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1 March 2000In response to the document " A first class service: quality in the NHS", a group set up by the BSHG has been working towards developing an agreed set of standards for clinical genetics practice. The group has begun its work by identifying the components of clinical governance as it applies to clinical genetics and surveying initiatives already underway in the regional genetics centres. In its report "Towards clinical governance in clinical genetic practice" (text available soon from the BSHG website), the working party discusses the issues involved in clinical audit of clinical genetics practice (in particular, the difficulty of establishing valid outcome measures), the development of clinical guidelines, arrangements for continuing professional development and appraisal, education and training both of genetics personnel and those in other clinical disciplines, clinical risk management, the importance of involving patient groups, and accreditation of centres for service and training. The BSHG is taking the development of clinical governance forward in consultation with the Joint Medical Genetics Committee.  

15 March 2000The final report of the Euroscreen 2 project on the "Ethics of genetic screening" was presented to the European Commission at the end of 1999. Euroscreen, funded under the European Union's BIOMED programme, has involved ethicists, sociologists, philosophers and other experts from many European countries, both within and outside the EU. In its final newsletter (Spring 2000) project members summarise the three major strands of the work of Euroscreen 2 in the areas of commercialisation of genetic screening and testing (particularly with regard to genetic tests supplied directly to the public), insurance, and public awareness and understanding of genetics. 

22 March 2000In the spirit of its avowed aim to involve the public in its work, the Human Genetics Commission is consulting the public on proposals for its work programme. It suggests work in the areas of storage and use of genetic information (in the light of proposals for the UK Population Biomedical Collection), developments in genetic testing (including "gene chip" technology), consequences of genetic reproductive choices, provision of genetic services (training requirements, infrastructure etc), and gene patenting. Respondents are invited to rank these areas in order of priority, to suggest ways of encouraging public involvement in debate, and to comment on the value and usefulness of the consultation exercise itself. Responses are required by 10 April 2000, the date set for a public consultative meeting to discuss the Commission's work plan. 

21 March 2000Genetics is an area of modern science and technology that is increasingly in the spotlight of media attention. One has only to reflect on the uproar about genetically modified food to realise how the very word "genetic" can arouse and inflame public fear and hostility. In this climate, the report of the House of Lords Science and Technology Committee on Science and Society is very timely. The Committee warns that unless scientists, politicians and policy makers take public concerns seriously, and find new ways of engaging the public in shaping the direction of scientific research and policy, the gulf between scientific aspirations and public support for them will widen still further. The Committee offers no panacea but makes a variety of recommendations, including: that the research councils and others work actively to improve scientists' communication skills; that a better understanding should be developed of how people perceive and understand information about risk; that public involvement in science policy-making should move from being an "optional add-on" to an essential part of the process; that a culture of openness should be developed among scientific advisors, research councils and individual scientists; that the Press Complaints Commission should adopt the Royal Society's guidelines for press reportage of science and that these should apply to news reporters as well as science journalists. Practical suggestions are made about how each of these recommendations might be brought about. Action is needed urgently to redress a situation in which 46% of people questioned in  MORI poll quoted by the Lords Committee did not think that government scientists tell the truth (38% thought that they do tell truth and 16% didn't know). In another poll, the possibility of "genetic testing" was seen as moderately beneficial for society, while both genetic modification and cloning got a resounding thumbs down. If the public is to be properly involved in guiding the future direction of genetic technology so that any future answers to such questions (whether positive or negative) are based on good understanding and meaningful participation, now is the time to make a start. 

13 March 2000The Royal Society has submitted a statement on therapeutic cloning to the expert group set up by the Chief Medical Officer to advise the government on issues to do with cloning. The statement discusses the different types of stem cells that exist in embryos and adults, and their potential therapeutic use to repair organ damage resulting from disease or trauma. The Royal Society group recommends that, rather than focusing on the types of stem cells that might be obtained by transplanting a patient's nuclei to enucleated eggs (and thereby running into serious ethical as well as practical difficulties), research should instead be directed towards producing multipotent stem cells by techniques that involved fusing nuclei with the cytoplasm of cells other than eggs. The group stresses, however, that there is as yet no way of knowing whether such an approach would be successful. In the meantime it recommends the establishment of a bank of stem cell types of adult origin; these types of cells, although more restricted in their potential than embryonic cells, could still prove useful in therapeutic applications if problems of host rejection can be overcome. 

27 March 2000The US Secretary for Health's Advisory Committee on Genetic Testing (SACGT) has been considering the adequacy of oversight of genetic testing. A period of public consultation and a public meeting has culminated in the publication of some preliminary recommendations. The committee found that many people have fears about discrimination resulting from genetic testing, and most consider that government oversight is necessary. The committee recommends that the Food and Drug Administration should be responsible for assessing and approving genetic tests. It also recommends that discrimination in health insurance or employment on the basis of genetic information should be made illegal, and that legislation should  be enacted to protect the privacy of genetic information. SACGT affirms the continuing importance of public involvement, and of education both for the public and for health providers. In the area of research, it commends the efforts of the various agencies of the Department of Health and Human Services to coordinate (via CDC's Office of Genetics and Disease Prevention) research data on the correlation between genotype and phenotype. It recommends increased funding for such research. 

15 March 2000Three papers in the March issue of the Journal of Medical Genetics address the question of how to manage women who have concerns about their risk of breast cancer on the basis of their family history (see Breast cancer summary for background information). Gray et al discuss the setting up and some preliminary results from the TRACE project in Wales, "a randomised controlled trial of genetic assessment for women who are at increased risk of breast cancer because of their family history" [Gray, J. et al. (2000) J Med Genet 37, 192-196 (Abstract)]. Women were admitted to the trial if they fulfilled family history criteria that indicated an increased risk of breast cancer. Women in the control arm of the trial received "standard" assessment in a clinic run by a breast surgeon, while women in the trial group attended a multidisciplinary clinic including both surgical staff and trained genetics staff who assessed their genetic risk. Those assessed as at high risk in either group were offered lifetime surveillance and the option of prophylactic mastectomy; those in the trial group, in addition, were offered genetic testing for BRCA1 or BRCA2 mutations if they had a living affected relative in whom a mutation could be found. The bulk of the results from the TRACE project will be reported in future papers; the first in this series, by Brain et al, analyses the motivation of women recruited into the TRACE project [Brain, K. et al. (2000) J Med Genet 37, 197-20 (Abstract)]. The (UK) Cancer Family Study Group sets out suggested guidelines for assessing genetic risk on the basis of family history, and for management of women who fall into different risk categories [Eccles, D.M. (2000) J Med Genet 37, 203-209 (Abstract)]. Family history criteria and risk estimates for these categories (using the Cyrillic 2.1 programme) are presented (for more details, see section in breast cancer summary). The initial risk assessment is intended to be carried out in primary care. Women at low genetic risk would be reassured, those at moderate risk referred to a breast unit, and those at high risk referred in addition to the regional genetics service.

Comment: The Cancer Family Study Group stresses that its guidelines are preliminary, and may be modified in the light of further evidence on, for example, the efficacy of breast screening in different age groups, the effectiveness of preventive measures, and the usefulness of risk assessment methods that take epidemiological factors (such as parity and age at first pregnancy) into account as well as genetic criteria. The Group also points out that at present the available NHS services do not match all aspects of these guidelines, for example mammographic screening for moderate/high risk women under the age of 50 is not readily available in all regions. The results from the TRACE project should help inform both the development of future guidelines, and models for service development. 

6 March 2000In the United Kingdom in 1998, 69% of all Health Authorities or Health Boards offered antenatal serum screening to all pregnant women (see Down syndrome page, and   item in November 1999 newsletter). This represents a steady increase over the last 5-10 years, with a corresponding decrease in the use of screening policies based on maternal age alone. In the meantime, however, the diagnostic capability of ultrasound scanning has also improved, and Howe et al argue that a combination of maternal age and mid-trimester ultrasound scanning can achieve detection rates approaching those of serum screening, while avoiding some of the problems with universal serum screening [Howe, D.T. et al. (2000) BMJ 320, 606-610]. The authors claim that over a six-year period, 68% of Down syndrome cases were detected antenatally by offering amniocentesis both to women over the age of 35 and also in pregnancies where fetal anomalies suggestive of Down syndrome were seen in an ultrasound scan at 19 weeks. This detection rate is considerably better than those used that have previously been used in comparisons with serum screening. The authors point out that the comparisons are markedly affected by the age structure of the population, and that an increase in the percentage of pregnancies in women over 35 leads to a corresponding increase in the effectiveness of screening policies based primarily on maternal age.

Comment: This paper is certain to generate a great deal of correspondence from both the proponents and the opponents of universal serum screening. The arguments will revolve around the magnitude of the marginal effectiveness of universal serum screening, and whether it is large enough to justify the costs. Whatever the conclusions, the debate highlights the need to keep population screening programmes under review, as pointed out by Raeburn in an accompanying editorial [Raeburn, S. (2000) BMJ 320, 592-593]. Such programmes are notoriously easier to begin than to end; it is for this reason that the National Screening Committee was set up to vet all proposals for new programmes. 

1 March 2000Over 50% of US states have enacted legislation that prohibits the use of genetic information for assessing risk in health insurance. It is widely assumed that this is a response to evidence of "genetic discrimination" against asymptomatic people who have found as a result of genetic testing that they have a genetic predisposition to a particular disease. The authors of a recent survey question this assumption [Hall, M.A. and Rich, S.S. (2000) Am J Hum Genet 66, 293-307 (Abstract)]. In interviews with representatives of insurance companies, insurance agents (brokers), genetic counsellors and state regulators of the insurance industry they could found very little evidence for genetic discrimination, either in states with prohibitory laws or those without. Insurance application forms did not ask about genetic tests, though some did enquire about family history; in these cases, however, the information was used to to supplement information about the applicants' existing health problems (i.e. the applicants were not asymptomatic). Insurers had little knowledge about the laws affecting use of genetic information, but were in any case mostly uninterested in such information as they considered it was of limited usefulness in risk assessment for this type of insurance product.

Comment: The weakness of this study is that it applies only to health insurance. As the authors point out, genetic information is likely to be far more relevant to risk assessment for life or long-term disability insurance. Most people in the US stay in health insurance plans for only a few years, and within that span of time genetic predispositions are unlikely to become apparent if the applicant is asymptomatic at the time of the application. It is reassuring, nevertheless, that insurers are not eager to become involved in genetics, even in states where it is not prohibited. This could, however, change if information about genetic predispositions becomes more precise and more common. Health insurers might then be forced to take this information into account in order to avoid adverse selection: the preferential purchase of insurance by people who know they are at higher risk, thus distorting the insurance "pool". In a recent article in the New Scientist, Virginia Warren (a consultant in Public Health Medicine at BUPA) argues that the requirement in the UK that people who have taken a genetic test must disclose its results to a potential insurer (though the insurer cannot require anyone to take a genetic test) will actually protect us against the widespread use of genetic information in insurance. Her argument is that insurers, in general, do not want to use genetic information, and will steer clear of it unless forced by evidence of adverse selection to take it into account (New Scientist, 12 February, 2000, pp. 48-49).

20 March 2000A major obstacle to assessing the desirability of population screening for hereditary haemochromatosis has been uncertainty about the penetrance of haemochromatosis-associated mutations in the HFE gene (see Haemochromatosis page for background information). Willis et al have attempted to estimate penetrance by performing a retrospective analysis of HFE genotypes in liver biopsy specimens from patients with liver disease (cirrhosis or liver cancer) over a 20 year period among the population of approximately 250,000 served by the Norfolk and Norwich district hospital in the UK [Willis, G et al. (2000) Gut 46, 401-404 (Abstract)]. They estimated that fewer than 2% of people with haemochromatosis-related genotypes have been treated by phlebotomy during this period. The percentage of liver disease patients with these genotypes (particularly homozygosity for the C282Y mutation) was significantly higher than the frequency of these genotypes in the population as a whole. However, when the number of C282Y homozygotes among liver disease patients was compared with the total number of births or deaths of  C282Y homozygotes expected within the total population over 20 years, it appeared that only about 2.5% of C282Y homozygotes in this population could expect a diagnosis of liver disease within their lifetime. Assuming that liver disease accounts for about half the phenotypic manifestation of haemochromatosis, Willis et al suggest that the penetrance is only about 5%.

Comment: The work of Willis et al does not lend support to calls for population screening for haemochromatosis. Although their study has some limitations, even a three- or four-fold underestimate would still suggest a relatively low penetrance and an unfavourable cost/benefit ratio. In this connection, Hickman et al, in a report in the same issue of Gut, suggest that measurement of unsaturated iron-binding capacity, following by genetic testing for those with an elevated measurement, is a suitable automatable method for population screening [Hickman, P.E. (2000) Gut 46, 405-409 (Abstract)]. They calculate the cost of detecting one "case" as about AUS$2300 (around £1000), but no counselling costs are included in this estimate, and the definition of a "case" must be questioned if iron overload is not always associated with disease. In an editorial, Adams suggests that the way forward in the haemochromatosis debate is for both haemochromatosis physicians and public health specialists to become more aware of the the contribution of each other's expertise: physicians advocating population screening need to understand the importance of knowing the penetrance of the mutations and the population attributable risk, while public health specialists need to appreciate the morbidity associated what has almost certainly been an underdiagnosed disease [Adams, P. (2000) Gut 46, 301-303]. Greater awareness could make screening unnecessary.  

28 March 2000A consortium led by genomics firm Celera and the scientists of the Berkeley Drosophila Genome Project has just published the complete sequence of the genome of the fruit fly Drosophila melanogaster, in a series of special articles (and a fold-out map) in the journal Science (24 March issue). The fly genome contains about 13,600 genes - fewer, surprisingly, than the 18,000 found in the genome of the nematode worm Caenorhabditis elegans, which was published at the end of 1998. The Drosophila genome will have enormous importance for human genetics as well, as many genes are essentially shared throughout the animal kingdom, and studies on their function in genetically tractable model organisms such as Drosophila will give insights into their role in humans. Of 289 human genes known to be associated with genetic disease, counterparts to 177 have been detected in the Drosophila DNA sequence. Celera Genomics is also working fast on the human genome, in competition with the publicly funded international effort, and is currently tipped to finish the human sequence by some time next year. Sequencing of the mouse genome is also underway.