This paper examines some ethical issues arising from whole-genome association studies for multigenic diseases, focusing on the case of autism. Events occurring following the announcement of a genetic test for autism in France (2005–2009) are described to exemplify the ethical controversies that can arise when genetic testing for autism is applied prematurely and inappropriately promoted by biotech companies. The authors argue that genetic tests assessing one or a few genes involved in highly multigenic disorders can only be useful if: (1) (...) the genetic linkage found in the scientific study must be statistically convincing, reproducible and also applicable to the population to which the individual considered belongs (scientific validity); (2) the relative risk conferred by the ‘high-risk’ allele should be high enough to be significant to the patient (significant impact); (3) use of the test should lead to some improvement of outcome for the patient, resulting from adapted treatment if available, or at least from adjustment of lifestyle (or life goals) prompted by the new knowledge generated (clinical utility). Decisions concerning genetic testing for autism involve scientific judgement, value judgement and good knowledge of a constantly evolving therapeutic environment. The implementation of genetic tests for highly multigenic diseases thus requires strong mechanisms to ensure that they are used in a fashion that can benefit patients, and these mechanisms must be able to cope with rapid progress in scientific knowledge and therapeutic intervention. (shrink)

This article contends that social policy faces a crisis over whether a viable collective order can be constructed out of individual choices. The neo-liberal paradigm is now challenged by neo-conservatives, who argue for policies derived from traditional moral, religious and patriotic values. This raises issues about the nature of social bonds, the institutional order and collective life itself. The article argues that it provides an opportunity for social theorists and policy analysts to co-operate in re-examining these questions. However, these debates (...) indicate a need for social theorists to confront their relationship with Enlightenment accounts of how commerce and private property enable liberty and consensual government. In the face of recent evidence of ‘stalled well-being’ within increasing prosperity, the article argues for a new analysis of choice and solidarity. (shrink)

DNA arrays are now widely used in academia and industry, and expression profiling is recognised as a major tool for basic research as well as for drug development. It is also likely, in the near future, that DNA arrays will be used in clinical laboratories for diagnostic and prognostic purposes. Since several types of arrays are being used, the coherence of results obtained using these diverse platforms becomes an important issue: to what extent can data obtained in different laboratories and (...) with different equipment be combined? Several recent papers address this issue and demonstrate that the expected agreement is not necessarily found. Consistent results can be obtained, but this requires careful identification of the genes assessed by the arrays, and scrupulous adherence to strict experimental procedures. BioEssays 26:1236–1242, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Until quite recently, recombinant DNA technology was not able to deal with DNA molecules larger than 20–40 kb. This is a serious limitation for the study of mammalian, and in particular human genomes whose total length is approx. 3 × 106 kb, since the best resolution of genetic and chromosomal analysis is usually the rough equivalent of 1000–5000 kb. Three recently developed methods promise to bridge this gap: pulsed field gel electrophoresis, which can analyze megabase‐sized DNA fragments; cloning in yeast, (...) which can clone and propagate DNA fragments of several hundred kb; and jumping libraries, which allow ‘jumping’ over large distances along the chromosome. This review presents the current status of these very promising technologies. (shrink)

DNA arrays have become the preferred method for large-scale expression measurement. Such data are needed in view of the large amounts of sequence data available: expression levels in a number of different tissues or situations provide a first step toward functional characterisation of new entities revealed by DNA sequencing. Although the basic principle of measurement is in all cases based on hybridisation of a mixed probe derived from tissue RNA to large sets of DNA fragments representing many genes, a number (...) of different forms of implementation of this principle are at hand. They are briefly described and compared, emphasizing the important issue of sensitivity and sample requirements and the accessibility of the methods to academic scientists. When these factors are taken into account, it appears that, contrary to a largely prevalent impression, the “best” approach is not necessarily always provided by the widely advertised glass microarrays or oligonucleotide chips. BioEssays 21:781–790, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Progress in recombinant DNA technology and in mapping of the human genome makes it possible to diagnose genetic defects as early as 8–10 weeks after conception for an increasing number of genetic diseases. Further developments will bring wider applicability and increased sensitivity, making widespread application of this type of diagnosis possible. Logistical and ethical problems will however arise in the course of this development.

Expression signatures obtained from tumour samples are widely used to characterise tumour subtypes and to provide prognostic information. This commentary, based on a recent paper, questions the scientific validity of such signatures as a means of understanding the underlying biology.

Although DNA microarrays are now widely used in research settings, they have been slow to penetrate clinical practice in spite of their apparent advantages. This is due to the very different requirements for a clinical test in contrast to a research tool, and to a strict necessity for demonstrated clinical utility. There is a clear differentiation between two types of DNA array tests: “genomic” diagnostics, developed to ascertain the presence or absence of mutations, deletions or duplications, and for which clinical (...) evidence is already established, and tests using expression profiling for prognosis or predictive purposes, in which case the clinical correlate must be proven. Most array diagnostics currently used belong, understandably, to the “genomic” variety. It is to be expected that future improvements in tailored technology, as well as a logical trend towards measuring an ever‐increasing number of parameters, will ensure an important diagnostic role for DNA arrays in the coming decade. BioEssays 29:699–705, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Fragile X‐linked mental retardation is an enigmatic inheritable syndrome in which severe mental retardation, a cytogenetically detectable fragile site at Xq27.3 (FraX) and a number of dysmorphic features are associated. Genetic analysis shows that the mode of inheritance is more complex than a straightforward X‐linked recessive trait and probably involves a two‐step process for which several models have been proposed. Early attempts ‘at cloning the fragile site’ provided several DNA segments lying in its general vicinity, and large scale DNA mapping (...) methods were extensively applied in an effort to generate maps including this region. These efforts were complemented by more focussed methods such as microdissection; together these approaches have now provided a number of DNA segments within a 5cM interval around FraX, and with the help of these new probes the site is indeed being cloned. Unravelling the nature of the sequence(s) responsible for the mental retardation syndrome will probably take some time, however. (shrink)

Almost every human disease has both a genetic and an environmental component. Even a classical inherited condition such as hemophilia can be influenced by external factors—in fact, most of the pathogenic effects of the mutation can be avoided by judicious injections of clotting factor, leading to a nearly normal life expectancy. For infectious diseases, often considered as essentially environmental, there are well-documented inherited differences in susceptibility, one of the most striking being the resistance to HIV infection of homozygous carriers of (...) the delta-32 mutation in the CCR5 gene (Dragic et al. 1996). Nevertheless, a number of conditions are “mostly genetic,” others “mostly environmental,” while many .. (shrink)

This article reviews the recent contributions of Amartya Sen and John McMurtry to theory of international development and social justice. The author argues that both fail to give an adequate account of the current transformation of collective life and the provision of collective goods. Without such an analysis, theories of justice are incomplete.

The serological properties of the major histocompatibility (class I) antigens of mammals have raised many questions about the structure and function of these molecules. Over the past four years the cloning of their gene sequences has begun to provide some of the answers to these questions. The structural analyses have demonstrated close similarities between class I genes of man and mouse, established the existence of numerous class I pseudogenes in human and murine genomes, and indicated the importance of gene conversion (...) events in regulating the sequence diversity of this gene family. In addition, the ability to construct new class I genes in vitro and to transfect cultured murine cells with the synthetic sequences is permitting new tests of the functional organization of these genes in relation to their structure. (shrink)

This article challenges the basis of the new British government's conception of social justice, and hence its social policy programme. Under conditions of globalised exchange, with an international division of labour, the national economy cannot meaningfully be represented as a ?system of co?operation'; hence, the principle of reciprocity cannot justify favouring the claims of fellow citizens over those of foreigners. In these circumstances, restrained competition among members becomes a more important element in mutuality than individual labour contribution. Distributive justice must (...) be located in an institutional context that provides such restraint, and yet promotes participation for the common good. This requirement redirects attention towards the basic income approach to redistributive issues, and suggests alternative ethical justifications for its implementation. (shrink)

This paper examines the developments in the aftermath of Caesar’s assassination on the Ides of March 44 bce in the context of developments concerning the allocation of the consular provinciae of that year. It argues that the consuls, M. Antonius and P. Cornelius Dolabella, initially sought compromise with the conspirators, and the passage of the lex de permutatione provinciarum on the Kalends of June represents a genuine turning point. The historical implications of its provisions led to increasing hostility, and ultimately (...) the Mutinian War. Last, but not least, this paper seeks to demonstrate the integral role of C. Octavius in prompting this consequential change in attitude. (shrink)

The speeches of Nicias and Alcibiades in the debate leading up to the launching of the Sicilian expedition contain a significant number of words, phrases, and themes that recur in Thucydides' later chapters reporting the launching of the expedition and its ultimate fate in Sicily. The verbal and thematic echoes often consist of words of sight and hearing; among the recurring themes are rivalry and competition, the contrast between public and private expenditures, and the desire for acquisition and financial profit.