Pharmacogenetics: ethical issues and policy options

Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.     

Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors

The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.     

Place learning in scopolamine-treated rats: the roles of distal cues and catecholaminergic mediation

Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.     

Methylphenidate in treatment of adults with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) can persist into adulthood with a continuation of the pattern of childhood psychopathology, cognition and functioning. Adult comorbidities include substance use disorders, antisocial personality disorder, anxiety, and depression. Studies have shown that as in children, methylphenidate treatment for adults can lead to a robust, dose-dependent improvement in ADHD symptoms. Future research is needed to evaluate the safety and efficacy of long-term treatment with methylphenidate (MPH).     

The continuing need for disinterested research

For scientific knowledge to be trustworthy, it needs to be dissociated from material interests. Disinterested research also performs other important non-instrumental roles. In particular, academic science has traditionally provided society with reliable, imaginative public knowledge and independent, self-critical expertise. But this type of science is not compatible with the practice of instrumental research, which is typically proprietary, prosaic, pragmatic and partisan. With ever-increasing dependence on commercial or state funding, all modes of knowledge production are merging into a new, ‘post-academic’ research culture which is dominated by utilitarian goals. Growing concern about conflicts of interest is thus a symptom of deep-seated malaise in science and medicine. An expanded version of this paper was presented at an International Conference on “Conflict of Interest and its Significance in Science and Medicine” held in Warsaw, Poland on 5–6 April, 2002.     

Measuring differences in preactivation on the Internet: the content category superiority effect

Preactivation of particular content categories in memory yields latency differences in a visual recognition task. Two Internet studies demonstrate this content category superiority effect (CCSE). Target words are repeatedly flashed for 400 ms and then masked for 200 ms. Experiment 1 shows that differences in pre-activated memory content, related to participants' use of computer operating systems, influence z-scored visual word recognition latencies. Experiment 2 shows that this influence is susceptible to instruction. Participants expecting to find positive words recognized those words faster, whereas participants expecting to find negative words were faster on negative words. The CCSE provides a basis on which new measures of implicit memory content can be founded. Two such applications are discussed--the Motive Superiority Measure of implicit motives, and a latency-based measure of self-focused attention.     

The effects of approach and avoidance motor actions on the elements of creative insight

The authors propose that the nonaffective bodily feedback produced by arm flexion and extension informs individuals about the processing requirements of the situation, leading to the adoption of differential processing styles and thereby influencing creativity. Specifically, the authors predicted that arm flexion would elicit a heuristic processing strategy and bolster insight processes, whereas arm extension would elicit a systematic processing strategy and impair insight processes. To test these predictions, the authors assessed the effects of these motor actions on 3 central elements of creative insight: contextual set-breaking, restructuring, and mental search. As predicted, in 6 experiments, arm flexion, relative to arm extension, facilitated insight-related processes. In a 7th experiment, arm extension, relative to arm flexion, facilitated analytical reasoning, supporting a cognitive tuning interpretation of the findings.     

A signal detection model predicts the effects of set size on visual search accuracy for feature, conjunction, triple conjunction, and disjunction displays

Recently, quantitative models based on signal detection theory have been successfully applied to the prediction of human accuracy in visual search for a target that differs from distractors along a single attribute (feature search). The present paper extends these models for visual search accuracy to multidimensional search displays in which the target differs from the distractors along more than one feature dimension (conjunction, disjunction, and triple conjunction displays). The model assumes that each element in the display elicits a noisy representation for each of the relevant feature dimensions. The observer combines the representations across feature dimensions to obtain a single decision variable, and the stimulus with the maximum value determines the response. The model accurately predicts human experimental data on visual search accuracy in conjunctions and disjunctions of contrast and orientation. The model accounts for performance degradation without resorting to a limited-capacity spatially localized and temporally serial mechanism by which to bind information across feature dimensions.     

The perceived position of the hand in space

This paper reports a series of experiments of the perceived position of the hand in egocentric space. The experiments focused on the bias in the proprioceptively perceived position of the hand at a series of locations spanning the midline from left to right. Perceived position was tested in a matching paradigm, in which subjects indicated the perceived position of a target, which could have been either a visual stimulus or their own fingertip, by placing the index finger of the other hand in the corresponding location on the other side of a fixed surface. Both the constant error, or bias, and the variable error, or consistency of matching attempts, were measured. Experiment 1 showed that (1) there is a far-left advantage in matching tasks, such that errors in perceived position are significantly lower in extreme-left positions than in extreme-right positions, and (2) there is a strong hand-bias effect in the absence of vision, such that the perceived positions of the left and right index fingertips held in the same actual target position in fact differ significantly. Experiments 2 and 3 demonstrated that this hand-bias effect is genuinely due to errors in the perceived position of the matched hand, and not to the attempt at matching it with the other hand. These results suggest that there is no unifying representation of egocentric, proprioceptive space. Rather, separate representations appear to be maintained for each effector. The bias of these representations may reflect the motor function of that effector.