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Revisiting generality in biology: systems biology and the quest for design principles

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Abstract

Due to the variation, contingency and complexity of living systems, biology is often taken to be a science without fundamental theories, laws or general principles. I revisit this question in light of the quest for design principles in systems biology and show that different views can be reconciled if we distinguish between different types of generality. The philosophical literature has primarily focused on (the lack of) generality of specific models or explanations, or on the heuristic role of abstraction. This paper takes a different approach in emphasizing a theory-constituting role of general principles. Design principles signify general dependency-relations between structures and functions, given a set of formally defined constraints. I contend that design principles increase our understanding of living systems by relating specific models to general types. The categorization of types is based on a delineation of the scope of biological possibilities, which serves to identify and define the generic features of classes of systems. To characterize the basis for general principles through generic abstraction and reasoning about possibility spaces, I coin the term constraint-based generality. I show that constraint-based generality is distinct from other types of generality in biology, and argue that general principles play a unifying role that does not entail theory reduction.

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Notes

  1. Darwin’s theory of evolution through natural selection and principles of divergence may be an exception, since modeling of evolution resembles the attempt to treat biological processes as influenced by deeper laws (Depew and Weber 1995). Yet, there are major disagreements about the specific content and implications of the theory, e.g. the extent to which natural selection determines the direction of evolution, the dynamics and unit of natural selection, and the heuristic and explanatory value of adaptationism (Amundson 1994; Green 2014).

  2. The quest for design principles does not assume an ‘intelligent’ designer, nor does it necessarily entail adaptationism (see Green et al. 2015b).

  3. Developmental constraints refer to features that set the boundaries for possible processes in embryonic stages. For instance, developmental constraints are taken to explain the lack of variation in the number of cervical vertebrae or five-digit limbs among vertebrate species because the embryonic stages in the production of these cannot be altered without affecting other developmental processes. For an analysis of the historical role of developmental constraints in biology, see (Brigandt 2015).

  4. The model only includes internal inputs and is therefore deterministic with a finite number of network states.

  5. For a discussion of adaptationism in this context, see (Green 2014).

  6. The different labels for general principles in the table highlight theoretical differences between the approaches but the notions of design and organizing principles are often used interchangeably and have overlapping historical precursors (Green and Wolkenhauer 2013).

  7. In E. coli, chemotaxis involves mediation of a kinase-phosphorylation signal transduction pathway from methyl-accepting transmembrane receptors to six Che proteins that interact with a flagella motor that can change the tumbling frequency according to input signals. Adaptation to concentration of repellants and attractors is causally instantiated by ligand binding, methylation and demethylation of receptors.

  8. These assumptions are: (1) CheB only demethylates active receptors, (2) the kinetic rate constants of CheR and CheB are independent of the methylation state of the receptor complex, (3) the activity of unmethylated receptors are negligible, and (4) the concentration of bound CheR is independent of ligand-level.

  9. For practical implications of this principle for designing synthetic homeostatic circuits in synthetic biology, see also (Ang et al. 2010).

  10. Whereas Gould initially believed that laws of evolution could be based on regular adaptive processes, he came to realize that generality in evolution was most likely to be found in evolutionary processes that are insensitive to specific adaptations and variations (Haufe 2015).

  11. Huang (2004) refers to these different focal points as Type I and Type II explanations in evolutionary biology (the latter investigating what I call constraint-based generality).

  12. In the network model based on empirical data, they find that many of the motifs are closely overlapping and “more than 30 % of the FFL circuits are formed by 5 pairs of regulators with significant homology at the protein level” (Cordero and Hogeweg 2006, 1934). This finding speaks counter to the assumptions that the motifs result from selection of individual functional units (see also Green 2014).

  13. This role is akin to answering Batterman’s (2002) type II questions, described through case studies in physics. But whereas Batterman emphasizes how what he calls minimal models explain mainly by showing why details don’t matter, I emphasize the generic features that the functional equivalence class (or universality class) have in common. Thus, the accounts differ with respect to what is taken to be the salient feature of the answer to the why-question.

  14. I thank Mads Goddiksen for suggesting a comparison between the transfer of higher-order formalisms in systems biology and exemplars. One disadvantage of seeing design principles as examplars is, however, that it is not a part of Kuhn’s account to make sense of the redefinition of exemplars through interdisciplinary ‘bootstrapping’ (Nickles 1990, 24).

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Acknowledgments

I would like to thank William Bechtel, Maria Serban, Nicholaos Jones and two anonymous reviewers for very helpful comments to earlier versions of this paper.

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Correspondence to Sara Green.

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Green, S. Revisiting generality in biology: systems biology and the quest for design principles. Biol Philos 30, 629–652 (2015). https://doi.org/10.1007/s10539-015-9496-9

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