Patricia A. King

Neurocognitive enhancement: what can we do and what should we do?

Our growing ability to alter brain function can be used to enhance the mental processes of normal individuals as well as to treat mental dysfunction in people who are ill. The prospect of neurocognitive enhancement raises many issues about what is safe, fair and otherwise morally acceptable. This article resulted from a meeting on neurocognitive enhancement that was held by the authors. Our goal is to review the state of the art in neurocognitive enhancement, its attendant social and ethical problems, and the ways in which society can address these problems.

The Use of Race Variables in Genetic Studies of Complex Traits and the Goal of Reducing Health Disparities: A Transdisciplinary Perspective.

The use of racial variables in genetic studies has become a matter of intense public debate, with implications for research design and translation into practice. Using research on smoking as a springboard, the authors examine the history of racial categories, current research practices, and arguments for and against using race variables in genetic analyses. The authors argue that the sociopolitical constructs appropriate for monitoring health disparities are not appropriate for use in genetic studies investigating the etiology of complex diseases. More powerful methods for addressing population structure exist, and race variables are unacceptable as gross proxies for numerous social/environmental factors that disproportionately affect minority populations. The authors conclude with recommendations for genetic researchers and policymakers, aimed at facilitating better science and producing new knowledge useful for reducing health disparities.

Safety issues in cell-based intervention trials

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established.

Twenty years after. The legacy of the Tuskegee Syphilis Study. The dangers of difference.

It has been sixty years since the beginning of the Tuskegee syphilis experiment and twenty years since its existence was disclosed to the American public. The social and ethical issues that the experiment poses for medicine, particularly for medicines relationship with African Americans, are still not broadly understood, appreciated, or even remembered.[1] Yet a significant aspect of the Tuskegee experiments legacy is that in a racist society that incorporates beliefs about the inherent inferiority of African Americans in contrast with the superior status of whites, any attention to the question of differences that may exist is likely to be pursued in a manner that burdens rather than benefits African Americans. The Tuskegee experiment, which involved approximately 400 males with late-stage, untreated syphilis and approximately 200 controls free of the disease, is by any measure one of the dark pages in the history of American medicine. In this study of the natural course of untreated syphilis, the participants did not give informed consent. Stunningly, when penicillin was subsequently developed as a treatment for syphilis, measures were taken to keep the diseased participants from receiving it. Obviously, the experiment provides a basis for the exploration of many ethical and social issues in medicine, including professional ethics,[2] the limitations of informed consent as a means of protecting research subjects, and the motives and methods used to justify the exploitation of persons who live in conditions of severe economic and social disadvantage. At bottom, however, the Tuskegee experiment is different from other incidents of abuse in clinical research because all the participants were black males. The racism that played a central role in this tragedy continues to infect even our current well-intentioned efforts to reverse the decline in health status of African Americans.[3] Others have written on the scientific attitudes about race and heredity that flourished at the time that the Tuskegee experiment was conceived.[4] There has always been widespread interest in racial differences between blacks and whites, especially differences that related to sexual matters. These perceived differences have often reinforced and justified differential treatment of blacks and whites, and have done so to the detriment of blacks. Not surprisingly, such assumptions about racial differences provided critical justification for the Tuskegee experiment itself. Before the experiment began a Norwegian investigator had already undertaken a study of untreated syphilis in whites between 1890 and 1910. Although there had also been a follow-up study of these untreated patients from 1925 to 1927, the original study was abandoned when arsenic therapy became available. In light of the availability of therapy a substantial justification for replicating a study of untreated syphilis was required. The argument that provided critical support for the experiment was that the natural course of untreated syphilis in blacks and whites was not the same.[5] Moreover, it was thought that the differences between blacks and whites were not merely biological but that they extended to psychological and social responses to the disease as well. Syphilis, a sexually transmitted disease, was perceived to be rampant among blacks in part because blacks--unlike whites--were not inclined to seek or continue treatment for syphilis. The Dilemma of Difference In the context of widespread belief in the racial inferiority of blacks that surrounded the Tuskegee experiment, it should not come as a suprise that the experiment exploited its subjects. Recognizing and taking account of racial differences that have historically been utilized to burden and exploit African Americans poses a dilemma.[6] Even in circumstances where the goal of a scientific study is to benefit a stigmatized group or person, such well-intentioned efforts may nevertheless cause harm. …

The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions.

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Harms of Excluding Pregnant Women from Clinical Research: The Case of HIV‐Infected Pregnant Women

ince the beginning of the AIDS epidemic, the proportion of AIDS cases among women has continued to S rise. Women constituted 23 percent of the AIDS cases reported to the Centers for Disease Control and Prevention (CDC) in 1995, and 81 percent of these women were of childbearing age (13 to 44 years).’ It was not until 1991, however, that epidemiological studies of women were initiated. By comparison, the representation of HIV-infected women in clinical trials2 gradually has grown.3 Undoubtedly, a consequence of the increased numbers of women in clinical and epidemiological research is the earlier identification of and more appropriate treatments for HIV-related syndromes when women present in the clinical setting. Despite this expanded focus on women, however, clear information to guide the treatment of HIV-infected women who are pregnant is still lagging behind. Predating the HIV epidemic, researchers and the federal government have been reluctant to include or allow pregnant women in therapeutic trials, primarily because of potential harm to the developing fetus. Although an understandable concern, such policies inevitably result in inadequate information being available to guide clinical practice for HIV-infected pregnant women. Providers have often been left to wonder whether, on balance, it is better to provide or withhold treatment for HIV-infected pregnant women. The lack of information to guide treatment decisions for HIV-infected pregnant women is one example of the larger concern about the general insufficiency of information to guide treatment decisions for pregnant women with underlying medical conditions. It is our purpose (1) to describe how pregnant and nonpregnant HIV-infected women are included in clinical