Microbes, mathematics, and models

Microbial model systems have a long history of fruitful use in fields that include evolution and ecology. In order to develop further insight into modelling practice, we examine how the competitive exclusion and coexistence of competing species have been modelled mathematically and materially over the course of a long research history. In particular, we investigate how microbial models of these dynamics interact with mathematical or computational models of the same phenomena. Our cases illuminate the ways in which microbial systems and equations work as models, and what happens when they generate inconsistent findings about shared targets. We reveal an iterative strategy of comparative modelling in different media, and suggest reasons why microbial models have a special degree of epistemic tractability in multimodel inquiry

How stands the Tree of Life a century and a half after The Origin?

We examine the Tree of Life (TOL) as an evolutionary hypothesis and a heuristic. The original TOL hypothesis has failed but a new "statistical TOL hypothesis" is promising. The TOL heuristic usefully organizes data without positing fundamental evolutionary truth

Microbes, mathematics, and models

Microbial model systems have a long history of fruitful use in fields that include evolution and ecology. In order to develop further insight into modelling practice, we examine how the competitive exclusion and coexistence of competing species have been modelled mathematically and materially over the course of a long research history. In particular, we investigate how microbial models of these dynamics interact with mathematical or computational models of the same phenomena. Our cases illuminate the ways in which microbial systems and equations work as models, and what happens when they generate inconsistent findings about shared targets. We reveal an iterative strategy of comparative modelling in different media, and suggest reasons why microbial models have a special degree of epistemic tractability in multimodel inquiry

The study of socioethical issues in systems biology

Systems biology is the rapidly growing and heavily funded successor science to genomics. Its mission is to integrate extensive bodies of molecular data into a detailed mathematical understanding of all life processes, with an ultimate view to their prediction and control. Despite its high profile and widespread practice, there has so far been almost no bioethical attention paid to systems biology and its potential social consequences. We outline some of systems biology's most important socioethical issues by contrasting the concept of systems as dynamic processes against the common static interpretation of genomes. New issues arise around systems biology's capacities for in silico testing, changing cultural understandings of life, synthetic biology, and commercialization. We advocate an interdisciplinary and interactive approach that integrates social and philosophical analysis and engages closely with the science. Overall, we argue that systems biology socioethics could stimulate new ways of thinking about socioethical studies of life sciences.ESRC; AHR

How Causal are Microbiomes? A Comparison with the Helicobacter pylori Explanation of Ulcers

Human microbiome research makes causal connections between entire microbial communities and a wide array of traits that range from physiological diseases to psychological states. To evaluate these causal claims, we first examine a well-known single-microbe causal explanation: of Helicobacter pylori causing ulcers. This apparently straightforward causal explanation is not so simple, however. It does not achieve a key explanatory standard in microbiology, of Koch’s postulates, which rely on manipulations of single-microorganism cultures to infer causal relationships to disease. When Koch’s postulates are framed by an interventionist causal framework, it is clearer what the H. pylori explanation achieves and where its explanatory strengths lie. After assessing this ‘simple’, single-microbe case, we apply the interventionist framework to two key areas of microbiome research, in which obesity and mental health states are purportedly explained by microbiomes. Despite the experimental data available, interventionist criteria for explanation show that many of the causal claims generated by microbiome research are weak or misleading. We focus on the stability, specificity and proportionality of proposed microbiome causal explanations, and evaluate how effectively these dimensions of causal explanation are achieved in some promising avenues of research. We suggest some conceptual and explanatory strategies to improve how causal claims about microbiomes are made

Metagenomics and biological ontology.

types: Journal Article; ReviewMetagenomics is an emerging microbial systems science that is based on the large-scale analysis of the DNA of microbial communities in their natural environments. Studies of metagenomes are revealing the vast scope of biodiversity in a wide range of environments, as well as new functional capacities of individual cells and communities, and the complex evolutionary relationships between them. Our examination of this science focuses on the ontological implications of these studies of metagenomes and metaorganisms, and what they mean for common sense and philosophical understandings of multicellularity, individuality and organism. We show how metagenomics requires us to think in different ways about what human beings are and what their relation to the microbial world is. Metagenomics could also transform the way in which evolutionary processes are understood, with the most basic relationship between cells from both similar and different organisms being far more cooperative and less antagonistic than is widely assumed. In addition to raising fundamental questions about biological ontology, metagenomics generates possibilities for powerful technologies addressed to issues of climate, health and conservation. We conclude with reflections about process-oriented versus entity-oriented analysis in light of current trends towards systems approaches.This research was funded by the UK Arts and Humanities Research Council, and workshop funding was from the Wellcome Trust

The medical microbiome paradigm and its parallels with humoural medicine

The working concepts that have emerged in microbiome research bear an uncanny resemblance to one of the most ancient traditions of Western medicine: humoural medicine as promulgated by the medical practitioner and philosopher Galen in the second century CE. In particular, both Galenic medicine and medical microbiome research rely heavily on notions of imbalance and balance, with undesirable unbalanced states called ‘dyskrasia’ and ‘dysbiosis’ respectively. Therapeutically, both systems aim at restoration to a balanced state. Both traditions also hold that the composition of the focal entities (humours or microbiomes) determines not just every bodily state but mental ones too. Causality for each is conceived teleologically, meaning that parts of bodies ‘function for’ the maintenance of the whole. And ultimately, each framework asserts that external environments are part of the balance equation, thereby situating the humours or microbiomes in a unified multilevel theory that purportedly explains the very nature of health and perhaps even humans. As well as describing the parallels between these systems, we seek to explain them: Should we think of these resemblances as due to direct historical continuity, or due to incidental convergence? Finally, we address the implications of these abundant similarities. Should medical microbiome researchers be concerned that their field currently shares conceptual parallels with Galenic medicine, or is it something to celebrate? Ultimately, this is an evaluation all medical microbiome researchers will need to make for the future of their field

How Causal are Microbiomes? A Comparison with the Helicobacter pylori Explanation of Ulcers

Human microbiome research makes causal connections between entire microbial communities and a wide array of traits that range from physiological diseases to psychological states. To evaluate these causal claims, we first examine a well-known single-microbe causal explanation: of Helicobacter pylori causing ulcers. This apparently straightforward causal explanation is not so simple, however. It does not achieve a key explanatory standard in microbiology, of Koch’s postulates, which rely on manipulations of single-microorganism cultures to infer causal relationships to disease. When Koch’s postulates are framed by an interventionist causal framework, it is clearer what the H. pylori explanation achieves and where its explanatory strengths lie. After assessing this ‘simple’, single-microbe case, we apply the interventionist framework to two key areas of microbiome research, in which obesity and mental health states are purportedly explained by microbiomes. Despite the experimental data available, interventionist criteria for explanation show that many of the causal claims generated by microbiome research are weak or misleading. We focus on the stability, specificity and proportionality of proposed microbiome causal explanations, and evaluate how effectively these dimensions of causal explanation are achieved in some promising avenues of research. We suggest some conceptual and explanatory strategies to improve how causal claims about microbiomes are made

Varieties of Living Things: Life at the Intersection of Lineage and Metabolism

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

Dysbiosis and Its Discontents

International audienceDysbiosis 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