Prioritising African perspectives in psychiatric genomics research: Issues of translation and informed consent

Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through a consideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re‐examination of how researchers develop and present protocols to institutional ethics review boards.     

Development and perspectives of scientific services offered by genomic biological resource centres.

A number of fundamental technical developments like the evolvement of oligonucleotide microarrays, new sequencing technologies and gene synthesis have considerably changed the character of genomic biological resource centres in recent years. While genomic biological resource centres traditionally served mainly as providers of sparsely characterized cDNA clones and clone sets, there is nowadays a clear tendency towards well-characterized, high-quality clones. In addition, major new service units like microarray services have developed, which are completely independent of clone collections, reflecting the co-evolution of data generation and technology development. The new technologies require an increasingly higher degree of specialization, data integration and quality standards. Altogether, these developments result in spin-offs of highly specialized biotech companies, some of which will take a prominent position in translational medicine.     

Ethical Research Issues: Going Beyond the Declaration of Helsinki

La Vaque and Rossiter made a strong, supported argument that it is unethical to use a no treatment control group in a research study if a known, effective treatment is available. Their argument is based on the supposition that the Declaration of Helsinki is the ethical world standard for research with humans. Their argument appears to be straightforward, but is not simple to apply. The issues are very complex, include issues not discussed in their argument, and can lead to a different conclusion as pointed out in this paper. The World Medical Association developed the Declaration of Helsinki as one of their official policies. The Declaration of Helsinki, however, is not accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations or even by the United States Federal Government. Perhaps it is not mentioned because its ethical provisions are aspirational rather than mandatory as implied by La Vaque and Rossiter. Researchers and clinicians should also be aware of other ethical issues not directly discussed in the La Vaque and Rossiter paper. The Belmont Report is the basis for the ethical protection of human research subjects for at least 17 federal agencies and does not mention the Declaration of Helsinki. The Belmont Report mentions several ethical principles that form the basis for informed consent, risk/benefit assessment, confidentiality of data, subject selection, Institutional Review Boards, and other protections needed when doing research with human subjects. At least 2 of these core principles have direct implications to the discussion related to the use of placebo controls. The ethical principle of fidelity is also important in guiding research activities with human subjects. Researchers should be familiar with the La Vaque and Rossiter argument, the Belmont Report, and the federal policies developed to implement the provisions of that report, for example, Regulation 45 CFR 46.     

An insight into the possible mechanism of working of two-cistronic gene expression systems and rational designing of newer systems

The initial attempts at hyper-expressing buffalo/goat growth hormone (GH)-ORFs inEscherichia coli directly under various strong promoters were not successful despite the presence of a functional gene. High level expression of GH was achieved as a fusion protein with glutathione-S-transferase (GST). To produce native GH in an unfused state, we adapted an established strategy of two-cistronic approach in our system. In this strategy, utilizing one of the highly efficient reported sequences as the first cistron led to a nearly 1000-fold enhancement in the level of expression under anE. coli promoter (trc). In search of a newer first-cistron sequence as well as to see the generality of the two-cistronic approach, we explored the ability of different lengths of a highly expressing natural gene to act as an efficient first cistron. Surprisingly,GST, which is naturally highly expressible inE. coli, could not be fitted into a successful two-cistronic construct. In addition, placement of the entire two-cistronic expression cassette (which had earlier given high-level GH expression undertrc promoter) under theT7 promoter inE. coli failed to hyper-express GH. These results suggest that the successful exploitation of the two-cistron arrangement for hyper-expression of eukaryotic ORFs in bacteria is not as straightforward as was previously thought. It appears probable that factors such as the sequence context, together with the length and codons used in the first cistron are important as well.