Human genetic banking: altruism,benefit and consent

This article considers how we should frame the ethical issues raised by current proposals for large‐scale genebanks with on‐going links to medical and lifestyle data, such as the Wellcome Trust and Medical Research Council's ‘UK Biobank’. As recent scandals such as Alder Hey have emphasised, there are complex issues concerning the informed consent of donors that need to be carefully considered. However, we believe that a preoccupation with informed consent obscures important questions about the purposes to which such collections are put, not least that they may be only haphazardly used for research (especially that of commercial interest)—an end that would not fairly reflect the original altruistic motivation of donors, and the trust they must invest. We therefore argue that custodians of such databases take on a weighty pro‐active duty, to encourage public debate about the ends of such collections and to sponsor research that reflects publicly agreed priorities and provides public benefits.     

Human genetic banking: altruism, benefit and consent

This article considers how we should frame the ethical issues raised by current proposals for large-scale genebanks with on-going links to medical and lifestyle data, such as the Wellcome Trust and Medical Research Council's 'UK Biobank'. As recent scandals such as Alder Hey have emphasised, there are complex issues concerning the informed consent of donors that need to be carefully considered. However, we believe that a preoccupation with informed consent obscures important questions about the purposes to which such collections are put, not least that they may be only haphazardly used for research (especially that of commercial interest)--an end that would not fairly reflect the original altruistic motivation of donors, and the trust they must invest. We therefore argue that custodians of such databases take on a weighty pro-active duty, to encourage public debate about the ends of such collections and to sponsor research that reflects publicly agreed priorities and provides public benefits.     

The incidence and diversity of Wolbachia in gallwasps (Hymenoptera; Cynipidae) on oak

Wolbachia bacteria infect approximately 20% of all insect species, and cause a range of alterations to host reproduction, including imposition of thelytoky. The incidence and phenotypic impact of Wolbachia remains to be established in many insect taxa, and considerable research effort is currently focused on its association with particular reproductive modes and the relative importance of the various pathways via which infection occurs. Gallwasps represent an attractive system for addressing these issues for two reasons. First, they show a diversity of reproductive modes (including arrhenotoky, thelytoky and cyclical parthenogenesis) in which the impact of Wolbachia infection can be examined. Second, they occupy two intimately linked trophic niches (gall-inducers and inquilines) between which there is potential for the horizontal exchange of Wolbachia infection. In the arrhenotokous gallwasp lineages screened to date (the herb-galling 'Aylacini' and the rose-galling Diplolepidini), Wolbachia infection always induces thelytoky. The impact of Wolbachia in other arrhenotokous clades, and in the cyclically parthenogenetic clades remains unknown. Here we use polymerase chain reaction (PCR) screening and sequence data for two Wolbachia genes (wsp and ftsZ) to examine the prevalence and incidence of Wolbachia infection in 64 species (a total of 609 individuals) in two further tribes: the arrhenotokous inquilines (tribe Synergini), and the cyclically parthenogenetic oak gallwasps (tribe Cynipini). We ask: (i) whether Wolbachia infection has any apparent impact on host reproduction in the two tribes and (ii) whether there is any correlation between Wolbachia infection and the apparent lack of an arrhenotokous generation in many oak gallwasp life cycles. We show: (i) that Wolbachia infection is rare in the Cynipini. Infected species show no deviation from cyclical parthenogenesis, and infection is no more common in species known only from a thelytokous generation; (ii) that there is a higher incidence of infection within the arrhenotokous inquilines, and generally in gallwasp tribes without cyclical parthenogensis; (iii) all Wolbachia-positive inquiline species are known to possess males, implying either that Wolbachia infection does not result in loss of sex in this tribe or, more probably, that (as for some rose gallwasps) Wolbachia infection leads to loss of sex in specific populations; and (iv) although we find some inquilines and gall inducers to be infected with Wolbachia having the same wsp sequence, these hosts are not members of the same gall communities, arguing against frequent horizontal transmission between these two trophic groups. We suggest that exchange may be mediated by the generalist parasitoids common in oak galls.     

An analytical perspective on detection,screening, and confirmation in phycology,with particular reference to toxins and toxin‐producing species

Knowledge concerning the ability of microalgae to produce metabolites of interest such as toxins or high‐value secondary metabolites requires exhaustive details to be supplied on how the research was conducted. These should include the microalgal species and strain characterization, the culture conditions, the cell density, and physiological state at the time of harvesting, the harvesting method, the sample pre‐treatment protocol, and the subsequent instrumental analytical separation/detection system. In this comment, we discuss issues that affect algal research from an analytical chemistry perspective, particularly (i) the need to specify detection capabilities of the entire method (i.e., limits of detection or threshold detection levels), which we illustrate in relation to classification of a species or strain as being “toxin producing” or “non‐toxin producing”; and (ii) the requirements that have to be satisfied to confirm a microalgal species (new or not) as a producer of a particular chemical of interest for phycologists, which again we illustrate in relation to toxins. A successful collaboration among phycologists and analytical chemists will only be achieved as a result of a synergistic collaboration between the two disciplines, with a reciprocal understanding at least at a background level.     

Ethics guidelines for research with the recently dead

The objective of the multidisciplinary expert Consensus Panel on Research with the Recently Dead (CPRRD) was to craft ethics guidelines for research with the recently dead. The CPRRD recommends that research with the recently dead: (i) receive scientific and ethical review and oversight; (ii) involve the community of potential research subjects; (iii) be coordinated with organ procurement organizations; (iv) not conflict with organ donation or required autopsy; (v) use procedures respectful of the dead; (vi) be restricted to one procedure per day; (vii) preferably be authorized by first-person consent, though both general advance research directives and surrogate consent are acceptable; (viii) protect confidentiality; (ix) not impose costs on subjects' estates or next of kin and not involve payment; (x) clearly explain ultimate disposition of the body.     

Using data to improve surrogate consent for clinical research with incapacitated adults

Current practice relies on surrogates to enroll incapacitated adults in research. Yet, it is unclear to what extent this practice protects adults who have lost the ability to consent for themselves. To address this question, we conducted two literature searches to identify articles which report empirical data on three issues central to protecting adults who have lost the ability to consent: (1) adults' willingness to participate in research should they lose the ability to consent; (2) adults' willingness to allow a surrogate to make research decisions for them; and (3) the extent to which surrogates' enrollment decisions are consistent with their charges' preferences and values. These searches identified 21 articles, representing 20 distinct datasets. The data indicate that many adults are willing to participate in research should they lose the ability to consent, and many are willing to allow their family members to make research decisions for them if they become incapacitated. The data also raise concern that surrogates may be making research enrollment decisions that, in some cases, are inconsistent with their charges' preferences and values. These findings suggest that modifications to current practice should be considered to better protect adults who have lost the ability to consent. One option would be to require, in addition to surrogate permission and subject assent, sufficient evidence that enrollment is consistent with the individual's preferences and values.     

Assessing the functional implications of soil biodiversity in ecosystems

Soil communities are among the most species-rich components of terrestrial ecosystems. A major challenge for soil ecologists is to formulate feasible research strategies that will preserve and capitalize on the biodiversity resources of the soil. This article considers the role of soil organism diversity by concentrating on: (i) the relationship between soil biodiversity and ecosystem function; (ii) what issues need to be explored; (iii) studies carried out in the Ecotron controlled environment facility; and (iv) how stable isotope techniques can improve our understanding of the relationship between soil biodiversity and ecosystem function. It is advocated that: (i) the objective of any soil biodiversity study should always be the generation of general concepts, rather than local, system-specific observations; and (ii) any empirical study can be properly interpreted only within a quantitative ecological framework.     

The emergence of abstract ideas: evidence from networks and babies

What is abstraction? In our view, abstraction is generalization. Specifically, we propose that abstract concepts emerge as the natural product of associative learning and generalization by similarity. We support this proposal by presenting evidence for two ideas: first, that children''s knowledge about how categories are organized and how words refer to them can be explained as learned generalizations over specific experiences of words referring to categories; and second, that the path of concepts from concrete to more abstract can be observed throughout development and that even in their more abstract form, concepts retain some of their original sensory basis. We illustrate these two facts by examining, in two kinds of learners--networks and young children--the development of three abstract ideas: (i) the idea of word; (ii) the idea of object; and (iii) the idea of substance.     

Management of agricultural wet grasslands for breeding waders: integrating ecological and livestock system perspectives—a review

Although agriculture is pointed to as being one of the major causes of biodiversity loss, it is now recognised that some farming practices, grazing in particular, represent central issues in the on-running debate on wildlife conservation. This paper analyses the relationship between agricultural pasture management and bird preservation, by focusing on the illustrative case study of breeding waders in wet grasslands. After a brief account of the knowledge on research investigating the effect of grazing management on wader distribution or abundance, we reviewed (i) sward structure (i.e. mean sward height and frequency of tussocks) requirements, and (ii) breeding phenologies of five wader species commonly associated with wet grasslands for nesting in Europe. We found differences between species in these two aspects of their biology. Investigating grassland management thus underlines that the question of the timing of grazing should be considered. Moreover, the fragmented characteristic of agricultural landscapes (i.e. a mosaic of fields) in which waders breed emphasises the spatial nature of this management. We examine three spatial scales (i.e. field, set of adjacent fields, landscape) relevant to bird biology and influenced by agricultural activities. Based on these findings, we analyse which livestock system constraints are essential to take into account in order to minimise conflicts between livestock production and conservation aims in marshes. Finally, we highlight possible directions for future research.     

Research, Informed Consent, and the Limits of Disclosure

According to this paper, respect for informed consent implies that subjects should often be told a good deal more than ethical guidelines explicitly or implicitly require. Unless subjects are informed of the researchers' personal characteristics, views, and sponsors whenever they would be likely to consider them significant, their autonomy is being overridden. However, overriding subjects' autonomy is sometimes required by the interests of researchers in not being discriminated against or suffering intrusions into their privacy. This paper resolves the conflict between informed consent and the interests of researchers by recommending that (i) subjects generally should be told of the personal characteristics of researchers when relevant as part of the researchers' job and (ii) that subjects should be told of researchers' views when conceptually connected to the research and (iii) that subjects should almost always be told about sponsorship. While the paper explicitly limits the role of informed consent, these recommendations go significantly beyond most guidelines in their requirements about what information should be disclosed.     

Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal

Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent.     

The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the analytical (theoretical/philosophical) research

BackgroundConducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet, approaching the parents of these infants at such a difficult time raises challenges to obtaining valid informed consent for such research. In this study, we asked, What light does the analytical literature cast on an ethically defensible approach to obtaining informed consent in perinatal clinical trials?MethodsIn a systematic search, we identified 30 studies. We began our analysis by applying philosophical frameworks, which were then refined as concepts emerged from the analytical studies, to present a coherent picture of a broad literature.ResultsBetween them, the studies addressed four themes. The first three were the ethical basis for parental informed consent for neonatal and/or perinatal research, the validity of parental consent in this context, and the range of possible options in methods for gaining consent. The last was the issue of risk and the possibility of a double-standard or asymmetry in the current approaches to the requirement for consent for research and consent for clinical treatment.ConclusionsIn addressing these issues, the analysed studies showed that, whilst there are a variety of possible defences for seeking parental ‘consent’ to neonatal and/or perinatal clinical trials, these are all consistent with the strongly and widely held view that it is important that parents do give (or decline) consent for such research. So far as the method of obtaining consent is concerned, none of the existing consent processes reviewed by the research is satisfactory, and there are philosophical reasons for supposing that at least some parents will fail to give valid consent in a neonatal context. Furthermore, in giving parental ‘consent’ in a perinatal context, parents are authorising infant participation, not giving ‘proxy consent’. Finally, there are reasons for giving weight to both parental ‘consent’ and the infant’s best interests in both research and clinical treatment. However, there are also reasons to treat these factors differently in the two contexts, and this may be partly due to the differing relevance of risk in each case. A significant gap is the lack of any detailed discussion of a process of emergency and/or urgent ‘assent’, in which parents assent or refuse their baby’s participation as best they can during the emergency and later give full consent to continuing participation and follow-up.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1562-3) contains supplementary material, which is available to authorized users.     

ON THE NEED FOR IMPROVED PROTECTIONS OF INCAPACITATED AND NON‐BENEFITING RESEARCH SUBJECTS

In this article, it is claimed that the protective provisions for adults with impaired decision‐making capacity are misguided, insofar as they do not conclusively state whether research on this group should be permitted only as an exception, and as they arbitrarily allow for some groups to benefit from such research while others will not. Moreover, the presumed or former will of the subject is given insufficient weight, and the minimal risk standard does not make sense in this context. Because of these problems, the present guidelines allow for the possibility of vulnerable people being exploited, something that is hidden behind a guise of solidarity. Instead we need to address the real issues at stake by rewriting the present statutes. It is suggested that new guidelines should be in some continuity with earlier efforts. However, in order to protect these subjects there is additional need for appointed representatives who monitor research and for legal obligations to compensate for any injuries suffered. Without these or similar measures we won't have an adequate system in place for the protection of non‐benefiting persons who are unable to consent to research.     

UNCERTAIN TRANSLATION,UNCERTAIN BENEFIT AND UNCERTAIN RISK: ETHICAL CHALLENGES FACING FIRST‐IN‐HUMAN TRIALS OF INDUCED PLURIPOTENT STEM (IPS) CELLS

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First‐in‐human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross‐fertilisation of knowledge and better clinical outcomes.     

On the use of the transmission disequilibrium test to detect pseudo‐autosomal variants affecting traits with sex‐limited expression

We herein describe the realization of a genome‐wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission disequilibrium test to avoid spurious associations due to population stratification. By doing so, we obtained genome‐wide significant signals for both diseases with SNPs located in the pseudo‐autosomal region in the vicinity of the pseudo‐autosomal boundary. By further analyzing these signals, we demonstrate that the observed transmission disequilibria are artifactual. We determine that transmission bias at pseudo‐autosomal markers will occur (i) when analyzing traits with sex‐limited expression and (ii) when the allelic frequencies at the marker locus differ between X and Y chromosomes. We show that the bias is due to the fact that (i) sires will preferentially transmit the allele enriched on the Y (respectively X) chromosome to affected sons (respectively daughters) and (ii) dams will appear to preferentially transmit the allele enriched on the Y (respectively X) to affected sons (respectively daughters), as offspring inheriting the other allele are more likely to be non‐informative. We define the conditions to mitigate these issues, namely by (i) extracting information from maternal meiosis only and (ii) ignoring trios for which sire and dam have the same heterozygous genotype. We show that by applying these rules to scrotal hernia and cryptorchidism, the pseudo‐autosomal signals disappear, confirming their spurious nature.     

Informed consent and collaborative research: perspectives from the developing world

Introduction: Informed consent has been recognized as an important component of research protocols and procedures of disclosure and consent in collaborative research have been criticized, as they may not be in keeping with cultural norms of developing countries. This study, which is part of a larger project funded by the United States National Bioethics Advisory Commission, explores the opinions of developing country researchers regarding informed consent in collaborative research. Methods: A survey of developing country researchers, involved in human subject research, was conducted by distributing a questionnaire with 169 questions, which included questions relating to informed consent. In addition, six focus group discussions, eight in-depth interviews and 78 responses to open-ended questions in the questionnaire provided qualitative data. Results: 203 surveys were considered complete and were included in the analysis. Written consent was not used by nearly 40% of the researchers in their most recent studies. A large proportion of respondents recommended that human subject regulations should allow more flexibility in ways of documenting informed consent. 84% of researchers agreed that a mechanism to measure understanding should be incorporated in research studies as part of the process of informed consent. Discussion: This paper is an empirical step in highlighting the ethical issues concerning disclosure. Health researchers in developing countries are well aware of the importance of consent in health research, and equally value the significance of educating human subjects regarding study protocols and associated risks and benefits. However, respondents emphasize the need for modifying ethical regulations in collaborative research.     

知情同意：定义、模式和挑战

从知情同意产生和发展的历史、知情同意的含义和模式方面来说明产生于一定历史背景下的知情同意,在临床和研究领域,以及生物信息库的建设中,具有一定的局限性,也面临着挑战。面对这样的挑战,不应该拘泥于对知情同意概念本身如何准确表述、模式如何创新,而更应该从知情同意所要达到的目的——保护患者、受试者和样本提供者的权益来考虑。     

Pharmacogenetics: the bioethical problem of DNA investment banking

Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development--protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or 'work', the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context.