Figure 3.

Uniformity, heterogeneity and reductionism. (a) Illustration of a homogenous population of cells responding to single stimuli. Each cell responds uniformly to either activator (green or red) and generates one output to each stimulus. (b) Heterogeneous populations of cells responding to one (bi and ii) and two (biii) different stimuli. Separate spatially distinct clusters of cells process and respond to each activator to generate specific outputs. When both activators are present together (biii) the separate regions respond and multiple outputs can be generated. This arrangement permits the endothelium to simultaneously process different stimuli in parallel. (c) Illustration showing a reductionist approach to drug discovery. The normal, steady-state behaviour present in health (ci) may be disrupted in disease (cii). The endothelium may compensate for this alteration by upregulating proteins in other cells to restore a near normal steady-state in disease (ciii). A reductionist approach to drug discovery, that measures the individual components, may attribute this upregulation to the dysfunction in disease rather than the compensatory mechanism employed by the endothelium to overcome the disease. Targeting this upregulated protein may force the endothelium into another new steady-state that is not beneficial (civ) which lacks the compensatory mechanism (cv) present before pharmacological intervention.