The need for integration systems biology

Systems analysis has been a part of ecology for a long time. It originates in the work of Eugene P. Odum, who in his classical book Fundamentals of Ecology in 1953 made a plea for considering the ecosystem as a unit in its own right, with characteristics that refer to the whole and that are amenable to investigation in the same way as a physiologist investigates a single organism. Odum also recognized that an ecosystem had properties that were not measurable at the levels of populations or communities but were characteristic of the system as a unitary whole. Such properties were called emergent properties. From the beginning, systems ecology relied strongly on mathematical analysis of energy fluxes and nutrient cycles, using differential equations and computer simulation. Systems ecology remained an integrative but limited part of ecology, next to the much larger fields of community and population ecology, but in the 1990s it saw a renaissance, spurred by research programmes on acid rain and climate change, which called for large-scale approaches (Schindler 1987).

It is interesting to see how around the year 2000 the developments in ecology were mirrored by similar developments in molecular biology, leading to the birth of a new field, systems biology (Ideker et al. 2000; Kitano 2002). In molecular biology, the immediate cause was a feeling that the trend towards more and more reductionism was reaching its limits and in some respects was even impeding progress (Van Regenmortel 2004; Strange 2005). According to the reductionist paradigm, understanding is to be gained from studying processes underlying, and thus determining, the phenomenon of interest. Therefore biological processes should be deconstructed into their component parts and the physicochemical properties studied to achieve understanding. Reductionism argues that any biological process ultimately finds its foundation in the laws of chemistry and physics. What is missing in this description is that many biological phenomena do not only depend on the properties of the component parts, but also on other biological phenomena. Gene expression takes place in a certain cellular context, which is moulded by expressions of other genes. Even the expression of a single gene may require gene products from at least 10 other genes; for example, components of the polymerase complex, transcription factors, enhancers, and modifiers. Recognizing the complexity of gene expression, molecular biologists started to analyse the network of interactions between the expression of different genes.

Despite the explosive use of the term systems biology in the biochemical literature since 2004, according to Cornish-Bowden and Cardenas (2005) not all activities grouped under this heading can be regarded as true systems biology. Systems biology is not to be considered as a way of integrating information from diverse components into a model of the system as a whole, it must be seen as a view on the whole to understand the parts. So systems biology argues from the whole to the components, not the other way around. Seen in this way, systems biology and reductionism are not necessarily in conflict with each other.

Westerhoff and Palsson (2004) give an historical perspective on the origin of systems biology. These authors recognized two independent lines of development: one originating in the discovery of DNA, followed by recombinant technology, and large-scale sequencing, the other originating in non-equilibrium thermodynamics, followed by Jacob and Monod's work on the lac operon and molecular kinetics (Fig. 7.1). The second timeline was dominated by modelling of molecular processes but this was often seen as rather theoretical and not based in 'real' biology due to the lack of adequate data. The quantum leap of data acquisition in the first timeline, brought about by the genomics revolution, caused a sudden convergence of the two developments and marked the birth of systems biology.

The structure of systems biology can also be viewed as an activity in which the two lines of

DNA the genetic DNA material structure

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