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26 September 2003In its White Paper, Our Inheritance, Our Future, the UK Government announced its intention to set up a genetics education centre that would act as an “enabler” to facilitate the incorporation of genetics into the training of a wide range of healthcare professionals. The Department of Health has now issued further information about the plans for the centre and is inviting expressions of interest from organisations who would like to be included in the short list for tendering for the contract. The closing date for submissions is 24 October.
The NHS Genetics and Education Development Centre will not be directly involved in delivering genetics education, but will work with professional groups to identify the learning needs of different types of health professionals, outline skills and competency frameworks, and develop curricula. It will also support genetics teaching by commissioning and developing teaching materials, running seminars and workshops to “train the trainer”, and establishing an expert resource service of learning resources in genetics. The Centre will be affiliated to the NHS University and will be expected to work closely with a variety of organisations including the Genetics Knowledge Parks, the Public Health Genetics Unit, the National electronic Library for Health, and groups involved in other initiatives in genetics education sponsored by the Department of Health.
The Centre’s initial contract will be for three years, extendable by a further two years.
29 September 2003The Nuffield Council on Bioethics, in its latest report Pharmacogenetics: ethical issues recognises that it is too early to know exactly how the science of pharmacogenetics will be applied in practice, but stresses that it is not too soon to begin considering the potential ethical, legal, social and policy implications.
The report encourages continued research, including the incorporation of pharmacogenetic investigation into clinical drug trials, with the aim of enabling the development of new drugs that will be safe and effective in specific patient groups. Patients asked to participate in such trials should be fully informed about the nature of the trial, how their samples will be used and how they will be stored. If the samples are anonymised, participantsshould be asked for broad consent covering possible future uses. For identifiable samples, consent should only be sought for the proposed current use, although broad consent for future use could be sought at a later stage. Although the report states that it is unlikely that trials will produce useful information regarding any one individual’s medical treatment, the opportunity for a patient to receive such information, if possible, should be discussed at the time of obtaining consent.
The report raises the concern that pharmacogenetics could lead to the stratification of populations into smaller groups based on genetic variants, with the risk that some of these groups might be too small to be of interest to the pharmaceutical industry; if this were to happen, remedies such as orphan drug legislation must be considered. Populations might also be stratified on the basis of race or ethnic group, as determined by genetic variants. While this may be useful for identifying populations to sample, researchers must be aware of the possibilities of negative stereotyping or causing prejudice.
Individuals should not be overly concerned about insurers having access to pharmacogenetic test information, as it is covered by the current moratorium on the use of genetic test results by insurers. Insurance companies have also stated that they believe such information would be of low value in setting premiums for policies. Nevertheless, the report recommends continuing the moratorium beyond its current expiry date of 2006.
The promise of "personalised medicine" is likely to be still some way in the future, the report concludes, but the professionals who will eventually be involved in delivering the service - particularly GPs and pharmacists - need to begin acquiring an understanding of the science of pharmacogenetics and of how to communicate that information to patients.
19 September 2003A new report from the King’s Fund describes the results of a study by BBC reporter Roger Harrobin on the way in which health risks are reported by the news media. Predictably, Harrobin found that scientists and public health experts are critical of news coverage of health issues, and indeed when the numbers of news stories about specific health threats were compared with the numbers of deaths attributed to those threats, it was clear that proportionately far more coverage is devoted to remote risks such as vCJD than to known mass killers such as smoking and obesity. No-one expects the news media to be instruments for conveying public health policy, however, and we all recognise that if journalists plugged away at the same well-known issues their stories would simply by “spiked” by their editors.
However, Harrobin suggests a number of developments that “might encourage a closer fit between risks to public health and news reporting”. These include: journalists actively helping the public to understand risk and put it in perspective; a greater awareness by Government that the intensity of news coverage is not necessarily a measure of public concern (and so should not directly affect public policy); a better understanding of how the public perceive risk; stronger advocacy in the news media about major public health risks; and more skilful presentation of health issues by scientists and public health experts, tailored to the requirements of each type of news outlet.
The King’s Fund report coincides with an inquiry by the Royal Society about how the results of scientific research are made public. Chaired by Professor Patrick Bateson, the Royal Society’s working group is concentrating mainly on what “checks and filters” (including peer review) research results should go through before they are communicated to the public, and on whether and how the public should be informed about these quality checks. The group is also investigating what roles scientific and medical journals should play in communicating research results to the wider public. Evidence should be submitted to the working group by 26 September 2003.
25 September 2003The funders of UK Biobank have released for consultation their plans for ethical oversight and governance of the project. Biobank aims to obtain genetic profiles, medical and lifestyle information from 500,000 middle-aged UK volunteers and to follow their health over the next 15-20 years, in order to investigate how genetic and other factors interact to affect disease susceptibility.
An Interim Advisory Group has made detailed recommendations about the way in which consent should be sought from prospective participants, and the information they should be given in order to enable them to make their decision. The IAG recommends that participants should be made aware, among other things, that not all future research uses of their information can be anticipated, but that they will be kept informed about the progress of the project and have a right to withdraw at any time. They will also be told about arrangements for keeping their data confidential (essentially, sensitive data will be “reversibly anonymised” by means of a secure coding system) and for ensuring that only approved researchers and projects are given access to the anonymised data. It will be made clear that there will be no feedback of individual health information to participants as a result of research use of the Biobank database, because Biobank is not a health care project and because the significance, to individuals, of most of the population-level information generated by the research will be uncertain. An Ethics and Governance Council will be appointed to safeguard the interests of participants and the wider public, and will report publicly on its work.
The scientific direction and objectives of Biobank will be supervised by a 17-member Scientific Committee chaired by Professor John Bell. Sub-groups of this committee will be response for specific areas: recruitment, questionnaire and measurement, data management, and sample storage.
A Board of Directors chaired by Sir Alan Langlands will fulfil the legal functions required under company law and charity law, with overall responsibility for the “direction, management and control of UK Biobank Limited”. Other members of the Board have yet to be announced.
Those who wish to comment on Biobank’s ethics and governance proposals are asked to do so by 24 October.
30 September 2003In the coming years, developments in genetic science will have an increasing impact on health care and health services. Many surveys have come to the conclusion that health professionals are not well-prepared for the changes that will come as genetics spreads from specialist centres to affect wider clinical practice. In a move towards tackling this problem, the Department of Health and The Wellcome Trust commissioned the PHGU to undertake a project to develop a national strategy for the education of health professionals in genetics.
The project report, “Addressing Genetics, Delivering Health”, is the culmination of a two-year process whose key feature was the involvement of representatives from the professional groups themselves. Workshop participants from the fields of general practice, post-graduate medicine, nursing and midwifery, pharmacy, dietetics and health service management worked with the project team to identify their own learning needs and the resources that will be required to meet those needs. Input from patients was considered crucial, so an additional workshop explored the needs of those who use genetic services, and their views about what the health professionals involved in their care need to know.
Key conclusions from the project include the need to: incorporate genetics into major clinical policy initiatives such as the National Service Frameworks; relate genetics education directly to clinical practice and current services; develop accessible, authoritative and up-to-date learning resources, for example on the web; involve patient groups in scoping what practitioners need to know; make genetics a compulsory, examinable part of curricula; and stress the place of genetics as part of an integrated clinical network.
The report recommends the establishment of a national Steering Group for Genetics Education to provide a strategic overview, and of a national Centre for Genetics Education to coordinate programmes, develop and commission learning resources, and champion the place of genetics in health-professional education. In its recent White Paper, the Government has already announced its intention to establish such a Centre, and the Department of Health has called for expressions of interest in the tender.
5 September 2003The role of enzymes that repair oxidative DNA damage in modifying cancer risk is the focus of intense study. Writing in the Journal of the National Cancer Institute, Paz-Elizur et al have suggested an association between lowered 8-oxoguanine DNA N-glycosylase (OGG) activity, an enzyme involved in the repair of oxidative DNA damage, and an increased risk of non-small-cell lung cancer (NSCLC) [Paz-Elizur, T et al, JNCI 2003; 95: 1312-1319]. This finding also formed the basis of a front-page article in The Times (September 3, 2003). The study, which included cases (n=68) and controls (n=68) frequency matched for age and sex, found individuals with the lowest OGG activity to have an increased risk of NSCLC when compared to individuals with high OGG activity (OR=4.8, 95% CI=1.5-15.9). In addition, the authors found the estimated relative risk of NSCLC in smokers with low OGG activity to be 124-fold higher than for non-smokers with a normal level of OGG activity. This led the authors to suggest that smoking cessation in individuals with reduced OGG activity may prove an effective strategy in preventing lung cancer, although the authors acknowledge that large-scale, prospective epidemiologic studies are required to test the clinical efficacy of such an intervention.
Comment:This study provides some initial evidence that plasma OGG activity may be predictive of lung cancer risk. However, the number of patients involved in the study was small and considerably more evidence will be required to validate this result. The research does not exclude the possibility that plasma OGG activity is related to environmental exposures, or is a consequence of the disease itself. While the study highlights a potential role for the enzyme in the modification of individual lung cancer risk, the findings should be interpreted with caution and require further investigation in large-scale, prospective studies, a conclusion supported in an accompanying editorial [Caporaso, N, JNCI 2003; 95: 1263-1265].
29 September 2003An article in Science [Kirkness, E. F. et al. (2003) Science 301, 1898-1903] reports a comparative study of the human, dog and mouse genomes. Comparison of different mammalian genomes is useful for the identification and study of genes linked to human disease, and the domestic dog genome is useful because breeding programs have created a population that shows huge variation in physical characteristics between breeds, but which within breeds have very closely related genes. The study of genetic disease is also easier using large dog pedigrees than small human families, and dogs suffer from 360 known genetic diseases with equivalent forms in humans. The authors found that nearly twice as much unique human genome sequence could be aligned with the dog genome than with the mouse genome, despite the fact that the dog genome was less complete (1.5x coverage rather than 8x coverage for the mouse), although not all of the human genes were aligned with dog sequences for their entire length. More than 4% of intergenic (non-coding) DNA sequence was found to be conserved between the human, dog and mouse.
Comment: This article contributes to the growing body of information on mammalian genomes, and provides evidence that even relatively crude genome sequences can yield valuable (and as the authors point out, cost-effective) information. As additional mammalian genome sequences are published – with projects to sequence the genomic DNA of species including the chimp and the cow well underway – the insight into the genetic features underlying human development and disease should deepen.
10 September 2003A report in The Lancet [Tkachev, D. et al. (2003) Lancet 362, 798-805] identifies some defects in expression of myelin-related genes present in both individuals with schizophrenia and those with psychotic bipolar disorder (also called manic depression), two forms of mental illness with markedly distinct symptoms and treatments. Myelin is a substance produced by specialised cells (oligodendrocytes and Schwann cells) that coats nerve cell axons, allowing them to conduct impulses between the brain and other parts of the body. Tkachev and colleagues investigated oligodendrocyte-specific and myelin-associated gene expression in the prefrontal cortex of brains from patients with schizophrenia and bipolar disorder using two techniques, quantitative PCR and microarray analysis. Expression of many (but not all) of these genes was reduced in oligodendrocyte cells from the diseased brain samples relative to those from the controls, suggesting that oligodendrocyte function (particularly with respect to myelin production) was abnormal. The authors propose that the correlation between the gene expression changes in schizophrenia and bipolar disorder provide evidence for common pathological pathways in the two diseases.
Comment: The importance of oligodendrocyte cells and myelination in psychotic disease is reinforced by this study, and evidence for similarities between two quite distinct diseases is presented. The study size is small (only fifteen samples for each disease and for controls, and not all of these were included in the analysis of microarray data) and there is considerable scope for further investigation. A commentary by Davis and Harutunian on the report raises a number of pertinent questions to be addressed, including the issue of differences in gene expression in different regions of the brain; they suggest that regional patterns of altered gene expression might vary between the two diseases. They also query whether a similar overlap in gene expression would be observed between the brains of patients with schizophrenia and those with non-psychotic forms of bipolar disease.
9 September 2003A new report published by the Health Technology Assessment (HTA) programme re-assesses options for screening for Fragile X syndrome, an inherited form of learning disability that affects about 1 in 4000 males and 1 in 8000 females [Song, FJ et al (2003) Health Technol Assess Vol 7, no. 16]. The disease is caused by expansion of a tract of repeated sequence on the X chromosome; for women carrying a “pre-mutation” (55-200 repeats) there is a risk that the sequence can expand to a full mutation (more than 200 repeats) in their children. This risk is thought to be about 60% for pre-mutation carriers from affected families and about 10% for carriers from the general population. All males, and about half of females, who carry a full mutation are affected by the disease (see Fragile X page for further background information). Two previous HTA studies reached differing conclusions about the relative merits of cascade testing in affected families, and screening of all pregnant women to detect those carrying a pre-mutation so that they can be offered antenatal diagnosis to determine if the unborn baby is affected [Murray, J et al (1997) Health Technol Assess Vol 1, no. 4; Pembrey, M et al (2001) Health Technol Assess Vol 5, no. 7]. Song et al have attempted to resolve the issue with a new analysis of the published literature and development of a simulation model for comparing cost-effectiveness of different approaches. They conclude that cascade testing in affected families is a very cost-effective way of detecting fragile X pregnancies but that universal prenatal screening, although much more expensive, might overall be a better strategy because the total number of cases detected would be higher (39 over the first 10 years compared with 15 for the cascade approach). They suggest that both strategies should be evaluated further in pilot studies.
Comment: The merits of screening programmes for fragile X syndrome are controversial, particularly in terms of how potential benefits are assessed. Song et al calculate the effectiveness of different approaches in reducing the number of fragile X births, and compare the costs of screening with the lifetime cost of caring for affected individuals. Most geneticists prefer to regard the goal of screening programmes as providing informed choice to families, and place more weight on less readily quantifiable factors such as emotional reactions or effects on social and family relationships. In the case of fragile X screening, pre-mutation-carrying women with no family history of the disease would have to decide whether to opt for invasive antenatal diagnosis on the basis of a 10% risk of the child having a full mutation, knowing also that if the affected child was a girl there would be around a 50% chance of her showing clinical signs of the disease. The social and emotional weight of such knowledge and decisions could be considerable. Song et al conclude from a brief analysis of published studies that both cascade and population screening programmes are “feasible and acceptable” but, as they suggest, large-scale trials would be needed to evaluate these and other factors more fully.