FUNDAMENTAL ISSUES IN SYSTEMS BIOLOGY SummaryIn the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology.Systems biology is best understood as consisting of two streams. One, which we shall call 'pragmatic systems biology', emphasizes large-scale molecular interactions; the other, which we shall refer to as 'systems-theoretic biology', emphasizes system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems and how causality operates at different levels of organization. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realization. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers.
KeywordsGenomics, systems biology, systems theory, philosophy of biology 3
FUNDAMENTAL ISSUES IN SYSTEMS BIOLOGYAs genomics matures from a data-collecting enterprise to an explanatory science, and as those scientific endeavours take on disciplinary contours, a range of underlying issues are being explicitly and implicitly addressed by the scientists involved. These reflections are an important part of the way a discipline constitutes itself as a field by setting out central problems and achievements alongside a history of conceptual and empirical precursors. One of the most widely discussed fields in emergent genomics is systems biology, and it raises several important questions that need to be resolved if the science is to advance.The issues that are most fundamental are how the systems that are the focus of systems biology are defined, and how those definitions affect the research agendas that arise from earlier scientific legacies.
Preceding interpretations of genomicsThe early days of genomics began with fairly simple conceptualizations that emphasized the shift from identifying genes to sequencing and mapping entire genomes. (1) As the data poured in and the field achieved wide recognition, these definitions were expanded to give greater emphasis to functional analyses. (2,3) Although much of the discussion of the status of genomes has been conducted via evaluations of the evolving metaphors in genomic discourse -from the ineptness of the blueprint metaphor to analogies with jazz scores and Theseus's 4 ship - (4,5,6) there are also some excellent systematic discussions of genome conceptualizations. (7) Two issues concerning the status of knowledge in genomics are frequently discussed. The first is that early genomics shared the reductionist aspirations of genetics, which led to a preoccupation with sequence structure and deterministic accounts of function. (3, 8) Persistent (and prescient) demands for a more hierarchical and less simplistically deterministic understanding of molecular processes were voiced even in the early years of genomics. (9,10) These calls increased with ...