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10 May 2000Last week the Science and Technology Committee of the Council of Europe's Parliamentary Assembly (which consists of delegates from the national parliaments of the COE's 41 member states) decided to back an internet appeal by two Parliamentary Assembly members against the patenting of human genes (see news release).  During the next meeting of the Assembly (Strasbourg, 26-30 June), a meeting of four of its committees will be convened with a view to calling for a moratorium on the application of the European Directive 98/44/CE, on the legal protection of biotechnological inventions. The Council of Europe, which predates the European Union, was established after the Second World War "to strengthen democracy, human rights and the rule of law throughout its member states". It has been active in the area of the ethical issues surrounding human genetics and genomics, in particular with its 1997 Convention on Human Rights and Biomedicine, but its ability to influence EU policy is uncertain. 

15 May 2000An international consortium of laboratories has published an almost-complete sequence for human chromosome 21 [Hattori, M. et al (2000) Nature 405, 311-319; see also commentary by Reeves [Nature (2000) 405, 283-284]. This is the chromosome associated with Down syndrome, the most common inherited cause of mental retardation: the syndrome occurs in individuals who have three rather than the normal two copies of chromosome 21. A surprise emerging from the complete sequence of the chromosome is the very small number of genes it contains: only about 225 compared with more than twice that number on the similarly-sized long arm of chromosome 22. This small number may explain why possession of an extra copy of the chromosome is not usually lethal either very early in development or soon after birth, as it is for every other chromosome. The relatively small number of genes on chromosome 21 has increased hopes that knowledge of its genetic content might help in achieving an understanding of which genes contribute most to the characteristics of Down syndrome. Eventually this knowledge might lead to treatments to alleviate some of these problems.

25 May 2000Today sees the launch of the report "Genetics and Health". Written by Ron Zimmern and Christopher Cook, this is the official report of the Nuffield Trust Genetics Scenario Project, which aimed to explore the "policy issues for genetic science and their implications for health and health services". The report summarises the conclusions reached by eight separate "stakeholder" workshops held over a period of six months and followed by a two-day policy evaluation workshop in November 1999. The stakeholder groups were given the task of pinpointing the key issues arising from the growing use of genetic technology in medicine, identifying the main areas of uncertainty in the evolution of genetic science, and formulating their principal recommendations to government for the development of medical genetics to benefit the population as a whole. The main themes from the stakeholder workshops were captured, written up and used to inform the policy evaluation workshop, which formulated policy recommendations in several key areas: the regulatory framework for genetics, educational strategies for the public and health professionals, the principles governing the use and confidentiality of genetic information, planning for the financial requirements of new health care interventions arising from genetic science, the relationship between government and the commerical sector (mainly the pharmaceutical companies), the development of the academic and commercial science base, and the strategies for the development of genetic services within the National Health Service. The Nuffield Trust plans to hold a meeting later in the year, with the aim of formulating an action plan based on the conclusions of the Scenario Project report. The full text of the report will soon be available on the internet, at http://www.official-documents.co.uk/document/nuffield/policyf/genetics.htm  

3 May 2000The Human Genetics Commission recently published on its web site a very useful outline of the government and non-government bodies involved in regulation and policy development in the area of genetics (The UK regulatory and advisory framework for human genetics). It covers firstly the work of the government advisory committees such as the Human Genetics Commission and the Genetics and Insurance Committee, outlining briefly why and when they were set up, the work they have done, current activities and future plans. Statutory bodies such as the Human Fertilisation and Embryology Authority and the Committee on the Safety of Medicines are also included, with useful notes about the aspects of their work that are related to genetics. The paper also mentions the work of some of the major non-governmental groups in this area, such as the Nuffield Council on Bioethics, the Medical Research Council and The Wellcome Trust, with notes about their current projects and how some of these tie in with government initiatives. Later, the paper moves into the broader areas of biotechnology and agriculture, again explaining how the genetic aspects of these topics are dealt with. In the wider sphere of international initiatives in bioethics, the activities of the Council of Europe, UNESCO, OECD and WHO are described. A final section deals with the implications of devolution for policy development in genetics and genetic technology, with an explanation of the remit of the UK Government and the devolved administrations in Wales, Scotland and (in theory at this stage) Northern Ireland. An annex at the end of the paper contains a map showing diagramatically all the bodies that relate in some way to human genetics, and lists links to their web sites. Although aspects of this paper will date quite rapidly, it is a must for anyone who is confused by the plethora of regulatory bodies past and present, their powers, their terms of reference and their relationships to one another. 

23 May 2000The Biomedical Ethics section of the Wellcome Trust's Medicine in Society Programme is calling for proposals for research on the ethical, legal and public policy implications of pharmacogenetics, and of human biomedical sample collections for DNA and other analysis. In pharmacogenetics, the suggested areas of research include questions of equity of access, the economic consequences for society and the health service, and the possible shift from more socially-based support systems towards "pharmaceutical solutions" to problems of ill health. The questions surrounding human tissue collections include consent embracing unknown future uses of the material, the possible commercial exploitation of such collections, and the tension between privacy and "social sharing" of genetic information. The next deadline for applications is 1 September 2000. Further details about the funding programme, together with background papers, can be found on the Wellcome Trust's web site.

3 May 2000Two fascinating papers in the Journal of Medical Ethics discuss concepts of disability, and whether attempts to avoid the birth of disabled individuals, or to cure disability by gene therapy, constitute discrimination against the disabled [Reindal, S.M. (2000) J Med Ethics 26, 89-94 (Abstract) and Harris, J. (2000) J Med Ethics 26, 95-100 (Abstract)]. Solveig Reindal argues that they do: that an "impairment" (when part of one's body does not function, or functions with difficulty) only results in "disability" because of adverse social conditions or attitudes, that eugenics is a form of discrimination against the disabled because it implies that they have no right to live, and that a disabled couple would be morally right in choosing to give birth to a disabled child. In the view of John Harris, however, to espouse a totally "social" model of disability is to deny that there is such a thing as a disabling impairment at all. He defines disability as "a physical or mental condition we have a strong rational preference not to be in". In his view, a disabled couple should never be prevented from having a disabled child, but a deliberate choice to do so, in preference to having a child without the disability, would be morally wrong. For the same reason, he argues, it is not morally wrong for a couple to choose to avoid giving birth to a disabled child. Harris denies that his position endorses discrimination against disabled people; he agrees that disability does indeed have a social dimension, that social discrimination against disabled people is wrong and society should work to overcome it. He does not agree, however, that a desire to cure, or prevent the birth of, people with disabilities in itself a form of discrimination against existing disabled people.

Comment: The development of prenatal diagnosis for many different single-gene diseases, offering at-risk couples the option of choosing not to give birth to a disabled child, has raised profound questions about what we regard as "disability" and the value we place on the lives of disabled people. The advent of pre-implantation genetic diagnosis and the possible future prospect of gene therapy, either somatic or germ-line, to cure such disabilities, add further weight to these questions. It is essential that the development of new genetic and reproductive technologies goes hand in hand with a determination to protect the human rights of disabled people and that the disabled are regarded as having a legitimate voice in the development of genetics policy. 

19 May 2000Allison Streetly comments in the BMJ on two recent reports published by the Health Technology Assessment programme on aspects of screening for sickle cell disease and thalassaemia [Davies, S.C. et al (2000) Health Technol Assess 4(3) (Executive summary) and Zeuner, D et al (1999) Health Technol Assess 3(11) (Executive summary)]. These autosomal recessive diseases are significant causes of ill-health in areas with relatively large populations of African, Afro-Caribbean, Mediterranean, Indian or Pakistani origin. Both of the HTA reviews point out that, in spite of 1993 recommendations by the UK Standing Medical Advisory Committee that antenatal and neonatal screening should be routine in such regions, and that preconception carrier testing should be encouraged, the provision and quality of these services throughout the country is patchy. They report the results of analyses from which they have calculated the birth prevalence at which universal neonatal screening for sickle-cell disease might be justified, and the population disease burden at which antenatal screening for haemoglobinopathies becomes cost-effective. They point out that because genetic choice is an important outcome, it might be desirable to implement programmes in some areas that fall below these levels. Areas where further research is needed are also highlighted, for example on the benefits and harms of haemoglobinopathy screening, and on equity of access to services. In her commentary Streetly points out in addition that national policy and coordination are needed because regions with affected populations do not map neatly to Health Authority boundaries, and nationally agreed care standards are needed to ensure that screening programmes go hand in hand with high-quality care for affected individuals. 

22 May 2000Boyd et al report that, among 189 Jewish women diagnosed and treated for invasive ovarian cancer at the Memorial Sloan Kettering Cancer Center in New York, those (88 in total) with one of the three well-characterised BRCA1 or 2 mutations found in Ashkenazi Jews tended to survive longer than those without such a mutation [Boyd, J. et al (2000) JAMA 283, 2260-2265 (Abstract)]. The Jewish patients were identified from a consecutive series of almost 1000 patients treated at the centre. The vast majority of patients in the study, both with and without mutations, had advanced-stage disease. The study also showed that BRCA1-linked disease showed a stronger age-related penetrance than BRCA2-linked disease, with BRCA2-linked cases rarely diagnosed under the age of 60. Remission after chemotherapy appeared to be longer in hereditary than in sporadic cases.

Comment: The relative survival of hereditary and sporadic ovarian cancer patients is controversial, with some studies reporting enhanced survival of patients with hereditary disease and some the reverse. Boyd et al suggest that the strengths of their study are that they compared survival between groups that both had advanced-stage disease, that all the patients received the same type of treatment at the same institution, and that in restricting their study group to Jewish women they could be fairly sure that all BRCA1- or 2-linked cases had been identified. Whatever the real answer on survival, this study concurs with several others in showing that almost all hereditary ovarian cancer occurs after child-bearing age; this has important implications for counselling, as it suggests that prophylactic oophorectomy may be delayed until the woman's family is complete.  

9 May 2000A brief report in the Lancet suggests that the use of genetic testing to tailor drug therapy may be a reality in the not-too-distant future. Arranz et al have looked for associations between polymorphisms in neurotransmitter-receptor-related genes and response to the antipsychotic drug clozapine, which is known to be of variable effectiveness in the treatment of schizophrenia [Arranz, M.J. et al (2000) Lancet 355, 1615-1616]. They report that in studies on 600 patients, 133 of whom were classified as responders and 67 as non-responders, six polymorphisms were associated with clozapine response: the positive predictive value for this combination of polymorphisms was 76.7%, with a sensitivity of 96% for a satisfactory improvement on treatment. In particular, 80% of patients who had a combination of two particular genotypes, both in the 5-HT2A receptor, responded well to clozapine; this genotype combination was carried by about half of the total sample of patients.

Comment: Many of the usual caveats apply to this paper: relatively small sample size, retrospective analysis of treatment response, and the need for independent reproducibility of the results. However, if the work is confirmed in further studies, it could pave the way to more effective (and cost-effective) treatment of psychiatric illness such as schizophrenia. 

12 May 2000A series of brief articles in the BMJ puts a personal face on the question of how to manage asymptomatic haemochromatosis and, indirectly, on the issue of whether population screening for haemochromatosis is a good idea [BMJ (2000) 320, 1314-1317; also see Haemochromatosis page]. A patient and her GP write movingly of their experience of treatment for asymptomatic haemchromatosis that was discovered as a result of a research study into the genetics of diabetes and its association with haemochromatosis. Treatment for haemochromatosis - regular venesection - is often described as simple and inexpensive but it is clear from these personal accounts that it can in practice place a considerable burden both on the patient and on their supporting GP. The patient, a woman in her late 60s, often felt exhausted and debilitated and had to organise her life around the treatment regime, including cancelling a much-wanted holiday abroad. She thinks that it would probably have been better not to have known of her diagnosis, as she had felt perfectly well before treatment began. However, a senior lecturer in haematology, commenting on the case, points out that the patient's serum ferritin levels, at over five times the recommended limit, were very likely to lead to severe organ damage and could simply not be ignored. In his view the solution is to improve methods of treatment and/or to find ways of alleviating its side-effects.

Comment: Treatment for haemochromatosis may indeed be straightforward when compared to many more painful and invasive medical procedures but it is clear from these accounts that it is still by no means a trivial undertaking. The assessment of proposals for population screening must take into account the considerable burden that would be imposed by the necessity to treat large numbers of asymptomatic people. Without a better understanding of the penetrance of the disease, it seems premature to begin such programmes.