Reductionism and proxy failure: From neuroscience to target-based drug discovery

Area of Science:

• Pharmacology
• Biochemistry
• Drug Discovery

Background:

• Reductionist methodologies break down complex phenomena into lower-level components.
• This approach can lead researchers to focus on proxies rather than the original object of study.
• Proxies may progressively diverge from the actual phenomenon under investigation.

Purpose of the Study:

• To illustrate the evolution of reductionist methodologies in scientific research.
• To analyze the shift from observing phenomena to optimizing lower-level proxies.
• To demonstrate this trend using the historical development of drug discovery.

Main Methods:

• Comparative analysis of historical drug discovery approaches.
• Examination of the philosophical underpinnings of reductionism.
• Case study illustrating the transition from phenotypic and rational drug discovery to target-based drug discovery.

Main Results:

• Reductionism leads to a progressive divergence of research focus from the original phenomenon.
• Target-based drug discovery represents a significant shift towards optimizing molecular targets (proxies).
• This shift potentially overlooks complex biological systems and emergent properties.

Conclusions:

• The increasing reliance on reductionist approaches and proxies in drug discovery warrants critical evaluation.
• Understanding the divergence between proxies and original phenomena is crucial for effective scientific inquiry.
• Future research should consider integrating holistic and systems-level approaches alongside reductionist methods.