On the Epistemological Crisis in Genomics

There is an epistemological crisis in genomics. At issue is what constitutes scientific knowledge in genomic science, or systems biology in general. Does this crisis require a new perspective on knowledge heretofore absent from science or is it merely a matter of interpreting new scientific developments in an existing epistemological framework? This paper discusses the manner in which the experimental method, as developed and understood over recent centuries, leads naturally to a scientific epistemology grounded in an experimental-mathematical duality. It places genomics into this epistemological framework and examines the current situation in genomics. Meaning and the constitution of scientific knowledge are key concerns for genomics, and the nature of the epistemological crisis in genomics depends on how these are understood.     

Prokaryotic systematics in the genomics era

As an essential and basic biological discipline, prokaryotic systematics is entering the era of genomics. This paradigmatic shift is significant not only for understanding molecular phylogeny at the whole genome level but also in revealing the genetic or epigenetic basis that accounts for the phenotypic criteria used to classify and identify species. These developments provide an opportunity and a challenge for systematists to reanalyze the molecular mechanisms underlying the taxonomic characteristics of prokaryotes by drawing the knowledge from studies of genomics and/or functional genomics employing platform technologies and related bioinformatics tools. It is expected that taxonomic books, such as Bergey’s Manual of Systematic Bacteriology may evolve into a systematics library indexed by phylogenomic information with an comprehensive understanding of prokaryotic speciation and associated increasing knowledge of biological phenomena.     

Sharing the Knowledge: Sharing Aggregate Genomic Findings with Research Participants in Developing Countries

Returning research results to participants is recognised as an obligation that researchers should always try to fulfil. But can we ascribe the same obligation to researchers who conduct genomics research producing only aggregated findings? And what about genomics research conducted in developing countries? This paper considers Beskow's et al. argument that aggregated findings should also be returned to research participants. This recommendation is examined in the context of genomics research conducted in developing countries. The risks and benefits of attempting such an exercise are identified, and suggestions on ways to avoid some of the challenges are proposed. I argue that disseminating the findings of genomic research to participating communities should be seen as sharing knowledge rather than returning results. Calling the dissemination of aggregate, population level information returning results can be confusing and misleading as participants might expect to receive individual level information. Talking about sharing knowledge is a more appropriate way of expressing and communicating the outcome of population genomic research. Considering the knowledge produced by genomics research a worthwhile output that should be shared with the participants and approaching the exercise as a ‘sharing of knowledge’, could help mitigate the risks of unrealistic expectations and misunderstanding of findings, whilst promoting trusting and long lasting relationships with the participating communities.     

Governing genomics in the 21st century: between risk and uncertainty

Abstract

The paper reconstructs the governance of genomics by sketching the main features, modes of operation and tactics of the emerging genomics apparatus. Genomic governance in the 20th century is characterized by the simultaneous operation of a process of the stabilization of knowledge regimes, in particular via patenting. Furthermore, we observe a heterogenization and globalization of the actors and knowledge creating systems in genomics governance. A variety of different mechanisms and strategies of governance are mobilized simultaneously. The transition of governing via risk to governance by uncertainty is another important feature of contemporary genomics governance. The implications of these trends for the regulation of genomics are considerable and might lead to the emergence of new patterns and spaces of conflict and controversy. The governance of genomics in the 21st century could become a more complex challenge than currently anticipated by many policy makers and the scientific community.     

Exploring Complex Ornamental Genomes: The Rose as a Model Plant

Despite its high economic importance, little is known about rose genetics, genome structure, and the function of rose genes. Reasons for this lack of information are polyploidy in most cultivars, simple breeding strategies, high turnover rates for cultivars, and little public funding. Molecular and biotechnological tools developed during the genomics era now provide the means to fill this gap. This will be facilitated by a number of model traits as e.g., a small genome, a large genetic diversity including diploid genotypes, a comparatively short generation time and protocols for genetic engineering. A deeper understanding of genetic processes and the structure of the rose genome will serve several purposes: Applications to the breeding process including marker-assisted selection and direct manipulation of relevant traits via genetic engineering will lead to improved cultivars with new combinations of characters. In basic research, unique characters, e.g., the biosynthesis and emission of particular secondary metabolites will provide new information not available in model species. Furthermore comparative genomics will link information about the rose genome to ongoing projects on other rosaceous crops and will add to our knowledge about genome evolution and speciation. This review is intended as a presentation and is the compilation of the current knowledge on rose genetics and genomics, including functional genomics and genetic engineering. Furthermore, it is intended to show ways how knowledge on rose genetics and genomics can be linked to other species in the Rosaceae in order to utilize this information across genera.     

Genomics: Applications,Challenges, and Opportunities for the U.S. Environmental Protection Agency

Genomics information has great potential to enhance assessment of risks to human health and the environment. Although understanding genomic responses with respect to adverse ecological and human health outcomes is not, as yet, established, it is important to consider the likely future impacts of genomics technologies on risk assessment and decision-making. Four areas are identified as those likely to be influenced by the generation of genomics information within, and the submission of such information to, the U.S. Environmental Protection Agency (USEPA): risk assessment, prioritization of contaminants and contaminated sites, monitoring, and reporting provisions. For each of these risk assessment and regulatory applications, representative activities are presented to illustrate the application. Three major challenges for the USEPA associated with genomics are also identified in the areas of research, technical development, and capacity. The USEPA's initial activities to address these challenges are discussed. The Agency recognizes it must be prepared to use genomics information, and that many scientific, policy, ethical, and legal concerns will need to be addressed. The USEPA also recognizes it is essential to continue to collaborate with other federal agencies, academia, the regulated community, and other stakeholders in order to benefit from ongoing advances in genomics in the wider scientific and regulatory communities.     

Generation Challenge Programme (GCP): standards for crop data

The Generation Challenge Programme (GCP) is an international research consortium striving to apply molecular biological advances to crop improvement for developing countries. Central to its activities is the creation of a next generation global crop information platform and network to share genetic resources, genomics, and crop improvement information. This system is being designed based on a comprehensive scientific domain object model and associated shared ontology. This model covers germplasm, genotype, phenotype, functional genomics, and geographical information data types needed in GCP research. This paper provides an overview of this modeling effort.     

Functional genomics as a tool in virus research

Genomics is the study of an organism’s entire genome. It started out as a great scientific endeavor in the 1990s which aimed to sequence the complete genomes of certain biological species. However viruses are not new to this field as complete viral genomes have routinely been sequenced since the past thirty years. The ‘genomic era’ has been said to have revolutionized biology. This knowledge of full genomes has created the field of functional genomics in today’s post-genomic era, which, is in most part concerned with the studies on the expression of the organism’s genome under different conditions. This article is an attempt to introduce its readers to the application of functional genomics to address and answer several complex biological issues in virus research.     

Governing genomics in the 21st century: between risk and uncertainty

The paper reconstructs the governance of genomics by sketching the main features, modes of operation and tactics of the emerging genomics apparatus. Genomic governance in the 20th century is characterized by the simultaneous operation of a process of the stabilization of knowledge regimes, in particular via patenting. Furthermore, we observe a heterogenization and globalization of the actors and knowledge creating systems in genomics governance. A variety of different mechanisms and strategies of governance are mobilized simultaneously. The transition of governing via risk to governance by uncertainty is another important feature of contemporary genomics governance. The implications of these trends for the regulation of genomics are considerable and might lead to the emergence of new patterns and spaces of conflict and controversy. The governance of genomics in the 21st century could become a more complex challenge than currently anticipated by many policy makers and the scientific community.     

The application of genetics and nutritional genomics in practice: an international survey of knowledge, involvement and confidence among dietitians in the US, Australia and the UK

As a result of expanding scientific understanding of the interplay between genetics and dietary risk factors, those involved in nutritional management need to understand genetics and nutritional genomics in order to inform management of individuals and groups. The aim of this study was to measure and determine factors affecting dietitians’ knowledge, involvement and confidence in genetics and nutritional genomics across the US, Australia and the UK. A cross-sectional study was undertaken using an online questionnaire that measured knowledge and current involvement and confidence in genetics and nutritional genomics. The questionnaire was distributed to dietitians in the US, Australia and the UK using email lists from the relevant professional associations. Data were collected from 1,844 dietitians who had practiced in the previous 6 months. The main outcomes were knowledge of genetics and nutritional genomics and involvement and confidence in undertaking clinical and educational activities related to genetics and nutritional genomics. Mean scores for knowledge, involvement and confidence were calculated. Analysis of variance and χ ² analysis were used to compare scores and frequencies. Multivariate linear regression was used to determine predictors of high scores. The results demonstrated significant differences in involvement (p < 0.001) and confidence (p < 0.001) but not knowledge scores (p = 0.119) between countries. Overall, dietitians reported low levels of knowledge (mean knowledge score 56.3 %), involvement (mean number of activities undertaken 20.0–22.7 %) and confidence (mean confidence score 25.8–29.7 %). Significant relationships between confidence, involvement and knowledge were observed. Variables relating to education, experience, sector of employment and attitudes were also significantly associated with knowledge, involvement and confidence. Dietitians’ knowledge, involvement and confidence relating to genetics and nutritional genomics remain low and further investigation into factors contributing to this is required.     

Road-maps and revelations: on the somatic ethics of genetic susceptibility

Understanding genomic susceptibility risk has been represented as key to a new era of personalized medicine, in which “empowered” individuals shape their lives according to a “somatic ethics” of genetic risk management. Based on a comprehensive analysis of websites and other documents produced by key companies within the personal genomics industry, I argue that the rhetoric of empowerment these companies employ constructs an “ideal subject” of personal genomics while also expressing tensions implicit within the idea of a somatic ethics based on genetic susceptibility. Using Kaushik Sunder Rajan's concept of “genomic fetishism,” I show how these tensions arise from the relationship the rhetoric of personal genomics constructs between risk and uncertainty, and relate them to broader tensions within “risk thinking” as a mode of governmentality that extends beyond genomics.     

Molecular advances in severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-     

Differentiating genomics companies

As the value of raw sequence data diminishes, genomics companies are evolving new competencies as providers of information, therapeutic products, or novel technology.     

Lotus japonicus as a platform for legume research

The major role of 'model plants' is to provide knowledge and technologies obtained in related systems to researchers studying crop plants. Lotus japonicus was chosen as a model system first for legume genetics and then for legume genomics. A large number of L. japonicus mutants that have alterations in legume-specific phenomena have been generated and phenotypically characterized, and genomics has drastically accelerated the molecular characterization of these mutants. Substantial resources of information and experimental materials, including genomic and cDNA sequences, corresponding DNA libraries and high-density linkage maps demonstrate that L. japonicus is an excellent model system. Transfer of knowledge from L. japonicus to other legumes, especially crop legumes, is a matter for urgent consideration.     

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.     

Generation of a P1 artificial chromosome library of the Southern pufferfish

We describe the generation of a P1 artificial chromosome genomic library from the Southern pufferfish, Spheroides nephelus. The arrayed library consists of approximately 30,000 clones and has an average insert size of 125-150 kb. The coverage is estimated to encompass seven to eight genome equivalents. The library has been used for isolating numerous genomic clones and for establishing contigs of several multigene families. Analysis of several of the clones from this library suggests a preponderance of CA repeat tracts relative to their abundance in humans. The library and high-density filters have been made available to the scientific public through genomics distribution companies.     

树商陆：潮湿的潘帕斯大草原景观的实践与表达

学名为Phytolacca dioica的树种将会贯穿全文。此树种在乌拉圭的通用名叫做树商陆，是本研究缘起的核心。它是潘帕斯大草原的标志性物种，也是乌拉圭景观特质的基础。树商陆在研究和教育工作领域的目标和意义在于将艺术、人类、社会和自然科学联系起来。对树商陆在潘帕斯大草原湿润气候下所表现出的景观价值进行研究。提高了公众对自然元素同景观价值、地方故事间关系的认知度和敏感度。这加强了对遗产以及领土和文化融合的集体责任感。理论往往需要适用于方法论，并协作实践性的工作。例如现场活动与ICT（门户网站http://www.ombues.edu.uy）的相互关联，这便如不断往返于科学文化的普及与流行文化的智慧， 用跨学科的方式建构知识。     

Structural proteomics in drug discovery

High-throughput, automated or semiautomated methodologies implemented by companies and structural genomics initiatives have accelerated the process of acquiring structural information for proteins via x-ray crystallography. This has enabled the application of structure-based drug design technologies to a variety of new structures that have potential pharmacologic relevance. Although there remain major challenges to applying these approaches more broadly to all classes of drug discovery targets, clearly the continued development and implementation of these structure-based drug design methodologies by the scientific community at large will help to address and provide solutions to these hurdles. The result will be a growing number of protein structures of important pharmacologic targets that will help to streamline the process of identification and optimization of lead compounds for drug development. These lead agonist and antagonist pharmacophores should, in turn, help to alleviate one of the current critical bottlenecks in the drug discovery process; that is, defining the functional relevance of potential novel targets to disease modification. The prospect of generating an increasing number of potential drug candidates will serve to highlight perhaps the most significant future bottleneck for drug development, the cost and complexity of the drug approval process.     

Gatekeepers or Intermediaries? The Role of Clinicians in Commercial Genomic Testing

Background

Many commentators on “direct-to-consumer” genetic risk information have raised concerns that giving results to individuals with insufficient knowledge and training in genomics may harm consumers, the health care system, and society. In response, several commercial laboratories offering genomic risk profiling have shifted to more traditional “direct-to-provider” (DTP) marketing strategies, repositioning clinicians as the intended recipients of advertising of laboratory services and as gatekeepers to personal genomic information. Increasing popularity of next generation sequencing puts a premium on ensuring that those who are charged with interpreting, translating, communicating and managing commercial genomic risk information are appropriately equipped for the job. To shed light on their gatekeeping role, we conducted a study to assess how and why early clinical users of genomic risk assessment incorporate these tools in their clinical practices and how they interpret genomic information for their patients.

Methods and Findings

We conducted qualitative in-depth interviews with 18 clinicians providing genomic risk assessment services to their patients in partnership with DNA Direct and Navigenics. Our findings suggest that clinicians learned most of what they knew about genomics directly from the commercial laboratories. Clinicians rely on the expertise of the commercial laboratories without the ability to critically evaluate the knowledge or assess risks.

Conclusions

DTP service delivery model cannot guarantee that providers will have adequate expertise or sound clinical judgment. Even if clinicians want greater genomic knowledge, the current market structure is unlikely to build the independent substantive expertise of clinicians, but rather promote its continued outsourcing. Because commercial laboratories have the most “skin in the game” financially, genetics professionals and policymakers should scrutinize the scientific validity and clinical soundness of the process by which these laboratories interpret their findings to assess whether self-interested commercial sources are the most appropriate entities for gate-keeping genomic interpretation.