News

22 March 2005

A US company, DNA Direct, is offering breast and ovarian cancer genetic susceptibility test kits for sale directly to the public (see Harding A (2005) BMJ 330, 617) for between $586 and $3312 (roughly £300 and £1750), depending on the complexity of mutation screening selected. The company says that it provides the same service that an individual would get from any healthcare provider, except that results and counselling are given by telephone or via the internet “that redefines traditional, face-to-face genetic counselling”. Previously, the genetic test manufacturer, Myriad, restricted use of the test kits to patients referred via a doctor or cancer clinic, but because DNA Direct employs doctors and counsellors, Myriad reportedly considers their arrangement satisfactory (see CBS news report).

However, experts are worried that effective, tailored genetic counselling cannot be delivered other than in person, and that there is a danger that interpretation of complex test results and their implications by such means may not be adequate. Dr Francis Collins, Director of the National Human Genome Research Institute, observed that although DNA Direct is “a cut above most genetic testing companies” because it does employ clinicians, he was nevertheless concerned about cutting the primary care physician out of the equation. "As often is the case, science is running ahead of public policy", he said, noting that although genetic testing has enormous potential, the majority of claims on commercial genetic testing websites are not scientifically sound.

7 March 2005

Law Lords will today begin considering a challenge to the legality of licensing clinics to create ‘saviour siblings.’ The organisation Comment on Reproductive Choice (CORE) is challenging the ability of the Human Fertilisation and Embryology Authority to license clinics to conduct pre-implantation genetic diagnosis (PGD) and tissue typing to select among healthy embryos. Using these techniques, doctors can choose an embryo with the same HLA type as a sibling to implant into the mother; the new child would be able to provide a bone marrow transplant for its ill brother or sister.

The High Court ruled on the case in 2002. The judge decided that the HFEA had indeed exceeded its powers by licensing PGD with tissue typing. The Court of Appeal later overruled the High Court’s judgment in April 2003 (see newsletter May 2003). The judges in their decision noted that the High Court had believed that “…it was inconceivable that Parliament intended to leave an activity such as tissue typing, which had potential for misuse, outside the control of the [Human Fertilisation and Embryology Act 1990].” However, the Court of Appeal judges unanimously agreed that Parliament had given the HFEA the responsibility of weighing the difficult ethical and legal issues surrounding these technologies and therefore the HFEA was legally able to license clinics to conduct this work.

Shahani and Raj Hashmi were the first couple able to pursue PGD and tissue typing in order to try for a child to save their son, Zain, who suffers from beta thalassaemia. Unfortunately, their attempts have not been successful, resulting in a series of miscarriages. Each request for these technologies is reviewed individually and many other families are hoping to undergo the procedures to help their children. Recently, the HFEA announced that it was relaxing its requirements for PGD and tissue typing no longer requiring that the child to be born must benefit from the procedure as well as the sibling. However, if CORE is successful in overturning the Court of Appeal’s decision, families will have to abandon their hopes of receiving this treatment in the United Kingdom. The House of Lords hearing will last two days. A decision is not expected for at least six weeks.

24 March 2005

The House of Commons Science & Technology Select Committee has published its Report on Human Reproductive Technologies and the Law. The report, which controversially only represents the views of half the committee, advocates major changes to the current practice of regulating reproduction and embryo research. The report, in many of its recommendations, advocates a stepping back from regulation at a governmental level and giving more power to parents and doctors to make decisions, “…ensuring that reproductive decisions remain primarily in the private domain, governed by professional ethics and the law of consent.” The authors believe that this would provide a more flexible regulatory framework and benefit medical research. The report states that the Human Fertilisation and Embryology Authority (HFEA) has been overly cautious in licensing new research and this bureaucracy has hindered the advancement of medical research in general.

For example, the report recommends that the HFEA be abolished and replaced with the Regulatory Authority for Fertility and Tissue (RAFT). The Department of Health (DH) has already stated that the current work of the HFEA and the new Human Tissue Authority (HTA) will be combined in 2008. However, the report recommends that RAFT should have reduced functions from the HFEA. It would only be responsible for ensuring that laboratories meet technical and management standards. Parents would no longer need to go to a regulator to determine if they could have pre-implantation genetic diagnosis (PGD) to create a ‘saviour sibling’ to cure an ill child or if they were appropriate candidates for IVF under welfare of the child rules. They themselves would make those decisions with their doctor, with proper ethics oversight as required by the situation.

One specific recommendation that has been highlighted by the press is that parents should be allowed to choose the sex of their child when undergoing fertility treatment. The Select Committee believes that “The onus should be on those who oppose sex selection for social reasons using PGD to show harm from its use.” This position contradicts findings from a consultation held by the HFEA in 2003. The HFEA reported then that 80% of people in the UK did not want to use PGD for non-medical reasons such as sex selection. Likewise, a survey of 4,000 Americans, conducted in 2004, showed that while there was approval of PGD for helping save the life of a child, respondents did not believe it should be used for sex selection (see PHGU newsletter May 2004).

Other recommendations in the report include more research into the social impacts of assisted reproduction, that standards for providing in vitro fertilisation treatment should be improved, and that abortion issues be dealt with in a new Act which would be published in draft format and subject to pre-legislative scrutiny. Members of Parliament should be given a free vote on any legislation concerning assisted reproduction and embryo research and that a system of clinical ethics committees (committees that discuss ethics in clinical practice) be considered to act in parallel with research ethics committees. Also a single national commission should be created to develop policy issues in the areas of assisted reproduction, embryo research and human genetics. This commission would expand the remit of the Human Genetics Commission, which would disappear, and would include issues that the HFEA currently considers together with those that would fall under the HTA.

The views of the five dissenting Committee members, almost half the Committee membership, are presented in a Special Report and a press release. According to the release, the dissenting members believe that the report is “…flawed in adopting an extremely libertarian approach…” to the issues. “It was an unbalanced approach…which neither reflected the evidence received nor represented the views of a majority of the Committee.” They state that there had been moves to make the report more balanced through redrafting, however other commitments made it impossible for members to attend all of the Committee sessions. Limited time was given to discussion of amendments to the report, which they believe “…further distracted from the report.” It was agreed that a Special Report, recording the dissenting view, would be issued with the main report. However, the text, except for the opening sentence stating that there was a dissenting view, was subsequently removed from the Special Report. According to the press release, it is available in the proceedings of the Special Report itself. Because of the division amongst the members, it was decided that no press conference would be held.

It is unclear how this report will influence decision making on these issues. The terms of reference for the committee were to consider the future of the HFE Act and the HFEA. The Department of Health has announced plans to review the Human Fertilisation and Embryology Act 1990, to consider if it is now 'out of date' in respect to reproductive technologies. This report may influence those discussions. Many others, such as the authors of the Bioscience Innovation and Growth Team report, have advocated a reduction in the bureaucracy associated with medical research if the UK is to maintain its leadership position worldwide. However, the dissenters argue that there is still a place for a precautionary approach in regulating these technologies. Both sides agree that ethical review continues to be a mandatory part of the research process.

10 March 2005The new East of England Stem Cell Network (EESCN), a unique initiative that brings together local experts in stem cell research from the academic, clinical and commercial sectors was formally launched this week (see press release). The EESCN seeks to promote innovation in stem cell research and its applications, and strengthen the East of England’s position as a global leader in this field; the region is already an established centre of excellence in stem cell science and its applications, comprising not only the Cambridge Stem Cell Institute and the UK Stem Cell Bank at Potters Bar, but also expertise in developmental biology, epigenetics, clinical translation of research into practice and the ethics and regulation of stem cell technology.

Co-ordinated by the Cambridge Genetics Knowledge Park in partnership with the Cambridge Stem Cell Institute, the Eastern Region Biotechnology Initiative and Cambridge Network, the EESCN aims to foster collaboration between network members, to promote stem cell research on a national and international level and encourage investment, and to address the social, regulatory and legal implications of stem cell technology. Network members include academic and clinical research centres, patient groups, individual scientific, legal and venture capital enterprises, and business development agencies.

Dr Mary Archer, Chair of EESCN, welcomed delegates to the launch, saying: “The government commitment to stem cell research is now significant and gives a very strong lead, but we need more proven roads to therapy”. Cambridge Stem Cell Institute Director Professor Roger Pedersen, who also spoke at the launch, commented: "Cambridge and the East of England represent the largest biotech cluster in the whole of Europe. As such, our area has the greatest concentration of intellectual capital in the areas of genomics, proteomics and cell developmental biology. These are the platform disciplines for the UK stem cell enterprise. Therefore we look forward to tremendous contributions from Cambridge and the East of England as stem cell research moves forward to the clinic and delivers the therapeutic benefits of regenerative medicine".

For more information on stem cell science and the activities of the Network, see the EESCN website.

1 March 2005The Spanish government has approved four research projects using embryonic stem (ES) cells (see press release). One project will use stem cells to design treatments for diabetes, while the other will work on neurodegenerative diseases. The other two projects will explore the mechanisms of turning stem cells into specific cells and tissue types. These are the first projects to be approved in Spain since legislation was passed last year to allow ES cell research. Under Spanish law researchers can use unused frozen embryos created for fertility treatment providing that the embryos are more than five years old and that donors have given their informed consent for their use in research. With these approvals, Spain joins Sweden, Belgium and the UK as active participants in ES cell research. Spain does not currently allow embryos to be created for research purposes, but may introduce therapeutic cloning in new medical research legislation in 2005, according to an announcement made last year.

15 March 2005The Government and the Association of British Insurers have agreed to extend the existing voluntary moratorium on the use of predictive genetic test results by insurers by five years to 2011. The moratorium had been set to expire in 2006 and is overseen by the Genetics and Insurance Committee (GAIC). GAIC, formed in 1999, is also responsible for evaluating genetic tests and their applicability for insurance underwriting purposes and approving their use in this manner. GAIC has only approved one predictive genetic test up until now, that of Huntington’s disease for use in determining premiums for life insurance policies over £500,000.

In addition to the extension, the parties have agreed a new Concordat, a policy agreement on the use of genetic test results by insurers in underwriting insurance policies. It is designed, according to the Government press release, to reassure people about taking genetic tests. The parties have agreed that genetic test results will not be used to deny people insurance cover. No one will be required to disclose the results of a predictive genetic test unless approved by GAIC and is for insurance cover of over £500,000 or critical illness and income protection insurance of over £300,000. The insurers have also agreed to a set of measures designed to reassure people, including not to put pressure on those seeking insurance to take a predictive genetic test or to ask individuals to reveal another person’s test results. Health Secretary, John Reid, said, “Choosing to have a predictive genetic test can be life saving, and nobody should be put off having such a test because of fears it will be used against them by insurers.”

However, some believe that the new Concordat is not sufficient to prevent genetic discrimination. Genewatch UK believes that there are two significant provisions missing from the agreement. Individuals do not know if, after the moratorium expires, whether any predictive genetic test information they may have received while the moratorium was in place will be used against them. Also, the Concordat does not prevent employers from seeking predictive genetic test information. As Dr Helen Wallace, Deputy Director of Genewatch, notes, “People making the difficult decision whether to take a genetic test need to know that the results will never be used against them in the future. They should not have to think about the impacts on insurance or their job.” The Concordat will be reviewed in 2008.

8 March 2005A new National Service for pre-implantation genetic diagnosis (PGD) in Scotland, jointly funded by the Scottish NHS boards and based at Glasgow Royal Infirmary, is to be launched on 1 April 2005. PGD is a procedure whereby embryos conceived by in vitro fertilisation (IVF) are examined to determine their sex and to identify if they are affected by a serious genetic disorder (such as Huntington’s Disease or Duchenne Muscular Dystrophy), with a view to selection and subsequent implantation of disease-free embryos. Currently, Scottish couples in need of PGD for genetic disorders have to travel for London for treatment, but it is hoped that the new service will be able to offer some forms of treatment from June this year. At present the Glasgow centre is only licensed for some chromosomal tests, so until additional test licences are granted couple requiring molecular genetic tests may still have to travel to London.

The new PGD service is a collaborative venture between the Assisted Conception Services at Glasgow Royal Infirmary and the West of Scotland Regional Genetics Service based in the Duncan Guthrie Institute at Yorkhill Hospital. Scottish Health Minister Andy Kerr commented: "I am delighted that this service will be introduced as a National Service and will benefit patients who live throughout the whole of Scotland” (see press release). The Scottish Executive anticipates that around 15 couples a year will use the service initially, with this number expected to increase.

10 March 2005

Tobacco smoking is known to have a carcinogenic effect on various organs, and maternal smoking during pregnancy is known to have detrimental effects for both the mother and fetus, increasing the risk of intrauterine growth retardation, obstetric complications and other adverse health effects. A new paper in the latest edition of the Journal of the American Medical Association (JAMA) now reports that maternal smoking is also associated with increased chromosomal instability in fetuses. Spanish researchers interviewed 800 pregnant women referred for amniocentesis and prenatal genetic testing for a variety of reasons such as maternal age, previous history of fetal abnormality or spontaneous abortion, or increased risk indicated by standard prenatal screening [de la Chica et al. (2005) JAMA 293, 1212-1222]. Women were asked about their exposure to smoking, other potential mutagens and consumption of alcohol, tea and coffee. They identified 25 women for whom smoking was considered their only significant exposure to a mutagenic agent, along with a matched control group of 25 pregnant non-smokers with no known significant passive exposure to tobacco smoke. All the smoking mothers had at least a 10-year history of smoking and smoked in excess of at least 10 cigarettes per day during pregnancy.

Fetal cells were extracted from amniotic fluid samples and a standard cytogenetic approach (karyotype analysis of at least 25 high-quality metaphase samples per patient) used to identify structural chromosomal abnormalities in the fetal cells. The proportion of fetal cell samples showing chromosomal instability, the frequency and type of chromosomal lesions, and the frequency of structural abnormalities in fetal cells were recorded and used for statistical analysis. The authors note that the mean maternal age was higher (3 years) in the smoking group than the control group, although they suggest that increased maternal age tends to correlate with a higher level of numerical but not structural chromosomal abnormalities

Results showed an approximately 3.5 fold increase in the incidence of structural chromosomal abnormalities (primarily deletions and translocations) in the fetal cells from smokers compared with those from non-smokers, with deletions and translocations accounting for a majority of these changes.The authors also report that abnormalities in a particular chromosomal location (band 11q23) were more frequent in the smokers group, and propose a potential link between this phenomenon and childhood leukaemia, although without any evidence to support this proposal.

This study represents the first direct evidence findings of genotoxic damage to fetal epithelial cells in pregnancies where mothers smoke tobacco, contributing to previous work that has already implicated smoking in pregnancy in mutagenic effects on the fetus, as outlined in an editorial article accompanying the report [DeMarini DM and Preston RJ (2005) JAMA 293, 1264-1265]. These authors point out that the chromosomal abnormalities reported in the study were actually produced by errors of replication in the fetal cells during cell culture after extraction of the original fetal cells, and so cannot necessarily be attributed to the effects of smoking. It will be necessary for further studies to replicate and reinforce the findings of this paper.

Comment: The potential mutagenic effects of maternal smoking on fetal cells is an important public health issue, given the potential immediate and long term health effects for affected fetuses, and one that undoubtedly warrants further investigation. Whether confirmation of the association between tobacco consumption and fetal genotoxicty would influence maternal smoking behaviour any more than existing messages about the dangers to fetal health is not known.

15 March 2005

Three new studies published in Science Express have implicated a single gene in the disease age-related macular degeneration (AMD), with one report suggesting that the presence of the genetic defect may account for up to 50% of the risk of an individual developing AMD [Alberts et al. (2005) Science: 1110189]. The macula is a small area in the centre of the retina, the part of the eye that focuses incoming light to form images and relays this information to the brain. There are two main forms of age-related macular degeneration; around 10% of cases are wet (exudative) AMD, where tissue degeneration causes a fluid build-up under the retina; this form of the disease can sometimes be treated with laser therapy. However, the majority of cases are dry (atrophic or non-exudative) AMD, a slow deterioration in the function of the visual cells for which there is currently no treatment. Both forms of the disease affect central vision. Overall, AMD represents the leading cause of blindness among the over sixties and currently affects around half a million people in the UK, with this figure likely to rise as the population ages.

Researchers screened individuals with AMD and family members, as well as unrelated individuals without AMD. They found that those people with one or more copies of a particular variant of the CFH (complement factor H) gene were more likely to have AMD than those who lacked the genetic variant. The CFH mutation was reportedly present in half of all those tested who had AMD, and showed a particularly strong association with wet AMD. The risk of developing AMD for individuals homozygous for the CFH mutation was found to be several times greater than for people without the variant. Dr Margaret Pericak-Vance, Director of the Duke Center for Human Genetics in the US and a co-author of one Science paper, commented: "The finding may ultimately lead to new methods for identifying those at high risk for macular degeneration and suggests new pathways for drug development", adding that in the shorter-term, it could aid the identification of individuals at high risk of developing AMD and allow preventative lifestyle changes to decrease that risk, such as avoiding smoking and obesity (see BBC news report).

22 March 2005

A new Taiwanese study published in Occupational and Environmental Medicine reports evidence of increased levels of DNA damage among female motorway toll-booth operators, when compared with a similar group of female office workers. Researchers from Taiwan's National Defence Medical Center measured levels of 8-hydroxydeoxyguanosine (8-OhdG) in the urine, and of nitric oxide (NO) in the blood of both groups as indicators of the levels of oxidative DNA damage (that is, damage induced by reactive oxygen intermediates, or ROIs). When smokers were excluded from analyses, because tobacco smoke has a significant effect on urinary 8-OHdG levels, 8-OHdG levels were found to be around 90% higher, and NO levels 30% higher, among the toll-booth operators than they were among the office workers (see BBC news report).

Although the study size was very small (47 subjects and 27 controls) and the researchers themselves note that they did not take into account other genetic and environmental factors that can influence 8-OHdG metabolism, they nevertheless propose that exposure to traffic fumes can induce DNA damage via increased levels of ROI activity. Since this could in turn increase the risk of cancer, they call for increased control of traffic pollution in order to protect the health of people exposed to traffic fumes [Lai CH et al. (2005) Occup Environ Med. 62, 216-222]. Further studies will be required to investigate the genotoxic effect of such fumes more reliably.