It’s Time to Reconsider The Principles of Humane Experimental Technique

2020 ◽  
Vol 48 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Michael Balls
Keyword(s):  
Experimental Technique ◽  
Species Differences ◽  
Animal Experimentation ◽  
New Drugs ◽  
Animal Testing ◽  
Human Welfare ◽  
Preclinical Testing ◽  
Testing Strategies ◽  
Animal Use ◽  
The Three Rs

In the 60 years since the publication of The Principles of Humane Experimental Technique, the Three Rs ( Reduction, Refinement, Replacement) proposed by William Russell and Rex Burch have gradually been accepted throughout the world as ways of facing up to the ethical and scientific dilemmas involved in animal experimentation. However, the scale of animal use and the use of animals as models of humans has continued, seemingly almost unchallenged in much of the scientific community, despite the warnings about models, species differences and human variation spelled out in the The Principles. In this Comment, it is proposed that it is time to move away from the animal welfare focus of the Three Rs, in favour of a wider concept of humanity, which also embraces human welfare. In addition, since less than 10% of new drugs successfully pass from preclinical testing, which is highly reliant on animal procedures, to acceptance for clinical use, it is argued that the aim should not be to directly replace animal testing with non-animal methods with similar aims and which produce similar results, but to take advantage of developments in cell and molecular biology and in computer science, to devise new, different, appropriate, specific and intelligent stand-alone preclinical testing strategies that are applicable to particular human situations.

Reduction in Animal Use 35 Years after Russell & Burch's Principles of Humane Experimental Technique

1995 ◽  
Vol 23 (1) ◽  
pp. 51-60
Author(s):  
Michael F.W. Festing
Keyword(s):  
Experimental Design ◽  
Experimental Technique ◽  
Large Scale ◽  
New Drugs ◽  
F1 Hybrids ◽  
F1 Hybrid ◽  
Wide Range ◽  
Animal Use ◽  
Research Scientists ◽  
The Way

“Reduction” in animal use can be achieved by better experimental strategy and improved experimental design. In 1959, one strategy for discovering new drugs involved the random testing of thousands of chemicals in animal models of disease. This strategy was deplored by Russell & Burch in The Principles of Humane Experimental Technique (1959) as being inefficient and inhumane, and has now been almost completely superseded, following fundamental research resulting in an improved understanding of the mechanisms of drug action. Random screening is still done on a large scale, but by using in vitro methods. Good experimental design involves the control of variation. In 1959, it was not clear whether isogenic (inbred or F1 hybrid) strains of mice and rats were more uniform than outbred stocks and whether they should therefore be used preferentially in bioassays. It is now generally accepted that F1 hybrids and inbred strains tend to be more uniform, but, as precision also depends on sensitivity, which is unpredictable, there is no general rule for choosing the best strain for a bioassay. Choice should be based on pilot studies. However, the use of more-uniform, specific pathogen-free animals, which were only just becoming available in 1959, has certainly reduced the number of animals which are used. Other aspects of experimental design, such as the need to avoid bias, have a wide range of applicability; the importance of simplicity and the ability to calculate uncertainty are, apparently, not always appreciated by research scientists. The concept of “reduction” has been useful in focusing attention on the need for improved experimental design. In the long-run, animal welfare legislation and improved training for research scientists should lead to improvements, not only in the way in which animals are kept, but also in the way in which experiments are planned and analysed.

The Origins and Early Days of the Three Rs Concept

2009 ◽  
Vol 37 (3) ◽  
pp. 255-265 ◽  
Author(s):  
Michael Balls
Keyword(s):  
Experimental Technique ◽  
Animal Experimentation ◽  
The University ◽  
The Relationship ◽  
The Three Rs

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.

It’s Time to Include Harm to Humans in Harm–Benefit Analysis — But How to Do It, That is the Question

2021 ◽  
pp. 026119292110622
Author(s):  
Michael Balls
Keyword(s):  
Species Differences ◽  
Animal Experiments ◽  
Animal Experimentation ◽  
Benefit Analysis ◽  
Indirect Benefit ◽  
New Approach ◽  
Vested Interests ◽  
Current Availability ◽  
The Impact ◽  
The Three Rs

The Three Rs ( reduction, refinement, replacement) concept put forward by Russell and Burch now appears to be widely accepted. However, their warnings concerning reliance on animals as models for humans, the insurmountable problem of species differences and the impact of human variation, have been downplayed or even ignored. Schemes for harm–benefit analysis have been introduced, but the focus has largely been on harm to the animals, rather than on the direct and indirect benefit to humans, which is much more difficult to evaluate. Greater recognition should be given to the direct or indirect harm to humans resulting from the current over-reliance of biomedical research and testing on data obtained from animal experiments. That will be hard to achieve in the current climate, given the vigorous defence of animal experimentation by those with vested interests, confusion over responsibilities for regulating animal experimentation, hierarchies of regulatory authorities which require or limit experiments on animals, and exaggerated claims about the current availability of new approach methodologies (NAMs) and relevant and reliable strategies for their use. Those who defend animal experimentation at almost any cost must bear part of the responsibility for the human harms which result. Meanwhile, much greater effort should be put into the development, validation and application of new approaches not involving animals.

The Use of Biomarkers as Alternatives to Current Animal Tests on Food Chemicals

1998 ◽  
Vol 26 (4) ◽  
pp. 421-480
Author(s):  
Krys Bottrill
Keyword(s):  
Animal Studies ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
In Vitro Test ◽  
Animal Testing ◽  
Dietary Biomarkers ◽  
Recent Developments ◽  
Mechanistic Basis ◽  
The Three Rs

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.

scholarly journals Clinical Drug Trials on Human Beings viz-a-viz Sanctions related to Animal Experimentation: Need to do Introspection?

2012 ◽  
Vol 46 (3) ◽  
pp. 113-116
Author(s):  
Roosy Aulakh ◽  
Chander Shekhar Gautam ◽  
Prabhjot Singh Cheema
Keyword(s):  
Animal Experimentation ◽  
New Drugs ◽  
Drug Trials ◽  
Human Beings ◽  
Animal Protection ◽  
Research Organizations ◽  
Legal Sanctions ◽  
Clinical Drug Trials ◽  
Health Care Law ◽  
Clinical Drug

ABSTRACT Health care law is totally localized in its nature, but research for the development of new drugs has crossed man-made geographical limits. Weaker legal sanctions, poverty, illiteracy and inaccessibility to legal system have all contributed to make India a favored hub for contact research organizations. Many recent clinical drug trials in India have sparked controversy. However, in India today, we are more bothered about animal protection, but show little concern for volunteers in human trials. It is gradually becoming difficult to conduct research on animals; however, research on human beings is far easier. Sanctions against violation of rights of human volunteers in clinical trials are often only a perceived phenomenon. They are not protected as they should be. Regulatory framework needs thorough introspection, debate, reconsideration and strict implementation. These guidelines should not only be recommendatory but mandatory in nature and those who indulge in violations, shall be punished as per the law of the land effectively. How to cite this article Gautam CS, Aulakh R, Cheema PS. Clinical Drug Trials on Human Beings viz-a-viz Sanctions related to Animal Experimentation: Need to do Introspection? J Postgrad Med Edu Res 2012;46(3):113-116.

Beyond Animal Rights

2019 ◽  
pp. 22-44
Author(s):  
Celia E. Deane-Drummond
Keyword(s):  
Social Justice ◽  
Human Dignity ◽  
Theoretical Approach ◽  
Animal Rights ◽  
Categorical Imperative ◽  
Animal Experimentation ◽  
Comparative Approach ◽  
Social Agenda ◽  
Moral World ◽  
Animal Use

This chapter sets out the philosophical context for current debates in animal ethics, including abolitionist versions of animal rights that are against all forms of animal use, including animal experimentation and agriculture. The author argues that while a more muted version of animal rights is more convincing, rights language has proved inadequate to the modest task of shifting to more humane treatments of other animals. There are also theoretical problems associated with the use of rights language that itself is premised on a particular approach to social justice. Utilitarian advocates following Peter Singer do not fare much better in that his liberationist agenda is ethically ambiguous by his association of speciesism with racist and even sexist views. This approach could just as easily diminish women and those of colour, or deny human dignity, all of which have a strong political and social agenda, rather than elevating concern for other animals. Even anti-speciesism still relies on a comparative approach that begins by widening the moral world of humans to sentient others, even while, ironically perhaps, denying the special significance of the human species. Christine Korsgaard has made the most convincing case so far for rehabilitating Immanuel Kant’s categorical imperative so that it is extended to other animals. Rather more promising is the largely theoretical approach of Peter Scott’s argument for postnatural right and Cynthia Willett’s interspecies ethics to begin to map out the multispecies frameworks.

The Development of the Three Rs Concept

1995 ◽  
Vol 23 (3) ◽  
pp. 298-304 ◽  
Author(s):  
W.M.S. Russell
Keyword(s):  
Experimental Technique ◽  
Laboratory Animal ◽  
Toxicity Testing ◽  
Statistical Technique ◽  
Culture Technique ◽  
Animal Science ◽  
Experimental Animals ◽  
Pharmacology And Toxicology ◽  
The Three Rs ◽  
Laboratory Animal Science

In 1955–57, in the course of a study initiated by Charles Hume and the Universities Federation for Animal Welfare, Rex Burch and I conceived of the Three Rs of humane experimental technique — replacement, reduction and refinement. Except for the foundation, in 1969, and the early work, of FRAME, the next two decades saw little development of the Three Rs, and widespread scepticism about the possibilities of replacement, especially in activity and toxicity testing. In the 1980s and early 1990s, advances in tissue culture technique led to spectacular progress in fundamental pharmacology and toxicology. There have also been important recent advances in aspects of refinement discussed in our book published in 1959, notably in anaesthesia and analgesia, and in the application of ethology. However, there has been less progress in reduction, except for one ingenious new statistical technique for reducing numbers of animals used for testing vaccines. Developments we scarcely touched on in 1959 include the application of the Three Rs to the production and testing of vaccines, the education of experimenters in laboratory animal science (both of these developments pioneered in The Netherlands), and the replacement of animals in teaching by the use of computers and audiovisual displays. A priority for the future is the application of the Three Rs to work with primates. New uses for experimental animals continue to arise, but, after recent successes, we can now have considerable confidence in the progress of humane experimental technique.

Developments in the Collection of Statistical Information on the Number of Animals used in Experiments and other Scientific Purposes in the European Union

2000 ◽  
Vol 28 (1) ◽  
pp. 133-145
Author(s):  
Ursula G. Sauer ◽  
Roman Kolar
Keyword(s):  
European Union ◽  
European Commission ◽  
Genetically Engineered ◽  
Laboratory Animals ◽  
The European Union ◽  
Member States ◽  
Statistical Report ◽  
Animal Use ◽  
The Three Rs ◽  
The Eu

In 1999, the European Commission presented its second report on the numbers of laboratory animals used in the European Union (EU). The plausibility of the data and the usefulness of the format of the registration tables remain questionable, for reasons previously discussed in connection with the Commission's first statistical report. In addition, it is impossible to derive sound information on trends in animal use in the EU and its Member States from the second statistical report. The European Commission and the Member States have agreed on new tables to be used for future statistics on the use of experimental animals in the EU. These new tables have been significantly extended and improved. Several categories of little relevance have been revised, and ambiguous expressions have been clarified. However, several problems either persist or have been newly created. Moreover, some important data (i.e. categories for pain and distress, as well as for several specific purposes of use; the origin of some animal species; types of institutions; and the use of genetically engineered animals) are still not required. Nevertheless, these are highly relevant to animal welfare and must be regarded as indispensable for a well-aimed application of the statistics to set priorities concerning the Three Rs.

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