In the news

The final regulations relating to the US Genetic Information Nondiscrimination Act (GINA) on employment have been published, and will come into effect in January 2011.

The GINA (see previous news) prohibits discrimination on the basis of genetic information in the areas of insurance (including health insurance) and employment. Now the Equal Employment Opportunity Commission has released final regulations clarifying the precise provisions of the Act with respect to employment, taking effect from 10th January 2011. Broadly, employers are not permitted to request or demand genetic data from current or prospective employees, or to use in employment decisions or make public genetic information, or to take action against an employee who uses the GINA legislation to object to or block requests or actions by the employer.

The Department of Health and Human Services is reportedly also preparing a similar clarification with respect to genetic information and health insurance. 

PLoS Currents is an open-access publication forum for very fast dissemination of new research, intended to reduce the traditionally very lengthy process of submission, peer review and publication to the absolute minimum. The advantage of this initiative is to allow rapid sharing of research findings with appropriate scrutiny and review from relevant experts, whilst ensuring that the work is citable, archived in PubMed Central, and searchable in PubMed.

PLoS Currents: Evidence on Genomic Tests provides reviews and summaries on the validity and utility of genomic tests and applications, and aims to highlight gaps in current knowledge. This is a very valuable endeavour since this sort of information has no central repository and can be surprisingly difficult to access. Genomic is used in the broadest sense, encompassing various forms of related diagnostics and applications such as proteomic tests.

PHG Foundation Director Dr Hilary Burton recently joined the editorial board for PLoS Currents: Evidence on Genomic Tests, joining editorsDavid Dotson and Muin Khoury of the Centers for Disease Control and Prevention in Atlanta, US and Katrina Goddard of the Kaiser Permanente Center for Health Research, Portland, US.

Dr Burton commented: “Evidence (most notably on the utility of genomic tests) can be difficult to gather, particularly in the context of rare disorders, where traditional large epidemiological studies are impossible. I hope that this venture will provide a valuable way of sharing evidence from experts around the world and building up our body of knowledge in order to improve population health. I am delighted to be joining this exciting enterprise, and look forward to bringing in the wealth of experience from our colleagues in the UK”. 

Plans to create the first Danish stem cell centre have been set out by the Danish Council for Strategic Research and the Novo Nordisk Foundation.

The planned new Danish Stem Cell Center, DanStem, will be based at the University of Copenhagen and will open from 2011, focusing on basic and applied stem cell research for diabetes and cancer therapeutics. The Danish Council for Strategic Research has provided DKK 65 million (€8.7 million) funding over five years, while the private Novo Nordisk Foundation has contributed an additional DKK 350 million (€47 million) over ten years for basic research. DKK 30 million has reportedly been allocated ‘to support national collaboration in order to ensure synergy with stem cell research at other Danish universities'.

Private co-financing was apparently agreed to be essential for this new venture and certainly, the input from Novo Nordisk dwarfs that from the Danish government. The success of this heavily commercially-subsidised model will be watched with interest by other countries considering how best to fund future research in stem cells and regenerative medicine. One key issue will no doubt be ownership of IP on potential new tools and therapeutics.

The first ever stroke patient to receive neural stem cell therapy has been treated in a Glasgow hospital.

This marks the beginning of the first clinical trial of its kind for stroke patients. The patient, described as ‘an elderly man’, has received an initial very low dose with the aim of assessing safety.  If his progress is found to be satisfactory when reviewed in December, the rest of the cohort of up to 12 patients will be treated shortly afterwards with progressively higher doses over the coming year. All of the patients are men over 60 with stroke disability who have shown no improvement in their condition over a number of years: This is in order that reactions to the treatment can be compared across patients who have similar profiles, and to reduce the likelihood that any observed improvement is due to spontaneous partial recovery. If the results of these trials are promising, then larger trials on more diverse groups of patients will be the next step.

Stroke is the third largest cause of death, and the single largest cause of disability in the developed world, and currently has no effective treatments following the acute phase of the first few hours. The trial is being carried out with the company ReNeuron Group, who claim that pre-clinical testing has indicated that the treatment is capable of reversing functional deficits associated with stroke disability. If this proves to be the case in this trial, then the impact could be enormous: in the UK stroke patients are estimated to occupy more than 25% of long term hospital beds and to present an annual cost in excess of £5 billion. The results from this trial will take some time to be known though; this initial phase is largely to test safety, and the efficacy phase with more diverse patients won’t take place for at least another two years.

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The US National Human Genome Research Institute (NHGRI) has announced plans to divert DNA sequencing research funding towards projects focusing on health applications.

NHGRI is the major publicly-funded human genome research body in the US, funding three sequencing centres. Plans announced at the recent annual meeting of the American Society of Human Genetics reveal that funding to these large-scale sequencing centres will be reduced as three new funding areas are established. These will be an initiative to identify and catalogue the mutations that cause rare genetic diseases; projects that will use DNA sequence data to direct patient management (see previous news for examples); and efforts to develop robust, general bioinformatics tools for analysing sequence data.

Although funding for basic sequencing research remains important, these moves to invest smaller amounts in preparing the way for the actual clinical benefits of human genome sequencing are vital. In the UK, the PHG Foundation is taking a similar approach, but looking at the wider barriers and drivers for application of whole genome sequencing for medical purposes, including logistic, economic, ethical, legal, social and regulatory considerations.

Germany's national academy of sciences Leopoldina has published a new report on predictive genetic testing.

Predictive genetic diagnostics as an instrument of disease prevention is the output from a working group of experts from Leopoldina, the Berlin-Brandenburg Academy of Sciences and Humanities and the German Academy of Science and Engineering Acatech. It considers not only medical but also ethical, economic and legal issues related to predictive genetic testing of healthy individuals, and sets out a range of recommendations.

There is an express rejection of eugenic principles such as ‘wanting to eliminate certain genes from all individual genomes of a population’. Recommendations include planning for the wider uptake of genetic testing within health services for patients with or at risk of ‘genetically determined and essentially treatable diseases’, including production of evidence relating to effectiveness and cost-effectiveness, development of medical guidelines for predictive genetic diagnostics, training for medical professionals, and expansion of newborn screening programmes. The report also calls for more basic and translational research into genetic contributions to complex diseases, and societal education about the ‘possibilities and limits of genetic medicine’, especially in schools.

Perhaps the most significant recommendations relate to a new German law on genetic testing (the Gendiagnostikgesetz) intended to protect against abuse of genetic information, which stipulates that the results of genetic testing and analysis should be expunged from medical records after ten years. Conversely, the report says that there should not be a set deadline, and that data should be stored for longer as it may be relevant to the future health of the patient or family members. Similarly, the report calls for amendment of the law’s definition of newborn screening as universal genetic screening, since this means that only doctors (not nurses or midwives) can obtain parental permission for testing, a situation thought not to be in the best interests of the newborns since it limits uptake (see press release).

In other respects the recommendations are highly conservative, calling for a ban on direct-to-consumer (DTC) services on that grounds that such tests ‘do not fulfil the requirements of medical and ethically acceptable predictive genetic diagnostics’ due to a questionable scientific basis and the lack of associated formal genetic counselling – despite the fact that this sort of counselling is not really required for tests with very low predictive ability such as those for common diseases. They also propose that genetic investigation of healthy individuals with no family history of serious disease should be confined to the research setting until the ethical and social implications have been more fully investigated.

Comment: In seeking to ensure that the benefits of genetic testing for individuals and families with serious inherited forms of disease are not limited, the report is a very positive step for German health policy. Vehement rejection of genetic testing for other situations may in some ways also be beneficial, in focusing attention on those with significant medical needs. However, in other respects it could be an over-reaction to perceived harms that are, in reality, highly improbable.

Lung cancer tumours in smokers have different mutations to those in non-smokers, it has been reported, suggesting that the disease may be fundamentally different between the two groups.

The findings were those of a pilot study presented at the 9th Annual Frontiers in Cancer Prevention Research Conference of the American Association for Cancer Research (AACR) earlier this week. The AACR press release reports that the researchers looked at both tumours and healthy tissue from 30 patients who had never smoked, and from 53 current or ex-smokers, and found that the never-smoker tumour genomes contained twice as many genome alterations as those of smokers and were of distinctly different types.  One of the researchers, Kelsie Thu, has said that these results suggest that the never-smoker tumours develop through different routes, could be more genomically unstable, and should perhaps be studied as a separate group.

These reported results are interesting, but it should be noted that the sample sizes in the study are relatively small, that the precise methods used and detailed results haven’t been disclosed, and that the work has not yet been either peer-reviewed or published. If however the reported findings are borne out by further and larger study, a more finely detailed understanding of the underlying biology of lung cancer in different patient groups could, as the researchers suggest, lead to improved detection rates and new and more specific therapeutic approaches for the cancer that has both the highest incidence and mortality rate in the UK and worldwide. 

The UK Open Access Implementation Group has resolved to take action in order to increase take-up of open access publishing amongst UK researchers.

The group - currently consisting of ten leading organisations from research and academia, including Universities, the UK Research Councils and the Wellcome Trust – concluded in a meeting at the Wellcome Trust that a persuasive summary of the key advantages of open access is needed.  They intend to “coordinate evidence, policies, systems, advice and guidance, to make open access an easy choice for authors”.

Open access refers to a publishing model whereby anyone can freely view the results of scientific research without requiring a subscription to the journal. Rather than readers paying to view the article, open access is usually funded by the author of the article paying to publish. Despite it being the stated policy of the UK Research Councils that all publicly funded research should be published in this manner, and provision for the publication fees being calculated into research grants, some scientists are reluctant to publish in open access journals because they feel that these lack the prestige and impact of the top traditional journals. The Implementation Group say that the evidence shows that open access is beneficial to all parties, and that they must now develop a practical plan make those benefits evident to researchers.

A new survey from the Genetics and Public Policy Centre at Johns Hopkins University has found that customers of direct-to-consumer (DTC) genetic testing companies are generally satisfied.

Researchers sought to understand the motivations, attitudes, responses and understanding of customers to further inform ongoing debate about the regulation of DTC genetic testing companies (see previous news). A random sample of 1,048 US customers of the three major companies offering personal genomics DTC (23andMe, deCODEme and Navigenics) were surveyed online between June 2009 and March 2010.

Early adopters of DTC genetic tests (who tend to be affluent and well educated) indicated that they were generally satisfied with the testing services. The top reason cited for pursuing testing was curiosity (94%), though 77% also pursued testing to help improve their health. Interestingly, 58% said they learned information that would help improve their health, and as a result of testing, 34% said they were being more careful about their diet and 14% were exercising more.

Despite the complexity of the information, and fears that people would be unable to understand their results, 88% of customers reported that their risk results were easy to understand, and only around 5% misinterpreted two example risk reports presented in the survey. Regarding regulation, around two-thirds of participants felt that such tests should be available without government oversight, although consumer protection agencies (such as the Federal Trade Commission in the US) should monitor companies’ claims for scientific accuracy.

This study provides long-overdue evidence that consumers are satisfied with DTC genetic testing services, and are generally able to interpret their results. It also indicates that there may be direct health benefits resulting from the tests in terms of behaviour modification.

Although long term follow-up is needed to investigate whether the behavioural changes cited are permanent or transitory, this survey indicates not only the absence of harm caused by DTC genetic testing services, but also the possibility of benefits. While it is unclear whether the results from these early adopters are broadly applicable to the general public, nonetheless the findings of this study concord with the PHG Foundation’s own recommendations regarding the regulation of DTC genetic services (see previous news). 

The first large-scale Arab population biobank is to be set up in Qatar, for research into common local diseases, notably diabetes, cardiovascular diseases and cancer.   

The Qatar Foundation for Education, Science, and Community Development and Qatar's Supreme Council of Health have announced that the new Qatar Biobank is to be established with expert assistance from Imperial College, London. It will collate biological samples and linked medical and lifestyle data from up to 100,000 participants and follow their long-term health outcomes to facilitate research into genetic and environmental causes of major diseases. The new biobank will be the largest population-based study of this kind in an Arabic country, recruiting Qatari and south-east Asian participants, and it is hoped that the data will form a valuable contribution to international biobanking efforts. An initial pilot phase will recruit 2000 participants, with plans to increase to 100,000 over six years.    

Dr Hanan Al Kuwari, Chair of the Qatar Biobank Steering Committee said that the facility would work closely with the government to identify health targets or areas for further investment, adding “This will enable Qatar not only to practice evidence based medicine but also evidence based public health".

The US federal government has said that patents should not be granted for genomic DNA (human or otherwise), on the basis that it is a product of nature, even when isolated from the body. 

The ground-breaking assertion reverses the previous situation whereby government bodies (along with everyone else) actively filed DNA patents wherever possible. It forms part of an amicus brief responding to the ongoing legal battle over US patents for the BRCA 1 and BRCA2 genes (see previous news), in which the US Justice Department supports the patentability of modified but not merely isolated DNA sequences. However, the US Patent and Trademark Office said it will be continuing to consider applications for gene-related patents as before.  

Critics fear that restricting the scope of gene patents will have a detrimental effect on biomedical development by limiting potential financial returns on investment in research. Others contend this is unlikely because the manipulation of genes (for example, to create novel gene therapies or biosynthetic organisms) would still be patentable. Commercial incentives for some applications such as diagnostic testing would certainly be restricted – many would argue, appropriately – to the precise testing method, and not to the DNA being analysed. 

An expert US group has concluded there is insufficient evidence to support genomic profiling for cardiovascular disease (CVD) risk prediction.

The EGAPP (Evaluation of Genomic Applications in Practice and Prevention) Working Group is a US panel that assesses the evidence about new genetic tests and applications (see previous news). Prevention of CVD is a public health priority, and in recent years new genomic and proteomic biomarkers – including those emerging from discoveries of genetic variants through GWAS - have been evaluated for their ability to improve current prediction methods based on traditional risk factors. The latest recommendation statement by EGAPP reviews currently available evidence, concluding that there is “insufficient evidence to recommend testing for the 9p21 genetic variant or 57 other variants in 28 genes to assess risk of CVD in the general population” [EGAPP Working Group, Genet Med. 2010 Oct 29, Epub ahead of print].   The EGAPP group found that the analytic validity of available genomic profiling tests for individual gene variants was potentially satisfactory, where available, but there was inadequate evidence available. Similarly, evidence for clinical validity was inadequate for 59% of the gene variant/disease associations tested. Only the association between the 9p21 variant and risk of heart disease was reasonably strong, but the improvement in risk prediction from testing for this variant was found to be ‘at best, small’. Overall, there was no evidence of health benefit from using such genomic profiling tests singly or in combination, so the group recommended against use in clinical practice unless new evidence of benefit emerges. 

CVD is an enormous public health issue.With genomic tests for CVD being available to the population through clinicians as well as direct-to-consumer, there need to be well established recommendations for cardiac risk assessments for both physicians and patients; this is a useful contribution to the confusing picture.  A PHG Foundation report released earlier this year, Predicting the risk of coronary heart disease with conventional, genetic and novel molecular biomarkers, similarly concluded that genetic and other biomarkers are in fact ‘unlikely to improve substantially our ability to predict the risk of CHD in individuals’ in the near future. However, risk prediction is a highly complex area, and new work due out soon has been considering the issue of how to reliably assess and compare the impact of risk prediction models, to allow accurate evaluation of how new data – such as genomic profiles – do or do not improve outcomes.

 A new Canadian initiative is seeking to promote the importance of science – and particularly publicly funded science – for the public good.

The Professional Institute of the Public Service of Canada, which includes science researchers and policy-makers, has launched Public Science, an online information service ’to underline the importance of science for the public good and to mobilize scientists and the public to press politicians to make a clear commitment to policies that support public science’. Key aims are apparently to showcase the public benefits of scientific endeavour, increase public support for research, and address what is referred to as a ‘worrying trend away from evidence-based policy-making’.  

Measures to explain the value and impact of publicly-funded science to the ultimate beneficiaries are an excellent idea, and ultimately could have a positive impact on understanding and support for evidence-based policy decisions – though policy development is of course a highly complex process that must take into account both the scientific evidence and a whole host of other factors besides, economic, social, logistic, political and many more. 

Realising the benefits of genetics for health.

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Regulating direct-to-consumer personal genome testing.

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Regulating direct-to-consumer genetic tests: What is all the fuss about?

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Being more realistic about the public health impact of genomic medicine

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The ethics of direct-to-consumer genetic testing.

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Ancestry and disease in the age of genomic medicine

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Human genome: Genomes by the thousand

Nature. 2010 Oct 28;467(7319):1026-7

Genomics: In search of rare human variants

Nielsen R. Nature. 2010 Oct 28;467(7319):1050-1. 

Genomics: The search for association.

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Epigenetic modifications and human disease.

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Stress and the epigenetic landscape: a link to the pathobiology of human diseases?

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Misleading communication of risk

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Genetics and genomics in general practice.

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Long shadow of the stem–cell ruling

Nature. 2010 Oct 28;467(7319):1031-3.

Stem-cell laws in China fall short
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Epigenetic drugs take on cancer
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Sustaining the data and bioresource commons
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Confronting real time ethical, legal, and social issues in the Electronic Medical Records and Genomics (eMERGE) Consortium.

Clayton EW et al. Genet Med. 2010 Oct;12(10):616-20.

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