Heterogeneous assemblages of bioethics and science: the “pre-embryo” debate in America

This paper explores the “pre-embryo” debate in America to analyze the relationship between scientific uncertainty and moral decision-making. This paper explores how an ethical debate among bioethicists around the term “pre-embryo” has been transformed into a scientific “fact” debate between developmental biology and embryology. This transformation is driven by the scientism of ethical reasoning that stresses scientific claims to increase the credibility of ethical claims. This paper concludes that the “pre-embryo” debate is not an ethical controversy over a unified science but rather credibility struggles between two heterogeneous assemblages of science and bioethics.     

Freedom of Choice About Incidental Findings Can Frustrate Participants' True Preferences

Ethicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general consensus is that disclosed information should benefit participants. However, there is no agreement that genetic information will benefit participants, rather it may cause problems such as anxiety. One could get past this disagreement about disclosure of incidental findings by letting participants express their preferences in the consent form. We argue that this freedom of choice is problematic. In transferring the decision to participants, it is assumed that participants will understand what they decide about and that they will express what they truly want. However, psychological findings about people's reaction to probabilities and risk have been shown to involve both cognitive and emotional challenges. People change their attitude to risk depending on what is at stake. Their mood affects judgments and choices, and they over‐ and underestimate probabilities depending on whether they are low or high. Moreover, different framing of the options can steer people to a specific choice. Although it seems attractive to let participants express their preferences to incidental findings in the consent form, it is uncertain if this choice enables people to express what they truly prefer. In order to better understand the participants' preferences, we argue that future empirical work needs to confront the participant with the complexity of the uncertainty and the trade‐offs that are connected with the uncertain predictive value of genetic risk information.     

Road-maps and revelations: on the somatic ethics of genetic susceptibility

Understanding genomic susceptibility risk has been represented as key to a new era of personalized medicine, in which “empowered” individuals shape their lives according to a “somatic ethics” of genetic risk management. Based on a comprehensive analysis of websites and other documents produced by key companies within the personal genomics industry, I argue that the rhetoric of empowerment these companies employ constructs an “ideal subject” of personal genomics while also expressing tensions implicit within the idea of a somatic ethics based on genetic susceptibility. Using Kaushik Sunder Rajan's concept of “genomic fetishism,” I show how these tensions arise from the relationship the rhetoric of personal genomics constructs between risk and uncertainty, and relate them to broader tensions within “risk thinking” as a mode of governmentality that extends beyond genomics.     

The death of dignity is greatly exaggerated: Reflections 15 years after the declaration of dignity as a useless concept

Fifteen years ago, Ruth Macklin shook the medical community with her claim in the BMJ that dignity is a useless concept. Her essay provoked a storm of reactions. What have we learned from the debate? In this article I analyse the responses to her essay and the following debate to investigate whether she was right that “[d]ignity is a useless concept in medical ethics and can be eliminated without any loss of content.” While some of the commentaries misconstrued her claim and argue against strawmen, others forcefully maintained that the concept of dignity has functions beyond “respect for persons and their autonomy.” One important point that came out of the debate is that dignity is a generic concept that covers more ground than “respect for persons or their autonomy.” In particular, dignity seems to have a wide range of protective functions as well as having reciprocal, relational, and social aspects. Dignity appears more attributional and norm-formative than respect for persons and autonomy. While the claim that dignity is unclear, vague, and can be used sloganistically seems highly relevant, it is argued that this vagueness fulfils important functions in ethics. Moreover, dismissing dignity because of its lack of clarity has implications for “respect for persons” and “autonomy,” which are also used vaguely and sloganistically. No doubt medical ethics should use as a clear concept as the context requires. Nonetheless, dignity still seems to be a widely used generic concept in ethical debates and doing as much ethical work as “respect for persons” or “respect for autonomy.” Therefore, the death of dignity seems to be greatly exaggerated.     

Crossing disciplinary lines: reconciling social and genomic perspectives on the histories and legacies of the transatlantic trade in enslaved Africans

Over the past two decades, advances in the field of genomics have presented new opportunities to shed light upon the origins of enslaved Africans and their contemporary descendants. While this possibility has caused enthusiasm among members of the public, it has provoked contention within the academic sphere. This paper represents an attempt to reconcile these opposing disciplinary divisions, by examining, explaining, and discussing the processes involved in the production of genetic “ancestry” estimates, in order to moderate the aura of absolute “truth” that is often associated with such techniques. Our discussion focuses on two case studies – the academic use of ancient DNA analyses to estimate the geographic origins of historically enslaved individuals, and the commercialization of DNA “ancestry” testing techniques aimed at African-American roots-seekers – and draws upon recent ethnographic data relating to the experiences of test creators and test-takers, in order to contribute to this debate.     

Ectogestation ethics: The implications of artificially extending gestation for viability,newborn resuscitation and abortion

Recent animal research suggests that it may soon be possible to support the human fetus in an artificial uterine environment for part of a pregnancy. A technique of extending gestation in this way (“ectogestation”) could be offered to parents of extremely premature infants (EPIs) to improve outcomes for their child. The use of artificial uteruses for ectogestation could generate ethical questions because of the technology’s potential impact on the point of “viability”—loosely defined as the stage of pregnancy beyond which the fetus may survive external to the womb. Several medical decisions during the perinatal period are based on the gestation at which infants are considered viable, for example decisions about newborn resuscitation and abortion, and ectogestation has the potential to impact on these. Despite these possible implications, there is little existing evidence or analysis of how this technology would affect medical practice. In this paper, we combine empirical data with ethical analysis. We report a survey of 91 practicing Australian obstetricians and neonatologists; we aimed to assess their conceptual understanding of “viability,” and what ethical consequences they envisage arising from improved survival of EPIs. We also assess what the ethical implications of extending gestation should be for newborn and obstetric care. We analyze the concept of viability and argue that while ectogestation might have implications for the permissibility of neonatal life-prolonging treatment at extremely early gestation, it should not necessarily have implications for abortion policy. We compare our ethical findings with the results of the survey.     

PRINCIPLISM AND THE ETHICAL APPRAISAL OF CLINICAL TRIALS

For nearly two decades, the process of reviewing the ethical merit of research involving human subjects has been based on the application of principles initially described in the U.S. National Commission's Belmont Report, and later articulated more fully by Beauchamp and Childress in their Principles of Biomedical Ethics. Recently, the use of ethical principles for deliberating about moral problems in medicine and research, referred to in the pejorative sense as “principlism”, has come under scrutiny. In this paper we argue that these principles can provide a foundation for the source of ethical appraisal of human research, but are not themselves wholly adequate for this purpose. Therefore, we further propose that (1) principles should be understood as heuristics that can be “specified” as described by DeGrazia (1992), and (2) that the principle-based approach should be supplemented by formally incorporating “sensitivity to context” into the evaluation of clinical trials     

Pathogenicity in the tubercle bacillus: molecular and evolutionary determinants

In contrast to the great majority of mycobacterial species that are harmless saprophytes, Mycobacterium tuberculosis and other closely related tubercle bacilli have evolved to be among the most important human and animal pathogens. The need to develop new strategies in the fight against tuberculosis (TB) and related diseases has fuelled research into the evolutionary success of the M. tuberculosis complex members. Amongst the various disciplines, genomics and functional genomics have been instrumental in improving our understanding of these organisms. In this review we will present some of the recent key findings on molecular determinants of mycobacterial pathogenicity and attenuation, the evolution of M. tuberculosis, genome dynamics, antigen mining for improved diagnostic and subunit antigens, and finally the identification of novel drug targets. The genomics revolution has changed the landscape of TB research, and now underpins our renewed efforts to defeat this deadly pathogen.     

Metaphors in search of a target: the curious case of epigenetics

Carrying out research in genetics and genomics and communicating about them would not be possible without metaphors such as “information,” “code,” “letter” or “book.” Genetic and genomic metaphors have remained relatively stable for a long time but are now beginning to shift in the context of synthetic biology and epigenetics. This article charts the emergence of metaphors in the context of epigenetics, first through collecting some examples of metaphors in scientific and popular writing and second through a systematic analysis of metaphors used in two UK broadsheets. Findings show that while source domains for metaphors can be identified, such as our knowledge of electrical switches or of bookmarks, it is difficult to pinpoint target domains for such metaphors. This may be indicative both of struggles over what epigenetics means for scientists (natural and social) and of difficulties associated with talking about this, as yet, young field in the popular press.     

Social and ethical checkpoints for bottom-up synthetic biology, or protocells

An alternative to creating novel organisms through the traditional “top-down” approach to synthetic biology involves creating them from the “bottom up” by assembling them from non-living components; the products of this approach are called “protocells.” In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology. Protocells have not yet been developed, but many expect this to happen within the next five to ten years. Accordingly, we identify six key checkpoints in protocell development at which particular attention should be given to specific ethical, social and regulatory issues concerning bottom-up synthetic biology, and make ten recommendations for responsible protocell science that are tied to the achievement of these checkpoints.     

Targeting novel folds for structural genomics

The ultimate goal of structural genomics is to obtain the structure of each protein coded by each gene within a genome to determine gene function. Because of cost and time limitations, it remains impractical to solve the structure for every gene product experimentally. Up to a point, reasonably accurate three‐dimensional structures can be deduced for proteins with homologous sequences by using comparative modeling. Beyond this, fold recognition or threading methods can be used for proteins showing little homology to any known fold, although this is relatively time‐consuming and limited by the library of template folds currently available. Therefore, it is appropriate to develop methods that can increase our knowledge base, expanding our fold libraries by earmarking potentially “novel” folds for experimental structure determination. How can we sift through proteomic data rapidly and yet reliably identify novel folds as targets for structural genomics? We have analyzed a number of simple methods that discriminate between “novel” and “known” folds. We propose that simple alignments of secondary structure elements using predicted secondary structure could potentially be a more selective method than both a simple fold recognition method (GenTHREADER) and standard sequence alignment at finding novel folds when sequences show no detectable homology to proteins with known structures. Proteins 2002;48:44–52. © 2002 Wiley‐Liss, Inc.     

The cultural construction of gendered bodies: Biology and metaphors of production and destruction*

One way of conceiving of the anthropological task is that of countering the degradations and “dehumanizations” of the “other” to which the species is prone by promoting “transcendent humanization.” However efficiently and professionally anthropologists gather their materials and form them into their ethnographic and ethnologic analyses, may not this “ethical impulse” be postulated as the “final cause” of our efforts? But what could such a sonorous phrase mean ? And what is its relationship to the systematic study of the “differences that make or do not make a difference” in culture to which anthropology has long been devoted? I will argue that it involves a dynamic of categories and that this dynamic is itself an object of systematic study. Recently, for example, some anthropologists have been writing “against culture,” seeing the culture concept and associated theory more as barriers than as benefits to pan‐human understanding. I will argue that this is an instance of “transcendent humanization.” One cannot but be sympathetic to the thrust and merits of this argument. But at the same time one wants to ask what implications it holds for the systematic study and understanding of the other. This article, then, examines some elementary vectors in the “dynamic of the categorical” involved in these and related recent debates which also may be seen in terms of transcendence and humanization: the debate over relativism and the recently emergent debate over “enlightenment mythmaking” in anthropology.     

Synthetic communication signals influence wild harbour porpoise (Phocoena phocoena) behaviour

We used our novel and programmable Porpoise Alarm (PAL, patd.) to synthesize life-like, electronic harbour porpoise communication signals based on those described for captive animals. In the Little Belt, Denmark, we employed PAL (source level 158 ± 1 dB p–p re 1 μPa@1 m; centroid frequency 133 ± 8.5 kHz) to synthesize three aggressive click train types termed “A”, “F3” and “M1” to naive, free-living harbour porpoises. Via theodolite tracking (372 h of total visual effort spread over 10 expeditions) we found that, depending on signal type, porpoises either avoid or become attracted to PAL: Signal types “A” and “F3” are slight deterrents, porpoises increasing minimum range (+23 to 32 m, respectively), whereas “M1” attracts porpoises, reducing range (by ? 29 m). As determined via archival acoustic detectors (AADs), both signals “F3” and “M1” led the animals to significantly intensify their click rate (by +10% and 68%, respectively) while signal “A” led to a significant reduction ( ? 59%). We propose that equipping fishing gear with PAL emitting signal “F3” could potentially reduce porpoise by-catch by increasing (1) awareness through enhanced echolocation and (2) distance to the nets. Detection probability and radius of PAL/AAD tandems could be improved by emitting signal “M1” to focus porpoise echolocation signals on the AAD. The signal may also be useful in luring animals away from hazards, which may be helpful for conservation measures prior to the onset of harmful acoustic activities such as pile-driving, seismic exploration or ammunition clearance.     

Public consultation in ethics an experiment in representative ethics

Genome Canada has funded a research project to evaluate the usefulness of different forms of ethical analysis for assessing the moral weight of public opinion in the governance of genomics. This paper will describe a role of public consultation for ethical analysis and a contribution of ethical analysis to public consultation and the governance of genomics/biotechnology. Public consultation increases the robustness of ethical analysis with a more diverse set of moral experiences. Consultation must be carefully and respectfully designed to generate sufficiently diverse and rich accounts of moral experiences. Since dominant groups tend to define ethical or policy issues in a manner that excludes some interests or perspectives, it is important to identify the range of interests that diverse publics hold before defining the issue and scope of the discussion and the premature foreclosure of ethical dialogue. Consequently, a significant contribution of ethical dialogue strengthened by social analysis is to consider the context and non-policy use of power to govern genomics and to sustain social debate on enduring ethical issues.     

Being a burden to others and wishes to die: The importance of the sociopolitical context

All articles in May 2019’s special issue of Bioethics offer profound insights into the issue of “being a burden to others” in relation to wishes to die, which are highly relevant for ethical debates about end-of-life care and physician-assisted dying. In this reply, we wish to stress the importance of acknowledging and analyzing the sociopolitical context of the phenomenon “being a burden” in relation to wishes to die and we will show how this analysis could benefit from a care ethical approach. As discussions in care ethics have made clear, caring practices are both social and political practices. An empirical and ethical analysis of “being a burden” therefore needs to take institutional and societal norms and structures into account, in addition to first-person experiences and concepts such as caring needs, relational autonomy, and interdependency. Besides the relevance of the sociopolitical context for the phenomenon “being a burden” as such, the sociopolitical context also seems relevant for the investigation of the phenomenon, which we will illustrate by reflecting on “being a burden” in relation to the practice of physician-assisted dying in the Netherlands.     

Computational exploration of the binding mode of heme‐dependent stimulators into the active catalytic domain of soluble guanylate cyclase

Soluble guanylate cyclase (sGC), the main target of nitric oxide (NO), has been proven to have a significant role in coronary artery disease, pulmonary hypertension, erectile dysfunction, and myocardial infarction. One of its agonists, BAY 41‐2272 (Riociguat), has been recently approved for treatment of pulmonary arterial hypertension (PHA), while some others are in clinical phases of development. However, the location of the binding sites for the two known types of agonists, heme‐dependent stimulators and heme‐independent activators, is a matter of debate, particularly for the first group where both a location on the regulatory (H‐NOX) and on the catalytic domain have been suggested by different authors. Here, we address its potential location on the catalytic domain, the unique well characterized at the structural level, by an “in silico” approach. Homology models of the catalytic domain of sGC in “inactive” or “active” conformations were constructed using the structure of previously described crystals of the catalytic domains of “inactive” sGCs (2WZ1, 3ET6) and of “active” adenylate cyclase (1CJU). Each model was submitted to six independent molecular dynamics simulations of about 1 μs. Docking of YC‐1, a classic heme‐dependent stimulator, to all frames of representative trajectories of “inactive” and “active” conformations, followed by calculation of absolute binding free energies with the linear interaction energy (LIE) method, revealed a potential high‐affinity binding site on the “active” structure. The site, located between the pseudo‐symmetric and the catalytic site just over the loop β₂–β₃, does not overlap with the forskolin binding site on adenylate cyclases. Proteins 2016; 84:1534–1548. © 2016 Wiley Periodicals, Inc.     

Reducing the Ecological Impact of Field Research

Researchers and students at biological field stations, especially in remote areas, are subject to leaving “footprints,” as we conduct research, work, and live in sensitive ecosystems. These footprints include travel, personal trash and waste, and field equipment (e.g. flagging, tree markers, plot markers, trail markers, monitoring devices, etc.). In this commentary, we argue that the field of primatology's commitment to minimum impact research should be more explicitly and visibly integrated into our ethical protocols with regard to field research and instruction in sensitive environments. We review current ethical codes and potential solutions to reducing our “researcher footprints” while conducting fieldwork. Using Costa Rica as an example, we address how sustainable fieldwork differs among varying cultural contexts and argue that researchers should be made responsible and accountable for how our presence, research, and teaching might impact the environment. We conclude by recommending a set of guidelines to be added to ethical protocols regarding research design, station policies, and the conduct of research and teaching in the field. Am. J. Primatol. 75:1‐9, 2013. © 2012 Wiley Periodicals, Inc.     

Bioprophecy and the politics of the present: notes on the establishment of Mexico's national genomics institute (INMEGEN)

In 1999, a small group of genomic entrepreneurs and local politicians started mobilizing the idea of founding a national genomics institute in Mexico. Approximately four years later, and after 18 months of congressional debate, the Mexican National Institute of Genomic Medicine (INMEGEN) was established by presidential decree. As scholars, we are interested in how the call for a high-tech, high-cost genomics institute was able to gain political traction in a country, where many people struggle to secure access to even the most basic level of health care. Those behind the establishment of the INMEGEN used what we call technologies of bioprophecy to present it as a modernizing institution that would move the nation into the “new world order” by bringing not only biological and economic health, but also scientific prestige to Mexico.     

Democratic governance of genomics: the case of UK Biobank

Biobanks are collections of human biological tissue used for genomics research. This promises a better understanding of the gene-based contribution to common disease and development of a more personalized approach to healthcare with safer drugs and more effective treatment. However, biobanks are also controversial owing to the ethical, legal, social and political issues raised about their collection and use of biological samples. Therefore, their democratic governance is not only a normative challenge but also an empirical one. This paper is concerned with both challenges: it attempts to “evaluate” processes of democratic governance of genomics by focusing on the case of UK Biobank. The overall argument is that although the UK Biobank performs well in terms of general democratic governance structures, there are epistemological and practical limits to specific democratic governance processes.