In the news

The OECD has issued a new report examining policy issues surrounding the development and use of biomarkers in health, which it says ‘may improve patient welfare by delivering better health outcomes’ in the long-term.

It considers the different environments in which biomarkers are being development, the potential applications in health care (as tools for prediction, diagnosis and management of disease, as well as to improve the safety and efficacy of medicines) and the potential barriers to discovery, commercialisation and clinical uptake.

The report, which draws on strongly on previous work in on the evaluation of biomarkers led by the PHG Foundation, has six key conclusions:

Comment: The report highlights specific areas where it proposes that policy development can specifically support biomarker development and use in health systems. This sort of work can make a significant difference to our ability to capitalise on the science that drives biomarker discovery, in terms of improved health care. But who will fund such activities? Concerted action from multiple stakeholders including governments, health services, patient groups and charities is needed.

New projects are to investigate the genomics of chronic wound repair.

Chronic wounds are defined as those that have not healed within three months; such non-healing tissue lesions can be a particular problem in certain patient groups such as the elderly and diabetics, and also predispose hospital patients to infections.

The National Institute of Nursing Research (NINR) in the US has announced plans to provide around $2 million in funding for projects that will investigate the genomics of predisposition to and repair of chronic wounds. The aim is to find new ways of identifying those individuals most at risk of developing such wounds, and effective new interventions to treat them, possibly tailored to specific genetic features of different patient groups.

The call for applications outlines various areas of potential research, including underlying genomic and epigenetic mechanisms; development of new technologies to assess wounds (including bacterial infection) and deliver genome-based treatments; and assessment of the clinical utility of genome-based strategies for chronic wound management.

Comment: Chronic wounds are a significant health problem among the elderly, disabled, and other populations, so it will be very interesting to see whether genomics can offer any novel angles for tackling an old problem in this relatively new area of application. 

As the cost of DNA sequencing dives, the amount of sequence data available is soaring – yet it is ultimately meaningless without the capacity to manage and interpret it all.

The questions professionals are asking – and ones we highlight in our recent report - are where is the storage capacity for all that information, and how can it be shared across healthcare systems?

Sequencing informatics specialists are looking to the cloud for solutions. As part of a $15 million initiative with Google Ventures, DNAnexus will be providing a freely accessible website where researchers can download sequence read files, including all sequences from the 1,000 Genomes Project.

Dell is also supporting biomedical research, donating cloud computing technology, funding, and employee engagement to support a clinical trial of personalized medicine in the field of paediatric cancer research. The support is expected to speed computational processes, manage and store the resulting data, and provide a forum for analytics and collaboration.

A study of depressed people who have tried to take their own lives has revealed 43% of them share a specific variant of the gene RGS2.

The study was conducted by Dr John Mann, chief neuroscientist at the New York State Psychiatric Institute, on 412 Caucasians with major depression, 154 of whom had attempted suicide.

Dr Mann, who presented his findings to the Society for Neuroscience meeting in Washington DC, said further studies were needed to confirm the research, which has yet to be peer-reviewed.

The gene affects how strongly receptors in the body respond to chemicals released by nerve cells. It is among several that might ultimately be used to screen people with serious depression to identify those that need the closest supervision while being treated.

A new clinical trial in the US will investigate whether genetically targeted lung cancer treatments are more effective if used soon after diagnosis. 

National body the Alliance for Clinical Trials in Oncology, funded by the US National Cancer Institute, is leading the trial to determine whether such treatments could actually cure lung cancer if given earlier. Typically, drugs such as erlotinib, which targets tumours with mutations in the epidermal growth factor receptor (EGFR), are given to patients with suitable tumours if they recur after surgery. In the new trial, some patients will be given the drugs immediately after surgery to see if they have better outcomes. 

Although recruiting the required 400 patients is expected to be difficult, since patients must be diagnosed earlier than usual and with relevant tumour mutations to be eligible, this is an important conceptual trial. Alongside moves to improve tumour diagnosis, classification and targeted treatment, research to show how best to deploy these new developments for patient benefit is critical. 

Experts at the Clinical Oncological Society of Australia were warned last week that the country’s health system was failing to keep pace with the speed of discovery in genomics.

Speaking at the Annual Scientific Meeting, Dr David Thomas of the Peter MacCallum Cancer Center in Melbourne referred to the ‘quantum leap’ in genomics knowledge that had ‘fundamentally changed the paradigm of cancer care’, but warned that: “Obstacles to progress are no longer biotechnological, but relate to our restricted capacity to assess and make use of the knowledge…We need systemic change to create a system that can evolve as rapidly as genomic development so that new research can be integrated more quickly into clinical care".

He called for new interactions between the government, ethics committees, pharmaceutical companies, regulatory bodies, research funding bodies and the public to address this gap.

Meanwhile, Cancer Research UK (CRUK) has begun recruitment of cancer patients to trials that form part of their Stratified Medicine Programme, which aims to create a world-class genetic testing service for NHS cancer patients in the UK by identifying genetic tumour features that will allow the use of more effective targeted treatments. However, Director James Peach warned that: "This programme marks the beginning of the journey, and there is much to be done before we can bring the benefits of personalised medicine to every cancer patient".

Revised standards for the UK sickle cell and thalassaemia screening programme, which has been running for ten years, have been released.

Both sickle cell disease (also known as sickle cell anaemia) and thalassaemia are groups of related recessive genetic disorders that affect haemoglobin, the molecule in red blood cells that delivers oxygen.

The second edition of the standards, which applies to antenatal and newborn screening elements, includes new material on how the programmes are linked as well as on objectives, the evidence base for standards and performance indicators.

Of note, offering screening and counselling to the fathers of affected children has been identified as an area requiring more emphasis; conversely, the need to address issues arising from non-paternity was also highlighted. Parents of babies identified as carriers of the diseases (as opposed to affected by the diseases) are to receive more information.

The updated standards will take effect in the UK National Health Service (NHS) from April 2012. 

Research cuts are driving sequencing companies to take their machines into the clinic, according to an article in Nature.

As the US federal government reduces funding for research, with predictions for bigger cuts to follow, scientists are increasingly reluctant to fork out on big spend items, such as sequencing machines. Several makers of these machines are lowering their earnings forecast and laying off staff as a result.In a bid to get revenue back on track, many of these companies are looking to the clinic where whole genome sequencing is beginning to make inroads. Illumina, for example, will set up a business unit to promote the use of its tools in clinical diagnostics, and hopes that the imminent release of a lower-cost version of its MiSeq sequencing machine will boost sales. Life Technologies is touting a US$9-million deal to sell forensic-analysis systems in Russia, and underscored its double-digit growth in China, saying that it will increasingly turn its attention to Asia.

Most countries have reasonably protected budgets for scientific research, despite the recession, though it still makes sense for companies to look towards the Asian markets as a growth area. However, whilst the predicted move of genome sequencing into clinical application is an important development, health budgets in many countries may be more squeezed than research ones.

The news that stem-cell pioneers Geron Corp are ceasing all trials of stem cells to treat spinal cord injuries (see previous news) has received a mixed reception. Patient groups have expressed sadness and disappointment in the decision, which Fergus Walsh, writing for the BBC described as ‘extraordinary’ given the huge investment of time and resources. 

Citing research costs, regulatory complexities and uncertain economic conditions, Geron announced it was pulling the plug on eleven years of research and are seeking partners to take over the work. Instead they will direct resources to two new cancer therapies currently under trial.   Geron has not reported on the effectiveness of the treatment, known as GRNOPC1, which some commentators have felt were doomed from the start.   Robert Lanza, Chief Scientific Officer of Marlborough, Massachusetts-based Advanced Cell Technology Inc., said “It was a very difficult choice to go in and treat spinal cord injury. There was considerable concern in the scientific community that that might not have been the ideal first indication”. Advanced Cell is testing the use of stem cells in patients with macular degeneration, a leading cause of vision loss.

Comment: Any form of clinical trial is a very expensive and risky investment for a company; with troubled markets, Geron may simply have made a business decision to focus on areas that are more likely to deliver prompt returns on their investments; cancer therapeutics is a well-established area. If the trial is not showing efficacy, that is of course bad news. However in some senses it would be even worse if a company cannot justify financial investment in a promising treatment, as it means that the incentives for commercial development are missing.

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A consensus report has been released following an expert meeting organized by The National Food Institute, Danish Technical University, on microbiological genomic identification systems. The meeting bought together scientists and managers to discuss the development of a global system to allow genomic data to be aggregated, shared and used in an effective way to tackle global public health challenges in relation to infectious diseases.

The report states that new genomic technologies such as whole-genome sequencing hold promise for early detection, prevention and control of current and emerging infectious diseases. However, effective use will require collaboration between a number of stakeholders including clinicians, epidemiologists, bioinformaticians as well as regulators and ethicists.

It outlines the concept of a system that would allow sharing of genomic information as well as technical and implementation issues. Experts agreed that a global system should be achievable in the next 5-10 years, but requires a paradigm shift in the way data is accessed across disciplines. Traditionally the focus has been on single pathogens in particular disciplines e.g. virology or bacteriology, the new system would require merging data across disciplines. They also call for a transparent system with a key component being translational activities that provide information to end-users and other stakeholders.

Technical issues include ensuring standardisation and harmonisation of data formats, as well as interoperability with existing systems. Barriers to implementation include obstacles to the free sharing of genomic data; however, the experts felt that communication is key, both between stakeholders and in general, so that the value of such a system is understood by all those involved.

New genomic technologies are having an increasingly important impact in pubic health. Medical practice is set to be revolutionized by both pathogen sequencing (see previous news) as well as human genome sequencing (see press release). However, both these areas require cross-collaborative work and the development of transparent and equitable systems to ensure their effective implementation within healthcare.

A new PHG Foundation report provides a new angle on epidemiology and risk, examining conceptual and methodological issues.

Epidemiology, risk and causation covers a range of philosophical issues including the nature of causation and risk communication, the proper use of statistical significance testing, and the social determinants of health. It is the product of extensive academic work building on a series of expert workshops held in Cambridge in 2010. 

Report author Alex Broadbent notes that epidemiology, the core science of public health, has been relatively neglected by philosophers, ethicists and social sciences, but poses lots of important issues that philosophy can - and arguably should - productively address.

An example of the use of non-invasive prenatal diagnosis (NIPD) for the identification of a chromosomal microdeletion has been published in the New England Journal of Medicine.

NIPD, the brainchild of Professor Dennis Lo, has a range of current and potential applications, including for the identification of fetal sex and RhD-status, and the presence of selected genetic and chromosomal abnormalities. The first commercial tests for trisomy 21 (Down’s Syndrome) recently went on sale in the US (see previous news).

The technique has limitations, but the new report details a single example of the identification of a fetal 4-Mb deletion on chromosome 12 using a maternal blood sample taken at 35 weeks. The microdeletion, inherited from the father and observed in an older child of the couple with developmental delay, had been previously diagnosed using the standard invasive techniques of amniocentesis and array-based comparative genomic hybridization.

Comment: Although this is an isolated case of a diagnosis performed late in pregnancy, it is a valuable example of how NIPD might in theory be employed earlier to diagnose familial much smaller chromosomal abnormalities than aneuploidies. Couples could then obtain this information without risk to the pregnancy, and with more time to make a decision about whether or not to proceed with an affected pregnancy. 

A new report - Towards Precision Medicine - published by the National Research Council earlier this month highlights the need for new systems to incorporate the ever growing health and disease-related information into a single resource that can help improve health outcomes.

The report concludes that a new disease taxonomy would be required, because existing structures (such as the existing ICD) could not optimally incorporate the wealth of biological data now being collected such as molecular, phenotypic and clinical in addition to environmental and health outcome data. The new taxonomy could facilitate the creation of new systems that allow large volume of data to not only become available for research use but also become more directly incorporated into the health care records system potentially leading to changes in how population-based research is currently conducted.

The report also made six recommendations, including undertaking pilot studies to start creating the underlying framework to support such a system. These studies would allow assessment of different practical and conceptual issues, including creating minimum data standards and how to best allow data sharing whilst maintaining data confidentiality and complying with relevant research ethics. Such a system is required in order to allow both researchers and health care practitioners to realise the full promise of ‘precision medicine’, whereby the best available care could be provided to each individual patient.

Comment: The creation of such an extensive data resource could allow researchers to start classifying diseases in myriad ways, allowing enhanced disease classification and diagnosis, which in turn could lead to more accurate and ‘personalised’ treatment for individual patients. A research endeavour as large as this will take many years to establish with the eventual goal being to replace the century old ICD used by the World Health Organization (WHO). The authors rightly mix optimism with caution when saying in their summary that “this infrastructure….is a grand challenge that, if met, would modernize the ways in which biomedical research is conducted and, over time, lead to dramatically improved patient care”.

Findings suggesting that simply having a close relative with a BRCA1 or BRCA2 mutation raises a woman’s risk of developing breast cancer (see previous news) have been contradicted by a new study.

This more recent research analyses data from 3,000 women in Canada, the US and Australia. The research team found that even where a woman is from a family identified as high-risk due to the presence of inherited BRCA1/2 mutations, if she does not carry one of these mutations then she is at no greater risk of developing breast or ovarian cancer than a woman in the general population.

Comment: These apparently contradictory results highlight the difficulty of drawing general conclusions from isolated research projects, however well conducted. The new study involves around twice as many women as the earlier UK based one, which lends weight to their conclusions, but the most reliable results would require a meta-analysis of data from a number of different studies.

New information overturns scientists’ understanding about brain DNA, says a study published in Nature.

Contrary to previous belief, brain cell DNA is not static but changes minutely thousands of times over a person’s lifetime. The research also shows that brain cells are genetically different from other cells of the body, and are genetically distinct from each other.

The changes are brought about by retrotransposons - mobile gene elements that are able to shuttle in and out of genes, copying and pasting themselves into different parts of the genome over time. Retrotransposons may make up more than 40 percent of the human genome according to the most recent estimates.

The findings could take us further in understanding the development of forms of neurological disease, although caution was expressed by Dr Virginia Warren, assistant medical director for Bupa: “These findings provide the building blocks for understanding some basic mechanisms in the brain. They don't provide all the answers, but it's a good place to start”, she said.

The British Supreme Court has upheld the validity of a patent for a gene sequence held by the company Human Genome Sciences.

The patent had been contested by rival company Eli Lilly on the basis that the broad claims of potential uses for the sequence of the neutrokine-alpha gene made in the patent application did not prove the industrial application of the sequence. A specific medical application was subsequently been identified by HGS in partnership with GlaxoSmithKline, and Benlysta (belimumab) was approved as a new treatment for the autoimmune disease lupus in Europe and the US earlier this year.

The European Patent Office earlier denied the same appeal against the patent by Eli Lilly, saying that the disclosure of industrial application was sufficient; the British Court of Appeal disagreed. However, the Supreme Court has now upheld the patent in relation to these claims, and criticised the Court of Appeal for not having followed EPO case law in reaching their decision.

Comment: This decision has been hailed as good news for British bioscience research, particularly by strengthening the scope for ‘blue-sky’ research to yield potentially valuable intellectual property (increasing scope for research investment) and by affirming close alignment between British and European patent law in the absence of good reasons for divergence.  

A new international genomics project will try to uncover the genetic basis of epilepsy and further the search for new diagnostic and therapeutic options.

Epilepsy is a chronic neurological condition that affects around 1 in 100 people and comes in many different forms; a small proportion of epilepsies are inherited in the form of a monogenic disease, but many more are thought to involve multiple contributory genetic factors. Now the National Institute of Neurological Diseases and Stroke has provided funding of US $25 million as part of a genetics of epilepsy ‘Center without Walls’ collaborative research initiative.

Led by Professor David Goldstein, director of the Duke Center for Human Genome Variation, the project will also involve researchers in the University of California, San Francisco, the University of Melbourne, and other international research institutes. It will entail analysis of genomes from 4,000 epilepsy patients. Professor Goldstein said: "This grant allows us to study the genomes of epilepsy patients on a sufficiently large scale that we should be able to identify many new genes involved in the risk of epilepsy". 

This year’s theme for the fourth annual Building Bridges in Medical Science conference was translational science and interdisciplinary research. 

The PHG Foundation was one of the sponsors of this event, which gave a number of perspectives on bench-to-bedside research. This ranged from discussions of the role of universities by Professor Sir Leszek Borysiewicz, the current Vice Chancellor of the University of Cambridge, to the social determinants of health by Professor Sir Michael Marmot. Useful partnerships that can be formed between industry and universities and the changing landscape of translational research were also discussed; Dr Ruth McKernan (CSO of Pfizer Regenerative Medicine) said “Post-genomic scientific challenges are too great for a single organisation, and partnerships are the only sensible way forward”.

The importance of interdisciplinary research was illustrated by Professor Luke O’Neill of Trinity College, Dublin, using research into inflammation as an example, and Professor Sir Alan Ferscht, who is well known for his work on the tumour suppressor protein p53. Progress had been made possible in these areas, they said, through collaborations not only between different fields in biology but also by researchers in chemistry, physics and maths. Nobel Laureate James Watson’s talk highlighted how such research has always been a part of major scientific discoveries.

Comment: The PHG Foundation is concerned with acceleration of the effective translation of genomic and biomedical innovations into public health and healthcare practice. It considers that translational research is a crucial step in this process, but concentrates on the more neglected but equally essential downstream stages of developing policy and practice guidance that allow clinical implementation. Multi-disciplinarity is important both within the PHG Foundation and as part of collaborative projects that bring together experts from diverse fields to bridge the gap between research and practice.

Laboratory-bred mosquitoes carrying a ‘death gene’ that kills their offspring could help eliminate dengue fever.

The mosquitoes are in effect sterilised, using a genetic approach known as tetracycline-controlled transcriptional activation (tTA). The tTA gene is spliced into the insect's genome in such a way that the protein it makes increases the gene's activity, thus making more and more tTA protein. The cell’s capacity to make other essential proteins is depleted, eventually killing the insect.

This cycle is turned off in the bred insects, but the active tTA gene is passed to their wild-born offspring.

While the idea of mass release of sterile insects is not new, previous attempts have faltered as laboratory-bred males struggled to compete with their wild counterparts for females. The genetically modified (GM) mosquitoes seem to fare better. The GM males made up 16% of males in the study area, and fathered 10% of the larvae.

"We were really surprised how well they did" said Luke Alphey, chief scientific officer at Oxitec, the company carrying out the research: “You'll never get the males as competitive as the wild ones, but they don't have to be, they just have to be reasonably good".

The next step is to demonstrate that deploying GM males suppresses the insect population enough to reduce dengue incidence. If so, the sterile mosquitoes could form a significant part of an integrated anti-dengue programme.

 A new collaboration aims to sequence the entire genomes of more than 2,000 families affected by autism. 

The two-year partnership between global leader in whole genome sequencing, BGI, and the US autism science and advocacy organisation, Autism Speaks, will yield the largest library of sequenced genomes of individuals with autism spectrum disorders (ASD).

Data will be collected from the more than 10,000 US-based participants in the Autism Genetic Resource Exchange (AGRE) and added to that from participants in China. AGRE provides DNA, clinical, and medical information to autism researchers worldwide enabling them to focus time on finding answers rather than on gathering data.

“This collaboration will transform the field and greatly accelerate basic and translational research in autism and related developmental disabilities”, said Autism Speaks Vice President for Scientific Affairs Dr Andy Shih. 

 A new gene therapy technique is showing promise as a treatment for the rare genetic disorder, Choroideraemia.

The disease is caused by an inherited faulty REP1 gene. Without a functioning copy of the gene, the eye’s light detecting cells die off. Often diagnosed in childhood, most sufferers will have lost their sight by their 40s.

The experimental technique aims to stop the cells from dying by injecting working copies of the gene into the eye. It is the first time that anyone has tried to correct a genetic defect in the light-sensing cells that line the back of the eye.

Professor Robert MacLaren, who has been treating the patient, says it could be two years before doctors can confirm that the patient’s vision has stopped deteriorating. However, if the gene therapy works, it could be used to treat a wide variety of eye disorders, including the most common form of blindness in the elderly, macular degeneration.

Genomes on prescription.

Maher B. Nature. 2011 Oct 5;478(7367):22-4. 

Genomic medicine has failed the poor.

Baker S. Nature. 2011 Oct 19;478(7369):287.

Genomics is not enough.

Chakravarti A. Science. 2011 Oct 7;334(6052):15.

The coming explosion in genetic testing - is there a duty to recontact?

Pyeritz RE. N Engl J Med. 2011 Oct 13;365(15):1367-9.

Exome sequencing as a tool for Mendelian disease gene discovery.

Bamshad MJ et al. Nat Rev Genet. 2011 Sep 27;12(11):745-55.

Understanding type 1 diabetes through genetics: advances and prospects.

Polychronakos C, Li Q. Nat Rev Genet. 2011 Oct 18;12(11):781-92.

The family history: The first genetic test, and still useful after all those years?

Pyeritz RE. Genet Med. 2011 Oct 7. [Epub ahead of print]

Genomics and the multifactorial nature of human autoimmune disease.

Cho JH, Gregersen PK. N Engl J Med. 2011 Oct 27;365(17):1612-23.

A priceless resource

Nature. 2011 Oct 26;478(7370):427.

Biobank research:who benefits from individual consent?

Stjernschantz Forsberg J, Hansson MG, Eriksson S. BMJ. 2011 Oct 4;343:d5647. 

The new date, new format, new goals and new sponsor of the Archon Genomics X PRIZE Competition.

Kedes L, Campany G. Nat Genet. 2011 Oct 27;43(11):1055-8. 

High-interest clones.

Nature. 2011 Oct 5;478(7367):5.

Stem cells. Where do human eggs come from?

Vogel G. Science. 2011 Oct 7;334(6052):27

Long-term outcomes for patients with cystic fibrosis in Australia.

Gaskin KJ, Wilcken B. Med J Aust. 2011 Oct 3;195(7):370-1

In praise of simplicity

New Scientist (2011) 211 (2834):3

The ethics of personal genetic profiling

Hood C (2011) Genomics, Society and Policy Journal 6 (3) 

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