In the news

An international group of ethical and legal experts has made recommendation for stem cell research intended to promote data sharing and prevent legal barriers to medical advances. 

The Hinxton Group has made five key recommendations with respect to human embryonic stem cells and induced pluripotent stem cells:

The group says that their recommendations are intended to ‘uphold overriding societal goals’ by promoting global justice and human dignity in seeking to ensure that the medical benefits of stem cell research are made widely accessible. These are worthy aims – but someone also needs to produce a plan for how the financial investment in commercial research can be justified, if patent protection were to be relaxed for such stem cell discoveries and products. 

Initial results from late stage clinical trials suggest that a new cancer drug could have a significant impact on survival rates. 

The drug, known as RG7204, has just completed its phase III clinical trial, which is the final stage before a drug is made generally available to patients. The drug blocks a mutated form of the BRAF protein that is found in half of melanomas and which is responsible for tumour growth and metastasis (spread throughout the body). Patients treated with RG7204 survived longer and had slower growing tumours. It was so effective that participants in the control group who had been receiving standard chemotherapy have now been offered treatment with the new drug instead.

Malignant melanoma is the most aggressive form of skin cancer, and until now has had very few effective treatments after metastasis. Typically, fewer than one in four people survive one year after diagnosis with advanced disease. The new drug is not authorised for general use yet, and so currently remains available only to patients in clinical trials. The full results from the trial will be presented later this year however, and assuming these bear out the preliminary results – given the lack of other options and low survival rate of patients - the drug could very quickly be approved for use in clinics. This is another example of new 'personalised' medicines that are effective in a subgroup of patients whose tumours have particular genetic features.

New data suggests that more than 100,000 people at high risk of the common genetic condition familial hypercholesterolaemia (FH) have not been offered diagnostic testing. 

FH is genetic and there is a high chance that close family members of people diagnosed with the condition may also be affected. Clinical guidance recommends that genetic and cholesterol testing should be offered to them (an approach known as cascade screening). Diagnosis of FH is important because management with cholesterol-lowering medication, lifestyle and dietary advice can prevent the early onset of serious cardiac disease and premature death. An audit by the Royal College of Physicians found that 85% of hospital trusts could not access funding for FH genetic testing, leading to the estimate of 100,000 undiagnosed across the UK. 74% did not offer any paediatric FH services. British Heart Foundation medical director Professor Peter Weissberg said: "It's long overdue that familial hypercholesterolaemia services come up to scratch to stop lives across the UK being needlessly lost". 

The need for improved and more equitable access to genetic testing and services for families with forms of inherited cardiac conditions across the UK was identified in a PHG Foundation report (see previous news), with recommendations for the development of specialist services. Though moves have been made in the right direction, clearly there is plenty still to be done to make the most of existing, cost-effective genetic testing to improve population health.  

The Leopoldina, Germany's national academy of sciences, has released a new statement supporting the use of preimplantation genetic diagnosis (PGD) to prevent the birth of children affected by serious genetic diseases.

Hitherto, it has been presumed that PGD is not permissible under embryo protection laws, but in 2010 the federal supreme court ruled that this was not the case. A Leopoldina working group has agreed with this finding, concluding that as healthy embryos are not harmed by the procedure then it is exempt, and should be allowed for serious and incurable hereditary diseases such as Duchenne Muscular Dystrophy and Fragile-X Syndrome (for which termination of affected pregnancies is also legal). They call for the establishment of a suitable regulator to ensure that PGD is used appropriately.

This statement follows on from a report on the use of predictive genetic testing released by the Leopoldina last year (see previous news) and serves to further emphasise Germany’s moves to distinguish clearly between the use of genetic testing for serious medical conditions, and for more trivial purposes. The German parliament is likely to vote on the regulation of preimplantation genetic diagnosis later this year. 

The number of disorders included in the standard newborn screening panel in the United Arab Emirates (UAE) has increased from five to sixteen, it has been reported.

The Ministry of Health said that the national newborn screening programme would be further expanded next year to include testing for a total of 30 conditions. Maternity and Childhood Central Administration Director Dr Hajar Al Hosani said that the programme has covered 98% of all newborns in ministry hospitals to date and has successfully identified hundreds of serious genetic diseases; she also advised parents to consider pre-conception screening for recessive genetic disorders.

New technical developments are making it increasingly cost-effective to provide newborn screening for increased numbers of rare genetic disorders (see previous news), and many countries are expanding their programmes with conditions relevant to their populations. The difficulty is sometimes in determining whether early diagnosis is beneficial – if there is no clear clinical advantage, is it still worthwhile in preventing unnecessary clinical investigations, and to inform parental reproductive choices? 

The French government is to debate whether or not current laws prohibiting any research on human embryos or human embryonic stem (HES) cells should be eased.

A 2004 amendment to the law made it possible for researchers to gain special dispensation allowing them to use material from superfluous embryos created for in vitro fertilization (IVF) for important projects aimed at understanding or treating serious diseases. Now there is reportedly mounting pressure for the government to create clear regulation allowing such research without the need for legal dispensation. 

The argument that a clearer regulatory structure is required to encourage international collaborative research and investment, as well as to clarify the position for French researchers, is sound. However, it remains far from clear how acceptable a change in the law to regularise the use of human embryonic material for medical research will be.

The Human Fertilisation and Embryology Authority (HFEA) is seeking opinions on various aspects of sperm and egg donation by 8th April 2011, to shape future UK regulation in this area.

Views are sought on the ethical acceptability of issues ranging from reimbursement and benefits for donors, to increasing the current limit of a maximum of ten families from a single sperm donor. The HFEA is also considering whether to regulate donation within families, which can raise additional ethical concerns. For example, donation from the sister of an infertile woman is rarely considered controversial – though there are worries that family members might come under pressure to donate – but from a mother to a daughter or a father to a son (or vice versa) can cause more debate.  

It is suggested that situations that are further removed from those that might occur legally and without artificial intervention cause the most public unease. The HFEA proposes options such as prohibiting the mixing of sperm and eggs between close genetic relatives, or going further and prohibiting the mixing of sperm and eggs between any close relatives, such as would be prohibited from sexual relations by incest laws. As technology advances and more things become possible, debating the ethical issues of what society considers desirable, or even acceptable, becomes increasingly important. 

Research undertaken in the US suggests people  are willing to pay for predictive tests for their risk of developing certain diseases, even where there is no prevention or cure available.

 Research undertaken in the US suggests people  are willing to pay for predictive tests for their risk of developing certain diseases, even where there is no prevention or cure available.

Researchers at Tufts Medical Center devised an imaginary situation in which almost 1500 participants were told they had a 10 or 25% risk of developing Alzheimer's disease, arthritis, breast cancer or prostate cancer, and then asked whether they would pay for a predictive test. They found that respondents would be willing to pay an average of between US$320 and $622 for a test, depending on the disease, their risk estimate, and the reliability of the test. Overall levels of willingness to have predictive testing were high, ranging from 70% to 88%.A positive test would reportedly be likely to prompt re-evaluation of priorities, with respondents saying they would spend more time with their families, sort out their personal finances or maybe even travel more.

The survey suggested that in theory people were surprisingly willing to not only undergo but also pay for predictive disease testing for serious adult-onset conditions. One possible flaw is that most people are aware that for some of the diseases in question there are preventative and treatment options (e.g. for breast cancer); however, the majority said they favoured prediction even for Alzheimer’s disease. One motivation cited for testing was reassurance, suggesting respondents expected a negative result. Of course, there are in practice very few perfectly predictive tests, even for genetic diseases, so that providers offering tests for serious diseases should ensure that people have access to robust pre-test counselling that sets out the full implications of a positive result. Of interest, most respondents also reported they would share information with families and did not seem to be concerned with where their testing data went.

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The chair of the Human Fertilisation and Embryology Authority (HFEA), Professor Lisa Jardine, has spoken out against any future attempts to repeal the current legal protection for human embryos.

The Human Fertility and Embryology Act enshrines this status and requires special regulation of all medical uses and research involving human embryos, with licences granted only for important applications where alternatives (such as animal embryos) are not feasible. This oversight is currently provided by the HFEA – although an announcement last year revealed that the HFEA was to close, with transfer of its regulatory functions to other bodies (see previous news).

The Academy of Medical Sciences (AMS) today released a new report recommending changes to speed up the approval process for health research applications amid concerns that excessive regulation is impeding scientific progress (see previous news). The new overarching Health Research Agency (HRA) proposed by the review would assume the function now performed by the HFEA in governing research involving human embryos.

Before this review was published, HFEA Chair Professor Lisa Jardine told the Guardian newspaper: "My worry is that to achieve a consistent approach to research licensing, the safeguarding of the 'special status of the embryo' will be lost…I very much doubt that the general public, let alone those groups who are fundamentally opposed to such research on moral grounds, would wish to see this happen without full debate".

Opponents fear that the special status of such embryos, whilst currently protected in law, could be compromised in the long-term if the proposed new regulator had a conflict of interest by way of a mandate to increase research application approvals.

A new report to the UK government by the Academy of Medical Sciences (AMS) has set out proposals for a new overarching regulatory body for health research.

A new pathway for the regulation and governance of health research is the result of an inquiry led by Sir Michael Rawlins, who said they had found “unequivocal evidence that health research in this country is being jeopardised by a regulatory and governance framework that has become unnecessarily complex and burdensome” coupled with a lack of evidence for increased safety for research subjects as a result of this regulation.

The report recommends that a new independent Health Research Agency (HRA) be established with two key, integrated national functions: research governance and ethics approval, including specialized forms of research ethics regulation. The new HRA would incorporate the functions of multiple existing regulatory groups previously listed as facing closure (see previous news), including the Human Fertilisation and Embryology Authority (HFEA), Human Tissue Authority (HTA) and Gene Therapy Advisory Committee. The aim would be to substantially reduce the regulatory burden and delay imposed by current arrangements for medical research – for example, the necessity to obtain approval from multiple individual health trusts for large multi-centre studies, or from multiple – reducing average approval time from years to months.

Other key measures outlined in the report include an improved UK environment for clinical trials, calling for the proposed HRA to work with the Medicines and Healthcare Products Regulatory Agency (MHRA) in this area, and for efforts to reform the 2004 EU Clinical Trials Directive. The AMS group also calls for a new approach to accessing patient data for research purposes that balances individual protection and public benefit, and for measures to create and embed a new culture that values health research within the National Health Service (NHS).

Health Secretary Andrew Lansley MP said that the Government welcomed the report and would consider carefully how to implement the recommendations, whilst Minister of State for Universities and Science David Willetts commented: “As the government works to rebalance and grow the economy, it is vital that the UK continues to be an attractive environment to undertake clinical trials”.  

The US-based company Sequenom has said it will begin a clinical validation study for a non-invasive prenatal test for Down’s Syndrome (trisomy 21) this month.

Sequenom CEO Harry Hixson said it was "an important step in confirming the trisomy 21 test performance in a large sample cohort" following positive results from a recent verification study. The SensiGene T21 test uses next-generation sequencing technology combined with the technique for identification and analysis of fetal DNA from the mother’s blood pioneered by Professor Dennis Lo of the Chinese University of Hong Kong; Sequenom holds much of the intellectual property (IP) rights for the commercial use of this method. Market launch of an earlier test for trisomy 21 (SEQureDx) by the company, originally due in 2009, was delayed - to the frustration of clinicians and patients around the world - and it appears to have been superseded by the current version. 

Professor Lo continues to develop the innovative technique for new applications (see previous news), and the future for safe, early prenatal diagnosis looks bright. Hong Kong has a growing reputation for genomic research and development, thanks both to internationally renowned individuals and facilities, not least the Beijing Genomics Institute (BGI) genome sequencing centre based there. BGI Hong Kong, R&D centre for theShenzhen-based BGI, will reportedly have the capacity to sequence 1,300 human genomes a day. 

A 6-year old boy has undergone a life-saving bone marrow transplant following diagnosis by DNA sequencing.

The boy, suffering from an aggressive inflammatory bowel disease, had been through over 100 surgeries over the previous 3 years with very little success. The doctors treating him at the Medical College of Wisconsin had been unable to make a firm diagnosis of his condition, and were thus unable to determine whether a risky bone marrow transplant would be beneficial. They decided to sequence the patient’s exome (the active genes within the genome) in order to search for rare single gene mutations with a frequency lower than 1% in the general population, since more common disorders had been ruled out. They found a mutation in the XIAP gene that had not previously been known to cause the Crohn-like symptoms exhibited by the patient. The sequencing approach they used was not a clinically validated test at the time.

Further tests based on the diagnosis indicated that the boy had a high probability of death if untreated, and this led to the decision to perform the transplant. The child’s parents were counselled for several hours prior to the test being administered, to ensure their awareness of the risks of ‘off target’ or unexpected results, i.e. the uncovering of further conditions that had not thus far been identified. The treatment is reported to have been very effective and the doctors involved say that this is a major step in DNA sequencing’s advancement from a research tool to a clinical one; they point out that the tools used to make the diagnosis were not available when the child first presented 4 years ago. A further 30 patients at the hospital have now been put forward for ‘sequencing treatment’. Clinical applications of exome sequencing capitalising on the increasing speed and affordability of next-generation sequencing are multiplying rapidly (see previous news); the PHG Foundation is currently engaged in a major review of the wider implications of this trend.

US Commentators have expressed concern that the government should avoid overly oppressive regulation of genetic tests, including direct-to-consumer services, lest it stifle innovation.

Writing in the Health Affairs blog, Ronald Weiss emphasizes that genetic tests are not a single entity, and hence require different forms of regulation depending on their nature, purpose and application. Notably, he makes the distinction between tests administered by clinicians and those delivered direct-to-consumer, fearing that attempts to curb the latter - said to represent under 1% of all clinical laboratory testing in the US - may have an adverse impact on the former.

Joshua Lipson expresses similar concerns and notes that consumers of personal genomic testing typically ‘self-selects for education and scientific skepticism’ and does not require excessive protection. Recent surveys suggest generally high levels of satisfaction among customers (see previous news); however, this is not to say that DTC testing cannot have risks if customers fail to understand the meaning and limitations of results.

Meanwhile, one of the leading providers such testing, 23andMe, is reported to be considering new pricing structure for 2011 in an attempt to encourage new customers (see GenomeWeb). The Personal Genome Service is currently offered for US$199 plus a monthly subscription fee, a drop from an initial price of $999 when launched in 2007; last month it was on special offer at $99. This may indicate flagging consumer uptake, or attempts expand their operations into new markets. 

Researchers at the University of New South Wales (UNSW) performed a randomised survey of more than 1000 adults for their attitudes towards genetic testing for depression. This is a complex disorder involving multiple genetic and environmental factors and tests for genetic predisposition are unlikely to have significant predictive value. Moreover, whilst prompt diagnosis and treatment of clinical depression is beneficial, interventions to prevent the condition developing in unaffected adults are unlikely to be useful.

Interest was greatest among those with a personal history or perceived increased risk of depression, coupled with a belief that testing might improve prevention or prompt treatment. 63% of those interviewed indicated interest in genetic tests for depression if performed via a clinician, and 40% for direct-to-consumer testing. The most common concerns were of discrimination from health insurers or employers.

Study lead Dr Alex Wilde commented: “The findings are surprising given that we also found widespread belief that genetic links to mental illness would increase rather than decrease stigma and also because the validity and utility of the testing is still in question”. She called for legislation to prevent genetic discrimination in Australia, calling European and US laws ‘inadequate’.

This sort of study does highlight key concerns about DTC genetic testing – that people may infer incorrect conclusions based on results, and that disclosure of results could result in discrimination. However, as this survey was purely on attitudes towards testing it is rather limited; it would be more useful to study the actual impact of people having such tests, rather than rushing to legislate against potential harms. For example, a recent study found only 5% of those who had paid for personal genomics testing had misinterpreted the results (see previous news). 

The Challenge of Feeding Scientific Advice into Policy-Making

Schenkel R. Science. 2010 Dec 24: 1749-1751.

Policy-making needs science

Alberts B. Science. 2010 Dec 3;330(6009):1287.

Genomics, type 2 diabetes, and obesity.

McCarthy MI. N Engl J Med. 2010 Dec 9;363(24):2339-50.

Intellectual property. Turning patent swords into shares.

Van Overwalle G. Science. 2010 Dec 17;330(6011):1630-1. 

Network medicine: a network-based approach to human disease.

Barabási AL, Gulbahce N, Loscalzo J. Nat Rev Genet. 2011 Jan;12(1):56-68.

Sickle-cell disease.

Rees DC, Williams TN, Gladwin MT. Lancet. 2010 Dec 11;376(9757):2018-31.

Genetics. First-class control of HIV-1.

McMichael AJ, Jones EY. Science. 2010 Dec 10;330(6010):1488-90

Pharmacogenomics: will the promise be fulfilled?

Altman RB et al. Nat Rev Genet. 2011 Jan;12(1):69-73.

On synthetic biology

Lancet. 2011 Jan 1:377(9759):2.

NDM-1- a cause for worldwide concern.

Moellering RC Jr. N Engl J Med. 2010 Dec 16;363(25):2377-9. 

Personal genomes: no bad news?

Chadwick R. Bioethics. 2011 Feb;25(2):62-5

Progress and Promise of Genome-wide Association Studies for Human Complex Trait Genetics

Stranger BE, Stahl EA, Raj T. Genetics. 2010 Nov 29. [Epub ahead of print]

Newborn screening conditions: What we know, what we do not know, and how we will know it.

Levy HL. Genet Med. 2010 Dec;12(12 Suppl):S213-4.

Modifier genes in Mendelian disorders: the example of cystic fibrosis.

Cutting GR. Ann N Y Acad Sci. 2010 Dec;1214(1):57-69. 

Factor V Leiden thrombophilia.

Kujovich JL. Genet Med. 2010 Nov 24. [Epub ahead of print]

Leprosy and the human genome.

Misch EA et al. Microbiol Mol Biol Rev. 2010 Dec;74(4):589-620.

Revealing the Dark Matter of the Genome

Blaxter M. Science. 2010 Dec 22. [Epub ahead of print]

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