Collaboration and competition: ethics in toxicology

Abstract

From animal research through adverse events in clinical trials to health scares around food contamination, toxicology has frequently been a focus of scientific and societal concern. As these concerns shift with each new drug, new technology or public health scare, how can toxicology stay current, relevant and ethical? Two of the biggest ethical challenges in pharmaceutical toxicology are the use of animals in testing and the high safety-related attrition rates in new drug development. Both of these require progress in the discipline that will only be driven by research funding. Yet, very little is invested in these two fields compared with investment in new efficacy models, new disease targets and new technologies. How can this be addressed? Here, we explore current paradigms in toxicology that may have the potential for perceived or actual unethical ramifications. We discuss the underpinnings of such practices and make recommendations for change around peer review, resourcing, transparency and data sharing. These ideas build on the analysis presented in the 2004 Paton Prize lecture (Purchase, 2004) where issues around conflict of interest (COI), collaboration and competition in the context of ethical behaviours were highlighted. These areas are clearly relevant to many aspects of scientific research but here we focus on toxicology and specifically toxicology in the pharmaceutical industry.

Use of Zebrafish in Drug Discovery Toxicology

“…Low sensitivity for clinical safety issues is the primary focus of efforts to improve preclinical toxicology testing, but mammalian models are also laborious, costly, and fraught with ethical questions concerning animal testing, , affording other motivations for developing and implementing alternative assays. Regulatory requirements for new drug discoveries are rigorous; thus, acceptance of alternative toxicology assays by government agencies will rely on well-established predictivity of clinical toxicity .…”

A Multiparametric Assay Platform for Simultaneous In Vivo Assessment of Pronephric Morphology, Renal Function and Heart Rate in Larval Zebrafish

“…Preclinical studies on drug discovery, drug-induced developmental toxicity and safety of chemical compounds require convenient animal models in combination with accurate technologies and reliable test assays. Despite yielding the highest predictivity, preclinical toxicology testing in mammalian models is laborious, time consuming, cost intensive, and burdened with ethical questions concerning animal testing [1,2]. In contrast, the zebrafish (Danio rerio) is in line with the 3Rs (replacement, reduction, and refinement) concept in animal research [3,4], and offers a cost-effective non-mammalian vertebrate model system [5].…”

Collaboration, competition and publication in toxicology: views of British Toxicology Society members

“…Secondly, that toxicology is a multidisciplinary science and therefore training in other disciplines feeds the pool of toxicologists. This second theme touches on a concept explored in the initial opinion article 1 where we proposed that toxicology must be willing to redefine its boundaries as a discipline and draw strength and diversity from other sciences. One important discussion point regarding resourcing of toxicology is the distinction between education and training.…”

“…Steps have been proposed to overcome this for toxicology as a discipline; 12 the BTS could play a role in delivering an integrated and unified approach to address COI, peer review and unreproducible data across all basic and applied pharmacology and toxicology. 1 …”

“…We previously explored the ethical concerns of conflict of interest (COI), transparency, reproducibility and funding of animal research and suggested new ways of working for discussion. 1 This opinion paper triggered a number of questions and areas to explore regarding current attitudes to toxicology research in the UK. In addition to these ethical concerns, many believe that toxicology as a discipline is under threat from several directions both in the UK and in Europe.…”