Stem Cell News

News articles are provided by the PHG Foundation.

The Government review states that new and consolidated ALBs will, where appropriate, ‘be expected to exploit commercial opportunities and maximise commercial discipline across the sector’. This charge could potentially be at odds with the normal function of research ethics and regulation, which is typically to protect the interests and sensibilities of patients and the wider public where they may be at odds with the scientific research aims or practices; Maximizing commercial opportunities could conflict directly with this, so it will be important for the priorities and responsibilities of a new regulator to be very clearly delineated to maintain public trust, whilst supporting scientific and medical research. 

It has been another tumultuous few weeks for the world of consumer genetics. Following recent their announcement that the US Food and Drug Administration (FDA) would seek to regulate direct-to-consumer (DTC) genetic testing services as medical devices, communicated through a series of letters to the most prominent DTC genomics companies (see previous news), it has now sent a further 14 device notification letters out to a select but growing group of genetic test providers (see Genomics Law Report). The move occurred during the FDA’s widely publicised meeting on the regulation of laboratory-developed-tests (LDTs, see previous news), during which the matter of DTC tests was extensively discussed.

Director of the Office of Population Health Genomics Dr Peter O'Leary said that the guidelines would ‘strengthen WA’s position as an innovative leader in genetic research and data linkage’ (see press release). 

A small proportion of Parkinson's disease patients have a rare, inherited form of the disease; the majority of cases are sporadic, having a complex (and as yet poorly understood) basis involving a range of interacting genetic and environmental causes. A large scale study into the genetics of Parkinson's disease is being run by genetic testing company 23andme (see previous news) with financial backing from both Google and its co-founder Sergey Brin, who has a family history of the disease and has reportedly invested around US$10 / £6 million of his own in addition to some US$6 / £4 million from the search engine company (see Telegraph article). 

A report from the European Science Foundation (ESF) released last month examines key issues in human stem cell research and regenerative medicine, which it hails as having the promise to be ‘one of the most fascinating and controversial scientific developments of the 21st century’ (see press release). Regulation of stem cell research varies widely between different European countries: some prohibit human embryonic stem (HES) cell research; seven permit the production of human stem cells from spare in vitro fertilisation (IVF) embryos; three (the UK, Belgium and Sweden) allow the creation of embryos purely for research, albeit under strict regulation; and six have no legislative policies at all.

A planned new facility at the Karolinska Institutet in Sweden hopes to create the world’s largest biobank by creating a national infrastructure to join individual Swedish biobank projects (see Swedish Research Council). 

Chief executive Henny Braund said, “We urgently need to increase the number of people on our register, and saliva testing will help us do that much more quickly and effectively” (see press release). It is also hoped that the kits will facilitate testing of family members to identify tissues matches for people who need transplants. 

The increasing availability of genetic tests available direct-to-consumer (DTC) has led to extensive international debate about the regulation of such services (see previous news). In particular, genomic profiles that offer individual risk prediction for a plethora of different common diseases have raised a number of ethical questions relating to the potential harms of giving this kind of probabilistic, and potentially misleading, information to individuals (see previous news) without formal genetic counselling or professional medical advice.

These issues are further elaborated in a new paper in the Journal of Medical Ethics, specifically in relation to testing for genetic susceptibility to autism [Jordan BR & Tsai DFC, JME (2010) doi: 10.1136/jme.2009.031385]. Autism is an increasingly prevalent neurodevelopment disorder which manifests in childhood and is broadly characterised by impaired social interaction and repetitive behaviour. Although twin studies suggest that the disorder is highly heritable, genome-wide association studies for both SNPs (see previous news) and CNVs (see previous news) have thus far failed to explain much of the genetic basis of this multifactorial disease; diagnosis still involves numerous psychological tests combined with professional judgement, and risk prediction remains impossible. Nonetheless, a genetic susceptibility test is frequently conjectured in the media and is actively being developed commercially (though is not currently offered by any of the major DTC genomics companies).

The authors question whether “a responsible test for autism could ever be commercially viable”, and suggest that this kind of genetic susceptibility test for multigenic diseases can only be useful if:

The International Society for Stem Cell Research (ISSCR) has a launched a new website for people considering stem cell treatments for different conditions.

The Biotechnology and Biological Sciences Research Council (BBSRC), together with the Engineering and Physical Sciences Research Council (EPSRC) initiated a project last year to develop a dialogue with the public regarding their concerns and aspirations in the emerging field of synthetic biology. They have now published a report on the findings from a series of public workshops and stakeholder interviews on the on the science and issues surrounding synthetic biology (see press release) and will use the findings to inform their strategic plans on funding and policy in this area.

The process initially involved interviews with various stakeholders such as consumers, scientists, religious groups, industry and regulators in order to provide some background and inform the workshops. They were asked about the field as well as potential applications and ethical consideration. Three workshops then explored different aspects of synthetic biology; the first explored views on science and technology, the second views on synthetic biology and how this is funded and regulated and the final workshop explored specific applications of synthetic biology. The discussions encompassed a number of applications of synthetic biology including medical, energy, environmental and food. Areas for future dialogues were also identified.

In general, the findings of these workshops showed that there was support for synthetic biology; especially if it can help address current concerns such as the energy crisis and treatment of diseases. However, the acceptability of research was dependant on how much progress could be made in each application area. There were concerns about control of biological organisms, who benefits, health or environmental impacts, misuse and governance. A number of conclusions were reached as to how to regulate innovation, the unique nature of this field and developing the capabilities of scientists to think through responsibilities. It was felt that continued dialogue was needed in order ensure that different stakeholder views are considered and incorporated into developing practices.

The recent report of the creation of a bacterial cell controlled by a synthetic genome (see previous news) has also stimulated a lot of debate in this field and lead to a hearing in the US Congress (see Reuters news). Although the hearing concluded that there are no immediate security, environmental or ethical concerns arising from developments in this field, there is some concern from researchers about the impact of regulations and patents in this field (see BBC news).

Following the revelation last week that the  US Food and Drug Administration (FDA) now plans to start regulating consumer genomic services as ‘devices’ (see previous news), and the recent launch of the National Institutes of Health (NIH) Genetic Testing Registry (see previous news), various additional regulatory involvements in genomic medicine have now been announced.

The US National Institutes of Health (NIH) has issued a call for input and feedback on recently announced plans to create a Genetic Testing Registry from stakeholders including researchers, test developers and manufacturers. The Genetic Testing Registry (GTR) will provide information for consumers on the availability, validity and usefulness of genetic tests (see previous news).

Since the announcement last week that Pathway Genomics was intending to offer personal genome scans over-the-counter in the United States (US) (see previous news), the world of consumer genomics has been thrown into disarray. Until this announcement, regulatory bodies such as the US Food and Drug Administration (FDA) have done little more than keep a watchful eye on the area of direct-to-consumer (DTC) genetics tests. However, following the announcement that these tests might become available in high street stores, rather than just over the internet,  the FDA wasted no time in issuing a letter to the company the very next day asking for proof that the test had proper FDA approval or to explain why such approval is not necessary (see MSNBC news). A US official has since said that "selling a test over the counter without an FDA clearance, particularly for the type of claims they have, is not legal" (see the Economist). Within 48 hours of the original announcement, the retail stores involved reversed their decision to offer consumer genetic tests, pending a resolution by the FDA (see the Wall Street Journal).

The FDA has grappled with how to regulate the growing number of DTC genetic tests for several years, and it is still rather unclear how exactly these types of tests should be regulated (see the Genomics Law Report for an extensive summary of the current regulatory landscape). Nonetheless, at the end of a turbulent week, the US House of Representatives Committee on Energy and Commerce today launched an investigation into DTC genetic testing (see the official announcement). In a letter sent to three prominent American DTC companies (23andMe, Pathway Genomics and Navigenics) the Committee has requested information within the next few weeks on how individual risk of disease is determined and policies regarding the collection, storage, and processing of individual genetic samples.

Bizarrely, today’s announcement was accompanied by a rather contradictory revelation that students at University of California, Berkeley, will be offered free genome scans when they arrive (see New Scientist). This move is likely to draw both widespread excitement and condemnation in almost equal measures, due to the perceived usefulness of this information in future for individuals to improve their own health, and pertinent ethical concerns over data privacy and misinterpretation of the information (see coverage in the New York Times).

Comment: Given the lack of evidence of utility of these types of tests (see previous news), it seems a little premature to dismiss a number of very real concerns associated their increasing availability without good reason, and some level of regulation is certainly warranted. Before such tests can be offered legitimately with claims of improving health, evidence is needed that they are both scientifically valid and clinically useful.

That said, given the nature of the tests – most of which currently only analyse common variants and have very limited predictive power for individuals – regulators must be clear what ‘harm’ they are trying to prevent. Direct harms are unlikely to result from in vitro saliva-based tests, and the analytical accuracy of the genotyping assay itself is very high. Therefore, the possible indirect harms that could result from misinterpreting the information, such as psychological distress or false reassurance, are the main reason to regulate the tests. However, to date, there is very little evidence that these harms are actually occurring or causing a problem; moreover, regulating ‘interpretation’ is very difficult. Thus, there is a need to provide oversight of all DTC testing services, genetic or otherwise, to address these issues without taking an overly paternalistic approach that limits individual choice unnecessarily. Transparency of information, ensuring access to support from trained professionals, and preventing overhyped or misleading claims that are not backed up with robust evidence may be the best approach.

Perhaps the greatest harm of all is immeasurable – namely a possible loss of faith throughout society in the power of genetics. Once people realise that a genome scan is not a crystal ball, but a tool to investigate biology, there could be a backlash against the enormous worldwide investment in genomics research. Therefore companies, regulatory bodies, and professionals have a duty to diffuse the hype surrounding these tests and ensure that individuals are well informed enough to understand what they are buying.

The potential role of genomics in medicine is changing rapidly as technological developments make quick, affordable genome sequencing increasingly feasible. Governments, health services, doctors, scientists and the wider public around the world are interested in how genomic medicine is likely to develop. In the UK, the House of Lords Science and Technology Committee led a consultation on this issue, resulting in the publication of the report Genomic Medicine in July 2009 (see previous news). This report looked at the implications of advances in genomics for UK health services. A subsequent Government response in December 2009 largely failed to engage with the urgency of recommendations in the original Report (see previous news), though it did make a commitment to establish a new cross-departmental Human Genomics Strategy Group (HGSG) charged with developing a strategic vision for genomics in the National Health Service (see GenomeWeb news).

Switzerland has announced a major new three-year programme of research in stem cells and regenerative medicine. The aim of the NRP 63 programme, which is to receive CHF 10 million (£3.6 million; €4.2 million) from the Swiss National Fund, is to ‘better understand how stem cells work’ and lay ‘solid groundwork for future medical applications’. The twelve projects within the programme will be based at academic institutions and include research on adult human stem cells and embryonic and adult stem cells from other organisms. There is no reference to the more controversial human embryonic stem cell research.

The Vatican, which governs the Roman Catholic Church, is reportedly also to support research into adult intestinal stem cells as potential medical treatments for disease in the US. Ethically opposed to the use of embryonic stem cells because it involves the destruction of human embryos, the Catholic Church is apparently seeking to boost awareness of its official support for somatic stem cell research with support and, it is suggested, funding (see MSNBC news report).

Last month the Health Secretary Andy Burnham announced that the Academy of Medical Sciences (AMS) has been commissioned to produce a review of the current regulatory and governance framework for medical research in the UK, which AMS president Professor Sir John Bell described as ‘stifling’ and working group chair Sir Michael Rawlins as ‘unnecessarily complex and burdensome’ (see AMS response).

This move follows a report published by the AMS earlier this year challenging the Government to act promptly in making the most of opportunities offered by medical research to improve health, and calling for a proportionate regulatory framework (see previous news).

The review will focus on research involving humans, human tissue and data, and will include epidemiological research and experimental medicine, as well as conventional clinical trials. The AMS is calling for evidence to inform the current review from all relevant stakeholders by 1st June 2010.

Comment: This research from China provides only a starting point for rational drug design, but is nevertheless a promising development following relatively quickly after the identification of the FTO gene as a significant player in obesity. In the UK recently there has been criticism of government attitudes to obesity  and their effects on the medical profession; National Obesity Forum chair Dr David Haslam reportedly praised recent initiatives to prevent and reduce obesity levels by encouraging healthier lifestyles, but that too few resources were available for the treatment of those who were already obese, such as drugs or surgery [White C. BMJ (2010) 340:c1716. doi: 10.1136/bmj.c1716]

A new paper in Nature reports on the use of an approach termed pronuclear transfer to prevent transmission of mitochondrial disease. Genetic forms of mitochondrial disease, whilst rare, can have devastating consequences, so there is considerable interest in finding ways to prevent them in affected families. Work last year used a technique called metaphase II spindle transfer to combine monkey egg cells with healthy mitochondria (from which the nucleus had been removed) with the nucleus from a monkey carrying mitochondrial mutations. The resultant egg cells, when fertilised, gave rise to apparently healthy baby monkeys that were the genetic offspring of the diseased mother – but with normal mitochondria (see previous news).

The latest research uses a different approach, pronuclear transfer – using human zygotes produced by in vitro fertilisation (IVF) rather than egg cells [Craven L. et al. (2010) doi:10.1038/nature08958]. Pronuclei are the bodies containing genetic material derived from the sperm and egg cells that are present in the zygote following fertilisation, but before the two fuse to form a single nucleus. The researchers created zygotes using egg cells from women with mitochondrial mutations and healthy sperm cells, then transferred either one or two pronuclei from the zygotes into another zygote from a healthy mother (ie. with mitochondria that did not contain mutations) from which the pronuclei had been removed. The resultant zygotes were grown to the blastocyst stage (70-100 cell embryos, day 5-6 after fertilisation). The proportion of zygotes reaching this stage was around 8% - half that of artificially created zygotes that had not been manipulated.

The researchers also looked at the proportion of donor (ie. mutated) mitochondrial DNA (mtDNA) in embryos grown following pronuclear transfer and found it quite variable; one contained no donor mtDNA at all, the ideal scenario, but others showed levels ranging from 2- 40%. Refinement of the pronuclear transfer technique to minimise the amount of celullar material transferred along with the pronuclei reduced this to below 2%.

The authors conclude that the technique, along with the previously published alternative approach, has the potential to be used to ‘treat’ (rather, prevent or ameliorate) human mtDNA disease, and weight the relative advantages and disadvantages of each. They are careful to note that this sort of genetic manipulation is only appropriate for use in families affected by serious forms of disease that ‘can affect multiple family members with catastrophic consequences’, as per the example of a woman with seven affected children, of which six died shortly after birth and the seventh has very serious medical problems (see BBC news report).

Comment: Calls for further investment in this line of research seem justified, given the severity of the conditions it is intended to prevent. However, there are two areas that will continue to require scrutiny. The first is the safety of the procedure; the researchers themselves point out that artificial manipulation of embryos can result in abnormal development. The second is bioethical concerns; generic issues relating to any form of cloning, and specifics relating to this particular technique – which involves the creation and manipulation of multiple zygotes, as opposed to unfertilised egg cells.

The US National Institutes of Health (NIH) has announced that is creating a “public database that researchers, consumers, health care providers, and others can search for information submitted voluntarily by genetic test providers” (see press release). The aim of the Genetic Testing Registry (GTR) is to improve the levels of information accessible to consumers about the availability, validity and usefulness of genetic tests. Although the exact scope of the GTR will no doubt develop, it will initially focus on tests that “involve an analysis of human chromosomes, deoxyribonucleic acid, ribonucleic acid, genes and/or gene products (e.g. enzymes and other types of proteins), which is predominantly used to detect heritable or somatic mutations, genotypes, or phenotypes related to disease and health.”

The NIH states that over 1,600 genetic tests are currently available to patients and consumers, but there is no single database collating information about them. The GTR should provide a trustworthy resource for consumers and medical professionals and encourage test providers to be more transparent about the evidence associated with their tests. In addition, the test data will be integrated with information in other genetic, scientific, and medical databases to facilitate translation of research findings into practice. As part of the development process, the NIH will involve numerous stakeholders and federal regulatory bodies to determine the best way to develop and present the GTR.

Comment: Irrespective of the ongoing debate surrounding the legitimacy of consumer genetic testing, there is an urgent global need to construct an accessible evidence base for all diagnostic tests, to encourage accuracy, reliably, validity and effectiveness, and to ensure that any claims are consistent with the scientific evidence. There is currently no systematic evidence base for diagnostic tests, neither those used by clinicians nor those available to the public; furthermore, unlike pharmaceuticals, there is no agreed mechanisms for generating or assessing evidence about diagnostic tests. Simply achieving transparency about the level of evidence associated with novel tests is the first step towards redressing this balance, and would provide both health care providers and consumers with the necessary tools and information to make informed decisions.

In the UK, the PHG Foundation has repeatedly highlighted the need for such an evidence base (see our Diagnostics Summit report). In the US, a mandatory registry of laboratory tests was also proposed several years ago by the Secretary’s Advisory Committee on Genetics, Health and Society (see previous news); however, when proposals for implementation were developed last year by the Genetics and Public Policy Centre (see previous news), the registry became limited to genetic tests. Although this is a clear example of genetic exceptionalism, the GTR may represent an important first step towards realising these goals, and could ultimately inform the development of a test registry with a much wider remit and greater regulatory clout. Moreover, while the aims of the GTR are certainly laudable, it remains to be seen whether a voluntary database will be effective; nonetheless, it may be the only option given the global nature of both genomics research and the genetic testing market. In fact, the voluntary nature of the database may itself provide an indication of the quality of service offered by different companies, and reputable companies will finally be able to distinguish themselves from those selling the genetic equivalent of ‘snake oil’.

The annual report of the Chief Medical Officer for 2009, released this week, highlights the issue of rare diseases. These diseases, many of which are genetic in origin, are typically chronic, progressive conditions that begin in childhood, including neurological, muscular, heart and metabolic disorders.

Under the title ‘Rare is common’, CMO Sir Liam Donaldson notes that whilst individually rare (affecting fewer than five in every 10,000 people), the large number of different rare diseases means that collectively they are significant – affecting one in 17 people (around 3 million) in England alone, and more than 30 million in Europe. In particular, the report highlights the problems encountered by affected children and adults in obtaining an accurate diagnosis, and accessing appropriate, specialist health services to help them manage their conditions.

The report calls for appointment of a National Clinical Director to oversee treatment and surveillance of rare diseases; improved coordination of specialist services via a strengthened network of reference centres; more funding for research and international cooperation to share information about these conditions; training of additional specialist health professionals to meet future needs; and raised public and professional awareness about rare diseases.

Speaking in The Times newspaper, Sir Liam said: “These are the Cinderella conditions...This is about patchy and fragmented services, poor co-ordination and lack of clinical awareness about the diagnosis. It’s not just poverty of access, but poverty of visibility and representation”.

In a letter also published in The Times, PHG Foundation Programme Director Dr Hilary Burton welcomed Sir Liam’s focus on rare diseases and noted that in fact in many cases: “diagnostic tests are already available, and there is interest in expanding the conditions currently included in the panel of diseases for which newborn babies receive routine screening”.

Currently in the UK, newborns receive screening for phenylketonuria (PKU), congenital hypothyroidism, sickle cell disorders, cystic fibrosis and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The purpose of early screening for such conditions is where early diagnosis can improve health outcomes for the affected child, in some cases with profound effect – for example, prompt dietary control of PKU prevents irreversible mental retardation.

The UK Department of Health has also been considering plans to speed access to new therapeutics for patients with rare diseases (see previous news).

The UK Human Tissue Authority (HTA) has issued an official warning that unlawful collections of umbilical cord blood have been taking place in the UK, and that such instances ‘may compromise safety and quality standards’ (see press release).

Cord blood banking is growing in popularity in the UK; last year some 15,000 collections were made of which around one quarter were for public, charitable or research recipients (see BBC news) such as to the NHS Cord Blood Bank, whilst the remainder were via commercial providers who charge £1000-2000 for collection and storage of the samples. Whilst stem cells from cord blood can currently be used for treatment for a few serious diseases such as leukaemia, private companies typically market their services to parents on the basis that stem cells will be the key to successful treatment of a whole range of diseases in the near future.

Banking has been regulated in the UK by the HTA since 2008 (see previous news); collections may only be made under an HTA licence, requiring suitably trained staff. This is to ensure not only the quality, safety and traceability of the sample obtained, but also to ensure that collection procedures do not divert key medical attention from either the mother or baby, which has caused concern in the past (see previous news). 

Now the HTA is contacting more than 150 organisations to warn them about the dangers of unlawful cord blood collection, whether by parents themselves or by unlicensed medical staff. They are also urging parents who wish to chose cord blood banking (for example, via a commercial provider) to make sure that arrangements for proper collection are made well in advance, to avoid midwives or other unlicensed medical professionals being put under pressure by parents to make illegal collections.

The CDC National Office for Public Health Genomics (NOPHG) in the US has announced plans to create a new Knowledge  Synthesis Center using the methods of the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative. EGAPP produces periodic reviews which summarise the available evidence for validity and clinical utility of selected genomic tests and other applications (see previous news for examples). This sort of information is potentially very helpful for policy-makers and health professionals trying to determine whether or not a given test is useful or not.

The new project, a collaboration between the CDC and National Institutes for Health (NIH), will provide funding for a dedicated centre to ‘conduct, update, and publish systematic evidence reviews to address selected questions for the evaluation of a set of health-related genomic tests’ (see announcement). This will include production of topic briefs on the use of selected genomic applications for improving health and preventing disease, and related issues, to form part of an online knowledge silo for EGAPP, and research into improved methodology for performing systematic reviews of published evidence.

A total of around $1.5 million funding over three years is available to create and run the new centre, and applications are being are sought.

The Joint NIH-FDA Leadership Council will concentrate on important public health issues, and seek to integrate regulatory considerations into biomedical research planning. The programme will combine work in translational and regulatory science including efforts not only to develop new clinical tools, but also means to assess the safety and efficacy of these tools. This sort of approach can be very important in making sure that innovation is used appropriately and to the best effect to improve health; for example, the PHG Foundation is currently working with other experts to develop quality standards to allow a fair evaluation and comparison of different disease risk prediction models.

It is expected that the new US partnership will have a particular impact on the development of genetic and pharmacogenetic tests for clinical application, as well as drugs for rare diseases (many of which are genetic in origin) and stem cell therapeutics. Sharon Terry, president and CEO of the Genetic Alliance, said: "The exercise of understanding how to endow discovery science with regulatory sufficiency, and retool the regulatory system to be flexible, iterative, and adaptive, will yield great fruit," (see GenomeWeb news).

The official definition of human embryonic stem (HES) cells in US National Institutes of Health (NIH) guidelines is to be broadened from those ‘derived from the inner cell mass of blastocyst stage human embryo’ (ie. from embryos that have reached the blastocyst stage at four or five days old, 70-100 cells), to include also those derived from earlier stage embryos.

Dr Lana Skirboll, director of the Office of Science Policy of the NIH, reportedly said: "We are making what I think is a relatively small technical change to the definition of human embryonic stem cells…This changes none of the ethical requirements in the guidelines" (see Reuters news). This move was prompted by an application from a commercial source to list cell lines derived from eight-cell stage embryos, and will make some commercial and academic research programmes potentially eligible for government funding.

Derivation of HES cells from a cell taken from an eight-cell stage embryo could possibly allow implantation and normal development of the remaining seven-cell embryo. This is what happens in pre-implantation prenatal diagnosis (PGD); one cell is removed for genetic analysis and, if healthy, the seven-cell embryo is implanted and can grow into a normal fetus.

A new facility called BIOFAB (International Open Facility Advancing Biotechnology) has been established with funding from the US National Science Foundation (NSF), the Lawrence Berkeley National Laboratory (LBNL) and the BioBricks Foundation (BBF). BIOFAB intends to create standardised DNA parts that will be made freely available to academic and commercial groups seeking to use synthetic biology to create organisms for different purposes (see press release).

The ‘parts’ will be crucial genetic control elements, initially from the laboratory bacterial strain E. coli, which will be characterised and standardised with a view to creating standard elements that can be used to create de novo biological systems. The hope is that these will substantially decrease the time and cost of developing new synthetic organisms, which have all sorts of potential applications such as the production of biofuels, drugs and other therapeutics.

BIOFAB will use resources such as the BioBrick Public Agreement, a proposed legal framework to support the free exchange and use of standardised biological components; it will also include research into ethical issues such as safety and security. Common concerns about bioengineering include issues relating to the deliberate design of dangerous new biological weapons, and wider worries about the inadvertent creation of organisms with other detrimental effects on nature.

The Academy of Medical Sciences (AMS) has published a new report challenging the next government of the UK to make medical science a central tenet and make the most of the opportunities for health offered by advances in the field (see press release).

Reaping the rewards: a vision for UK medical science, which notes the abundance and world-leading excellence of biomedical research in the UK and the unique opportunities for medical research via the National Health Service (NHS), says that the UK has an ‘unparalleled competitive advantage’ for commercial medical research that could ‘improve the health of the population both here and abroad’.

However, it warns competitors such as the US, China, Singapore and Canada are actively growing their own medical research sectors and that the UK is losing out as clinical trials and research move to other countries. The report sets out seven key challenges that the AMS says must be addressed over the next five years to reverse this trend and capitalise on public sector investment in medical research:

Broadly, the report calls for a more coordinated approach to research across the public, private and third sectors; a ‘proportionate, risk-based regulatory framework’, incentives for excellence and innovation, and the need for medical science to ‘underpin cost-effective international development measures that enable poorer countries to address their health needs’. As such it notes that health research should be central to UK foreign policy.

The new study published in PLoS ONE has linked epigenetic changes with cardiomyopathy, a form of heart disease characterised by weakening of the heart or a change in muscle structure that diminishes the ability of the heart to function effectively. There are three main forms of cardiomyopathy – dilated, where the heart becomes enlarged and weakened; hypertrophic, where the heart muscle becomes thickened, forcing the heart to work harder to pump blood out of the heart; and restrictive, where the heart muscle becomes stiff and hence unable to properly fill with blood (for more information, see The Cardiomyopathy Association).   

Differences in DNA methylation are currently understood to be involved in the control of gene expression, which may in turn contribute to complex disease susceptibility or progression. Strong links have already been found between differential methylation and cancer, and there are efforts underway to examine the link with other complex diseases such as schizophrenia, diabetes and inflammatory bowel disease.

Researchers in Cambridge have found differences in DNA methylation in hearts from a small number of people with end-stage cardiomyopathy who were undergoing heart transplantation and the healthy hearts of age-matched victims of road traffic accidents [Movassagh M et al. (2010) PLoS ONE 5(1): e8564, doi:10.1371/journal.pone.0008564].The differential methylation correlated with differences in gene expression patterns between the heart failure and control groups.

They conclude that differential DNA methylation, along with other epigenetic mechanisms, may influence the development of heart failure in response to environmental factors, including dietary influences, effectively representing a ‘missing link’ between genetic and environmental causes of heart failure. The researchers also comment that, although certain genes are known to play an important role in heart failure, sometimes mutations are not found in those genes and thus it may be methylation rather than mutation that leads to disease. 

Comment: This is small study, but provides very interesting insight into a possible role for epigenetic changes in heart failure. The researchers now hope to identify ‘hotspots’ in the genome to help identify those people at greater risk of developing heart disease, and in particular those people at greatest risk of developing heart disease rapidly. This would allow treatments to be targeted to those at greatest risk, and also enable closer monitoring of those at higher risk, to help prevent and delay heart failure.

Cancer cell genomes are known to contain a variety of structural rearrangements that are thought to play a role in the development of cancer. The involvement of structural changes in driving tumour formation has long been recognised, at scales ranging from whole chromosome translocations (such as the Philadelphia translocation associated with chronic myelogenous leukemia), down to much smaller-scale rearrangements. However, much remains unknown about the nature and role of these changes in driving cancer.

Now, a new paper reports high resolution mapping of the chromosome rearrangements in human breast cancer cells. In all, 24 different breast cancers were examined for the number, position and nature of these structural changes [Stephens PJ et al. (2009) Nature 462(7276):1005-10]. Most rearrangements occurred within chromosomes (as opposed to between different chromosomes) and the most common type were tandem duplications; the authors propose that this may due to a specific (unknown) defect in DNA maintenance in breast cancer cells that generates - or fails to correct - this type of rearrangement.

The researchers also observed correlation between the chromosomal rearrangements and different sub-types of breast cancer; for example, oestrogen- and progesterone-receptor negative, basal-like tumours typically had many tandem duplications, whereas oestrogen-receptor positive luminal type tumours had fewer rearrangements and mostly within repeat regions of the genome.

In many cases rearrangements affected genes and resulted in altered or novel gene products, but none of these were recurrent, suggesting that many different, individually rare mutations may be active in breast cancer cells. However, the authors themselves note that much larger numbers of tumours need to be studied before conclusions may be drawn.

Comment: The observation that breast cancer cell genomes, even from a small sample, show a higher diversity and number of structural rearrangements than expected suggests the need for major new research into how different genomic changes are involved in cancer. It will be interesting to see how far genomic features mirror other characteristics by which tumours are classified into these sub-classes; it may also help to identify key targets for new therapeutics common to some tumour sub-groups, improving prospects for more personalised treatment of breast cancer.