Modellers of biological, ecological, and environmental systems cannot take for granted the maxim 'simple means general means good'. We argue here that viewing simple models as the main way to achieve generality may be an obstacle to the progress of ecological research. We show how complex models can be both desirable and general, and how simple and complex models can be linked together to produce broad-scale and predictive understanding of biological systems.

Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term’s historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth.

Background: The concept of a tree of life is prevalent in the evolutionary literature. It stems from attempting to obtain a grand unified natural system that reflects a recurrent process of species and lineage splittings for all forms of life. Traditionally, the discipline of systematics operates in a similar hierarchy of bifurcating (sometimes multifurcating) categories. The assumption of a universal tree of life hinges upon the process of evolution being tree-like throughout all forms of life and all of biological time. In multicellular eukaryotes, the molecular mechanisms and species-level population genetics of variation do indeed mainly cause a tree-like structure over time. In prokaryotes, they do not. Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes. In the following we will consider this circumstance from philosophical, scientific, and epistemological perspectives, surmising that phylogeny opted for a single model as a holdover from the Modern Synthesis of evolution.

The identification of geographical patterns in microbial distributions has begun to challenge purely ecological explanations of biogeography and the underlying principle of "everything is everywhere: but the environment selects". How did 'everything is everywhere' arise out of nineteenth century microbiology, and from Beijerinck's experimental and theoretical work in particular? What is the relationship of this principle to the plant and animal biogeography that flourished throughout this formative period of microbiology's history? Understanding Beijerinck's legacy for twentieth century microbial biogeography reveals issues that are still pertinent to contemporary discussions of microbial biodiversity and biogeography.

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 ...

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SummarySynthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems.

We address three fundamental questions: What does it mean for an entity to be living? What is the role of inter-organismic collaboration in evolution? What is a biological individual? Our central argument is that life arises when lineage-forming entities collaborate in metabolism. By conceiving of metabolism as a collaborative process performed by functional wholes, which are associations of a variety of lineage-forming entities, we avoid the standard tension between reproduction and metabolism in discussions of life -a tension particularly evident in discussions of whether viruses are alive. Our perspective assumes no sharp distinction between life and non-life, and does not equate life exclusively with cellular or organismal status. We reach this conclusion through an analysis of the capabilities of a spectrum of biological entities, in which we include the pivotal case of viruses as well as prions, plasmids, organelles, intracellular and extracellular symbionts, unicellular and multicellular life-forms. The usual criterion for classifying many of the entities of our continuum as non-living is autonomy. This emphasis on autonomy is problematic, however, because even paradigmatic biological individuals, such as large animals, are dependent on symbiotic associations with many other organisms. These composite individuals constitute the metabolic wholes on which selection acts. Finally, our account treats cooperation and competition not as polar opposites but as points on a continuum of collaboration. We suggest that competitive relations are a transitional state, with multi-lineage metabolic wholes eventually outcompeting selfish competitors, and that this process sometimes leads to the emergence of new types or levels of wholes. Our view of life as a continuum of variably structured collaborative systems leaves open the possibility that a variety of forms of organized matter -from chemical systems to ecosystems -might be usefully understood as living entities. This essay will not attempt to provide a definition that answers Schrödinger's question. We shall instead address it by describing a spectrum of biological entities that illustrates why no sharp dividing line between living and non-living things is likely to be useful. The more positive goal of these reflections will be to offer a KEYWORDS