Vulnerable Subjects? The Case of Nonhuman Animals in Experimentation

The concept of vulnerability is deployed in bioethics to, amongst other things, identify and remedy harms to participants in research, yet although nonhuman animals in experimentation seem intuitively to be vulnerable, this concept and its attendant protections are rarely applied to research animals. I want to argue, however, that this concept is applicable to nonhuman animals and that a new taxonomy of vulnerability developed in the context of human bioethics can be applied to research animals. This taxonomy does useful explanatory work, helping to pinpoint the limitations of the 3Rs/welfare approach currently adopted in the context of animal experimentation. On this account, the 3Rs/welfare approach fails to deliver for nonhuman animals in experimentation because it effectively addresses only one element of their vulnerability (inherent) and paradoxically through the institution of Animal Ethics Committees intended to protect experimental animals in fact generates new vulnerabilities that exacerbate their already precarious situation.     

Bioethics, vulnerability, and protection

What makes individuals, groups, or even entire countries vulnerable? And why is vulnerability a concern in bioethics? A simple answer to both questions is that vulnerable individuals and groups are subject to exploitation, and exploitation is morally wrong. This analysis is limited to two areas. First is the context of multinational research, in which vulnerable people can be exploited even if they are not harmed, and harmed even if they are not exploited. The type of multinational research likely to raise the most ethical concerns is that in which the investigators or sponsors are from a powerful industrialised country or a giant pharmaceutical company and the research is conducted in a developing country. Second is the situation of women, who are made vulnerable in cultural settings or in entire countries in which they are oppressed and powerless. In the face of cultural values and practices, or governmental policies, these women suffer serious consequences for their health and even lives. Examples are provided, and it is suggested that in some cases vulnerable individuals can be harmed but not exploited. On the positive side, recent developments reveal a new awareness of exploitation and efforts to enhance the ability of developing countries to protect themselves and their citizens from exploitation at the hands of powerful sponsors of research. In addition, human rights principles are increasingly being used to monitor the actions (or inaction) of governments regarding women's reproductive rights and vulnerability with respect to HIV/AIDS, and to take remedial actions.     

VULNERABILITY IN RESEARCH AND HEALTH CARE; DESCRIBING THE ELEPHANT IN THE ROOM?

Despite broad agreement that the vulnerable have a claim to special protection, defining vulnerable persons or populations has proved more difficult than we would like. This is a theoretical as well as a practical problem, as it hinders both convincing justifications for this claim and the practical application of required protections. In this paper, I review consent-based, harm-based, and comprehensive definitions of vulnerability in healthcare and research with human subjects. Although current definitions are subject to critique, their underlying assumptions may be complementary. I propose that we should define vulnerability in research and healthcare as an identifiably increased likelihood of incurring additional or greater wrong. In order to identify the vulnerable, as well as the type of protection that they need, this definition requires that we start from the sorts of wrongs likely to occur and from identifiable increments in the likelihood, or to the likely degree, that these wrongs will occur. It is limited but appropriately so, as it only applies to special protection, not to any protection to which we have a valid claim. Using this definition would clarify that the normative force of claims for special protection does not rest with vulnerability itself, but with pre-existing claims when these are more likely to be denied. Such a clarification could help those who carry responsibility for the protection of vulnerable populations, such as Institutional Review Boards, to define the sort of protection required in a more targeted and effective manner.     

Use of administrative claims data for comparative effectiveness research of rheumatoid arthritis treatments

Observational studies, particularly those using large administrative claims databases, have become increasingly popular sources of comparative effectiveness or comparative safety research. Studies using claims data often face challenges and criticisms due to the lack of certain clinical information, such as lifestyle risk factors, disease severity, and questionable accuracy of disease diagnoses. A novel, claims-based algorithm to evaluate the clinical effectiveness of rheumatoid arthritis medications has been developed and its performance seems promising, although further validation is needed.     

The Vulnerability of Study Participants in the Context of Transnational Biomedical Research: From Conceptual Considerations to Practical Implications

Outsourcing clinical trials sponsored by pharmaceutical companies from industrialized countries to low‐ (middle)‐income countries – summarized as transnational biomedical research (TBR) – has lead to many concerns about ethical standards. Whether study participants are particularly vulnerable is one of those concerns. However, the concept of vulnerability is still vague and varies in its definition. Despite the fact that important international ethical guidelines such as the Declaration of Helsinki by the World Medical Association or the Ethical Guidelines for Biomedical Research Involving Human Subjects by the Council of International Organizations of Medical Sciences refer to vulnerability as ethical principle, each of their approaches are different. To overcome these shortcomings, we analyze and unite different approaches of vulnerability and develop practical criteria in order to operationalize the concept especially for the context of TBR. These criteria refer to the context of a study as well as the characteristics and the current living situation of study participants. Based on a case study of an HIV‐vaccine‐trial conducted in India we demonstrate how those criteria can be applied in a retrospective way to identify potential ethical conflicts. The criteria can also indicate a prospective function for ethical pre‐assessment. For this, we provide an outlook for three major topics: 1. Vulnerability as a normative concept: Different ways of protection; 2. The relevance of transparency and 3. Vulnerability as an instrument to increase decision participation of human subjects.     

Other Dark Sides of Resilience: Politics and Power in Community-Based Efforts to Strengthen Resilience

ABSTRACT

Oceanic people and places are increasingly labelled as either ‘resilient’ or ‘vulnerable’ to disasters and climate change. Resilience is often described in disaster discourse as a strategy designed to overcome vulnerability by helping communities to ‘bounce back’ in the wake of ‘natural’ disasters. Using ethnographic research conducted with Community Disaster and Climate Change Committees (CDCs) in Vanuatu in the wake of Tropical Cyclone Pam, this paper seeks to problematise disaster responses that see the ‘community’ as a space to be acted upon by outsiders, or where people will respond in a unified way to the challenges of rebuilding after disaster. Using political ecology framings this paper critiques the ideas of resilience that appear entrenched in community-based disaster and climate change adaptation discourse and practice in Oceania. Rather than presupposing resilience or vulnerability, this paper details the dispersal and distribution power and agency amongst individual actors and groups that either supported or manipulated, the distribution of goods by Community Disaster Committees. In this way, it moves beyond the limitations of conceptual framings of resilience in disaster management and climate change into a more considered appraisal of power, by exploring what James Ferguson has termed ‘the politics of distribution’ in the context of disaster.     

Understanding: Between belief and unbelief

This paper addresses issues raised in Taylor’s work concerning how communities may come to work in normatively secular ways. For Taylor, it seems to be sufficient for believers (and nonbelievers) to acknowledge that their own ‘construals’ are not shared by everyone. However, this leaves open the question of how the acknowledgement of difference may be turned into respect. A common strategy is to require that faith‐based truth claims are ‘bracketed out’, treating secular and religious discourse as ‘nonoverlapping magisteria’. This secularising strategy is, however, problematic on a number of counts. The article makes a case for a less confrontational, more cosmopolitan conversation between secular and religious reason in a postsecular age, examining in particular the possibilities for conversation between science and mysticism. It concludes that it is possible to retain a commitment to naturalism and yet also accept some of the most mystical of propositions, thereby establishing a bridge between ‘secular’ and ‘religious’ forms of reasoning.     

Research vulnerability: an illustrative case study from the South African mining industry

The concept of 'vulnerability' is well established within the realm of research ethics and most ethical guidelines include a section on 'vulnerable populations'. However, the term 'vulnerability', used within a human research context, has received a lot of negative publicity recently and has been described as being simultaneously 'too broad' and 'too narrow'. The aim of the paper is to explore the concept of research vulnerability by using a detailed case study - that of mineworkers in post-apartheid South Africa. In particular, the usefulness of Kipnis's taxonomy of research vulnerability will be examined. In recent years the volume of clinical research on human subjects in South Africa has increased significantly. The HIV and TB pandemics have contributed to this increase. These epidemics have impacted negatively on the mining industry; and mining companies have become increasingly interested in research initiatives that address these problems. This case study explores the potential research vulnerability of mineworkers in the context of the South African mining industry and examines measures that can reduce this vulnerability.     

Fleshing Out Vulnerability

In the literature on medical ethics, it is generally admitted that vulnerable persons or groups deserve special attention, care or protection. One can define vulnerable persons as those having a greater likelihood of being wronged – that is, of being denied adequate satisfaction of certain legitimate claims. The conjunction of these two points entails what we call the Special Protection Thesis. It asserts that persons with a greater likelihood of being denied adequate satisfaction of their legitimate claims deserve special attention, care or protection. Such a thesis remains vague, however, as long as we do not know what legitimate claims are. This article aims at dispelling this vagueness by exploring what claims we have in relation to health care – thus fleshing out a claim‐based conception of vulnerability. We argue that the Special Protection Thesis must be enriched as follows: If individual or group X has a greater likelihood of being denied adequate satisfaction of some of their legitimate claims to (i) physical integrity, (ii) autonomy, (iii) freedom, (iv) social provision, (v) impartial quality of government, (vi) social bases of self‐respect or (vii) communal belonging, then X deserves special attention, care or protection. With this improved understanding of vulnerability, vulnerability talk in healthcare ethics can escape vagueness and serve as an adequate basis for practice.     

IS PAYMENT A BENEFIT?

What I call ‘the standard view’ claims that IRBs should not regard financial payment as a benefit to subjects for the purpose of risk/benefit assessment. Although the standard view is universally accepted, there is little defense of that view in the canonical documents of research ethics or the scholarly literature. This paper claims that insofar as IRBs should be concerned with the interests and autonomy of research subjects, they should reject the standard view and adopt ‘the incorporation view.’ The incorporation view is more consistent with the underlying soft‐paternalist justification for risk‐benefit assessment and demonstrates respect for the autonomy of prospective subjects. Adoption of the standard view precludes protocols that advance the interests of subjects, investigators, and society. After considering several objections to the argument, I consider several arguments for the standard view that do not appeal to the interests and autonomy of research subjects.     

Applying complementary species vulnerability assessments to improve conservation strategies in the Galapagos Marine Reserve

Marine biodiversity can be protected by identifying vulnerable species and creating marine protected areas (MPAs) to ensure their survival. A wide variety of methods are employed by environmental managers to determine areas of conservation priority, however which methods should be applied is often a subject of debate for practitioners and scientists. We applied two species vulnerability assessments, the International Union for the Conservation of Nature (IUCN) red list of threatened species and FishBase’s intrinsic vulnerability assessment, to fish communities in three coastal habitats (mangrove, rocky and coral) on the island of San Cristobal, Galapagos. When using the IUCN red list of threatened species, rocky reefs hosted the greatest number of vulnerable species, however when applying the FishBase assessment of intrinsic vulnerability mangroves hosted the greatest abundance of ‘very-highly’ vulnerable species and coral ecosystems hosted the greatest abundance of ‘highly’ vulnerable species. The two methods showed little overlap in determining habitat types that host vulnerable species because they rely on different biological and ecological parameters. Since extensive data is required for IUCN red list assessments, we show that the intrinsic vulnerability assessment from FishBase can be used to complement the IUCN red list especially in data-poor areas. Intrinsic vulnerability assessments are based on less data-intensive methods than the IUCN red list, but nonetheless may bridge information gaps that can arise when using the IUCN red list alone. Vulnerability assessments based on intrinsic factors are not widely applied in marine spatial planning, but their inclusion as a tool for forming conservation strategies can be useful in preventing species loss.     

Enriching the concept of vulnerability in research ethics: An integrative and functional account

The concept of vulnerability is widely used in research ethics to signal attention to participants who require special protections in research. However, this concept is vague and under‐theorized. There is also growing concern that the dominant categorical approach to vulnerability (as exemplified by research ethics regulations and guidelines delineating vulnerable groups) is ethically problematic because of its assumptions about groups of people and is, in fact, not very guiding. An agreed‐upon strategy is to move from categorical towards analytical approaches (focused on analyzing types and sources of vulnerability) to vulnerability. Beyond this agreement, however, scholars have been advancing competing accounts of vulnerability without consensus about its appropriate operationalization in research ethics. Based on previous debates, we propose that a comprehensive account of vulnerability for research ethics must include four components: definition, normative justifications, application, and implications. Concluding that no existing accounts integrate these components in a functional (i.e., practically applicable) manner, we propose an integrative and functional account of vulnerability inspired by pragmatist theory and enriched by bioethics literature. Using an example of research on deep brain stimulation for treatment‐resistant depression, we illustrate how the integrative‐functional account can guide the analysis of vulnerability in research within a pragmatist, evidence‐based approach to research ethics. While ultimately there are concerns to be addressed in existing research ethics guidelines on vulnerability, the integrative‐functional account can serve as an analytic tool to help researchers, research ethics boards, and other relevant actors fill in the gaps in the current landscape of research ethics governance.     

Individual-scale inference to anticipate climate-change vulnerability of biodiversity

Anticipating how biodiversity will respond to climate change is challenged by the fact that climate variables affect individuals in competition with others, but interest lies at the scale of species and landscapes. By omitting the individual scale, models cannot accommodate the processes that determine future biodiversity. We demonstrate how individual-scale inference can be applied to the problem of anticipating vulnerability of species to climate. The approach places climate vulnerability in the context of competition for light and soil moisture. Sensitivities to climate and competition interactions aggregated from the individual tree scale provide estimates of which species are vulnerable to which variables in different habitats. Vulnerability is explored in terms of specific demographic responses (growth, fecundity and survival) and in terms of the synthetic response (the combination of demographic rates), termed climate tracking. These indices quantify risks for individuals in the context of their competitive environments. However, by aggregating in specific ways (over individuals, years, and other input variables), we provide ways to summarize and rank species in terms of their risks from climate change.     

Oxytocin Motivates Non-Cooperation in Intergroup Conflict to Protect Vulnerable In-Group Members

Intergroup conflict is often driven by an individual''s motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake.     

Male Wistar rats are more susceptible to lasting social anxiety than Wild-type Groningen rats following social defeat stress during adolescence

Adolescence is an important period for the development of adult social competences. Social stress during adolescence may contribute not only to an inadequate social development but also to adult vulnerability to social anxiety. There seems to be a clear individual differentiation, however, in the vulnerability to the long-term negative consequences of social stress. The current study further explores this individual vulnerability and is aimed at the influence of social stress during adolescence on adult social anxiety and its context specificity. Rats from different strains (Wistar and Wild-type Groningen rats) were exposed to the resident-intruder paradigm five times during 10 min each in the period between postnatal day 45 and 58. Three and 7 weeks later, the animals were re-exposed to the context in the presence of either a dominant male or an anestrous female behind a wire mesh screen. Wistar rats that were socially defeated spent less time exploring the social stimulus in comparison with socially defeated Wild-type rats and their non-defeated controls. We conclude that the stressed Wistar rat shows signs of generalized social anxiety indicating that the Wistar rat can be considered as a vulnerable phenotype to effects of adolescent social stress.     

The path to Weimar Serbia? Explaining the resurgence of the Serbian far right after the fall of Milosevic

A number of European countries are experiencing a rise in the blue-collar and ethnic majority vote for the ultra-nationalist far right. The situation seems particularly ominous in Serbia, where the far right is enjoying a resurgence of electoral support, coming close to capturing the presidency in 2004. This study analyses the results of five post-Milosevic elections and finds support for the argument that the majority's economic vulnerability and a sense of ‘ethnic threat’ are the major contextual predictors of far right support. In light of the demonstrated ability of the Serbian far right to mobilize economically vulnerable sections of the population, implementation of neo-liberal economic reforms might unintentionally bring them to power. The maintenance and development of the welfare state might counteract the electoral appeal of authoritarian ultra-nationalists.     

“Bioethics in Action” and Human Population Genetics Research

Recent disputes about human population genetics research have been provoked by the field's political vulnerability (the historic imbalance of power between the geneticists and the people they study) and conceptual vulnerability (the mismatch between scientific and popular understandings of the genetic basis of collective identity). The small, isolated groups often studied by this science are now mobilizing themselves as political subjects, pressing sovereignty claims, and demanding control over the direction and interpretation of research. Negotiations between the geneticists and the people asked to donate DNA have resulted not only in explicit bioethics protocols but also in diffuse anxiety over the incommensurability between expert and non-expert views about genetic evidence for identity claims. This article compares two disputes over genetics research: the Human Genome Diversity Project and the use of genetics to prove identity claims among the Melungeons of Tennessee. The case studies illustrate “bioethics in action”: how particular controversies and interests drive the production of bioethics discourses and techniques (such as informed consent protocols). They also illustrate some limits on the usual apparatus of bioethics in overcoming this science's multiple vulnerabilities.     

Examining the microclimate hypothesis in Amazonian birds: indirect tests of the ‘visual constraints’ mechanism

Proposed mechanisms for the decline of terrestrial and understory insectivorous birds in the tropics include a related subset that together has been termed the ‘microclimate hypothesis’. One prediction from this hypothesis is that sensitivity to bright light environments discourages birds of the dimly lit rainforest interior from using edges, gaps, or disturbed forest. Using a hierarchical Bayesian framework and capture data across time and space, we tested this by first determining vulnerability based on differences in within‐species capture rates between disturbed and undisturbed forest for 64 bird species at the Biological Dynamics of Forest Fragments Project in central Amazonian Brazil. We found that 35 species (55%) were vulnerable to anthropogenic habitat degradation, whereas only four (6%) were more commonly captured in degraded forest. To infer visual sensitivity, we then examined two different characters: eye size (maximum pupil diameter) relative to body mass and the initiation time of dawn song, which presumably reflects a species’ visual capacity under low light intensities. We predicted that species with large relative eye sizes and birds with earlier dawn songs would exhibit increased vulnerability in degraded habitats with bright light. Contrary to our predictions, however, vulnerability was positively correlated with the mean start time of dawn song. This indicates that species that wait to initiate dawn song are also more vulnerable to habitat degradation. After correcting for body size, there was no effect of eye size on vulnerability. Together, our results do not provide quantitative support for the light sensitivity mechanism of the microclimate hypothesis. More sensitive experimental tests, such as behavioral assays with controlled light environments, especially in a comparative framework, are needed to rigorously evaluate the role of light sensitivity as an aspect of the microclimate hypothesis among Neotropical birds.     

Does predation select for or against avian coloniality? A comparative analysis

Some studies have supported predation as a selective pressure contributing to the evolution of coloniality. However, evidence also exists that colonies attract predators, selecting against colonial breeding. Using comparative analyses, we tested the reduced predation hypothesis that individuals aggregate into colonies for protection, and the opposite hypothesis, that breeding aggregations increase predation risk. We used locational and physical characteristics of nests to estimate levels of species' vulnerability to predation. We analysed the Ciconiiformes, a large avian order with the highest prevalence of coloniality, using Pagel's general method of comparative analysis for discrete variables. A common requirement of both hypotheses, that there is correlated evolution between coloniality and vulnerability to predation, was fulfilled in our data set of 363 species. The main predictions of the reduced predation hypothesis were not supported, namely that (1) solitary/vulnerable species are more prone to become colonial than solitary/protected species and (2) colonial/protected species are more likely to evolve towards vulnerability than solitary/protected species. In contrast, the main predictions of the increased predation hypothesis were supported, namely that colonial/vulnerable species are more prone (1) to become protected than solitary/vulnerable species and/or (2) to become solitary than colonial/protected species. This suggests that the colonial/vulnerable state is especially exposed to predation as coloniality may often attract predators rather than provide safety.     

On the Alleged Right to Participate in High‐Risk Research

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non‐minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non‐therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high‐risk research’. I argue that this idea is ill‐founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.