“Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research,” a new paper by a team of international experts including authors from Human Toxicology Project Consortium partners Humane Society International, The Humane Society of the United States, and Unilever, calls for a systems-biology approach to biomedical research and drug discovery. The approach borrows insights from toxicology, where adverse outcome pathways (AOPs) – a framework for documenting the physiological path between chemical exposure and “adverse outcomes” such as illness, injury, or environmental harm – are being used to integrate data from a variety of new scientific technologies. The authors propose that this same framework can be expanded to disease research, and can greatly improve our ability to identify effective drugs and therapeutics.
“…[M]any human illnesses such as cancers, diabetes, immune system and neurodegenerative disorders, and respiratory and cardiovascular diseases are caused by a complicated interplay between multiple genetic and environmental factors,” the authors write. Technology developments over the last two decades have made it possible to measure how genes determine our susceptibility to diseases, as well as how genes, proteins, cells, and tissues react to various environmental exposures. Application of such developments to drug discovery “require(s) a new research paradigm to unlock their full potential.” Just as AOPs integrate these new types of information to help reveal toxicity mechanisms and protect people and the environment from potential effects of chemical exposure, disease pathways can be used to understand risk and disease mechanisms, leading to more effective cures. According to the authors, “The disease AOP approach would better exploit advanced experimental and computational platforms for knowledge discovery, since the emergence of AOP networks will identify knowledge gaps and steer investigations accordingly.”
Progress in disease research and drug discovery has been slow, the authors say, because of continued reliance on inappropriate and unproductive animal models. The AOP framework encourages the use of emerging human-specific cell- and tissue-based models – such as 3D tissue constructs and organs-on-chips – combined with increasingly advanced computational models. The powerful combination can accelerate our understanding of disease, while reducing the use of animals.
The paper was published in the open access journal, Environmental Health Perspectives: http://ehp.niehs.nih.gov/wp-content/uploads/123/11/ehp.1510345.alt.pdf