In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro systems have revealed important (...) regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

The idea that conventionalized general knowledge – sometimes referred to as a frame – guides the perception and interpretation of the world around us has long permeated various branches of cognitive science, including psychology, linguistics, and artificial intelligence. In this paper we provide experimental evidence suggesting that frames also play a role in explaining certain long-distance dependency phenomena, as originally proposed by Deane. We focus on a constraint that restricts the extraction of an NP from another NP, called subextraction, which (...) Deane claims is ultimately a framing effect. In Experiment 1 we provide evidence showing that referents are extractable to the degree that they are deemed important for the proposition expressed by the utterance. This suggests that the world knowledge that the main verb evokes plays a key role in establishing which referents are extractable. In Experiment 2 we offer evidence suggesting that the acceptability of deep subextractions is correlated with the overall plausibility of the proposition, suggesting that complex structures can evoke complex frames as well, if sufficiently frequent and semantically coherent, and therefore more easily license deeper subextractions. (shrink)

Bioethics needs an expanded moral vision. It is now time for bioethics to take full account of the problems of health disparities and structural injustice that are made newly urgent by the COVID-19 pandemic and the effects of climate change. Nancy M. P. King, Gail E. Henderson, and Larry R. Churchill make the case for a more social understanding and application of justice, a deeper humility in assessing expertise in bioethics consulting, a broader and more relevant research agenda, and (...) greater appreciation of the profound health implications of global warming. (shrink)

Recent empirical work has offered strong support for ‘biased pluralism’ and ‘economic elite’ accounts of political power in the United States, according a central role to ‘business interest groups’ as a mechanism through which corporate influence is exerted. Here, we propose an additional channel of influence for corporate interests: the ‘policy-planning network,’ consisting of corporate-dominated foundations, think tanks, and elite policy-discussion groups. To evaluate this assertion, we consider one key policy-discussion group, the Council on Foreign Relations. We first briefly review (...) the origins of this organization and then review earlier findings on its influence. We then code CFR policy preferences on 295 foreign policy issues during the 1981–2002 period. In logistic regression analyses, we find that the preferences of more affluent citizens and the CFR were positive, statistically significant predictors of foreign policy outcomes while business interest group preferences were not. These findings are discussed with a consideration of the patterns of CFR ‘successes’ and ‘failures’ for the issues in our dataset. Although a full demonstration of a causal connection between corporate interests, the policy-planning network and policy outcomes requires further research, we conclude that this has been shown to be a plausible mechanism through which corporate interests are represented and that ‘biased pluralism’ researchers should include it in their future investigations. (shrink)

This book evaluates some of the most common ethical issues confronted by reproductive endocrinologists, embryologists, and their teams. The authors apply core ethical principles and approaches to problem solving to each of the cases raised. This work is a guide for both those on the front lines of patient care as well as for students in the field, whatever their background. By outlining sample cases, the book is an instigator for ethical discussions among ethicists, medical practitioners and students.

The prospect of using cell-based interventions to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior—brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause (...) for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment. (shrink)

Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

Threshold- and signal-detection-based models have dominated theorizing about recognition memory. Building upon these theoretical frameworks, we have argued for a dual-process model in which conscious recollection and familiarity contribute to memory performance. In the current paper we assessed several memory models by examining the effects of levels of processing and the number of presentations on recognition memory receiver operating characteristics . In general, when the ROCs were plotted in probability space they exhibited an inverted U shape; however, when they were (...) plotted inzspace they exhibited a U shape. An examination of the ROCs showed that the dual-process model could account for the observed ROCs, but that models based solely on either threshold or signal-detection processes failed to provide a sufficient account of the data. Furthermore, an examination of subjects' introspective reports using the remember/know procedure showed that subjects were aware of recollection and familiarity and were able to consistently report on their occurrence. The remember/know data were used to accurately predict the shapes of the ROCs, and estimates of recollection and familiarity derived from the ROC data mirrored the subjective reports of these processes. (shrink)

As a gynecologic surgeon with a focus on infertility, I frequently hold complex discussions with patients, exploring with them the risks and benefits of surgical options. In the past, we physicians may have expected our patients to simply defer to our expertise and choose from the options we presented. In our contemporary era, however, patients frequently request options not favored by their physicians and even some they've found themselves online. In reproductive endocrinology and infertility, the range of options that may (...) be offered or that patients may themselves seek out is continuously widening. Physicians certainly seek to find the option that will result in the best outcome for their patients, but the information to guide us in achieving the best outcome can be vague or conflicting. Add to this the financial and emotional pressures bearing on patients seeking assisted reproduction. In this essay, I explore the extent to which clinicians in reproductive medicine should follow patient requests with which they disagree or instead try to persuade the patient to do something else or simply refuse outright to meet the request. And if persuasion is to be used, what would be legitimate methods? Clearly, coercion is unacceptable, but the line between persuasion and coercion can be elusive. At what point can or should clinicians resist such requests—and to what degree? (shrink)

Clinical gene transfer research has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee. This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.Clinical GTR is governed by the same (...) oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration. (shrink)

The three important target articles make a strong case for regarding racism as a public health crisis. Each calls for advocacy by the bi...

Informed consent in clinical research is widely regarded as broken, but essential nonetheless. The most recent attempt to reform it comes as part of the first revisions to the Common Rule since it became truly “common” in 1991. This change, the addition of a “key information” requirement for most consent forms, is intended to support and promote a reasoned decision-making process by potential subjects. The key information requirement is both promising and problematic. It is promising because it encourages clarity and (...) honesty about research participation, creativity in information disclosure, and mutual learning through the investigator-subject relationship. It is problematic because those goals — which have remained aspirational since the beginning — may be difficult to achieve in what has become an excessively compliance-oriented regulatory regime. (shrink)

Giving up the increasingly troubled distinction between “experiment” and “treatment” would make it easier to focus on informed consent and harder to beg questions about uncertainty and shared decisionmaking in medicine.

The Covid‐19 pandemic has concentrated bioethics attention on the “lifeboat ethics” of rationing and fair allocation of scarce medical resources, such as testing, intensive care unit beds, and ventilators. This focus drives ethics resources away from persistent and systemic problems—in particular, the structural injustices that give rise to health disparities affecting disadvantaged communities of color. Bioethics, long allied with academic medicine and highly attentive to individual decision‐making, has largely neglected its responsibility to address these difficult “upstream” issues. It is time (...) to broaden our teaching, research, and practice to match the breadth of the field in order to help address these significant societal inequities and unmet health needs. (shrink)

Despite great advances in understanding genetic mechanisms, there still exists a bias toward equating genes with innate modules that determine important developmental events. But genes are equally relevant to understanding developmental plasticity shaped by ecological events. In other words, the term 'genetic inheritance' does not specify ontogenetic mechanisms. Here we present a case history of a species assumed to be under the control of prespecified genetic wiring to direct critical behavioral events such as communication and mating. We show, however, that (...) exogenetic processes stemming from the species's ontogenetic niche provide an alternative view of the flexibility of development especially with respect to behavioral performance. (shrink)

The principle of informed consent is so firmly established in bioethics and biomedicine that the term was soon bowdlerized in common practice, such that engaging in the informed decision-making process with patients or research subjects is now often called “consenting” them. This evolution, from the original concept to the rather questionable coinage that makes consent a verb, reveals not only a loss of rhetorical precision but also a fundamental shift in the potential meaning, value, and implementation of the informed consent (...) process. Too often, the sharing of information has been replaced by the mere acquisition of agreement with the authority ostensibly offering a choice.Scholars of informed consent agree that its salience and its legitimacy derive from a fiduciary duty to inform, in order to respect, protect, and promote autonomous decision making by those to whom the duty is owed. (shrink)

On September 8, 2015, the Department of Health and Human Services issued a Notice of Proposed Rule Making to revise the Federal Policy for the Protection of Human Subjects, widely known as the “Common Rule.” The NPRM proposes several changes to the current system, including a dramatic shift in the approach to secondary research using biospecimens and data. Under the current rules, it is relatively easy to use biospecimens and data for secondary research. This approach systematically facilitates secondary research with (...) biospecimens and data, maximizing the capacity for substantial public benefit. However, it has been criticized as insufficiently protective of the privacy and autonomy interests of biospecimen and data sources. Thus, the NPRM proposes a more restrictive regime, although more so for biospecimens than data. Both the status quo and the NPRM's proposal are critically flawed. (shrink)

First-in-human research has several characteristics that require special attention with respect to ethics and human subjects protections. At least some nanomedical technologies may also have characteristics that merit special attention in clinical research, as other papers in this symposium show. This paper considers how to address these characteristics in the consent form and process for FIH nanomedicine research, focusing principally on experimental nanotherapeutic interventions but also considering nanodiagnostic interventions.It is essential, as a starting point, to recognize that the consent form (...) and process are by no means the primary protectors of human subjects. Instead, consideration of the form and content of informed consent becomes relevant only after a clinical trial has been reviewed and deemed scientifically and ethically acceptable.Two convergent types of challenges to informed consent are posed by nanomedicine FIH research. First, some issues appear generally applicable to FIH research, but have specific nanomedicine implications. (shrink)

One of my favorite bioethics quotes is nearing 50 years old:Let us not forget that progress is an optional goal, not an unconditional commitment, and that its tempo in particular, compulsive as it may become, has nothing sacred about it. Let us also remember that a slower progress in the conquest of disease would not threaten society, grievous as it is to those who have to deplore that their particular disease be not yet conquered, but that society would indeed be (...) threatened by the erosion of those moral values whose loss, possibly caused by too ruthless a pursuit of scientific progress, would make its most dazzling triumphs not worth having.Despite its age, this invocation seems to me increasingly relevant as time... (shrink)

Complete moral consensus on the status of the human embryo is neither feasible nor necessary for the formulation of ethically acceptable public policy for human embryo research. Significant consensus on permissible human embryo research can rest upon diverse but overlapping moral traditions. Thus, human embryo research policy should do more than reflect mere abstract assertions about the moral status of human embryos. Rather, the moral underpinnings of human embryo research should be derived from a range of values, including the facilitation (...) of human procreation, the advancement of applied scientific knowledge, the reduction of human suffering, and the protection of vulnerable persons from coercion and exploitation. (shrink)

Biodefense and emerging infectious disease animal research aims to avoid or ameliorate human disease, suffering, and death arising, or potentially arising, from natural outbreaks or intentional deployment of some of the world’s most dreaded pathogens. Top priority research goals include finding vaccines to prevent, diagnostic tools to detect, and medicines for smallpox, plague, ebola, anthrax, tularemia, and viral hemorrhagic fevers, among many other pathogens (National Institute of Allergy and Infectious Diseases [NIAID] priority pathogens). To this end, increased funding for conducting (...) research, developing research facilities, and purchasing (stockpiling) developed vaccines, diagnostic tools, and therapeutics .. (shrink)

Medical teams care for severely premature infants under conditions of emergency and uncertainty that make parental involvement very difficult. Parents can be invited into a decisional relationship with the team that enables them to assess more fully the meaning of their child's illness.

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver (...) of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood—the standard treatment for hemorrhagic shock—is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

Gene therapy is still a very crude way of treating very complicated problems. It's hard to get new genes to go where they're needed, and hard to keep them from going where they're not wanted. The worst‐case scenario is that they find their way into a patient's germ cells—eggs or sperm—and end up harming the patient's offspring. Yet this possibility is hard to study in human trials, and would be hard to deal with in the clinic. It should, instead, simply (...) be avoided. Doing so requires fundamentally changing our approach to gene therapy. (shrink)

Respect for autonomy is a central value in reproductive ethics, but it can be a challenge to fulfill and is sometimes an outright puzzle to understand. If a woman requests the transfer of two, three, or four embryos during fertility treatment, is that request truly autonomous, and do clinicians disrespect her if they question that decision or refuse to carry it out? Add a commitment to justice to the mix, and the challenge can become more complex still. Is it unfair (...) for insurance policies to exclude from coverage the costs of giving fertility to those who lack it or restoring fertility in those who have lost it? What does “just reproduction” look like in the face of multifarious understandings of both justice and autonomy and in light of increasingly complex and costly reproductive technologies? In today's dialogue about reproduction, medicine, and ethics in the United States, old ethical issues—such as whether women ought to be allowed to access pregnancy termination—are more contested than they have been in decades, while new technologies—like those used to edit the genes of human embryos—suggest that our species could face unprecedented questions about who should exist. As we considered the discussions accompanying these issues and contemplated a special report responding to them, we found ourselves consistently circling back to two ethical commitments: respect for autonomy and the pursuit of justice. As one of the nine essays in this collection asks, why should certain women receive help to establish a pregnancy while others are thrown in jail when they miscarry or their child is stillborn? Respect for autonomy is required where individuals have the ability to make fully informed and voluntary choices. Yet does respecting autonomy require acceding to all the choices of patients or consumers of medical care? We consider these and related questions in this special report from the Hastings Center Report. (shrink)

The majority of obstetrician‐gynecologists in practice operate very infrequently. Most residents graduate with strong surgical skill sets, given residency requirements. Nonetheless, their practices become dominated by obstetrics, and their gynecologic surgical skills deteriorate. While cesarean sections are surgical in nature, the skill sets needed in these surgeries differ from the skills used in general gynecologic surgery. As gynecology has taken a back seat to obstetrics in our specialty, not only surgical skills but also diagnostic and management skills have deteriorated.

_Bioethics, Public Moral Argument, and Social Responsibility_ explores the role of democratically oriented argument in promoting public understanding and discussion of the benefits and burdens of biotechnological progress. The contributors examine moral and policy controversies surrounding biomedical technologies and their place in American society, beginning with an examination of discourse and moral authority in democracy, and addressing a set of issues that include: dignity in health care; the social responsibilities of scientists, journalists, and scholars; and the language of genetics and (...) moral responsibility. (shrink)

The volume presents essays on the philosophical explanation of the relationship between body and soul in antiquity from the Presocratics to Galen. The title of the volume alludes to a phrase found in Plato, Aristotle and Plotinus, referring to aspects of living behaviour involving both body and soul, and is a commonplace in ancient philosophy, dealt with in very different ways by different authors.

Hastings Center Report, Volume 52, Issue 3, Page 3-3, May–June 2022.

Decision making during reproduction is complex for a variety of medical and social reasons. Anyone who has had a conversation with a family member about the “best time” to have a baby can attest to this — there is no “best time” or “best way.” Multiple pressures from any number of sources combine in a minefield of hazards made ever more complicated by restrictive laws in the US. Add to this a screening result of potential chromosomal aneuploidy and decision making (...) becomes ever more complex. Societal stigma and lack of adequate and accurate information during counseling certainly plays a role in the high number of terminations in the setting of diagnosed chromosomal aneuploidy, yet other factors also push families in this direction including medical considerations and the abysmal lack of social support programs. (shrink)