Fund For The Replacement Of Animals In Medical Experiments Research Articles

Personal Reflections on Russell and Burch, FRAME, and the HSUS

The coincidence of anniversaries associated with the publication of William Russell and Rex Burch's The Principles of Humane Experimental Technique, the founding of the Fund for the Replacement of Animals in Medical Experiments (FRAME), and the establishment of the collaboration between FRAME and the University of Nottingham, provides an opportunity to reflect on Russell and Burch's legacy and how it was carried forward by FRAME. The Principles, published in 1959, was the pioneering work in what later became the alternatives or Three Rs field of replacement, reduction, and refinement of animal use. Such was the book's initial and undeserved obscurity, however, that FRAME, following its founding in 1969, pioneered a similar approach independently of Russell and Burch's work. The Humane Society of the United States (HSUS) was also an early champion of the alternatives framework, and through the establishment of the Russell and Burch Award, helped unite Russell and Burch with what had emerged as the alternatives community. Thanks largely to FRAME, Russell and Burch were able to participate in Three Rs activity before their deaths. They lived long enough to see their ideas take hold, but not long enough to see the emerging revolution currently under way in toxicity testing, toward the use of non-animal methods.

FRAME, the Three Rs and the Russell Archive at the University of Nottingham

The objectives of the Fund for the Replacement of Animals in Medical Experiments (FRAME) are spelled out, as laid down in the Charity's Trust Deed of 1969, and the support of the Charity's trustees, consultants, patrons and staff in all that has been achieved during its first 40 years, are recognised. The recent establishment of the W.M.S. and Claire Russell Archive at the University of Nottingham is recognised as a further important link between FRAME and the University.

The Dr Hadwen Trust for Humane Research: 39 years of Replacement Science

The year 2009 will not be remembered mainly because it is the Chinese year of the ox, but probably, for many, because it is Charles Darwin's bicentenary, the 150th anniversary of the publication of his masterpiece, The Origin of Species, the 50th anniversary of the publication by Russell and Burch of The Principles of Humane Experimental Technique, where they introduced the concept of Three Rs, and also the 40th anniversary of the foundation of the Fund for the Replacement of Animals in Medical Experiments (FRAME). FRAME will always remain our senior, since the Dr Hadwen Trust for Humane Research is only celebrating its 39th anniversary this year! After four decades of learning, challenging, contesting, creating, promoting and advancing the Three Rs concept, the idea of the replacement of the use of animals in research has itself become a science, giving the old sterile debate between pro- and anti-vivisectionists a new dimension. Although scientific progress has been the main reason for such changes, it is important to remember that, without the people and organisations whose aim has been devoted to this cause, these changes might never have happened. Still, as illustrated by the 2008 statistics on animal procedures, many more changes will have to be made, and it is by considering the progress achieved during the last 40 years that we can find the strength and motivation to pursue our goal of scientific research and testing that no longer relies on animal-based techniques.

Establishing a Three Rs Programme at the Canadian Council on Animal Care

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.

Refinements in husbandry, care and common procedures for non-human primates

Preface Whenever animals are used in research, minimizing pain and distress and promoting good welfare should be as important an objective as achieving the experimental results. This is important for humanitarian reasons, for good science, for economic reasons and in order to satisfy the broad legal principles in international legislation. It is possible to refine both husbandry and procedures to minimize suffering and improve welfare in a number of ways, and this can be greatly facilitated by ensuring that up-to-date information is readily available. The need to provide such information led the British Veterinary Association Animal Welfare Foundation (BVAAWF), the Fund for the Replacement of Animals in Medical Experiments (FRAME), the Royal Society for the Prevention of Cruelty to Animals (RSPCA) and the Universities Federation for Animal Welfare (UFAW) to establish a Joint Working Group on Refinement (JWGR) in the UK. The chair is Professor David Morton and the secretariat is provided by the RSPCA. This report is the ninth in the JWGR series. The RSPCA is opposed to the use of animals in experiments that cause pain, suffering, distress or lasting harm and together with FRAME has particular concerns about the continued use of non-human primates. The replacement of primate experiments is a primary goal for the RSPCA and FRAME. However, both organizations share with others in the Working Group, the common aim of replacing primate experiments wherever possible, reducing suffering and improving welfare while primate use continues. The reports of the refinement workshops are intended to help achieve these aims. This report produced by the British Veterinary Association Animal Welfare Foundation (BVAAWF)/Fund for the Replacement of Animals in Medical Experiments (FRAME)/Royal Society for the Prevention of Cruelty to Animals (RSPCA)/Universities Federation for Animal Welfare (UFAW) Joint Working Group on Refinement (JWGR) sets out practical guidance on refining the husbandry and care of non-human primates (hereinafter primates) and on minimizing the adverse effects of some common procedures. It provides a valuable resource to help understand the physical, social and behavioural characteristics and needs of individual primates, and is intended to develop and complement the existing literature and legislative guidelines. Topics covered include refinements in housing, husbandry and common procedures such as restraint, identification and sampling, with comprehensive advice on issues such as primate communication, assessing and facilitating primate wellbeing, establishing and maintaining social groups, environmental and nutritional enrichment and animal passports. The most commonly used species are the key focus of this resource, but its information and recommendations are generally applicable to other species, provided that relevant individual species characteristics are taken into account.

The Third FRAME Toxicity Committee: Working toward Greater Implementation of Alternatives in Toxicity Testing

FRAME (the Fund for the Replacement of Animals in Medical Experiments; http://www. frame.org.uk) is a scientific charity, which has, for over 30 years, been advocating and conducting its own research on the application of the Three Rs (reduction, refinement and replacement) to animal experimentation. FRAME develops and validates scientifically based replacement alternative methods to facilitate their acceptance by scientists and regulators. As part of these activities, FRAME established a FRAME Toxicity Committee in 1979, and a report of its work was published in 1982, and discussed in the proceedings of a subsequent meeting, published in 1983. A Second Toxicity Committee formed in 1988, reported its work in 1990, which was discussed in the proceedings of a subsequent conference, published in 1991. The work of these committees was extremely successful and influential in laying the foundation for later activities in alternatives research. A Third FRAME Toxicity Committee was formed in 1999, since much progress had been achieved in the previous decade, especially with regard to the successful validation of several non-animal replacement methods and the start of their regulatory acceptance. Moreover, some new test methods are on the point of being validated, and many new techniques and discoveries are impacting on toxicity testing. Also, interest in reduction and refinement in toxicology has increased. However, there is considerable scope and need for the further implementation of the Three Rs in toxicity testing, especially due to recent plans for the large-scale testing of high-production volume, hormonally-active and existing chemicals, and the increasing use of transgenic animal models. The new committee comprises 18 experts from industry, academia, animal welfare, legislative and regulatory bodies, with one observer from the UK Government Home Office. The main objective is to review progress made in the application of the Three Rs in the development and safety evaluation of medicines, biologicals, cosmetics, agrochemicals and other products, as well as industrial chemicals, and to make recommendations as a basis for further sensible progress according to sound scientific and ethical criteria. The main committee is to be augmented by several working parties that will focus on specific scientific issues: 1) targeted risk assessment versus hazard identification; 2) data sharing; 3) endocrine disruption; and 4) carcinogenicity testing. The Committee is also to publish a status report on the current situation regarding alternatives in toxicity testing, based on the recommendations of the Second Toxicity Committee, and will organise a conference to discuss its overall conclusions and recommendations.

Optimising Resources by Reduction: The FRAME Reduction Committee

The Fund for the Replacement of Animals in Medical Experiments (FRAME) Reduction Committee, formed in 1998, comprises experienced professionals in the fields of statistics, experimental design, animal welfare and alternatives. The committee undertakes projects designed to contribute to reduction by addressing the implementation of recommendations made at an European Centre for the Validation of Alternative Methods (ECVAM) workshop on reducing the use of laboratory animals. The use of improved experimental design and statistical analysis techniques are key means of achieving reduction. Literature surveys have shown that there is scope for improvement in these areas. Projects include organising workshops that explain how these techniques can be used to achieve reduction, the creation of guidelines for journal editors and the compilation of a directory of training material on experimental design and statistical analysis. The first FRAME Reduction Committee international symposium will be held in October 2002.

Refining laboratory mouse husbandry

The available statistics suggest that some 7 million mice are used annually for scientific procedures in the European Union. More mice are used than any other species. There has been a great deal of attention given to application of the ‘3Rs’ (replacement of animal use, reduction of numbers used, and refinement of techniques) in scientific procedures but there may be room for considerable further improvement in the quality of animals’ lives through improved husbandry. In view of this, about 10 years ago, the British Veterinary Association Animal Welfare Foundation (BVAAWF), the Fund for the Replacement of Animals in Medical Experiments (FRAME), the Royal Society for the Prevention of Cruelty to Animals (RSPCA), and the Universities Federation for Animal Welfare (UFAW) established a Joint Working Group on Refinement tasked with arranging working parties to define improvements in the husbandry of laboratory animals. This is the third report produced by the Joint Working Group (previous reports covered the removal of blood and rabbit husbandry). The 14 authors comprise experts in a variety of aspects of murine biology, care, and welfare.

The Fund for the Replacement of Animals in Medical Experiments (FRAME): The First 25 Years

The establishment of FRAME in 1969 and the Charity's development during its first 25 years are reviewed, with emphasis on FRAME'S campaigns, FRAME publications, the FRAME Research Programme, the FRAME Toxicity Committee, and FRAME'S role in the drafting and passage through Parliament of the Animals (Scientific Procedures) Act 1986.

The in vitro effects and metabolism-mediated cytotoxicity of phorone, a glutathione-depleting agent

The use of S-9 liver fractions to examine metabolism-mediated cytotoxicity in vitro has the inherent problem that not only are activating enzyme systems added, but also deactivation pathways, such as that involving glutathione. The in vivo manipulation of these activating and deactivating systems prior to S-9 preparation is possible with animals, but not with humans. Hence, the possibility of depleting glutathione in target cells and S-9 fractions was evaluated using phorone, a known glutathione-depleting agent. 3T3-L1 mouse fibroblast-like cells and V79 Chinese hamster lung fibroblasts were used as the target cells, and cytotoxicity was assessed by the FRAME (Fund for the Replacement of Animals in Medical Experiments) kenacid blue method. Phorone was found to have a moderate intrinsic cytotoxicity and to effectively deplete cellular glutathione. When phorone was used in the two-component S-9 fraction/target cell system, its toxicity to 3T3-L1 cells was markedly increased, which suggests transformation to a toxic metabolite. The use of S-9 fractions from animals pretreated with phenobarbitone and β-naphthoflavone resulted in greatly increased phorone toxicity, which indicates the involvement of cytochrome P-450 enzymes in its metabolism. The metabolism-mediated toxicity of phorone was reduced by the addition of exogenous glutathione.

THE ANIMALS (SCIENTIFIC PROCEDURES) ACT 1986

Hollands reviews the activities of the Committee for the Reform of Animal Experimentation (CRAE) in securing passage of Britain's 1986 Animals (Scientific Procedures) Act. Founded in 1978 to seek reform of the law governing animal experimentation, CRAE allied itself with the British Veterinary Association and the Fund for the Replacement of Animals in Medical Experiments (FRAME) to influence government policy. Accepting that the abolishment of all animal research was an unrealistic goal, CRAE set four objectives for new legislation: the restriction of pain, a substantial decrease in the number of experimental animals used, the development and use of alternative research methods, and public accountability. Hollands asserts that these goals have been achieved in the 1986 Act, with its strong provisions for animal research oversight by the Home Secretary. He also notes increased interest by scientific groups in monitoring animal experimentation.

The frame interlaboratory programme on in vitro cytotoxicology

FRAME (the Fund for the Replacement of Animals in Medical Experiments) has established a research programme in collaboration with four research centres and a number of industrial companies, to determine whether cell cultures can reliably be used to replace live animal procedures in routine tests on the relative acute toxicities of chemicals. Following the development of the test protocol, initial trials were carried out to establish intralaboratory and interlaboratory reproducibility and the criteria for choice of cell types, end-points and metabolizing systems. A set of coded chemicals is being collected for use in blind trials and summaries of existing knowledge of the in vivo toxicity of these compounds are being produced. More recently, FRAME has established an international validation scheme for in vitro alternative methods.