Reconciling Regulation with Scientific Autonomy in Dual-Use Research.

In debates over the regulation of communication related to dual-use research, the risks that such communication creates must be weighed against against the value of scientific autonomy. The censorship of such communication seems justifiable in certain cases, given the potentially catastrophic applications of some dual-use research. This conclusion however, gives rise to another kind of danger: that regulators will use overly simplistic cost-benefit analysis to rationalize excessive regulation of scientific research. In response to this, we show how institutional design principles and normative frameworks from free speech theory can be used to help extend the argument for regulating dangerous dual-use research beyond overly simplistic cost-benefit reasoning, but without reverting to an implausibly absolutist view of scientific autonomy.

Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy.

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.

Ethical issues surrounding controlled human infection challenge studies in endemic low-and middle-income countries.

Controlled human infection challenge studies (CHIs) involve intentionally exposing research participants to, and/or thereby infecting them with, micro-organisms. There have been increased calls for more CHIs to be conducted in low- and middle-income countries (LMICs) where many relevant diseases are endemic. This article is based on a research project that identified and analyzed ethical and regulatory issues related to endemic LMIC CHIs via (a) a review of relevant literature and (b) qualitative interviews involving 45 scientists and ethicists with relevant expertise. In this article we argue that though there is an especially strong case for conducting CHIs in endemic (LMIC) settings, certain ethical issues related to the design and conduct of such studies (in such settings) nonetheless warrant particularly careful attention. We focus on ethical implications of endemic LMIC CHIs regarding (a) potential direct benefits for participants, (b) risks to participants, (c) third-party risks, (d) informed consent, (e) payment of participants, and (f) community engagement. We conclude that there is a strong ethical rationale to conduct (well-designed) CHIs in endemic LMICs, that certain ethical issues warrant particularly careful consideration, and that ethical analyses of endemic LMIC CHIs can inform current debates in research ethics more broadly.

Surveillance and control of asymptomatic carriers of drug-resistant bacteria.

Drug-resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until and/or unless a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug-resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of resistant infections. Accumulating evidence suggests that such transmission occurs not only in hospital settings but also in the general community, although considerably more data are needed to assess the extent of this problem. Asymptomatic carriage of drug-resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug-resistant bacteria, noting important knowledge gaps; and (ii) explore the particular implications of existing public health ethics frameworks for policy-making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration.

Is the non-identity problem relevant to public health and policy? An online survey.

BACKGROUND: The non-identity problem arises when our actions in the present could change which people will exist in the future, for better or worse. Is it morally better to improve the lives of specific future people, as compared to changing which people exist for the better? Affecting the timing of fetuses being conceived is one case where present actions change the identity of future people. This is relevant to questions of public health policy, as exemplified in some responses to the Zika epidemic. There is philosophical disagreement about the relevance of non-identity: some hold that non-identity is not relevant, while others think that the only morally relevant actions are those that affect specific people. Given this disagreement, we investigated the intuitions about the moral relevance of non-identity within an educated sample of the public, because there was previously little empirical data on the public's views on the non-identity problem. METHODS: We performed an online survey with a sample of the educated general public. The survey assessed participants' preferences between person-affecting and impersonal interventions for Zika, and their views on other non-identity thought experiments, once the non-identity problem had been explained. It aimed to directly measure the importance of non-identity in participants' moral decision-making. RESULTS: We collected 763 valid responses from the survey. Half of the participants (50%) had a graduate degree, 47% had studied philosophy at a university level, and 20% had read about the non-identity problem before. Most participants favoured person-affecting interventions for Zika over impersonal ones, but the majority claimed that non-identity did not influence their decision (66% of those preferring person-affecting interventions, 95% of those preferring impersonal ones). In one non-identity thought experiment participants were divided, but in another they primarily answered that impersonally reducing the quality of life of future people would be wrong, harmful and blameworthy, even though no specific individuals would be worse off. CONCLUSIONS: Non-identity appeared to play a minor role in participants' moral decision-making. Moreover, participants seem to either misunderstand the non-identity problem, or hold non-counterfactual views of harm that do not define harm as making someone worse off than they would have been otherwise.

Ethics, health policy, and Zika: From emergency to global epidemic?

Zika virus was recognised in 2016 as an important vector-borne cause of congenital malformations and Guillain-Barré syndrome, during a major epidemic in Latin America, centred in Northeastern Brazil. The WHO and Pan American Health Organisation (PAHO), with partner agencies, initiated a coordinated global response including public health intervention and urgent scientific research, as well as ethical analysis as a vital element of policy design. In this paper, we summarise the major ethical issues raised during the Zika epidemic, highlighting the PAHO ethics guidance and the role of ethics in emergency responses, before turning to ethical issues that are yet to be resolved. Zika raises traditional bioethical issues related to reproduction, prenatal diagnosis of serious malformations and unjust disparities in health outcomes. But the epidemic has also highlighted important issues of growing interest in public health ethics, such as the international spread of infectious disease; the central importance of reproductive healthcare in preventing maternal and neonatal morbidity and mortality; diagnostic and reporting biases; vector control and the links between vectors, climate change, and disparities in the global burden of disease. Finally, there are controversies regarding Zika vaccine research and eventual deployment. Zika virus was a neglected disease for over 50 years before the outbreak in Brazil. As it continues to spread, public health agencies should promote gender equity and disease control efforts in Latin America, while preparing for the possibility of a global epidemic.

Necessity and least infringement conditions in public health ethics.

The influential public health ethics framework proposed by Childress et al. includes five "justificatory conditions," two of which are "necessity" and "least infringement." While the framework points to important moral values, we argue it is redundant for it to list both necessity and least infringement because they are logically equivalent. However, it is ambiguous whether Childress et al. would endorse this view, or hold the two conditions distinct. This ambiguity has resulted in confusion in public health ethics discussions citing the Childress et al. framework, as demonstrated by debate between Resnik and Wilson and Dawson. We analyse this debate to resolve these ambiguities. Finally, we argue that the necessity/least infringement principle of the Childress et al. framework applies only in cases in which only one intervention is to be implemented to achieve one specific goal. In other cases, it is not essential to require that only the least infringing intervention be implemented.

Victims, vectors and villains: are those who opt out of vaccination morally responsible for the deaths of others?

Mass vaccination has been a successful public health strategy for many contagious diseases. The immunity of the vaccinated also protects others who cannot be safely or effectively vaccinated-including infants and the immunosuppressed. When vaccination rates fall, diseases like measles can rapidly resurge in a population. Those who cannot be vaccinated for medical reasons are at the highest risk of severe disease and death. They thus may bear the burden of others' freedom to opt out of vaccination. It is often asked whether it is legitimate for states to adopt and enforce mandatory universal vaccination. Yet this neglects a related question: are those who opt out, where it is permitted, morally responsible when others are harmed or die as a result of their decision? In this article, we argue that individuals who opt out of vaccination are morally responsible for resultant harms to others. Using measles as our main example, we demonstrate the ways in which opting out of vaccination can result in a significant risk of harm and death to others, especially infants and the immunosuppressed. We argue that imposing these risks without good justification is blameworthy and examine ways of reaching a coherent understanding of individual moral responsibility for harms in the context of the collective action required for disease transmission. Finally, we consider several objections to this view, provide counterarguments and suggest morally permissible alternatives to mandatory universal vaccination including controlled infection, self-imposed social isolation and financial penalties for refusal to vaccinate.

Capabilities and Incapabilities of the Capabilities Approach to Health Justice.

This first part of this article critiques Sridhar Venkatapuram's conception of health as a capability. It argues that Venkatapuram relies on the problematic concept of dignity, implies that those who are unhealthy lack lives worthy of dignity (which seems politically incorrect), sets a low bar for health, appeals to metaphysically problematic thresholds, fails to draw clear connections between appealed-to capabilities and health, and downplays the importance/relevance of health functioning. It concludes by questioning whether justice entitlements should pertain to the capability for health versus health achievements, challenging Venkatapuram's claims about the strength of health entitlements, and demonstrating that the capabilities approach is unnecessary to address social determinants of health.

Gain-of-Function Research: Ethical Analysis.

Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens. Such research, when conducted by responsible scientists, usually aims to improve understanding of disease causing agents, their interaction with human hosts, and/or their potential to cause pandemics. The ultimate objective of such research is to better inform public health and preparedness efforts and/or development of medical countermeasures. Despite these important potential benefits, GOF research (GOFR) can pose risks regarding biosecurity and biosafety. In 2014 the administration of US President Barack Obama called for a "pause" on funding (and relevant research with existing US Government funding) of GOF experiments involving influenza, SARS, and MERS viruses in particular. With announcement of this pause, the US Government launched a "deliberative process" regarding risks and benefits of GOFR to inform future funding decisions-and the US National Science Advisory Board for Biosecurity (NSABB) was tasked with making recommendations to the US Government on this matter. As part of this deliberative process the National Institutes of Health commissioned this Ethical Analysis White Paper, requesting that it provide (1) review and summary of ethical literature on GOFR, (2) identification and analysis of existing ethical and decision-making frameworks relevant to (i) the evaluation of risks and benefits of GOFR, (ii) decision-making about the conduct of GOF studies, and (iii) the development of US policy regarding GOFR (especially with respect to funding of GOFR), and (3) development of an ethical and decision-making framework that may be considered by NSABB when analyzing information provided by GOFR risk-benefit assessment, and when crafting its final recommendations (especially regarding policy decisions about funding of GOFR in particular). The ethical and decision-making framework ultimately developed is based on the idea that there are numerous ethically relevant dimensions upon which any given case of GOFR can fare better or worse (as opposed to there being necessary conditions that are either satisfied or not satisfied, where all must be satisfied in order for a given case of GOFR to be considered ethically acceptable): research imperative, proportionality, minimization of risks, manageability of risks, justice, good governance (i.e., democracy), evidence, and international outlook and engagement. Rather than drawing a sharp bright line between GOFR studies that are ethically acceptable and those that are ethically unacceptable, this framework is designed to indicate where any given study would fall on an ethical spectrum-where imaginable cases of GOFR might range from those that are most ethically acceptable (perhaps even ethically praiseworthy or ethically obligatory), at one end of the spectrum, to those that are most ethically problematic or unacceptable (and thus should not be funded, or conducted), at the other. The aim should be that any GOFR pursued (and/or funded) should be as far as possible towards the former end of the spectrum.

Ethical aspects of malaria control and research.

Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria--and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy.

Burden of Proof in Bioethics.

A common strategy in bioethics is to posit a prima facie case in favour of one policy, and to then claim that the burden of proof (that this policy should be rejected) falls on those with opposing views. If the burden of proof is not met, it is claimed, then the policy in question should be accepted. This article illustrates, and critically evaluates, examples of this strategy in debates about the sale of organs by living donors, human enhancement, and the precautionary principle. We highlight general problems with this style of argument, and particular problems with its use in specific cases. We conclude that the burden ultimately falls on decision-makers (i.e. policy-makers) to choose the policy supported by the best reasons.

Biosecurity and Open-Source Biology: The Promise and Peril of Distributed Synthetic Biological Technologies.

In this article, we raise ethical concerns about the potential misuse of open-source biology (OSB): biological research and development that progresses through an organisational model of radical openness, deskilling, and innovation. We compare this organisational structure to that of the open-source software model, and detail salient ethical implications of this model. We demonstrate that OSB, in virtue of its commitment to openness, may be resistant to governance attempts.

Moderate eugenics and human enhancement.

Though the reputation of eugenics has been tarnished by history, eugenics per se is not necessarily a bad thing. Many advocate a liberal new eugenics--where individuals are free to choose whether or not to employ genetic technologies for reproductive purposes. Though genetic interventions aimed at the prevention of severe genetic disorders may be morally and socially acceptable, reproductive liberty in the context of enhancement may conflict with equality. Enhancement could also have adverse effects on utility. The enhancement debate requires a shift in focus. What the equality and/or utility costs of enhancement will be is an empirical question. Rather than philosophical speculation, more social science research is needed to address it. Philosophers, meanwhile, should address head-on the question of how to strike a balance between liberty, equality, and utility in cases of conflict (in the context of genetics).

Ethical considerations for vaccination programmes in acute humanitarian emergencies.

Humanitarian emergencies result in a breakdown of critical health-care services and often make vulnerable communities dependent on external agencies for care. In resource-constrained settings, this may occur against a backdrop of extreme poverty, malnutrition, insecurity, low literacy and poor infrastructure. Under these circumstances, providing food, water and shelter and limiting communicable disease outbreaks become primary concerns. Where effective and safe vaccines are available to mitigate the risk of disease outbreaks, their potential deployment is a key consideration in meeting emergency health needs. Ethical considerations are crucial when deciding on vaccine deployment. Allocation of vaccines in short supply, target groups, delivery strategies, surveillance and research during acute humanitarian emergencies all involve ethical considerations that often arise from the tension between individual and common good. The authors lay out the ethical issues that policy-makers need to bear in mind when considering the deployment of mass vaccination during humanitarian emergencies, including beneficence (duty of care and the rule of rescue), non-maleficence, autonomy and consent, and distributive and procedural justice.

Les urgences humanitaires entraînent une rupture des services de soins de santé essentiels et elles rendent souvent les communautés vulnérables dépendantes des organismes externes pour leurs soins. Dans les milieux où les ressources sont comptées, cela peut se produire sur fond d'extrême pauvreté, de malnutrition, d'insécurité, de faible niveau d'alphabétisation et d'infrastructures insuffisantes. Dans ces circonstances, fournir nourriture, eau et abri, tout en limitant les épidémies de maladies transmissibles, devient une préoccupation centrale. Lorsqu'il existe des vaccins sûrs et efficaces pour limiter les risques d'épidémies, leur éventuel déploiement est un facteur clé pour satisfaire les besoins sanitaires d'urgence. Les considérations éthiques sont essentielles pour se prononcer sur le déploiement de la vaccination. La distribution de vaccins en quantités limitées, les groupes cibles, les stratégies de vaccination, la surveillance et la recherche lors de situations d'urgence humanitaire graves impliquent tous des considérations éthiques souvent nées de la tension entre le bien individuel et le bien commun. Les auteurs exposent les questions éthiques que les décideurs doivent garder à l'esprit lorsqu'ils envisagent le déploiement d'une vaccination de masse pendant les urgences humanitaires, notamment la bénéficience (devoir de diligence et devoir d'assistance), la non-maléficience, l'autonomie et le consentement, ainsi que la justice de répartition et l'équité procédurale.

Las emergencias humanitarias causan el desplome de los servicios de atención de salud esenciales y, a menudo, provocan que la atención sanitaria de las comunidades vulnerables pase a depender de organismos externos. En entornos con recursos limitados esto puede darse en un contexto de pobreza extrema, desnutrición, inseguridad, bajos niveles de alfabetización e infraestructuras deficientes. Bajo estas circunstancias, suministrar alimentos, agua y refugio, así como limitar la aparición de brotes de enfermedades transmisibles representan las principales preocupaciones. Cuando se dispone de vacunas eficaces y seguras para reducir el riesgo de aparición de brotes de enfermedades, la distribución potencial de las mismas constituye un factor clave en las situaciones de emergencia sanitaria. Las consideraciones éticas son fundamentales a la hora de decidir sobre la distribución de las vacunas. La asignación de vacunas con suministro limitado, los grupos destinatarios de las mismas, las estrategias de entrega, así como la monitorización y los estudios durante las emergencias humanitarias graves implican consideraciones éticas que, a menudo, derivan de un enfrentamiento entre el beneficio individual y el bien común. Los autores exponen los problemas éticos que los responsables políticos deben tener en cuenta a la hora de considerar cómo distribuir la vacunación masiva durante las emergencias humanitarias, lo cual incluye principios como la beneficencia (el deber de atención y la regla del rescate), la no maleficencia, la autonomía y el consentimiento, así como la justicia distributiva y procesal.

Quantifying the impact of individual and collective compliance with infection control measures for ethical public health policy.

Infectious disease control measures often require collective compliance of large numbers of individuals to benefit public health. This raises ethical questions regarding the value of the public health benefit created by individual and collective compliance. Answering these requires estimating the extent to which individual actions prevent infection of others. We develop mathematical techniques enabling quantification of the impacts of individuals or groups complying with three public health measures: border quarantine, isolation of infected individuals, and prevention via vaccination/prophylaxis. The results suggest that (i) these interventions exhibit synergy: They become more effective on a per-individual basis as compliance increases, and (ii) there is often substantial "overdetermination" of transmission. If a susceptible person contacts multiple infectious individuals, an intervention preventing one transmission may not change the ultimate outcome (thus, risk imposed by some individuals may erode the benefits of others' compliance). These results have implications for public health policy during epidemics.

Ethics review of COVID-19 human challenge studies: A joint HRA/WHO workshop.

This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required for COVID-19 human challenge studies and create the frameworks to ensure rigorous and timely review of these studies. This report evaluates the utility of the WHO's international guidance document Key criteria for the ethical acceptability of COVID-19 human challenge studies (WHO Key Criteria) as a practical resource for the ethics review of COVID-19 human challenge studies. It also assesses the UK HRA's approach to these complex ethics reviews, including the formation of a Specialist Ad-Hoc Research Ethics Committee (REC) for COVID-19 Human Challenge Studies to review all current and future COVID-19 human challenge studies. In addition, the report outlines the reflections of REC members and researchers regarding the ethics review process of the first COVID-19 human challenge studies. Finally, it considers the potential ongoing scientific justification for COVID-19 human challenge studies, particularly in relation to next-generation vaccines and optimisation of vaccination schedules. Overall, there was broad agreement that the WHO Key Criteria represented an international consensus document that played a powerful role in setting norms and delineating the necessary conditions for the ethical acceptability of COVID-19 human challenge studies. Workshop members suggested that the WHO Key Criteria could be practically implemented to support researchers and ethics reviewers, including in the training of ethics committee members. In future, a wider audience may be engaged by the original document and potential additional materials, informed by the experiences of those involved in the first COVID-19 human challenge studies outlined in this document.