Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research.

Area of Science:

• Biomedical research
• Toxicology
• Systems biology

Background:

• Current biomedical research faces challenges in understanding disease causation and drug discovery, partly due to reliance on 20th-century frameworks and animal models.
• Failures in health research and clinical translation highlight the need for a paradigm shift in understanding human disease.
• Advanced technologies offer new possibilities but require a modernized conceptual approach for maximal benefit.

Purpose of the Study:

• To propose a new conceptual framework for biomedical research and drug discovery.
• To advocate for a shift towards human-specific models and systems biology in disease research.
• To address the limitations of traditional approaches in understanding complex human diseases.

Main Methods:

• Repurposing the 21st-century transition in toxicology towards human-specific research.
• Conceiving human disease as resulting from integrated extrinsic and intrinsic causes.
• Utilizing modern human-specific models to study disease pathways at multiple biological levels.
• Applying systems biology tools to integrate and interpret data on disease causation and pathophysiology.

Main Results:

• The proposed framework facilitates a dynamic, systems-level, and human-specific understanding of disease.
• It offers a pathway to overcome current roadblocks in disease research, drug discovery, and clinical translation.
• Analogous to adverse outcome pathways in toxicology, this approach enhances disease pathway elucidation.

Conclusions:

• A new paradigm integrating human-specific models and systems biology is crucial for advancing biomedical research.
• This approach promises significant progress in understanding human disease and improving drug discovery and translation.
• Initiating a discourse on the challenges and questions associated with this new framework is essential.