Addressing the challenge for expedient ethical review of research in disasters and disease outbreaks

Guideline 20 of the updated International Ethics Guidelines for Health‐related Research Involving Humans (2016) by the Council for International Organizations of Medical Sciences (CIOMS) provides guidance on research in disasters and disease outbreaks against the background of the need to generate knowledge quickly, overcome practical impediments to implementing such research, and the need to maintain public trust. The guideline recommends that research ethics committees could pre‐screen study protocols to expedite ethical reviews in a situation of crisis, that pre‐arrangements be made regarding data sharing and biomedical sample sharing, and that sponsors and research ethics committees seek to minimize risk to researchers conducting research during a disaster. This paper critiques these recommendations against the background of the findings of a survey of public health officials and chairs of research ethics committees in the Caribbean during 2016, which sought to determine the best template for the expeditious ethical review of research proposals in emergency and epidemic situations in the Caribbean, and whose findings can serve as a model for other low‐ and middle‐income countries.     

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.     

The acetycholinesterase gene ofAnopheles stephensi

1. The acetylcholinesterase (AChE) gene from the important malaria vector Anopheles stephensi has been isolated by homology to the Drosophila acetylcholinesterase gene. 2. The complete sequence and intron-exon organization has been determined. The encoded protein has 69% identity to Drosophila AChE and 38 and 36% identity to Torpedo AChE and human butyrylcholinesterase, respectively.     

Conceptual,methodological and ethical issues in genetic engineering (1989)

An introduction to the potential of gene therapy to alleviate illness and death particularly for many rare human genetic disorders and specific forms of cancer is presented. At present, genetic engineering, that is gene therapy to correct some of these disorders based on new molecular biology procedures is a possibility in the near future especially those with single gene mendelian inherited transmission. After a short, comprehensive overview about the molecular biology of genetic engineering, a presentation of many of the ethical issues now under discussion by the international scientific community, world govenmental agencies and concerned laymen about the complex and sensitive ethical issues is provided. A report about a case history of investigators in the United States who disregarded current restrictions emphasized the concern of the scientific community as well as the governmental agencies in maintaining stepwise, careful approach to the introduction of the new, molecular methodologies. The continued maintenance of many of these restrictions, suggested by some ethicists, even after the threat of uncontrolled biological disorder as a result of these new procedures was found to be erroneous is discussed and challenged.     

Adjusting the focus: A public health ethics approach to data research

This paper contends that a research ethics approach to the regulation of health data research is unhelpful in the era of population‐level research and big data because it results in a primary focus on consent (meta‐, broad, dynamic and/or specific consent). Two recent guidelines – the 2016 WMA Declaration of Taipei on ethical considerations regarding health databases and biobanks and the revised CIOMS International ethical guidelines for health‐related research involving humans – both focus on the growing reliance on health data for research. But as research ethics documents, they remain (to varying degrees) focused on consent and individual control of data use. Many current and future uses of health data make individual consent impractical, if not impossible. Many of the risks of secondary data use apply to communities and stakeholders rather than individual data subjects. Shifting from a research ethics perspective to a public health lens brings a different set of issues into view: how are the benefits and burdens of data use distributed, how can data research empower communities, who has legitimate decision‐making capacity? I propose that a public health ethics framework – based on public benefit, proportionality, equity, trust and accountability – provides more appropriate tools for assessing the ethical uses of health data. The main advantage of a public health approach for data research is that it is more likely to foster debate about power, justice and equity and to highlight the complexity of deciding when data use is in the public interest.     

The Anopheles albimanus white gene: molecular characterization of the gene and a spontaneous white gene mutation

We have cloned and characterized the white gene of Anopheles albimanus. Comparison of the deduced amino acid sequence of this white gene with its homologs from six species of Diptera show that the An. albimanus gene is most similar to the white gene of An. gambiae (92% identity). A spontaneous white-eyed mutant An. albimanus was caused by an approximately 10 kb insertion into a CT dinucleotide repeat region of intron 2 of the white locus. The flanks of this insertion are long (at least 400 bp), nearly perfect inverted terminal repeat sequences. This cloned white gene should be useful as a marker for germ line transformation of An. albimanus. This revised version was published online in July 2006 with corrections to the Cover Date.     

A killer-rescue system for self-limiting gene drive of anti-pathogen constructs

A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2:1 release (engineered:wild) or after four 1:2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.     

基因兴奋剂

人类基因组计划的完成为基因治疗提供了依据,同时也给基因兴奋剂的产生创造了条件。本文通过综述基因兴奋剂的概念、产生的分子机制,讨论了可能被用作基因兴奋剂的基因,并从基因、转录和蛋白质三个水平探讨了基因兴奋剂的检测策略。     

The effect of landscape processes upon gene flow and genetic diversity in an Australian freshwater fish, Neosilurus hyrtlii

1. Flow regime and riverine architecture are two important landscape characteristics that influence genetic diversity and gene flow in riverine species.
2. Using population genetic markers (mtDNA, microsatellites and allozymes), this study aimed to investigate genetic diversity and gene flow in the freshwater fish, Neosilurus hyrtlii , across two major drainage divisions in northern and central Australia (the Gulf of Carpentaria and Lake Eyre basins). These basins lie adjacent to each other and differ in their hydrological inputs and riverine structure, providing an ideal opportunity to identify the impact of landscape processes upon population dynamics of freshwater fish.
3. Populations were strongly structured among basins, among catchments within basins and were weakly structured within catchments in the Lake Eyre Basin, providing support for the Stream Hierarchy Model.
4. Interestingly, mtDNA and microsatellite diversity was much higher in the Gulf of Carpentaria Basin compared to the Lake Eyre Basin. It was concluded that this difference was due to the extreme hydrological variability in this basin and boom-bust population cycles resulting in smaller effective population sizes in the Lake Eyre Basin.     

以科研促进基因工程的教学

基因工程课程是生物专业一门重要的必修基础课程;培养学生综合素质是该课程的重点。因此,将科研充实到教学环节中,实现教学内容、教学方法的先进性,将有利于提高教学效果和质量。     

No ethical divide between China and the West in human embryo research

This is a discussion of the reaction to the recent research article publication in the journal Protein & Cell by a group of scientists at Sun Yat‐sen University using the CRISPR/Cas9 technique on editing non‐viable human zygotes. Many commentators condemned the Chinese scientists for overstepping ethical boundaries long accepted in Western countries and accused China of having lax regulations on genomic research in general. We argue that not only did this research follow strict ethical standards and fully comply with current regulations, but China also has a well‐developed regulatory framework governing such research comparable to many developed countries. We see the reactions among Western commentators as a misunderstanding of the current situation and an expression of a lack of willingness to acknowledge China as an equal partner in the international debate about proper limits to the development of new biotechnologies.     

Ethical Issues in Field Trials of Genetically Modified Disease‐Resistant Mosquitoes

Mosquito‐borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito‐borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases. This article focuses on ethical issues raised by field trials of disease‐resistant, genetically modified mosquitoes. Some of these issues include: protecting the public and the environment from harm, balancing benefits and risks, collaborating with the local community, avoiding exploitation, and safeguarding the rights and welfare of research subjects. One of the most difficult problems involves protecting the welfare of community members who will be impacted by the release of mosquitoes but who are not enrolled in the study as research subjects. To address this concern, field trials should take place only when the targeted disease is a significant public health problem in an isolated area, the benefits of the trial for the community are likely to outweigh the risks, community leaders approve of the trial, and there are measures in place to protect the welfare of un‐enrolled community members, such as informing the community about the study and offering free treatment to people who contract mosquito‐borne diseases. Since the justification of any field trial depends on a careful examination of the scientific and ethical issues, proposed studies should be evaluated on a case‐by‐case basis.     

Ethical models underpinning responses to threats to public health: a comparison of approaches to communicable disease control in Europe

Increases in international travel and migratory flows have enabled infectious diseases to emerge and spread more rapidly than ever before. Hence, it is increasingly easy for local infectious diseases to become global infectious diseases (GIDs). National governments must be able to react quickly and effectively to GIDs, whether naturally occurring or intentionally instigated by bioterrorism. According to the World Health Organisation, global partnerships are necessary to gather the most up-to-date information and to mobilize resources to tackle GIDs when necessary. Communicable disease control also depends upon national public health laws and policies. The containment of an infectious disease typically involves detection, notification, quarantine and isolation of actual or suspected cases; the protection and monitoring of those not infected; and possibly even treatment. Some measures are clearly contentious and raise conflicts between individual and societal interests. In Europe national policies against infectious diseases are very heterogeneous. Some countries have a more communitarian approach to public health ethics, in which the interests of individual and society are more closely intertwined and interdependent, while others take a more liberal approach and give priority to individual freedoms in communicable disease control. This paper provides an overview of the different policies around communicable disease control that exist across a select number of countries across Europe. It then proposes ethical arguments to be considered in the making of public health laws, mostly concerning their effectiveness for public health protection.     

Clinical research law in Jordan: an ethical analysis

An ethical analysis of Jordan's Clinical Research Law, which became effective in 2001, was performed. Accordingly, this paper discusses the major components, key strengths and weaknesses of this law. As an initial effort, the Law addresses important aspects of research ethics and, hence, should serve as an example for other Arab Countries in the Middle East. Unique aspects of the Law include the requirement that those conducting any study have insurance that can compensate for research injuries and a system of fines and punishments for noncompliance with the Law. There are, however, some key items missing in the Jordanian Law. For example, the Law does not mention the requirement of a favourable assessment of risks and benefits, the fair selection of subjects, or articles regarding the protection of the rights and welfare of children and other vulnerable subjects participating in research. The paper concludes with the suggestion that new amendments should be considered for future revisions of the Clinical Research Law in Jordan.     

基因编辑技术及其在中国的研究发展

基因编辑技术是一种能够对生物体的基因组及其转录产物进行定点修饰或者修改的技术,早期基因编辑技术包括归巢内切酶、锌指核酸内切酶和类转录激活因子效应物。近年来,以CRISPR/Cas9系统为代表的新型技术使基因编辑的研究和应用领域得以迅速拓展。本文对基因编辑技术的原理、技术发展及其应用进行了阐述,对我国在基因编辑机制研究及技术发展、基因编辑动植物模型构建、基因治疗等领域的研究进展进行了回顾,并对基因技术的发展前景及趋势进行了展望。     

Making gene drive biodegradable

Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases''.     

Bystanders and ethical review of research: Proceed with caution

Scientists seeking to conduct research with human subjects must first submit their proposals to research ethics committees (Institutional Review Boards [IRBs], in the United States). Some of these studies pose risks to “bystanders,” i.e., people who may be affected by the research but who are not enrolled as study subjects. Should IRBs expand their scope to include oversight over possible harms to bystanders as well as research subjects? This paper presents arguments against this step. Prior review of research with human subjects, despite its evident burden on the research enterprise, is a necessary caution, because the tension between the objectives of humane treatment of research subjects and sound scientific design and procedure has in the past led to serious abuses. This rationale is inapplicable in the case of bystanders. Moreover, in view of the many and varied effects of both research practices and scientific advances on the broader public over time, those who may be considered to be “bystanders” may potentially expand without limit; requiring IRBs to anticipate these distant and long-term effects as part of prior ethical review could greatly increase its burden and its deterrent effect on research. While conducting research without concern for serious potential harm to bystanders may be irresponsible and unethical, expanding the scope of prior review by IRBs to include risks to bystanders is not required by the principles governing human subjects research, and the costs and burdens of this expansion may outweigh any expected gains.     

植物景观遗传学研究进展

植物景观遗传学是新兴的景观遗传学交叉学科的一个重要研究方向。目前植物景观遗传学的研究虽落后于动物,但其在生物多样性保护方面具有的巨大潜力不可忽视。从景观特征对遗传结构、环境因素对适应性遗传变异影响两个方面,系统综述了近十年来国际上植物景观遗传学的研究焦点和研究进展,比较了植物景观遗传学与动物景观遗传学研究在研究设计和研究方法上的异同,并基于将来植物景观遗传学由对空间遗传结构的描述发展为对景观遗传效应的量化分析及预测的发展框架,具体针对目前景观特征与遗传结构研究设计的系统性差、遗传结构与景观格局在时间上的误配、适应性位点与环境变量的模糊匹配、中性遗传变异与适应性遗传变异研究的分隔、景观与遗传关系分析方法的局限等五个方面提出了研究对策。     

Reflections on research ethics in a public health emergency: Experiences of Brazilian women affected by Zika

In Brazil, the epicenter of the Zika crisis, brown, black, and indigenous poor women living in municipalities with scarce resources were disproportionally affected. The gendered consequences of the epidemic exposed how intersectional lenses are central to understand the impact of public health emergencies in the lives of women and girls. The demand for Zika-affected children and women to be research participants is relevant for an ethical analysis of participant protection procedures during a crisis. We investigated how women experienced research participation by analyzing their narratives. Two-year-long longitudinal qualitative study in Brazilian sites located in the epidemic's epicenter was performed using mixed methods: ethnography with women from two distinct states and individual semi-structured interviews with five women in different Zika-affected states, four of which were community leaders. All women in the study were mothers or grandmothers of Zika-affected children. Thematic analysis was used for data evaluation. Women perceived being pressured to participate in research and a lack of benefit sharing. Structural determinants of gender inequality, such as its effect on power distribution, were found to impact research participant protection. Formal procedures for research protocols approvals were insufficient in protecting participants because these instruments were unable to account for structural aspects. Communitarian mobilization, through WhatsApp groups, was found to be an important mechanism to create conditions to challenge oppressive structures. Strengthening public health, effective community-based participation in research planning and implantation of ethical strategies that promotes gender equality can have transformative effect on unequal power structures and promote participant protection.     

Antibiotic resistance as a tragedy of the commons: An ethical argument for a tax on antibiotic use in humans

To the extent that antibiotic resistance (ABR) is accelerated by antibiotic consumption and that it represents a serious public health emergency, it is imperative to drastically reduce antibiotic consumption, particularly in high‐income countries. I present the problem of ABR as an instance of the collective action problem known as ‘tragedy of the commons’. I propose that there is a strong ethical justification for taxing certain uses of antibiotics, namely when antibiotics are required to treat minor and self‐limiting infections, such as respiratory tract infections, in otherwise healthy individuals. Taxation would allow a reduction in consumption (given certain behavioural economics assumptions) and/or ensure that individuals internalize or compensate for their contribution to the erosion of the common good of antibiotic effectiveness. I suggest that revenue from the tax could be used to fund conservation and innovation strategies. Taxation might be a coercive policy, especially for certain individuals, but the ethical case for coercive policies is very strong when the good to be preserved is important enough and when they force individuals to do something they have a moral obligation to do anyway. I argue that, in the case of mild and self‐limiting infections, individuals have a moral duty of easy rescue and a moral duty of fairness to make their contribution to the preservation of the common good of antibiotic effectiveness by foregoing antibiotics. I also suggest that taxing antibiotics in such cases is an all things considered ethically justified policy even if it would introduce inequalities in access to healthcare.