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   |   By Alison Hall   |   Published 21 December 2007

Following scrutiny by the Joint Committee of both Houses of Parliament over the summer, the re-named Human Fertilisation and Embryology Bill was introduced into the House of Lords in early November. Previous plans to merge the regulation of tissue and embryos and form a single regulatory authority, RATE, have now been scrapped and the significant reforms introduced by the Bill include extending the regulatory scope of the Human Fertilisation and Embryology Authority to cover all human embryos created outside the body. Thus inter-species embryos may be created for research, provided that such use is justified as being necessary and desirable, that the proposed use is licensed and appropriate safeguards adopted (such that embryos cannot be retained beyond 14 days of development or allowed to continue developing in either a woman or animal). The Bill imposes a statutory ban on sex selection for non-medical reasons and codifies the basis for screening and selecting embryos both for treatment and research. This is significant given technological advances which enable fetal sex to be identified in the first trimester using non-invasive techniques.

Since the Bill will take effect by amending the Human Fertilisation and Embryology Act 1990 (HFEA), there was substantive debate at second reading concerning proposed amendments to existing abortion law (since the HFEA amends the Abortion Act 1967). This is relevant because the House of Commons Science and Technology Committee recently considered whether the extent of technological change since 1990 warranted changes to the time limits for, and reform of the process of termination of pregnancy, the majority report concluding that there is a strong case for reform. Other widely debated areas at second reading concerned the removal of the ‘need for a father’ provisions from existing legislation. There was also questioning of the need for regulatory reform of embryo research, particularly interspecies hybrids (so to facilitate the production of stem cells) given recent reports of research which bypass the need for embryonic cells by reprogramming adult somatic cells to convert to stem cells.

All these topics were revisited in the more structured committee stage debates. Amongst the topics covered were the regulation of cell lines by the Bill; the regulation of human/animal hybrids and difficulties around framing a workable definition of interspecies embryo; the extent to which saviour siblings can and should be created to treat serious disease in a sibling and the extent to which this is ethically justifiable; whether cells or embryos from a child not able to give consent can be used for research, and mandatory counselling for prospective parents of donor conceived/IVF children.

Significantly the Government agreed to reconsider the definition of animal/human hybrids and the regulation of cell lines. An updated version of the Bill is likely to be published in advance of the Lord’s Report debate on 15 January 2008.

News story   |   By Dr Philippa Brice   |   Published 20 December 2007

The UK Human Fertilisation and Embryology Authority (HFEA) has granted a licence to University College Hospital in London, permitting pre-implantation genetic diagnosis (PGD) for familial hypercholesterolaemia (FH), an inherited condition typified by very high levels of low-density lipoprotein (LDL) cholesterol and early onset cardiovascular disease (see HFEA statement).

The most severe form of FH is caused by the presence of two copies of disease-associated variants of the LDL-R (LDL receptor) gene; homozygotes for this variant have very serious disease that can be fatal in childhood or early adulthood. However, PGD could also identify embryos that are heterozygous (have only one copy of) a disease-associated variant; this generally causes a milder form of FH, which is treatable with drugs and an appropriate dietary regimen, and which is thought to affect as many as one in every 500 individuals in the UK. However, the HFEA has restricted the licence to selection against embryos with the homozygous, more serious form of the condition only.

Presumably this means that only embryos identified with two copies of the disease-linked genetic variant may be disposed of, and no distinction may be made between embryos that are entirely free from the FH-linked variant (and would be disease-free), and those that are heterozygous for the disease variant and would be affected by the milder form of FH. Some would suggest that it is unethical to fail to select the healthiest embryos to implant (as part of the in vitro fertilisation process); others have expressed concern at the possibility of screening out embryos that will not be affected by a serious form of disease.

The couple on whose behalf the licence application has been made are both heterozygous carriers with mild FH, who have a homozygous daughter with severe FH, as well an unaffected son. They are quoted as saying: “We had no idea that we both carried a gene for high cholesterol until the double gene was expressed in our first child. We are very lucky that our child has responded so well to the very high-dose drug regime. We have been led to understand that other children with the same double gene may not be so lucky” (see Times report).

News story   |   By Dr Philippa Brice   |   Published 14 December 2007

An editorial in the journal Nature reports a new policy to increase the availability of published genome sequences to researchers [Nature 2007 Dec 6;450(7171):762].

Articles are already freely available to researchers in the 100 or so poorest countries through the World Health Organization's Health InterNetwork Access to Research (Hinari) initiative. Papers reporting full genome sequences have been granted enhanced levels of accessibility, in recognition that they “represent the completion of a key and fundamental research resource, describing and reflecting on what has been revealed but not usually providing insights into mechanism”. The new 'creative commons' licence for these papers will permit all non-commercial publishers to copy, distribute, transmit and adapt pdf and html versions of the paper, provided that it is for non-commercial purpose.

The journal says that the new move is a formalization of the existing policy of free access to genome sequences, which was conceived in line with the Human Genome Project’s Bermuda Agreement "…that all human genomic sequence information, generated by centres funded for large-scale human sequencing, should be freely available and in the public domain in order to encourage research and development and to maximise its benefit to society".

News story   |   By Dr Philippa Brice   |   Published 13 December 2007

EURORDIS, a non-governmental alliance of patient organisations and individuals active in the field of rare diseases (including more than 260 organisations in over 30 countries), which is supported by the European Commission, has released a consultation document on rare diseases, summarizing the necessary elements for an efficient pan-European policy in this area.

Rare diseases: Europe’s Challenges defines rare diseases as “life-threatening or chronically debilitating diseases with a low prevalence and a high level of complexity”, noting that many (though not all) of these conditions are genetic diseases, such as Duchenne muscular dystrophy, Von-Hippel Lindau disease and Huntington Disease. Low prevalence is assessed as affecting fewer than 5 per 10,000 persons in the European Union, with most of the estimated 5-8,000 conditions being much rarer than this. However, the report makes the point that collectively these diseases are significant, estimating that around 15 million people in the EU are currently affected or will be affected in the future by one of these rare diseases.

The benefits of research into rare diseases, including impact on the understanding of common conditions such as obesity and diabetes, are emphasized, and set against the ‘orphan’ status of most such conditions, where pharmaceutical research is low because of the very limited market for each disease. There has already been some recognition of this, with initiatives intended to drive research in this area; the EC has recently joined with the European Medicines Agency and the US Food and Drug Administration to produce a common application form to gain obtain 'orphan status' for drugs for rare diseases [News in brief, BMJ 2007;335:1174 (8 December)]. The consultation document notes that rare diseases are also orphans with respect to health policies, partly because of the way their significant contribution to morbidity and mortality is masked in healthcare information systems by the absence of appropriate classification systems. In some cases relatively common conditions such as autism or epilepsy can mask an underlying rare disease, such as Fragile X Syndrome or tuberous sclerosis, respectively.

The document calls for a global approach to prevent significant morbidity or premature mortality, where feasible, and to improve quality of life or socio-economic potential of affected individuals in member states as far as possible, by improved and equitable systems for the timely identification and treatment of rare diseases, and provision of relevant information to patients and their families. It proposes that this may be achieved by:

  • Strengthening the cooperation between EU programmes including Public Health Programmes, Framework Programmes for Research and Technological Development, and the Orphan Drugs strategy
  • Encouraging EU Member States to develop national health policies to ensure equal access and availability of prevention, diagnosis, treatment and rehabilitation for people with RD.
  • Developing and sharing common policy guidelines in Europe

and states that there “is probably no other area in public health where the collaboration between the 27 different national approaches can be as efficient and effective as RD”. Fourteen specific questions relating to these objectives are posed, with responses requested by 14 February 2008.

News story   |   By Dr Maria Adams   |   Published 12 December 2007

Cancer researchers from Asia attending the International Union against Cancer (UICC) symposium in Nanjing, China in November, have developed plans for a regional network to share data on cancer epidemiology and prevention. As reported in the journal Nature, the Asian Cancer Registry and Information Network, as it will be called, is intended to house data from cancer registries in countries in an area that spans from the Philippines to Turkey. Although many of these countries have national registries already, lack of standardisation makes it impossible to compare the information they contain.

The network is reportedly applying for ¥60 million (US$542 000) over 3 years to create the first regional centre in Japan. As well as holding standardized data for epidemiological research, cancer risk assessment and prevention planning, the network will provide an opportunity to investigate why some cancers occur more commonly in some Asian nations than others and identify Asian-specific genetic sequences that affect the reactions to particular drugs. The organizers also hope that the network will help to build international cooperation in this historically divided region. "Most of the data used in cancer studies are from Westerners,” says Sumio Sugano, a genomics specialist at the University of Tokyo. “This is a chance to use Asian data.”

News story   |   By Dr Philippa Brice   |   Published 6 December 2007

A new report from the Muscular Dystrophy Campaign, a UK charity, presents evidence that “patients with neuromuscular diseases are faced with a fragmented, sub-standard system of care, with significant variations in survival across the UK” (see press release). The majority of neuromuscular diseases are inherited, genetic forms, including Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Charcot-Marie-Tooth disease, and myasthenia gravis.

The new report, Building on the Foundations: Establishing a Specialist Neuromuscular Service across England, notes that the average survival of DMD patients ranges from 18 years in the South West and 30 years in the North East, with serious inequality of access to specialist services for patients from different regions. The report also says that some patients do not receive an accurate genetic diagnosis or advice on risk of disease in future pregnancies, citing the example of a patient who only discovered that he had BMD when he attended a specialist centre for the first time more than ten years after becoming ill, and found that contrary to earlier medical advice that his condition was not hereditary, his two daughters were both carriers for the disease.

Report co-author Professor Mike Hanna of the Institute of Neurology commented: "Too often specialist care is vulnerable and heavily dependent on a handful of leading clinicians with a research interest in this field, rather than embedded in a properly resourced, long term service". The Muscular Dystrophy Campaign is calling on the Department of Health to provide adequate specialized service provision via multi-disciplinary teams to all patients with neuromuscular diseases.

News story   |   By Alison Hall   |   Published 5 December 2007

The Human Genetics Commission (HGC) has published More Genes Direct: A report on developments in the availability, marketing and regulation of genetic tests supplied direct to the public. This document builds upon the recommendations made in an earlier report Genes Direct which was published in 2003, the year after regulations implementing the In Vitro Diagnostic (IVD) Directive into UK law were enacted. These recommendations include developing an independent system of pre-market review to ensure that genetic tests offered direct to the public satisfy requirements for clinical validity and clinical utility, supported by a code of practice and appropriate educational initiatives.

At the time of the publication of Genes Direct, the HGC acknowledged that few genetic tests were being offered to the public. That situation has now changed. More Genes Direct (Appendix A) lists a range of tests that are currently offered ‘direct-to-public’ (via a non-medical intermediary) and ‘direct-to-consumer’ (without an intermediary between consumer and test provider). It also draws upon a meeting organised by the HGC in 2007 to make a series of consolidated recommendations. The HGC reiterates its call for a proportionate response, which falls short of an outright ban upon direct genetic tests (unlike other jurisdictions such as Switzerland and France, which have introduced statutory prohibition), concluding that most genetic tests that provide predictive health information should not be offered as direct genetic tests. However, it suggests that a pre-requisite for allowing such tests is to introduce a new offence of misuse of genetic information.

The HGC also presses for review of the classification system, which currently deems most genetic tests to be ‘low risk’, and for an alternative regulatory mechanism to be considered for lifestyle tests that currently fall outside the IVD directive. Because of the information that they are likely to yield, the HGC recommends that certain tests should only be made available via a health professional. For this category of tests, direct to public advertising should be restricted. Multiple stakeholders should be encouraged to develop a code of practice that takes account of guidance from the OECD and relevant international standards.

Comment: A proportionate regulatory approach, which takes account of both the seriousness and complexity of the information that a genetic test may yield, offers a pragmatic solution to the regulation of this complex area. However some commentators have questioned whether a methodology that builds upon genetic exceptionalism and additional regulation is the most effective strategy and that a better use of existing regulatory structures might suffice.

News story   |   By Dr Philippa Brice   |   Published 4 December 2007

A US gene therapy trial of a treatment for active inflammatory arthritis (including rheumatoid arthritis) has been given permission to resume after a Food and Drug Administration (FDA) hearing concluded that the death of a trial participant in July this year (see previous news) was due to a fungal infection completely unrelated to the gene therapy. There was concern that the immunosuppression induced by the delivery of the therapeutic DNA (encoding the TNF-alpha receptor), in combination with the subject’s current arthritis medication, might have contributed to the death, and the trial was suspended while investigations were carried out.

A meeting of the federal Recombinant DNA Advisory Committee (RAC) held on 3rd December at the National Institutes of Health (NIH) has reviewed the death and also concluded that it was unrelated to the gene therapy treatment, but suggested that the design of the study is altered slightly, to include more haematological monitoring of participants and greater care to exclude any with signs of current infection or a history of opportunistic infections for treatment. They also noted that more information should be sought on the potential effect of immunosuppressant drug treatment on risk.

The phase I/II clinical trial will continue with some modifications; of the 35/127 patients due to receive a second dose of the gene therapy agent, all will be informed of the death of the trial participant and any with a raised temperature will not receive the therapeutic (see press release).

Keywords : Gene Therapy

News story   |   By Dr Maria Adams   |   Published 4 December 2007

Researchers believe they have made an important insight as to why malaria results in mild, flu-like symptoms in some individuals but causes death in others. The answer might lie in the interaction between the infected human and the parasite Plasmodium falciparum, which causes the disease (see news report).

Each year there are an estimated 350–500 million cases of malaria worldwide, causing over one million deaths, most of them young children in sub-Saharan Africa. According to figures released by the World Health Organisation (WHO), in some countries with a heavy malaria burden, the disease may account for as much as 40% of public health expenditure, 30-50% of inpatient admissions and up to 60% of outpatient visits.

Despite the immense health implications, the reason why some people are affected more severely than others is unknown. Earlier in vitro studies of P. falciparum failed to identify differences in gene expression between strains, but a recent study published in the journal Nature [Daily JP et al. (2007) Nature Nov 28; Epub ahead of print] indicates that gene expression in the parasite as it circulates in the bloodstream depends on interaction between the parasite and its human host.

The researchers analysed blood samples from 43 patients in Senegal. Analysis of P. falciparum in these samples identified three distinct gene expression profiles. In one group of patients it appears that parasites are likely to utilise substrates such as glycerol and lactic acid in the patient's blood as an energy source. Parasites in this group also shows strong induction of genes encoding proteins involved in invasion pathways. In the second group, parasites are likely to utilise glucose and oxidative phosphorylation, whereas P. falciparum gene expression in the third group is indicative of a stress response. Notably, patients in this third group had a longer duration of illness, higher body temperature and elevated markers of inflammation.

Although the authors do not know what causes these three distinct patterns of gene expression in P. falciparum from patients, if the distinct profiles represent persistent physiological differences, they might indicate potential therapeutic approaches to control malaria.

Typically, P. falciparum is grown in vitro under glucose-rich conditions and in a relatively low oxygen concentration; in these conditions the parasite depends on anaerobic glycolysis for energy. This new study demonstrates the importance of studying organisms in a more natural environment (i.e. a human host) in order to identify physiologically relevant mechanisms and potential therapeutic approaches.  

News story   |   By Dr Philippa Brice   |   Published 3 December 2007

The Nuffield Council on Bioethics has published a new report and policy recommendations, Public health: ethical issues, which examines “the responsibilities of governments, individuals and other parties, such as the food and drink industry, in achieving a healthy society” (see news article).

The report is has been produced by a Working Group and incorporates material from a workshop, public consultation (see previous news) and stakeholder meetings held over the past three years; it concludes that both the state and relevant industries have a duty to promote good health throughout society, and makes recommendations for policy development in four key areas: infectious disease, obesity, alcohol and tobacco, and water fluoridation.

The report sets out what it terms a ‘stewardship model’ for appropriate state intervention to promote public health, stopping short of coercion of adults to lead healthy lives and minimising interventions that are  “introduced without the individual consent of those affected” or “perceived as unduly intrusive”. At the same time, it notes the multi-factorial origins of disease, including genetic and socio-economic factors, and warns against an overemphasis on individual behaviour as the causative factor in ill-health.

The report emphasises the importance of reliable evidence on both the causes of ill health and the efficacy and effectiveness of interventions, saying that “evidence should be based on peer-reviewed research” and claims of absolute safety or certainty should be treated with caution. With respect to genetic research relevant to public health, the report stresses that accurate reporting of evidence is of particular importance “given the potential for adverse consequences on population health”, and states that all those who report or communicate research findings have a duty to do so in a responsible manner, identifying the source and status of information; it also commends “initiatives that provide independent information that is accessible to the public on the accuracy and reliability of medical stories reported in the media”.

Keywords : BioethicsPublic Health

Research articles

Research article   |   By Dr Caroline Wright   |   Published 18 December 2007

In classical genetics, two copies of each gene are expressed from the autosomal chromosomes, one maternal and one paternal in origin. As a result, recessive diseases only manifest when two copies of the disease gene are present, inherited from parents who are both carriers. In some cases, however, only a single copy of a gene is expressed, which can have huge implications for an individual’s vulnerability to disease, as any mutation in the single active copy will act like a dominant trait. When silencing of just a single allele is correlated with the parent of origin, this phenomenon is known as imprinting. It is mediated by epigenetic changes to the DNA – methylation of specific cytosine residues – resulting in heritable silencing or activation of a particular gene from one parent only. Despite predictions that around 1% of human genes are imprinted, identification of these genes is complex and precise imprinting patterns remain elusive.


In recent work published in Genome Research, researchers use computational modeling to predict the genome-wide imprint status of human genes directly from the sequence [Luedi, P.P.  et al. (2007) Genome Res 17:1723-1730]. The predictive algorithm was developed using 40 known human imprinted genes and multiple known or putative non-imprinted genes. Applying this algorithm to the entire human genome, they identified over 150 novel human imprinted gene candidates with high confidence, scattered across the genome, each with assigned parent of origin. Two of these genes were subsequently verified experimentally: KCNK9, a maternally expressed oncogene implicated in epilepsy and bipolar disorder, and DLGAP2, a paternally expressed potential tumour suppressor gene linked with bladder cancer. The authors went on to investigate the conservation of imprinting across different species. Interestingly, a comparison of imprint predictions in humans and mice revealed that less than 40% of the genes were imprinted in both species, which may have important ramifications for the use of laboratory animals as disease models and for environmental risk assessments.


Comment: Although parent-of-origin effects have been known for centuries (probably first observed in mules, the offspring of a female horse and a male donkey), a detailed understanding of genomic imprinting is still lacking. This study makes an important contribution to this growing field, firstly by demonstrating that the imprint status of a gene can be predicted from its sequence, and secondly by identifying multiple candidate imprinted genes.

Research article   |   By Dr Caroline Wright   |   Published 10 December 2007

It has been a good year for stem cells. Following the Nobel Prize for Physiology and Medicine (see previous news article), and the production of stem cells from human skin (see previous news article), scientists have now provided a conclusive demonstration of their huge therapeutic potential. Reported in the online advanced edition of Science, a humanized sickle cell anaemia mouse model has been successfully treated with a combination of gene and cell therapy [Hanna J. et al (2007) Science doi: 10.1126/science.1152092].


The method follows on from a series of studies showing that human, monkey and mouse skin cells can be developmentally reprogrammed in vitro into induced pluripotent stem cells (iPS), by using a retrovirus to insert four transcription factor genes into the cells. These cells have the capacity to differentiate into any of the specialised cell types present in the body. The cells can also be genetically reprogrammed in vitro using gene therapy in order to correct any disease causing mutations, and then differentiated into the appropriate cell type before transplantation back into the patient. As these cells can be taken from the patient, they have huge potential for therapeutic use by avoiding issues of immune-mediated tissue rejection.


The technique was tested on so-called ‘knock-in’ mice, in which mouse haemoglobin genes were replaced with human counterparts, with the homozygous sickle cell anaemia variant that causes the mice to exhibit typical symptoms of the disease. Skin cells were removed from the mice and reprogrammed into iPS. The sickle cell mutation in the genome of these cells was then corrected by gene targeting, and the cells differentiated into haematopoetic (blood) progenitor cells before being transplanted back into the mice. After 12 weeks, around 70% of the peripheral blood cells present in the mice were derived from these iPS cells and the red blood cell count had returned to within the normal range with significantly fewer misshapen cells. Problems with renal function associated with sickle cell anaemia were also substantially ameliorated by the treatment.


Comment: This study underlines the therapeutic potential of stem cells combined with gene therapy, whilst avoiding any tricky ethical entanglements by using iPS instead of embryonic stem cells. However, before this technology can be trialled in humans, the technique must be refined to avoid using an oncogene (c-Myc) for reprogramming and a retrovirus for introducing the transcription factors genes, in order to lessen the risk of cancer with the current approach.