L’exposome réfère à un domaine émergent de recherche qui a pour visée de développer une science intégrée de l’ensemble des expositions auxquelles est soumis un individu tout au long de sa vie et qui influencent sa santé. Deux principales orientations se font jour. L’une se concentre sur l’étude de l’exposome interne qui permettrait d’identifier l’essentiel des expositions impactant la santé en mesurant avec précision les effets au niveau de l’environnement biochimique du corps. L’autre entend intégrer les expositions sociales, (...) écologiques et les expositions biologiques et internes, ou autrement dit, faire davantage de place à l’étude de l’exposome externe et ainsi développer un modèle holiste de la santé environnementale. À partir de l’examen de la littérature scientifique, de l’analyse de la première génération d’études exposomiques (2010-2020) et d’entretiens menés auprès d’épidémiologistes engagés dans ces recherches, cet article propose un état des lieux des promesses et réalisations de ce domaine émergent quant à l’intégration des expositions, tout en ayant l’ambition d’apporter un regard critique sur ces dernières. Après avoir présenté l’exposome et ses diverses interprétations, nous examinerons quel type d’intégration est en jeu dans chacune de ces deux orientations et nous en questionnerons l’intérêt et la pertinence. Notre analyse se concentre plus particulièrement sur la seconde orientation : quels gages cette tendance la plus holiste donne-t-elle en vue d’un renouvellement de nos manières d’intégrer les facteurs environnementaux et génétiques, sociaux et biologiques, dans notre approche des expositions et de l’explication des maladies? (shrink)

In recent years, exposome research has been put forward as the next frontier for the study of human health and disease. Exposome research entails the analysis of the totality of environmental exposures and their corresponding biological responses within the human body. Increasingly, this is operationalized by big-data approaches to map the effects of internal as well as external exposures using smart sensors and multiomics technologies. However, the ethical implications of exposome research are still only rarely discussed in (...) the literature. Therefore, we conducted a systematic review of the academic literature regarding both the exposome and underlying research fields and approaches, to map the ethical aspects that are relevant to exposome research. We identify five ethical themes that are prominent in ethics discussions: the goals of exposome research, its standards, its tools, how it relates to study participants, and the consequences of its products. Furthermore, we provide a number of general principles for how future ethics research can best make use of our comprehensive overview of the ethical aspects of exposome research. Lastly, we highlight three aspects of exposome research that are most in need of ethical reflection: the actionability of its findings, the epidemiological or clinical norms applicable to exposome research, and the meaning and action–implications of bias. (shrink)

In this commentary, I discuss the scientific changes brought by the exposome, asking what is new about this approach and line of research. I place the exposome in a historical perspective, by analyzing the conditions under which the exposome has been conceived, developed and established in the context of contemporary epidemiological research. I argue that the exposome has been developed by transferring approaches, methods and conceptualizations from other lines of research in the life and health sciences. (...) I thus discuss the conceptual and methodological innovations of the exposome as a result of the merging and adaptation of these elements for new uses and purposes. On this basis, I argue that the novelty of the exposome should be seen in incremental rather than revolutionary terms and, in this sense, the exposome shares significant elements with other projects and repertoires in postgenomics. I conclude by discussing the consequences of this analysis for the potential limitations and future development of exposome research. (shrink)

Exposome research is put forward as a major tool for solving the nature-versus-nurture debate because the exposome is said to represent “the nature of nurture.” Against this influential idea, we argue that the adoption of the nature-versus-nurture debate into the exposome research program is a mistake that needs to be undone to allow for a proper bioethical assessment of exposome research. We first argue that this adoption is originally based on an equivocation between the traditional nature-versus-nurture (...) debate and a debate about disease prediction/etiology. Second, due to this mistake, exposome research is pushed to adopt a limited conception of agential control that is harmful to one's thinking about the good that exposome research can do for human health and wellbeing. To fully excise the nature-versus-nurture debate from exposome research, we argue that exposome researchers and bioethicists need to think about the exposome afresh from the perspective of actionability. We define the concept of actionability and related concepts and show how these can be used to analyze the ethical aspects of the exposome. In particular, we focus on refuting the popular “gun analogy” in exposome research, returning results to study participants and risk-taking in the context of a well-lived life. (shrink)

Recently, it has been argued that the use of Big Data transforms the sciences, making data-driven research possible and studying causality redundant. In this paper, I focus on the claim on causal knowledge by examining the Big Data project EXPOsOMICS, whose research is funded by the European Commission and considered capable of improving our understanding of the relation between exposure and disease. While EXPOsOMICS may seem the perfect exemplification of the data-driven view, I show how causal knowledge is necessary for (...) the project, both as a source for handling complexity and as an output for meeting the project’s goals. Consequently, I argue that data-driven claims about causality are fundamentally flawed and causal knowledge should be considered a necessary aspect of Big Data science. In addition, I present the consequences of this result on other data-driven claims, concerning the role of theoretical considerations. I argue that the importance of causal knowledge and other kinds of theoretical engagement in EXPOsOMICS undermine theory-free accounts and suggest alternative ways of framing science based on Big Data. (shrink)

How is scientific data used to represent phenomena and as evidence for claims about phenomena? In this paper, I propose that a specific type of claims – evidential claims – is involved in data practices to define and restrict the representational and evidential content of a dataset. I present an account of data practices in the epidemiology of the exposome based on the notion of evidential claims, which helps unpack the approaches, assumptions and warrants that connect different stages of (...) research. I identify three different strategies to generate different types of evidential claims in this case. The macro strategy, which individuates the dataset that serves as the initial evidential space for research. The micro strategy, which is used to generate evidential claims about the microscopic and individual component of target phenomena. The association strategy, that uses evidence from the other strategies to identify a dataset as representation of the different levels and relations of exposure and disease. Differentiating between these strategies sheds light on the multi-faceted landscape of biomedical research on environment and health; and the roles of data and evidence in the process of inquiry. (shrink)

In current philosophical discussions on evidence in the medical sciences, epidemiology has been used to exemplify a specific version of evidential pluralism. According to this view, known as the Russo–Williamson Thesis, evidence of both difference-making and mechanisms is produced to make causal claims in the health sciences. In this paper, I present an analysis of data and evidence in epidemiological practice, with a special focus on research on the exposome, and I cast doubt on the extent to which evidential (...) pluralism holds in this case. I start by focusing on the claim that molecular data allows for the production of mechanistic evidence. On the basis of a close look at the ways in which molecular data is used in exposome research, I caution against interpretations in terms of mechanistic evidence. Secondly, I expand my critical remarks on the thesis by addressing the conditions under which data is categorised as evidence in exposome research. I argue that these show that the classification of a dataset as a type of evidence is dependent on the ways in which the data is used. This is in contrast with the approach of evidential pluralism, where evidence is classified in different types on the basis of its intrinsic properties. Finally, I come back to what I consider the core of the thesis and suggest that the epidemiological research analysed in the paper indicates different interpretations of evidential pluralism and its applicability in the health sciences. (shrink)

The success of the Human Genome Project has prompted interest in advancing the nascent field of exposomics. The exposome, which is dynamic and variable and changes over time, consists of all the internal and external exposures an individual has over a lifetime beginning with the prenatal period and early childhood. Efforts are underway to decipher the human epigenome by identifying the effects of all deleterious environmental exposures according to duration of exposure and time period. In this article, we argue (...) that the deciphering of the human exposome should be accompanied by sustained efforts to address the ethical, social and legal implications (ELSI) of exposomics. This will require financial investments from the National Institutes of Health (NIH), the European Union and other public and private funding agencies, analogous to support provided by NIH to address ELSI issues in genomics. (shrink)

It is estimated that 300,000 children 0–14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high‐income countries. In spite of this, the etiologies of pediatric cancer are largely unknown. Environmental exposures have long been thought to play an etiologic role. However, to date, there are few well‐established environmental risk factors for pediatric malignancies, likely due to (...) technical barriers in collecting biological samples prospectively in pediatric populations for direct measurements. In this review, we propose the use of novel or underutilized biospecimens (dried blood spots and teeth) and molecular approaches for exposure assessment (epigenetics, metabolomics, and somatic mutational profiles). Future epidemiologic studies of pediatric cancer should incorporate novel exposure assessment methodologies, data on molecular features of tumors, and a more complete assessment of gene‐environment interactions. (shrink)

The environment can elicit biological responses such as oxidative stress (OS) and inflammation as a consequence of chemical, physical, or psychological changes. As population studies are essential for establishing these environment-organism interactions, biomarkers of OS or inflammation are critical in formulating mechanistic hypotheses. By using examples of stress induced by various mechanisms, we focus on the biomarkers that have been used to assess OS and inflammation in these conditions. We discuss the difference between biomarkers that are the result of a (...) chemical reaction (such as lipid peroxides or oxidized proteins that are a result of the reaction of molecules with reactive oxygen species) and those that represent the biological response to stress, such as the transcription factor NRF2 or inflammation and inflammatory cytokines. The high-throughput and holistic approaches to biomarker discovery used extensively in large-scale molecular epidemiological exposome are also discussed in the context of human exposure to environmental stressors. We propose to consider the role of biomarkers as signs and to distinguish between signs that are just indicators of biological processes and proxies that one can interact with and modify the disease process. (shrink)

I propose an approach that expands philosophical views of scientific change, on the basis of an analysis of contemporary biomedical research and recent developments in the philosophy of scientific change. Focusing on the establishment of the exposome in epidemiology as a case study and the role of data as a context for contrasting views on change, I discuss change at conceptual, methodological, material, and social levels of biomedical epistemology. Available models of change provide key resources to discuss this type (...) of change, but I present the need for an approach that models transfer, alignment, and influence as key processes of change. I develop this as a pragmatic approach to scientific change, where processes might change substantially depending on specific circumstances, thus contributing to and complementing the debate on a crucial epistemological issue. (shrink)

What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this (...) be translated to humans? To date, literature on fathers is scarce. Human studies do not always incorporate appropriate tools to evaluate paternal influences or epigenetic effects. In reviewing the literature, I stress the need to explore and recognize paternal contributions to offspring's health within the Developmental Origins of Health and Disease hypothesis, and coin this new concept the Paternal Origins of Health and Disease paradigm. A better understanding of preconceptional origins of disease through the totality of paternal exposures, or the paternal exposome, will provide evidence-based public health recommendations for future fathers. A father's hereditary contribution exceeds that of his DNA sequence. The environment can regulate systems such as the sperm epigenome, which is inheritable as well and may steer the genome and health status of his offspring. We here suggest a new concept, the Paternal Origins of Health and Disease, as part of the DOHaD theory. (shrink)

In this paper, we analyse the relation between the use of environmental data in contemporary health sciences and related conceptualisations and operationalisations of the notion of environment. We consider three case studies that exemplify a different selection of environmental data and mode of data integration in data-intensive epidemiology. We argue that the diversification of data sources, their increase in scale and scope, and the application of novel analytic tools have brought about three significant conceptual shifts. First, we discuss the EXPOsOMICS (...) project, an attempt to integrate genomic and environmental data which suggests a reframing of the boundaries between external and internal environments. Second, we explore the MEDMI platform, whose efforts to combine health, environmental and climate data instantiate a reframing and expansion of environmental exposure. Third, we illustrate how extracting epidemiological insights from extensive social data collected by the CIDACS institute yields innovative attributions of causal power to environmental factors. Identifying these shifts highlights the benefits and opportunities of new environmental data, as well as the challenges that such tools bring to understanding and fostering health. It also emphasises the constraints that data selection and accessibility pose to scientific imagination, including how researchers frame key concepts in health-related research. (shrink)

Social scientists have shown that scientific characterizations of the egg and the sperm are shaped by gender stereotypes and cultural values. How have such characterizations been transformed by a recent embrace of -omics, when studies of reproduction increasingly go beyond genomics to incorporate proteomics, transcriptomics, exposomics, and other -omics perspectives? Scientists studying reproduction and analyzing eggs, sperm, and embryos are in some ways reimagining the roles, identities, and functions of gametes as fundamentally shaped by other molecular entities and environments. Such (...) relational understandings of substances and processes, however, continue to operate through a teleology that often conscripts more nuanced -omics reflection into familiar genomic visions of sex and reproduction. While ideas of the gene as an alienable object may be unraveling, -omics efforts to go beyond the egg and the sperm are frequently constricted by an understanding of reproduction that remains tied to individualized bodies and by a genomically infused interpretation of the gamete as life itself. (shrink)

Large part of contemporary science is in fact technoscience, in the sense that it crucially depends on several technologies for the generation, collection, and analysis of data. This prompts a re-examination of the relations between science and technologies. In this essay, I advance the view that we’d better move beyond the ‘subordination view’ and the ‘instrumental’ view. The first aims to establish the primacy of science over technology, and the second uses technology instrumentally to support a realist position about theoretical (...) entities. I suggest that we should instead concentrate on how science and technology interact. This will reveal that technology has a poietic character, namely it actively partakes in the production of knowledge. But this poietic character can only be understood within the cognitive activity of scientific communities. Current research in molecular epidemiology, notably the projects funded within the ‘European exposome initiative’, serves as a motivation for such discussion and as an illustration of the claims made. (shrink)

Current research in molecular epidemiology uses biomarkers to model the different disease phases from environmental exposure, to early clinical changes, to development of disease. The hope is to get a better understanding of the causal impact of a number of pollutants and chemicals on several diseases, including cancer and allergies. In a recent paper Russo and Williamson address the question of what evidential elements enter the conceptualisation and modelling stages of this type of biomarkers research. Recent research in causality has (...) examined Ned Hall’s distinction between two concepts of causality: production and dependence. In another recent paper, Illari examined the relatively under-explored production approach to causality, arguing that at least one job of an account of causal production is to illuminate our inferential practices concerning causal linking. Illari argued that an informational account solves existing problems with traditional accounts. This paper follows up this previous work by investigating the nature of the causal links established in biomarkers research. We argue that traditional accounts of productive causality are unable to provide a sensible account of the nature of the causal link in biomarkers research, while an informational account is very promising. (shrink)

The first 1000 days of life, from conception to 2 years, are a critical window for the influence of environmental exposures on the assembly of the oral microbiome, which is the precursor to dental caries (decay), one of the most prevalent microbially induced disorders worldwide. While it is known that the human microbiome is susceptible to environmental exposures, there is limited understanding of the impact of prenatal and early childhood exposures on the oral microbiome trajectory and oral health. A barrier (...) has been the lack of technology to directly measure the foetal "exposome", which includes nutritional and toxic exposures crossing the placenta. Another barrier has been the lack of statistical methods to account for the high dimensional data generated by‐omic assays. Through identifying which early life exposures influence the oral microbiome and modify oral health, these findings can be translated into interventions to reduce dental decay prevalence. (shrink)

The unprecedented development of medical informatics is constantly transforming the concept of expertise in medical sciences in a way that has far-reaching consequences for both the theory of knowledge and the philosophy of informatics. Deep medicine is based on the assumption that medical diagnosis should take into account the wide array of possible health factors involved in the diagnostic process, such as not only genome analysis alone, but also the metabolome (analysis of all body metabolites important for e.g. drug-drug interactions), (...) microbiome (i.e. analysis of all bodily microorganisms interacting with host cells) or exposome (analysis of all environmental factors triggering potentially harmful cell mutations, such as UV radiation, heavy metals, various carcinogens, etc.). Deep data analysis is of tantamount importance for personalized diagnosis but, at the same time, hardly achievable by a regular human being. However, adequately designed artificial intelligence (e.g. a deep neural network) can undeniably be of great help for finding correlations between symptoms and underlying diseases. Nowadays AI applies to nearly every aspect of medicine, starting from the data analysis of scientific literature, through the diagnostic process, to the act of communication between physicians and their patients. Medical image processing algorithms greatly enhance the chances of successful recognition of melanoma or intestinal polyps. Communication tools designed for physicians use techniques known from social media to provide users with an opportunity to consult the case with colleagues from the same discipline. Natural language processing tools significantly improve doctor-patient communication by the automation of note-taking. Is this enough to support the claim that the non-epistemic competences in medicine are becoming more and more important? Can we attribute expertise only to a person? How is medical informatics changing the way most people usually understand human-computer interactions? (shrink)

A paradigm shift in the human chronotoxicity of xenobiotics would study two‐sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems‐based networks are under the influence of well‐synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24‐hour (periodic) diurnal rhythms and answering whether these disruptions in synchronization would affect (...) response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system's elements. Desynchronized interfaces during critical life windows or in time‐repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes. (shrink)