Engaging Diverse Social and Cultural Worlds: Perspectives on Benefits in International Clinical Research From South African Communities

The issue of benefits in international clinical research is highly controversial. Against the background of wide recognition of the need to share benefits of research, the nature of benefits remains strongly contested. Little is known about the perspectives of research populations on this issue and the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. This exploratory study contributes to filling this void by examining perspectives of people in low‐income South African communities on benefits in international clinical research. Twenty‐four individuals with and without experience of being involved in clinical research participated in in‐depth interviews. Respondents felt that ancillary care should be provided to clinical research participants, while a clinical study conducted in particular community should bring better health to its members through post‐trial benefits. Respondents' perspectives were grounded in the perception that the ultimate goal of international clinical research is to improve local health. We argue that perspectives and understandings of the respondents are shaped by local moral traditions rather than clinical research specificities and require attention as valid moral claims. It is necessary to acknowledge such claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting expectations.     

The benefit sharing vision of H3Africa

One of the central ethical tenets of research in developing countries is the sponsor's obligation to benefit host participants and communities. Two known models of benefits provision dominate the ethical discourse of research in developing countries. The first model, known as the “reasonable availability,” endorses the obligation to provide interventions proven to be effective at the end of a study. This contrasts with the second model, known as “fair benefits,” which endorses other forms of benefits that host communities may deem as fair beyond those derived directly from the study's findings. This paper explores a third benefit model consistent with the writings of the Human Hereditary and Health in Africa (H3Africa) research initiative. The H3Africa—a North‐South collaborative initiative predicated by U.S. National Institutes of Health, the Wellcome Trust and the African Society of Human Genetics upholds a benefit model that endorses capacity building as the primary obligation of its research agenda. This is evident by the endorsement of mechanisms to strengthen capacity building in its research projects. While capacity building remains a plausible means of improving the expertise, quality and independence of research in Africa, sustainable measures are needed to realizing the full potential for African‐led research on the continent.     

Women in developing countries and benefit sharing

The aim of this paper is to show that any process of benefit sharing that does not guarantee the representation and participation of women in the decision-making process, as well as in the distribution of benefits, contravenes a central demand of social justice. It is argued that women, particularly in developing countries, can be excluded from benefits derived from genetic research because of existing social structures that promote and maintain discrimination. The paper describes how the structural problem of gender-based inequity can impact on benefit sharing processes. At the same time, examples are given of poor women's ability to organise themselves and to achieve social benefits for entire communities. Relevant international guidelines (e.g. the Convention on Biodiversity) recognise the importance of women's contributions to the protection of biodiversity and thereby, implicitly, their right to a share of the benefits, but no mechanism is outlined on how to bring this about. The authors make a clear recommendation to ensure women's participation in benefit sharing negotiations by demanding seats at the negotiation table.     

Research Stakeholders’ Views on Benefits and Challenges for Public Health Research Data Sharing in Kenya: The Importance of Trust and Social Relations

Background

There is increasing recognition of the importance of sharing research data within the international scientific community, but also of the ethical and social challenges this presents, particularly in the context of structural inequities and varied capacity in international research. Public involvement is essential to building locally responsive research policies, including on data sharing, but little research has involved stakeholders from low-to-middle income countries.

Methods

Between January and June 2014, a qualitative study was conducted in Kenya involving sixty stakeholders with varying experiences of research in a deliberative process to explore views on benefits and challenges in research data sharing. In-depth interviews and extended small group discussions based on information sharing and facilitated debate were used to collect data. Data were analysed using Framework Analysis, and charting flow and dynamics in debates.

Findings

The findings highlight both the opportunities and challenges of communicating about this complex and relatively novel topic for many stakeholders. For more and less research-experienced stakeholders, ethical research data sharing is likely to rest on the development and implementation of appropriate trust-building processes, linked to local perceptions of benefits and challenges. The central nature of trust is underpinned by uncertainties around who might request what data, for what purpose and when. Key benefits perceived in this consultation were concerned with the promotion of public health through science, with legitimate beneficiaries defined differently by different groups. Important challenges were risks to the interests of study participants, communities and originating researchers through stigmatisation, loss of privacy, impacting autonomy and unfair competition, including through forms of intentional and unintentional ''misuse'' of data. Risks were also seen for science.

Discussion

Given background structural inequities in much international research, building trust in this low-to-middle income setting includes ensuring that the interests of study participants, primary communities and originating researchers will be promoted as far as possible, as well as protected. Important ways of building trust in data sharing include involving the public in policy development and implementation, promoting scientific collaborations around data sharing and building close partnerships between researchers and government health authorities to provide checks and balances on data sharing, and promote near and long-term translational benefits.     

BENEFITS TO RESEARCH SUBJECTS IN INTERNATIONAL TRIALS: DO THEY REDUCE EXPLOITATION OR INCREASE UNDUE INDUCEMENT?

There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally‐sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. It proceeds from the premise that there are good grounds for thinking that, at least some, international research sponsors exploit trial participants because they do not provide the research population with a fair share of the benefits of research. This provides a prima facie argument for increasing the benefits for research participants. Concern over undue inducement is a legitimate moral concern; however, if this concern is to prevent research populations from receiving their fair share of benefits from research there must be sufficient evidence that these benefits will unduly influence patients’ decision‐making regarding trial participation. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants’ motivations and the influence of payments on research subjects’ behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects’ behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants.     

Collaborative research partnerships inform monitoring and management of aquatic ecosystems by Indigenous rangers

Aquatic ecosystems are critical to the long-term viability and vibrancy of communities and economies across northern Australia. In a region that supports significant cultural and ecological water values, partnerships between Indigenous and non-Indigenous stakeholders can benefit aquatic ecosystem management. We present, as a case study from the Kimberley region of Western Australia, a collaborative research program that successfully documented Indigenous and Western Scientific knowledge of remote wetlands, using a variety of field-based activities, questionnaires, interviews and workshops. The sharing of knowledge between Indigenous and non-Indigenous research partners facilitated a comprehensive understanding of ecosystem values, threats, processes, management priorities and aspirations. These formed the basis of a management plan and monitoring tools, designed to build the capacity of an Indigenous ranger group to engage in research, monitoring and management of wetlands. The project provides a useful example of the benefits of collaborations in the context of remote-area management where local communities are responsible for environmental management and monitoring, such as is the case in northern Australia and presumably other areas of the world.     

The evolution of cooperation by negotiation in a noisy world

Cooperative interactions among individuals are ubiquitous despite the possibility of exploitation by selfish free riders. One mechanism that may promote cooperation is ‘negotiation’: individuals altering their behaviour in response to the behaviour of others. Negotiating individuals decide their actions through a recursive process of reciprocal observation, thereby reducing the possibility of free riding. Evolutionary games with response rules have shown that infinitely many forms of the rule can be evolutionarily stable simultaneously, unless there is variation in individual quality. This potentially restricts the conditions under which negotiation could maintain cooperation. Organisms interact with one another in a noisy world in which cooperative effort and the assessment of effort may be subject to error. Here, we show that such noise can make the number of evolutionarily stable rules finite, even without quality variation, and so noise could help maintain cooperative behaviour. We show that the curvature of the benefit function is the key factor determining whether individuals invest more or less as their partner's investment increases, investing less when the benefit to investment has diminishing returns. If the benefits of low investment are very small then behavioural flexibility tends to promote cooperation, because negotiation enables cooperators to reach large benefits. Under some conditions, this leads to a repeating cycle in which cooperative behaviour rises and falls over time, which may explain between‐population differences in cooperative behaviour. In other conditions, negotiation leads to extremely high levels of cooperative behaviour, suggesting that behavioural flexibility could facilitate the evolution of eusociality in the absence of high relatedness.     

Administrator of global biodiversity: The secretariat of the convention on biological diversity

The paper presents a case study analysing the effects of the Secretariat of the Convention on Biological Diversity as an intergovernmental organisation. Within the study, the effects of organisations are measured by their outcome, i.e. the influence on the behaviour of other actors such as national governments. Three forms of outcomes are being distinguished, namely knowledge brokerage and diffusion, capacity building, and negotiation facilitation. In addition, the paper tries to explain the observed effects on the basis of internal and external variables. The CBD Secretariat has been established in 1992 and is now located in Montreal with about 70 employees. As most other secretariats of international conventions, it is the main organiser and facilitator of the convention process. The empirical material shows that the Secretariat has a measurable influence on the intergovernmental cooperative process which can be attributed to the effective internal management processes and the qualities of its leaders. Lacking capacity building functions and highly selective effects with regard to the provision of knowledge are explained by the limited formal autonomy and the structure of the global biodiversity problem.     

A research agenda for helminth diseases of humans: health research and capacity building in disease-endemic countries for helminthiases control

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and low-income regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North-South "partnerships". There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the "North" and the developing countries of the "South". We argue that investing in South-South collaborative research policies and capacity is as important as their North-South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination.     

Host control over infection and proliferation of a cheater symbiont

Host control mechanisms are thought to be critical for selecting against cheater mutants in symbiont populations. Here, we provide the first experimental test of a legume host’s ability to constrain the infection and proliferation of a native‐occurring rhizobial cheater. Lotus strigosus hosts were experimentally inoculated with pairs of Bradyrhizobium strains that naturally vary in symbiotic benefit, including a cheater strain that proliferates in the roots of singly infected hosts, yet provides zero growth benefits. Within co‐infected hosts, the cheater exhibited lower infection rates than competing beneficial strains and grew to smaller population sizes within those nodules. In vitro assays revealed that infection‐rate differences among competing strains were not caused by variation in rhizobial growth rate or interstrain toxicity. These results can explain how a rapidly growing cheater symbiont – that exhibits a massive fitness advantage in single infections – can be prevented from sweeping through a beneficial population of symbionts.     

Interspecific conflict and the evolution of ineffective rhizobia

Microbial symbionts exhibit broad genotypic variation in their fitness effects on hosts, leaving hosts vulnerable to costly partnerships. Interspecific conflict and partner‐maladaptation are frameworks to explain this variation, with different implications for mutualism stability. We investigated the mutualist service of nitrogen fixation in a metapopulation of root‐nodule forming Bradyrhizobium symbionts in Acmispon hosts. We uncovered Bradyrhizobium genotypes that provide negligible mutualist services to hosts and had superior in planta fitness during clonal infections, consistent with cheater strains that destabilise mutualisms. Interspecific conflict was also confirmed at the metapopulation level – by a significant negative association between the fitness benefits provided by Bradyrhizobium genotypes and their local genotype frequencies – indicating that selection favours cheating rhizobia. Legumes have mechanisms to defend against rhizobia that fail to fix sufficient nitrogen, but these data support predictions that rhizobia can subvert plant defenses and evolve to exploit hosts.     

Justice and Medical Research: A Global Perspective

Economic globalization has profound implications for health. The scale of injustice at a global level, reflected in inexorably widening disparities in wealth and health, also has critical implications for health related research – in particular when the opportunities for exploiting research subjects are carefully considered. The challenge of developing universal guidelines for international clinical research is addressed against the background of a polarizing, yet interdependent, world in which all are ultimately threatened by lack of social justice. It is proposed that in such a world there is a need for new ways of thinking about research and its relevance to health at a global level. Responsibility to use knowledge and power wisely requires more radical changes to guidelines for research ethics than are currently under consideration.     

Venom is beneficial but not essential for development and survival of Nasonia

1. Parasitoid wasps sting and inject venom into arthropod hosts, which alters host metabolism and development while keeping the host alive for several days, presumably to induce benefits for the parasitoid young. 2. This study investigates the consequences of host envenomation on development and fitness of wasp larvae in the ectoparasitoid Nasonia vitripennis, by comparing wasps reared on live unstung, previously stung, and cold‐killed hosts. Developmental arrest and suppression of host response to larvae are major venom effects that occur in both stung and cold‐killed hosts, but not in unstung hosts, whereas cold‐killed hosts lack venom effects that require a living host. Thus, cold‐killed hosts mimic some of the effects of venom, but not others. 3. Eggs placed on live unstung hosts have significantly higher mortality during development; however, successfully developing wasps from these hosts have similar lifetime fecundity to that of wasps from cold‐killed or stung hosts. Therefore, although venom is beneficial, it is not required for wasp survival. 4. While wasps developing on both cold‐killed and stung hosts have similar fitness levels, rearing multiple generations on cold‐killed hosts results in significant fitness reductions of wasps. 5. It is concluded that the largest benefits of venom are induction of host developmental arrest and suppression of host response to larva (e.g. immune responses), although more subtle benefits may accrue across generations or under stressful conditions.     

“2020年后全球生物多样性框架”的谈判进展以及对我国的建议

“2020年后全球生物多样性框架”是当前《生物多样性公约》谈判的焦点议题, 了解该议题的谈判进展将对我国顺利举办第15次缔约方大会(COP15)产生积极的作用。本文在梳理相关谈判进程的基础上, 分析了各方主要观点, 并就我国应对国际谈判并以东道国身份推进该框架的制定进程提出了建议。各方对制定框架的时间表、程序和一般性原则形成了较为一致的共识, 认为应尽快确定“2020年后全球生物多样性框架”的程序及时间表, 基于“爱知生物多样性目标”的执行经验、科学结论和和广泛的信息来源, 与“可持续发展目标”及其他国际进程衔接, 重视利用情景和模型, 并支持更多利益相关方参与制定过程。同时, 各方认为框架应主要包括土地利用、保护和恢复生物多样性的措施、解决生物多样性丧失的根本原因、主流化、能力建设、资源调动、国家承诺等要素。为应对国际谈判, 建议我国在《公约》谈判会议中适时提出以下观点: 重视实现可持续利用相关的目标; 提升评估指标体系的合理性; 科学制定措施。此外, 建议我国采取以下措施积极推进框架制定进程: 充分利用国际高级别会议, 提升政治重视程度; 积极与主要国际进程协作, 推进该框架深入讨论; 重视调动利益相关方积极性。     

Challenges faced by research ethics committees in El Salvador: results from a focus group study

Objective:  To identify perceived barriers to capacity building for local research ethics oversight in El Salvador, and to set an agenda for international collaborative capacity building.
Methods:  Focus groups were formed in El Salvador which included 17 local clinical investigators and members of newly formed research ethics committees. Information about the proposed research was presented to participants during an international bioethics colloquium sponsored and organized by the St. Jude Children's Research Hospital in collaboration with the National Ethics Committee of El Salvador and the University of El Salvador. Interviews with the focus group participants were qualitatively analyzed.
Results:  Participants expressed the need to tailor the informed consent process and documentation to the local culture; for example, allowing family members to participate in decision-making, and employing shorter consent forms. Participants indicated that economic barriers often impede efforts in local capacity building. Participants valued international collaboration for mutual capacity building in research ethics oversight.
Conclusions:  Research ethics committees in El Salvador possess a basic knowledge of locally relevant ethical principles, though they need more training to optimize the application of bioethical principles and models to their particular contexts. Challenges increase the value of collaborative exchanges with ethics committee members in the United States. Further research on facilitating communication between host country and sponsor country ethics committees can maximize local research ethics expertise, and thus raise the standard of protecting human participants involved in international research.     

新世纪的中国昆虫系统学

对未来我国昆虫系统学在能力建设、物种编目、理论研究、技术创新和国际合作等方面提出一系列建议。在昆虫系统学能力建设方面,政府和科学家应该在生物分类学能力评估、基础硬件建设、各级生物标本馆中建立伙伴关系（包括标本采集、标本馆管理、 科学研究、 知识共享和标本与资料交换）等方面重点开展工作。在物种编目方面,我国的昆虫物种编目有赖于各级政府和机构继续关注标本的收集和保藏,继续启动一些考察项目,以满足发现和认识昆虫物种的实际需求。在物种水平上研究以往昆虫系统学家的工作,进行地区性和世界性的昆虫类群的订正更是非常必要的。在理论研究方面,我国昆虫系统应该在下列方面积极探索：物种概念、进化理论、比较生物学理论和高级分类系统研究。在技术创新方面,我国的昆虫系统学家应该在数据库与网络技术应用、图形图像处理技术、专家鉴定系统技术、分类性状分析技术、分子生物学技术、系统发育推断程序、信息统一管理技术和知识传播技术等方面进行深入研究,以满足昆虫系统学的发展需求。在国际合作方面,要进一步推动我国昆虫系统学研究机构加入生物分类学全球战略联盟、加入各种相关国际相关组织,要促进物种信息管理系统的建立与共享,要推动研究项目国际化。     

Regional Maritime Regime Building: Prospects in Northeast and Southeast Asia

Maritime issues are rising to the forefront of Asian security concerns. But maritime management regimes can constrain conflict and create confidence in co-operation. Such regimes can define the range of permissible state behavior and resolve dilemmas stemming from the sharing of common resources. Regimes originate through imposition, spontaneous processes, or negotiation and are supplied when there is sufficient demand for the functions they perform. Integrative forces that support regime formation are the existence of other international arrangements in the region; ethnic, cultural, or historical interstate relationships; and clear indications of benefits to be gained. Often a shock or crisis enhances regime formation or its robustness. Disintegrative forces include political or territorial differences, competition for leadership, and opposition to regionalism. In regional co-operation on maritime issues, Southeast Asia is clearly more advanced than Northeast Asia. However, the absence of robust multilateral maritime regimes in Asia reflects state perceptions that the costs outweigh the benefits. The primacy of dis-integrative factors argues strongly for an ad hoc, issue-specific, evolutionary process for multilateral maritime regime building in Asia.     

Coevolution of virulence and immunosuppression in multiple infections

Many components of host–parasite interactions have been shown to affect the way virulence (i.e. parasite‐induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive adaptation of parasites affects and coevolves with virulence in multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double‐edged sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host (as more opportunities for transmission will be forgone if the host dies). The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade‐off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.     

Building International Indigenous People’s Partnerships for Community-Driven Health Initiatives

In this article we present an international Indigenous people’s partnership project co-led by two Indigenous communities, Musqueam (Coast Salish, Canada) and Totoras (Quichua, Ecuador), as a community-driven health initiative. The Musqueam-Totoras partnership includes Indigenous organizations, universities, international agencies, government, and nongovernmental organizations to address Indigenous health concerns in both communities. Our collaborative approach provides a framework to (a) increase the development expertise of Indigenous people internationally, (b) increase skills among all participants, and (c) facilitate Indigenous knowledge mobilization and translation to promote cultural continuity. This international Indigenous people’s partnership between north and south reflects the diversity and commonalities of Indigenous knowledge, contributes to cultural revitalization, and minimizes the impact of assimilation, technology, and globalization. Indigenous people’s partnerships contribute to self-determination, which is a prerequisite to the building and maintenance of healthy communities and the promotion of social justice. The exchange of Indigenous knowledge upholds Indigenous values of respect, reciprocity, relevance, and responsibility. Given the history of colonization and the negligence of governments in the exercising of these values with respect to Indigenous communities, this contemporary exchange among Indigenous people in the Americas serves to reclaim these values and practices. International cooperation empowering Indigenous people and other marginalized groups has become fundamental for their advancement and participation in globalized economies. An international Indigenous people’s partnership provides opportunities for sharing cultural, historical, social, environmental, and economic factors impacting Indigenous health. These partnerships also create beneficial learning experiences in community-based participatory research and community-driven health initiatives, provide culturally sensitive research ethics frameworks, increase capacity building, and address basic human needs identified by participating communities.     

A niche perspective on the range expansion of symbionts

Range expansion results from complex eco‐evolutionary processes where range dynamics and niche shifts interact in a novel physical space and/or environment, with scale playing a major role. Obligate symbionts (i.e. organisms permanently living on hosts) differ from free‐living organisms in that they depend on strong biotic interactions with their hosts which alter their niche and spatial dynamics. A symbiotic lifestyle modifies organism–environment relationships across levels of organisation, from individuals to geographical ranges. These changes influence how symbionts experience colonisation and, by extension, range expansion. Here, we investigate the potential implications of a symbiotic lifestyle on range expansion capacity. We present a unified conceptual overview on range expansion of symbionts that integrates concepts grounded in niche and metapopulation theories. Overall, we explain how niche‐driven and dispersal‐driven processes govern symbiont range dynamics through their interaction across scales, from host switching to geographical range shifts. First, we describe a background framework for range dynamics based on metapopulation concepts applied to symbiont organisation levels. Then, we integrate metapopulation processes operating in the physical space with niche dynamics grounded in the environmental arena. For this purpose, we provide a definition of the biotope (i.e. living place) specific to symbionts as a hinge concept to link the physical and environmental spaces, wherein the biotope unit is a metapopulation patch (either a host individual or a land fragment). Further, we highlight the dual nature of the symbionts' niche, which is characterised by both host traits and the external environment, and define proper conceptual variants to provide a meaningful unification of niche, biotope and symbiont organisation levels. We also explore variation across systems in the relative relevance of both external environment and host traits to the symbiont's niche and their potential implications on range expansion. We describe in detail the potential mechanisms by which hosts, through their function as biotopes, could influence how some symbionts expand their range – depending on the life history and traits of both associates. From the spatial point of view, hosts can extend symbiont dispersal range via host‐mediated dispersal, although the requirement for among‐host dispersal can challenge symbiont range expansion. From the niche point of view, homeostatic properties of host bodies may allow symbiont populations to become insensitive to off‐host environmental gradients during host‐mediated dispersal. These two potential benefits of the symbiont–host interaction can enhance symbiont range expansion capacity. On the other hand, the central role of hosts governing the symbiont niche makes symbionts strongly dependent on the availability of suitable hosts. Thus, environmental, dispersal and biotic barriers faced by suitable hosts apply also to the symbiont, unless eventual opportunities for host switching allow the symbiont to expand its repertoire of suitable hosts (thus expanding its fundamental niche). Finally, symbionts can also improve their range expansion capacity through their impacts on hosts, via protecting their affiliated hosts from environmental harshness through biotic facilitation.