In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often‐ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science—including genomewide association studies and polygenic indexes—can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. (...) SBG research that compares individuals within a group according to a “sensitive” phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk‐benefit profile. (shrink)

Large-scale sequencing tests, including whole-exome and whole-genome sequencing, are rapidly moving into clinical use. Sequencing is already being used clinically to identify therapeutic opportunities for cancer patients who have run out of conventional treatment options, to help diagnose children with puzzling neurodevelopmental conditions, and to clarify appropriate drug choices and dosing in individuals. To evaluate and support clinical applications of these technologies, the National Human Genome Research Institute and National Cancer Institute have funded studies on clinical and research sequencing under (...) the Clinical Sequencing Exploratory Research program as well as studies on return of results. Most of these studies use sequencing in real-world clinical settings and collect data on both the application of sequencing and the impact of receiving genomic findings on study participants. They are occurring in the context of controversy over how to obtain consent for exome and genome sequencing. (shrink)

Institutional review boards are almost universally considered to be overworked and understaffed. They also require substantial commitments of time and resources from their members. Although some surveys report average IRB memberships of 15 people or more, federal regulations require only five. We present data on IRB meetings at eight of the top 25 academic medical centers in the United States funded by the National Institutes of Health. These data indicate substantial contributions from primary reviewers and chairs during protocol discussions but (...) little from other members, which implies that it may be possible for smaller IRBs to accomplish the same tasks with no reduction in the quality of review. (shrink)

ABSTRACT:A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on (...) rule following, the framework is designed to build researchers’ capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers’ intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework. (shrink)

Purpose Recent research has found unrealistic optimism among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. Methods A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the (...) bias in other contexts. Results One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators and mental image, were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism. Conclusion Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing. (shrink)

Theory of Mind is the ability to predict and understand the mental state of another. While ToM is theorized to play a role in language, we examined whether such a mentalizing ability plays an important role in establishing shared understanding in conversation. Pairs of participants engaged in a Lego model building task in which adirectorinstructed abuilderon how to create duplicate models from a prototype that only the director could see. We manipulated whether the director could see or could not see (...) the builder’s workspace. As predicted, the Mind in the Eyes test predicted accuracy when the workspace was hidden. A high mentalizing ability was an advantage when instructing, resulting in fewer errors, but may be a disadvantage when following instructions. This research indicates that ToM plays a key role in communicating information effectively in conversation. (shrink)

Theory of Mind is the ability to predict and understand the mental state of another. While ToM is theorized to play a role in language, we examined whether such a mentalizing ability plays an important role in establishing shared understanding in conversation. Pairs of participants engaged in a Lego model building task in which a director instructed a builder on how to create duplicate models from a prototype that only the director could see. We manipulated whether the director could see (...) or could not see the builder’s workspace. As predicted, the Mind in the Eyes test predicted accuracy when the workspace was hidden. A high mentalizing ability was an advantage when instructing, resulting in fewer errors, but may be a disadvantage when following instructions. This research indicates that ToM plays a key role in communicating information effectively in conversation. (shrink)

This collection addresses a post-WWII shift in the hierarchy of scientific explanations, where the highest goal moves from reductionism towards some ...

Recent studies indicate that patients who are diagnosed with vegetative states may retain more awareness than their clinical assessments suggest. Disorders of consciousness traditionally have been diagnosed on the basis of outwardly observable behaviors alone, but new functional imaging studies have shown surprising levels of brain activity in some patients, indicating that even higher-level cognitive functions like language processing and visual imagery may be preserved. For example, one recently developed method purports to detect voluntary mental imagery solely on the basis (...) of neural response patterns observed with functional magnetic resonance imaging. This line of research has already led to some widely reported cases of patients who were discovered to have more brain activity than expected. In November 2009, Rom Houben, a Belgian man who was thought to be in a coma for 23 years, was diagnosed with locked-in syndrome through the use of neuroimaging; however, that assessment was later overturned by further testing. (shrink)

In this paper, we review recent neuroimaging investigations of disorders of consciousness and different disciplines' understanding of consciousness itself. We consider potential tests of consciousness, their legal significance, and how they map onto broader themes in U.S. statutory law pertaining to advance directives and surrogate decision-making. In the process, we outline a taxonomy of themes to illustrate and clarify the variance in state-law definitions of consciousness. Finally, we discuss broader scientific, ethical, and legal issues associated with the advent of neuroimaging (...) for disorders of consciousness and conclude with policy recommendations that could help to mitigate confusion in this realm. (shrink)

The United States’ ambitious Precision Medicine Initiative proposes to accelerate exponentially the adoption of precision medicine, an approach to health care that tailors disease diagnosis, treatment, and prevention to individual variability in genes, environment, and lifestyle. It aims to achieve this by creating a cohort of volunteers for precision medicine research, accelerating biomedical research innovation, and adopting policies geared toward patients’ empowerment. As strategies to implement the PMI are formulated, critical consideration of the initiative's ethical and sociopolitical dimensions is needed. (...) Drawing on scholarship of nationalism and democracy, we discuss the PMI's construction of what we term “genomic citizenship”; the possible normative obligations arising therefrom; and the ethical, legal, and social challenges that will ensue. Although the PMI is a work in progress, discussion of the existing and emerging issues can facilitate the development of policies, structures, and procedures that can maximize the initiative's ability to produce equitable and socially sensitive outcomes. Our analysis can also be applied to other population-based, precision medicine research programs. (shrink)

Voluntariness of consent to research has not been sufficiently explored through empirical research. The aims of this study were to develop a more comprehensive approach to assessing voluntariness and to generate preliminary data on the extent and correlates of limitations on voluntariness. We developed a questionnaire to evaluate subjects’ reported motivations and constraints on voluntariness. 88 subjects in five different areas of clinical research—substance abuse, cancer, HIV, interventional cardiology, and depression—were assessed. Subjects reported a variety of motivations for participation. Offers (...) of financial incentives were common but not influential, pressures from others were rare, and no threats were reported. However, certain financial incentives and—paradoxically—altruistic motivations led some subjects to feel more constrained. Consistent with previous studies, no one pattern of motivation was common to all research subjects. There was little evidence of constrained voluntariness, but some suggestion of areas of concern. Voluntariness appears to be susceptible to systematic empirical investigation. (shrink)

For the theorists of crisis, the revolutionary state comes into existence through violence, and due to its inability to provide an authoritative katechon (restrainer) against internal and external violence, it perpetuates violence until it self-destructs. Writing during extreme economic depression and growing social and political violence, the crisis theorists––Joseph de Maistre, Juan Donoso Cortés, and Carl Schmitt––each sought to blame the chaos of their time upon the Janus-faced postrevolutionary ideals of liberalism and socialism by urging a return to pre-revolutionary moral (...) and religious values. They are united by three counterrevolutionary principles, all of which are purported to remedy revolutionary violence: traditional constitutional fidelity, the philosophy of the decision, and opposition to bourgeois liberalism. This essay is followed by the first complete English translation and publication of Donoso’s letter of October 24, 1851, which contains Donoso’s only reference to the “discussing class,” a political entity later popularized by Schmitt in his 1922 work Political Theology. (shrink)

The advent of new technologies has rekindled some hopes that it will be possible to identify genetic variants that will help to explain why individuals are different with respect to complex traits. At least one leader in the development of “whole genome sequencing”—the Chinese company BGI—has been quite public about its commitment to using the technique to investigate the genetics of intelligence in general and high intelligence in particular. Because one needs large samples to detect the small effects associated with (...) small genetic differences in the sequence of those base pairs, to make headway with the new sequencing technologies, one also needs to enlist much larger numbers of study participants than geneticists have enrolled before. In an effort to increase the size of a sample, one team of researchers approached the Center for Talented Youth at Johns Hopkins University. They wanted to gain access to records concerning participants in CTY's ongoing Study of Exceptional Talent, and they wanted to approach those individuals to see if they would be willing to share samples of their DNA.We agreed that CTY's dilemma about whether to give the researchers access to those records raised larger questions about the ethics of research into the genetics of intelligence, and we decided to hold a workshop at The Hastings Center that could examine those questions. Our purpose was to create what, borrowing from Sarah Richardson, we came to call a “transformative conversation” about research into the genetics of general cognitive ability—a conversation that would take a wide and long view and would involve a diverse group of stakeholders, including both people who have been highly critical of the research and people who engage in it. This collection of essays, which grew out of that workshop, is intended to provide an introduction to and exploration of this complex and important area. (shrink)

Participants in clinical studies are frequently unable to remember study information for the duration of their participation in the research. Along with a nine-member work group and a seven-member advisory group, we determined that six elements of consent are necessary to uphold the validity of consent over time: awareness of ongoing participation; understanding the right to withdraw; understanding that withdrawal will not influence other treatment options; knowledge of the general purpose of the research; knowledge of potential risks of participation; and (...) understanding of the differences between traditional, individualized clinical care and standardized treatment during research participation. Based on these important elements, we developed an Assessment of Sustained Informed Consent as a tool to periodically review a protocol’s essential elements with its participants. We hope this will be a useful means of confirming research participants’ continued knowledge of the critical elements of consent, and of identifying those subjects who need reminding. (shrink)

Unrealistic optimism is a bias that leads people to believe, with respect to a specific event or hazard, that they are more likely to experience positive outcomes and/or less likely to experience negative outcomes than similar others. The phenomenon has been seen in a range of health-related contexts—including when prospective participants are presented with the risks and benefits of participating in a clinical trial. In order to test for the prevalence of unrealistic optimism among participants of early-phase oncology trials, we (...) conducted a survey with patients over 18 years of age who were enrolled in a phase I, phase I/II, or phase II clinical cancer trial in the New York City area between August 2008 and October 2009. Participants in our study were asked to compare their own chances of experiencing a range of risks and benefits related to the trial they were enrolled in with the chances of the other trial participants. We found a significant optimistic bias in their responses. Respondents tended to overestimate the benefits of the trial they were enrolled in and underestimate its risks. In addition, we found no significant relationship between respondents’ understanding of the trial’s purpose and how susceptible they were to unrealistic optimism. Our findings suggest that improving the consent process for oncology studies requires more than addressing deficits in understanding. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ought We to Require Emotional Capacity as Part of Decisional Competence?Paul S. Appelbaum* (bio)AbstractThe preceding commentary by Louis Charland suggests that traditional cognitive views of decision-making competence err in not taking into account patients’ emotional capacities. Examined closely, however, Charland’s argument fails to escape the cognitive bias that he condemns. However, there may be stronger arguments for broadening the focus of competence assessment to include emotional capacities, centering (...) on the ways in which emotions aid humans in processing information. Before emotional capacities are added to the list of functions essential for decisional competence, though, the feasibility and utility of such a reorientation must be demonstrated.To what extent ought persons’ capacities to experience emotion be taken into account when determining whether they should be deemed competent to make their own decisions? In the previous article, Louis Charland (1998) argues that traditional models of decision-making competence—of which the MacArthur Competence Treatment Study is a typical example—are mistaken in focusing narrowly on persons’ cognitive abilities to the neglect of emotional factors. In contrast, he suggests, constructs of competence ought explicitly to require a capacity to experience emotions, which he believes is central to meaningful decision making, before deeming persons competent.Charland, as he acknowledges, is not the first to suggest that the presence of some degree of emotional capacity is a necessary element of competence, but his argument is among the most elaborate to date and is certainly worth closer examination. Looked at carefully, however, Charland’s argument does not make quite the case for the determination of emotional capacity in competence assessment that he claims for it. Indeed, as I demonstrate below, Charland may share the same “pernicious [End Page 377] cognitive bias” that he ascribes to more traditional approaches. However, despite what I identify as the problems in Charland’s argument, others have raised more disturbing questions about the lack of attention to emotional issues in competence assessment. Thus, I am not ready to reject entirely the possibility that determinations of decisional competence ought to consider emotional factors. I conclude by outlining the questions that remain to be answered to identify more clearly the potential benefits of such an approach.The Construct of Decision-Making CompetenceSome preliminary comments about the nature of the dominant construct of decision-making competence may provide a useful frame for my response to Charland’s paper. Contemporary ideas of competence are tied inextricably to the ideal of self-determination in modern Western societies. Such societies are committed to respect for individual choice, both as a good in its own right and on the grounds that each person knows best what choices will maximize his or her own welfare. In general, therefore, states will not intervene to prevent persons from acting on their decisions, even when the choices they make—like the decision to smoke or to refuse potentially life-saving medical care—may objectively be thought to be detrimental to them.In some cases, however, the presumption that people will act in their own interests, as well as the notion that there is something intrinsically valuable in respecting their choices, fails (Buchanan and Brock 1989). When people’s minds are so disordered that they cannot be said to be making meaningful choices, other values come into play. Such people are called “incompetent.” When persons reach that point, the state’s interest in protecting its citizens becomes primary and someone else must make decisions on their behalf. Note that the size of this group must be sharply limited, lest a liberal society’s commitment to self-determination be undermined: There is no more profound infringement of the rights of citizens than the determination that they are incompetent. Thus, the criteria for incompetence must be selected in a deliberately narrow fashion—alternately, one might say that the standards for competence are made intentionally broad—so that all but a tiny percentage of citizens will be permitted to make decisions on their own.In the Anglo-American world, the process of formulating criteria of competence by and large has been left to the common law courts. Over the course of centuries they have identified the capacities that are, in... (shrink)

(2002). Clarifying the Ethics of Clinical Research: A Path toward Avoiding the Therapeutic Misconception. The American Journal of Bioethics: Vol. 2, No. 2, pp. 22-23.

In lieu of an abstract, here is a brief excerpt of the content:Appreciating Anorexia:Decisional Capacity and the Role of ValuesThomas Grisso (bio) and Paul S. Appelbaum (bio)Keywordscompetence, consent, anorexia, appreciation, decision makingTan and her colleagues (2006) reported that persons with anorexia nervosa typically manifest no difficulty satisfying the criteria for abilities associated with competence to consent to or refuse treatment. Their results led them to conclude that these patients generally had no problem grasping the nature of anorexia and its (...) possible consequences (understanding), typically did not have difficulty processing information when making treatment decisions (reasoning), and usually neither denied that they had a disorder nor manifested distorted beliefs about the potential consequences of treatment for the disorder.Nevertheless, these authors found, some anorexia patients said that they knew they might die and that they would rather die than suffer the alternative consequences (e.g., loss of identity, feeling of being disgusting). They point out that these beliefs, suggesting questionable competence, were not identified by the usual criteria for competence to consent to treatment. Therefore, they propose that we should consider a modification of the criteria for competence to consent to treatment. They argue for inclusion of "pathological values" as the basis for a finding of incompetence. Their notion of a pathological value (as we summarize it based on their Discussion) includes (a) a personal value (b) on which treatment refusal is based, that (c) is not authentic, and (d) is due to a mental disorder.Second, Tan and colleagues were concerned that the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), currently used widely to assess competence to consent to treatment, did not seem to take values into account when examining deficits related to lack of appreciation or reasoning. They point out that most patients with anorexia nervosa in their study had "pathological values" that influenced their thinking about treatment, yet they did not obtain poor scores on the instrument's appreciation scale, which assesses whether patients deny that they have the illness or offer reasons for accepting or refusing treatment that are based on delusional premises or a serious distortion of reality. Moreover, almost all of the anorexia patients in the study obtained adequate scores on reasoning, which examines the ability to process options and consequences when weighing a treatment decision. [End Page 293]Reasons for Caution in Altering Criteria for CompetenceA fundamental step in considering Tan and her co-worker's proposal is to examine whether it is necessary to add a concept of "pathological values" to the legal construct of competence to consent to treatment. Modifying the legal doctrine of consent is important if that is needed to improve its validity or reliability. But modifications of the doctrine would have considerable costs, including a long process of producing logical and empirical evidence for its necessity, developing methods to assess the new concept, and then a process of debate, persuasion, and education to change laws, ethical guidelines, and medical training. Moreover, principles of theory building urge parsimony. A theory should employ no more concepts or assumptions than are required to account for the phenomena that the theory seeks to organize or explain. So one must be sure that modifications are truly necessary before adding complexity to the theory of decisional competence.In addition, there is an inherent danger in altering a concept like competence to consent to treatment on the basis of the study of any one mental disorder. It is not at all clear how the modification might influence findings of competence when applied to other disorders. Using a study of patients with anorexia nervosa as the impetus for changing the competence concept runs this risk. For example, anorexia is one of a class of mental disorders that is characterized by a failure to abstain from behavior (here, limiting food intake and other behaviors designed to reduce weight) that has negative consequences for the person. Other conditions in this category might include substance abuse disorders and impulse control disorders (e.g., pathological gambling). Even if one concludes that revised criteria for competence would reduce false-positive findings of competence in this group of disorders, one would have to consider carefully its impact on the full range of disabling mental conditions.Moreover, the sensitivity... (shrink)

Volume 19, Issue 5, May 2019, Page 22-24.

Whole genome and exome sequencing techniques raise hope for a new scale of diagnosis, prevention, and prediction of genetic conditions, and improved care for children. For these hopes to materialize, extensive genomic research with children will be needed. However, the use of WGS/WES in pediatric research settings raises considerable challenges for families, researchers, and policy development. In particular, the possibility that these techniques will generate genetic findings unrelated to the primary goal of sequencing has stirred intense debate about whether, which, (...) how, and when these secondary or incidental findings should be returned to parents and minors. The debate is even more pronounced when the subjects are adolescents, for whom decisions about return of SFs may have particular implications. In this paper, we consider the rise of “genomic citizenship” and the main challenges that arise for these stakeholders: adolescents' involvement in decisions relating to return of genomic SFs, the types of SFs that should be offered, privacy protections, and communication between researchers and adolescents about SFs. We argue that adolescents' involvement in genomic SF-related decisions acknowledges their status as valuable stakeholders without detracting from broader familial interests, and promotes more informed genomic citizens. (shrink)

Genomic research—including whole genome sequencing and whole exome sequencing—has a growing presence in contemporary biomedical investigation. The capacity of sequencing techniques to generate results that go beyond the primary aims of the research—historically referred to as “incidental findings”—has generated considerable discussion as to how this information should be handled—that is, whether incidental results should be returned, and if so, which ones.Federal regulations governing most human subjects research in the United States require the disclosure of “the procedures to be followed” in (...) the research as part of the informed consent process. It seems reasonable to assume—and indeed, many commentators have concluded—that genomic investigators will be expected to inform participants about, among other procedures, the prospect that incidental findings will become available and the mechanisms for dealing with them. Investigators, most of whom will not have dealt with these issues before, will face considerable challenges in framing meaningful disclosures for research participants.To help in this task, we undertook to identify the elements that should be included in the informed consent process related to incidental findings. We did this by surveying a large number of genomic researchers (n = 241) and by conducting in‐depth interviews with a smaller number of researchers (n = 28) and genomic research participants (n = 20). Based on these findings, it seems clear to us that routine approaches to informed consent are not likely to be effective in genomic research in which the prospect of incidental findings exists. Ensuring that participants’ decisions are informed and meaningful will require innovative approaches to dealing with the consent issue. We have identified four prototypical models of a consent process for return of incidental findings. (shrink)

In much of the current academic and public discussion, conspiracy theories are portrayed as a negative phenomenon, linked to misinformation, mistrust in experts and institutions, and political propaganda. Rather surprisingly, however, philosophers working on this topic have been reluctant to incorporate a negatively evaluative aspect when either analyzing or engineering the concept conspiracy theory. In this paper, we present empirical data on the nature of the concept conspiracy theory from five studies designed to test the existence, prevalence and exact form (...) of an evaluative dimension to the ordinary concept conspiracy theory. These results reveal that, while there is a descriptive concept of conspiracy theory, the predominant use of conspiracy theory is deeply evaluative, encoding information about epistemic deficiency and often also derogatory and disparaging information. On the basis of these results, we present a new strategy for engineering conspiracy theory to promote theoretical investigations and institutional discussions of this phenomenon. We argue for engineering conspiracy theory to encode an epistemic evaluation, and to introduce a descriptive expression—such as ‘conspiratorial explanation’—to refer to the purely descriptive concept conspiracy theory. (shrink)