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19 April 2004Colorectal cancer is the third most common form of cancer in the UK, and the second most common cause of cancer deaths after lung cancer. Early detection is an important factor in reducing mortality, and it is predicted that deaths from the disease could be reduced by 15% by the introduction of screening programmes. A number of genes associated with colorectal cancer risk have been identified, and the two most common forms of hereditary colorectal cancer are familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), although individuals with these syndromes account for only around 2-5% of colon cancers. Regular screening is particularly important for families affected by colorectal cancer, including individuals with known genetic predispositions for the disease, and there are also plans to introduce national screening (see the NHS colorectal screening website). However, current procedures for detection such as sigmoidoscopy and colonoscopy are invasive and unpleasant. Faecal occult blood testing (FOB) followed by referral for colonoscopy for individuals with positive results is an alternative screening method, but has a relatively high false-positive rate.

A research letter in The Lancet this month reports an assessment of the use of faecal DNA analysis for suitability as a screening method [Müller HM et al. (2004) Lancet 363, 1283-1285]. Analysis of faecal DNA for known genetic markers of cancer (such as mutations in the APC gene) has already been reported. Alterations in DNA methylation status are also common in colorectal and other forms of cancer. The authors of this paper set out to evaluate whether analysis of these epigenetic changes was a feasible approach for screening.

The methylation status of various candidate genes was determined in faecal DNA samples from patients with colorectal cancer, and the ten most promising marker genes were selected. Stool samples were obtained from 23 colorectal cancer patients and 26 age-matched healthy controls, all of whom had undergone colonoscopy for various reasons. Methylation status of the ten candidate marker genes in faecal DNA was determined, and a significant difference between the cancer and control samples was observed for five of the genes, with the greatest differentiation observed for the SFRP2 gene. Findings were also assessed in an independent test group of 13 patients and 13 controls, and three of the five genes (including SFRP2) showed a significant difference in methylation status. The SFRP2 marker was concluded to show a sensitivity and specificity of 77-90% for the identification of colorectal cancer in faecal DNA, and the authors suggest that an improved specificity would probably be observed if a control group of genuinely healthy individuals (as opposed to those who were sufficiently symptomatic to warrant a colonoscopy) were used. The authors suggest that analysing faecal DNA for a panel of genetic and epigenetic markers could potentially be an effective method of screening, and warrants further investigation.

Comment: Faecal DNA testing shows promise as an effective and less invasive form of screening; this is meaningful because uptake of screening (with concomitant reduction in mortality rates for colorectal cancer) is significantly affected by the unpleasant nature of current forms of screening. This paper provides some evidence to support the inclusion of both genetic and epigenetic markers of colorectal cancer in a screening panel, but the most reliable panel of diagnostic markers is yet to be determined.

For more information on the genetics of colorectal cancer, see the disease profile section.

27 April 2004In 2002 the European Commission released a special publication on their strategic vision for life sciences and biotechnology up to 2010, comprising a policy paper and an action plan. The EC has now presented a report on the progress in implementation of this strategy. In their press release, the EC notes the vital contribution of biotechnology to a range of industries but cautions that successful harnessing of the benefits offered “depends on finding solutions to the significant ethical, societal, economic and environmental issues” it generates.

The report highlights the completion of a reformed EU regulatory framework for Genetically Modified Organisms (GMOs), and emphasises the requirement for EU Member States to implement and apply this GMO legislation. Financial support for research in life sciences and biotechnology, in the form of the EU 6th Framework Programme for Research, has reportedly increased by 20% compared with the previous Framework Programme. More than €810 million was allocated in the first year of this programme to projects in a range of areas including 'life sciences, genomics and biotechnology for health'. The report also outlines future plans and considers newly emerging, but potentially controversial issues such as genetic testing. The importance of a coherent programme of implementation across Member States is emphasised, and a more concerted effort between the Commission, Member States and the private sector is called for.

22 April 2004A group from the European Commission (EC) has released a set of 25 recommendations on human genetic testing for medical purposes. The EC Expert Group, chaired by Eryl McNally, comprises representatives from patient organisations, the pharmaceutical and biotech industry, scientists and academics from different disciplines (law, philosophy, ethics and medicine) with interests in genetic testing. They have worked on the production of a report and the accompanying set of 25 key recommendations for over a year, and have released them in advance of a European citizens’ and stakeholders’ conference on ethical, social and legal aspects of human genetic testing in research and healthcare applications, to be held in Brussels on the 6th and 7th May this year. The 25 recommendations cover a range of topics from regulation, standardisation and quality assurance of genetic testing to ethical, legal and social issues. They call for universal standard definitions to be determined and adhered to, for the institution of a regulatory framework to assure standards of quality for all EU genetic-testing services (including a system of accreditation for genetic-testing laboratories) and test development. Educational and professional requirements in EU countries should be co ordinated, with continued professional training offered for healthcare professionals.

It is proposed that medically relevant genetic testing should be considered an integral part of health service provision; but should never be imposed; the provision of key information, and in some cases specialised genetic counselling is considered an essential requirement for certain genetic tests. With respect to serious rare genetic diseases, the expert group acknowledges that few countries have screening programmes and states that an EU-wide network for diagnostic testing of rare genetic diseases be created and financially supported as a matter of urgency, along with an EU-level incentive system for the development of genetic tests for rare diseases. Where treatment is available for such diseases, EU Member States should introduce universal neonatal screening as a priority. Measures to ensure that appropriate genetic testing is available for all patient populations (such as different ethnic groups, or different sexes) are also proposed.

The group suggests that ‘genetic exceptionalism’ (the notion that genetic data are different from other forms of medical information) should be avoided throughout the EU, although it is acknowledged that public perceptions that genetic testing is different exist and need to be addressed. The working group underlines the importance of knowledge dissemination in the arena of genetic testing, and calls for the allocation of resources for public education and the organisation of opportunities for public dialogue between different stakeholders. It is stressed that the confidentiality and privacy of test results must be maintained, and that measures to protect individuals against discrimination on the basis of personal medical data including genetic data should be instituted.

Additional recommendations are that the EC should fund research relating to the impact of genetic testing on social, cultural and economic aspects of healthcare provision, that the EU should establish and support a framework for partnerships between different stakeholders (such as scientists from industry and academia) and that development of the field of pharmacogenetics should be actively encouraged.

20 April 2004In the first successful prosecution using ‘familial searching’, Surrey Police have announced that Craig Harman has been found guilty of causing the death of a lorry driver, Michael Little. In 2003, Harman threw a brick from an overhead bridge through the window of Little’s lorry. Little managed to pull his lorry off the road but within minutes he died of a heart attack. Harman, who has admitted to manslaughter, will be jailed for six years. Harman was found through the use of familial searching, where forensic experts use police records to trace a suspect through a relative’s DNA. Harman’s DNA had been recovered from the brick, but he could not be traced because he did not have a criminal record. Forensic experts searched UK National DNA Database and found a close relative of Harman. This connection combined with other evidence led them to Harman himself.

The Forensic Science Service conducts familial searching in collaboration with the UK National DNA Database. The service has only been available for a few months. Supporters say it provides police with additional information in searching for suspects in crimes, as has been shown in the Harman case. But the practice could raise questions. For example, could information on crimes committed by genetically-linked family members lead to research on a genetic disposition to criminal behavioural? The Human Genetics Commission found, in preparing their report on the use of personal genetic information, that those consulted were hesitant about forensic DNA samples being used in behavioural research. Such searching could also throw up questions regarding paternity and confidentiality. Detectives will need to consider how they use any potentially sensitive information. However, if the goal is to apprehend and punish those committing crimes, many will argue that familial searching is a welcome addition to the police arsenal.

14 April 2004Dr Mohammed Taranissi is calling for the Human Fertilisation and Embryology Authority (HFEA) to relax its rules to allow greater access to pre-implantation genetic diagnosis (PGD). He believes parents should be allowed to create ‘designer babies’ in cases not currently covered by the HFEA’s rules. He has submitted an application to the HFEA to use PGD to create a baby to provide stem cells for a boy, Joshua, who suffers from Diamond Blackfan anaemia (DBA). Normally, during this procedure, embryos are screened to determine those that are free of the inherited disease afflicting the sibling. Next the healthy embryos are tissue-typed to choose those that match the sibling. Any matching embryos are implanted into the mother. However, DBA is not always inherited; it can occur sporadically. Because in this case PGD cannot prevent the new baby from having the disease, the HFEA has in the past refused an application of this type, that of the Whitaker family (see June 2003 newsletter). This family eventually had the procedure done in the United States.

Dr Taranissi believes that it is wrong to refuse such applications and will consider legal action if the HFEA holds to its position. He states that parents should have the right to take advantage of PGD technology if there is a possibility that an ill child will benefit, even if the new baby might also contract that illness. In the case of DBA, he claims that the odds of the new baby suffering from it is one in six million and therefore the risk is small compared with the potential benefits to Joshua. A bone marrow transplant, from a donor with an exact tissue match, has an 85% chance of curing Joshua. However, some will claim that as the risk to his sibling cannot be quantified and any risk is unjustified, PGD should not be carried out. Others will question if the procedure is necessary in these cases. The Whitaker child has not undergone a bone marrow transplant, although his sibling’s cord blood has been banked for this purpose. He is currently undergoing conventional treatment.

15 April 2004An Icelandic woman has won the right to withhold her deceased father’s genetic data from being entered into Iceland’s Health Sector Database (HSD). The HSD is the database created by the biotechnology company deCODE Genetics to exploit the medical records, family trees and genetic information of Iceland’s 270,000 inhabitants. The database works on the premise of presumed consent. Only those who actively opt out are not included in the database; all others are presumed to have consented and their information is automatically transferred to the HSD.

Ragnhildur Gudmundsdóttir applied to the HSD asking that they not include her deceased father’s data in the database. The HSD refused her request, stating that there was no provision in their rules allowing relatives of the deceased to prevent their data from being included in the database. As a result, she brought the case to court. Icelandic law does not give rights to the deceased, however she argued that she had a personal interest in the inclusion of her father’s data as that information might be used to predict information about her own health. Although there were procedures in place to anonymise the data, they were not sufficient to ensure that she could not be linked to her father’s data. Therefore inclusion of his data and the use of it might invade her right under the Icelandic Constitution to ‘…enjoy the privacy of…her life, home and family.’ The Supreme Court upheld her argument.

As a result, deCODE officials have agreed to change their procedures but warn that this might adversely affect their ability to conduct epidemiological studies. Mannvernd, the Association of Icelanders for Ethics in Science and Medicine, countered that the judgment will help restrict the lengths to which commercial companies such as deCODE can intrude into an individual’s private life. Others maintaining medical population databases, such as UK Biobank, will no doubt take note of this ruling.

21 April 2004Following the completion of a reference human genome sequence in 2003, the ‘post-genomic’ challenge is to decipher the genome; although many thousands of genes have been identified, the function of most remains unknown. The H-Invitational Consortium, an international consortium of more than 150 scientists, gathered from 67different institutions in 12 countries, has analysed 41,118 full-length cDNAs from sequencing centres around the world. Sets of cDNA (complementary DNA) are derived from cellular RNA, which is copied into DNA to produce a set of DNA molecules corresponding to genes that are being expressed (ie. are active) in the cell. This represents a relatively small portion of the whole genomic DNA, but the one of most interest to geneticists. The results of the consortium’s work have now been made publically available in the form of the H-Invitational Database or H-InvDB (see press release).

The consortium, led by Takashi Gojobori of the Institute of Advanced Industrial Science and Technology in Japan, has validated the existence of 21,037 functional genes and identified 5,155 novel gene candidates. The H-InvDB also provides annotations on the genes including information on alternative splicing (the production of different gene variants from a single parent gene, such that a single gene may provide the information to produce several different proteins), tissue specific expression of the gene and disease-related information. The H-InvDB is expected to provide a valuable resource for further research in functional genomics, including investigations into the properties of previously unknown genes. Dr Gojobori said: "We are confident now that anyone in academia or industry who uses our database will gain far deeper insight into the meaning of human disease than was previously possible". The consortium has also published results from the two-year study in the open access journal Public Library of Science Biology.

14 April 2004A new initiative, the NEWMOOD project, was launched at the annual Human Genome Meeting in Berlin last week. The project is a multinational study into the genetics of depression and mood disorders. A team of researchers in thirteen laboratories from ten different countries, co-ordinated by Professor Bill Deakin of the University of Manchester, will search for genes related to depression with the aim of driving the discovery of novel drug targets. Current anti-depressant drugs largely work by increasing levels of the neurotransmitter serotonin in the brain, but are ineffective in up to half of patients; it is hoped that NEWMOOD will identify alternative targets, as well as furthering understanding about depression and potentially creating new animal models for study of the disease. Clinical depression, a condition that affects some 120 million people worldwide and is thought to be to be increasing in incidence, is known to have both genetic and environmental causes. The five-year project has been awarded funding of € 7.3 million by the European Union Sixth Framework Programme (FP6). Researchers plan to compare gene expression in healthy and depressed rats, mice and humans, with a view to identifying key genes involved in the initiation of the disease process. The project will use microarrays to study the expression of several hundred genes with a putative link to depression, involved in processes including metabolism, growth and cell communication.

21 April 2004Professor Ian Wilmut of the Roslin Institute in Edinburgh has applied to the Human Fertilisation and Embryology Authority for a licence to produce and use cloned human embryos for work on motor neurone disease (see BBC news item). This is the first application for a therapeutic cloning licence in the UK, although the procedure has been legal for research purposes since 2001. Professor Wilmut has stressed that his team has no intention of performing reproductive cloning, which is illegal; embryos created for research purposes would be destroyed once they were no longer required.

Professor Wilmut is renowned for his groundbreaking work in cloning that led to the birth of Dolly the sheep, the first mammal to be cloned from an adult cell, in 1996. The firm behind the animal cloning carried out at the Roslin Insitute, PPL Therapeutics, is on the verge of bankruptcy and sold the cloning technology to Exeter Life Sciences at the start of 2004. Dolly suffered from various medical complaints and died prematurely, raising concerns about the safety of cloning from adult cells.

Motor neurone disease (MND) refers to a group of diseases caused by degeneration of motor neurones (nerve cells) that control muscles involved in movement, speech, swallowing and breathing. MND is a progressive and fatal condition, taking on average three to four years to run its course. It affects about 5,000 people in the UK, and there is no cure. Professor Wilmut's team want to use DNA from a motor neurone disease patient and implant it into a human egg from which the DNA has been removed, to create an embryo with the genetic material of an MND patient. Cells from the embryo would be used for research into the disease. Professor Wilmut is quoted as having said: "Because at this early stage the embryo does not have that key human characteristic of being aware to me it would be immoral not to take this opportunity to study diseases". However, opposition to the cloning licence application is anticipated; a spokesman for the charity Life UK said that the term therapeutic cloning “makes no difference whatsoever to the fact that a human being is being deliberately created and then destroyed" and called instead for researchers to use alternative resources such as umbilical cord blood cells.

6 April 2004Health Secretary John Reid has announced the chairs of eight Task Groups that will have an important role in the consultation process for the government’s White Paper on Public Health, that is expected to be published this summer. The eight Task Group Chairs will head the groups outlined in Choosing Health? A Consultation on Improving People’s Health, launched in early March. The consultation is focusing on several key public health issues: smoking, combating obesity through healthy eating and physical activity, combating the spread of sexually transmitted infections and encouraging the creation of healthy workplaces.In order to better inform the government, the Task Groups will provide recommendations on improving people’s health, organised under the following headings:

Better Health for Young People (Chair: Paul Ennals, Chief Executive, National Children’s Bureau)
Working for Health/Opportunities in Employment (Chair: Will Hutton, Chief Executive, The Work Foundation)
Consumers and Markets (Chair: Ed Mayo, Chief Executive, National Consumer Council)
Leisure (Chair: Baroness Pitkeathley, Chair, New Opportunities Fund)
Maximising the NHS Contribution (Primary Care) (Chair: Prof Chris Drinkwater, GP, University of Northumbria and NHS Alliance)
Maximising the NHS Contribution (Across the NHS as a Whole) (Chair: Ken Jerrold, Chief Executive, Durham & Tees Valley SHA)
Working With and For Communities (Chair: Dame Yve Buckland, Chair, Health Development Agency)
Focusing on Delivery (Co-Chairs: Mike Farrar, Chief Executive, South Yorkshire SHA, and Tony Elson, Chief Executive, Kirklees Metropolitan Council)

Each Task Group will bring together stakeholders representing community groups, those who are working projects in these specific areas, and other experts. Information gained from the Task Groups will be added to the other strands of the consultation, such as responses from the public and events being organised around the country to bring the issues to the forefront.

27 April 2004UK Biobank has announced that it is seeking applicants for positions on its Ethics and Governance Council (EGC). Positions will be advertised in the national press during the last week of April, with a closing date of 26 May. After reviewing the applications, an Appointments Committee will make their recommendations for appointment to the Medical Research Council and the Wellcome Trust. The Appointments Committee members are: Rev Dr John Polkinghorne (Chair), Prof Martin Bobrow, Mr Niall Dickson, Dr William W Lowrance and Prof Genevra Richardson.

UK Biobank "...will be the world's biggest resource for the study of the role of nature and nurture in health and disease." Project collaborators will collect health and lifestyle data from 500,000 volunteers aged between 45-69 years. Environmental and lifestyle information from these volunteers will be linked with biological samples taken from them as well as their medical records. This information will form a sample collection and database. Researchers will apply to UK Biobank for access to the information for use in research projects. The results of these projects should provide a better understanding of the factors that cause disease in later life, which in turn will help in the development of prevention strategies, as well as improve diagnosis and the treatment of illness.

The EGC is an important part of the oversight procedures for the UK Biobank project through its role in ensuring conformity to UK Biobank’s Ethics and Governance Framework. The Framework, developed by an Interim Advisory Group last autumn, lays out the standards by which the Biobank project will be conducted. It details how participants will be enrolled in Biobank, including consent procedures and whether any information found through subsequent research using their data will be fed back to the volunteers. The Framework addresses ownership of the sample collection and database, access to these resources and how any claims for intellectual property rights will be handled. It also discusses the accountability procedures for UK Biobank, requiring that an independent body of publicly appointed individuals, the EGC, be created to oversee conformity to the Framework. Once the positions are filled, the EGC is expected to begin work in September. UK Biobank expects to begin recruiting volunteers in 2005. Anyone interested in applying for the EGC should contact Lesley Watson (l.watson@ welcome.ac.uk) for further information.

26 April 2004Funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council, the UK Stem Cell Bank was set up to provide “ethically-sourced, quality-controlled adult, foetal and embryonic stem cell lines” for national and international research. The Steering Committee of the UK Stem Cell Bank has recently released a Draft Code of Practice for the use of Human Stem Cell Lines. This document observes that research involving human tissues must not only benefit human health but also adhere to the highest ethical and scientific standards in accordance with UK and EU legislation and guidance. The Code of Practice is therefore intended to be based on principles of good research practice applied to the use of human stem cell lines for basic and clinical research leading to the development of therapeutic interventions, to ensure that such research is performed within a suitably transparent, regulated and ethical framework.

The Code of Practice outlines the remit and governance of the UK Stem Cell Bank and summarises current legislation relevant to stem cells and stem cell lines. Compliance with the Codes of Practice produced by the Steering Committee is a condition for authorisation of research using embryonic stem cells, and of accession of all cell lines from the Stem Cell Bank, but the draft notes that researchers using stem cell lines from other UK sources should also comply with the Code and seek approval from the Steering Committee for their projects. The Code further stipulates that the Steering Committee must sanction all imports and exports of embryonic stem cell lines to and from the UK, and that it will audit the transfer of cell lines to third parties. Non?embryonic stem cell line transfers to third parties are exempt, but in this case no accreditation of the cell lines as being derived from the Stem Cell Bank is permitted. The Code outlines principles (and current regulations) of quality assurance and risk management, whilst noting that the responsibility for the institution and maintenance of appropriate systems to maintain quality and safety rests with the senior management of bodies using stem cells for research. Key elements of quality assurance in the production of stem cells and stem cell lines for both clinical use and research purposes are set out, as are sandards for the selection and screening of stem cell donors.

The special moral status and intrinsic value of the human embryo and the associated limitations placed on its use are noted, based on which the Steering Committee has decided that embryonic stem cell lines may be used only for specific goals based around the development of therapies for serious human diseases. This restriction is also extended to the use of somatic foetal and adult stem cells, on the basis that they are human tissues and in some cases derived following termination of a human life. Codes of practice for the derivation, authentication, characterization and use of primary stem cells and stem cell lines are provided in the draft document, along with guidance on national and international transport and tracking, cryopreservation, storage and appropriate disposal measures. The right of the Steering Committee to seek periodic independent audit of the research carried out using stem cell lines derived from the UK Stem Cell Bank (whether in the UK or abroad) is asserted. Further sections within the Code of Practice explore issues related to data management and Intellectual Property; with the exception of any IP generated during the initial period of MRC/BBSRC funding (which will be assigned to the MRC, with revenues to be used for supporting the Stem Cell Bank), the Bank will not take any direct interest in intellectual property related to deposited cell lines.

Comments on the draft are invited (until 28 May 2004) for discussion by the UK Stem Cell Bank Steering Committee in their July 2004 meeting.

28 April 2004A team of researchers from the Tokyo University of Agriculture have published a paper in Nature reporting the creation, birth and survival into adulthood of a parthenogenetic mouse – that is, created solely from female cells [Kono T et al. (2004) Nature 428, 860-864]. Parthenogenesis (derived from the Greek for ‘virgin birth’) is a special form of reproduction by development of an unfertilized female gamete to form a new organism. It occurs naturally in certain conditions among some invertebrates such as bees and ants, and some vertebrate animals including reptiles and snakes. However, this publication is the first example of successful mammalian parthenogenesis, which does not occur in nature; although artificially induced parthenogenesis has been demonstrated in mammals, all previous attempts have resulted in incomplete and abnormal embryonic development. This is due to a phenomenon that occurs in mammalian sexual reproduction called genomic imprinting – the di