The methodological and ethical concerns of genetic studies of same-sex sexual behavior.

Same-sex sexual behavior has long interested genetics researchers in part because, while there is evidence of heritability, the trait as typically defined is associated with fewer offspring. Investigations of this phenomenon began in the 1990s with linkage studies and continue today with the advent of genome-wide association studies. As this body of research grows, so does critical scientific and ethical review of it. Here, we provide a targeted overview of existing genetics studies on same-sex sexual behavior, highlight the ethical and scientific considerations of this nascent field, and provide recommendations developed by the authors to enhance social and ethical responsibility.

Why Is Studying the Genetics of Intelligence So Controversial?

From the very beginning, studies of the nature and nurture of intelligence have been closely associated with an interest in intervening, and those interventions have been surrounded by controversy. The nature of those controversies has not always been the same, however. Since the mid-nineteenth century, when Francis Galton imagined a science that would assess the extent to which a trait like "genius" was due to nature or due to nurture, science and technology have changed dramatically, and so have the interventions that have been envisioned in light of those developments. A scientist today can search for particular stretches of DNA and assess whether differences in those stretches are associated with differences in a human trait of interest; a genetic counselor today can genetically test an individual (be it an embryo, fetus, newborn, child, or adult) and provide information about what that genetic result means, allowing for interventions that can range from terminating a pregnancy to prescribing chemotherapy. So when one asks a question like, "Why is studying the genetics of intelligence controversial?," it is important to realize up front that the answer will be, "It can be controversial for a variety of different reasons, and those reasons have evolved over time." The purpose of this essay is to provide a survey of the controversies that surround genetic studies of intelligence. With the survey in place, I will then draw out several lessons both for scientists who study the genetics of intelligence as well as for science studies scholars (bioethicists, philosophers, historians, sociologists) who reflect and comment on the controversies surrounding that research.

R. A. FISHER, LANCELOT HOGBEN, AND THE 'COMPETITION' FOR THE CHAIR OF SOCIAL BIOLOGY AT THE LONDON SCHOOL OF ECONOMICS IN 1930: CORRECTING THE LEGEND.

From 1930 to 1937 Lancelot Hogben FRS occupied the Chair of Social Biology at the London School of Economics and Political Science. According to standard histories of this appointment, he and R. A. Fisher FRS both applied for the position, but Hogben was selected over Fisher. The episode has received attention in large part because of the later prominence of the two figures involved. The surviving archival records, however, tell a remarkably different story. Neither Fisher nor Hogben was ever an official candidate for the chair. Indeed, Fisher seems not to have applied for the position at all, and Hogben was approached only behind the scenes of the official search. The purpose of this paper is to correct and complete the history of this episode.

A Children's Rights Framework for Genomic Medicine: Newborn Screening as a Use Case.

The year 2023 marked the 60th anniversary of screening newborns in the United States for diseases that benefit from early identification and intervention. All around the world, the goal of NBS is to facilitate timely diagnosis and management to improve individual health outcomes in all newborns regardless of their place of birth, economic circumstances, ability to pay for treatment, and access to healthcare. Advances in technology to screen and treat disease have led to a rapid increase in the number of screened conditions, and innovations in genomics are expected to exponentially expand this number further. A system where all newborns are screened, coupled with rapid technological innovation, provides a unique opportunity to improve pediatric health outcomes and advance children's rights, including the unique rights of sick and disabled children. This is especially timely as we approach the 100th anniversary of the 1924 Geneva Declaration of the Rights of the Child, which includes children's right to healthcare, and the 1989 United Nations Convention on the Rights of the Child that expanded upon this aspect and affirmed each child's right to the highest attainable standard of health. In this manuscript, we provide background on the evolving recognition of the rights of children and the foundational rights to healthcare and non-discrimination, provide two examples that highlight issues to access and equity in newborn screening that may limit a child's right to healthcare and best possible outcomes, detail ways the current approach to newborn screening advances the rights of the child, and finally, propose that the incorporation of genomics into newborn screening presents a useful case study to recognize and uphold the rights of every child.

Victims of eugenic sterilisation in Utah: cohort demographics and estimate of living survivors.

Background: Eugenicists at the beginning of the twentieth century feared that the "unfit" were outbreeding the "fit" and promoted interventions like sterilisation as a solution to the perceived problem. Over 60,000 people were sterilised across the United States, victims of eugenic programs implemented in 32 states. Utah had a particularly aggressive eugenic sterilisation program, hailed by eugenicists for sterilising such a large proportion of its population, and lasting well into the 1970s. The goal of the present study was to determine who, at the demographic level, was targeted by this eugenic practice in Utah, and to also estimate how many survivors of the program might still be alive in 2023. Methods: We used archival records and data abstracted from charts at the Utah State Developmental Center to construct an observational cohort of people sterilised under Utah's coercive, eugenic sterilisation program. We described the demographics of the cohort and presented a life table analysis to estimate the number of survivors still living in 2023. Findings: At least 830 men, women, and children (modal age of 15-19, 53.6% female) were sterilised in Utah institutions under a program that was launched in 1925, peaked in the 1940s, and concluded in the 1970s. The life table analysis predicts approximately 54 survivors (36 women, 18 men), with an average age of 78. Interpretation: Many people sterilised under Utah's eugenics law are likely living today. While some states have taken steps to reckon with their roles in depriving people of their reproductive rights, Utah lacks even an official acknowledgment of this shameful, medical history. Given the advanced age of the potential survivors, time is running out for a reconciliation that can be experienced by those who were most harmed by the practice. Funding: This research was supported by three grants from the National Human Genome Research Institute at the U.S. National Institutes of Health (RM1HG009037, R25HG010020, R01HG010567).

Wrestling with Social and Behavioral Genomics: Risks, Potential Benefits, and Ethical Responsibility.

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.

Teneille Brown, Leslie Francis, and James Tabery respond.

This is a response to the letter to the editor "Prioritizing the Prevention of Early Deaths during Covid-19," by Govind Persad.

When Is Age Choosing Ageist Discrimination?

When the Covid-19 pandemic reached the United States in spring 2020, many states and hospitals announced crisis standards of care plans that used age as a categorical exclusion criterion. Such age choosing was quickly flagged as discriminatory, and so some states and hospitals shifted to embedding age as a tiebreaker deeper in their plans. Different rationales were given for using age as a tiebreaker: that younger patients were more likely to survive than older patients, that saving younger patients would save more life years, and that younger patients deserved a chance to live through life's stages. We provide a critical analysis of these three rationales, noting the differences between them, and then questioning the ethical and legal justifications for such age choosing.

From a genetic predisposition to an interactive predisposition: rethinking the ethical implications of screening for gene-environment interactions.

In a widely acclaimed study from 2002, researchers found a case of gene-environment interaction for a gene controlling neuroenzymatic activity (low vs. high), exposure to childhood maltreatment, and antisocial personality disorder (ASPD). Cases of gene-environment interaction are generally characterized as evincing a genetic predisposition; for example, individuals with low neuroenzymatic activity are generally characterized as having a genetic predisposition to ASPD. I first argue that the concept of a genetic predisposition fundamentally misconstrues these cases of gene-environment interaction. This misconstrual will be diagnosed, and then a new concept--interactive predisposition--will be introduced. I then show how this conceptual shift reconfigures old questions and raises new questions for genetic screening. Attempts to screen embryos or fetuses for the gene associated with low neuroenzymatic activity with an eye toward selecting against the low-activity variant fall prey to the myth of pre-environmental prediction; attempts to screen newborns for the gene associated with low neuroenzymatic activity with an eye toward early intervention will have to face the interventionist's dilemma.

Developmental systems theory: what does it explain, and how does it explain it?

We examine developmental systems theory (DST) with two questions in mind: What does DST explain? How does DST explain it? To answer these questions, we start by reviewing major contributions to the origins of DST: the introduction of the idea of a "developmental system", the idea of probabilistic epigenesis, the attention to the role of information in the developmental system, and finally the explicit identification of a DST. We then consider what DST is not, contrasting it with two approaches that have been foils for DST: behavioral genetics and nativist cognitive psychology. Third, we distill out two core concepts that have defined DSTthroughout its history: epigenesis and developmental dynamics. Finally, we turn to how DST explains, arguing that it explains by elucidating mechanisms.

The double-edged sword: does biomechanism increase or decrease judges' sentencing of psychopaths?

We tested whether expert testimony concerning a biomechanism of psychopathy increases or decreases punishment. In a nationwide experiment, U.S. state trial judges (N = 181) read a hypothetical case (based on an actual case) where the convict was diagnosed with psychopathy. Evidence presented at sentencing in support of a biomechanical cause of the convict's psychopathy significantly reduced the extent to which psychopathy was rated as aggravating and significantly reduced sentencing (from 13.93 years to 12.83 years). Content analysis of judges' reasoning indicated that even though the majority of judges listed aggravating factors (86.7%), the biomechanical evidence increased the proportion of judges listing mitigating factors (from 29.7 to 47.8%). Our results contribute to the literature on how biological explanations of behavior figure into theories of culpability and punishment.

R. A. Fisher, Lancelot Hogben, and the origin(s) of genotype-environment interaction.

This essay examines the origin(s) of genotype-environment interaction, or G x E. "Origin(s)" and not "the origin" because the thesis is that there were actually two distinct concepts of G x E at this beginning: a biometric concept, or G x EB, and a developmental concept, or G x ED. R. A. Fisher, one of the founders of population genetics and the creator of the statistical analysis of variance, introduced the biometric concept as he attempted to resolve one of the main problems in the biometric tradition of biology--partitioning the relative contributions of nature and nurture responsible for variation in a population. Lancelot Hogben, an experimental embryologist and also a statistician, introduced the developmental concept as he attempted to resolve one of the main problems in the developmental tradition of biology--determining the role that developmental relationships between genotype and environment played in the generation of variation. To argue for this thesis, I outline Fisher and Hogben's separate routes to their respective concepts of G x E; then these separate interpretations of G x E are drawn on to explicate a debate between Fisher and Hogben over the importance of G x E, the first installment of a persistent controversy. Finally, Fisher's G x EB and Hogben's G x ED are traced beyond their own work into mid-20th century population and developmental genetics, and then into the infamous IQ Controversy of the 1970s.

Ethics of triage in the event of an influenza pandemic.

The prospect of a severe influenza pandemic poses a daunting public health threat to hospitals and the public they serve. The event of a severe influenza pandemic will put hospitals under extreme stress; only so many beds, ventilators, nurses, and physicians will be available, and it is likely that more patients will require medical attention than can be completely treated. Triage is the process of sorting patients in a time of crisis to determine who receives what level of medical attention. How will hospitals sort patients to determine priority for treatment? What criteria will be used? Who will develop these criteria? This article formulates an answer to these questions by constructing a conceptual framework for anticipating and responding to the ethical issues raised by triage in the event of a severe influenza pandemic.

Biometric and developmental gene-environment interactions: looking back, moving forward.

A history of research on gene-environment interaction (G x E) is provided in this article, revealing the fact that there have actually been two distinct concepts of G x E since the very origins of this research. R. A. Fisher introduced what I call the biometric concept of G x E (G x EB), whereas Lancelot Hogben introduced what I call the developmental concept of G x E (G x ED). Much of the subsequent history of research on G x E has largely consisted of the separate legacies of these separate concepts, along with the (sometimes acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, more recent attempts to distinguish between different concepts of G x E are considered, paying particular attention to the commonly made distinction between "statistical interaction" and "interactionism," and Michael Rutter's distinction between statistical interaction and "the biological concept of interaction." I argue that the history of the separate legacies of G x EB and G x ED better supports Rutter's analysis of the situation and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G x E in the etiology of complex traits.