Gain-of-function research and model organisms in biology.

So-called 'gain-of-function' (GOF) research is virological research that results in a virus substantially more virulent or transmissible than its wild antecedent. GOF research has been subject to ethical analysis in the past, but the methods of GOF research have to date been underexamined by philosophers in these analyses. Here, we examine the typical animal used in influenza GOF experiments, the ferret, and show how despite its longstanding use, it does not easily satisfy the desirable criteria for an animal model We then discuss the limitations of the ferret model, and how those epistemic limitations bear on ethical and policy questions around the risks and benefits of GOF research. We conclude with a reflection on how philosophy of science can contribute to ethical and policy debates around the risks, benefits and relative priority of life sciences research.

A simulation study of cooperative and autonomous vehicles (CAV) considering courtesy, ethics, and fairness.

Autonomous vehicles (AV) can be programmed to act cooperatively. Previous research on cooperative and autonomous vehicles (CAV) suggests they can substantially improve traffic system operations in terms of mobility and safety. However, these studies do not explicitly take each vehicle's potential gain/loss into consideration and ignore their individual levels of willingness to cooperate. They do not account for ethics and fairness either. In this study, several cooperation/courtesy strategies are proposed to address the above issues. These strategies are grouped into two categories based on non-instrumental and instrumental principles. Non-instrumental strategies make courtesy/cooperation decisions based on some courtesy proxies and a user-specified courtesy level, while instrumental strategies are based only on courtesy proxies related to local traffic performance. Also, a new CAV behavior modeling framework is proposed based on our previous work on cooperative car-following and merging (CCM) control. With such a framework, the proposed courtesy strategies can be easily implemented. The proposed framework and courtesy strategies are coded in SUMO microscopic traffic simulator. They are evaluated considering different levels of traffic demand on a freeway corridor consisting of a work zone and three weaving areas of different types. Interesting findings are drawn from the simulation results, one of which is that the instrumental Local Utilitarianism strategy performs the best in terms of mobility, safety, and fairness. In the future, auction-based strategies can be considered to model how CAV make decisions.

COVID-19 risk perception and vaccine acceptance in individuals with self-reported chronic respiratory or autoimmune conditions.

BACKGROUND: COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of non-pharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions. METHODS: We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors. RESULTS: In the initial survey, individuals reporting a chronic disease had both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls. CONCLUSIONS: It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized.

The ethics of AI-assisted warfighter enhancement research and experimentation: Historical perspectives and ethical challenges.

The military applications of AI raise myriad ethical challenges. Critical among them is how AI integrates with human decision making to enhance cognitive performance on the battlefield. AI applications range from augmented reality devices to assist learning and improve training to implantable Brain-Computer Interfaces (BCI) to create bionic "super soldiers." As these technologies mature, AI-wired warfighters face potential affronts to cognitive liberty, psychological and physiological health risks and obstacles to integrating into military and civil society during their service and upon discharge. Before coming online and operational, however, AI-assisted technologies and neural interfaces require extensive research and human experimentation. Each endeavor raises additional ethical concerns that have been historically ignored thereby leaving military and medical scientists without a cogent ethics protocol for sustainable research. In this way, this paper is a "prequel" to the current debate over enhancement which largely considers neuro-technologies once they are already out the door and operational. To lay the ethics foundation for AI-assisted warfighter enhancement research, we present an historical overview of its technological development followed by a presentation of salient ethics research issues (ICRC, 2006). We begin with a historical survey of AI neuro-enhancement research highlighting the ethics lacunae of its development. We demonstrate the unique ethical problems posed by the convergence of several technologies in the military research setting. Then we address these deficiencies by emphasizing how AI-assisted warfighter enhancement research must pay particular attention to military necessity, and the medical and military cost-benefit tradeoffs of emerging technologies, all attending to the unique status of warfighters as experimental subjects. Finally, our focus is the enhancement of friendly or compatriot warfighters and not, as others have focused, enhancements intended to pacify enemy warfighters.

Machine Learning in Infectious Disease for Risk Factor Identification and Hypothesis Generation: Proof of Concept Using Invasive Candidiasis.

Background: Machine learning (ML) models can handle large data sets without assuming underlying relationships and can be useful for evaluating disease characteristics, yet they are more commonly used for predicting individual disease risk than for identifying factors at the population level. We offer a proof of concept applying random forest (RF) algorithms to Candida-positive hospital encounters in an electronic health record database of patients in the United States. Methods: Candida-positive encounters were extracted from the Cerner HealthFacts database; invasive infections were laboratory-positive sterile site Candida infections. Features included demographics, admission source, care setting, physician specialty, diagnostic and procedure codes, and medications received before the first positive Candida culture. We used RF to assess risk factors for 3 outcomes: any invasive candidiasis (IC) vs non-IC, within-species IC vs non-IC (eg, invasive C. glabrata vs noninvasive C. glabrata), and between-species IC (eg, invasive C. glabrata vs all other IC). Results: Fourteen of 169 (8%) variables were consistently identified as important features in the ML models. When evaluating within-species IC, for example, invasive C. glabrata vs non-invasive C. glabrata, we identified known features like central venous catheters, intensive care unit stay, and gastrointestinal operations. In contrast, important variables for invasive C. glabrata vs all other IC included renal disease and medications like diabetes therapeutics, cholesterol medications, and antiarrhythmics. Conclusions: Known and novel risk factors for IC were identified using ML, demonstrating the hypothesis-generating utility of this approach for infectious disease conditions about which less is known, specifically at the species level or for rarer diseases.

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.

COVID-19 risk perception and vaccine acceptance in individuals with chronic disease.

Background: COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of nonpharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions. Methods: We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors. Results: In the initial survey, individuals reporting a chronic disease had stronger both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls. Conclusions: It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized.

Human Infection Challenge Studies: a Test for the Social Value Criterion of Research Ethics.

Human infection challenge studies involving the intentional infection of research participants with a disease-causing agent have recently been suggested as a means to speed up the search for a vaccine for the ongoing coronavirus disease 2019 (COVID-19) outbreak. Calls for challenge studies, however, rely on the expected social value of these studies. This value represents more than the simple possibility that a successful study will lead to the rapid development and dissemination of vaccines but also some expectation that this will actually occur. I show how this expectation may not be realistic in the current political moment and offer potential ways to make sure that any challenge trials that arise actually achieve their goals.

Bioengineering horizon scan 2020.

Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.

How Should the WHO Guide Access and Benefit Sharing During Infectious Disease Outbreaks?

In response to the 2013-2016 Ebola virus disease (EVD) outbreak primarily affecting Guinea, Sierra Leone, and Liberia, the World Health Organization (WHO) set out Guidance for Managing Ethical Issues in Infectious Disease Outbreaks, which covered social distancing, research in outbreak settings, and clinical care. This article assesses the Guidance's recommendations on research and long-term storage of biological specimens during infectious disease outbreaks and argues that the Guidance does not provide adequate direction for responders', researchers', and organizations' actions. It considers local persons' access to benefits of research in the aftermath of outbreaks and preparedness for outbreaks, drawing on lessons from both the 2013-2016 EVD outbreak and ongoing research in the Democratic Republic of the Congo.

A transatlantic perspective on 20 emerging issues in biological engineering.

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

Underprotection of Unpredictable Statistical Lives Compared to Predictable Ones.

Existing ethical discussion considers the differences in care for identified versus statistical lives. However, there has been little attention to the different degrees of care that are taken for different kinds of statistical lives. Here we argue that for a given number of statistical lives at stake, there will sometimes be different, and usually greater, care taken to protect predictable statistical lives, in which the number of lives that will be lost can be predicted fairly accurately, than for unpredictable statistical lives, where the lives are at stake because of a low-probability event, such that most likely no one will be affected by the decision but with low probability some lives will be at stake. One reason for this difference is the statistical challenge of estimating low probabilities, and in particular the tendency of common approaches to underestimate these probabilities. Another is the existence of rational incentives to treat unpredictable risks as if the probabilities were lower than they are. Some of these factors apply outside the pure economic context, to institutions, individuals, and governments. We argue that there is no ethical reason to treat unpredictable statistical lives differently from predictable statistical lives. Moreover, lives that are unpredictable from the perspective of an individual agent may become predictable when aggregated to the level of a societal decision. Underprotection of unpredictable statistical lives is a form of market failure that may need to be corrected by altering regulation, introducing compulsory liability insurance, or other social policies.

Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission.

The current Ebola virus outbreak has highlighted the uncertainties surrounding many aspects of Ebola virus virology, including routes of transmission. The scientific community played a leading role during the outbreak-potentially, the largest of its kind-as many of the questions surrounding ebolaviruses have only been interrogated in the laboratory. Scientists provided an invaluable resource for clinicians, public health officials, policy makers, and the lay public in understanding the progress of Ebola virus disease and the continuing outbreak. Not all of the scientific communication, however, was accurate or effective. There were multiple instances of published articles during the height of the outbreak containing potentially misleading scientific language that spurred media overreaction and potentially jeopardized preparedness and policy decisions at critical points. Here, we use articles declaring the potential for airborne transmission of Ebola virus as a case study in the inaccurate reporting of basic science, and we provide recommendations for improving the communication about unknown aspects of disease during public health crises.

Balancing the Duty to Treat Patients with Ebola Virus Disease with the Risks to Dialysis Personnel.

In 2014, the author was invited to present at the American Society for Nephrology's annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal safety, duty to community, and duty to colleagues were illustrated, and suggestions for designing ethics into medical practice were given. This article is a summary of that presentation.