can be used in studying the genomics and drug resistance of tumors in different organs. One general way in which great reduction may occur is by the right choice of strategies in the planning and performance of whole lines of research. High discrimination models, on the other hand, "reproduce one particular property of the original, in which we happen to be interested." Regulations for Animal Well-being In response to increased public concern for the treatment and well-being of animals used in research, many new regulations and laws were passed to help protect animals. In some cases, the level of statistical expertise appears to be so low that investigators are either unaware of the potential value of obtaining statistical advice, or they are unable to obtain appropriate statistical advice because there are so few biometricians with experience in their field of interest.