BackgroundCurrent anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athlete's health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public.DiscussionWe review this recent development of increasingly severe anti-doping control measures and find them based on questionable ethical grounds. The ethical foundation of the war on doping consists of largely unsubstantiated assumptions about fairness in sports and the concept of a "level playing field". Moreover, it relies on dubious claims about the protection of an athlete's health and the value of the essentialist view that sports achievements reflect natural capacities. In addition, costly antidoping efforts in elite competitive sports concern only a small fraction of the population. From a public health perspective this is problematic since the high prevalence of uncontrolled, medically unsupervised doping practiced in amateur sports and doping-like behaviour in the general population (substance use for performance enhancement outside sport) exposes greater numbers of people to potential harm. In addition, anti-doping has pushed doping and doping-like behaviour underground, thus fostering dangerous practices such as sharing needles for injection. Finally, we argue that the involvement of the medical profession in doping and anti-doping challenges the principles of non-maleficience and of privacy protection. As such, current anti-doping measures potentially introduce problems of greater impact than are solved, and place physicians working with athletes or in anti-doping settings in an ethically difficult position. In response, we argue on behalf of enhancement practices in sports within a framework of medical supervision.SummaryCurrent anti-doping strategy is aimed at eradication of doping in elite sports by means of all-out repression, buttressed by a war-like ideology similar to the public discourse sustaining international efforts against illicit drugs. Rather than striving for eradication of doping in sports, which appears to be an unattainable goal, a more pragmatic approach aimed at controlled use and harm reduction may be a viable alternative to cope with doping and doping-like behaviour.

Switzerland has an unusual position on assisted suicide: it is legally condoned and can be performed by non-physicians. Euthanasia is illegal, but there is a debate about decriminalisation that also discusses participation by non-physicians

The alpha-chain of the nicotinic acetylcholine receptor carries the binding sites both for cholinergic ligands and for most experimentally induced or naturally occurring antibodies to the native receptor. By means of expression cloning in Escherichia coli, fusion proteins were derived from specific fragments of a complementary DNA encoding the mouse alpha-chain, allowing the mapping of the toxin-binding site to residues 160-216 and the main immunogenic region to residues 6-85. This approach permits the independent study of different functional domains of a complex receptor molecule and should be generally applicable to other proteins for which complementary DNA clones are available.

We have cloned and sequenced a fragment of the chicken genome approximately 9 kilobases in length that comprises the genes encoding the 6 and 'y subunits of the nicotinic acetyicholine receptor. The two genes are homologous and have identical structures: both consist of 12 exons, some of which precisely correspond to predicted structural domains of the receptor subunits. The 8 and y subunit gehes are encoded by the same DNA strand and are very closely linked, there being only 740 base pairs between the last codon of 8 and the initiator codon of y. Blot analysis demonstrates that the genes we describe are unique in the genome. Comparison of the predicted protein sequence for the correspodding subunits of chicken and of the elasmobranch Torpedo reveals a high degree of conservation in Aome but not all of the protein domains.The nicotinic acetylcholine receptor (AcChok) mediates synaptic transmission at the vertebrate neuromuscular junction. Located in the folds of the postsynaptic membrane, the AcChoR is a cation channel whose opening is triggered by acetylcholine. AcChoR activation normally results in an influx of Na' that depolarizes the postsynaptic membrane and leads to muscle contraction. The AcChoR is the best understood of all ligand-gated ion channels due to its relative abundance in the electrocytes of Torpedo or Electrophorus, from which workable quantities of receptor can be purified. The receptor is a pentamer of four different subunits in the stoichiometty a2f8W. All subunits are glycosylated and span the membrane. They assemble into a barrel-shaped structure whose central cavity is thought to be the gatpd ion channel (for recent reviews see refs. 1-3). That the four subunits participate in the assembly of a single functional AcChoR molecule was elegantly verified by showing that all four mRNA species must be injected in Xenopus oocytes to allow detection of physiologically active receptor (4). Microsequencing of the amino ends of the four purified Torpedo subunits demonstrated that they were related and suggested that they had evolved from an ancestral gene by a series of duplications (5).Several laboratories recently succeeded in cloning and sequencing some (6-9) or all (10-12) of the cDNAs encoding the four subunits of Torpedo AcChoR. It was found that there is significantly more homology between the deduced protein sequences of the a-,8 and y-8 pairs than between any other combinations of subunits, suggesting that an initial duplication of the ancestral gene had given rise to two protogenes, one of which later yielded the y and 8 genes while the other gave rise to the a and p genes (12). Moreover, all subunits were shown to have four very hydrophobic stretches three of them closely grouped-of sufficient length to span the membrane. This finding suggested a model for the transmembrane insertion of the receptor whereby each subunit weaves four times through the membrane to yield an assembly of twenty transmembrane a helices, a subset of which constitutes the channel per se (8,9,12). A relate...

Background: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator.