What is a Humanized Mouse? Remaking the Species and Spaces of Translational Medicine

Copyright © 2012 SAGE Publications. Author's draft version; post-print. Final version published by Sage available on Sage Journals Online http://online.sagepub.com/This article explores the development of a novel biomedical research organism, and its potential to remake the species and spaces of translational medicine. The humanized mouse is a complex experimental object in which mice, rendered immunodeficient through genetic alteration, are engrafted with human stem cells in the hope of reconstituting a human immune system for biomedical research and drug testing. These chimeric organisms have yet to garner the same commentary from social scientists as other human–animal hybrid forms. Yet, they are rapidly being positioned as central to translational medicine in immunological research and pharmaceutical development. This article explores the complex relations between species and spaces they seek to enact. Humanizing mice simultaneously moves these animal forms towards the intimate geographies of corporeal equivalence with humans and the expansive geographies of translational research. These multiple trajectories are achieved by the way humanized mice function as both uncertain ‘epistemic things’ and as expansive ‘collaborative things’, articulating mouse genetics with other research, notably stem cell science. In the context of post-genomics, their indeterminacy is critical to their collaborative value; their expansive potential follows as much from their biological openness as from specific expectations. Yet, these new research organisms have both accumulative and disruptive capacities, for there are patterns of interference between these trajectories, remaking boundaries between experimental practices and clinical contexts

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

A Digital Humanities Approach to the History of Science

Comparative historical research on the the intensity, diversity and fluidity of public discourses has been severely hampered by the extraordinary task of manually gathering and processing large sets of opinionated data in news media in different countries. At most 50,000 documents have been systematically studied in a single comparative historical project in the subject area of heredity and eugenics. Digital techniques, like the text mining tools WAHSP and BILAND we have developed in two successive demonstrator projects, are able to perform advanced forms of multi-lingual text-mining in much larger data sets of newspapers. We describe the development and use of WAHSP and BILAND to support historical discourse analysis in large digitized news media corpora. Furthermore, we argue how text mining techniques overcome the problem of traditional historical research that only documents explicitly referring to eugenics issues and debates can be incorporated. Our tools are able to provide information on ideas and notions about heredity, genetics and eugenics that circulate in discourses that are not directly related to eugenics (e.g., sport, education and economics)

Scientific Nonknowledge and Its Political Dynamics: The Cases of Agri-Biotechnology and Mobile Phoning

While in the beginning of the environmental debate, conflicts over environmental and technological issues had primarily been understood in terms of "risk", over the past two decades the relevance of ignorance, or nonknowledge, was emphasized. Referring to this shift of attention to nonknowledge the article presents two main findings: first, that in debates on what is not known and how to appraise it different and partly conflicting epistemic cultures of nonknowledge can be discerned and, second, that drawing attention to nonknowledge in technology conflicts results in significant institutional effects and new constellations of actors in public debates. To illustrate and substantiate this political dynamics of nonknowledge we draw upon examples from the areas of agri-biotechnology and mobile phoning. In a first step, we develop in greater detail the concept of scientific cultures of nonknowledge and identify three such cultures involved in the social conflicts within the two areas. Subsequently, we analyze the specific dynamics of the politicisation of nonknowledge looking at the variety of actors involved and the pluralisation of perceptions and evaluations of what is not known. Then, we point out some of the institutional reactions to the political and cultural dynamics of scientific nonknowledge. We argue that the equal recognition of the diverse cultures of nonknowledge is a key prerequisite for socially legitimate and "robust" decision-making under conditions of politicised scientific nonknowledge. © The Author(s) 2010