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The Canadian and United States' approaches to oversight of animals in research are both based on the "3Rs" principles outlined in Russell and Burch's classic text, The Principles of Humane Experimental Technique. Each country seeks to protect the welfare of animals, while permitting the legitimate goals of scientific research to be attained according to the legal principles, cultures, and strengths and constraints of their jurisprudential and societal traditions. Canada is one of the most decentralized federations in the world, and regulation of activities is based to a great extent on custom and practice. The United States is more hierarchical and, at least with respect to laws governing animal research, more centralized. Accordingly, the Canadian approach is rooted in the concepts of social contracts, with a greater emphasis on guidance and policy and less reliance on legislation. No federal (national) direct legislation of laboratory animal welfare exists, although the federal government uses its criminal and spending authorities to shape behavior. The central feature of the Canadian system is the Canadian Council on Animal Care, which was formed to support universities and government departments involved in animal-based science. Animal care committees play a central role in implementing the guidelines and policies in facilities that carry out animal research. The United States has enacted two federal (national) laws applicable to animals in research. The Animal Welfare Act is a more traditional, command-and-control law that gives authority to the US Department of Agriculture to promulgate regulations, inspect facilities, and enforce violations. The Health Research Extension Act, which amended the US Public Health Services (PHS) Act, applies to any activity conducted or supported by the PHS, including research efforts supported by the US National Institutes of Health. It is largely nonregulatory and establishes a system of assurances and policies that covered research facilities must follow. States play only a minor role in animal research protection. As in Canada, institutional animal care and use committees are tasked with self-regulation of activities that use animals for research.

The oversight of animal ethics and care in Canada relies on a national peer review system, the Canadian Council on Animal Care (CCAC). For close to 50 years, the CCAC has brought about high standards for experimental animal ethics and care through the development of relevant standards and a code of ethics, and through training and the certification of institutional programs. Since 1998, the CCAC has been awarding its Certificate of GAP (Good Animal Practice) to institutions that meet its national standards. The certificate is a prerequisite to receiving research funding from Canadian and American granting agencies and from charitable organizations that fund animal-based research, and is a requirement for institutions wishing to import certain species of research animals into Canada. In addition to these funding and importation requirements, five provinces reference CCAC standards in regulations to their animal welfare legislation, and the province of Ontario specifically legislates in this area through its Animals for Research Act.

The principles of humane experimental technique, first described by Russell and Burch in 1959, focus on minimising suffering to animals used for scientific purposes. Internationally, as these principles became embedded in the various systems of oversight for the use of animals in science, attention focused on how to minimise pain, distress and lasting harm to animals while maximising the benefits to be obtained from the work. Suffering can arise from the experimental procedures, but it can also arise from the manner in which the animals are housed and cared for. Increased attention is therefore being paid to the entire lifetime experience of an animal, in order to afford it as good a quality of life as possible. Russell and Burch were also concerned that animals should not be used if alternatives to such use were available, and that animals were not wasted through poor-quality science. This concept is being revisited through new efforts to ensure that experiments are well designed and properly reported in the literature, that all results--positive, negative or neutral--are made available to ensure a complete research record, and that animal models are properly evaluated through periodic systematic reviews. These efforts should ensure that animal use is truly reduced as far as possible and that the benefits derived through the use of animals truly outweigh the harms.

When a book about the ethics of animal research has a chimpanzee on its cover, one can be fairly sure of two things: that the editor is intending to be controversial; and that the main thrust of th...

When asked about the use of animals in biomedical research, people often state that the research is only acceptable if pain and distress are minimised. However, pain is caused when the aim is to study pain itself, resulting in unalleviated pain for many of the animals involved. Consequently, the use of animals in pain research is often considered contentious. To date, no research has explored people's views toward different types of animal-based pain research (e.g. chronic or acute pain). This study used a web-based survey to explore people's willingness to support the use of mice in chronic versus acute pain research. The majority of the participants opposed the use of mice for either chronic (68.3%) or acute (63.1%) pain research. There was no difference in the levels of support or opposition for chronic versus acute pain research. Unsupportive participants justified their opposition by focusing on the perceived lack of scientific merit, or the existence of non-animal alternatives. Supporters emphasised the potential benefits that could arise, with some stating that the benefits outweigh the costs. The majority of the participants were opposed to pain research involving mice, regardless of the nature and duration of the pain inflicted, or the perceived benefit of the research. A better understanding of public views toward animal use in pain research may provide a stronger foundation for the development of policy governing the use of animals in research where animals are likely to experience unalleviated pain.

Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37-64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies.

A case-study approach was used to identify opportunities and challenges to the implementation of the Three Rs in vaccine testing in Canada. Data was obtained through interviews with 16 Canadian stakeholders involved in the production, testing and evaluation of vaccines. Participants identified inconsistent regulatory testing requirements, the lack of biological functionality of some in vitro methods, the benchmarking of in vitro against in vivo assays, and high caution towards method changes as major challenges to implementation. Opportunities to implementation were identified as the desire for and steps taken towards harmonization of test methods between countries, collaborations on new method development, the poor performance of traditional animal methods, the domino effect of one regulatory authority accepting a method after another, and stakeholder concerns for the ethical care and use of animals used in vaccine testing. These results suggest that industry and the Canadian government are open to implementing the Three Rs in vaccine quality control, but methods adopted must be reliable and biologically relevant. Improving the harmonization of regulatory requirements will assist in furthering the implementation of alternative methods.

The anniversary of the Fund for the Replacement of Animals in Medical Experiments (FRAME) provides an opportunity to celebrate the Charity's achievements over the past 40 years, and in particular, its contribution to the international acceptance of the Three Rs as the basis of an ethic for animal experimentation, and its role as a leader in the implementation of the Three Rs in the life sciences. The Canadian Council on Animal Care (CCAC) has based its work on the Three Rs, especially since the establishment of its fundamental CCAC Policy Statement on the Ethics of Animal Investigation (1989). Following recommendations from the evaluation of its programmes by external committees established by the national granting agencies, the CCAC recently launched a Three Rs Program. This programme will build on the work of FRAME and other similar Three Rs organisations, to further the promotion and implementation of the Three Rs in Canadian science.

To ensure the safety of Canada's shellfish, the Canadian Shellfish Sanitation Program (CSSP) relies on the mouse bioassay to detect toxins known to cause paralytic shellfish poisoning (PSP). This assay uses a large number of mice and requires death as an endpoint. Canadian research has led to the development of a pre-column High Performance Liquid Chromatography (HPLC) method that is more sensitive and more reliable than the mouse bioassay. However, it is not being used by Canadian regulators despite its acceptance by the AOAC and adoption by the United Kingdom. An ethnography study of stakeholders in the CSSP was conducted to determine the opportunities and obstacles to adopting analytical testing methods. The results of the study indicate that the major obstacles are a lack of certified reference materials (CRMs) and the direction of resources towards the development of new instrument-based methods rather than towards the refinement of the existing pre-column HPLC method for regulatory use. To move away from the mouse bioassay, Canada should invest in: basic research to develop a complete set of CRMs for PSP toxins; method refinement to increase sample throughput; and exercises to gain international acceptance of the pre-column HPLC method.

The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30–40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18–0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.

In 1959, Russell and Burch published The Principles of Humane Experimental Technique, which included concrete advice on factors that they considered would govern progress in the implementation of these principles (enunciated as the 3Rs [Replacement, Reduction, and Refinement in animal-based studies]). One challenge to the implementation of the 3Rs was identified as information retrieval. Here, we further explore this challenge—the need for ‘research on research’—and the role that systematic reviews and reporting guidelines can play in implementation of the 3Rs. First, we examine the 2-fold nature of the challenge of information retrieval: 1) the identification of relevant publications spread throughout a large population of nonrelevant publications and 2) the incomplete reporting of relevant details within those publications. Second, we evaluate how systematic reviews and reporting guidelines can be used generally to address this challenge. Third, we assess the explicit reporting of the 3Rs in a cohort of preclinical animal systematic reviews. Our results show that Reduction methods are the most commonly reported by authors of systematic reviews but that, in general, reporting on how findings relate to the 3Rs is limited at best. Although systematic reviews are excellent tools for resolving the challenge of information retrieval, their utility for making progress in implementation of the 3Rs may be limited unless authors improve their reporting of these principles.

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

By considering reduction before refinement, we risk allowing some animals to experience greater pain and distress. A variety of approaches can help balance reduction and refinement while promoting ...

The first International Symposium on Regulatory Testing and Animal Welfare (ISRTAW), held 21–23 June 2001, in Québec City, Canada, brought together 160 experts from 22 countries from North and South America, Europe and Asia. The experts included representatives from national research and regulatory agencies, universities, and industry involved in chemicals, pesticides and drug safety testing. Representatives from European, Canadian and US animal welfare groups also participated in the discussions. The Symposium was organised by the International Council for Laboratory Animal Science (ICLAS) and the Canadian Council on Animal Care (CCAC), with the support and assistance of many sponsors and advisors. ICLAS is a worldwide organisation whose purpose is to foster the international harmonisation of animal care and use practices. CCAC is the national agency responsible for overseeing the ethical use of animals in Canadian science. Both organisations are committed to fostering an environment in which global efforts to harmonise testing procedures using animals in a more-humane manner can be realised.

2The experts included representatives from national research and regulatory agencies, universities, and industry involved in chemicals, pesticides, and drug safety testing. Representatives from European, Canadian, and US animal welfare groups also participated in the discussions. The Symposium was organized by the International Council for Laboratory Animal Science (ICLAS 1 ) and the Canadian Council on Animal Care (CCAC 1 ), with the support and assistance of many sponsors and advisors listed elsewhere in the issue. ICLAS is a worldwide organization whose purpose is to foster international harmonization of animal care and use practices. CCAC is the national agency responsible for overseeing the ethical use of animals in Canadian science. Both organizations are committed to fostering an environment in which global efforts to harmonize testing procedures using animals in a more humane manner can be realized.

Canada's oversight of animal use in science has evolved in a different manner than many other countries. Arising from a study in 1966, the Canadian Council on Animal Care (CCAC) was established as a peer review system heavily reliant on the contribution of volunteer experts to contribute to the development of standards and the assurance of compliance both within institutions and nationally through the CCAC's Assessment and Certification program. Institutions found to be in compliance with CCAC's standards receive a Certificate of GAP-Good Animal Practice® as a tangible sign of their commitment to maintaining publically acceptable standards of animal care and use. Academic institutions must obtain and maintain a valid Certificate of GAP-Good Animal Practice® in order to be eligible for funding by the two main granting agencies that fund animal-based research. While there is no federal legislation in Canada in the area of oversight of the use of animals for scientific purposes, many of the provinces have made reference to the CCAC guidelines and policies in the regulations to their animal welfare acts, making it a provincial requirement to adhere to CCAC standards. One province, Ontario, has enacted legislation in the form of the Ontario Animals for Research Act. Institutions within this province are therefore subject to both CCAC standards and the requirements of the Animals for Research Act.

The genetic engineering of animals for their use in science challenges the implementation of refinement and reduction in several areas, including the invasiveness of the procedures involved, unanticipated welfare concerns, and the numbers of animals required. Additionally, the creation of genetically-engineered animals raises problems with the Canadian system of reporting animal numbers per Category of Invasiveness, as well as raising issues of whether ethical limits can, or should, be placed on genetic engineering. A workshop was held with the aim of bringing together Canadian animal care committee members to discuss these issues, to reflect on progress that has been made in addressing them, and to propose ways of overcoming any challenges. Although previous literature has made recommendations with regard to refinement and reduction when creating new genetically-engineered animals, the perception of the workshop participants was that some key opportunities are being missed. The participants identified the main roadblocks to the implementation of refinement and reduction alternatives as confidentiality, cost and competition. If the scientific community is to make progress concerning the implementation of refinement and reduction, particularly in the creation and use of genetically-engineered animals, addressing these roadblocks needs to be a priority.

The Canadian Council on Animal Care (CCAC) is scheduled to publish Guidelines on the Care and Use of Wildlife on its website http://www.ccac.ca in January 2003. The underlying ethical basis of all CCAC guidelines and policies requires adherence to the concept of the Three Rs of Russell and Burch (reduction, refinement and replacement). However, the development of these guidelines raised particular challenges in implementing this ethical concept. Where the aim of field studies is to understand the ecology, ecophysiology or behaviour of wildlife, replacement by a non-animal method, or even replacement of one species with a less sentient species, may not be an option. On the other hand, the humane treatment of wild vertebrates for research is both an ethical and a scientific necessity. Traumatised animals may exhibit abnormal physiological, behavioural and ecological responses that defeat the purposes of the investigation and may have an impact on the local ecosystem. Assessment of what constitutes humane treatment is often a challenge in wildlife research, as it may differ in different contexts. Animal care committees are useful in this respect, as they focus on the ethical implications of the research through requiring practical steps to be in place prior to the study. In addition, the guidelines outline a process for reporting outcomes of research to assist in improving welfare outcomes for study animals.

There are two components to the review of animal based protocols in Canada: review for the merit of the study itself, and review of the ethical acceptability of the work. Despite the perceived importance for the quality assurance these reviews provide; there are few studies of the peer-based merit review system for animal-based protocols for research and education. Institutional animal care committees (ACC)s generally rely on the external peer review of scientific merit for animal-based research. In contrast, peer review for animal based teaching/training is dependent on the review of pedagogical merit carried out by the ACC itself or another committee within the institution. The objective of this study was to evaluate the views of ACC members about current practices and policies as well as alternate policies for the review of animal based teaching/training. We conducted a national web-based survey of ACC members with both quantitative and qualitative response options. Responses from 167 ACC members indicated broad concerns about administrative burden despite strong support for both the current and alternate policies. Participants' comments focused mostly on the merit review process (54%) relative to the efficiency (21%), impact (13%), and other (12%) aspects of evaluation. Approximately half (49%) of the comments were classified into emergent themes that focused on some type of burden: burden from additional pedagogical merit review (16%), a limited need for the review (12%), and a lack of resources (expertise 11%; people/money 10%). Participants indicated that the current system for pedagogical merit review is effective (60%); but most also indicated that there was at least some challenge (86%) with the current peer review process. There was broad support for additional guidance on the justification, criteria, types of animal use, and objectives of pedagogical merit review. Participants also supported the ethical review and application of the Three Rs in the review process. A clear priority from participants in the survey was updating guidance to better facilitate the merit review process of animal-based protocols for education. Balancing the need for improved guidance with the reality of limited resources at local institutions will be essential to do this successfully; a familiar dilemma to both scientists and policy makers alike.

World aquaculture has grown tremendously during the last 50 years from a production of less than a million tonnes in the early 1950s to 59.4 million tonnes in 2004 (FAO 2004). In Canada, aquaculture production has trebled in the past decade from 66 to 155 metric tonnes (DFO 2005a). According to the Network of Centres of Excellence for Aquaculture (Aquanet 2004), Canada has a significant potential to increase its aquaculture production and expand into the culture of new species, as anticipated growth is expected to continue in step with population growth and dietary trends. Demand for seafood in North America alone is expected to increase by up to 40 per cent by 2010 (Gilbert 2002). As the industry continues to grow, it will have to address public concerns about the quality of the food supply. Recent food related concerns about contaminants, diseases and overall wholesomeness of food (e.g., BSE, avian influenza, levels of mercury, and genetically modified foods) have consumers seeking assurances regarding the source and methods of production of their food. The 2005 strategic plan from the Department of Fisheries and Oceans Canada acknowledges that it will need to work with the aquaculture industry and the Canadian Food Inspection Agency to build credible systems for assuring the quality and safety of farmed seafood products (DFO 2005b). These systems will include quality assurance and control, traceability and on-farm food safety, as well as the environmental sustainability of aquaculture operations. If this mirrors the systems for assuring quality and safety of terrestrial farmed animal products, then assuring quality will include assurance that food has been raised according to certain standards of animal welfare. For example, according to Agriculture and Agri-Food Canada, in addition to complying with legislation and being guided by the Codes of Practice, Canadian producers advance farm animal welfare through continuous learning and adaptation, and via on-farm quality assurance programs that include farm animal welfare components. Felicity Huntingford has examined the “role” of animal welfare in aquaculture from her standpoint as a biologist in the fish biology group at the University of Glasgow. Dr Huntingford was one of the authors of the Fisheries Society of the

Evidence exists, particularly in the welfare literature of nonhuman animals on the farm, that the interaction between nonhuman animals and the personnel who care for them can have a strong effect on the animals' behavior, productivity, and welfare. Among species commonly used for biomedical research, mice appear to be the least-preferred species in animal care facilities. A review of the literature and observations of animal care staff interacting with mice indicated that the following factors may influence this: their small size, their particular behavioral characteristics, and husbandry constraints (such as housing in ventilated racks). In addition, this study questioned whether animal care personnel have a different perception of genetically engineered animals and whether this, in turn, has an effect on their interactions with these animals. The ability to carefully observe an animal's behavior is key in carrying out an animal-wellness assessment and in minimizing pain and distress. Attention to human-animal interactions in the research setting represents an opportunity for refinement for large numbers of animals and potentially for reduction of animal use.

In Canada, promotion of the Three Rs concept of alternatives occurs largely through the Canadian Council on Animal Care. Institution-based animal care committees are required to conduct an ethical review of all protocols which use animals in research, teaching or testing. Investigators are expected to use animals only when their best efforts to find an alternative have failed. Those using animals are required to employ the most humane methods on the smallest number of animals possible. The Joseph F. Morgan Research Foundation was established to promote the development and use of alternative methods in Canada. The focus of the Foundation has been on the use of alternative methods for testing purposes. However, the Foundation also encourages the acceptance of each of the Three Rs throughout Canadian science. The Foundation is therefore in the process of developing a refinement alternatives programme.