PHG Foundation | www.phgfoundation.org

8 November 2004

The first drug targeted at a specific ethnic group is expected to take a step closer to the market today, as phase III clinical trial results demonstrating 'significant survival benefit" in a group of 1000 African Americans are expected to be presented today at the annual meeting of the American Heart Association. US company NitroMed are seeking a licence from the US Food and Drug Administration (FDA) for their drug BiDil to treat heart failure in African Americans. BiDil is a combination of two pre-existing drugs, isosorbide dinitrate and hydralazine, not previously considered effective for the treatment of heart failure, but NitroMed claim that when use is restricted to African American populations the drug is beneficial.

BiDil is already causing controversy as a potential first step towards genetically targeted drugs. It is known that certain ethnic groups are more prone than others to particular diseases, and that certain drugs may be more or less efficacious in different groups. US African Americans are twice as likely to develop heart failure than Caucasians. Ethnicity can also be a predictor of drug response; for example, beta-blockers tend to be less effective in black people. The goal of pharmacogenetics is the concept of ‘individualised medicine’, whereby the most appropriate drugs for an individual, based on both their medical condition and their genetic make-up, could be selected; certain genetic variants can affect the way in which individuals respond to specific drugs. Attempts to develop effective drugs, especially for groups for whom few such drugs are currently available, have been widely welcomed.

However, the fact that BiDil has been tested in and will be marketed solely for African Americans has caused some concern. Professor Mark Johnson, lecturer in diversity in health and social care at De Montfort University in Leicester, told the BBC: "Race is the lazy man's way to get a genetic marker. Genetic markers are not necessarily easily reflected as a visible marker” (see BBC news report). Dr Helen Wallace, deputy director of GeneWatch, a UK campaign group that monitors developments in genetic technologies, said that BiDil was a "worse than crude" attempt to define humans in genetic groups, adding: “Racial differences are not really understood…There are more genetic differences within ethnic groups than between them". She also noted the importance of environmental factors in affecting the response of individuals to treatments and warned against an over-emphasis on genetic factors.

NitroMed, who claim that BiDil's mechanism of action is intended to address the nitric oxide deficiency “we believe to be associated with heart failure in African Americans” defended the decision to test the drug solely in black people, saying that was decided after discussions with the FDA. If results show the drug to be as effective as expected, it is likely to receive FDA approval next year.

19 November 2004The Department of Trade and Industry launched their five-year strategy for creating wealth from knowledge this week. The Government hopes that this programme will position the UK as the leading global location for scientific research. The plan identifies the exploitation of science and technology, the development of partnerships with industry, new approaches to regulation and driving reform in the European Union, as key areas that need to be addressed, in order to achieve this ambition. Specific measures have also been announced in order to further this goal. These include:

Actions to tackle animal rights extremism.
Strengthening international science and technology links, and undertaking new work with high-tech clusters in the United States.
Raising public awareness of, engagement with, and support for, science and innovation.
Establishing a new multi-million pound fund for ‘Newton Awards’, available for high profile, cross-disciplinary research with potential for breakthroughs in areas likely to help UK public policy and business priorities.
Promoting the role of regional development agencies in providing information on excellence and best practice in industry, and relevant business support.

Other measures will aim to reduce the current regulatory burden on businesses, encourage entrepreneurship, and promote the role of women and ethnic groups in business creation. However, the new strategy will also result in the reduction in core staff at the DTI by 20%, and the continued relocation of posts out of London and the South East.

Commenting on the plan in a speech earlier this week, Tony Blair stated that the Government’s ambition was for the UK, ‘to become the science capital of the world’. Specifically identifying stem cell science as an example of a new area where ‘the UK can lead the world’, he added that this country ‘has one of the most comprehensive schemes of stem cell regulation in the world’ and that this gave the UK ‘confidence to recognise that science can be a force for good and to grasp the opportunities that it presents to us. The Government is sending a strong signal today - which we will reinforce around the world in the coming months - that the UK is the place to carry out scientific research like this. The UK can be the world leader in stem cell research and biotechnology. The DTI Plan will help ensure that the UK continues to create a climate where this sort of research can flourish.’

2 November 2004The Human Fertilisation and Embryology Authority (HFEA) has approved the screening of embryos, using pre-implantation genetic diagnosis (PGD), for inherited bowel cancer, Familial adenomatous polyposis (FAP). If a parent is a carrier of FAP, there is normally a 50% chance that a child will inherit the condition. FAP sufferers develop small non-cancerous growths (polyps) in their bowel, which become cancerous as they grow older. The University College London has now been licensed by the HFEA to screen for FAP. In PGD, during the in vitro fertilisation process, embryos are screened to see if they carry the faulty gene. Healthy embryos without the faulty gene (up to 2 in women under 40) are implanted. Some scientists hope that FAP could be reduced or wiped out if the gene is not passed on to future generations.

However, this raises ethical questions. FAP does not manifest itself until early adulthood. Opponents argue that medicines should be developed to treat the condition, rather than using controversial genetic techniques to try to ‘solve’ the problem. Also, some claim that this continues the UK ‘down the slippery slope’ towards designer babies. Where do we stop when it comes to choosing a child’s attributes? For the happy families who have won the right to screen for FAP the answer is clear; they will be able to prevent a terrible disease from being spread to future generations. For others the answer may not be so clear. There have been calls for the HFEA to put these decisions to the public to ensure the issues are debated fully.

For further information on FAP and the genetics of colorectal cancer, see the disease profile section.

30 November 2004The House of Lords has refused Natallie Evans’ petition to appeal a High Court decision refusing her access to frozen embryos created by herself and her then-partner, Howard Johnston. Ms Evans is now considering whether to go to the European Court of Human Rights in her bid to have IVF treatment.

Ms Evans was left infertile by cancer treatment. She and her partner had begun IVF treatment but the couple split up and now Mr Johnston is refusing her request to use the embryos. Ms Evans has stated that this would be her only chance of having children of her own, as her ovaries were removed when she was diagnosed with cancer. She had argued that if she had become pregnant naturally, her partner would have had no part of her decision whether or not to have the child. Mr Johnston countered that he should not be forced to have to take financial and emotional responsibility for a child he did not want. The High Court had ruled that both partners must give consent to use the embryos, as set down in the Human Embryology and Fertilisation Act 1990; this was later confirmed by an Appeal Court decision. The House of Lords have now subsequently ruled that Ms Evans’ new petition did not raise any point of law that should be considered by the House at this time. Consent by both partners will continue to be required to use frozen embryos in IVF treatment

17 November 2004A new era for the practice of genetics began this week when the Human Tissue Act received Royal Assent on 15 November, after months of debate in the House of Lords. Many of the amendments made in the House of Lords were a response to the concerns of the genetics, research and academic communities as to the Act’s potentially burdensome effects. What has resulted is a more balanced piece of legislation that includes the following:

· A power for the Human Tissue Authority (the HTA) to give ‘deemed consent’ for tissues to be used or DNA analysed for the benefit of another, where the donor has not responded to reasonable requests for consent (despite being given notice of the application to the HTA), where there is no reason to believe that the donor has died or is incompetent;
· No requirement for consent where material from living persons is used, or DNA analysed, for all types of education and training, including that relating to research;
· A reduction in the penalties which can be imposed by magistrates so that they no longer have the power to imprison those who are found guilty of an offence;
· The system of Inspectorates is removed from the Act and instead the Human Tissue Authority has the flexibility to organise its workforce in whatever way it chooses pending the merger of the Human Tissue Authority and Human Fertilisation and Embryology Authority in 2008;
· A formal obligation for the Secretary of State to consult appropriately before making regulations.

The implications of the Act remain uncertain until the codes of practice and regulations to be issued by the Human Tissue Authority and the Secretary of State are published and until the Mental Capacity Bill and draft Coroner’s Rules are finalised. In any event, the Act will come into force at least 3 months after the code of practice relating to the removal and storage of material, is issued by the Human Tissue Authority – thought to be in the latter part of 2005.

Further information and comment on the Human Tissue Act can be found on the Cambridge Genetics Knowledge Park website at: http://www.cgkp.org.uk/topics/human_tissue/index.html

19 November 2004The High Court will review an application for judicial review of the process undertaken by the Human Fertilisation and Embryology Authority (HFEA) in granting a license to the Newcastle Fertility Centre to conduct therapeutic cloning experiments. If the High Court approves the application, the review process will take place next year.

Peng Voong, a public policy analyst with the Lawyer’s Christian Fellowship (LCF) filed the application. His case includes two claims, that the HFEA, as a public body, has not been forthcoming and transparent in its reasons for granting the license and that the HFEA could not lawfully grant the license. Schedule 2, paragraph 3(6) of Human Fertilisation and Embryology Act 1990 states that the HFEA can grant a license for research using embryos if that research is deemed ‘necessary.’ In addition, the Human Fertilisation and Embryology (Research Purposes) Regulations 2001 state that a license may be issued for the purposes of increasing knowledge of the development of embryos, increasing knowledge about serious disease or to enable knowledge to be applied in developing treatments for serious disease. Whether the Newcastle research is ‘necessary’ or whether it meets these other conditions will no doubt be argued if the case comes before the High Court.

The Newcastle Fertility Centre were licensed earlier this year by the HFEA to use cell nuclear replacement (CNR), the technique used to clone Dolly the sheep, to create stem cells that are genetically identical to those of a patient (see newsletter August 2004). In this procedure, the nucleus of a skin cell is removed and placed into an unfertilised egg. The egg is then stimulated to divide until a group of cells is formed. Stem cells are then isolated and reprogrammed to grow as the cells needed by the patient. However, the HFEA, in granting the license, stated that, “[t]he purpose of this research is to increase knowledge about the development of embryos and enable this knowledge to be applied in developing treatments for serious disease. This research is preliminary, it is not aimed at specific illnesses, but is the foundation for further development in the treatment of serious disease.”

Opponents of cloning have gathered in support of Mr Voong’s case. While he is acting on his own, and not on behalf of the LCF, that organisation and the Pro-Life Alliance have both signalled their support. Julia Millington of the Pro-Life Alliance has told the press, “Human cloning is profoundly unethical, particularly when the cloned embryos are manufactured for their constituent parts and thereafter destroyed.” She continued, “The HFEA has power to grant human cloning licenses but only if certain rigorous conditions are met. We believe that this license does not fulfil the conditions of the Human Fertilisation and Embryology Act.” The LCF, in a press release, has stated, “This legal challenge is essentially about upholding the rule of law by revealing the flawed decision making process of the HFEA, including its failure to act transparently.” The HFEA has said that is does not comment on legal proceedings.

24 November 2004The Medical Research Council (MRC) has released a new report, Assisted Reproduction; a safe, sound future, that recommends improved monitoring and additional evaluation of assisted reproductive technologies (ARTs). This includes in vitro fertilisation and intra-cytoplasmic sperm injection. The Human Fertilisation and Embryology Authority (HFEA) had asked the MRC to advise them on the scientific evidence showing any potential health risks when using these technologies. The MRC formed an independent working group “…with a wide remit to look into the whole area of ART research, focussing on possible risks to the embryo and child.” The working group reviewed the current literature and discussed the issues with stakeholder groups. They concluded that the key priorities for the field needed to be, first, establishing a monitoring framework for ART to improve the evidence base for new ART technologies. Within this, the existing HFEA database on ART procedures needs to be expanded so that information can be used in research, to aid clinical evaluation by linking data to health outcomes. For example, long-term follow-up studies of children conceived through ART are recommended, however consideration would need to be given to the ethical issues around telling children how they were conceived. Second, a new evaluation system is needed to ensure safety, efficacy and effectiveness of ART techniques. Systematic analysis should be carried out on new treatments being evaluated, with the evaluation process moving over time to existing treatments. In general, good practice and guidelines need to be standardised and there are calls for increased public discussion in shaping research priorities.

9 November 2004Researchers from the University of Durham have published an independent report on the legal and ethical issues raised by the use of the National DNA Database (NDNAD). The report, Genetic Information & Crime Investigation: Social, Ethical and Public Policy Aspects of the Establishment, Expansion and Police Use of the National DNA Database, comes out of a wider study being conducted by the authors of police uses of DNA profiling and the NDNAD, funded by the Wellcome Trust. This report examines the history of DNA profiling and databasing in England and Wales, assesses the work of the NDNAD, how samples and profiles of individuals are managed and governed, and looks at the ethical issues of the current and future developments arising from DNA profiling and databasing.

The authors present a series of recommendations they feel are necessary to ensure that proper oversight and public scrutiny are given to the issues. For instance, a comprehensive review should be conducted of NDNAD’s scientific and technological foundations, as the authors state there has never been such a review on NDNAD published in the scientific peer reviewed literature. An independent oversight body with lay representation should be created to look at how the NDNAD works, in order to promote transparency and public acceptance. The oversight body should over explore key issues that question the balance between individual rights and the public interest. These include “…whose profiles should be retained the database for speculative searching, the arrangements for the retention of biological samples in addition to profiles, and the proper uses of the personal information derivable from any analysis of the genetic information contained in profiles and samples.” There should be independent review of research projects using forensic genetic data in the NDNAD, as these projects help to determine how the NDNAD will be progress in the future and therefore warrant greater scrutiny. On the subject of retained samples, the authors recommend that they should be kept for a limited period of time and not kept indefinitely. In addition, the Information Commissioner should be invited to consider whether the profiles derived from the analysis of biological samples should be treated as potentially sensitive personal information.

The authors consider “…the most contentious aspect of the current uses of the NDNAD "...to be the retention of DNA profiles from those not charged or convicted with a recordable offence and the continuous speculative checking of this information." This issue must be examined further, and guidelines and principles established, they believe if the practice is going to continue. In addition the authors recommend that voluntary donors of DNA be fully informed, have consented to the practice and are able to revoke their consent at a later date if desired, as the concept of ‘irrevocable consent’ is “…especially troubling and has no parallel in other research or medical settings in which tissue samples are donated.” In addition, the idea of expanding the NDNAD to create a universal database for England and Wales should not be pursued by Government as “…the continuous speculative searching of such a database is likely to be ruled a disproportionate breach of private and family life under Article 8 of the [European Convention on Human Rights].”

The authors hope this report will prompt discussions on the issues surrounding the NDNAD and its future implications. In addition, they hope to expand awareness of database beyond those who are involved with it.

23 November 2004The United Nations (UN) Sixth Committee (Legal) has decided that there is no possibility of breaking the deadlock on a treaty to ban all types of human cloning. The latest debate on this issue took place on 19 November, after which it was announced that a decision on a treaty could not be reached. Instead the Sixth Committee has agreed to debate a non-binding draft resolution submitted by Italy for an international convention against the reproductive cloning of human beings. While the resolution calls for a ban on reproductive cloning, individual countries will be able to legislate as they wish in regards to therapeutic cloning. It also calls for countries to prohibit genetic engineering techniques contrary to human dignity.

The debates on this issue have been extensive (see PHGU newsletter articles October 2004, December 2003, October 2003). The US and Costa Rica, together with over 50 other countries, had fought for a ban on both reproductive and therapeutic cloning. The opposing group, led by Belgium and the United Kingdom, favoured a ban on reproductive cloning but not on therapeutic cloning. The latest vote was postponed, as there were fears by the United States that a vote against a total ban would have a negative effect on President Bush’s chances in the Presidential elections in early November. However, while Mr Bush won the election, the US did not win the total ban on cloning it had wanted. More discussion on this subject is forthcoming, however, as debates on the wording of the draft resolution will be held in February 2005.

12 November 2004The US Government department of Health and Human Services (HHS) has announced a new Family History Initiative. Launched by the Office of the Surgeon General in association with various other agencies including the National Human Genome Research Institute (NHGRI) and the Centers for Disease Control and Prevention (CDC), this project aims to encourage US families to learn more about their family health history by providing a tool to facilitate construction of a family health history. Common complex diseases are known to arise from the interaction of multiple genetic and environmental factors. It is hoped that the Family History Initiative will increase the use of family histories in disease prevention and health promotion, as an immediately accessible, no-cost form of ‘personalized genomic tool’. Francis S. Collins, director of the NHGRI, commented: "Family history can be a window into a person's genome…tracking illnesses from one generation of a family to the next can help doctors infer the illnesses for which we are at risk, and thus enable them to create personalized disease-prevention plans" (see HHS news report).

Many individuals are unaware of their relatives' medical histories. The web-based family history tool, "My Family Health Portrait" is available as a downloadable program or in PDF print format in both English and Spanish; the software requires the use of the Windows operating system with .NET framework installed. It explains how to complete a family tree with information about six common diseases, including heart disease, cancer and diabetes, as well as additional information. The web-tool creates a diagram from this information that can be used by a health care professional to improve diagnosis, treatment, and prevention plans for individuals who provide their personal family health portrait.

The Surgeon General has also declared Thanksgiving (November 25th 2004), when many US families meet up, as the first annual National Family History Day. Family members are encouraged to use such gatherings as an opportunity to discuss their health history.

17 November 2004The Department of Health has published its White Paper on Public Health, ‘Choosing Health: Making Healthier Choices Easier.’ It sets out “…key principles for supporting the public to make more healthier and informed choices in regards to their health.” It follows the public consultations, ‘Choosing Health?’ launched in March 2004, as well as the ‘Choosing Activity’ and ‘Choosing a Better Diet’ consultations that also took place earlier this year. In addition, several working parties were created, such as the Better Health for Young People and Working for Health/Opportunities in Employment task groups, to report on specific areas of interest (see PHGU newsletter April 2004).

The key priorities listed in the White Paper are to help reduce the numbers of people who smoke, strive to reduce obesity and improve diet and nutrition, encourage increased exercise, encourage and support sensible drinking, help improve sexual health and to improve individuals’ mental health. One of the more controversial plans is to reduce smoking in public places. The White Paper calls for all government departments and the NHS to be, with some exceptions, smoke-free by 2006. By the end of 2008, all enclosed public places and workplaces, again with some exceptions, will be smoke-free. Exceptions are expected to include public houses that do not serve food and private members clubs, if they so wish. Other plans include creating NHS health trainers, who will be trained to help individuals who wish to make lifestyle changes. Primary care trusts will provide support for cookery clubs and food co-ops in order to encourage more people to eat fruit and vegetables. Investment will be made in improving parks and public places to encourage walking, cycling and public transport.

In general, most of those who responded to the consultation felt that a majority of lifestyle choices should be left to the individual. The government hopes that the actions they have planned will help individuals make healthier choices. However, for vulnerable groups such as children and young people, it was felt some intervention was needed. There will be restrictions placed on foods high in salt, sugar and fat promoted to children, restrictions on tobacco advertising, information on alcoholic drink containers to encourage healthy drinking and initiatives to promote physical activity and sport in and out of school.

Little mention is made of genetics in the White Paper; the activities and changes that are planned focus on the environmental exposures and social factors that may be adversely affecting the public’s health. However, the White Paper acknowledges that the number of public health specialists needs to be increased, as well as new skills developed within the profession. Public health genetics is specifically noted as one specialty to be assessed for the future

23 November 2004The World Health Organization (WHO) has announced approval of the first international standard for a human genetic test. An International Reference Panel has been established for genetic testing for Factor V Leiden, a common genetic risk factor for venous thrombosis; tests for the presence or absence of the Factor V Leiden mutation are one of the most frequently performed in clinical laboratories. The new standard, agreed at the 55th session of the WHO Expert Committee on Biological Standardization (WHO ECBS), is intended to improve accuracy and quality of laboratory testing for Factor V Leiden throughout the world. Dr David Wood, Coordinator of Quality Assurance and Safety of Biologicals at the WHO commented: "Establishment of the first international standard for a genetic test is an important milestone. Genetic testing procedures are playing a vital and growing part in clinical medicine. This new standard will help to ensure that the tests are giving accurate results worldwide" (see press release).

The Factor V Leiden reference panel was developed by the UK National Institute for Biological Standards and Control (NIBSC), in partnership with the clinical National Quality Assessment scheme for Blood Coagulation and the Royal Hallamshire Hospital in Sheffield. Assessment of the standard for the Factor V Leiden genetic test was carried out by an international panel of investigators in conjunction with the International Society on Thrombosis and Hemostasis (ISTH). Establishing international standards for genetic testing is considered to be of increasing importance as the practice expands; it is estimated that millions of genetic tests are performed world-wide each year. The WHO ECBS plans to establish standards for other genetic tests in the future.

19 November 2004The verdict of a citizens’ jury of 16-19 year olds on issues surrounding ‘designer babies’ have been released. A total of 14 youths from South Wales gathered for a three-day consultation to address the question ‘Designer Babies: what choices should we be able to make?’ with a view to informing “those with an interest in the future of genetics and reproductive decision making”, notably the Human Fertilisation and Embryology Authority (HFEA) and the Human Genetics Commission (HGC). The venture, funded by the Wellcome Trust and organized by the University of Glamorgan, the Wales Gene Park and Techniquest, was undertaken in order to gather informed views of this age group, which are generally under-represented in public policy debate and also considered to be of particular relevance as they are part of the first generation likely to be directly affected by public policy in this area.

The jury agreed by a strong majority that people should be permitted to ‘design’ babies to prevent genetic conditions from being passed on, although they were divided as to whether permission for this should depend on severity of the condition in question. There was also a majority in favour of the creation of ‘saviour siblings’ to cure existing children with serious medical conditions; in this instance ten out of fourteen jurors thought that permission for such a procedure should depend on the severity of the condition. However, the majority were opposed to the creation of ‘designer’ babies without medical grounds, stating that this would imply that “the designed child is a possession of the parent”. The jurors also ruled in favour of continued regulation on a case-by-case basis, to ensure that parents will not abuse or discriminate against the designed child, but did not feel that parental age should be a factor in decision making. They also noted that it would be impractical to attempt to prevent people from going abroad for treatment to avoid UK regulation, and that the HFEA should include members below the age of 20.

Finally, there was a majority verdict that the term ‘designer babies’ conveyed a false impression and should be abandoned in favour of reference to the selection of embryos with or without particular features. In conclusion, most of the jurors felt that ‘designer baby’ technology would be useful for society, but also risky; they were divided as to whether the use of such technology was morally acceptable and should be encouraged, and whether they would consider using it for their own children in the future. The full report is available from the Wales Gene Park we