The Constraints of the Modern Synthesis and the Delayed Recognition of Epigenetic Memory
The emergence of DNA methylation as a recognized mechanism for cellular differentiation in the 1970s was not merely a technical challenge; it was a conceptual struggle against the prevailing orthodoxy of the Modern Synthesis. The Modern Synthesis, which solidified in the mid-20th century, achieved a powerful mathematical and theoretical integration of Mendelian genetics and Darwinian natural selection. However, in doing so, it established a rigid framework that prioritized the gene as the sole, immutable unit of inheritance. This commitment effectively marginalized developmental processes and environmental interactions, creating an intellectual environment where mechanisms like those proposed by Robin Holliday, John E. Pugh, and Arthur D. Riggs in 1975 were often viewed as secondary, ephemeral, or even heretical to the core tenets of the discipline. At the heart of the Modern Synthesis was the "Central Dogma" of molecular biology, as articulated by Francis Crick. This dogma...