In the news

The Cancer Research Campaign and the Imperial Cancer Research fund (soon to merge) are to provide an information pack for GPs to help them make more appropriate referral decisions about women concerned about their genetic risk of breast cancer (see report in BBC News On-line). Research over the last few years has consistently shown that GPs lack the skills necessary to classify women's risk on the basis of their family history, and that as a consequence they inappropriately refer many low-risk women to Regional Genetics Centres.

Section 60 of the Health and Social Care Act (2001) enables the Secretary of State for Health to approve the use of patient identifiable information, without informed consent, to support essential health service activities that are deemed to be in the public interest and for which it would be impracticable to obtain consent or to use anonymised data. A Patient Information Advisory Group has been set up to consider applications under Section 60 and advise Ministers. It would be very cumbersome for the PIAG to consider separate applications for potentially scores of uses by a large number of different bodies, so the Department of Health has proposed establishing "class regulations" under Section 60 that would enable patient identifiable information to be used without consent for a specific set of six broad but limited purposes. These include, for example, obtaining anonymised data from individual patient records to support medical purposes, and identifying patients who would be suitable subjects to invite to participate a medical research project.

The Department of Health's proposals are currently in a consultation phase, which closes on 31 January. The full set of proposals is set out in a background paper, together with examples of their potential applications. An additional paper sets out illustrative draft regulations along the lines that wouuld be required; these are likely to be modified as a result of the consultation. The consultation asks for respondents' views both on the proposals for class regulations, and on the merits of applications under Section 60 that have been submitted by several bodies including the UK Association of Cancer Registries, the Department of Health Policy Research Programme and the Public Health Laboratory Service.

The American Diabetes Association and the University of Florida have teamed up to launch a screening programme that will eventually be rolled out to see all newborn infants in the US state of Florida offered testing for genetic susceptibility to Type 1 diabetes. Babies who test positive in the voluntary programme will be monitored in subsequent years for the appearance of autoantibodies that indicate the first signs of disease. The hope is that screening will enable at least some children who develop Type 1diabetes to be identified at a very early stage, and that early treatment might prevent some of the most severe effects of the disease such as blindness, kidney failure and neurological damage. Eventually, some preventive measures may become possible, and the information obtained from the screening and monitoring programme may give some clues to the factors that translate a genetic susceptibility into the development of disease. The scheme has been piloted at four Florida hospitals over the last four years, with the result that more than 9000 children have been identified as "at risk" and enrolled for monitoring. The press release announcing the expansion of the screening programme does not specify what genetic variants are tested for or give any information about the sensitivity, specificity, or positive or negative predictive value of the test.  

In a debate on the House of Lords Select Committee on Science and Technology Report on Genetic Databases, peers commented on some aspects of the Government's response to the report's recommendations (the Government response is not available on line but can be ordered from The Stationery Office). The Committee's report was very supportive of the aims of research designed to unravel the contribution of genetic factors to common disease and recommended a number of measures to strengthen the UK's capacity for such research, in particular in the area of bioinformatics, computer science and statistical genetics. This was acknowledged as a priority in the Government's response. The Select Committee also drew attention to inadequacies and inconsistencies in the implementation of information technology in the NHS, in particular in the development of electronic patient records. In its response, the Government listed 14 different organisations and initiatives in this area, but peers were concerned that the approach was heavily bureaucratic and probably too slow for systems to be in place in time for the launch of the proposed BioBank UK project, and that the Government had not adequately addressed the need for standardised data and mandatory NHS numbers in all health records. However, the widest divergence between the Select Committee's recommendations and the Government response concerned the Committee's view that a Medical Data Panel should be established to set policy and approve projects involving the secondary use of NHS and medical research data. The Government responded that the proposed roles of the Medical Data Panel were covered already by the system of Research Ethics Committees and the new Patient Information Advisory Group set up in 2001 under Section 60 of the Health and Social Care Act. In the debate, some peers expressed concern that the operation of the PIAG, seemed unnecessarily cumbersome and inefficient and would hamper research, while research ethics committees were already overburdened and sometimes showed an inconsistency in approach. In his reply on behalf of the Government, Lord Hunt mentioned that the Government is considering proposals for a system of broad class approval by the PIAG for types of primary research projects in which "the likelihood of detriment to patients is small, the infringement of privacy is minimal and necessary and appropriate safeguards are in place" (see news item on Section 60 consultation).  

UK Secretary of State for Health, Alan Milburn, has announced that centres of excellence to be known as "Genetics Knowledge Parks" are to be established in London, Cambridge, the North West, Newcastle, Oxford and Wales. The Genetics Knowledge Parks are part of a £30 million package of initiatives in genetics that also includes increased funding over the next three years to support genetics services, and the designation of two genetic testing laboratories as Reference Laboratories that will develop and assess new tests and provide education and training in genetics for other health professionals. The two laboratories chosen to be Reference Laboratories are the North West Regional Genetics Laboratory in Manchester, and the Wessex Regional Genetics Laboratory in Salisbury.

The Genetics Knowledge Parks encompass a wide range of partnerships and activities. The Cambridge Genetics Knowledge Park will draw together the region's academic, clinical and commercial strengths to assist the transfer of genetic knowledge into health benefits for individuals and the population as a whole, and wealth for the UK. Based in Newcastle, the Northern Genetics Knowledge Park will build up regional strength in post-genomic technologies and their translation into innovative healthcare, and promote genomics education through the activities of the Centre for Life. London's IDEAS Park aims to provide a genetics information service for both health professionals and members of the public, and to promote debate on the understanding of genetics. NoWGEN, the North West Genetic Knowledge Park, will create a multidisciplinary Centre for Applied Genetics that will work on new service models for genetics as well as providing training opportunities and facilitating knowledge transfer. Oxford's Genetics Knowledge Park will focus its activities on the development of molecular genetic testing in clinical practice. The Genetics Knowledge Park in Wales will be built around a consortium of the University of Wales College of Medicine, the University of Cardiff, and the "science discovery centre" Techniquest.

The £11 million allocated for the development of current genetic services throughout England will enable the appointment of 11 new clinical genetics consultants, 28 genetic counsellors and more than 40 genetic scientists, and the purchase of "state of the art" equipment for genetic testing, with the aim of reducing waiting times for consultations and reporting times for test results. Further details of all the new initiatives in genetics are available in a Department of Health press release.  

YourGenome.org, a website produced by the Wellcome Trust Sanger Institute, is a new addition to web-based sources of information and educational material on genetics and genome science. The site has three graded levels designed for the needs of beginners (lay people and secondary school students up to GCSE level), those with intermediate knowledge of the subject (A-level students) and advanced users (undergraduate level - still in preparation at the time of writing). Information about basic genetics and genomics is supplemented by answers to lists of frequently asked questions, news about advances in genome science, and a news forum page that allows users to add their own news story. YourGenome.org aims to spark participation and feedback by running polls on controversial questions and competitions for essays and pictures on topics in genomics.  

The UK Government has been successful in an appeal against a ruling by the High Court last November that the Human Fertilisation and Embryology Act did not cover embryos created by cell nuclear replacement because the creation of these embryos does not involve fertilisation (see report in BBC News On-line and Stem cells and cloning page). Three Appeal Court judges held that such embryos do fall within the meaning of the Act and that therefore research involving their creation can be regulated by the Human Fertilisation and Embryology Authority. As a result of this decision, scientists wishing to carry out research involving cell nuclear replacement (CNR) as a means of obtaining embryonic stem cells will be able to apply to the HFEA for a licence. The use of any CNR embryos for reproductive cloning is illegal both under regulations forming part of the Human Fertilisation and Embryology Act (passed by Parliament in early 2001), and under the Human Reproductive Cloning Act (December 2001). 

Recent articles in Science magazine and the BMJ discuss the issues surrounding the expansion of neonatal screening to encompass a wider range of genetic disorders of metabolism [Marshall, E. (2001) Science 294, 2272-2274; Leonard, J.V. and Desateux, C. (2002) BMJ 324, 4-5]. At present newborn infants in the UK are routinely screened only for only one of these diseases - phenylketonuria - but the development of new technology, in particular tandem mass spectrometry, makes it possible to screen rapidly and relatively inexpensively for up to 20-40 rare diseases of this type by measuring levels of metabolites characteristic of each disease. Eliot Marshall reports in Science that in the United States there is an increasing impetus towards expanding neonatal screening programmes in this way, with several states beginning to use tandem mass spectrometry to test for a range of diseases including medium chain acyl CoA dehydrogenase (MCAD) deficiency. The largest of these is California, which launches a pilot programme this month. Marshall also reports that tandem mass spectrometry is being used in the neonatal screening service in New South Wales (Australia) and is being developed in a somewhat patchy way in the UK and some other European countries. The influence of lobby groups such as the March of Dimes seems to have built up an unstoppable momentum towards expanded neonatal screening in the US. Although expert opinion in the UK is generally cautious, there are nevertheless increasing calls for MCAD screening to be introduced as a service. However, as Leonard and Desateux point out in the BMJ, there are many issues to be considered, including the problem of false positives, the unknown false negative rate, and the practical problem that the best time for MCAD screening is not the same as that at which the Guthrie blood sample is currently collected. Specific questions such as these are likely to apply to all the individual diseases that could potentially be tested for using tandem mass spec, and for many there is the additional problem of whether it is ethical to test for a disease for which there is no effective treatment. 

Three eminent scientists have resigned from the editorial board of the electronically published Journal of Regenerative Medicine, in protest over its publication of a paper reporting the cloning of human embryos (see report in BBC News On-line). Dr Robin Lovell-Badge of the National Institute for Medical Research in London, and Dr Davor Solter of the Max Planck Institute for Immunobiology in Freiburg, are very critical of the paper by scientists from the US company Advanced Cell Technology, who claimed that they had succeeded in producing a cloned embryo that survived to the six-cell stage (see report in November 2001 newsletter). Their concerns echo those of Dr John Gearhart of Johns Hopkins University, who resigned from the editorial board of the journal last year. All three scientists, who are experts in the field but were not asked to referee the paper before publication, question whether the "embryo" was in fact alive and point out that, even if it was, no data are presented to show that its DNA came from the donor cell. 

More than 80% of people with a clinical diagnosis of the iron overload disease hereditary haemochromatosis are homozygous for the C282Y mutation in the HFE gene. As about 1 in 200 people in populations of European extraction are homozygous for this allele, there have been calls for population screening followed by prophylactic treatment (regular phlebotomy) for those identified. However, the penetrance of haemochromatosis-associated mutations has been unclear, with some studies suggesting that it is very low. Beutler et al now report a very large study, involving more than 41,000 people, who were tested for C282Y and a second haemochromatosis-associated mutation, H63D, and for symptoms of iron overload [Beutler, E. et al (2002) Lancet 359, 211-218]. A range of classical clinical signs and symptoms associated with haemochromatosis were no more frequent in the 152 individuals who were homozygous (C282Y/C282Y) or compound heterozygotes (C282Y/H63D) for haemochromatosis-associated mutations than they were in matched controls. One exception was a history of liver disease, but this feature was still observed in only 10% of those with genetically-defined haemochromatosis, and there was no evidence that the liver symptoms worsened with age or shortened lifespan. Only one individual had clinically-defined haemochromatosis.

Comment: This large study provides compelling evidence that the penetrance of haemochromatosis-associated genotypes is far lower than would be needed to justify a population screening programme.