Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments

This paper summarizes a more detailed report produced by the Federation of European Laboratory Animal Science Associations (FELASA 2005), which describes and explores a set of principles for the conduct of ethical review of laboratory animal use. It presents a synopsis of results from a questionnaire that elicited information on how each of 20 countries represented in FELASA currently approaches such ethical review. This information suggests that, although local practices differ, there is an emerging consensus on the key elements that any ethical review process should involve. Drawing on the questionnaire findings, this summary also includes a brief discussion to support and amplify a series of recommendations, covering the objectives of ethical review; legal requirements; the scope of work reviewed and the 'level' at which review is approached; general principles for the organization of ethical review processes; the factors considered in the review; needs for ongoing review after initial authorization; participants in the review process; wider impacts of the review process; and strategies that can help to ensure quality and consistency of review outcomes. For further information and examples of current practice, as well as more detailed discussion to support the recommendations, readers are urged to refer to the complete report, available at http://www.lal.org.uk/pdffiles/FELASA_ethics_FULL_Report. pdf or via: http://www.felasa.eu/recommendations.htm.     

Discussion for animal experiments in space: ethical standard and responsibility of researchers for space experiments using laboratory animals.

International efforts to standardize regulations and study designs and to promote the principles of Reduction, Replacement, and Refinement (the 3 Rs) have reduced and refined animal use. In NASA ARC and KSC, researchers are responsible only for activities related directly to the conduct of their animal experiments. The IACUC plays an important role in conformity with NIH policies. Even if researchers design protocols of the space life science in Japan, the animal experiments should be carried out under the global harmonized conditions in accordance with NIH/NASA policies, guides and rules. It is important that researchers himself must look forward the ethical animal experiment.     

比较医学动物实验计算机辅助设计系统的研发

目的开发一款辅助研究者设计比较医学动物实验方案和学习实验设计的应用软件。方法根据实验动物应用的"科学、伦理、经济"原则筛选比较医学动物实验技术资料,运用关系数据库架构原理分析和组织入选数据,通过解析比较医学动物实验规律和特点设计程序框架和模块,采用C++语言、MFC库进行面向用户的程序设计。结果建立了程序相关资源库和模型选择、实验动物、环境条件、实验步骤、方案输出5个功能模块,并完成整个软件测试。结论研发成功比较医学动物实验计算机辅助设计系统,该系统能够基于微型计算机为用户提供有效、易用的动物实验辅助设计和自助学习功能。     

Development of a plant growth support system for experiments on the ISS

The European Modular Cultivation System (EMCS) is one of a wide range of laboratory modules under construction by ESA that will be placed on the International Space Station (ISS). In the present study the development and construction of an important component in the EMCS, the Plant Cultivation Container (PCC), is described. The PCC as a "flower pot" will automatically provide the plants with water and liquid nutrients as needed. The PCC is located inside the plant growth unit, the Experiment Container (EC), on the EMCS and interfaces with the EMCS. The essential parts of the PCC are a Peltier element, a micro valve, a monitoring RH sensor with an integrated platinum RTD temperature sensor, a RH sensor that detects air leaving the PCC and controls the peristaltic pump, a DC-DC board that provides correct current to the Peltier element, and a switch/connector board. The PCC is presently being tested out at ESTEC/ESA.     

Actor-network theory: a tool to support ethical analysis of commercial genetic testing

Social, ethical and policy analysis of the issues arising from gene patenting and commercial genetic testing is enhanced by the application of science and technology studies, and Actor-Network Theory (ANT) in particular. We suggest the potential for transferring ANT's flexible nature to an applied heuristic methodology for gathering empirical information and for analysing the complex networks involved in the development of genetic technologies. Three concepts are explored in this paper--actor-networks, translation, and drift--and applied to the case of Myriad Genetics and their commercial BRACAnalysis genetic susceptibility test for hereditary breast cancer. Treating this test as an active participant in socio-technical networks clarifies the extent to which it interacts with, shapes and is shaped by people, other technologies, and institutions. Such an understanding enables more sophisticated and nuanced technology assessment, academic analysis, as well as public debate about the social, ethical and policy implications of the commercialization of new genetic technologies.     

I. P. Pavlov on vivisection and the modern ethical requirements for animal experiments]

It is shown that Pavlov's opinion is in agreement with the modern requirements for experiments in living animals: use of living animals in experiments is recommended only in the cases when there is no alternative and scientific-practical significance of the planned experiments is justified; minimization (as much as possible) of discomfort, distress and pain of animals under study without sacrifice of the quality of scientific research; use of appropriate number of animals necessary for obtaining reliable results which are adequate to a given experimental situation and general state of the animals inadmissibility of using extra number of animals; drawing up a protocol concerning the experimental procedure and results; reflection in the protocol the techniques of sedation, anesthesia, and euthanasia; constant care of the improvement of the theoretical and practical qualification of a researcher in the ethical questions and experimental technique. Pavlov's views led his time and at present they agree with modern concepts on the experimental ethics.     

Actor-Network Theory: a tool to support ethical analysis of commercial genetic testing

Social, ethical and policy analysis of the issues arising from gene patenting and commercial genetic testing is enhanced by the application of science and technology studies, and Actor-Network Theory (ANT) in particular. We suggest the potential for transferring ANT's flexible nature to an applied heuristic methodology for gathering empirical information and for analysing the complex networks involved in the development of genetic technologies. Three concepts are explored in this paper—actor-networks, translation, and drift—and applied to the case of Myriad Genetics and their commercial BRACAnalysis genetic susceptibility test for hereditary breast cancer. Treating this test as an active participant in socio-technical networks clarifies the extent to which it interacts with, shapes and is shaped by people, other technologies, and institutions. Such an understanding enables more sophisticated and nuanced technology assessment, academic analysis, as well as public debate about the social, ethical and policy implications of the commercialization of new genetic technologies.|spagf|ro|epagf|     

The embryonic development of Schistosoma mansoni eggs: proposal for a new staging system

Schistosomiasis is a water-borne parasitic illness caused by neoophoran trematodes of the genus Schistosoma. Using classical histological techniques and whole-mount preparations, the present work describes the embryonic development of Schistosoma mansoni eggs in the murine host and compares it with eggs maintained under in vitro conditions. Two pre-embryonic stages occur inside the female worm: the prezygotic stage is characterized by the release of mature oocytes from the female ovary until its fertilization. The zygotic stage encompasses the migration of the zygote through the ootype, where the eggshell is formed, to the uterus. Fully formed eggs are laid still undeveloped, without having suffered any cleavage. In the outside environment, eight embryonic stages can be defined: stage 1 refers to early cleavages and the beginning of yolk fusion. Stage 2 represents late cleavage, with the formation of a stereoblastula and the onset of outer envelope differentiation. Stage 3 is defined by the elongation of the embryonic primordium and the onset of inner envelope formation. At stage 4, the first organ primordia arise. During stages 5 to 7, tissue and organ differentiation occurs (neural mass, epidermis, terebratorium, musculature, and miracidial glands). Stage 7 is characterized by the nuclear condensation of neurons of the central neural mass. Stage 8 refers to the fully formed larva, presenting muscular contraction, cilia, and flame-cell beating. This staging system was compared to a previous classification and could underlie further studies on egg histoproteomics (morphological localizome). The differentiation of embryonic structures and their probable roles in granulomatogenesis are discussed herein. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Human tissue for in vitro research as an alternative to animal experiments: a charitable "honest broker" model to fulfil ethical and legal regulations and to protect research participants

Research with human tissue offers the possibility not only of improving preclinical pharmaceutical research and safety assessment, but also of the substitution of some animal experiments. Surgically removed human tissue is discarded after pathological evaluation. This tissue would be of enormous value for research, especially in the pharmaceutical branch, if it were readily available in an ethically and legally approved manner. But there are public concerns about the use of human tissue, especially for "commercial" purposes, such as in the pharmaceutical industry. The question is whether the ethical boundaries are sufficiently respected in the course of striving for industrial profit. To overcome this problem, a clear procedure for tissue donation, collection, supply and allocation must be established, which is guaranteed to be independent of special interests. The persisting problem seems to be the lack of an authority which asks for informed consent, coordinates tissue as well as blinded data collection, and supplies research facilities with tissue samples in a transparent manner. Therefore, a charitable, state-controlled foundation acting as an "honest broker" was initiated, to cover the ethical and legal aspects, as well as to protect the research participants in their use of human tissue as an alternative to animal experiments.     

Establishment of an efficient germ-free animal system to support functional microbiome research

正Germ-free animals are indispensable models for human and animal functional microbiome research Germ-free animals are animals that typically have no microorganisms living in or on them. These animals have become irreplaceable research tools for studying the relationships among single bacteria strains, multiple bacteria strains and hosts.     

Magnetic resonance imaging using a clinical whole body system: an introduction to a useful technique in small animal experiments.

A clinical whole body magnetic resonance imaging (MRI) system with high resolution coils was used to obtain non-invasive images of the living rat. The results demonstrate the feasibility of the set-up and the advantages of this new imaging technique: detailed information, no extra costs, longitudinal studies without killing animals and simple anaesthesia. It is concluded that in small animal experimentation, this use of high resolution coils in whole body magnetic resonance systems may be particularly helpful in establishing effects of experimental procedures. Whenever non-invasive visualization is required, especially in longitudinal animal studies, e.g. biomaterial research or tumour investigation, this use of MRI will offer challenging possibilities.     

Mapping out structural features in clinical care calling for ethical sensitivity: a theoretical approach to promote ethical competence in healthcare personnel and clinical ethical support services (CESS)

Clinical ethical support services (CESS) represent a multifaceted field of aims, consultancy models, and methodologies. Nevertheless, the overall aim of CESS can be summed up as contributing to healthcare of high ethical standards by improving ethically competent decision-making in clinical healthcare. In order to support clinical care adequately, CESS must pay systematic attention to all real-life ethical issues, including those which do not fall within the 'favourite' ethical issues of the day. In this paper we attempt to capture a comprehensive overview of categories of ethical tensions in clinical care. We present an analytical exposition of ethical structural features in judgement-based clinical care predicated on the assumption of the moral equality of human beings and the assessment of where healthcare contexts pose a challenge to achieving moral equality. The account and the emerging overview is worked out so that it can be easily contextualized with regards to national healthcare systems and specific branches of healthcare, as well as local healthcare institutions. By considering how the account and the overview can be applied to i) improve the ethical competence of healthcare personnel and consultants by broadening their sensitivity to ethical tensions, ii) identify neglected areas for ethical research, and iii) clarify the ethical responsibility of healthcare institutions' leadership, as well as specifying required institutionalized administration, we conclude that the proposed account should be considered useful for CESS.     

Use of factorial designs to optimize animal experiments and reduce animal use

Optimization of experiments, such as those used in drug discovery, can lead to useful savings of scientific resources. Factors such as sex, strain, and age of the animals and protocol-specific factors such as timing and methods of administering treatments can have an important influence on the response of animals to experimental treatments. Factorial experimental designs can be used to explore which factors and what levels of these factors will maximize the difference between a vehicle control and a known positive control treatment. This information can then be used to design more efficient experiments, either by reducing the numbers of animals used or by increasing the sensitivity so that smaller biological effects can be detected. A factorial experimental design approach is more effective and efficient than the older approach of varying one factor at a time. Two examples of real factorial experiments reveal how using this approach can potentially lead to a reduction in animal use and savings in financial and scientific resources without loss of scientific validity.     

The scope for improving the design of laboratory animal experiments.

The factors which need to be taken into account in designing a 'good' experiment are reviewed. Such an experiment should be unbiased, have high precision, a wide range of applicability, it should be simple, and there should be a means of quantifying uncertainty (Cox 1958). The relative precision due to the use of randomized block designs was found to range from 96% to 543% in 5 experiments involving 30 variables. However, a survey of 78 papers published in two toxicology journals showed that such designs were hardly used. Similarly, designs in which more than one factor was varied simultaneously ('factorial designs') were only used in 9% of studies, though interactions between variables such as dose and strain of animal may be common, so that single factor experiments could be misleading. The consequences of increased within-group variability due to infection and genetic segregation were quantified using data published by G?rtner (1990). Both substantially reduced precision, but toxicologists continue to use non-isogenic laboratory animals, leading to experiments with a lower level of precision than is necessary. It is concluded that there is scope for improving the design of animal experiments, which could lead to a reduction in animal use. People using animals should be required to take formal training courses which include sessions on experimental design in order to minimize animal use and to increase experimental efficiency.     

Strengthening medical appraisal: reactions to proposals for a new appraisal system to support revalidation

This paper introduces the first stage of the NHS Revalidation Support Team's (RST) proposals to strengthen medical appraisal. It reports on four focus groups held at London Deanery in 2010, with the aim of gauging initial reactions from general practitioners (GPs). The four groups consisted of two groups of appraisers and two groups of appraisees. After presentation of the proposals to strengthen appraisal, participants were invited to make comparisons between existing appraisal, and the new proposals, Interestingly, the matter which attracted most discussion was a proposal to include an element of self-assessment by the appraisee prior to appraisal, and not, as might have been expected, the proposals for assessment of the appraisee's progress towards revalidation by the appraiser. Since these focus groups, the model of strengthened medical appraisal referred to in this paper has been the subject of testing in the pathfinder pilot, a large scale pilot involving 3000 doctors in various settings in England. The evaluation of the pathfinder pilot was published (July 2011). After further refinement of the appraisal process, including taking into account new GMC and Royal College publications and more testing and piloting, the final version of medical appraisal to support revalidation, known as the Medical Appraisal Guide (MAG) is due to be published in March 2012, in time to permit the expected commencement of revalidation in late 2012.     

Sample Power and ExpDesign: tools for improving design of animal experiments

Proper experimental design, involving the correct number of animals, should be a basic skill for any scientist working with animals. The authors describe a university-developed and freely available tutorial program and an interactive computer-assisted learning program, both of which guide students through the steps necessary for designing animal experiments and estimating optimal sample sizes.