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The Origins and Early Days of the Three Rs Concept

Michael Balls

Some questions are answered concerning the origins of the Three Rs (Replacement, Reduction, Refinement) concept in relation to animal experimentation, expounded 50 years ago by Russell and Burch in The Principles of Humane Experimental Technique, by reference to some key publications and to correspondence in the W.M.S. and Claire Russell Archive, which is currently being established at the University of Nottingham. Some insight is also given into the relationship between Russell and Burch, the first use of “alternatives” in the Three Rs context, and the background to the publication of the book.
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The Progress of Humane Experimental Technique Since 1959: A Personal Viewa

Rex L. Burch

This is very much a personal interpretation of the Three Rs and the efforts by scientists connected with the more humane use of animals. It is intended to illustrate that scientists are given a job to do and, if it involves animals, they have little choice but to use them. It is also intended to illustrate that so many of those so involved are the very people who have made gigantic efforts in finding ways of replacing, reducing and/or refining techniques which require animals.
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Physiologically-based Simulation Modelling for the Reduction of Animal Use in the Discovery of Novel Pharmaceuticals

Simon Thomas

The global pharmaceutical industry is estimated to use close to 20 million animals annually, in in vivo studies which apply the results of fundamental biomedical research to the discovery and development of novel pharmaceuticals, or to the application of existing pharmaceuticals to novel therapeutic indications. These applications of in vivo experimentation include: a) the use of animals as disease models against which the efficacy of therapeutics can be tested; b) the study of the toxicity of those therapeutics, before they are administered to humans for the first time; and c) the study of their pharmacokinetics — i.e. their distribution throughout, and elimination from, the body. In vivo pharmacokinetic (PK) studies are estimated to use several hundred thousand animals annually. The success of pharmaceutical research currently relies heavily on the ability to extrapolate from data obtained in such in vivo studies to predict therapeutic behaviour in humans. Physiologically-based modelling has the potential to reduce the number of in vivo animal studies that are performed by the pharmaceutical industry. In particular, the technique of physiologically-based pharmacokinetic (PBPK) modelling is sufficiently developed to serve as a replacement for many in vivo PK studies in animals during drug discovery. Extension of the technique to incorporate the prediction of in vivo therapeutic effects and/or toxicity is less well-developed, but has potential in the longer-term to effect a significant reduction in animal use, and also to lead to improvements in drug discovery via the increased rationalisation of lead optimisation.
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FRAME, the Three Rs and the Russell Archive at the University of Nottingham

Michael Balls

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.
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FRAME: The Early Days

Andrew N. Rowan

The article reviews the early history of FRAME from the perspective of its first “Scientific Administrator”. The roles of Mrs Hegarty the founder, and other early contributors to FRAME’s development are described. In addition, the article discusses FRAME’s strategic approach to the subject and how Mrs Hegarty’s background influenced the development of that approach.
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An Investment in the Three Rs Can be Very Profitable

Rodger Curren

The Principles of Humane Experimental Technique by William Russell and Rex Burch provides exceptional value, both to practitioners of alternative methodologies and to bibliophiles who enjoy the pursuit of an out-of-print book. I was stimulated to find an original edition by my first visits to FRAME and its Chairman, Michael Balls. The search continued for several years, until I was able to find an edition suitable for presentation to him. During this hunt, I was able to learn a great deal about the Three Rs of Replacement, Reduction and Refinement, and the programmes that FRAME initiated to educate scientists and the general public about alternative approaches. Very importantly, I was able to use many of FRAME’s successful strategies to build up a similar organisation in the United States, the Institute for In Vitro Sciences. The double value of this book is now revealed — not only are its concepts scientifically and ethically valuable, but the price now being charged by secondhand booksellers means a more than ten-fold increase in the value of my investment!
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The Dr Hadwen Trust for Humane Research: 39 years of Replacement Science

Sebastien Farnaud

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.
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The Importance of Anniversaries

Vicky Robinson

This year marks a number of important anniversaries for the Three Rs and those organisations involved in their advancement. These include the 50th anniversary of the publication of Russell and Burch’s book, The Principles of Humane Experimental Technique, the 40th anniversary of FRAME, and the 5th anniversary for the UK’s National Centre for the 3Rs. These anniversaries provide an important opportunity to reflect on past achievements and future challenges.
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FRAME — Reflections on the Future and Challenges to Success

Chris Flower

FRAME is 40 years of age and has contributed much to reasoned debate on the need to use animals in responsible scientific enquiry. It has done this through the promotion of good science as best practice, as well as promotion of the Three Rs of Reduction, Refinement and Replacement of animal experimentation. However, unless the debate widens to question society at large over its attitudes to personal risk, to accepting responsibility rather than apportioning blame, and to its simplistic adoption of regulation as the panacea, we could see the pursuit of the Three Rs degenerate into a formulaic process, leading to imperfect animal models being replaced by imperfect alternatives which would not serve to improve our science. We must not lose sight of the ultimate goal of conducting good science without the need to use animals.
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Depolarising Primate Experimentation: The Good, the Bad and the Determined

Michelle Hudson

Until I began working at FRAME, I was not really aware of the Three Rs or FRAME’s work to promote and progress them. It soon became clear to me that it made scientific sense and that it could make a difference to many thousands of laboratory animals. As an alternatives advocate, I regularly experience optimism, frustration and determination. This is illustrated most clearly by the primate research dilemma. Here, I describe the positive and negative experiences I have had whilst working toward the goal of replacing primate experiments, and how these have led me to undertake a multidisciplinary PhD project on primate use in biomedical research. The aim is to examine how research scientists view the opportunities and challenges involved in the use of primates in biomedical science, and to investigate the feasibility of phasing out their use. As a result of the research, I hope to provide a new perspective, to depolarise the debate and bring about a constructive dialogue between all parties as to how and when primate research could be replaced.
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2017-01-09T06:38:00+00:00 Tags: , , , , , |