In the news

  • Newsletter Edition
The PHG Foundation monthly newsletter features news and views about genetics and genetics research, from a public health perspective. The newsletter is written by staff of the PHG Foundation.

In the news

News story   |   Published 2 April 2005

The Human Genetics Commission (HGC) and the UK National Screening Committee (NSC) have rejected a proposed national scheme to collect a DNA profile of every baby at birth, the BBC has reported. The Joint Working Group, formed by members from both organisations, concluded that while genetic profiling might provide clinical benefits in the future, at the moment the scientific evidence is limited. They recommend that the government revisit the issue in five years. The group had been tasked, as part of the Genetics White Paper, to consider the positive and negative aspects of the genetic profiling of babies at birth. Their report, Profiling the newborn: a prospective genetic technology?, has now been published.

 

Profiling was defined as, “…the analysis of a person’s entire genome in order to reveal the majority of the genetic variations.” The Working Group concluded that given the current state of scientific and medical knowledge that it was not practicable for this scheme to go forward at this time. The report states that, “…this is not likely to be affordable in the public health context in less than 20 years. It also raises a number of important ethical, legal and social issues which need to be addressed before any such scheme could be acceptable.” For example, there is a concern that information that came from the profile could be used in the future to discriminate against individuals in the areas of employment, insurance and education. The police might also use the information “…for unwarranted purposes.” If such a profile were to be collected from newborns, the information it contained would need to be adequately protected from misuse.

In the meantime, they believe that regulation might be needed in the commercial sector. Genetic profiling is feasible and companies are already offering it on an individual basis, raising issues such as the provision of genetic risk information to children. The Working Group does see the potential for genetic profiling to be of clinical use in the future but calls for further research into its implications. Research is also needed into genetic testing in children and into public attitudes on this issue. The results of such research would give reviewers a better understanding of the implications of genetic profiling when it is next considered. - 2/4/05 Dr Susan Wallace


News story   |   By Dr Philippa Brice   |   Published 29 April 2005

The Law Lords have upheld an earlier court decision that the Human Fertilisation and Embryology Authority (HFEA) acted lawfully in permitting the Hashmi family to use pre-implantation tissue-typing to select tissue matched embryos for their son (see BBC news report). Zain Hashmi suffers from the serious genetic disorder beta thalassaemia major, requiring regular blood transfusions and drug treatment to keep him alive; his parents received permission from the HFEA to proceed with treatment to select embryos that were a tissue match for Zain, so that stem cells from the newborn child’s umbilical cord could be used for transplantation into Zain, and potentially cure him. The couple went ahead with the treatment, although thus far Mrs Hashmi has miscarried all the babies implanted after tissue selection. The High Court had originally imposed a ban on the Hashmis’ treatment in December 2002, but this was overturned in the Court of Appeal in 2003. The group Comment on Reproductive Ethics (CORE) then asked the House of Lords to examine the Human Fertilisation and Embryology Act (1990) to determine whether such tissue-typing was legal. Five Law Lords yesterday ruled unanimously that the HFEA had acted “lawfully and appropriately” in granting a licence to the Hashmis, as there was no legal basis for limiting the authority's power to permit screening of embryos for genetic disorders.

Josephine Quintavalle of CORE commented: “The Law Lords have in effect stated that unless there are specific prohibitions to the contrary, the Human Fertilisation & Embryology Authority (HFEA) can do whatever it pleases. This is not simply about babies being created in the laboratory as tissue matches, but the creation of babies of the right sex, hair colour, intelligence, and so on. Whatever the mother deems to be suitable in an embryo is what she can ask for, according to today’s interpretation of the law…This judgment effectively endorses the terrifying designer baby scenario which our country rightly abhors”. Law Lord Brown of Eaton-Under-Heywood said that: "In the unlikely event that the authority were to propose licensing genetic selection for purely social reasons, Parliament would surely act at once to remove that possibility" (see Telegraph report). The HFEA stated that they were "pleased with the clarity that this ruling brings for patients".


News story   |   Published 21 April 2005

The BBC has reported that geneticists in Manchester are concerned that women are claiming a false family history of breast cancer in order to get treatment (see BBC news story). Treatment can include the removal of their breasts. Such women may be suffering from a psychological disorder similar to Munchausen’s Syndrome by Proxy. People suffering from this syndrome may fabricate or induce illness in order to receive attention and treatment. The number of women fabricating their family history in this way is small, an estimated 1% of patients. However, as the genetic basis of other diseases is discovered, one might ask whether this phenomenon will increase.

Worryingly, geneticists are unable to verify the family history claimed by patients because of restrictions imposed by the Data Protection Act 1998 regarding consent. If a patient will not consent to allowing a doctor to access the appropriate medical records, their family history cannot be confirmed. Patients may then undergo unnecessary surgery and family members might be led to believe they have an increased risk of cancer themselves. As Professor Gareth Evans, consultant in medical genetics at St Mary’s Hospital, Manchester, told the BBC, ‘What we are concerned about are people who actually are fabricating it, know they’re fabricating it, and they’re the last people who are actually going to sign a consent form that’s going to let you find out that they haven’t actually had what they say they’ve had.’


News story   |   Published 2 April 2005

The first of April marks the end of anonymity rights for people donating sperm and eggs. As reported by the BBC, children conceived through donations made after 31 March 2005 will have the right, at age 18, to have details about their genetic parent. That means the first requests cannot be made to the Human Fertilisation and Embryology Authority (HFEA) until 2023. Donations made prior to 1 April continue to fall under anonymity rules.

The rules for anonymity were changed when the Human Fertilisation and Embryology Authority (Disclosure of Donor Information) Regulations 2004 came into force in July 2004. The Regulations require that an applicant, such as an individual who was born through the use of donor eggs or sperm, can request detailed information about the donor from the HFEA, if that donation takes place after 31 March 2005. In addition to identity, the applicant can ask for the sex, height, weight, ethnic group, colour of skin, country of birth and marital status of the donor. The applicant can ask if the donor was adopted, the donor’s personal and family medical history, and what screening tests have been carried out on the donor. They can also ask about the donor’s children, the donor’s religion, and why the donor donated their eggs or sperm.

Concern has been raised as to whether the removal of anonymity for donors will inhibit people from donating. In a speech by Melanie Johnson, MP, she noted that there are many views on both sides of the issue (see PHGU newsletter January 2004). In some countries, while there may have been an initial drop in donors, the rates did improve with a shift to people who were more comfortable with the idea of being contacted. She also raised the question of whether it was right to withhold genetic information being held in a database from donor-conceived people, when those who are adopted are able to access information about their genetic parent. However, Dr Alan Pacey of the British Fertility Society, while citing the Society’s support of the removal of anonymity, cautioned in a press release last year that people might seek fertility services overseas if the donor rate does drop and donations become scarce. Education is needed to encourage donors; the National Gamete Donation Trust has been running a campaign, Give Life, Give Hope, to educate and encourage potential donors.


News story   |   Published 4 April 2005

The Department of Health (DH) has announced the membership of the Human Tissue Authority (HTA). They are:

  • Baroness Hayman, Chair (announced 5 February 2005)
  • Prof Michael Banner, Director, ESRC Genomics Forum
  • Dr David Davies, Licensed anatomist, reader and lecturer in neuroscience
  • Mrs Shirley Harrison, Company Director
  • Prof James Ironside, Prof of Clinical Neuropathology, Univ of Edinburgh
  • Mrs Jane Jeffs, Retired Chief Officer of Community Health Councils (appointed by National Assembly of Wales)
  • Prof El-Nasir Lalani, Prof of Molecular and Cellular Pathology and Honorary Consultant Histopathologist
  • Ms Sharmila Nebhrajani, Chief Operating Officer and Finance Director, BBC New Media & Technology
  • Dr Andrew Reid, HM Coroner, Inner North London
  • Mr Keith Rigg, Consultant General & Transplant Surgeon, Nottingham City Hospital NHS Trust
  • Dr Katherine Robson-Brown, Archaeologist, Univ of Bristol
  • Ms Helen Shaw, Co-Director of INQUEST
  • Prof Sir James Underwood, Prof of Pathology, Univ of Sheffield and President, Royal College of Pathologists
  • Mrs Michaela Willis, Chief Executive Officer, National Bereavement Partnership
  • Two members are yet to be named, a member to be appointed by the Department of Health, Social Services and Public Safety, Northern Ireland, and a member with experience in nursing.

The HTA came into existence as of 1 April 2005, created as required by the Human Tissue Act 2004, which comes into force 1 April 2006. According to the DH, “The HTA will be the regulating authority for matters relating to activities such as anatomical and post-mortem examinations, transplantations and the storage of human material for education, training and research.” It will also act as the competent authority for the EU Tissue and Cells Directive, adopted in April 2004. The HTA will be responsible for writing Codes of Practice to implement the Act and the Directive, covering issues such as consent; definition of death; existing holdings; removal, storage and disposal of human tissue; and import and export of human tissue and organs.

The DH plans, in 2008, to combine the work of the HTA with that of the Human Fertilisation and Embryology Authority (HFEA) to create a new authority, the Regulatory Authority for Fertility and Tissue (RAFT), that will be responsible for the regulation and inspection of a wide range of uses of human tissue. However, RAFT’s proposed remit may change due to ongoing discussions. The House of Commons Science and Technology Committee’s recent report on Human Reproductive Technologies and the Law recommends that RAFT take on only the oversight of technical standards and quality management in regards to assisted reproduction. An expanded version of the Human Genetics Commission would be responsible for advising Government on relevant developments in treatments and research, a role currently held by the HFEA. The DH has announced they are conducting a review of the Human Fertilisation and Embryology Act 1990 with a public consultation exercise to be conducted in 2005. They will be considering the recommendations of the Select Committee as well as submissions from interested parties. Comments can be sent to review-hfe-act@dh.gsi.gov.uk.

Keywords : ukHuman Tissue

News story   |   Published 28 April 2005

The National Geographic Society and IBM Corporation have teamed together to launch the Genographic Project, a 5-year project to trace human history [Pennisi E, (2005) Science 308,340]. Spencer Wells, of the National Geographic, will lead the project. Ten teams will collect approximately 100,000 human DNA samples from 1000 indigenous populations. Information from DNA from preserved human remains will also be collected. From this data, patterns of human migration will be determined. The project’s website already has an interactive Atlas of the Human Journey, which provides information on data already known about human migration as well as theories being explored. Estimated at approximately $40 million, the project costs will be split between National Geographic, IBM and the Watt Family foundation.

In addition, individuals can become involved in the project as well. For $99.00, interested people can buy a Public Participation Kit. They are asked to swab the inside of their check and return the DNA sample. Participants receive information on the material or paternal genetic markers passed to them by their ancestors. Participants can track the progress of their sample, through the use of an anonymous code. They will be given their results on line and can see how their lineage integrates with the project as a whole. By answering some additional ‘phenotyping’ questions that will “help place your DNA in cultural context,” participants can add their data to the project’s global database. The project website reminds potential participants of the limitations of their participation. “This is not a genealogy test and you won't learn about your great grandparents. You will learn, however, of your deep ancestry, the ancient genetic journeys and physical travels of your distant relatives.”

Elizabeth Pennisi notes in her article that there similarities between this project and the Human Genome Diversity Project (HGDP), a project that faced difficulties several years ago when indigenous groups feared researchers collecting their tissue and DNA would exploit that information for commercial gain. The Geographic Project states that they will not conduct biomedical research with its data and so may avoid some of the problems faced by the HGDP. However, ethical and practical concerns may be raised about the gathering and use of the participant samples. While the website makes clear that samples will not be tested for “health, health status or any inherited health conditions,” no information is given on ownership of the samples and what will happen to them. For example, are there plans to destroy the samples after the project ends? In addition, one problem may affect the range of participants samples the project might receive – the website acknowledges that in some countries, such as China, the export of genetic material requires government approval. They note that ways will need to be found to ensure the broad level of participation needed to produce their survey of the world’s populations.


News story   |   Published 11 April 2005

The Department of Health (DH) has announced that the Gene Therapy Advisory Committee (GTAC) has published their eleventh annual report at their annual public meeting in Manchester. The report gives details on the eleven gene therapy trials GTAC has approved in 2004, together with summaries of completed gene therapy trials and an analysis of 96 trials that have been carried out in the UK. The new trials focus on cancer, HIV and coronary heart disease. Over 70% of all applications to GTAC are for trials focusing on cancer, including colorectal cancer, prostate cancer, leukaemia and breast cancer. The DH is proud of its leading position in Europe in this field. The Health Minister, Lord Warner, stated in the press release that, “The government is committed to ensuring that the UK remains at the forefront of innovative medical research and has provided the funding towards new gene therapy clinical trials for inherited diseases such as Duchenne Muscular Dystrophy, cystic fibrosis and childhood blindness.” GTAC is likely to consider these new trials in 2005 or 2006.

The first gene therapy trial was approved in 1993. Gene therapy is described by the DH as involving, “…the deliberate introduction of genetic material into human cells for therapeutic, preventative or diagnostic purposes.” While progress has been slow, Prof Norman Nevin, Chairman of GTAC, notes in their report that some trials have shown promise, such as immunotherapy in cancer treatment. “My view is that we are beginning to learn more and more about the circumstances in which gene therapy may ultimately provide an alternative treatment strategy.” GTAC acts as the UK national ethics committee for gene therapy trials; no trial can go forward until it has been approved by GTAC as meeting the ethical criteria for research involving human subjects. GTAC also advises the government on developments in gene therapy research.

News story   |   By Dr Ireena Dutta   |   Published 26 April 2005

The House of Commons Select Committee on Health has concluded that patients are failing to benefit from new medical technologies due to the way the NHS is structured, how it makes decisions about purchasing and implementing new equipment and training, and the lack of coordination between health and social services. The Committee heard evidence from a number of organisations including the National Institute for Clinical Excellence, medical devices manufacturers and a number of patient groups. The report particularly highlighted the potential for telemedicine in clinical care provision. Telemedicine uses telecommunication, such as by videoconferencing, to provide diagnostic and therapeutic medical information between patient and doctor without either of them having to travel. It therefore has a range of advantages such as improving access to healthcare, reducing unnecessary travel, and linking medical specialists across regions. The Committee recommended that NHS Trusts provided more organisational and staff development to ensure that this technology was utilised, as well as identifying ‘clinical champions’ to promote it.

The report acknowledged that the Department of Health had recognised the benefits of new medical technologies, but progress in applying them had been slow. The seven hundred Trusts that collectively form the NHS had different and inconsistent policies and practices on new technology development, application and purchase, best practice was not available across the country and NICE recommendations were adopted very unevenly. Even where a technology has been recommended by NICE, the large number of 'entry points' into the NHS through Trusts resulted in the technology being evaluated locally, causing delays and duplication. The report also highlighted the gap between health and social care services and how the costs and benefits of the new technology were not being equally shared between these sectors. The NHS appeared reluctant to engage with a technology that was preventative and involved the management of vulnerable groups remotely, as this was generally seen to benefit those involved in the provision of social services and care. The Committee recommended that “greater effort should be made to strengthen the links between health and social services to ensure the roll out of these technologies in domestic and community settings is undertaken more effectively than at present”. The Committee’s other recommendations also built on the conclusions and recommendations of the recently established Healthcare Industries Task Force, a group that brings together Government and the medical technology industry.

News story   |   By Dr Ireena Dutta   |   Published 22 April 2005

The past few months have seen a number of new announcements made concerning funding for stem cell research in the UK and internationally. In March the Department of Trade and Industry announced the allocation of £1billion of funding to the life science and biotechnology sector. This allocation is from the £10billion science budget agreed in the 2004 Spending Review. It furthers the Government’s commitment to science and innovation that was initially outlined in the ten-year investment framework. The new allocation specifically covered areas such as stem cell research and bio-processing. Some of the additional funding will increase the budgets of the MRC and BBSRC, as well as assist UK universities collaborate with business and create new companies to exploit their research.

The EU has also allocated €12billion to a pan-European stem cell research collaboration involving groups in the UK, Sweden, Germany, Italy, France and Finland, which will investigate the therapeutic potential of human embryonic stem cells. However, some of the home nations of the scientists involved, such as Italy and Germany, have restrictive national legislation governing this type of research. This may lead to their representatives within the EU seeking to delay the project, or to remove their scientists from it completely. The confusion over the future of the project follows the recent decision by the European Parliament to change legislation governing the funding of embryonic stem cell research (see earlier story). This change proposes that embryonic stem cell research should be funded from the national budgets of member states where the research is legal and not by the EU. However the resolution has not been adopted by the European Commission and is not specifically mentioned in its recent announcement of the 7th Research Framework Programme.
Keywords : FundingGovernmentStem Cellseu

News story   |   By Dr Philippa Brice   |   Published 11 April 2005

NICE (formerly the National Institute for Clinical Excellence) became the new National Institute for Health and Clinical Excellence on 1 April 2005, taking on the additional functions of the former Health Development Agency to create a single organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health. This falls into three areas: public health, health technologies and clinical practice, under the control of the Centre for Public Health Excellence, the Centre for Health Technology Evaluation and the Centre for Clinical Practice, respectively.

NICE has launched a public consultation on the Centre for Public Health Excellence (CPHE) and how it will produce public health guidance. This is available from the NICE website until 10th June 2005. Broadly, guidance will relate either to specific public health interventions, or broader public health programmes, to prevent disease or improve health at population, community, organisational, group, family or individual levels. Genetics is not specifically mentioned in the consultation document, but it is stated that guidance produced by the CPHE will “recognise the wide spectrum of determinants of population and individual health”.


News story   |   By Dr Philippa Brice   |   Published 28 April 2005

Celera Genomics, the private company that released details of the human genome sequence simultaneously with the publicly funded Human Genome Project (HGP), has announced that their genome database subscription business will be terminated. The company, originally set up by the scientist Dr Craig Venter, was the subject of major controversy as it planned to sell human genome information; critics argued that it was unethical not to place such important data in the public domain. The Celera Discovery System reportedly had around 25 corporate and 200 academic subscribers at its peak (see New York Times report), but profits from the venture were much lower than originally anticipated, largely due to the freely available HGP data; in recent years the company has moved to focus on developing novel therapeutics instead.

30 billion base pairs of Celera data on human, rat and mouse genome sequences will now be made available for public access from July 2005 via the National Center for Biotechnology Information, although some proprietary data that is being used for the development of novel diagnostics will be retained. Dr Francis Collins, Director of the National Human Genome Research Institute (NHGRI), which led the international HGP, welcomed the move as a "wonderfully generous contribution" and a "strong endorsement of this kind of information ultimately being accessible to anybody". The animal genomes will be of particular value to the research community, because they are different strains from those sequenced by public sector initiatives, and the human data will useful for the further validation of HGP data.


News story   |   Published 26 April 2005

The European Commission has released a memo explaining its approach to ethical issues in funding projects under the proposed Seventh Framework Programme (FP7). This was prompted by questions of how controversial research, such that involving embryonic stem cells, will be considered under FP7. The Commission cites two statements in its FP7 proposal. Recital 25 reads, “Research activities supported by this Framework Programme should respect fundamental ethical principles, including those reflected in the Charter of Fundamental Rights of the European Union. The opinions of the European Group on Ethics in Science and New Technologies are and will be taken into account.” Secondly, Article 6 states, “All the research activities carried out under the Seventh Framework Programme shall be carried out in compliance with fundamental ethical principles.”

As for human embryonic stem cell research, the memo reiterates how funding is conducted under the current FP6 programme. It confirms that the European Union (EU) will not fund any research “…that involves human reproductive cloning, the creation of embryos for research (or therapeutic cloning) or any research that would alter the human genetic heritage.” The EU will not fund research in the Member State that is illegal in that State and funding priority is given to projects involving adult stem cells. Funding is available for projects that involve deriving and using human embryonic stem cells (HESC) from embryos ‘left-over’ from in vitro fertilisation procedures. The donors must have given explicit consent for their embryos to be used in research. However, the Commission notes that very little of the FP6 budget has been spent on this type of research. Only two projects have been funded, totalling approximately €500,000 and only 0.002% of the FP6 budget. On the other hand, the Commission is eager to fund the set up of a European registry of existing HESC lines, along the lines of the registry at the US National Institutes of Health. The Commission supports such a registry as it, “…would allow an ethical tracking of existing HESC lines in Europe and their optimal use.” While proposals have been received, they have been judged to be of ‘insufficient quality’ and the call for proposals has been reopened.

The memo does not indicate how or if it will fund HESC research under FP7. The European Parliament has already entered into this debate by passing a resolution in March 2005 calling for the specific exclusion of 'human cloning' from funding under FP7 and for embryonic stem cell research to be funded by the national budgets of Member States in which this research is legal and not by the EU (see PHGU newsletter article earlier this month). The Parliament also believes that EU funding should be focused on alternatives to HESC research, such as adult stem cell and umbilical cord stem cell research. A timeline on the FP7 website shows that there will be further discussions regarding FP7 before its launch at the end of 2006. - Dr Susan Wallace


News story   |   Published 26 April 2005

The European Commission has announced its plans for the Seventh Framework Programme (FP7), the EU's instrument for funding research and development. The Commission's plan will now be treated by the Codecision process of the European Parliament and the Council of the European Union. FP7 is scheduled to begin in 2007 and last seven years, until 2013. The budget is 72.73 billion euro and will be organised into four programmes: Cooperation, Ideas, People and Capacities.

More than half of the FP7 budget will be allocated to the ‘Cooperation’ programme, under which cooperative transnational research activities, such as those between universities, industry, research centres and public authorities, will be funded. Nine thematic areas are listed for collaborative research: health; food, agriculture and biotechnology; information and communication technologies; nanosciences, nanotechnologies, materials and new production technologies; energy; environment; transport; socio-economic sciences and the humanities; and security and space research. The European Research Council will set up under the ‘Ideas’ programme. It will fund basic or ‘frontier’ research proposed by individual teams competing at the European level. Under the ‘People’ programme, individuals will be able to apply for training and careers development funding, as well as funding for activities such as researcher exchange programmes. Finally, the ‘Capacities’ programme will focus on improving and strengthening research infrastructures.

The Commission has noted that under FP7 less emphasis will be placed on the mechanisms that will be used to fund projects. Under the Sixth Framework Programme, collaboration was a fundamental requirement for funding submissions, often requiring three of more Member States as participants and a strong emphasis was placed on the use of specific instruments for the delivery of funds. Under FP7, these requirements will be de-emphasised and there will be a wider range of funding mechanisms that can be used when responding to calls for proposals, which should be welcome news for researchers. Also, the Commission's proposal states that "All research activities...shall be carried out in compliance with fundamental ethical principles." This requirement is discussed further in a memo outlining ethical issues within FP7 (see related PHGU newsarticle).

Keywords : euRegulatory Framework

News story   |   By Dr Ireena Dutta   |   Published 4 April 2005

The Department of Trade and Industry have announced the launch of the second phase of awards from its Technology Programme. An open competition will decide the allocation of £100million of funding to support collaborative research and development. A number of key areas have been identified that UK industry can take advantage of, several of which have relevance to the life science sector. These include biopharmaceutical and bioprocessing, next generation lasers aimed at the manufacturing, healthcare and security industries and micro and nanotechnology. Calls for proposals are also sought in the fields of advanced materials, direct writing, emerging energy technologies, zero emission enterprise and validation of complex systems.

The Technology Programme forms part of the Government’s commitment to science and innovation and has a total budget of £320million over a three year period. The second phase of awards builds on the £145million that was made available last year. Promoting the importance of the awards, Lord Sainsbury, Minister for Science and Innovation, said, "Exploiting research can be a costly venture, even inhibiting for many businesses, but to keep Britain at the forefront of the global economy it is essential that we maintain inward investment in key innovative areas.”

The Technology Programme competition is open to industry and academia, including universities, other higher educational institutions, their spin-off companies and other research bodies, and further details of the application process can be found on the DTI website.

Keywords : Funding

News story   |   By Dr Ireena Dutta   |   Published 15 April 2005

A new resolution that impacts on the current terms of European Union funding for stem cell research was adopted last month by the European Parliament.

The main focus of the resolution is the trade in human egg cells, but it also includes a statement on the funding of embryo and embryonic stem cell research. Currently, the Parliament and the European Commission accepts the funding of research involving embryonic stem cells, but has specifically prohibited the EU’s research budget being used to create new human embryos for this work. The new resolution states that embryonic stem cell research carried out in member states where it is legal should be funded through the national budgets of these countries, and not by the EU. Furthermore, it proposes that EU funding should concentrate on alternative forms of stem cell research, using adult and umbilical cord cells. According to the three MEPs who promoted the new resolution, the European Parliament’s change of position was sparked by EU enlargement, with the inclusion of countries such as Poland, and concerns over the trade in human egg cells. The Human Fertilisation and Embryology Authority approved the use in the UK of eggs donated by woman in Romania, but some doubt has been cast over the methods by which these eggs were obtained.

Although the new resolution has been adopted by the Parliament, the EU Commission has yet to change its position, and the effect of these changes on the 7th Research Framework Programme of scientific funding remains unclear.

Keywords : euFunding

Research articles

Research article   |   By Dr Philippa Brice   |   Published 2 April 2005

Thiopurine drugs such as mercaptopurine and thioguanine are used to treat malignancies such as acute lymphoblastic leukemias (ALLs), as well as rheumatic disease, inflammatory bowel disease, dermatologic and other conditions. These drugs are metabolised by a key enzyme, thiopurine methyltransferase (TPMT), the activity of which is controlled by a common genetic polymorphism that affects drug efficacy and toxicity. Several alleles are associated with reduced or absent TPMT activity (when present in heterozygous or homozygous form, respectively); around 10% of the Caucasian population are heterozygous and 0.3% homozygous for mutant (inactive) TPMT alleles. Such individuals cannot completely metabolise thiopurine drugs and will have higher residual levels of thiopurines and intermediate metabolic products, which can lead to toxic side-effects, if treated with standard doses.

A new study published in the Journal of the American Medical Association (JAMA) reports an investigation into the association between TPMT genotype with prognosis among children receiving mercaptopurine for the treatment of childhood ALL [Stanulla M et al. (2005) JAMA 293, 1485-1489]. Children with deficient TPMT activity treated for ALL have an increased risk of severe haematopoietic toxicity if treated with normal dosages of thiopurines, but high dose mercaptopurine has also been associated with a better prognosis. Chemotherapy for ALL is often adjusted according to the risk of treatment failure, as deduced from prognostic factors. One such prognostic measure is that of minimal residual disease analysis, polymerase chain reaction (PCR) based detection of leukaemic-specific sequences, which is reportedly highly predictive of disease recurrence.

A total of 814 ALL patients aged 1-18 participated in the study; all were genotyped with respect to the TPMT gene, and minimal residual disease for analysis was performed on days 33 and 78 of their treatments, before and after administration of a 4-week course of mercaptopurine. 92.8% of the patients were homozygous for wild-type TPMT, 6.8% heterozygous, and 0.5% homozygous for mutant TPMT alleles. This latter group was treated with a 10-fold lower dose of mercaptopurine to prevent toxicity, and were excluded from further study; the heterozgotes and wild-type homozygotes received standard doses. Minimal residual disease levels on treatment day 33 were equivalent in both groups, but on treatment day 78 (following mercaptopurine treatment), significant differences were observed between the wild-type and heterozygous patient groups. The heterozygous patients were found to have a 2.9-fold reduction in risk of having measurable minimal residual disease (and hence good prognosis) at this point, but no increased risk of toxic side-effects.

The authors conclude that TPMT genotype has a substantial impact on disease prognosis after administration of mercaptopurine for the treatment of childhood ALL, proposing that this observation is due to genetically determined modulation of mercaptopurine dose intensity. The heterozygous patients treated with equivalent doses to wild-type patients in this study received effectively greater levels of mercaptopurine, since they were less able to metabolise it, and subsequently were more likely to show good prognostic signs. The researchers note that long-term outcome data will be required on these patients, but suggest that they may call for increasing doses of mercaptopurine according to TPMT genotype (an increase above standard doses for wild-type patients) in the early treatment of ALL, since this may improve overall outcomes. The report also calls for future assessments of treatment response to specific drugs to include analysis of genetic variation in drug-metabolizing enzymes and minimal residual disease.

Comment: This study adds an interesting angle to the study of pharmacogenetics (genetic factors that influence individuals’ responses to specific drugs, in terms of efficacy and toxicity). Pharmacogenetics is often perceived as identifying individuals for whom standard drug doses are inappropriate, due to the presence of less common genetic variants, but clearly the field can also contribute to refining and improving the treatment of patients with the most common genotypes too. This suggests that including genetic components to future clinical drug trials is extremely important.
Keywords : journal

Research article   |   By Dr Philippa Brice   |   Published 14 April 2005

The Human Genetics Commission (HGC) and the UK National Screening Committee (NSC) have rejected a proposed national scheme to collect a DNA profile of every baby at birth, the BBC has reported. The Joint Working Group, formed by members from both organisations, concluded that while genetic profiling might provide clinical benefits in the future, at the moment the scientific evidence is limited. They recommend that the government revisit the issue in five years. The group had been tasked, as part of the Genetics White Paper, to consider the positive and negative aspects of the genetic profiling of babies at birth. Their report, Profiling the newborn: a prospective genetic technology?, has now been published.

Profiling was defined as, “…the analysis of a person’s entire genome in order to reveal the majority of the genetic variations.” The Working Group concluded that given the current state of scientific and medical knowledge that it was not practicable for this scheme to go forward at this time. The report states that, “…this is not likely to be affordable in the public health context in less than 20 years. It also raises a number of important ethical, legal and social issues which need to be addressed before any such scheme could be acceptable.” For example, there is a concern that information that came from the profile could be used in the future to discriminate against individuals in the areas of employment, insurance and education. The police might also use the information “…for unwarranted purposes.” If such a profile were to be collected from newborns, the information it contained would need to be adequately protected from misuse.

In the meantime, they believe that regulation might be needed in the commercial sector. Genetic profiling is feasible and companies are already offering it on an individual basis, raising issues such as the provision of genetic risk information to children. The Working Group does see the potential for genetic profiling to be of clinical use in the future but calls for further research into its implications. Research is also needed into genetic testing in children and into public attitudes on this issue. The results of such research would give reviewers a better understanding of the implications of genetic profiling when it is next considered. - 2/4/05 Dr Susan Wallace

Keywords : journalbreast_cancer