Keep biology weird: The freedom to be curious: On disobedient worms and scientific freedom.

Caenorhabditis elegans embodies the expectations of a solution-driven take on biology on the one hand, and the mysteries and wonders of life that drives biologists to go to their labs on the other hand.

Development of standard clinical endpoints for use in dengue interventional trials: introduction and methodology.

BACKGROUND: As increasing numbers of dengue vaccines and therapeutics are in clinical development, standardized consensus clinical endpoint definitions are urgently needed to assess the efficacy of different interventions with respect to disease severity. We aimed to convene dengue experts representing various sectors and dengue endemic areas to review the literature and propose clinical endpoint definitions for moderate and severe disease based on the framework provided by the WHO 2009 classification. METHODS: The endpoints were first proposed and discussed in a structured expert consultation. After that, the Delphi method was carried out to assess the usefulness, validity and feasibility of the standardized clinical disease endpoints for interventional dengue research. RESULTS: Most respondents (> 80%) agreed there is a need for both standardized clinical endpoints and operationalization of severe endpoints. Most respondents (67%) felt there is utility for moderate severity endpoints, but cited challenges in their development. Hospitalization as a moderate endpoint of disease severity or measure of public health impact was deemed to be useful by only 47% of respondents, but 89% felt it could bring about supplemental information if carefully contextualized according to data collection setting. Over half of the respondents favored alignment of the standard endpoints with the WHO guidelines (58%), but cautioned that the endpoints could have ramifications for public health practice. In terms of data granularity of the endpoints, there was a slight preference for a categorical vs numeric system (e.g. 1-10) (47% vs 34%), and 74% of respondents suggested validating the endpoints using large prospective data sets. CONCLUSION: The structured consensus-building process was successful taking into account the history of the debate around potential endpoints for severe dengue. There is clear support for the development of standardized endpoints for interventional clinical research and the need for subsequent validation with prospective data sets. Challenges include the complexity of developing moderate disease research endpoints for dengue.

Bio-objects' political capacity: a research agenda.

This article explores the merits of foregrounding the dichotomy of politicization vs de-politicization for our understanding of bio-objects in order to study their production, circulation, and governance in European societies. By asking how bio-objects are configured in science, policy, public, and media discourses and practices, we focus on the role of socio-technical configurations in generating political relations. The bio-object thereby serves as an entry point to approach and conceptualize "the political" in an innovative way.

Orphan Drugs, Compounded Medication and Pharmaceutical Commons.

Regulatory agencies installed orphan drug regulations to stimulate research and development of new innovative treatments for life-threatening diseases with a low prevalence (rare diseases). We established a list of well-known food-related ingredients with clinical evidence for rare diseases in the open medical literature that obtained marketing authorization as an expensive "orphan drug", protected by intellectual property (IP) rights. We show that these ingredients are part of an established practice of medicinal compounding-a form of point of care manufacturing. We argue that these ingredients should be considered as "pharmaceutical commons", and that regulatory incentives for private companies and market protection mechanisms such as IP rights are not justified in this case.

Solidarity after nature: From biopolitics to cosmopolitics.

What is sustaining the divide between nature and nurture, even though sciences like epigenetics have been challenging it for at least two decades? Evelyn Fox Keller asked this question and considered it a logical problem rooted in terminological confusion within the sciences. In this article, we propose a complementary diagnosis of the problem: the nature-nurture divide is (re-)mobilized when society faces questions of inclusion and solidarity. With examples stemming from the fields of insurance and health care, immigration policy and epigenetics, we demonstrate how the nature-nurture divide is performed through techniques of classification for a politics of solidarity. We identify a common operation to these different examples that we coin 'biopolitical imputation'. We use this term to draw attention to how (Western) societal institutions, including science, create solvable problems out of complex situations, defining human actors and their agency along the lines of the nature-nurture divide as a moral guide. We argue that the tenacity of the nature-nurture divide is therefore not only a logical problem needing better scientific concepts, but also a cosmopolitical problem asking for a more profound reflection on the ontology and ethics of solidarity in order to move beyond the biopolitics of nature versus nurture.

An Epigenetic Prism to Norms and Values.

In this article, we ask to what extent the specific characteristics of epigenetics may affect the type of questions one can ask about human society. We pay particular attention to the way epigenetic research stirs debate about normative and moral issues. Are these issues implied by scientific evidence as an outcome of research? Or do moral and normative issues also shape how research is done and which problems it addresses? We briefly explore these questions through examples and discussions in (social-) scientific literature. In the final section, we propose an additional dimension and a refocusing of attention from issues of scientific evidence alone (asking what kind of evidence epigenetics produces and how it does so) to a broader picture on epigenetics as a mode of attention that encourages relational and process-oriented thinking with entities, values and scales that may not yet fit within conventional problem-frames that inform research funding and policy-making. We argue that the task of (post-)ELSI approaches is to take inspiration from the ecological complexity of epigenetics in order to bring more relations, relief and gradient in our ethical and political questions.

Dengue illness index-A tool to characterize the subjective dengue illness experience.

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual's overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community.

Development of standard clinical endpoints for use in dengue interventional trials.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.