학술논문

Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research
Document Type
article
Source
Environmental Health Perspectives. 123(11)
Subject
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Clinical Research
5.9 Resources and infrastructure (treatment development)
Development of treatments and therapeutic interventions
Generic health relevance
Good Health and Well Being
Animal Testing Alternatives
Biomedical Research
Computer Simulation
Drug Discovery
Genomics
Humans
Systems Biology
Toxicology
Environmental Sciences
Medical and Health Sciences
Biomedical and clinical sciences
Environmental sciences
Health sciences
Language
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 21st-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.