Exposures, mutations and the history of causality

The article by Trichopoulos and colleagues (in this issue) raises some interesting problems concerning the complex relations between exposures, cancer aetiology and pathogenesis, and in particular the role of mutations in DNA. I believe that, to better understand the intertwining between causes and mechanisms, it is useful to recall some of the most influential interpretations of causality.

An old, deeply rooted tradition on causality is represented by the aristotelian point of view, based on the central idea of material and efficient cause. This tradition had its maximum development in the medicine of the early 19th century, when Bichat stated that a necropsy can shed more light on disease than hundreds of physical examinations of patients. This tradition is founded (a) on morbid anatomy, that is on the identification of characteristic lesions left in the dead body by the cause of disease, and (b), especially after Virchow's contribution, on the identification of the cell as the main actor in the pathogenetic process. Another extension of this traditional paradigm is microbiology, with its search for agents that could meet Henle-Koch's criteria, that is a single, necessary and sufficient cause. The cause is an agent that is always identifiable in the lesions, can be observed, it is absent in healthy subjects, and induces the disease by inoculation into animals.

To such a tradition, which dominated science in the 19th century, a reaction arises in the first years of the last century, aiming to substitute the concept of functional “law” to that of material cause. The most important expression of this tendency can be …