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9 March 2001The additional protocol to the Council of Europe Convention on Human Rights and Biomedicine, prohibiting the cloning of human beings, came into force on 1 March, having been ratified by the required five member states (Slovakia, Slovenia, Greece, Spain and Georgia). The protocol has also been signed by an additional 24 countries, including several EU countries but excluding the UK, which is also not a signatory to the original Convention itself. Interestingly, the protocol leaves it up to individual countries to define what is meant by a "human being". If embryos created by cell nuclear replacement for research into embryonic stem cells (and only allowed to develop for up to 14 days) are not defined as "human beings", then the recent changes to the UK Human Fertilisation and Embryology Act permitting this research would not necessarily prevent the UK from signing the protocol.

27 March 2001An ad hoc committee appointed by the UK Health Departments has published a Code of practice and guidance on genetic paternity testing services. The need for the code of practice, which is voluntary, has arisen as a result of the increasing availability of paternity testing services supplied direct to the public, and the development of "motherless" testing, where only samples from the child (for example, a mouthwash or hair root sample) and the putative father are used. The Code, which will apply throughout the UK (though with some variations in Scotland, resulting from its different legal system), places the onus on the supplier of the testing service to ensure that, whatever type of paternity testing is done, consent is obtained both from the mother and the putative father, and from the adult(s) with legal capacity to consent on behalf of the child. Samples should always be taken by an independent person, unrelated to those tested. The sampler should follow a precise protocol and be able to verify that the samples come from the correct individuals. Suppliers should also ensure that their sampling and testing procedures are quality-controlled to prescribed standards, and that genetic information and samples are properly stored in a way that complies with the provisions of the Data Protection Act. The Code of Practice does not apply to tests carried out for forensic purposes. 

1 March 2001Just before the change of administration in the US, Donna Shalala, outgoing Secretary for Health and Human Services (HHS), released the HHS response to the report Enhancing the Oversight of Genetic Tests, produced by the Secretary's Advisory Committee on Genetic Testing. Her response indicated that HHS accepted essentially all of the SACGT's recommendations, and planned to push forward on several fronts in implementing them. The overall plan involves coordinating the activities of the Health Care Financing Adminstration in certifying laboratories undertaking genetic testing, the Food and Drug Administration in reviewing, approving and labelling all new genetic tests that have moved beyond the basic research stage, and the Centers for Disease Control and Prevention in collecting information to evaluate the analytical validity, clinical validity and clinical utility of genetic tests. The Secretary's response also stressed that procedures for obtaining informed consent are essential for all research protocols for genetic tests in which individually identifiable samples are used. Incoming HHS Secretary Tommy Thompson has not yet indicated his view on the proposals for oversight of genetic tests, but it seems likely that the Bush administration's approach will be broadly in line with that of its predecessor on this issue.  

28 March 2001On 9 February, the Human Genetics Commission held an information-gathering day on genetics and insurance. A report of the issues that were discussed during the day has now been published on the HGC's website. Presentations by a member of the actuarial profession, a geneticist, a representative of the insurance industry, and the Chief Executive of the Alzheimer's Society covered topics including the nature of insurance underwriting and actuarial evidence, the definition of "genetic information", the practical realities of genetic testing for late-onset conditions, the moral issue of fair and unfair discrimination in insurance, and the problems for genetic research posed by the need to disclose test results to insurers. Possible new models for insurance were discussed that might avoid some of the problems that could result from the use of genetic information. The HGC will be considering the issue of genetics and insurance further.

13 March 2001The results of a study published in Science suggest that musical ability, assessed as the ability to recognise pitch correctly, is highly heritable [Drayna, D. et al (2001) Science 291, 1969-1972]. The researchers tested the ability of 136 pairs of identical twins and 148 pairs of fraternal twins to detect discordant notes in segments of popular melodies. The identical twins achieved very similar scores (70-80% concordance), while fraternal twins showed only about 40% concordance in their scores.

Comment: These findings have been interpreted by the press - and indeed by the researchers themselves - as showing that parents are "wasting their money" on music lessons if their child has not inherited genes conferring musical ability. There seems little doubt that there is such a thing as "innate" musical ability, and that a child without this ability is unlikely to become a Beethoven or a Mozart, but the suggestion that children without this genetic gift should give up music smacks of genetic determinism at its worst. It ignores a great deal of work which shows that children who are not "naturally" musical can, if well taught, vastly improve their ability to sing in tune, recognise rhythm and play a musical instrument. Fatalistic ideas about the effects of one's genetic endowment must be resisted.  

19 March 2001As part of its current inquiry into the ethics of research on genetics and behaviour, the Nuffield Council on Bioethics is conducting a consultation to investigate public attitudes to this controversial issue. The inquiry will explore the ethical implications of research into the genetic contribution to traits such as addiction, sexual orientation and violent behaviour. Copies of the consultation document, which sets out the issues and invites public comment on specific questions, can be obtained via the Council's website. 

13 March 2001In a "Viewpoint" article in The Lancet, Vineis et al challenge predictions that population screening for genetic susceptibility to various diseases will become common practice [Vineis, P. et al (2001) Lancet 357, 709-712]. By working through several examples in which they calculate the theoretical "Number Needed to Screen" (NNS) to prevent one case of disease, they show that this number is generally at least 1000 and often much higher, even with the most generous assumptions about the contribution of a particular allele to development of the disease. In contrast, testing in families affected by rare, highly penetrant disease-causing mutations is far more effective (NNS generally fewer than 10), provided that the condition is treatable. Vineis et al also make the point that drawing a simple association between a single allele and disease susceptibility is fraught with problems because, for example, the same allele in different genetic backgrounds (i.e. in different individuals) can have different effects, and many effects of low-penetrance alleles are highly dependent on environmental exposure.

Comment: It is worthwhile to sound a note of caution about over-enthusiastic claims for population genetic screening. However, the possibilities clearly cannot be dismissed altogether. If specific tests are carefully validated in studies on large populations, if testing technology becomes cheap enough, if effective treatments and prevention are in place, and if perceived ethical and social barriers can be surmounted - a challenging set of "ifs" - then population genetic screening may find some applications. 

23 March 2001People with the genetic disease xeroderma pigmentosum have a defect in the repair of DNA damaged by exposure to agents such as ultraviolet light, making them highly susceptible to skin cancers. In a placebo-controlled, randomised and blinded trial, Yarosh et al have shown that in these people, daily application of a skin cream containing the bacterial DNA repair enzyme T4 endonuclease V (T4N5) reduced the rate of appearance of new skin cancers and pre-cancerous skin lesions [Yarosh, D. et al (2001) Lancet 357, 926-929]. Treatment was most effective in young patients aged less than 18 years.

Comment: For some single-gene diseases, understanding of the underlying molecular defect is beginning to lead to the development of new treatments. While gene therapy approaches are currently showing promise for haemophilia, severe combined immunodeficiency and Duchenne muscular dystropy, enzyme therapy approaches are proving effective for diseases such as some inborn errors of metabolism and, now, the cancer-prone syndrome xeroderma pigmentosum. Although a great deal more research work is needed to confirm its benefits, the protective effect of the T4N5 cream in xeroderma pigmentosum patients may also point to a more general use for this treatment to protect against sun-induced skin cancer. 

19 March 2001In many developed countries, it has been recommended that women with a family history indicating they are at increased risk of breast cancer should be offered a surveillance programme that is more intensive and/or begins at an earlier age than population screening programmes for those at average risk. These recommendations have been assumed to be particularly important for women carrying mutations in the BRCA1 or BRCA2 genes. However, there has been a lack of evidence to support such recommendations. A combined retrospective and prospective follow-up study by Brekelmans et al makes an important contribution to the evidence base [Brekelmans, C.T.M et al (2001) J Clin Oncol 19, 924-930 (Abstract); also see editorial by Armstrong, K. and Weber, B. (2001) J Clin Oncol 19, 919-920]. The 1198 women in the study included 128 with proven BRCA1 or BRCA2 mutations, plus 621 classified as "high risk" and 449 classified as "moderate risk" on the basis of their family history. The average age at the beginning of surveillance was 35-40 and the median period of surveillance was 3 years. The rates of cancer detection in the three groups were, respectively, 23.7, 7.0 and 2.7 times those expected in an average-risk population of the same age, though the confidence intervals for all groups were wide. BRCA1/2 mutation carriers were more likely than women in the other groups to develop cancer in the interval between yearly mammography, and to have higher-grade tumours.

Comment: Further large studies are needed to build on the evidence provided by Brekelmans et al, in order to get a better picture of the yield of mammographic surveillance in women in different genetic risk categories, and to determine the best surveillance protocol. Brekelmans et al suggest that BRCA1/2 mutation carriers may need to be checked more than once a year, and that magnetic resonance imaging may be more effective than standard mammography for early detection of tumours in high-risk women at young ages. 

8 March 2001On 2 March, to coincide with its first plenary meeting held in public, the Human Genetics Commission published the result of a survey commissioned from the social research company MORI, on public attitudes to human genetic information. The study used the People's Panel, a randomly recruited group of around 6000 people aged 16 and over, plus an additional group of Black and Asian respondents. The results of the the survey reveal substantial enthusiasm for the potential contribution of genetics to improving medical care and the prevention of disease. They also show that most people have quite a good grasp of the relative contributions of genetic and environmental factors in determining susceptibility to disease, suggesting that "genetic determinist" ideas do not hold sway. Perhaps paradoxically, though, people still fear that if others had access to their genetic information they would "know too much about them". There was strong support for the use of genetic information and technology in medical care (including, surprisingly, overwhelming support for germ-line gene therapy) but its use for more social purposes, such as choosing the sex of a child, was frowned upon, except in the sphere of forensic science and paternity testing. People were suspicious of all commercial uses of genetics, for example by employers or insurers. They were also hostile to the idea that commercial organisations should be allowed to own and profit from developing new ways of using human genetic information. Worryingly, people felt that advances in genetics were overtaking the ability of society to regulate them adequately, and felt ill-informed about the regulatory process. It is to be hoped that the Human Genetics Commission, by maintaining a high public profile and continuing to work hard to engage the public in its work, can begin to assuage these fears. 

1 March 2001Not long after the identification of the BRCA1 and BRCA2 genes associated with hereditary breast cancer, it was realised that these genes are very rarely mutated in sporadic breast tumours, suggesting that the underlying molecular pathways of carcinogenesis may be different in hereditary and sporadic breast cancer. Indeed, BRCA1- and BRCA2-associated breast tumours have some histopathological features that differ from those of sporadic tumours. Hedenfalk et al report the results of a study in which they used microarray technology to characterise these differences in molecular terms [Hedenfalk, I. et al (2001) N Engl J Med 344, 539-548]. They hybridised normal reference RNA, and tumour RNA from a breast cancer patient with a germ-line BRCA1 or BRCA2 mutation, to an array of cDNAs representing 6512 genes. The reference and tumour RNAs carried different fluorescent tags, enabling a picture to be built of up of genes that are expressed either more or less strongly in the tumour sample than in the reference. Statistical analysis of the results for a set of 23 BRCA1 tumours, 17 BRCA2 tumours, 34 sporadic tumours, and 39 tumours from women with a family history of breast cancer but no identified mutation in BRCA1 or BRCA2, showed that the BRCA1 and BRCA2 tumours had gene expression profiles that were distinct from each other and from the profiles of sporadic tumours. It was possible to use the gene expression profile to predict with reasonable accuracy whether a particular tumour came from a hereditary breast cancer patient or a patient with sporadic breast cancer.

Comment: New approaches such as microarray technology, together with the information emerging from the human genome project, are expanding research horizons beyond individual genes to the study of how large batteries of genes are regulated in different cells or tissues, or during different physiological processes. The development of a "molecular taxonomy" for disease promises to improve the accuracy of diagnosis, to reveal new targets for drug treatments, and to improve the specificity of treatment.