Anti-Alzheimer drugs: ethical aspects of research and practice

The development and use of drugs that aim at positively influencing the cognitive decline in patients suffering from Alzheimer's disease raises a number of ethical questions. These concern, amongst others, the significance of these drugs for the well-being and quality of life of patients, as well as the informed consent for the use of these medicines, in particular in the context of medical-scientific research. Assessing the value and significance of antidementia drugs not only depends on the positive effect on cognitive decline, but also on the broader meaning for the quality of life of the patient and her primary carer(s). The subjective experiences of those directly involved deserve more attention in research.     

Gene therapy: some results, many problems to solve.

Gene therapy is raising incredible hopes. The prospects of treating numbers of severe pathologies (hereditary, cancerous, degenerative or infectious) are vast. Nevertheless, the technological bolts to lift are still numerous, whether they be bringing the vectors into focus, the systems of expression of transgenes or the neutralization of immune responses of the host against the vector, the product of transgenes, or the knowledge of the considered pathologies of physiopathology. Solving these difficulties entails the gathering of multiple disciplines, from chemistry to medicine, passing through virology and immunology.     

Serum-free hybridoma culture: ethical, scientific and safety considerations

Despite considerable progress in the development of cell culture techniques, including the development of the serum- and protein-free media that now routinely support hybridoma and mammalian cell growth, fetal bovine serum (FBS) supplemented media are still commonly used: a practice that raises ethical, scientific and safety concerns. The use of FBS in hybridoma culture media is examined here, with regards to the development and production of monoclonal antibodies (mAbs), and it is our recommendation that researchers adopt serum-free cell culture methods to reduce animal use in this area.     

Beyond consent: ethical and social issues in genetic testing

Informed consent is a vital ethical doctrine in clinical medicine and, through genetic counselling, is being applied to genetic testing. But genetic testing raises issues that transcend the traditional concept of informed consent. Genetic tests are adopted without demonstrable clinical benefit, and the consequences of testing can reach beyond the individual to their families and communities. Understanding the social and cultural context of genetic testing will lead to more informed discussion and debate on these issues.     

Solidarity and equity: new ethical frameworks for genetic databases

Genetic database initiatives have given rise to considerable debate about their potential harms and benefits. The question arises as to whether existing ethical frameworks are sufficient to mediate between the competing interests at stake. One approach is to strengthen mechanisms for obtaining informed consent and for protecting confidentiality. However, there is increasing interest in other ethical frameworks, involving solidarity--participation in research for the common good--and the sharing of the benefits of research.     

Legal and ethical aspects of new wildlife food sources

The production of animals for new sources of food may be affected by a variety of laws relating to the keeping, trading, health, welfare and movement of animals. Other legislation, such as that applicable to wildlife and to human safety, are also relevant. Religious, cultural and ethical considerations may also influence attitudes towards a new food product. It is important that these factors are taken into account during the planning and progress of an enterprise since they may have a substantial impact on its viability.     

"Brain reading": achievements, perspectives and ethical problems

The new trend in brain research designated as brain reading is considered. This research deals with decoding the informational content of the brain processing via its physiological parameters. Such studies are based on rather complicated methods of mathematical analysis. Single records rather than averaged data are used to reveal their content. Three main streams of studies are distinguished, i.e. the object classification, the emotion recognition and brainotyping. Particularly, the studies directed to recognizing the type of thinking via EEG spectra, carried out in the author's laboratory, are reviewed. The possible outcome of the brain reading technique is considered. Finally it is argued that in the future, the broad application of this technique needs to be controlled with some ethical rules.     

Observations on ethical problems and terminal care.

Progress in medical diagnosis and therapy has raised new problems with far-reaching ethical implications. Medicine must remain a profession and not become a business. Textbooks must address ethical problems in the context of health care decisions and not restrict themselves to pathophysiology and practical therapeutics alone. The relative roles of the principles of autonomy, non-maleficence, beneficence, and justice must be balanced and appropriately applied to individual situations in biomedical ethics. When therapy becomes futile and the suffering of the patient does not justify any anticipated benefit, the patient (and/or patient surrogate) may request withholding or even withdrawing life-prolonging interventions. In the persistent vegetative state, even nutritional support by an unnatural (tube) route may ethically be denied at the patient's (or surrogate's) informed decision. New areas of ethical evaluation have been raised by the desire of some individuals to prolongation of their lives at high expense to the society such that other individuals are denied services because of limitation of available resources. There has been a long-standing conflict of interest between the acceptance by physicians and/or medical institutions of money or gifts from pharmaceutical companies whose drugs they prescribe, stock, or sell. This practice increases the cost of the drugs and is, in effect, a "sick tax," which is morally wrong.     

Gaucher's and Fabry's diseases: biochemical and genetic aspects

Gaucher and Fabry's diseases are lysosomal storage disorders. They are due to glucocerebrosidase or alpha galactosidase deficiency, respectively. Gaucher disease, transmitted as an autosomal recessive trait, is frequent among Ashkenazi Jews. Cloning of the gene has allowed the characterization of few common mutations. Some of them have a prognosis value, in favour of either a non neurological form (type 1) or more severe forms (types 2 and 3). There mutations were found in 70% of the alleles, the other alleles carrying private mutations. Fabry disease is transmitted as an X-linked recessive trait. Genetic counselling in at-risk families relies on the detection of carrier females. As the alpha galactosidase gene shows various mutations, the establishment of phenotype-genotype correlations is limited. These two diseases, well defined at the biochemical and genetic level, are good models of inherited diseases for the development of specific therapies.     

Gene therapy: trials and tribulations

The art and science of gene therapy has received much attention of late. The tragic death of 18-year-old Jesse Gelsinger, a volunteer in a Phase I clinical trial, has overshadowed the successful treatment of three children suffering from a rare but fatal immunological disease. In the light of the success and tragedy, it is timely to consider the challenges faced by gene therapy--a novel form of molecular medicine that may be poised to have an important impact on human health in the new millennium.     

Gene therapy: progress and predictions

The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines.