Although molecular biology has meant different things at different times, the term is often associated with a tendency to view cellular causation as conforming to simple linear schemas in which macro-scale effects are specified by micro-scale structures. The early achievements of molecular biologists were important for the formation of such an outlook, one to which the discovery of recombinant DNA techniques, and a number of other findings, gave new life even after the complexity of genotype–phenotype
relations had become apparent. Against this (...) background we outline how a range of scientific developments and conceptual considerations can be regarded as enabling and perhaps necessitating contemporary systems approaches. We suggest that philosophical ideas have a valuable part to play in making sense of complex scientific and disciplinary issues. (shrink)

Systems biologists often distance themselves from reductionist approaches and formulate their aim as understanding living systems “as a whole.” Yet, it is often unclear what kind of reductionism they have in mind, and in what sense their methodologies would offer a superior approach. To address these questions, we distinguish between two types of reductionism which we call “modular reductionism” and “bottom-up reductionism.” Much knowledge in molecular biology has been gained by decomposing living systems into functional modules or through detailed studies (...) of molecular processes. We ask whether systems biology provides novel ways to recompose these findings in the context of the system as a whole via computational simulations. As an example of computational integration of modules, we analyze the first whole-cell model of the bacterium M. genitalium. Secondly, we examine the attempt to recompose processes across different spatial scales via multi-scale cardiac models. Although these models rely on a number of idealizations and simplifying assumptions as well, we argue that they provide insight into the limitations of reductionist approaches. Whole-cell models can be used to discover properties arising at the interfaces of dynamically coupled processes within a biological system, thereby making more apparent what is lost through decomposition. Similarly, multi-scale modeling highlights the relevance of macroscale parameters and models and challenges the view that living systems can be understood “bottom-up.” Specifically, we point out that system-level properties constrain lower-scale processes. Thus, large-scale modeling reveals how living systems at the same time are more and less than the sum of the parts. (shrink)