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14 April 2002Agreement has been reached between the Australian Prime Minister and the leaders of Australia’s eight States and Territories to enact national legislation that would allow embryonic stem cell research using ‘spare’ IVF embryos that would otherwise be destroyed. However, a compromise had to be struck between the conservative Prime Minister, who favoured allowing research only on embryos already in existence on 5 April 2002, and the more liberal State Premiers, who objected to this restriction. The compromise agreement imposes this restriction for an initial year, during which an ethics committee will develop safeguards to ensure that embryos cannot be created solely for the purpose of research. If national agreement cannot be reached on these safeguards, the restriction would automatically expire after three years and the whole matter would have to be reconsidered. The law would also make it mandatory to seek the consent of couples donating embryos for research. Members of Australia’s State Parliaments and Federal Parliament will have a free vote on the proposed legislation, which is expected to be passed, but not without strong opposition from some church groups

29 April 2002The Wellcome Trust, the Medical Research Council and the Department of Health have announced that initial funding of £45 million has been approved for BioBank UK. The Wellcome Trust and the Medical Research Councill will each contribute £20 million, and £5 million will come from the Department of Health. The BioBank project will analyse genetic and lifestyle information for 500,000 volunteers aged 45-69 and follow their health over the next 10-15 years, with the aim of understanding how genetic and environmental factors combine to influence susceptibility to disease. A small group of regional centres will recruit volunteers, with one central coordinating centre designated to manage the project. Expressions of interest from potential participating centres will be sought over the next few months, with a view to development of detailed bids by the autumn. Ethical oversight for the project will be provided by an independent committee charged with representing the interests of the volunteers, the general public and the funders; details of the ethical framework have yet to be decided, and consultation on this aspect of the project will continue.

2 April 2002A US-based charitable trust has made a $US9.9 million grant to establish a Genetics and Public Policy Center at the Johns Hopkins University in Washington DC. The institute’s first work will be a Genetics and Human Reproduction Initiative, focusing on the ethical issues surrounding the use of genetic technology in human reproduction, in particular the prospects for "genetic enhancement" by selecting embryos with desired traits. The Center will develop the arguments for and against different policy options, rather than advocating a particular policy stance. It will also work towards educating leaders about the key issues and supporting public consultation.

25 April 2002The UK Human Genetics Commission (HGC) recently published its strategy for involving the public in its deliberations. The strategy document commits the HGC to continuing to hold its plenary meetings in public and to publishing full, attributable minutes of both the full Commission and its subgroups on its website. Future work will be informed by public consultations such as the one carried out in connection with the HGC’s work on personal genetic information, and by information-gathering days that are open to the public. The HGC has also established a 106-member Consultative Panel whose views will be sought both by correspondence and at meetings. The HGC recognises that there is no ideal way to involve "the public" in its activities, but pledges to try to move beyond traditional methods of public consultation towards "new ways of engaging people in the future debate and the decision making process".  

19 April 2002The Wellcome Trust and the Medical Research Council have published the results of a public consultation designed to inform the development of BioBank UK, a prospective study to correlate genetic, medical and lifestyle information for a cohort of 500,000 volunteers aged 45-69, with the aim of identifying gene-environment interactions that are important in susceptibility to common disease. Three groups of 20 people each, in Hertfordshire, the West Midlands and Glasgow, were given an introductory presentation about the project and participated in a subsequent interactive workshop. A number of issues emerged from the consultation. For example, it will be important that the goals and rationale of the project are explained clearly at the time of recruitment, as some people did not at first realise that participation would bring no individual health benefits (or disbenefits) to them. Many people will need to be convinced that the importance of the project justifies their participation. Similarly, the reasons for allowing commercial access to BioBank need careful justification. There was general agreement that security of the samples, and privacy and confidentiality of the information, are vital, but nevertheless a majority felt that access by police for forensic purposes would be acceptable if a court order were made. Interestingly, most people in this sample were not particularly worried about the prospect of research on psychiatric or behavioural characteristics. The company commissioned to carry out the consultation recommends that the same groups of people should be consulted further as plans for the project advance, and also that additional groups in areas with a more disadvantaged socioeconomic profile should be consulted. The full report of the consultation is available on the Wellcome Trust’s website. A decision on funding for the BioBank project is expected this spring.

12 April 2002Recent research on some "single-gene" diseases has begun to shed light on the complexity of the relationship between genotype and phenotype. Hirschsprung disease is a rare congenital disorder in which part of the rectum or colon lacks nerve cells, affecting bowel motility and resulting in severe constipation and bowel obstruction. The disease shows variable phenotype, for example some patients lack nerve cells in the rectum (short-segment disease) while in some a much larger segment of the colon is involved (long-segment disease). Mutations in any of several different genes have been shown to cause the disease. In some patients, disease is associated with loss-of-function mutations in the RET proto-oncogene and there is evidence that polymorphisms in this same gene (that is, genetic variants also found in normal individuals) can affect the phenotype of Hirschsprung patients. Fitze et al have analysed the relationship between RET mutations and polymorphisms and the disease phenotype in 76 patients with Hirschsprung’s disease [Fitze, G. et al (2002) Lancet 359, 1200-1205]. They found evidence that the disease phenotype is affected both by variants in different genes and between interactions between genetic variants in the same gene. For example, they found that the 18 patients who had RET mutations were significantly more likely to have the long-segment phenotype than those without RET mutations. In addition, patients homozygous for the AA form of the c135G/A polymorphism in the RET gene were much less likely to have RET mutations than those with the GA or GG genotypes. Moreover, in patients with the long-segment phenotype who had a RET mutation and the GA genotype, the RET mutation was usually on the same chromosome as the G allele, suggesting that these variants might interact to affect the expression of the gene.

Comment: The results of this study, which are also discussed in the accompanying editorial by McCabe, illustrate modes of genetic interaction, and ways in which these interactions can affect phenotype, that are likely also to be relevant to the pathogenesis of common polygenic disease such as coronary heart disease.

14 April 2002An international team of researchers has reported that four out of five baby boys treated by gene therapy for X-linked severe combined immunodeficiency (SCID) have remained healthy for two years after treatment [Hacein-Bey-Abina, S. et al (2002) N Engl J Med 346, 1195-1193]. X-linked SCID is caused by mutations in the gene encoding a common protein segment which forms part of five different cell-surface receptors that are essential for normal development of T cells and natural killer cells in the immune system. The boys were treated by removing their bone marrow cells and transducing them with a viral vector containing a normal copy of the defective gene. The cells were then infused back into the patients. In the four boys who responded to the treatment, T cells and natural killer cells containing the transduced normal gene were found in the blood within four months, and in higher numbers than are observed when affected babies are treated by bone marrow transplantation from tissue-matched donors. The boys also developed normal numbers of B cells, enabling them to mount near-normal antibody responses so that they could be successfully vaccinated against severe childhood diseases and did not need continuing immunoglobulin treatment.

Comment: This paper builds on the initial success in treating X-linked SCID that was reported by the same researchers in 2000 [Cavazzana-Calvo, M. et al (2000) Science 288, 669-672 (Abstract)]. Treatment by gene therapy appears to offer several advantages over treatment by bone marrow transplantation, and may become the treatment of choice for this disease. An accompanying editorial by Rosen gives useful background information about genetic immunodeficiency diseases and the history of attempts to treat them by bone marrow transplantation and gene therapy. (19/4/02)

23 April 2002A mutation in the CHEK2 gene, which encodes a protein involved in preventing division of cells that have damaged DNA, may be implicated in increased susceptibility to breast cancer in individuals who do not carry a mutation in either the BRCA1 or BRCA2 gene [The CHEK2-Breast Cancer Consortium (2002), advance on-line publication in Nature Genetics]. The CHEK2 mutation was found in 1.1% of control individuals in populations from Europe and North America but in 5.1% of patients from breast cancer families who were negative for BRCA1 and BRCA2 mutations (p=0.00000003). The frequency of the mutation in patients from breast cancer families who carried BRCA1 or BRCA2 mutations was the same as in controls. The penetrance of the CHEK2 mutation appears to be low, conferring approximately a two-fold increase in risk of breast cancer in women, and a ten-fold increased risk in men. Several different genetic variants have been proposed as low-penetrance susceptibility alleles for breast cancer, but the CHEK2 consortium claims that this is the first to show such high statistical significance.

Comment: It is difficult to predict the eventual clinical significance of this work, as it is uncertain whether genetic testing for a variant conferring a relative risk of two would be seen as worthwhile, or what intervention should be offered to individuals carrying the mutation. The findings also need independent confirmation from other research groups.