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 phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising microdosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psychological studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues are used, non-animal models may generate faster, cheaper results, more reliably predictive for humans, whilst yielding greater insights into human biochemical processes. Greater commitment to their development and implementation is necessary, however, to efficiently meet the needs of high-throughput chemical testing programmes, important emerging testing needs, and the ongoing development of human clinical interventions.
Describes factors increasing animal experimentation, and summarises non-animal research and testing methodologies, with pictures.
Summarises strategies for achieving reduction and refinement of laboratory animal use.
The scientific and logistical limitations incurred by the use of animal models of humans within biomedical research and toxicity testing are substantial, and increasingly recognized; as is social concern about, and consequent regulatory restriction of, laboratory animal use. In defiance of these factors, such use remains enormous. Based on best estimates, 11,154,961 living non-human vertebrates were subjected to fundamental or medically-applied biomedical research, toxicity testing, or educational use, within Japan, in 2004; which was second only to the US. Additionally, the use of genetically-modified animals, and the implementation of large-scale chemical testing programs, are increasing laboratory animal use internationally. These trends demonstrate the need for considerably greater awareness of, and compliance with, the principles of the 3Rs―namely, the replacement, reduction and refinement of laboratory animal use―within governmental, academic and commercial sectors. These principles are widely recognized as essential to good laboratory animal practice. They may increase research quality and the robustness of outcomes, result in reduced timeframes and resource consumption, and jointly benefit consumers, industry and laboratory animals. An overview of 3Rs principles, and of strategies likely to increase their implementation, is therefore provided. Combinations of such strategies may have synergistic effects, improving both scientific outcomes and animal welfare.