Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, (...) we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms—as discussed in the contemporary philosophy of science—may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched “flat”, i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams. (shrink)

This paper investigates the interface between philosophy and biochemistry. While it is problematic to justify the application of a particular philosophical model to biochemistry, it seems to be even more difficult to develop a special “Philosophy for Biochemistry”. Alternatively, philosophy can be used in biochemistry based on an alternative approach that involves an interdependent iteration process at a philosophical and (bio)chemical level (“Exeter Method”). This useful iteration method supplements more abstract approaches at the interface between philosophy and natural sciences, and (...) serves the biochemical community to systematically locate logical inconsistencies that arise from more theoretical aspects of the scientific process. Initial cycles of this iteration process identify the in vitro–in vivo problem as a central epistemological difficulty in biochemical research. While previous attempts have generated ad hoc rules to mend the gap between chemistry, biochemistry and biology in order to justify in vitro experimentation, this paper concludes that in vitro experimentation is heavily based on chemistry and cannot derive definite statements about biological processes. It can, however, generate results that will influence the direction of future biological research. The consequence is that the relationship between in vitro and in vivo experimentation is more of a psychological or social one than of a logical nature. Apart from highlighting these inconsistencies in biochemical thinking (“problem awareness”), the Exeter Method demands an improvement of biochemical terminology that contains separate and unequivocally defined terms for in vitro and in vivo systems. (shrink)