This paper critically examines the biology of species identity and the morality of crossing species boundaries in the context of emerging research that involves combining human and nonhuman animals at the genetic or cellular level. We begin with the notion of species identity, particularly focusing on the ostensible fixity of species boundaries, and we explore the general biological and philosophical problem of defining species. Against this backdrop, we survey and criticize earlier attempts to forbid crossing species boundaries in the creation (...) of novel beings. We do not attempt to establish the immorality of crossing species boundaries, but we conclude with some thoughts about such crossings, alluding to the notion of moral confusion regarding social and ethical obligations to novel interspecies beings. (shrink)

: "Therapeutic misconception" has been misconstrued, and some of the newer, mistaken interpretations are troublesome. They exaggerate the distinction between research and treatment, revealing problems in the foundations of research ethics and possibly weakening informed consent.

: The transplantation of adult human neural stem cells into prenatal non-humans offers an avenue for studying human neural cell development without direct use of human embryos. However, such experiments raise significant ethical concerns about mixing human and nonhuman materials in ways that could result in the development of human-nonhuman chimeras. This paper examines four arguments against such research, the moral taboo, species integrity, "unnaturalness," and human dignity arguments, and finds the last plausible. It argues that the transfer of human (...) brain or retinal stem cells to nonhuman embryos would not result in the development of human-nonhuman chimeras that denigrate human dignity, provided such stem cells are dissociated. The article provides guidelines that set ethical boundaries for conducting such research that are consonant with the requirements of human dignity. (shrink)

Advances in cognitive neuroscience make cosmetic neurology in some form inevitable and will give rise to extremely difficult ethical issuesConsider the following hypothetical case study. A well heeled executive walks into my cognitive neurology clinic because he is concerned that he is becoming forgetful. It turns out that he is going through a difficult divorce and my clinical impression is that his memory problems stem from the stress he is experiencing. I place him on a selective seratonin reuptake inhibitor, sertraline, (...) and in a few weeks he feels better. Around this time his 13 year old daughter has difficulty at school and is diagnosed by the school psychologist as having attention deficit disorder. I place her on adderall, a stimulant combination drug, which seems to help with her behaviour in school. My patient then comes to me because he is experiencing the “tip of the tongue” phenomena more frequently. He is concerned that his word finding difficulty interferes with his ability to function in high level meetings. I suggest we try a cholinesterase inhibitor to see if this helps. I am careful to explain that the Food and Drug Administration does not approve such a use for this medication. He wants to try it and is pleased with the results.A few months later, this patient visits me with his 16 year old son, a talented middle distance runner. His father thinks if he were just a bit better, among the elite high school runners in the state, he would be far more competitive as an applicant for selective colleges. We discuss various options. Because of a recent report that sildenafil, which is used conventionally for male impotence, may improve oxygen carrying capacity, I prescribe this medication. The son does not object.Encouraged by these pharmacologic successes, my patient …. (shrink)

As our knowledge of the functional and pharmacological architecture of the nervous system increases, we are getting better at treating cognitive and affective disorders. Along with the ability to modify cognitive and affective systems in disease, we are also learning how to modify these systems in health. “Cosmetic neurology,” the practice of intervening to improve cognition and affect in healthy individuals, raises several ethical concerns. However, its advent seems inevitable. In this paper I examine this claim of inevitability by reviewing (...) the evolution of another medical practice, cosmetic surgery. Cosmetic surgery also enhances healthy people and, despite many critics, it is practiced widely. Can we expect the same of cosmetic neurology? The claim of inevitability poses a challenge for both physicians and bioethicists. How will physicians reconsider their professional role? Will bioethicists influence the shape of cosmetic neurology? But first, how did cosmetic surgery become common? (shrink)

The scientific, ethical, and policy issues raised by research involving the engraftment of human neural stem cells into the brains of nonhuman primates are explored by an interdisciplinary working group in this Policy Forum. The authors consider the possibility that this research might alter the cognitive capacities of recipient great apes and monkeys, with potential significance for their moral status.

: In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in a given study (the subjective (...) interpretation). The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)

: Experiments involving the transplantation of human stem cells and their derivatives into early fetal or embryonic nonhuman animals raise novel ethical issues due to their possible implications for enhancing the moral status of the chimeric individual. Although status-enhancing research is not necessarily objectionable from the perspective of the chimeric individual, there are grounds for objecting to it in the conditions in which it is likely to occur. Translating this ethical conclusion into a policy recommendation, however, is complicated by the (...) fact that substantial empirical and ethical uncertainties remain about which transplants, if any, would significantly enhance the chimeric individual's moral status. Considerations of moral status justify either an early-termination policy on chimeric embryos, or, in the absence of such a policy, restrictions on the introduction of pluripotent human stem cells into early-stage developing animals, pending the resolution of those uncertainties. (shrink)

Experiments involving the transplantation of human stem cells and their derivatives into early fetal or embryonic nonhuman animals raise novel ethical issues due to their possible implications for enhancing the moral status of the chimeric individual. Although status-enhancing research is not necessarily objectionable from the perspective of the chimeric individual, there are grounds for objecting to it in the conditions in which it is likely to occur. Translating this ethical conclusion into a policy recommendation, however, iscomplicated by the fact that (...) substantial empirical and ethical uncertainties remain about which transplants, if any, would significantly enhance the chimeric individual’s moral status. Considerations of moral status justify either an early-termination policy on chimeric embryos, or, in the absence of such a policy, restrictions on the introduction of pluripotent human stem cells into early-stage developing animals, pending the resolution of those uncertainties. (shrink)

As our knowledge of the functional and pharmacological architecture of the nervous system increases, we are getting better at treating cognitive and affective disorders. Along with the ability to modify cognitive and affective systems in disease, we are also learning how to modify these systems in health. “Cosmetic neurology,” the practice of intervening to improve cognition and affect in healthy individuals, raises several ethical concerns. However, its advent seems inevitable. In this paper I examine this claim of inevitability by reviewing (...) the evolution of another medical practice, cosmetic surgery. Cosmetic surgery also enhances healthy people and, despite many critics, it is practiced widely. Can we expect the same of cosmetic neurology? The claim of inevitability poses a challenge for both physicians and bioethicists. How will physicians reconsider their professional role? Will bioethicists influence the shape of cosmetic neurology? But first, how did cosmetic surgery become common? (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)

Slowing the aging process would be one of the most dramatic and momentous ways of enhancing human beings. It is also one that mainstream science is on the brink of pursuing. The state of the science, together with its possible impact, make it an important example for how to think about research into all enhancement technologies.

United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" (§ 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition (§ 45CFR46.406) (DHHS 2001). During the 25 years since their adoption, these regulations have helped (...) IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations § § 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria. (shrink)

The term “therapeutic misconception” was coined in 1982 by Paul Appelbaum, Loren Roth, and Charles Lidz. Appelbaum and his colleagues interviewed participants in several psychiatric studies, including a drug trial with a placebo control arm. Appelbaum's group found that many people were unaware of the differences between participating in a study and receiving treatment in the clinical setting. Rather than understanding these differences, study participants tended to believe that therapy and research were governed by the same primary goal: to advance (...) the individual patient's best interests. Appelbaum's group labeled this mistaken belief the therapeutic misconception. (shrink)

The term “therapeutic misconception” was coined in 1982 by Paul Appelbaum, Loren Roth, and Charles Lidz. Appelbaum and his colleagues interviewed participants in several psychiatric studies, including a drug trial with a placebo control arm. Appelbaum's group found that many people were unaware of the differences between participating in a study and receiving treatment in the clinical setting. Rather than understanding these differences, study participants tended to believe that therapy and research were governed by the same primary goal: to advance (...) the individual patient's best interests. Appelbaum's group labeled this mistaken belief the therapeutic misconception. (shrink)

In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in a given study (the subjective interpretation). (...) The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)