Targeting versus tinkering: explaining why the clinic is frustrated with molecular mapping of disease mechanisms

Area of Science:

• Evolutionary biology
• Systems biology
• Medical research

Background:

• Many common diseases are viewed as physiological errors.
• Evolutionary pressures shape regulatory networks for reproductive fitness, with disease as a potential side-effect.
• Inflammatory and autoimmune diseases can arise from robust defense mechanisms against infections.

Purpose of the Study:

• To propose an evolutionary perspective on common diseases.
• To explain the frequent failure of reductionist drug-targeting strategies in clinical trials.
• To advocate for a "tinkering" research approach over reductionism for disease intervention.

Main Methods:

• Conceptual analysis of evolutionary biology and disease etiology.
• Hypothesizing the utility of a "tinkering" research strategy.
• Suggesting holistic approaches, such as analyzing diet and gut microbiome influences.

Main Results:

• Disease is presented not as an error, but as a byproduct of evolutionarily conserved regulatory networks.
• An evolutionary viewpoint can elucidate the limitations of targeting single molecules or pathways.
• A "tinkering" approach is hypothesized to be more effective for complex disease interventions.

Conclusions:

• Rethinking disease etiology through an evolutionary lens is crucial.
• A shift from reductionist to "tinkering" research strategies may yield better therapeutic tools.
• Investigating holistic interventions, like diet and microbiome manipulation for multiple sclerosis, exemplifies this new approach.