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.     

Challenges in genetic resources policy making: some lessons from participatory policy research with a special reference to Ethiopia

It is widely recognized that developing countries lack technical and institutional capacity to effectively implement genetic resources policy. This has led Bioversity International (the then IPGRI) to initiate a project called Genetic Resources Policy Initiative (GRPI) in six countries (Ethiopia, Egypt, Zambia, Peru, Vietnam and Nepal). Drawing from the literature and experiences of this project, this paper has attempted to document some of the lessons from the project and present the issues and challenges that need to be addressed for effective genetic resources policy. Recognizing its cross-cutting nature, the paper has argued that genetic resources policy has to be part of the broader development agenda to effectively deal with trade-offs and harmonize the conflicts. Essentially, the important policy question is to strike the balance and simultaneously promote the diversity of genetic resources and welfare outcomes. The major thrust of GRPI has been the multi-disciplinary, -sectoral, and -stakeholder (3M) approach. Despite all its theoretical merits, its implementation has been a serious challenge in practice. This has, among others, been due to ‘‘A project for all is a project for none’’ dilemma. Engaging decision makers in 3M deliberations has revealed that many of them tend to think that maintaining genetic diversity promotes traditional farming and retards agricultural development. Clearly, addressing each of these challenges and policy loopholes requires innovation in a diversity of institutions.     

NARRATIVES OF ‘TERMINAL SEDATION’, AND THE IMPORTANCE OF THE INTENTION‐FORESIGHT DISTINCTION IN PALLIATIVE CARE PRACTICE

The moral importance of the ‘intention–foresight’ distinction has long been a matter of philosophical controversy, particularly in the context of end‐of‐life care. Previous empirical research in Australia has suggested that general physicians and surgeons may use analgesic or sedative infusions with ambiguous intentions, their actions sometimes approximating ‘slow euthanasia’. In this paper, we report findings from a qualitative study of 18 Australian palliative care medical specialists, using in‐depth interviews to address the use of sedation at the end of life. The majority of subjects were agnostic or atheistic. In contrast to their colleagues in acute medical practice, these Australian palliative care specialists were almost unanimously committed to distinguishing their actions from euthanasia. This commitment appeared to arise principally from the need to maintain a clear professional role, and not obviously from an ideological opposition to euthanasia. While some respondents acknowledged that there are difficult cases that require considered reflection upon one's intention, and where there may be some ‘mental gymnastics,’ the nearly unanimous view was that it is important, even in these difficult cases, to cultivate an intention that focuses exclusively on the relief of symptoms. We present four narratives of ‘terminal’ sedation – cases where sedation was administered in significant doses just before death, and may well have hastened death. Considerable ambiguities of intention were evident in some instances, but the discussion around these clearly exceptional cases illustrates the importance of intention to palliative care specialists in maintaining their professional roles.     

Recommendations on COVID-19 triage: international comparison and ethical analysis

On March 11, 2020 the World Health Organization classified COVID-19, caused by Sars-CoV-2, as a pandemic. Although not much was known about the new virus, the first outbreaks in China and Italy showed that potentially a large number of people worldwide could fall critically ill in a short period of time. A shortage of ventilators and intensive care resources was expected in many countries, leading to concerns about restrictions of medical care and preventable deaths. In order to be prepared for this challenging situation, national triage guidance has been developed or adapted from former influenza pandemic guidelines in an increasing number of countries over the past few months. In this article, we provide a comparative analysis of triage recommendations from selected national and international professional societies, including Australia/New Zealand, Belgium, Canada, Germany, Great Britain, Italy, Pakistan, South Africa, Switzerland, the United States, and the International Society of Critical Care Medicine. We describe areas of consensus, including the importance of prognosis, patient will, transparency of the decision-making process, and psychosocial support for staff, as well as the role of justice and benefit maximization as core principles. We then probe areas of disagreement, such as the role of survival versus outcome, long-term versus short-term prognosis, the use of age and comorbidities as triage criteria, priority groups and potential tiebreakers such as ‘lottery’ or ‘first come, first served’. Having explored a number of tensions in current guidance, we conclude with a suggestion for framework conditions that are clear, consistent and implementable. This analysis is intended to advance the ongoing debate regarding the fair allocation of limited resources and may be relevant for future policy-making.     

Ovine lymphocyte antigens: a comparison of Australian and European antisera

Lymphocyte alloantigens were determined in 183 Australian merino sheep, using antisera from Australian and European laboratories. The study had two aims: (1) to compare reagents characterized in the different laboratories and to correlate antigen definition; and (2) to define lymphocyte antigens for use as genetic markers in two flocks of sheep which had been selectively bred for resistance or susceptibility to the intestinal parasite Trichostrongylus colubriformis, in order to extend a previous study which had indicated linkage between resistance to the parasite and the sheep major histocompatibility system. Good or excellent correspondence was found between four Australian and four European specificities and it was concluded that continued international collaboration would allow definition of markers for future genetic or disease susceptibility studies.     

诱集植物在害虫治理中的最新研究进展

诱集植物作为一种传统的害虫治理工具,在农业生产中的应用越来越广泛,其重要性也随着时间推移日益凸显。本文结合国内外研究现状,从特点、应用、优势和发展前景等方面综述了诱集植物在害虫生态控制中的重要作用。同时以香根草为例具体说明了诱集植物的应用方法,为诱集植物的利用与开发提供参考。     

BEACON: automated tool for Bacterial GEnome Annotation ComparisON

Background

Genome annotation is one way of summarizing the existing knowledge about genomic characteristics of an organism. There has been an increased interest during the last several decades in computer-based structural and functional genome annotation. Many methods for this purpose have been developed for eukaryotes and prokaryotes. Our study focuses on comparison of functional annotations of prokaryotic genomes. To the best of our knowledge there is no fully automated system for detailed comparison of functional genome annotations generated by different annotation methods (AMs).

Results

The presence of many AMs and development of new ones introduce needs to: a/ compare different annotations for a single genome, and b/ generate annotation by combining individual ones. To address these issues we developed an Automated Tool for Bacterial GEnome Annotation ComparisON (BEACON) that benefits both AM developers and annotation analysers. BEACON provides detailed comparison of gene function annotations of prokaryotic genomes obtained by different AMs and generates extended annotations through combination of individual ones. For the illustration of BEACON’s utility, we provide a comparison analysis of multiple different annotations generated for four genomes and show on these examples that the extended annotation can increase the number of genes annotated by putative functions up to 27 %, while the number of genes without any function assignment is reduced.

Conclusions

We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1826-4) contains supplementary material, which is available to authorized users.     

Community Members' Engagement with and Involvement in Genomic Research: Lessons to Learn from the Field

In this paper, we describe the potential role laypersons on ethics committees can play in ensuring community concerns are addressed in the design and implementation of genomic research. We draw inferences from the outcome of an empirical study of the impact of training of laypersons to address community engagement issues in ethics review of research protocol. While this paper does not advocate a particular solution, it describes the importance of community engagement in genomic research, the current limitations there are in engaging communities in the design of these research projects and how communities can be indirectly engaged in the design and implementation of genomic research through the engagement of laypersons on ethics committees. However, to ensure that these laypersons can play this role, their capacity needs to be built to play this role appropriately. There is evidence to show that where resources are invested in building the capacity of laypersons to play their role as community ‘watchdogs’ in research, they play this role aptly. Community engagement is important in genomic research as genomic researchers will increasingly require community perspectives in critical ethics decision making.     

Developing Clinical Research Relationship: Views from Within

The nature of the relationship between clinical investigator and research participant continues to be contested. The related discussions have largely focused on the doctor‐researcher dichotomy thought to permeate the work of a clinical investigator with research participants, whom in turn occupy two corresponding roles: patient and subject. This paper contributes to current debates on the topic by providing a voice to research participants, whose perspectives have been largely invisible. It draws on 42 in‐depth interviews conducted in Ghana and South Africa with respondents at different stages of involvement in clinical research, ranging from no experience in clinical research to enrollment in several clinical trials. The perspectives of all respondents were largely congruent and rooted in the common view that clinical research contributed to the improvement of local health. They went beyond the researcher/participant versus doctor/patient dichotomy, long established in research ethics, and preferred to view participants and investigators as partners working together to find ways to address local health needs. The conceptualization of investigator‐participant relations as a partnership reinforced expectations of care, transparency and accountability, which were viewed as necessary expressions of mutuality and respect within equal collaborations. It is important to engage with these views in order to avoid antagonizing societal expectations and to build up long‐term public trust, crucial for the continuous operation of clinical research.