Medical explanations have often been thought on the model of biological ones and are frequently defined as mechanistic explanations of a biological dysfunction. In this paper, I argue that topological explanations, which have been described in ecology or in cognitive sciences, can also be found in medicine and I discuss the relationships between mechanistic and topological explanations in medicine, through the example of network medicine and medical genetics. Network medicine is a recent discipline that relies on the analysis of various (...) disease networks in order to find organizing principles in disease explanation. My aim is to show how topological explanations in network medicine can help solving the conceptual issues that pure mechanistic explanations of the genetics of disease are currently facing, namely the crisis of the concept of genetic disease, the progressive geneticization of diseases and the dissolution of the distinction between monogenic and polygenic diseases. However, I will also argue that topological explanations should not be considered as independent and radically different from mechanistic explanations for at least two reasons. First, in network medicine, topological explanations depend on and use mechanistic information. Second, they leave out some missing gaps in disease explanation that require, in turn, the development of new mechanistic explanations. Finally, I will insist on the specific contribution of topological explanations in medicine: they push us to develop an explanation of disease in general, instead of focusing on single explanations of individual diseases. This last point may have major consequences for biomedical research. (shrink)

Prior to the genomic sequencing era, the bible for those working in clinical genetics was McKusick’s Mendelian Inheritance in Man, which appeared in multiple editions between the 1960s and the late 1990s. This catalogue was organized according to general patterns of inheritance and focused on phenotypes. Beginning in the mid-1980s, it was replaced by Online Mendelian Inheritance in Man, a continuously updated catalogue documenting molecular relationships between genetic variation and phenotypic expression. This paper explores this resource’s evolution with attention to (...) how disease is distinguished from clinically irrelevant variation and how phenotypic similarities are captured in cases where there is no obvious genotypic association. It is argued that hybrid compromises are encoded into OMIM®; in addition to serving its key original purpose of being a diagnostic catalogue, it also began to record detectable variations in the genome even if they were not known to be associated with phenotypically visible disorders or even phenotypic variations. Although the impacts of geneticization have been well recognized, particularly in popular media, this example allows exploration of some of the historic, epistemic, and methodological causes that underlie tendencies toward disease geneticization in contemporary medicine, while highlighting that such gene-focused strategies may in fact be warranted in some contexts. (shrink)