Special Issue "60 Years of the Three Rs and Their Impact on Animal Welfare"

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Animal Welfare".

Deadline for manuscript submissions: closed (31 October 2019).

Special Issue Editors

Prof. Vera Baumans
E-Mail Website
Guest Editor
Department of Animals, Science, and Society; Division Laboratory Animal Science; Utrecht University; PO Box 80166; 3508 TD Utrecht; the Netherlands
Interests: laboratory animals; welfare, behavior; housing; environmental enrichment
Dr. Penny Hawkins
E-Mail Website
Guest Editor
Research Animals Department, RSPCA, Horsham, United Kingdom
Interests: ethical review and the refinement of animal care and use to reduce suffering and improve welfare
Dr. Paulin Jirkof
E-Mail Website
Guest Editor
Department of Animal welfare, University of Zurich, Zurich, Switzerland
Interests: 3Rs; Pain Management; animal welfare; assessment of stress

Special Issue Information

Dear Colleagues,

Laboratory animals have been used for a wide range of purposes for many years, including understanding basic physiology in health and disease, pharmaceutical research and development, safety assessment, and applied veterinary research. Animal experiments in the fields of biology, animal welfare, veterinary science, and agricultural science are usually designed to translate directly to the studied species. The vast majority of animals, however, are used for medical research and safety testing. Here, animals are almost exclusively used as substitutes or “models” for humans.

Although the ethical and animal welfare concerns associated with animal use are widely recognized, and investment into humane alternatives is increasing, full replacement is currently not possible and over 100 million animals per year are used worldwide in research and testing. Mice and rats are currently the most frequently used animal species, but the use of zebrafish is continuing to rise rapidly.

The field of laboratory animal science, a multidisciplinary branch of science that contributes to the quality of animal experiments and to the welfare of laboratory animals, was established in the 1950s. The growing understanding that animals are not simply “research tools”, and that better welfare leads to better science, led directly to the concept of the Three R’s—replacement, reduction, and refinement—launched by Russell and Burch in 1959 in their book “The Principles of Humane Experimental Technique” (developed while the authors held scholarships from the Universities Federation for Animal Welfare). This year we will celebrate the 60th anniversary of the Three Rs!

Replacement means the substitution of living animals using in vitro techniques (e.g., established cell lines that do not use animal sera, or human tissues), the use of lower organisms (e.g., yeasts), human volunteers, computerized models, genomics, proteomics, or organ-on-a-chip techniques. Partial replacement means the use of invertebrates that are not believed to suffer (e.g., nematode worms), out-of-scope developmental stages, and cell lines using animal sera. Replacement can also include avoiding animal use, for example, by systematic reviews or meta-analyses of previously published data, or taking a different approach to resolving a human health problem.

Reduction means taking every measure to decrease the number of animals used to the minimum amount necessary in order to answer the scientific question, for example, by employing optimal biostatistical methods, standardizing animals in terms of genotype and microbiological quality, or standardizing (and accurately reporting) the experimental procedures and animals’ environment. Imaging methods, using historic controls, and tissue sharing can also be used to reduce animal numbers.

Refinement means decreasing discomfort and promoting wellbeing throughout every animal’s lifetime. There are many ways to achieve this, including providing adequate anesthesia, analgesia, and care; guaranteeing the skills of the researchers and animal technologists through education and training; and improving the experimental procedures and determining a humane endpoint, where the animal can be humanely killed so as to prevent avoidable suffering. Concerning housing conditions, refinement can be achieved by translating the behavioral and physiological needs of the animal into adequate housing and husbandry.

For this Special Issue, we invite submissions on any aspect of the Three Rs, related to any research field or species. These may include papers describing current good-practice and/or evaluation studies, as well as commentaries and opinion pieces that review what the Three Rs have achieved in specific areas, or taking a forward look. Submissions relating to the ethical implications of the Three Rs, as well as concepts such as the culture of care, are also welcome.

Prof. Vera Baumans
Dr. Penny Hawkins
Dr. Paulin Jirkof
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Animals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • three Rs
  • animal welfare
  • replacement
  • reduction
  • refinement
  • systematic reviews
  • culture of care, reproducibility
  • planning animal experiments
  • organ-on-a-chip

Published Papers (10 papers)

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Research

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Open AccessArticle
“But It’s Just a Fish”: Understanding the Challenges of Applying the 3Rs in Laboratory Aquariums in the UK
Animals 2019, 9(12), 1075; https://doi.org/10.3390/ani9121075 - 03 Dec 2019
Abstract
Adopting a social science perspective and qualitative methodology on the problem of laboratory fish welfare, this paper examines some underlying social factors and drivers that influence thinking, priorities and implementation of fish welfare initiatives and the 3Rs (Replacement, Reduction and Refinement) for fish. [...] Read more.
Adopting a social science perspective and qualitative methodology on the problem of laboratory fish welfare, this paper examines some underlying social factors and drivers that influence thinking, priorities and implementation of fish welfare initiatives and the 3Rs (Replacement, Reduction and Refinement) for fish. Drawing on original qualitative interviews with stakeholders, animal technologists and scientists who work with fish—especially zebrafish—to illustrate the case, this paper explores some key social factors influencing the take up of the 3Rs in this context. Our findings suggest the relevance of factors including ambient cultural perceptions of fish, disagreements about the evidence on fish pain and suffering, the discourse of regulators, and the experiences of scientists and animal technologists who develop and put the 3Rs into practice. The discussion is focused on the UK context, although the main themes will be pertinent around the world. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Open AccessArticle
Group and Single Housing of Male Mice: Collected Experiences from Research Facilities in Sweden
Animals 2019, 9(12), 1010; https://doi.org/10.3390/ani9121010 - 21 Nov 2019
Abstract
Animals used for scientific purposes are protected by EU legislation. Social animals should be kept in stable groups that enable species-typical social behavior and provide individuals with social comfort. However, when group-housing male mice, aggression within the homecage is a common husbandry and [...] Read more.
Animals used for scientific purposes are protected by EU legislation. Social animals should be kept in stable groups that enable species-typical social behavior and provide individuals with social comfort. However, when group-housing male mice, aggression within the homecage is a common husbandry and welfare problem. Excessive fighting and injuries due to aggression can cause pain and stress, resulting in individuals being euthanized or housed individually. In addition, stress can alter physiological parameters, risking scientific validity and generating larger sample sizes. Mouse aggression, and the consequences thereof, thus opposes the 3R goals of Refining the methods to minimize potential pain and suffering and Reducing the number of animals used. Animal technicians, veterinarians, and scientists using animals have valuable information on how these problems are experienced and handled in practice. We assembled these experiences from laboratory animal facilities in Sweden, mapping problems observed and identifying strategies used to prevent mouse aggression. In line with current literature, less aggression was perceived if mice were grouped before sexual maturity, re-grouping avoided and nesting material transferred at cage cleaning. Preventing aggression will minimize pain and suffering and enable housing of stable groups, leading to more reliable scientific outcomes and is thus of high 3Rs relevance. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Open AccessCommunication
Alternatives to Carbon Dioxide—Taking Responsibility for Humanely Ending the Life of Animals
Animals 2019, 9(8), 482; https://doi.org/10.3390/ani9080482 - 24 Jul 2019
Cited by 1
Abstract
Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and Veterinary Office discussed the drawbacks [...] Read more.
Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and Veterinary Office discussed the drawbacks and alternatives to CO2 in euthanasia protocols for laboratory animals. Dialogue was facilitated by brainstorming sessions in small groups and a “World Café”. A conclusion from this process was that alternatives to CO2 were urgently required, including a program of research and extension to meet the needs for humane killing of these animals. The next step will involve gathering a group of international experts to formulate, draft, and publish a research strategy on alternatives to CO2. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)

Review

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Open AccessReview
How Can Systematic Reviews Teach Us More about the Implementation of the 3Rs and Animal Welfare?
Animals 2019, 9(12), 1163; https://doi.org/10.3390/ani9121163 - 17 Dec 2019
Abstract
This paper describes the introduction of the systematic review methodology in animal-based research and the added value of this methodology in relation to the 3Rs and beyond. The 3Rs refer to Replacement, Reduction, and Refinement of animal studies. A systematic review (SR) is [...] Read more.
This paper describes the introduction of the systematic review methodology in animal-based research and the added value of this methodology in relation to the 3Rs and beyond. The 3Rs refer to Replacement, Reduction, and Refinement of animal studies. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question. Examples are given on how SRs lead to the implementation of the 3Rs and better science. Additionally, a broader context is given regarding societal, political, and scientific developments. Various examples of systematic reviews are given to illustrate the current situation regarding reporting, quality, and translatability of animal-based research. Furthermore, initiatives that have emerged to move further towards more responsible and sustainable research is of benefit for both animals and humans. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
Open AccessReview
Assessing Affective State in Laboratory Rodents to Promote Animal Welfare—What Is the Progress in Applied Refinement Research?
Animals 2019, 9(12), 1026; https://doi.org/10.3390/ani9121026 - 25 Nov 2019
Abstract
An animal’s capacity to suffer is a prerequisite for any animal welfare concern, and the minimization of suffering is a key aim of refinement research. In contrast to the traditional focus on avoiding or reducing negative welfare states, modern animal welfare concepts highlight [...] Read more.
An animal’s capacity to suffer is a prerequisite for any animal welfare concern, and the minimization of suffering is a key aim of refinement research. In contrast to the traditional focus on avoiding or reducing negative welfare states, modern animal welfare concepts highlight the importance of promoting positive welfare states in laboratory animals. Reliable assessments of affective states, as well as the knowledge of how to elicit positive affective states, are central to this concept. Important achievements have been made to assess pain and other negative affective states in animals in the last decades, but it is only recently that the neurobiology of positive emotions in humans and animals has been gaining more interest. Thereby, the need for promotion of positive affective states for laboratory animals is gaining more acceptance, and methods allowing the assessment of affective states in animals have been increasingly introduced. In this overview article, we present common and emerging methods to assess affective states in laboratory rodents. We focus on the implementation of these methods into applied refinement research to identify achieved progress as well as the future potential of these tools to improve animal welfare in animal-based research. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Other

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Open AccessOpinion
Applying the 3Rs: A Case Study on Evidence and Perceptions Relating to Rat Cage Height in the UK
Animals 2019, 9(12), 1104; https://doi.org/10.3390/ani9121104 - 09 Dec 2019
Abstract
This article investigates the barriers to implementing higher caging in animal research establishments in the UK. The use of animals in research and testing in the UK is regulated by the Animals (Scientific Procedures) Act 1986, which sets out how animal experiments must [...] Read more.
This article investigates the barriers to implementing higher caging in animal research establishments in the UK. The use of animals in research and testing in the UK is regulated by the Animals (Scientific Procedures) Act 1986, which sets out how animal experiments must be licensed and regulated. Within this, the Code of Practice currently allows laboratory rats to be housed in cages that are 20 cm high, even though adults can rear up to 30 cm. Most adult rats therefore cannot stand upright in ‘standard’ cages. We found that the main factors hindering the implementation of higher caging were classified into five different groups; health and safety, financial, animal welfare, scientific, and ‘human’. Suggestions to overcome these barriers are provided, as well as alternative animal welfare changes that can be put into place. We conclude that much of the desired evidence for moving to higher cages is already available, and therefore the focus should be on education and improving access to the existing evidence, in order to encourage facilities to work around existing financial and health and safety concerns. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Open AccessConcept Paper
The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments
Animals 2019, 9(11), 975; https://doi.org/10.3390/ani9110975 - 14 Nov 2019
Abstract
Training in the design of animal experiments focuses all too often on those aspects which can be approached mathematically, such as the number of animals needed to deliver a robust result, allocation of group size, and techniques such as randomization, blocking and statistical [...] Read more.
Training in the design of animal experiments focuses all too often on those aspects which can be approached mathematically, such as the number of animals needed to deliver a robust result, allocation of group size, and techniques such as randomization, blocking and statistical analysis. Important as they are, these are only a small part of the process of planning animal experiments. Additional key elements include refinements of housing, husbandry and procedures, health and safety, and attention at all stages to animal welfare. Advances in technology and laboratory animal science have led to improvements in care and husbandry, better provision of anesthetics and analgesics, refined methods of drug administration, greater competence in welfare assessment and application of humane endpoints. These improvements require continual dialogue between scientists, facility managers and technical staff, a practice that is a key feature of what has become known as the culture of care. This embodies a commitment to improving animal welfare, scientific quality, staff care and transparency for all stakeholders. Attention to both the physical and mental health of all those directly or indirectly involved in animal research is now an important part of the process of planning and conducting animal experiments. Efforts during the last 30 years to increase the internal and external validity of animal experiments have tended to concentrate on the production of guidelines to improve the quality of reporting animal experiments, rather than for planning them. Recently, comprehensive guidelines for planning animal studies have been published, to redress this imbalance. These will be described in this paper. Endorsement of this overarching influence of the Three R concept, by all the stakeholders, will not only reduce animal numbers and improve animal welfare, but also lead to more reliable and reproducible research which should improve translation of pre-clinical studies into tangible clinical benefit. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
Open AccessConcept Paper
3Rs-Related and Objective Indicators to Help Assess the Culture of Care
Animals 2019, 9(11), 969; https://doi.org/10.3390/ani9110969 - 14 Nov 2019
Abstract
Within animal research and testing, the need for an effective Culture of Care is widely recognized and described in terms of an establishment-wide commitment to improving the implementation of the 3Rs, animal welfare, scientific quality, care of the staff, and transparency for all [...] Read more.
Within animal research and testing, the need for an effective Culture of Care is widely recognized and described in terms of an establishment-wide commitment to improving the implementation of the 3Rs, animal welfare, scientific quality, care of the staff, and transparency for all stakeholders, including the public. Ideally, each establishment would determine what the Culture of Care means for them, and be able to assess and potentially benchmark their own culture. Some establishments already do this, using various indicators and formal or informal assessments. This paper provides examples of these approaches to assessing the Culture of Care, including surveys and surrogate measures. Many currently-used criteria and indicators tend to be human-centric and subjective, and we suggest using further objective indicators and animal-centric, 3Rs-based criteria. It is preferable to consider each of the 3Rs separately when assessing culture, and some indicators are suggested to facilitate this. Several documents produced by regulators in the UK and European Union are good sources of objective indicators of a good Culture of Care. This concept paper aims to complement the literature on assessing the Culture of Care, providing ideas and sources of information to help identify relevant and measurable criteria. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Open AccessCommentary
Humanely Ending the Life of Animals: Research Priorities to Identify Alternatives to Carbon Dioxide
Animals 2019, 9(11), 911; https://doi.org/10.3390/ani9110911 - 02 Nov 2019
Abstract
The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found that provide a safe and reliable [...] Read more.
The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found that provide a safe and reliable way to induce unconsciousness in groups of animals, and also cause less distress than CO2. Here, we revisit the current and historical literature to identify key research questions that may lead to the identification and implementation of more humane alternatives to induce unconsciousness in mice, rats, poultry, and pigs. In addition to the evaluation of novel methods and agents, we identify the need to standardise the terminology and behavioural assays within the field. We further reason that more accurate measurements of consciousness state are needed and serve as a central component in the assessment of suffering. Therefore, we propose a roadmap toward improving animal welfare during end-of-life procedures. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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Open AccessFeature PaperEssay
The 3Rs and Humane Experimental Technique: Implementing Change
Animals 2019, 9(10), 754; https://doi.org/10.3390/ani9100754 - 30 Sep 2019
Cited by 1
Abstract
In 1959, the Universities Federation for Animal Welfare (UFAW) Scholars Russell & Burch published the Principles of Humane Experimental Technique in which they laid out the principles of the Three Rs. However, the Three Rs owed much to others. It was UFAW and, [...] Read more.
In 1959, the Universities Federation for Animal Welfare (UFAW) Scholars Russell & Burch published the Principles of Humane Experimental Technique in which they laid out the principles of the Three Rs. However, the Three Rs owed much to others. It was UFAW and, in particular, UFAW’s Founder and Director, Major Charles Hume who identified the problem that needed to be tackled, and who developed the non-confrontational approach that was needed to both formulate the questions that needed answers and to obtain the answers from the research community. Russell & Burch’s work was also guided by an expert scientific and technical committee chaired by the Nobel Prize winner Sir Peter Medawar. This essay describes the history of the Three Rs using publications by the protagonists and others as well as material from UFAW’s archives. It describes the background to the employment of Russell & Burch, the methodology of Russell & Burch’s approach and the impact of their work up to the present day—where the Three Rs are incorporated in legislation throughout the world. Full article
(This article belongs to the Special Issue 60 Years of the Three Rs and Their Impact on Animal Welfare)
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