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- Title
Lessons from Toxicology: Developing a 21st-century Paradigm for Medical Research.
- Authors
Langley, Gill; Austin, Christopher P.; Balapure, Anil K.; Birnbaum, Linda S.; Bucher, John R.; Fentem, Julia; Fitzpatrick, Suzanne C.; Fowle III, John R.; Kavlock, Robert J.; Kitano, Hiroaki; Lidbury, Brett A.; Muotri, Alysson R.; Peng, Shuang-Qing; Sakharov, Dmitry; Seidle, Troy; Trez, Thales; Tonevitsky, Alexander; Stolpe, Anja van de; Whelan, Maurice; Willett, Catherine
- Abstract
Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21 st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved.
- Subjects
GENETICS of disease susceptibility; ATTRIBUTION (Social psychology); BIOLOGICAL models; CHRONIC diseases; CONCEPTUAL structures; DRUG design; ENVIRONMENTAL health; MEDICAL research; PARADIGMS (Social sciences); TOXICOLOGY; CAUSAL models; STATISTICAL models; EPIGENOMICS
- Publication
Environmental Health Perspectives, 2015, Vol 123, Issue 11, pA268
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/ehp.1510345