Recent efforts to elucidate the scientific validity of animal-based drug tests by the pharmaceutical industry, pro-testing lobby groups, and animal welfare organisations.

BACKGROUND: Even after several decades of human drug development, there remains an absence of published, substantial, comprehensive data to validate the use of animals in preclinical drug testing, and to point to their predictive nature with regard to human safety/toxicity and efficacy. Two recent papers, authored by pharmaceutical industry scientists, added to the few substantive publications that exist. In this brief article, we discuss both these papers, as well as our own series of three papers on the subject, and also various views and criticisms of lobby groups that advocate the animal testing of new drugs. MAIN TEXT: We argue that there still remains no published evidence to support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials. In fact, the data in these recent studies, as well as in our own studies, support the contention that tests on rodents, dogs and monkeys provide next to no evidential weight to the probability of there being a lack of human toxicity, when there is no apparent toxicity in the animals. CONCLUSION: Based on these data, and in particular on this finding, it must be concluded that animal drug tests are therefore not fit for their stated purpose. At the very least, it is now incumbent on-and we very much encourage-the pharmaceutical industry and its regulators to commission, conduct and/or facilitate further independent studies involving the use of substantial proprietary data.

Describing the Use of Animals in Animal-Assisted Intervention Research.

Currently, there has been growing attention to animal welfare in animal-assisted interventions (AAI). However, there is a lack of scrutiny regarding what steps to take to ensure animal wellbeing during AAI research. The Institutional Animal Care and Use Committee (IACUC) reviews, monitors, and approves all research involving animal subjects in order to ensure an animal's ethical and humane treatment. However, AAI publications rarely report IACUC approval. The purpose of this critical review was to determine the frequency of IACUC approval and to report the descriptions of animal use in AAI research publications. In the 139 articles reviewed, 14 (10%) studies reported attaining IACUC approval; 4/139 (3%) reported an adverse outcome on at least one animal used in the study. The publications inconsistently reported the training or certification and veterinary care of the animals. Lacking IACUC approval in AAI studies indicates that the field underutilizes this method of monitoring animal health and welfare. The IACUC should assess, approve, and monitor research protocols involving animals prior to conducting every study to safeguard AAI animal welfare.

Reproducibility Issues: Avoiding Pitfalls in Animal Inflammation Models.

In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives, that is, replacing, reducing, and refining animal experiments-the three R's of Russel and Burch (1959)-understanding the complex interactions of the cells of the immune system, the nervous system and the affected tissue/organ during inflammation critically relies on in vivo models. Consequently, scientific advancement and ultimately novel therapeutic interventions depend on improving the reproducibility of animal inflammation models. As a prelude to the remaining hands-on protocols described in this volume, here, we summarize potential pitfalls of preclinical animal research and provide resources and background reading on how to avoid them.

Overview of safety pharmacology.

Safety pharmacology entails the assessment of the potential risks of novel pharmaceuticals for human use. As detailed in the ICH S7A guidelines, safety pharmacology for drug discovery involves a core battery of studies on three vital systems: central nervous (CNS), cardiovascular (CV), and respiratory. Primary CNS studies are aimed at defining compound effects on general behavior, locomotion, neuromuscular coordination, seizure threshold, and vigilance. The primary CV test battery includes an evaluation of proarrhythmic risk using in vitro tests (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation in a large, anesthetized animal. Basic respiratory function can be examined in conscious animals using whole-body plethysmography. This allows for an assessment of whether the sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO2 . Other safety pharmacology topics detailed in this unit are the timing of such studies, ethical and animal welfare issues, and statistical evaluation.

Validating animal models for preclinical research: a scientific and ethical discussion.

The use of animals to model humans in biomedical research relies on the notion that basic processes are sufficiently similar across species to allow extrapolation. Animal model validity is discussed in terms of the similarity between the model and the human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with the use of non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. We discuss both the potential and the limitations of validating preclinical animal models for proof-of-concept studies, by using an approach similar to that applied to alternative non-animal methods in toxicology and safety testing. A major challenge in devising a validation system for animal models is the lack of a clear gold standard with which to compare results. While a complete adoption of the validation approach for alternative methods is probably inappropriate for research animal models, key features, such as making data available for external validation and defining a strategy to run experiments in a way that permits meaningful retrospective analysis, remain highly relevant.

Ethical management of food systems: plant based diet as a holistic approach.

While improvement in agricultural technology had enabled the production of abundant food, it has thus far failed to eliminate hunger. Malnutrition is expected to reach an all time high. Evidences have suggested that animal based diet has put immense pressure on the already fragile food system, contributing to problems in terms of global food security, health security, and environmental sustainability. Plant based dietary approaches may therefore, target some of these problems from the roots, and may be a solution to improving ethical issues and equity in the current food system. This paper examines how meat production and consumption contributed to the current crises in the food system through the lens of ethics--the moral compass--to find directions on how the present generation should eat, and how the food system could be maintained for a better future.

Animal-assisted therapy with children suffering from insecure attachment due to abuse and neglect: a method to lower the risk of intergenerational transmission of abuse?

Children suffering from insecure attachment due to severe abuse and/or neglect are often characterized by internal working models which, although perhaps adaptive within the original family situation, are inappropriate and maladaptive in other relationships and situations. Such children have a higher probability than the general population of becoming abusing or neglecting parents. Besides the usual goals of psychotherapy, an overall goal is to stop the cycle of abuse in which abused children may grow up to be abusing parents. Therapy with these children is complicated by their distrust in adults as well as difficulties in symbolization due to trauma during the preverbal stage. Animal-Assisted Therapy (AAT) provides avenues for circumventing these difficulties, as well as providing additional tools for reaching the inner world of the client. This article gives a brief background of the connection between insecure attachment and intergenerational transmission of abuse and neglect as well as a brief overview of the principles of AAT in a play therapy setting. A rationale for the use of AAT as a unique therapy technique for children having suffered from abuse and neglect is followed by a number of clinical examples illustrating AAT.

Proposal open for discussion: defining agreed diagnostic procedures in experimental diabetes research.

BACKGROUND: Animal experimentation has a long tradition in diabetes research and has provided invaluable benefits with regard to insulin discovery and treatment assessment. METHODS: The review focuses on chemical-induced diabetes in rats and surveys the protocols of diabetes induction, diabetes diagnosis, and glucose tolerance evaluation in a selection of recent research. RESULTS: This brief review of techniques in experimental diabetes highlights that there is no uniformity, whereas standardisation of procedures is desirable so that comparability will exist among experiments carried out in different settings. CONCLUSIONS: On this basis, questions are put and standards are proposed. It would be a platform to promote the exchange of ideas through expert consultation about practical issues related to animal research and a basis on which standards can be set according to user requirements and animal respect.

The moral basis of animal-assisted therapy.

Is nonhuman animal-assisted therapy (AAT) a form of exploitation? After exploring possible moral vindications of AAT and after establishing a distinction between "use" and "exploitation," the essay distinguishes between forms of animal-assisted therapy that are morally unobjectionable and those modes of it that ought to be abolished.

The establishment of ECVAM and its progress since 1993.

The background to the establishment of ECVAM in 1991 is summarised, and progress made since 1993 is briefly reviewed in relation to 12 recommendations made at the ECVAM Opening Symposium in 1994 and to statements on tests for chemicals and biologicals endorsed by the ECVAM Scientific Advisory Committee since 1997.