Moral enhancement, at the peak of pharmacology and at the limit of ethics.

The debate over the improvement of moral capacity or moral enhancement through pharmacology has gained momentum in the last decade as a result of advances in neuroscience. These advances have led to the discovery and allowed the alteration of patterns of human behavior, and have permitted direct interventions on the neuronal structure of behavior. In recent years, this analysis has deepened regarding the anthropological foundations of morality and the reasons that would justify the acceptance or rejection of such technology. We present a review of proposals for pharmacological interventions directed directly towards moral enhancement. In addition, we identify the ethical dilemmas that such interventions may generate, as well as the moral assessment of the authors of these studies. There is a moderate consensus on the risks of any intervention on the intimate structure of the human condition, its autonomy and identity, but there are large differences in explaining the reasons for this concern and especially in justifying such interventions. These findings show that it is necessary to investigate the moral assessment of authors and the ethical dimension within the field of pharmacology in order to identify future trends.

[Importance of research on alternatives to animal experiments in pharmaceutical sciences].

The Japanese animal protection law was amended in 2005 to include the 3Rs principle in animal experiments. According to this new law, the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Ministry of Agriculture, Forestry and Fisheries developed announced several guidelines in 2006. These guidelines indicated responsibility of the president of each research institute conducting animal experiments to meet obligating of the animal experiment committee (AEC) and the education to be provided to scientists. About half a year after this notification, I conducted a survey on how these guidelines were put into practice in the pharmaceutical colleges and universities. I received 29 answers from 24 institutes. It seemed that every institute was following, the guidelines, however, there were many institutes where the details were inadequate. For example, questions on the existence of alternative methods and degree of distress and pain were not asked in some questionnaires sent to the AEC. Education on proper conduct of animal experiments (3Rs, methods to evaluate and decrease distress and pain, and methods of euthanasia) was not conducted in many institutes. Further improvement seems necessary.

[Alternatives to animal experimentation v.s. animal rights terrorism].

Systematic modern animal experimentation was established by Bernard Claude who wrote "An Introduction to the Study of Experimental Medicine" in 1865. At this point, the public was already asking that the pain and distress of experimental animals be reduced. For this, scientists, William Russell and Rex Burch in 1959 proposed the principles of alternatives to animal experimentation, the "3Rs". Since that time, animal welfare advocates have promoted the 3Rs concept in biomedical research communities. However, cruel animal experiments have continued and there are reports of radical extremists showing their opposition by invasion, arson, theft and even bombing of institutions involved, resulting in killing of the animals. SHAC, one extremist group believed to be animal welfare activitists was recognized as a terrorist group after the 9.11 tragedy in USA and the government viewed their activities very seriously. In 2001, British animal extremists invaded Japanese universities and stole laboratory resources; one individual was arrested and sentenced to prison for three years; Japanese who assisted in the incident were arrested and one was sentenced for one year. In 2006, SHAC USA members were prosecuted and sentenced for up to 6 years for their terrorism activities including arson. We need to consider the background of these activities which are financially supported by animal welfare advocates. The way we, as scientists who conduct such experiments can respond is by promoting alternatives to this experimentation. In Japan, the animal welfare law was revised in 2005 stressing the importance of 3Rs in scientific activities with animals. The promotion of 3Rs should be strengthened in the pharmaceutical community.

[Current status of safety evaluation and alternative to animal testings in Japan].

In November 2005, the Japanese Center for the Validation of Alternative Methods (JaCVAM) was established as a part of the Division of Pharmacology at the National Center for Biological Safety and Research affiliated with Japan's National Institute of Health Sciences (NIHS). JaCVAM facilitates the validation, peer-review, and international harmonization of alternative to animals testing. Key objectives of JaCVAM are: 1) facilitate 3R's(*), prioritizing Reduction and Replacement, and 2) to ensure new test methods are validated, peer reviewed, officially accepted by the regulatory agencies, and made internationally compatible. In this paper, JaCVAM's current activities and future directions are shown in the validation and peer review of alternatives to testing for skin irritation, eye irritation, phototoxicity, skin sensitization, acute toxicity, genotoxicity and endocrine disruptor screening. (*) 3R's for animal testing (Reduction, Refinement, Replacement).

Incapacidade temporária para atividades habituais: relação com a pressão arterial e o uso de terapia farmacológica anti-hipertensiva no Estudo Pró-Saúde / Temporary disability for daily activities: relationship with the blood pressure and use of anti-hypertensive drug therapy in the Pró-Saúde study

A hipertensão arterial (HA) desempenha papel determinante na ocorrência de eventos clínicos graves, havendo entretanto controvérsias quanto ao seu impacto no cotidiano do portador. A incapacidade temporária para a realização de atividades habituais definida como uma restrição temporária na capacidade funcional habitual do indivíduo, é um indicador de saúde recomendado pela Organização Mundial da Saúde para uso em estudos populacionais. A partir do objetivo geral de investigar a associação entre hipertensão arterial e incapacidade temporária para atividades habituais, delineamos os seguintes objetivos específicos: A) Investigar se a elevação dos níveis pressóricos determina a freqüência e o período acumulado de incapacidade temporária para atividades habituais; B) Investigar se o uso de medicações anti-hipertensivas associa-se a alterações na freqüência e no período acumulado de incapacidade temporária para atividades habituais. Estudo seccional com dados de 2953 participantes obtidos de questionário auto-administrado no Estudo Pró-Saúde, uma coorte de funcionários técnicos administrativos de universidade localizada no estado do Rio de Janeiro. A exposição foi avaliada a partir do valor aferido da PA e do uso de drogas anti-hipertensivas. Conduzimos a análise separando os participantes em 4 grupos, combinando as informações quanto à PA aferida...

Arterial hypertension (AH) plays a determinant role in the occurrence of severe clinical events; however, there are controversies about its impact on daily life. The temporary disability for daily activities, which is defined as a temporary restriction in an individual’s usual level of functioning, is a health indicator proposed by the World HealthOrganization for utilization in population studies. Objectives: To investigate the association between arterial hypertension and temporary disability for daily activities, we proposed thefollowing specific objectives: A) To investigate whether elevated blood pressure (BP) determine the frequency or accumulated period of temporary disability for daily activities; 2) To investigate whether the use of anti-hypertensive drugs are associated with changes in the frequency or accumulated period of temporary disability for daily activities. Methods: Across-sectional study with data obtained from 2953 participants who answered a selfadministered questionnaire in the Pro-Saude Study, a cohort of university emplyees in Rio de Janeiro state. The exposure was evaluated using the measured value of BP and the report ofthe use of anti-hypertensive drugs. We conducted the analysis classifying the participants in 4 groups, combining the information about measured BP (< or ³ 140/90 mmHg) and the report of the use of anti-hypertensive drugs or not. The outcome was evaluated with a composite variable with information about the report and period of disability. Multivariate analyses were conducted using multinomial logistic regression. Results: 690 (23.4 %) were classified as hypertensives, and 704 (23.8 %) reported temporary disability. The use of anti-hypertensive drugs, among the participants with BP < 140/90 mmHg, was directly associated with theprevalence of temporary disability for daily activities for a longer period (OR=2.25, CI 95 %: 1.31 - 3.87)...

Permanência das representações do gênero em sexologia: as inovações científica e médica comprometidas pelos estereótipos de gênero / Permanence of gender stereotypes in sexology: when scientific innovations are challenged by traditional gender stereotypes

Numerosas mudanças surgiram no domínio da pesquisa em sexologia, notadamente no que concerne à função e disfunções sexuais e seus tratamentos. A disfunção erétil foi reconceitualizada como uma disfunção com origem orgânica, uma transformação em relação às abordagens anteriores acerca da impotência psicogênica, desenvolvidas nos anos 1960 e 1970. Essa mudança se baseia em muitas descobertas científicas e no avanço farmacológico realizado sob influência de urologistas norte-americanos. A disponibilização no mercado do sildenafil, em 1998, acionou novos tipos de tratamentos, centrados na atividade peniana. Os mesmos grupos de urologistas passaram recentemente a repensar as "disfunções sexuais femininas" segundo o mesmo modelo orgânico da função sexual. Novos produtos farmacêuticos estão em testagem clínica, tendo em vista a proposta de tratamentos da nova categoria de transtornos sexuais. A colocação no mercado do sildenafil não provocou reações contrárias às novas abordagens dos transtornos sexuais masculinos. Inversamente, o surgimento de novos conceitos da função sexual feminina suscita importantes debates. O British Medical Journal veiculou uma discussão, estabelecendo que a função sexual feminina não possuía origem orgânica, mas fundava-se em fatores psicológicos e relacionais da atividade sexual das mulheres. O debate centrou-se na "simplicidade" da sexualidade masculina, em oposição à "complexidade" da sexualidade feminina. Este artigo apresenta a analisa as novas concepções da função sexual masculina e feminina, e evidencia a permanência de estereótipos tradicionais da sexualidade masculina e feminina, e sua influência sobre as pesquisas científicas mais avançadas nessa esfera1.

Major changes have occurred in male and female sexual function/dysfunction research and treatments. Male erectile dysfunction has been re-conceptualized as an organic dysfunction, which marks a dramatic shift from previous conceptions of psychogenic impotence developed during the 60' and the 70's. This shift is based on major scientific discoveries, and pharmacological advances that took place since the early 80's under the influence of North American urologists. The release of sildenafil in 1998 was the corner stone of a new paradigm of treatments focusing on male penile activity, far remote from any psychological approaches. More recently, the same group of urologists started to reconsider Female Sexual Dysfunction using the same organic/biological model of sexual function. New pharmaceutical products are currently under trial for the treatment of this new category of female sexual disorder. But as opposed to the absence of public adverse reaction to the development of this approach of male function, many voices raised to oppose this new conception of female function. A major discussion took place in the British Medical Journal stating that female sexual function was not organically driven, but rather determined by the social, psychological and interpersonal context of female sexual activity and relations. One of the major dimensions of this discussion opposed the so-called "simplicity" of male sexual function to the "complexity" of female sexual function. This paper demonstrates the permanence of traditional social scripts of male and female sexuality and their influence in the most advanced scientific research in this field.

[Ethical, legal, and social issues of genome research--new phase of genome research desperately requires social understanding and safeguards on the use of medical records and other personal information].

This article provides an overview of the use of human materials and information (human subject) in the new phase of pharmacological research and development in the current context, especially as it relates to the progress of the human genome project. In a sense, humanity has been drastically reduced to an array of DNA sequences that can be universally used in comparing living things. Pharmacological studies now acquire a unique status in bridging chemical substances to human body function. To perform the full activity of the nature of pharmacology, it requires both genotype and personal information, i.e. medical records and life style information, as research resources. In the UK, the Medical Research Council, the Wellcome Trust, and the Department of Health had started to plan UK Biobank for promoting and supporting the new stage of medical and pharmacological research and development. UK Biobank will collect DNA samples, medical records, and life style information of 500,000 people between the age range of 45 to 69 years old. It will follow the changes in health status of the participants for more than 10 years. The Biobank will provide researchers chances to correlate the genotypic traits to phenotypic ones, i.e. common diseases. In relation to the secondary use of medical records in health research, National Health Service (NHS) initiated a new strategy on the governance of patient information. These movements clearly demonstrated the indispensable nature of infrastructures for promoting and supporting pharmacological and medical research. We discuss on the necessary policies in constructing the Japanese infrastructure.

Turn-of-the-century ethical issues in child psychiatric research.

National concern in 2000 about increased psychoactive drug prescription for preschoolers accentuated the 1990s thrust for more pharmacologic research in children. Preschoolers are prescribed potent drugs without adequate evidence for efficacy or safety at this plastic age of the rapidly developing brain. Implementation of needed preschool research poses special ethical complications. Children with mental disorder qualify for special protection under both rubrics. Parental informed consent is crucial for preschoolers, who appear incapable of assent because of their preoperational, magical, animistic, egocentric thinking, with inability to comprehend relative risks and benefits. Whether they can dissent is an open question. Possibly for research with direct benefit outweighing the risk, parental permission/consent could override attempted preschooler dissent. Subject recompense should be adjusted for age differences in perception of amount, although parent reimbursement needs to be realistic. Insurance for research risk is desirable. Placebo controls appear justified for preschoolers because there is little evidence base to say that a proven effective treatment already exists. Disruptive behavior disorders, including attention-deficit/hyperactivity, have enough evidence of preschool diagnostic validity to justify therapeutic trials. In preschool pharmacologic research, a brief trial of a nonpharmacologic treatment should precede the drug trial to ensure that placebo responders and responders to the alternative treatment are not exposed to drug risk.