Medicine and Health Sciences Commons^™

Ethical And Scientific Pitfalls Concerning Laboratory Research With Non-Human Primates, And Possible Solutions, Constança Carvalho, Augusta Gaspar, Andrew Knight, Luís Vicente

Andrew Knight, PhD

Basic and applied laboratory research, whenever intrusive or invasive, presents substantial ethical challenges for ethical committees, be it with human beings or with non-human animals. In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in laboratory based research. We examine the two ethical frameworks that support current legislation and guidelines: deontology and utilitarianism. While human based research is regulated under deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible to accurately predict the benefits …

Contribution Of Animal Models To Contemporary Understanding Of Attention Deficit Hyperactivity Disorder, Constança Carvalho, Mariana Vieira Crespo, Luísa Ferreira Bastos, Andrew Knight, Luís Vincente

Andrew Knight, PhD

Attention Deficit Hyperactivity Disorder (ADHD) is a poorly understood neurodevelopmental disorder of multifactorial origin. Animal-based research has been used to investigate ADHD etiology, pathogenesis and treatment, but the efficacy of this research for patients has not yet been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use.

We used the citation tracking facility within Web of Science to locate citations of original research papers on animal models related to ADHD published prior to 2010 identified in PubMed by relevant search terms. Human medical papers citing those animal studies were carefully analyzed by …

Conscientious Objection To Harmful Animal Use Within Veterinary And Other Biomedical Education, Andrew Knight

Andrew Knight, PhD

Laboratory classes in which animals are seriously harmed or killed, or which use cadavers or body parts from ethically debatable sources, are controversial within veterinary and other biomedical curricula. Along with the development of more humane teaching methods, this has increasingly led to objections to participation in harmful animal use. Such cases raise a host of issues of importance to universities, including those pertaining to curricular design and course accreditation, and compliance with applicable animal welfare and antidiscrimination legislation. Accordingly, after detailed investigation, some universities have implemented formal policies to guide faculty responses to such cases, and to ensure that …

Non-Animal Methodologies Within Biomedical Research And Toxicity Testing, Andrew Knight

Andrew Knight, PhD

Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked – and in some cases, prohibitive – logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Andrew Knight, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …