animal research

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Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

Zeeshan Ali, P. Charukeshi Chandrasekera and John J. Pippin

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

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Expectations for the Methodology and Translation of Animal Research: A Survey of the General Public, Medical Students and Animal Researchers in North America

Joffe supplementary information

Ari R. Joffe, Meredith Bara, Natalie Anton and Nathan Nobis

To determine what are considered acceptable standards for animal research (AR) methodology and translation rate to humans, a validated survey was sent to: a) a sample of the general public, via Sampling Survey International (SSI; Canada), Amazon Mechanical Turk (AMT; USA), a Canadian city festival (CF) and a Canadian children's hospital (CH); b) a sample of medical students (two first-year classes); and c) a sample of scientists (corresponding authors and academic paediatricians). There were 1379 responses from the general public sample (SSI, n = 557; AMT, n = 590; CF, n = 195; CH, n = 102), 205/330 (62%) medical student responses, and 23/323 (7%, too few to report) scientist responses. Asked about methodological quality, most of the general public and medical student respondents expect that: AR is of high quality (e.g. anaesthesia and analgesia are monitored, even overnight, and 'humane' euthanasia, optimal statistical design, comprehensive literature review, randomisation and blinding, are performed), and costs and difficulty are not acceptable justifications for lower quality (e.g. costs of expert consultation, or more laboratory staff). Asked about their expectations of translation to humans (of toxicity, carcinogenicity, teratogenicity and treatment findings), most expect translation more than 60% of the time. If translation occurred less than 20% of the time, a minority disagreed that this would "significantly reduce your support for AR". Medical students were more supportive of AR, even if translation occurred less than 20% of the time. Expectations for AR are much higher than empirical data show to have been achieved.

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Stakeholder Views on the Creation and Use of Genetically-Engineered Animals in Research

Elisabeth H. Ormandy

This interview-based study examined the diversity of views relating to the creation and use of genetically-engineered (GE) animals in biomedical science. Twenty Canadian participants (eight researchers, five research technicians and seven members of the public) took part in the interviews, in which four main themes were discussed: a) how participants felt about the genetic engineering of animals as a practice; b) governance of the creation and use of GE animals in research, and whether current guidelines are sufficient; c) the Three Rs (Replacement, Reduction, Refinement) and how they are applied during the creation and use of GE animals in research; and d) whether public opinion should play a greater role in the creation and use of GE animals. Most of the participants felt that the creation and use of GE animals for biomedical research purposes (as opposed to food purposes) is acceptable, provided that tangible human health benefits are gained. However, obstacles to Three Rs implementation were identified, and the participants agreed that more effort should be placed on engaging the public on the use of GE animals in research.

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Transparency and Public Involvement in Animal Research

Pandora Pound and Ricardo Blaug

To be legitimate, research needs to be ethical, methodologically sound, of sufficient value to justify public expenditure and be transparent. Animal research has always been contested on ethical grounds, but there is now mounting evidence of poor scientific method, and growing doubts about its clinical value. So what of transparency? Here we examine the increasing focus on openness within animal research in the UK, analysing recent developments within the Home Office and within the main group representing the interests of the sector, Understanding Animal Research. We argue that, while important steps are being taken toward greater transparency, the legitimacy of animal research continues to be undermined by selective openness. We propose that openness could be increased through public involvement, and that this would bring about much needed improvements in animal research, as it has done in clinical research.

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Ethics: Views from IACUC Members

Lise Houde, Claude Dumas and Thérèse Leroux

Institutional Animal Care and Use Committee (IACUC) members were interviewed on various ethical matters, including ethics, animal ethics, science and ethics, and the use of animals in research, in order to explore their implicit ethical framework. The results revealed that IACUC members entertain rich and diverse beliefs about ethics, that are part of an implicit ethical framework which relates to different domains of knowledge, such as biology (differences between human and animals), psychology (e.g. affective relationships with pets), and so on. The results also revealed that IACUC members hold quite a restrictive view on both animal ethics and animal use in research, and that they apply implicit ethical notions, such as respect and justice, to some elements (e.g. ethical rules) of the explicit ethical framework they are provided with when performing ethical evaluations of animal use. The study suggests that IACUC members should be provided with more up-to-date information on topics such as animal ethics and animal use in research.
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