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.

Fig. 1. Research, applied and regulatory toxicology. The schematic depicts a continuum from research toxicology through to regulatory toxicology with the middle ground of applied research toxicology. Research toxicology is aimed at expanding our knowledge base without a clear route to application of this new knowledge. In contrast, regulatory toxicology is defined as work done to support testing of a potential new product as well as its subsequent registration and ongoing stewardship. As well as regulatory and research toxicology, there is also a mid-ground of applied toxicology where research projects and experiments are specifically designed such that their output will have a direct impact on risk assessment. 3Rs: Reduction, refinement and replacement of animals; AI: artificial intelligence; CAR: constitutive androstane receptor; iPSC: induced pluripotent stem cells; miRNAs: microRNAs; MPS: microphysical systems; MOA: mode of action; SNPs: single nucleotide polymorphisms; TK/TD: toxicogenetics/toxicodynamics.

Fig. 2. The toxicology ethics iceberg. There are aspects of ethics such as conflict of interest (COI), animal testing, transparency and reproducibility that are highly visible. However, this is just the tip of the iceberg with many other confounding and underlying issues such as resourcing, data sharing, peer review, economics and politics.

Fig. 3. Resources, pressures and outcomes in toxicology. Resources into toxicology are scarce yet some are escaping through holes in the system. Resources come mainly from contract research organisations (CROs), industry and the research councils and charities. There are many pressures creating a squeeze; pressure from patients/government, pressure to publish, pressure to meet profit expectations and pressure to stay relevant. Limited resources combined with pressures create a number of consequences that may have the potential for perceived or actual unethical ramifications. Specifically, there may be competition rather than collaboration, unnecessary/repeated experiments, misguided investments into outdated research, lack of reproducibility and a lack of trained scientists entering toxicology. We propose open discussion and challenge to the current ideology along with interdisciplinary collaboration to share resources.