That holobionts are units of selection squares poorly with the observation that microbes are often recruited from the environment, not passed down vertically from parent to offspring, as required for collective reproduction. The taxonomic makeup of a holobiont’s microbial community may vary over its lifetime and differ from that of conspecifics. In contrast, biochemical functions of the microbiota and contributions to host biology are more conserved, with taxonomically variable but functionally similar microbes recurring across generations and hosts. To save what (...) is of interest in holobiont thinking, we propose casting metabolic and developmental interaction patterns, rather than the taxa responsible for them, as units of selection. Such units need not directly reproduce or form parent-offspring lineages: their prior existence has created the conditions under which taxa with the genes necessary to carry out their steps have evolved in large numbers. These taxa or genes will reconstruct the original interaction patterns when favorable conditions occur. Interaction patterns will vary in ways that affect the likelihood of and circumstances under which such reconstruction occurs. Thus, they vary in fitness, and evolution by natural selection will occur at this level. It is on the persistence, reconstruction, and spread of such interaction patterns that students of holobiosis should concentrate, we suggest. This model also addresses other multi-species collectively beneficial interactions, such as biofilms or biogeochemical cycles maintaining all life. (shrink)

Microbial ecology is flourishing, and in the process, is making contributions to how the ecology and biology of large organisms is understood. Ongoing advances in sequencing technology and computational methods have enabled the collection and analysis of vast amounts of molecular data from diverse biological communities. While early studies focused on cataloguing microbial biodiversity in environments ranging from simple marine ecosystems to complex soil ecologies, more recent research is concerned with community functions and their dynamics over time. Models and concepts (...) from traditional ecology have been used to generate new insight into microbial communities, and novel system-level models developed to explain and predict microbial interactions. The process of moving from molecular inventories to functional understanding is complex and challenging, and never more so than when many thousands of dynamic interactions are the phenomena of interest. We outline the process of how epistemic transitions are made from producing catalogues of molecules to achieving functional and predictive insight, and show how those insights not only revolutionize what is known about biological systems but also about how to do biology itself. Examples will be drawn primarily from analyses of different human microbiota, which are the microbial consortia found in and on areas of the human body, and their associated microbiomes (the genes of those communities). Molecular knowledge of these microbiomes is transforming microbiological knowledge, as well as broader aspects of human biology, health and disease. (shrink)

This paper reviews the debate on the notion of biological function and on functional explanation as this takes place in philosophy. It describes the different perspectives, issues, intuitions, theories and arguments that have emerged. The author shows that the debate has been too heavily influenced by the concerns of a naturalistic philosophy of mind and argues that in order to improve our understanding of biology the attention should be shifted from the study of intuitions to the study of the actual (...) practice of biological inquiry. (shrink)

Microbiologists are transitioning from the study and characterization of individual strains or species to the profiling of whole microbiomes and microbial ecology. Equipped with high-throughput methods for studying the taxonomic and functional characteristics of diverse samples, they are just beginning to encounter the conceptual, theoretical, and experimental problems of comparing taxonomy to function, and extracting useful measures from such comparisons. Although still unresolved, these problems are well studied in macro-ecology and are reiterated here as an historical precautionary for microbial ecologists. (...) Beyond expected and unresolved terminological vagueness, we argue that assessments and comparisons of taxonomic and functional profiles in micro-ecology suffer from theoretically unresolvable arbitrariness and ambiguities. We divide these into problems of scale, individuation, and commensurability. We argue that there is no technically/theoretically “correct” scale, individuation, or comparison of taxonomy and function, but there are nonetheless better and worse methodologies for profiling. (shrink)

The last decade has seen an explosion of research on the gut microbiota—the trillions of microorganisms that colonize the human gut. It is now clear that interindividual diversity in microbiota composition plays an important role in determining susceptibility to a wide variety of diseases. However, identifying the precise changes in microbiota composition that play causal roles has remained a largely unrealized goal. Here, we propose that functional classifications of microbes based on their interactions with and effects on the host—particularly the (...) host immune system—will illuminate the role of the microbiota in shaping human physiology. We outline the benefits of “functional” classification compared to phylogenetic classifications, and review current efforts at functional classification of the microbiota. Finally, we outline a theoretical framework for classifying host-microbiota interactions. Future advances enabling broader functional classifications of the microbiota promise to revolutionize our understanding of the role of gut microbes in health and disease. Functional classifications of the human microbiota reveal previously hidden patterns and will be key to cracking the microbiota composition code. This figure shows a theoretical comparison between phylogenetic classification and functional classification of a host-associated microbial community. (shrink)

This book is a critical survey of and guidebook to the literature on biological functions. It ties in with current debates and developments, and at the same time, it looks back on the state of discourse in naturalized teleology prior to the 1970s. It also presents three significant new proposals. First, it describes the generalized selected effects theory, which is one version of the selected effects theory, maintaining that the function of a trait consists in the activity that led to (...) its differential persistence or reproduction in a population, and not merely its differential reproduction. Secondly, it advances “within-discipline pluralism” (as opposed to between-discipline pluralism) a new form of function pluralism, which emphasizes the coexistence of function concepts within diverse biological sub-disciplines. Lastly, it provides a critical assessment of recent alternatives to the selected effects theory of function, namely, the weak etiological theory and the systems-theoretic theory. The book argues that, to the extent that functions purport to offer causal explanations for the existence of a trait, there are no viable alternatives to the selected effects view. -/- The debate about biological functions is still as relevant and important to biology and philosophy as it ever was. Recent controversies surrounding the ENCODE Project Consortium in genetics, the nature of psychiatric classification, and the value of ecological restoration, all point to the continuing relevance to biology of philosophical discussion about the nature of functions. In philosophy, ongoing debates about the nature of biological information, intentionality, health and disease, mechanism, and even biological trait classification, are closely related to debates about biological functions. (shrink)

The taxa that appear in biological classifications are commonly seen as representing information about the traits of their member organisms. This paper examines in what way taxa feature in the storage and retrieval of such information. I will argue that taxa do not actually store much information about the traits of their member organisms. Rather, I want to suggest, taxa should be understood as functioning to localize organisms in the genealogical network of life on Earth. Taxa store information about where (...) organisms are localized in the network, which is important background information when it comes to establishing knowledge about organismal traits, but it is not itself information about these traits. The view of species and higher taxa that is proposed here follows from examining three problems that occur in contemporary biological systematics and are discussed here: the problem of generalization over taxa, the problem of phylogenetic inference, and the problematic nature of the Tree of Life. (shrink)

. Early microbiome research found numerous associations between microbial community patterns and host physiological states. These findings hinted at community-level explanations. “Top-down” experiments, working with whole communities, strengthened these explanatory expectations. Now, “bottom-up” mechanism-seeking approaches are dissecting communities to focus on specific microbes carrying out particular biochemical activities. To understand the interplay between methodological and explanatory scales, we examine claims of “dysbiosis,” when host illness is proposed as the consequence of a community state. Our analysis concludes with general observations about (...) how methodologies relate to explanations, and the implications for microbiome research. (shrink)

I argue that there are at least four different ways in which the term ‘function’ is used in connection with the study of living organisms, namely: function as activity, function as biological role, function as biological advantage, and function as selected effect. Notion refers to what an item does by itself; refers to the contribution of an item or activity to a complex activity or capacity of an organism; refers to the value for the organism of an item having a (...) certain character rather than another; refers to the way in which a trait acquired and has maintained its current share in the population. The recognition of a separate notion of function as biological advantage solves the problem of the indeterminate reference situation that has been raised against a counterfactual analysis of function, and emphasizes the importance of counterfactual comparison in the explanatory practice of organismal biology. This reveals a neglected problem in the philosophy of biology, namely that of accounting for the insights provided by counterfactual comparison. (shrink)

The taxa that appear in biological classifications are commonly seen as representing information about the traits of their member organisms. This paper examines in what way taxa feature in the storage and retrieval of such information. I will argue that taxa do not actually store much information about the traits of their member organisms. Rather, I want to suggest, taxa should be understood as functioning to localize organisms in the genealogical network of life on Earth. Taxa store information about where (...) organisms are localized in the network, which is important background information when it comes to establishing knowledge about organismal traits, but it is not itself information about these traits. The view of species and higher taxa that is proposed here follows from examining three problems that occur in contemporary biological systematics and are discussed here: the problem of generalization over taxa, the problem of phylogenetic inference, and the problematic nature of the Tree of Life. (shrink)

Graphical AbstractMicrobiome research attributes to whole microbiomes a causal role in the occurrence of different health outcomes. I argue, following some distinctions about causal relationships and explanations made within a philosophical account of causation, the “interventionist account,” that such claims need more scrutiny.

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. (shrink)

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. (shrink)

This essay, written by a biologist, a microbial ecologist, a biological anthropologist, and an anthropologist‐historian, examines tensions and translations in microbiome research on animals in the laboratory and field. The authors trace how research questions and findings in the laboratory are extrapolated into the field and vice versa, and the shifting evidentiary standards that these research settings require. Showing how complexities of microbiomes challenge traditional standards of causation, the authors contend that these challenges require new approaches to inferences used in (...) ecology, anthropology, and history. As social scientists incorporate investigations of microbial life into their human studies, microbiome researchers venture into field settings to develop mechanistic understandings about the functions of complex microbial communities. These efforts generate new possibilities for cross‐fertilizations and inference frameworks to interpret microbiome findings. Microbiome research should integrate multiple scales, levels of variability, and other disciplinary approaches to tackle questions spanning conditions from the laboratory to the field. (shrink)

In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on misunderstandings concerning (...) the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk. (shrink)

The development of culture-independent strategies to study microbial diversity and function has led to a revolution in microbial ecology, enabling us to address fundamental questions about the distribution of microbes and their influence on Earth’s biogeochemical cycles. This article discusses some of the progress that scientists have made with the use of so-called “omic” techniques (metagenomics, metatranscriptomics, and metaproteomics) and the limitations and major challenges these approaches are currently facing. These ‘omic methods have been used to describe the taxonomic structure (...) of microbial communities in different environments and to discover new genes and enzymes of industrial and medical interest. However, microbial community structure varies in different spatial and temporal scales and none of the ‘omic techniques are individually able to elucidate the complex aspects of microbial communities and ecosystems. In this article we highlight the importance of a spatiotemporal sampling design, together with a multilevel ‘omic approach and a community analysis strategy (association networks and modeling) to examine and predict interacting microbial communities and their impact on the environment. (shrink)

I argue that there are at least four different ways in which the term ‘function’ is used in connection with the study of living organisms, namely: function as activity, function as biological role, function as biological advantage, and function as selected effect. Notion refers to what an item does by itself; refers to the contribution of an item or activity to a complex activity or capacity of an organism; refers to the value for the organism of an item having a (...) certain character rather than another; refers to the way in which a trait acquired and has maintained its current share in the population. The recognition of a separate notion of function as biological advantage solves the problem of the indeterminate reference situation that has been raised against a counterfactual analysis of function, and emphasizes the importance of counterfactual comparison in the explanatory practice of organismal biology. This reveals a neglected problem in the philosophy of biology, namely that of accounting for the insights provided by counterfactual comparison. (shrink)