Chlorarachniophytes are amoeboflagellate, marine protists that have acquired photosynthetic capacity by engulfing and retaining a green alga. These green algal endosymbionts are severely reduced, retaining only the chloroplast, nucleus, cytoplasm and plasma membrane. The vestigial nucleus of the endosymbiont, called the nucleomorph, contains only three small linear chromosomes and has a haploid genome size of just 380 kb ‐ the smallest eukaryotic genome known. Initial characterisation of nucleomorph DNA has revealed that all chromosomes are capped with inverted repeats (...) comprising a telomere and a single ribosomal RNA operon. The nucleomorph genome is the quintessence of compactness; average space between genes is a mere 65 bp, some genes overlap, others are cotranscribed. Intense reductive pressures upon nucleomorph genes have apparently squeezed their spliceosomal‐type introns down to only 18, 19 or 20 bases in length. Studies to date indicate the nucleomorph ‐ essentially a stripped‐down eukaryotic genome ‐ encodes principally genetic housekeeping functions such as translation, transcription and splicing. (shrink)

Modern biology has been heavily influenced by the gene‐centric concept. Paradoxically, this very concept – on which bioresearch is based – is challenged by the success of gene‐based research in terms of explaining evolutionary theory. To overcome this major roadblock, it is essential to establish new theories, to not only solve the key puzzles presented by the gene‐centric concept, but also to provide a conceptual framework that allows the field to grow. This paper discusses a number of paradoxes and illustrates (...) how they can be addressed by the genome‐centric concept in order to further resynthesize evolutionary theory. In particular, methodological breakthroughs that analyze genome evolution are discussed. The multiple interactions among different levels of a complex system provide the key to understanding the relationship between self‐organization and natural selection. Darwinian natural selection applies to the biological level due to its unique genetic and heterogeneous features, but does not simply or directly apply to either the lower non‐living level or higher intellectual society level. At the complex bio‐system level, the genome context (the entire package of genes and their genomic physical relationship or genomic topology), not the individual genes, defines the system and serves as the principle selection platform for evolution. (shrink)

Implicit God-like and ghost-in-the-machine metaphors underlie much current thinking about genomes. Although many criticisms of such views exist, none have succeeded in substituting a different, widely accepted view. Viewing the genome with its protein packaging as a brain gets rid of Gods and ghosts while plausibly integrating machine and information-based views. While the ‘wetware’ of brains and genomes are very different, many fundamental principles of how they function are similar. Eukaryotic cells are compound entities in which case the (...) nuclear genome might best be thought of more as a government than simply as a brain. (shrink)

The mammalian chromosome is longitudinally heterogeneous in structure and function and this is the basis for the specific banding patterns produced by various chromosome staining techniques. The two most frequently used techniques are G, or Giemsa banding and R, or reverse banding. Each type of stained band is characterised by variations in gene density, time of replication, base composition, density of repeat sequences, and chromatin packaging. It is increasingly apparent that R and G bands, which are complementary to each (...) other, represent separate compartments of the euchromatic human genome, with R bands containing the vast majority of genes. R bands are also more GC‐rich, contain a higher density of Alu repeats, and replicate earlier in S phase, than G bands. These properties may be interdependent and may have coevolved. (shrink)

The mammalian chromosome is longitudinally heterogeneous in structure and function and this is the basis for the specific banding patterns produced by various chromosome staining techniques. The two most frequently used techniques are G, or Giemsa banding and R, or reverse banding. Each type of stained band is characterised by variations in gene density, time of replication, base composition, density of repeat sequences, and chromatin packaging. It is increasingly apparent that R and G bands, which are complementary to each (...) other, represent separate compartments of the euchromatic human genome, with R bands containing the vast majority of genes. R bands are also more GC‐rich, contain a higher density of Alu repeats, and replicate earlier in S phase, than G bands. These properties may be interdependent and may have coevolved. (shrink)

Many viruses evolved mechanisms for capping the 5′‐ends of their plus‐strand RNAs as a means of hijacking the eukaryotic messenger RNA (mRNA) splicing/translation machinery. Although capping is critical for replication, the RNAs of these viruses have other essential functions including their requirement to be packaged as either genomes or pre‐genomes into progeny viruses. Recent studies indicate that human immunodeficiency virus type‐1 (HIV‐1) RNAs are segregated between splicing/translation and packaging functions by a mechanism that involves structural sequestration of the 5′‐cap. (...) Here, we examined studies reported for other viruses and retrotransposons that require both selective packaging of their RNAs and 5′‐RNA capping for host‐mediated translation. Our findings suggest that viruses and retrotransposons have evolved multiple mechanisms to control 5′‐cap accessibility, consistent with the hypothesis that removal or sequestration of the 5′ cap enables packageable RNAs to avoid capture by the cellular RNA processing and translation machinery. (shrink)

This article examines the mobilization of resources for the Human Genome Mapping Project in the United Kingdom. The Project was established through an award of additional funds to the Medical Research Council at a time of financial stringency within publicly funded science, accompanied by relatively little of the debate that had surrounded the U.S. initiative. It is argued, following Fujimura and Star’s terminology, that the project was “packaged” and repackaged by its proponents so that it aligned the, otherwise disparate, (...) agendas of several “social worlds.” Furthermore, by bringing together certain social worlds and not others, some issues were also excluded from discussion. In this instance, the social and ethical issues surrounding genetic mapping were accorded a much lower profile than in other national programs. (shrink)

Fluorescent in situ hybridization technology is one of the most exciting and versatile research tools to be developed in recent years. It has enabled research to progress at a phenomenal rate in diverse areas of basic research as well as in clinical medicine. Fluorescent in situ hybridization has applications in physical mapping, the study of nuclear architecture and chromatin packaging, and the investigation of fundamental principles of biology such as DNA replication, RNA processing, gene amplification, gene integration and chromatin (...) elimination. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the research (...) involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Eukaryotic genomes are packaged into a nucleoprotein complex known as chromatin. The term was introduced in 1879 by German cytologist Walther Flemming. While observing the processes of mitosis in a light microscope, Flemming coined the term to describe the easily stainable threads in the nucleus. He predicted that it would not have a long life: “The word chromatin may serve until its chemical nature is known, and meanwhile stands for that substance in the cell nucleus which is readily stained”. However, (...) Flemming’s prediction did not come true. Although the chemical nature of chromatin—a complex of nucleic acid and proteins—was already elucidated at the end of the 19th century, the.. (shrink)

Genomic function is dictated by a combination of DNA sequence and the molecular mechanisms controlling access to genetic information. Access to DNA can be determined by the interpretation of covalent modifications that influence the packaging of DNA into chromatin, including DNA methylation and histone modifications. These modifications are believed to be forms of “epigenetic codes” that exist in discernable combinations that reflect cellular phenotype. Although DNA methylation is known to play important roles in gene regulation and genomic function, its (...) contribution to the encoding of epigenetic information is just beginning to emerge. Here we discuss paradigms associated with the various components of DNA methylation/demethylation and recent advances in the understanding of its dynamic regulation in the genome, integrating these mechanisms into a framework to explain how DNA methylation could contribute to epigenetic codes. (shrink)

Eukaryotic genomes are packaged into nucleosomal chromatin, and genomic activity requires the precise localization of transcription factors, histone modifications and nucleosomes. Classic work described the progressive reassembly and maturation of bulk chromatin behind replication forks. More recent proteomics has detailed the molecular machines that accompany the replicative polymerase to promote rapid histone deposition onto the newly replicated DNA. However, localized chromatin features are transiently obliterated by DNA replication every S phase of the cell cycle. Genomic strategies now observe the rebuilding (...) of locus‐specific chromatin features, and reveal surprising delays in transcription factor binding behind replication forks. This implies that transient chromatin disorganization during replication is a central juncture for targeted transcription factor binding within genomes. We propose that transient occlusion of regulatory elements by disorganized nucleosomes during chromatin maturation enforces specificity of factor binding. (shrink)

Given their commitment to practices, science studies have bestowed considerable attention upon objects. We have the boundary object, the standardized package, the network object, the immutable mobile, the fluid object, even a fire object has entered the scene. However, these objects do not provide us with a way of understanding their historicity. They are timeless, motionless pictures rather than things that change over time, and while enacting ‘historical moments’ they do not make visible the histories they contain within them. What (...) kind of object could embody history and make that history visible? Inspired by Michel Serres, I suggest the folded object is a way to attend to the temporality and spatiality of objects. In this article I explore this new object by unravelling the history of a DNA reference sequence. I show how, ever since it was produced in the early 1980s, attempts have been made to filter race out of the sequence. That effort has failed due to what one could call ‘political noise’. Making and remaking the sequence have left traces that cannot be erased. (shrink)

The eukaryotic genome is packaged into a periodic nucleoprotein structure termed chromatin. The repeating unit of chromatin, the nucleosome, consists of DNA that is wound nearly two times around an octamer of histone proteins. To facilitate DNA‐directed processes in chromatin, it is often necessary to rearrange or to mobilize the nucleosomes. This remodeling of the nucleosomes is achieved by the action of chromatin‐remodeling complexes, which are a family of ATP‐dependent molecular machines. Chromatin‐remodeling factors share a related ATPase subunit and (...) participate in transcriptional regulation, DNA repair, homologous recombination and chromatin assembly. In this review, we provide an overview of chromatin‐remodeling enzymes and discuss two possible mechanisms by which these factors might act to reorganize nucleosome structure. BioEssays 25:1192–1200, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The eukaryotic genome is organized into different domains by cis‐acting elements, such as boundaries/insulators and matrix attachment regions, and is packaged with different degrees of condensation. In the M phase, the chromatin becomes further highly condensed into chromosomes. The first step for transcriptional activation of a given gene, at a particular time during development, in any locus, is the opening of its chromatin domain. This locus needs to be kept in this state in each early G1 phase during every (...) cell cycle. Certain distal enhance elements, including locus control regions (LCRs) and enhancers, are believed to perform this target chromatin domain opening process and several models have been proposed to explain distal enhance action. But they did not explain precisely how a given chromatin domain is opened. Based on various studies, we propose a hypothesis for the mechanism of opening chromatin on a large scale. One important mechanism may involved breaking one or two DNA strands and reducing the linking numbers within chromatin domain. The topological changes can overpass some complexes formed on DNA strands and can be transmitted from specific localized points over a broad region, until boundary elements or insulators are reached. These may initiate downstream events such as propagation of histone acetylation and the binding of transcription factors to proximal promoters and may further augment the action mediated by distal enhancer elements. BioEssays 25:507–514, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The organization of eukaryotic genomes as chromatin provides the framework within which regulated transcription occurs in the nucleus. The association of DNA with chromatin proteins required to package the genome into the nucleus is, in general, inhibitory to transcription, and therefore provides opportunities for regulated transcriptional activation. Granting access to the cis‐acting elements in DNA, a prerequisite for any further action of the trans‐acting factors involved, requires the establishment of local heterogeneity of chromatin and, in some cases, extensive remodeling (...) of nucleosomal structures. Challenging problems relate to the establishment of this heterogeneity at the level of the single nucleosome and to the mechanisms that operate when nucleosomal arrays are reorganized. Recent developments indicate that chromatin reconstitution in cell‐free systems allows the biochemical analysis of the interplay between transcription factors and chromatin components that brings about regulated transcription. (shrink)

Combining information from two or possibly several blocks of data is gaining increased attention and importance in several areas of science and industry. Typical examples can be found in chemistry, spectroscopy, metabolomics, genomics, systems biology and sensory science. Many methods and procedures have been proposed and used in practice. The area goes under different names: data integration, data fusion, multiblock analyses, multiset analyses and a few more. This book is an attempt to give an up-to-date treatment of the most used (...) and important methods within an important branch of the area; namely methods based on so-called components or latent variables. These methods have already obtained an enormous attention in for instance chemometrics, bioinformatics, machine learning and sensometrics and have proved to be important both for prediction and interpretation. The book is primarily a description of methodologies, but most of the methods will be illustrated by examples from the above-mentioned areas. The book is written such that both users of the methods as well as method developers will hopefully find sections of interest. In the end of the book there is a description of a software package developed particularly for the book. This package is freely available in R and covers many of the methods discussed. To distinguish the different type of methods from each other, the book is divided into five parts. Part I is introduction and preliminary concepts. Part II is the core of the book containing the main unsupervised and supervised methods. Part III deals with more complex structures and, finally, Part IV discusses alternative unsupervised and supervised methods. The book ends with Part V discussing the available software. Our recommendation for reading the book are as follows. A minimum read of the book would involve chapters 1, 2, 3, 5 and 7. Chapters 4, 6 and 8 are more specialized and chapters 9 and 10 contain methods we think are more advanced or less obvious to use. We feel privileged to have so many friendly colleagues who were willing to spend their time on helping us to improve the book by reading separate chapters. We would like to express our thanks to: Rasmus Bro, Margriet Hendriks, Ulf Indahl, Henk Kiers, Ingrid MaÌ⁽ge, Federico Marini, AÌ⁽smund Rinnan, Rosaria Romano, Lars Erik Solberg, Marieke Timmerman, Oliver Tomic, Johan Westerhuis and Barry Wise. Of course, the correctness of the final text is fully our responsibility! (shrink)

How eukaryotic genomes are packaged into compact cylindrical chromosomes in preparation for cell divisions has remained one of the major unsolved questions of cell biology. Novel approaches to study the topology of DNA helices inside the nuclei of intact cells, paired with computational modeling and precise biomechanical measurements of isolated chromosomes, have advanced our understanding of mitotic chromosome architecture. In this Review Essay, we discuss – in light of these recent insights – the role of chromatin architecture and the functions (...) and possible mechanisms of SMC protein complexes and other molecular machines in the formation of mitotic chromosomes. Based on the information available, we propose a stepwise model of mitotic chromosome condensation that envisions the sequential generation of intra‐chromosomal linkages by condensin complexes in the context of cohesin‐mediated inter‐chromosomal linkages, assisted by topoisomerase II. The described scenario results in rod‐shaped metaphase chromosomes ready for their segregation to the cell poles. (shrink)

Bogen and Woodward characterized data as embedded in the context in which they are produced (‘local’) and claims about phenomena as retaining their significance beyond that context (‘nonlocal’). This view does not fit sciences such as biology, which successfully disseminate data via packaging processes that include appropriate labels, vehicles, and human interventions. These processes enhance the evidential scope of data and ensure that claims about phenomena are understood in the same way across research communities. I conclude that the degree (...) of locality of both data and claims about phenomena varies depending on the packaging used to make them travel and on the research setting in which they are used. †To contact the author, please write to: ESRC Centre for Genomics in Society, University of Exeter, Byrne House, St. Germans Road, EX4 4PJ Exeter, United Kingdom; e‐mail: [email protected]. (shrink)

Local differences in chromatin organisation may profoundly affect the activity of eukaryotic genomes. Regulation at the level of DNA packaging requires the targeting of structural proteins and histone‐modifying enzymes to specific sites and their stable or dynamic interaction with the nucleosomal fiber. The “chromodomain”, a domain shared by many regulators of chromatin structure, has long been suspected to serve as a module mediating chromatin interactions in a variety of different protein contexts. However, recent functional analyses of a number of (...) different chromodomains revealed an unexpected diversity of interaction targets, including histones, DNA and even RNA. The chromodomains of today seem to have evolved from a common ancestral fold to fulfill various functions in different molecular contexts. Combining information gained from recent functional and structural studies of chromodomains with a bioinformatic classification of their structure could lead to the definition of sequence motifs with predictive quality for chromodomain function. BioEssays 26:133–140, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Retroviruses encode a small, basic nucleocapsid (NC) protein that is found complexed to genomic RNA within the viral particle. The NC protein appears to function not only in a histone‐like manner in packaging the RNA into the particle but also in specifically selecting the viral genomic RNA for packaging. A cysteine‐histidine (cys‐his) region, usually composed of 14 amino acids and reminiscent of the ‘zinc fingers’ of transcription factors, is the only highly conserved sequence element among the retroviral NC (...) proteins. This review discusses the biochemical properties of NC, and its possible role(s) in retroviral replication. We also speculate on how the biochemical properties may relate to its function in RNA recognition and packaging. (shrink)

Two groups of plant viruses have DNA in their genomes. One group, the caulimoviruses, are non‐integrating retroviruses that package dsDNA in virions. The other group, the geminiviruses, package small circular ssDNA and include the only DNA viruses known with bipartite genomes. The regulation of transcription of these viruses is not well characterized, but recent work is beginning to yield interesting results. Regulatory sequences from these viruses function in cells of species that are not hosts of the virus and are finding (...) use in constitutive expression of chimeric genes in transformed plants. Development of vectors based on plant viruses requires further characterization at the molecular level of viral life cycles. (shrink)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in (...) clinical reproductive applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

This paper develops an account of the metaphysics of fundamental laws I call “the Package Deal Account ” that is a descendent of Lewis’ BSA but differs from it in a number of significant ways. It also rejects some elements of the metaphysics in which Lewis develops his BSA. First, Lewis proposed a metaphysical thesis about fundamental properties he calls “Humean Supervenience” according to which all fundamental properties are instantiated by points or point sized individuals and the only fundamental relations (...) are geometrical spatial and temporal relations between these. While the BSA does not require HS Lewis seems to hope that it is true. In contrast, the PDA is not committed to HS or even to the fundamental arena in which fundamental properties are instantiated possessing geometrical structure and thus is able to accommodate relations and structures found in contemporary physics that apparently conflict with HS. Second, although Lewis’ BSA doesn’t require HS his Humeanism does require that fundamental properties are categorical. In contrast, the PDA allows for the possibility that fundamental properties are individuated in terms of laws and so are not categorical. Third, the PDA expands and develops the criteria for what counts in favor of a candidate system with more attention to the criteria employed by physicists in evaluating proposed theories. Fourth and most importantly, unlike Lewis’ BSA, the PDA does not presuppose metaphysically primitive elite properties/quantities that Lewis calls “perfectly natural” properties/quantities or presuppose a metaphysically preferred language whose terms denote such properties/quantities. It replaces Lewis’ account with an account on which natural properties are not metaphysically prior to the laws but are elements of a package that includes a fundamental arena that plays the role of space-time as well as fundamental laws and properties. By doing so it responds to some epistemological and metaphysical issues that have been raised regarding natural properties and their role in the BSA. In sum, the PDA goes further in explicating the notion of laws in terms of the aims and practices of science especially fundamental physics rather than in terms of prior metaphysics. I begin by reviewing Lewis’ account of perfectly natural properties and his Humean BSA of laws. (shrink)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. (...) Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates. (shrink)

The role of gene expression in evolutionary adaptation has been a subject of debate for over 40 years.cis‐regulation of transcription has been proposed to be the primary source of morphological novelty in evolution, though this is based on only a handful of examples. Recently the first genome‐wide studies of gene expression adaptation have been published, giving us an initial global view of this process. Systematic studies such as these will allow a number of key questions currently facing the field (...) of gene expression evolution to be addressed. (shrink)

This chapter contains section titled: Introduction Classical Molecular Biology Genomics and Post‐Genomics Proteomics Towards a Systems Biology? Philosophical Implications Conclusions: An Invitation References.

The governance of human (germline) genome modification at the international and transnational level -- The regulation of human germline genome modification in Canada (E Kleiderman) -- The regulation of human germline genome modification in the United States (Kerry Macintosh) -- The regulation of human germline genome modification in Mexico (M Medina Arellano) -- The regulation of human germline genome modification in Europe (J Almqvist, C Romano) -- The regulation of human germline genome modification in (...) the United Kingdom (J Lawford Davies) -- The regulation of human germline genome modification in Germany (T Faltus). (shrink)

Some properties – like charge – are natural, some – like grue are unnatural. The distinction between natural and unnatural properties is normally taken as primitive. However, Barry Loewer’s Package Deal Account (PDA) aims to provide an reductive account of natural properties, integrated with a reductive account of laws of nature. In addition, the account seems to be able to apply to natural properties at the level of fundamental physics, and higher-level, special science, properties. -/- If the account is successful, (...) then, it looks to be incredibly powerful and attractive. The PDA, however, is somewhat underexplored in the literature. So the first aim of the paper is to understand the PDA better -- to map the connections between naturalness and laws on the traditional BSA and to consider how those connections have to adapted in order to develop different versions of the PDA. -/- The second aim is to start to evaluate different versions of the PDA. In particular, perhaps the most promising version of the PDA construes it as an instance of a larger approach to Humeanism — one that has been very visible in the recent literature — that focuses on the role of 'ideal observers' or 'ideal scientists'. While such an approach might be feasible, I claim, it gets its proponents much less than they were originally hoping for. (shrink)

Genomics is increasingly becoming an integral component of health research and clinical care. The perceived difficulties associated with genetic research involving Aboriginal and Torres Strait Islander people mean that they have largely been excluded as research participants. This limits the applicability of research findings for Aboriginal and Torres Strait Islander patients. Emergent use of genomic technologies and personalised medicine therefore risk contributing to an increase in existing health disparities unless urgent action is taken. To allow the potential benefits of genomics (...) to be more equitably distributed, and minimise potential harms, we recommend five actions: ensure diversity of participants by implementing appropriate protocols at the study design stage; target diseases that disproportionately affect disadvantaged groups; prioritise capacity building to promote Indigenous leadership across research professions; develop resources for consenting patients or participants from different cultural and linguistic backgrounds; and integrate awareness of issues relating to Indigenous people into the governance structures, formal reviews, data collection protocols and analytical pipelines of health services and research projects. (shrink)

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical (...) and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)

The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct.

1900 was a remarkable year for science. Several ground-breaking events took place, in physics, biology and psychology. Planck introduced the quantum concept, the work of Mendel was rediscovered, and Sigmund Freud published The Interpretation of Dreams . These events heralded the emergence of completely new areas of inquiry, all of which greatly affected the intellectual landscape of the 20 th century, namely quantum physics, genetics and psychoanalysis. What do these developments have in common? Can we discern a family likeness, a (...) basic affinity between them, so that we can use the one to deepen our understanding of the other? One common denominator is that they open up realms of inquiry that are significantly different from the world of everyday experience, namely the realm of elementary particles, of genes and genomes, and of the unconscious. But to what extent can we meaningfully argue, for instance, that the genome is the biological unconscious, and the unconscious the psychic genome? To address these questions, I will build on the work of two key intellectual figures who have explored the affinities of these developments in depth, namely Erwin Schrödinger (a quantum physicist and avid reader of Schopenhauer who initiated molecular biology) and Jacques Lacan (who reframed the specificity of psychoanalysis with the help of 20 th century science: the era of structural linguistics, but also of quantum physics, molecular biology, bioinformatics and DNA). (shrink)

In this paper I argue that some human reproductive genome editing interventions can be therapeutic in nature, and thus that it is false that all such interventions just create healthy individuals. I do this by showing that the conditions established by a therapy definition are met by certain reproductive genome editing interventions. I then defend this position against two objections: (a) reproductive genome editing interventions do not attain one of the two conditions for something to be a (...) therapy, and (b) some reproductive genome editing interventions are therapeutic but in a nonstandard way. In the Conclusion I call for a more nuanced discussion of the nature of reproductive genome editing interventions. (shrink)

Background The rise in genomic and biobanking research worldwide has led to the development of different informed consent models for use in such research. This study analyses consent documents used by investigators in the H3Africa (Human Heredity and Health in Africa) Consortium. Methods A qualitative method for text analysis was used to analyse consent documents used in the collection of samples and data in H3Africa projects. Thematic domains included type of consent model, explanations of genetics/genomics, data sharing and feedback of (...) test results. Results Informed consent documents for 13 of the 19 H3Africa projects were analysed. Seven projects used broad consent, five projects used tiered consent and one used specific consent. Genetics was mostly explained in terms of inherited characteristics, heredity and health, genes and disease causation, or disease susceptibility. Only one project made provisions for the feedback of individual genetic results. Conclusion H3Africa research makes use of three consent models—specific, tiered and broad consent. We outlined different strategies used by H3Africa investigators to explain concepts in genomics to potential research participants. To further ensure that the decision to participate in genomic research is informed and meaningful, we recommend that innovative approaches to the informed consent process be developed, preferably in consultation with research participants, research ethics committees and researchers in Africa. (shrink)

How should we regulate genome editing in the face of persistent substantive disagreement about the moral status of this technology and its applications? In this paper, we aim to contribute to resolving this question. We first present two diametrically opposed possible approaches to the regulation of genome editing. A first approach, which we refer to as “elitist,” is inspired by Joshua Greene’s work in moral psychology. It aims to derive at an abstract theoretical level what preferences people would (...) have if they were committed to implementing public policies regulating genome editing in a context of ethical pluralism. The second approach, which we refer to as the democratic approach, defended by Francoise Baylis and Sheila Jasanoff et al., emphasizes the importance of including the public’s expressed attitudes in the regulation of genome editing. After pointing out a serious shortcoming with each of these approaches, we propose our own favored approach—the “enlightened democracy” approach—which attempts to combine the strengths of the elitist and democratic approaches while avoiding their weaknesses. (shrink)

Phage DNA packaging occurs by DNA translocation into a prohead. Terminases are enzymes which initiate DNA packaging by cutting the DNA concatemer, and they are closely fitted structurally to the portal vertex of the prohead to form a ‘packasome’. Analysis among a number of phages supports an active role of the terminases in coupling ATP hydrolysis to DNA translocation through the portal. In phage T4 the small terminase subunit promotes a sequence‐specific terminase gene amplification within the chromosome. This (...) link between recombination and packaging suggests a DNA synapsis mechanism by the terminase to control packaging initiation, formally homologous to eukaryotic chromosome segregation. (shrink)

?Packaging the Conservative Revolution? assesses the role of conservative think?tanks, particularly the American Enterprise Institute (AEI) and the Heritage Foundation, in engineering conservative prominence in national affairs. While AEI and Heritage have been particularly effective in promoting conservatism to legislators and the public, serious problems emerge from their analyses. The anti?welfare state bias of AEI projects reflects the dominance of Fortune 500 executives on its Board of Directors. Theoretical manipulation by AEI project directors raises questions about the purpose of (...) their work. Heritage, for its part, has proposed analogues to governmental programs. Notably, Heritage has provided important intellectual support to the traditionalist movement. As conservative think?tanks grow and influence national affairs, the impartiality and quality of their work become important factors in understanding national politics. (shrink)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of (...) nucleoprotein complexes, epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

Recent discussions of genomics and international justice have adopted the concept of ‘global public goods’ to support both the view of genomics as a benefit and the sharing of genomics knowledge across nations. Such discussion relies on a particular interpretation of the global public goods argument, facilitated by the ambiguity of the concept itself. Our aim in this article is to demonstrate this by a close examination of the concept of global public goods with particular reference to its use in (...) the context of genomic databases. We contend that the argument for construing genomics as a global public good depends on seeing it as a natural good by focusing on features intrinsic to genomics knowledge. We shall argue that social and political arrangements are relevant and that recognising this opens the door to construing the use of global public goods language as a strategic one. (shrink)

It is frequently said that biology is emerging from a long phase of reductionism. It would be certainly more correct to say that biologists are abandoning a certain form of reductionism. We describe this past form, and the experiments which challenged the previous vision. To face the difficulties which were met, biologists use a series of concepts and metaphors - pleiotropy, tinkering, epigenetics - the ambiguity of which masks the difficulties, instead of solving them. In a similar way, the word (...) “post-genomics” has different meanings, depending upon who uses it. Which of these meanings will become dominant in the future is an open question. (shrink)

In team-based tasks, successful communication and mutual understanding are essential to facilitate team coordination and performance. It is well-established that an important component of human conversation is the maintenance of common ground. Maintaining common ground has a number of associated processes in which conversational participants engage. Many of these processes are lacking in current synthetic teammates, and it is unknown to what extent this lack of capabilities affects their ability to contribute during team-based tasks. We focused our research on how (...) teams package information within a conversation, by which we mean specifically whether information is explicitly mentioned or implied, and how multiple pieces of information are ordered both within single communications and across multiple communications. We re-analyzed data collected from a simulated remotely-piloted aerial system task in which team members had to specify speed, altitude, and radius restrictions. The data came from three experiments: the “speech” experiment, the “text” experiment, and the “evaluation” experiment. We asked first whether teams settled on a specific routine for communicating the speed, altitude, and radius restrictions, and whether this process was different if the teams communicated in speech compared to text. We then asked how receiving special communication instructions in the evaluation experiment impacted the way the human teammates package information. We found that teams communicating in either speech or text tended to use a particular order for mentioning the speed, altitude, and radius. Different teams also chose different orders from one another. The teams in the evaluation experiment, however, showed unnaturally little variability in their information ordering and were also more likely to explicitly mention all restrictions even when they did not apply. Teams in the speech and text experiments were more likely to leave unnecessary restrictions unmentioned, and were also more likely to convey the restrictions across multiple communications. The option to converge on different packaging routines may have contributed to improved performance in the text experiment compared some of the conditions in the evaluation experiment. (shrink)

Summary This article discusses the intersection of science and culture in the marketplace and explores the ways in which radium quack and medicinal products were packaged and labelled in the early twentieth century US. Although there is an interesting growing body of literature by art historians on package design, historians of science and medicine have paid little to no attention to the ways scientific and medical objects that were turned into commodities were packaged and commercialized. Thinking about packages not as (...) mere containers but as multifunctional tools adds to historical accounts of science as a sociocultural enterprise and reminds us that science has always been part of consumer culture. This paper suggests that far from being receptacles that preserve their content and facilitate their transportation, bottles and boxes that contained radium products functioned as commercial and epistemic devices. It was the 1906 Pure Food and Drug Act that enforced such functions. Packages worked as commercial devices in the sense that they were used to boost sales. In addition, ‘epistemic’ points to the fact that the package is an artefact that ascribes meaning to and shapes its content while at the same time working as a device for distinguishing between patent and orthodox medicines. (shrink)