Diseases are Not Adaptations and Neither are Their Causes by Paul E. Griffiths & John Matthewson

In a recent article in this journal, Zachary Ardern criticizes our view that the most promising candidate for a naturalized criterion of disease is the “selected effects” account of biological function and dysfunction. Here we reply to Ardern’s criticisms and, more generally, clarify the relationship between adaptation and dysfunction in the evolution of health and disease.
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How to build an effective research network: lessons from two decades of the GARNet plant science community by Sabina Leonelli and al.

Successful collaborative research is dependent on excellent ideas and innovative experimental approaches, as well as the provision of appropriate support networks. Collaboration requires venues, infrastructures, training facilities, and, perhaps most importantly, a sustained commitment to work together as a community. These activities do not occur without significant effort, yet can be facilitated and overseen by the leadership of a research network that has a clearly defined role to help build resources for their community. Over the past 20 years, this is a role that the UKRI-BBSRC-funded GARNet network has played in the support of the UK curiosity-driven, discovery-led plant science research community. This article reviews the lessons learnt by GARNet in the hope that they can inform the practical implementation of current and future research networks.
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The Ontologies Community of Practice: A CGIAR Initiative for Big Data in Agrifood Systems by Sabina Leonelli and al.

The deployment of digital technology in Agriculture and Food Science accelerates the production of large quantities of multidisciplinary data. The Ontologies Community of Practice (CoP) of the CGIAR Platform for Big Data in Agriculture harnesses the international ontology expertise that can guide teams managing multidisciplinary agricultural information platforms to increase the data interoperability and reusability. The CoP develops and promotes ontologies to support quality data labeling across domains, e.g., Agronomy Ontology, Crop Ontology, Environment Ontology, Plant Ontology, and Socio-Economic Ontology.
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Data Science in Times of Pan(dem)ic by Sabina Leonelli

What are the priorities for data science in tackling COVID-19 and in which ways can big data analysis inform and support responses to the outbreak? It is imperative for data scientists to spend time and resources scoping, scrutinizing and questioning the possible scenarios of use of their work – particularly given the fast-paced knowledge production required by an emergency situation such as the coronavirus pandemic. In this paper I provide a scaffold for such considerations by identifying five ways in which the data science contributions to the pandemic response are imagined and projected into the future, and reflecting on how such imaginaries inform current allocations of investment and priorities within and beyond the scientific research landscape. The first two of these imaginaries, which consist of (1) population surveillance and (2) predictive modelling, have dominated the first wave of governmental and scientific responses with potentially problematic implications for both research and society. Placing more emphasis on the latter three imaginaries, which include (3) causal explanation, (4) evaluation of logistical decisions and (5) identification of social and environmental need, I argue, would provide a more balanced, sustainable and responsible avenue towards using data science to support human co-existence with coronavirus.
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Character identity mechanisms: a conceptual model for comparative-mechanistic biology by Günter P. Wagner and al.


There have been repeated attempts in the history of comparative biology to provide a mechanistic account of morphological homology. However, it is well-established that homologues can develop from diverse sets of developmental causes, appearing not to share any core causal architecture that underwrites character identity. We address this challenge with a new conceptual model of Character Identity Mechanisms (ChIMs). ChIMs are cohesive mechanisms with a recognizable causal profile that allows them to be traced through evolution as homologues despite having a diverse etiological organization. Our model hypothesizes that anatomical units at different levels of organization—cell types, tissues, and organs—have level-specific ChIMs with different conserved parts, activities, and organization. Relying on a methodology of conceptual engineering, we show how the ChIM concept advances our understanding of the developmental basis of morphological characters, while forging an important link between comparative and mechanistic biology.
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Multilayer intraclonal heterogeneity in chronic myelomonocytic leukemia by Lucie Laplane and al.


The functional diversity of cells that compose myeloid malignancies, i.e., the respective roles of genetic and epigenetic heterogeneity in this diversity, remains poorly understood. This question is addressed in chronic myelomonocytic leukemia, a myeloid neoplasm in which clinical diversity contrasts with limited genetic heterogeneity. To generate induced pluripotent stem cell clones, we reprogrammed CD34+ cells collected from a patient with a chronic myelomonocytic leukemia in which whole exome sequencing of peripheral blood monocyte DNA had identified 12 gene mutations, including a mutation in KDM6A and two heterozygous mutations in TET2 in the founding clone and a secondary KRAS(G12D) mutation. CD34+ cells from an age-matched healthy donor were also reprogrammed. We captured a part of the genetic heterogeneity observed in the patient, i.e. we analyzed five clones with two genetic backgrounds, without and with the KRAS(G12D) mutation. Hematopoietic differentiation of these clones recapitulated the main features of the patient’s disease, including overproduction of granulomonocytes and dysmegakaryopoiesis. These analyses also disclosed significant discrepancies in the behavior of hematopoietic cells derived from induced pluripotent stem cell clones with similar genetic background, correlating with limited epigenetic changes. These analyses suggest that, beyond the coding mutations, several levels of intraclonal heterogeneity may participate in the yet unexplained clinical heterogeneity of the disease.
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The role of host environment in cancer evolution by E. Solary and L. Laplane


Somatic mutations in oncogene and tumor suppressor genes accumulate in healthy tissues throughout life and delineate clones with limited expansion. Lifestyle‐related toxic insults increase the size and number of these clones that participate to tissue aging. Their identification has blurred the boundaries between clonal expansion and malignant tumor and has drawn more attention to the role of the host environment in tumor emergence and progression. Local tissue factors such as disrupted cell interactions and stromal cell senescence combine with systemic and distant alterations to initiate the reiterative process of clonal expansion, multilayer intrinsic diversification and clonal selection that eventually characterize overt tumor evolution. In turn, tumors remodel their close and distant environments, establishing positive feedback loops that contribute to disease progression. Strategies emerge to preserve the tumor suppressive properties of healthy tissue landscapes and delay age‐induced changes that eventually lead to cancer.
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Disciplinary Fields in the Life Sciences: Evolving Divides and Anchor Concepts by Alessandro Minelli


Recent and ongoing debates in biology and in the philosophy of biology reveal widespread dissatisfaction with the current definitions or circumscriptions, which are often vague or controversial, of key concepts such as the gene, individual, species, and homology, and even of whole disciplinary fields within the life sciences. To some extent, the long growing awareness of these conceptual issues and the contrasting views defended in their regard can be construed as a symptom of the need to revisit traditional unchallenged partitions between the specialist disciplines within the life sciences. I argue here that the current relationships between anchor disciplines (e.g., developmental biology, evolutionary biology, biology of reproduction) and nomadic concepts wandering between them is worth being explored from a reciprocal perspective, by selecting suitable anchor concepts around which disciplinary fields can flexibly move. Three examples are offered, focusing on generalized anchor concepts of generation (redefined in a way that suggests new perspectives on development and reproduction), organizational module (with a wide-ranging domain of application in comparative morphology, developmental biology, and evolutionary biology) and species as unit of representation of biological diversity (suggesting a taxonomic pluralism that must be managed with suitable adjustments of current nomenclature rules).
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Vital Norms Canguilhem’s “The Normal and the Pathological” in the Twenty-First Century by PO. Méthot and J. Sholl


Medicine exists “as the art of life” because individuals have come to identify certain states as being in need of correction “in relation to the dynamic polarity of life.” Written in wartime by French philosopher Georges Canguilhem (1904-1995), The Normal and the Pathological offers a powerful and unparalleled critique of biological and medical thought.
Drawing on the Œuvres complètes and on unpublished manuscripts, this collection of new essays situates The Normal and the Pathological in its own philosophical, scientific, and cultural context and brings Canguilhem’s writings into conversation with pressing epistemological issues in the biological and the social sciences. It also articulates his critique of norms and normality within current debates in the philosophy of medicine and medical humanities. Exploring the richness of Canguilhem’s philosophy, Vital Norms demonstrates how fertile his work remains for our understanding of health, disease, and illness in the twenty-first century.
“Vital Norms breaks new grounds in the philosophical and historical study of Georges Canguilhem’s masterpiece, The Normal and the Pathological. Collecting a series of engaging and insightful essays, it analyses Canguilhem’s rich and complex thought using archival material and published sources, and shows its enduring relevance for challenges posed by contemporary life sciences and medicine.” Camille Limoges (CIRST)
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