Social science and a post-genomic future: alternative readings of genomic agency

Abstract

This paper explores competing discourses that envision different socio-technical landscapes opened up by the completion of the map of the human genome in 2003. It examines the ways in which the map, and its organising principle and very rationale—the gene as the sole or prime agent through which to understand the body and its disordering (as disease)—has been interpreted in quite distinct ways. It suggests how the sequences of a genomic map have post-genomic con-sequences that depend on a social rather than simply biological reading of genomic agency. Various accounts of the map and genetic agency or described, within science, science policy and social science, especially across science and technology studies (STS). The paper concludes with a comparative summary of these positions and asks whether a deconstructive reading of genomic agency by STS analysts might be the basis for a critical re-constructive engagement with post-genomic policy discourse that avoids the over-determination of agency one often finds in the latter.     

Mapping the new molecular landscape: social dimensions of epigenetics

Epigenetics is the study of changes in gene expression caused by mechanisms other than changes in the DNA itself. The field is rapidly growing and being widely promoted, attracting attention in diverse arenas. These include those of the social sciences, where some researchers have been encouraged by the resonance between imaginaries of development within epigenetics and social theory. Yet, sustained attention from science and technology studies (STS) scholars to epigenetics and the praxis it propels has been lacking. In this article, we reflexively consider some of the ways in which epigenetics is being constructed as an area of biomedical novelty and discuss the content and logics underlying the ambivalent promises being made by scientists working in this area. We then reflect on the scope, limits and future of engagements between epigenetics and the social sciences. Our discussion is situated within wider literatures on biomedicine and society, the politics of “interventionist STS”, and on the problems of “caseness” within empirical social science.     

In search of the Holy Grail: Media discourse and the new human genetics

It has widely been recognized that the media play a key role in framing debates about genetic issues. This paper provides an overview of the major areas of debate within the social scientific literature on media, public understanding of science and human genetics. It evaluates current approaches to assessing the role of the media in influencing public policy debates. It argues that an analysis of the strategies of news sources should occupy a central role in furthering understanding about the ways in which various social actors seek to influence public policy agendas. At present, within the field of human genetics, only a handful of researchers have systematically examined the strategies of news sources from the perspective of the sources themselves. While recent research has focused upon identifying the major sources and how they are used in science reporting, there remains much to be done in uncovering the processes of negotiation and contestation among social actors prior to issues gaining media coverage.     

Yeast genomic databases and the challenge of the post-genomic era

Since the completion of the yeast genome sequence in 1996, three genomic databases, the Saccharomyces Genome Database, the Yeast Proteome Database, and MIPS (produced by the Munich Information Center for Protein Sequences), have organized published knowledge of yeast genes and proteins onto the framework of the genome. Now, post-genomic technologies are producing large-scale datasets of many types, and these pose new challenges for knowledge integration. This review first examines the structure and content of the three genomic databases, and then draws from them and other resources to examine the ways knowledge from the literature, genome, and post-genomic experiments is stored, integrated, and disseminated. To better understand the impact of post-genomic technologies, 20 collections of post-genomic data were analyzed relative to a set of 243 previously uncharacterized genes. The results indicate that post-genomic technologies are providing rich new information for nearly all yeast genes, but data from these experiments is scattered across many Web sites and the results from these experiments are poorly integrated with other forms of yeast knowledge. Goals for the next generation of databases are set forth which could lead to better access to yeast knowledge for yeast researchers and the entire scientific community. Electronic Publication     

Beyond the genome: Reconstituting the new genetics

The mapping and sequencing of the human genome has been the 'Holy Grail' of the new genetics, and its publication marks a turning point in the development of modern biotechnology. However, the question remains: what has been the impact of this discovery on how biotechnology develops in science, and in society at large? Using concepts developed in the social studies of science and technology, the paper begins by rehearsing the historical development of the Human Genome Project (HGP), and suggests that its translation into genomics has been achieved through a process of 'black-boxing' to ensure stabilization. It continues by exploring the extent to which the move to genomics is part of a paradigm shift in biotechnology resulting from the conceptual and organizational changes that have occurred following the completion of HGP. The discussion then focuses on whether genomics can be seen as part of the development of socially robust knowledge in late modernity. The paper suggests that there is strong evidence that a transformation is indeed taking place. It concludes by sketching a social scientific agenda for investigating the reconstitution of the new genetics in a post-genomic era using a 'situated' analytic approach based on an understanding of techno-scientific change as both emergent and contingent.     

High-resolution melt analysis to identify and map sequence-tagged site anchor points onto linkage maps: a white lupin (Lupinus albus) map as an exemplar

* The provision of sequence-tagged site (STS) anchor points allows meaningful comparisons between mapping studies but can be a time-consuming process for nonmodel species or orphan crops. * Here, the first use of high-resolution melt analysis (HRM) to generate STS markers for use in linkage mapping is described. This strategy is rapid and low-cost, and circumvents the need for labelled primers or amplicon fractionation. * Using white lupin (Lupinus albus, x = 25) as a case study, HRM analysis was applied to identify 91 polymorphic markers from expressed sequence tag (EST)-derived and genomic libraries. Of these, 77 generated STS anchor points in the first fully resolved linkage map of the species. The map also included 230 amplified fragment length polymorphisms (AFLP) loci, spanned 1916 cM (84.2% coverage) and divided into the expected 25 linkage groups. * Quantitative trait loci (QTL) analyses performed on the population revealed genomic regions associated with several traits, including the agronomically important time to flowering (tf), alkaloid synthesis and stem height (Ph). Use of HRM-STS markers also allowed us to make direct comparisons between our map and that of the related crop, Lupinus angustifolius, based on the conversion of RFLP, microsatellite and single nucleotide polymorphism (SNP) markers into HRM markers.     

Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy

Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.     

Revealing hidden interval graph structure in STS-content data.

MOTIVATION: STS-content data for genomic mapping contain numerous errors and anomalies resulting in cross-links among distant regions of the genome. Identification of contigs within the data is an important and difficult problem. RESULTS: This paper introduces a graph algorithm which creates a simplified view of STS-content data. The shape of the resulting structure graph provides a quality check - coherent data produce a straight line, while anomalous data produce branches and loops. In the latter case, it is sometimes possible to disentangle the various paths into subsets of the data covering contiguous regions of the genome, i.e. contigs. These straight subgraphs can then be analyzed in standard ways to construct a physical map. A theoretical basis for the method is presented along with examples of its application to current STS data from human genome centers. AVAILABILITY: Freely available on request.     

The dragon on the gold: myths and realities for data mining in biomedicine and biotechnology using digital and molecular libraries

To develop bioscience and personalized medicine in the post-genomic era, the biggest problem may be how to extract knowledge from the rich libraries of biomedical data. A particular dragon protects the gold therein: the dragon is the "curse of dimensionality" and its formidable fire weapon, which is burning researchers, is the "combinatorial explosion". This arises because many genomic, proteomic, clinical, and lifestyle factors may interact that cannot necessarily be considered on a simple pairwise or additive basis. A suggested theoretical solution--or at least "road map" that ameliorates management of these problems--borrows from several disciplines. It is undertaken also in the hope might also lead to research with broader impact on several unresolved issues in biotechnology: conversely, mathematical understanding of processes involving molecular libraries, such as cDNA libraries and DNA in the living cell itself, may open the opportunities to use biotechnology to construct nanotechnological storage and query systems.     

Deletion-based physical mapping of barley chromosome 7H

Chromosomal mutations in barley (Hordeum vulgare, 2n=2x=14, HH) chromosome 7H added to the common wheat (Triticum aestivum, 2n=6x=42, AABBDD) cultivar Chinese Spring were induced genetically by the gametocidal activity of certain alien chromosomes derived from wild species of the genus Aegilops. The rearranged barley chromosomes were characterized by C-banding, FISH and GISH. Twenty two deletion or translocation chromosomes in a hemizygous condition were selected for deletion mapping of 17 AFLP and 28 STS markers that are specific to 7H. Of the 22 breakpoints in chromosome 7H, seven involved the short arm (7HS), 12 the long arm (7HL) and three were in the centromeric region. The seven 7HS breakpoints separated all four 7HS-specific AFLP markers and split the 21 STS markers into six groups. One breakpoint occurred between two STS markers formerly occupying the same position in the genetic map. All seven 7HS breakpoints were separated from each other by either the AFLP or STS markers. The 12 breakpoints in 7HL divided the 13 7HL-specific AFLP markers into seven groups, and the seven STS markers into three groups. On the other hand, the 12 breakpoints in 7HL were divided into six groups by the AFLP markers and into two groups by the STS markers. This deletion-based map was in accordance with previously published genetic and physical maps using the same STS markers. The breakpoints, AFLP markers and STS markers were arrayed in a consistent order. Received: 5 February 2001 / Accepted: 19 February 2001     

RNA as a target for small molecules

Proteins are folded to form a small binding site for catalysis or ligand recognition and this small binding site is traditionally the target for drug discovery. An alternative target for potential drug candidates is the translational process, which requires a precise reading of the entire mRNA sequence and, therefore, can be interrupted with small molecules that bind to mRNA sequence-specifically. RNA thus presents itself as a new upstream target for drug discovery because of the critical role it plays in the life of pathogens and in the progression of diseases. In this post-genomic era, RNA is becoming increasingly amenable to small-molecule therapy as greater structural and functional information accumulates with regard to important RNA functional domains. The study of aminoglycoside antibiotics and their binding to 16S ribosomal RNA has been a paradigm for our understanding of the ways in which small molecules can be developed to affect the function of RNA.     

A long range restriction map of the distal human X chromosome short arm around the steroid sulfatase locus.

The distal short arm of the human X chromosome is of interest because it contains genes which escape X chromosome inactivation and because it is subject to frequent deletions in human patients. The steroid sulfatase gene has been particularly well studied as an example of a gene which escapes X inactivation and which is included in a number of these deletion events. For these reasons a physical map of the region around the STS gene would be of interest. We have constructed a rare cutting enzyme map of this area and have determined the position of several nearby markers with respect to STS. We have also oriented the 5' and 3' ends of the STS gene on this map and have determined the centromeric and telomeric portions of the region. Finally, we have shown that this map can be used to locate deletion breakpoints in STS deficient patients.     

Design and update of a classification system: the UCSD map of science

Global maps of science can be used as a reference system to chart career trajectories, the location of emerging research frontiers, or the expertise profiles of institutes or nations. This paper details data preparation, analysis, and layout performed when designing and subsequently updating the UCSD map of science and classification system. The original classification and map use 7.2 million papers and their references from Elsevier's Scopus (about 15,000 source titles, 2001-2005) and Thomson Reuters' Web of Science (WoS) Science, Social Science, Arts & Humanities Citation Indexes (about 9,000 source titles, 2001-2004)-about 16,000 unique source titles. The updated map and classification adds six years (2005-2010) of WoS data and three years (2006-2008) from Scopus to the existing category structure-increasing the number of source titles to about 25,000. To our knowledge, this is the first time that a widely used map of science was updated. A comparison of the original 5-year and the new 10-year maps and classification system show (i) an increase in the total number of journals that can be mapped by 9,409 journals (social sciences had a 80% increase, humanities a 119% increase, medical (32%) and natural science (74%)), (ii) a simplification of the map by assigning all but five highly interdisciplinary journals to exactly one discipline, (iii) a more even distribution of journals over the 554 subdisciplines and 13 disciplines when calculating the coefficient of variation, and (iv) a better reflection of journal clusters when compared with paper-level citation data. When evaluating the map with a listing of desirable features for maps of science, the updated map is shown to have higher mapping accuracy, easier understandability as fewer journals are multiply classified, and higher usability for the generation of data overlays, among others.     

A first generation bovine BAC-based physical map

A first generation clone-based physical map for the bovine genome was constructed combining, fluorescent double digestion fingerprinting and sequence tagged site (STS) marker screening. The BAC clones were selected from an Inra BAC library (105 984 clones) and a part of the CHORI-240 BAC library (26 500 clones). The contigs were anchored using the screening information for a total of 1303 markers (451 microsatellites, 471 genes, 127 EST, and 254 BAC ends). The final map, which consists of 6615 contigs assembled from 100 923 clones, will be a valuable tool for genomic research in ruminants, including targeted marker production, positional cloning or targeted sequencing of regions of specific interest.     

非编码RNA与RNA组学研究现状及发展态势

人类基因组计划的完成(2001年)宣告了后基因组时代的到来,也掀起新一轮的RNA研究热潮．作为后基因组时代的科学前沿,RNA组学近年来成为生命科学领域的研究热点,各种新型ncRNA的发现,让人们对遗传信息表达调控网络有了新的认识．结合RNA领域的最新研究进展,《 中国科学C辑：生命科学》 (Science in China Series C-Life Sciences)2009年第3期的8篇述评,从动植物小分子非编码 RNA、miRNA 与细胞分化发育、miRNA 与肿瘤发生及诊断治疗的靶点、核酶的结构与功能、遗传印记起源、miRNA 基因簇的进化等多个方面进行了综述,展现了ncRNA领域的研究现状和发展前景．     

Women,warfare, and the life of agency: Papua New Guinea and beyond

‘Agency’ entered anthropological discourse as a key word from the 1970s in renewed social‐philosophical theorizations (e.g. ‘structure and agency’) as major deterministic theories (e.g. Marxism, structuralism) became less persuasive. It came to play an increasing role in ethnography. Though agency, too, has been partly replaced in some of its earlier semantic range, it has been more fully retained in some areas of usage than others, especially in analyses of subordination in the face of power. This article considers several different conceptualizations of agency. Ethnographically, it focuses on women's differing forms of action in two episodes of warfare in the Highlands of Papua New Guinea. In contrasting these, the article concurs with critiques of approaches to ‘agency’ that turn it into a (liberatory) abstraction, and proposes a view of agency as lived relation of intervention and involvement in social action, inherently linked to values and constraints. The combination may be, but is not always, liberatory. The article considers the life and (partial) expiry of agency as a term of social science art.     

Ethical issues and GenomEUtwin.

The post-genomic era is witnessing a proliferation of large-scale and population based genetic and genomic research projects. Many countries have or are establishing research biobanks and, as with GenomEUtwin, there is great interest in building multinational projects that link genotypic and phenotypic information from different centers. Clearly, the conduct of these projects raises multiple ethical issues, and the knowledge generated will continually recast the ethical, legal and social implications (ELSI) of such research. Maximising the scientific profit from this work while minimizing the risks to the participants requires full integration of ethics components into the structure and functioning of these projects. GenomEUtwin is organized around five intellectual cores, including an Ethics Core which operates across the entire project. This paper describes the role of the Ethics Core and presents an overview of the guidelines on which the principles followed in GenomEUtwin are based. We outline the major ethical concerns of our project and highlight complexities arising from diverse national legislations. Finally, the role of empirically based ethics research is discussed for understanding the ethical, legal, social and economic implications of human genetics and genomics research.     

Interpreting evidence: why values can matter as much as science

Despite increasing awareness of the ways in which non-epistemic values play roles in science, many scientists remain reluctant to acknowledge values at stake in their own work. Even when research clearly relates to risk assessment and establishing public policy, contexts in which the presence of values is less likely to be contentious, scientists tend to present such research as merely involving empirical questions about what the evidence is. As a result, debates over policy-related science tend to be framed as purely epistemic debates over the state of the evidence. We argue that this neglects the important ways that ethical and social values play legitimate roles in judgments about what we take to be evidence for a particular policy. Using the case of recent disputes about the relative safety of home birth, we argue that although the debate has been framed as a purely scientific one about the empirical evidence for home birth, it actually involves disagreements about underlying value assumptions. If our claims are correct, then in order to move the debate forward, scientists will need to engage in a critical discussion about the values at stake.     

The opposite of witchcraft: Evans‐Pritchard and the problem of the person

The principal legacy of Evans‐Pritchard's 1937 ethnography Witchcraft, oracles and magic among the Azande has been to associate debates over the rationality of witchcraft with its social categorization as a facet of misfortune and enmity. In combination with Evans‐Pritchard's own scepticism regarding witches, this allowed the rationality debate to isolate witchcraft as a distinctive special case. This logical exceptionalism was at odds with Evans‐Pritchard's own assertion of witchcraft's ordinariness, and is not supported by comparable ethnography from the Ladakh region of the Himalayas or by the unabridged versions of Oracles, both of which point towards an indigenous understanding of witchcraft as one variation on a spectrum of everyday action and craft. Instead, a revised reading of Oracles suggests that even the most basic quotidian representations of personal agency raise larger questions as to anthropology's understanding of how humans ascribe action and personhood, a debate which stands at the heart of its status as a science.     

Effect of Intentional Bias on Agency Attribution of Animated Motion: An Event-Related fMRI Study

Animated movements of simple geometric shapes can readily be interpreted as depicting social events in which animate agents are engaged in intentional activity. However, the brain regions associated with such intention have not been clearly elucidated. In this study, intentional bias was manipulated using shape and pattern animations while measuring associated brain activity using event-related functional magnetic resonance imaging (fMRI). Twenty-five higher-intention involved and twenty-five lower-intention involved animations were presented to participants. Behavioral results showed that the degree of agency attribution of the mental state increased as intentional involvement increased. fMRI results revealed that the posterior superior temporal sulcus (STS), inferior temporal gyrus (ITG), inferior frontal gyrus (IFG), premotor, temporal pole, supramarginal gyrus, and superior parietal lobule (SPL) were activated while participants viewed the high-intention animations. In contrast, occipital, lingual, and middle frontal gyri were activated while the participants viewed the low-intention animations. These findings suggest that as agent attribution increases, the visual brain changes its functional role to the intentional brain and becomes a flexible network for processing information about social interaction.