Responsible animal-based research: three flags to consider

Flagging experiments is one way to reduce the amount of nonhuman animal-based research. Experiments flagged for the following 3 characteristics are highly questionable: few or no citations received in the years following publication, thus having little or no influence on subsequent research; large numbers of animals used; and invasive procedures, such as injections or anesthesia and surgery, used on animals who were then allowed to recover enough to be tested in some way. Selecting and analyzing a sample of articles describing such experiments (such as those by authors at Canadian universities) determines which journals, author-affiliated universities, and acknowledged funding sources have the most flags. One could also assess the work of individual scientists. Using recommendations supplied, efforts to reduce the suffering of animals and the waste of tax dollars can then focus especially on these entities.     

Cephalopods in neuroscience: regulations,research and the 3Rs

Cephalopods have been utilised in neuroscience research for more than 100 years particularly because of their phenotypic plasticity, complex and centralised nervous system, tractability for studies of learning and cellular mechanisms of memory (e.g. long-term potentiation) and anatomical features facilitating physiological studies (e.g. squid giant axon and synapse). On 1 January 2013, research using any of the about 700 extant species of “live cephalopods” became regulated within the European Union by Directive 2010/63/EU on the “Protection of Animals used for Scientific Purposes”, giving cephalopods the same EU legal protection as previously afforded only to vertebrates. The Directive has a number of implications, particularly for neuroscience research. These include: (1) projects will need justification, authorisation from local competent authorities, and be subject to review including a harm-benefit assessment and adherence to the 3Rs principles (Replacement, Refinement and Reduction). (2) To support project evaluation and compliance with the new EU law, guidelines specific to cephalopods will need to be developed, covering capture, transport, handling, housing, care, maintenance, health monitoring, humane anaesthesia, analgesia and euthanasia. (3) Objective criteria need to be developed to identify signs of pain, suffering, distress and lasting harm particularly in the context of their induction by an experimental procedure. Despite diversity of views existing on some of these topics, this paper reviews the above topics and describes the approaches being taken by the cephalopod research community (represented by the authorship) to produce “guidelines” and the potential contribution of neuroscience research to cephalopod welfare.     

The ethics of animal research: a UK perspective

The Nuffield Council on Bioethics, an independent body in the United Kingdom, has published a 2005 report titled The Ethics of Research Involving Animals. The Report, produced by a Working Party that represented a wide range of views, seeks to clarify the debate that surrounds this topic and aims to help people identify and analyze the relevant scientific and ethical issues. The Working Party considered the arguments surrounding whether animal research yields useful results, and recommends that its predictability and transferability should be evaluated more fully, particularly in controversial areas. Commonly encountered ethical questions and arguments were considered in order to understand what lies behind disagreement on the moral justification of animal research. Four possible ethical positions on animal research, which represent points on a continuum, are described. Despite the range of views that exist among members of the Working Party, the Report presents a "Consensus Statement" that identifies agreement on several important issues. Building on this statement, recommendations are made for improving the quality of the debate and promoting the 3Rs (refinement, reduction, and replacement).     

The interpretation and application of the three Rs by animal ethics committee members

The Three Rs form the basis of review of animal-use protocols by Animal Ethics Committees (AECs), but little research has examined how AECs actually interpret and implement the Three Rs. This topic was explored through in-depth, open-ended interviews with 28 members of AECs at four Canadian universities. In describing protocol review, AEC members rarely mentioned the Three Rs, but most reported applying some aspects of the basic concepts. Comments identified several factors that could impede full application of the Three Rs: incomplete understanding of the Three Rs (especially Refinement), trust that researchers implement Replacement and Reduction themselves, belief by some members that granting agency review covers the Three Rs, focus on sample size rather than experimental design to achieve Reduction, focus on harm caused by procedures to the exclusion of housing and husbandry, and lack of consensus on key issues, notably on the nature and moral significance of animal pain and suffering, and on whether AECs should minimise overall harm to animals. The study suggests ways to achieve more consistent application of the Three Rs, by providing AECs with up-to-date information on the Three Rs and with access to statistical expertise, by consensus-building on divisive issues, and by training on the scope and implementation of the Three Rs.     

Expanding the three Rs to meet new challenges in humane animal experimentation

The Three Rs are the main principles used by Animal Ethics Committees in the governance of animal experimentation, but they appear not to cover some ethical issues that arise today. These include: a) claims that certain species should be exempted on principle from harmful research; b) increased emphasis on enhancing quality of life of research animals; c) research involving genetically modified (GM) animals; and d) animals bred as models of disease. In some cases, the Three Rs can be extended to cover these developments. The burgeoning use of GM animals in science calls for new forms of reduction through improved genetic modification technology, plus continued attention to alternative approaches and cost-benefit analyses that include the large numbers of animals involved indirectly. The adoption of more expanded definitions of refinement that go beyond minimising distress will capture concerns for enhancing the quality of life of animals through improved husbandry and handling. Targeting refinement to the unpredictable effects of gene modification may be difficult; in these cases, careful attention to monitoring and endpoints are the obvious options. Refinement can also include sharing data about the welfare impacts of gene modifications, and modelling earlier stages of disease, in order to reduce the potential suffering caused to disease models. Other issues may require a move beyond the Three Rs. Certain levels of harm, or numbers and use of certain species, may be unacceptable, regardless of potential benefits. This can be addressed by supplementing the utilitarian basis of the Three Rs with principles based on deontological and relational ethics. The Three Rs remain very useful, but they require thoughtful interpretation and expansion in order for Animal Ethics Committees to address the full range of issues in animal-based research.     

The use of animal models for stroke research: a review

Stroke has been identified as the second leading cause of death worldwide. Stroke is a focal neurologic deficit caused by a change in cerebral circulation. The use of animal models in recent years has improved our understanding of the physiopathology of this disease. Rats and mice are the most commonly used stroke models, but the demand for larger models, such as rabbits and even nonhuman primates, is increasing so as to better understand the disease and its treatment. Although the basic mechanisms of stroke are nearly identical among mammals, we here discuss the differences between the human encephalon and various animals. In addition, we compare common surgical techniques used to induce animal models of stroke. A more complete anatomic knowledge of the cerebral vessels of various model species is needed to develop more reliable models for objective results that improve knowledge of the pathology of stroke in both human and veterinary medicine.     

N-acetylaspartate: a literature review of animal research on brain ischaemia

The present review examines and discusses the changes in N-acetylaspartate (NAA) concentration in the ischaemic brain from the existing literature of animal research. By summarizing the current knowledge on NAA metabolic pathways and reviewing the data obtained in animal models of global and focal ischaemia, the following conclusions emerge from this compilation: (i) both magnetic resonance spectroscopy (MRS) and the absolute HPLC method of NAA quantification give converging information; (ii) decreases in brain NAA concentration in acute stroke can be considered as an index of neuronal loss or dysfunction, although NAA redistribution by glial cells and NAA trapping in cell debris restrict its use as a quantitative neuronal marker; (iii) further studies on NAA metabolism in pathologic brain are required before using NAA measurement in the chronic stage of ischaemia for evaluating neuroprotective strategies.     

Regulation of animal biotechnology: research needs

Livestock that result from biotechnology have been a part of agricultural science for over 30 years but have not entered the market place as food or fiber. Two biotechnologies are at the forefront as challenges to the world's systems for regulating the market place: animal clones and transgenic animals. Both technologies have come before the Food and Drug Administration in the United States and it appears that action is imminent for clones. The FDA has asserted principles for evaluation of clones and asserts that "... remaining hazard(s) from cloning are likely to be subtle in nature." The science-based principles recognize that in some areas related to developmental biology and gene expression in clones, additional scientific information would be useful. The role of science then is to use the genomic tools that we have available to answer questions about epigenetic regulation of development and reprogramming of genes to the state found in germ cells. Transgenics pose additional challenges to regulators. If the transgenics are produced using cloning from modified cells then the additional scientific information needed will be related to the effects of insertion and expression of the transgenes. Other approaches such as retrovirally vectored transgenesis will elicit additional questions. These questions will be challenging because the science will have to be related to the expression and function of each gene or class of genes. For the promises of animal biotechnology to be fulfilled, scientists will have to resolve many questions for regulators and the public but tools to answer those questions are rapidly becoming available.     

Bitter taste receptor research comes of age: From characterization to modulation of TAS2Rs

The recognition of potentially harmful food components by the gustatory system is important for survival and well-being of vertebrates. The plethora of structurally diverse bitter substances present in nature is recognized by multiple bitter taste receptors belonging to the taste receptor 2 family (TAS2R) of heptahelical receptors resulting in a highly complex mechanism of bitterness perception. In particular, research on human bitter taste receptors allowed the characterization of the receptive range of most of the 25 TAS2Rs, which was a prerequisite for detailed experiments to elucidate the structure–function relationships of TAS2Rs and for the discovery of the first reasonably specific TAS2R antagonists. These new findings will be the focus of the present review.     

Fifty years of bird song research: a case study in animal behaviour

The growth of bird song research over the past half century has been catalysed by both technical and theoretical advances. The study of mechanisms has largely moved to the neurobiological level, where work on bird song has blossomed. At the behavioural level, development and function have been the prime foci of attention, and I briefly review the advances in these two areas. But, looking forwards, the well is far from dry: I suggest a few topics on which I expect that papers will appear in the journal in the next few decades. Copyright 2003 Published by Elsevier Science Ltd on behalf of The Association for the Study of Animal Behaviour.     

Balancing animal research with animal well-being: establishment of goals and harmonization of approaches

A resource is provided for the creation of an institutional program that balances the scientific mission of an institution with the well-being of the animals used in support of the research. The concept of harmonizing scientific goals with animal well-being was first suggested in the early part of the twentieth century and later revitalized in the literature of the 1950s. Harmonization can best be achieved through the promotion of a team initiative. The team should include, at a minimum, the scientist, veterinarian, institutional animal care and use committee, and animal care staff. It is the responsibility of this animal research team to promote and balance the generation of scientifically valid data with animal well-being. The team must strive to minimize or eliminate non-protocol variables that could adversely affect the validity and repeatability of the experimental data. Good experimental design coupled with excellent communication between team members can often minimize or eliminate many variables and result in both better science and animal well-being. To ensure the scientific validity of experimental data, scientists must be aware of the complex nature of the environment in which their animals are maintained. To ensure repeatablity of an experiment, scientists must document and publish both the inanimate and social environments in which their animals are housed. Better documentation of environmental variables and their correlation with experimental results will promote critical knowledge about the relationships between an animal's environment, its well-being, and science.     

Undergraduate animal behavior program: Teaching and research

The purpose of this paper is to present strategies for teaching animal behavior within a mixed traditional and nontraditional format. Based on our experience, it is very useful to use zoological parks as convenient locales for observational studies. Students gain many valuable experiences in a nontraditional course such as this. Various suggestions are made for animal behavior courses and student projects. Some of the potential pitfalls and problems associated with an animal behavior course are also discussed. Finally, future directions are suggested.