Genomic Medicine - Science and Technology Committee Contents


19 March 2008

A seminar was organised at the House of Lords to give the Committee an opportunity to discuss the Genomic Medicine Inquiry with academic experts, representatives from the Department of Health, the Department of Innovation University and Skills, the Department for Business Enterprise and Regulatory Reform and other organisations.

Members of the Sub-Committee present were: Lord Broers, Lord Colwyn, Baroness Finlay of Llandaff, Earl of Northesk, Baroness O'Neill of Bengarve, Lord Patel (Chairman), Baroness Perry of Southwark, Lord Sutherland of Houndwood, Lord Taverne and Lord Warner. In attendance were: Professor Tim Aitman (Specialist Adviser), Elisa Rubio (Clerk), Christine Salmon (Clerk) and Dr Cathleen Schulte (Committee Specialist).

The speakers were: Professor Tim Aitman (Specialist Adviser to the Committee; Professor of Clinical and Molecular Genetics, MRC Clinical Sciences Centre and Imperial College London); Professor Sir John Bell (Regius Professor of Medicine, Oxford University; President, Academy of Medical Sciences; and Chair, Office for Strategic Coordination of Health Research (OSCHR)); Dr Ros Eeles (Reader in Clinical Cancer Genetics, Institute of Cancer Research); Professor Wolf Reik (Associate Director of the Babraham Institute in Cambridge; Professor of Epigenetics, University of Cambridge); Professor Peter Donnelly (Professor of Statistical Science and Director of te Wellcome Trust Centre for Human Genetics, Oxford; and Chair, Wellcome Trust Case Control Consortium); Dr Ewan Birney (European Bioinformatics Institute); Professor Graeme Laurie (Professor of Jurisprudence, University of Edinburgh; and Chairman, Ethics and Governance Council UK Biobank).

Other participants were: Dr Adrian Pugh (Strategy and Policy Support Officer, Biotechnology and Biological Sciences Research Council); Dr Steve Sturdy (Deputy Director, Genomics Policy and Research Forum, Economic and Social Research Council); Nancy Lee (Policy Adviser, Strategic Planning and Policy Unit, Wellcome Trust); Yvonne Gritschneder (Policy Officer, British Heart Foundation); Dr Louise Jones (Experimental Cancer Medicine, Cancer Research UK); Dr Peter Sneddon (Head of R&D Programmes, National Institute for Health Research); Professor Peter Furness (Vice-President, Royal College of Pathologists); Professor Peter Farndon (Consultant Clinical Geneticist; and Director, UK Genetic Testing Network); Dr Neil Ebanezer (Policy Manager, NHS Genetics Team, Department of Health); Diana Paine (Team Leader, NHS Genetics Team, Department of Health); Michael Davies (Research Councils Unit, Department of Innovation, Universities and Skills); Dr David Griffiths-Johnson (Bioscience Unit, Department for Business Enterprise and Regulatory Reform); Dr Frances Flinter (Clinical Director and Consultant Clinical Geneticist at Guy's and St Thomas' NHS Foundation Trust; and Commissioner at the Human Genetic Commission); Dr Rob Elles (Chairman of the British Society of Human Genetics; and Director of Molecular Genetics, National Genetics Reference Laboratory and Regional Molecular Genetics Service); Professor Richard Trembath (Head, Division of Medical Genetics, Kings College London); Professor Sandy Thomas (Head, Foresight Unit in GO-Science); Dr Helen Munn (Director, Medical Science Policy, Academy of Medical Sciences); Dr Sarah Bunn (Biology and Health Parliamentary Adviser, Parliamentary Office of Science and Technology); Dr Hilary Burton (Programme Director, PHG Foundation); Dr Ian Frayling (Consultant in Genetic Pathology, University Hospital of Wales); and Dr John Crolla (Chair, Joint Committee on Medical Genetics).

Introduction to genetics and genomic medicine (Professor Tim Aitman)

Professor Aitman opened with a number of definitions. Genetics was the science of heredity and variation in living organisms, with the basic units of inheritance being called genes; and genomics was the study of an organism's entire genome, its whole hereditary information encoded in the DNA on the organism's chromosomes. The word genome derived from the fusion of "gene" and "chromosome".

There were two broad classes of genetic diseases:

  • Mendelian diseases are rare diseases caused primarily by defects in a single gene. Examples include cystic fibrosis, haemophilia and Huntington's disease.
  • Genetically complex diseases are more common, with a prevalence of up to 30 percent, and are caused by an interaction between genes and the environment. Examples include coronary heart disease, diabetes, obesity, arthritis and common cancers such as breast and prostate cancer.

Genome technologies had seen great advances in recent years, driven in part by large-scale sequencing projects such as the mapping and sequencing of the human genome. Automated DNA sequencing and high throughput genotyping technologies detected and measured sequence variations in the genome which were usually inherited. DNA microarrays were a powerful method of genomic investigation that allowed the expression of all the genes in the genome (20,000 - 30,000) to be measured in a single experiment. Use of DNA microarrays had led to new and more precise molecular classifications of disease states that were suggesting innovative treatment strategies for a range of diseases.

New genome technologies had dramatically advanced our ability to understand the inherited basis of common human diseases. New generation DNA sequencers introduced at the end of 2005 had led to spectacular increases in the quantity of data output, as they were able to sequence 1,000 million base pairs in a single run, often in a few hours. Similar increases in genotyping capacity had, in just the last two years, led to a revolution in identifying genes associated with common diseases. These technology advances had enabled a new strategic approach, the genome-wide association study, to be carried out. After the first publications of this type of study towards the end of 2006, there had been a flood of publications during 2007. Between 2005 and 2007 around 100 new genes for common diseases such as diabetes, arthritis and cancer were identified. By the end of 2008 it was predicted that another 400 will have been found.

Professor Aitman concluded that a new "genomic information" era had arrived and was increasingly touching healthcare professionals and the public. However, a number of questions arose: how clinically useful and reliable was genomic information in predicting and preventing common diseases? Were we ready to put genomic information to good use? Were the costs justifiable and affordable? And how should the UK take advantage of these potential advances in healthcare?

Translation of genomics into healthcare (Professor Sir John Bell)

Professor Sir John Bell described the impact of genomics on healthcare in two main areas: diagnostics and therapeutics. Advances in therapeutics were being driven by an increasing knowledge of disease genes and mechanisms and through an enhanced ability to predict drug efficacy and side effects. These advances were mostly at an early stage of development. On the other hand, advances in diagnostic testing using genomic tools were having a profound impact on clinical decision making and many new tests had already reached clinical practice.

Molecular diagnostic tests had led to an improved ability to stratify common diseases, to predict risk of future disease and to use drugs more effectively. For example, tests in cancer patients that use DNA microarrays to measure gene expression profiles and gene copy number could identify patient subgroups with very different prognostic outcomes, and treatment could be tailored to these different prognostic groups. This may not only improve treatment outcomes, but may also lead to more efficient use of existing therapies. The newly identified genes for common diseases could also be used to test healthy individuals for their risk of developing a range of common diseases, although these genes mostly have a small effect on disease susceptibility and the clinical utility of these tests in healthy subjects at present remained to be defined. In most cases it was anticipated that the range of new tests would be used in conjunction with existing means of risk prediction and disease classification. However in some specific diagnostic areas, such as the use of cytology screening for cervical cancer, molecular diagnostics were rapidly gaining ground as the method of first choice and may supersede conventional screening tests.

The new discipline of pharmacogenetics aimed to personalise drug treatment so as to optimise drug efficacy and to reduce the frequency of adverse drug reactions. It was well known that most drugs worked effectively in a minority of patients, and physicians frequently relied on a trial and error approach to prescribing. One way of improving drug efficacy was by using genetic tests to distinguish responders and non-responders, and examples existed where this approach had reached routine practice, for example in the use of Gleevec in chronic myeloid leukaemia and herceptin in breast cancer. Such genetic tests could be the most effective way of establishing personalised treatment programmes, and by increasing the proportion of patients who responded to a particular therapy may also be effective in reducing overall drug costs.

Sir John identified five main obstacles to translation of genetic testing more widely into the NHS:

  • the hospital organisational structure, which was currently not set up to use genetic testing across medical specialties and different pathological disciplines;
  • an increasing innovation gap in the NHS between new tests becoming available and their delivery into clinical practice;
  • the commissioning system at the local level, which was not oriented to the introduction of new diagnostic tests and methods;
  • the need to demonstrate clinical utility of new tests—not only must tests be reliable and accurate, but there should be evidence of clinical benefit and need; and
  • costs.

These obstacles to translation would require innovative solutions. For example, Sir John described the establishment of a central Molecular Pathology laboratory in Oxford, where genetic testing was carried out for all the conventional pathological specialties. The requirement to demonstrate clinical utility of new diagnostic tests posed significant regulatory challenges, as present regulatory structures were not suited to adapting to rapid changes in diagnostic technologies. New regulatory bodies and procedures may therefore be required.

The Office for Strategic Coordination of Health Research (OSCHR), chaired by Sir John, was a body set up by the Government to oversee the translational agenda undertaken by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR). The MRC undertook research leading to the discovery of new diagnostics, but responsibility for proof of concept and clinical utility trials rested with NIHR.

In conclusion, the likely impact of genomics on healthcare was very large but a steady hand and clear vision would be required to use genomics to deliver clinically useful and cost-effective advances in healthcare across the NHS.

Genomics in cancer (Dr Ros Eeles)

There were about 300,000 cases of cancer per annum in the UK, of which approximately 16 percent were breast cancer, 13 percent lung cancer, 13 percent bowel cancer and 12 percent prostate cancer.

There were two types of common alterations in genome sequence that were relevant to cancer susceptibility: somatic changes, which took place in cancer cells only and were not heritable; and germline alterations, which were found in sperm and egg DNA, and were passed down from generation to generation. Major progress was being made in cancer care by genomic profiling and sequencing. The Cancer Genome Project which was being undertaken at the Wellcome Trust Sanger Institute was looking at genomic changes in cancer cells to determine patterns of DNA sequence changes that related to cancer diagnosis and treatment outcome. Gene expression microarrays were useful molecular tools to refine pathological diagnosis, determine prognosis, guide treatment and predict response to treatment. Dr Eeles gave two examples of ongoing genomic clinical trials in cancer care: MINDACT (Microarray In Node-negative Disease may Avoid Chemotherapy Trial) which was using microarray data in tumour cells in breast cancer to ascertain whether chemotherapy could be avoided; and a second study, being carried out in the USA, that was investigating how the genetic make-up of patients determined response to hormone therapy in prostate cancer patients.

Dr Eeles went on to talk about the genetic alterations that were having an impact on public health and may lead to new screening and treatment programmes.

There were several different types of DNA sequence alterations that individuals could inherit, and examples were cited for the breast cancer predisposition genes. Alterations in the BRCA1 and BRCA2 genes were rare but they convey a high cancer risk and a woman with alterations in one of these genes was approximately ten times more likely to develop breast cancer in her lifetime than women without such alterations. BRCA1 and BRCA2 were therefore known as high risk or "high penetrance" genes. By contrast, alterations in the CASP8 and FGFR2 genes were much more common but the relative risk of developing breast cancer for carriers of these genes was very small. These genes were therefore of "low penetrance". It was of interest that prostate cancer patients who had alterations in the BRCA2 gene were twice as likely to die from the disease as those who did not have BRCA2 gene alterations, suggesting a common role for BRCA2 in breast and prostate cancer. It cost £962 to screen for mutations in the BRCA1 and BRCA2 genes in NHS Genetics laboratories. Tests for alterations in the CASP8 and FGFR2 genes were not currently available on the NHS, but could be bought by the public directly from genomic screening companies as part of a genomic screen that currently costs around £500. As the cost of sequencing and whole genome profiling had dramatically reduced, and continued to do so, it was likely that DNA sequence alterations would be detectable more quickly and cheaply in the future, permitting wider use of targeted screening of high risk groups.

In the past two years, there had been an explosion in genome-wide association studies in cancer that had identified low penetrance genes for a wide range of cancers and other diseases. Recently published studies covered breast, colon and prostate cancer and there were on-going studies in lung cancer, lymphoma, pancreatic, ovarian and testis cancer. However it was uncertain how these discoveries could be applied to the clinic, and it was also unknown how interaction of these low penetrance genes with the environment may impact on disease susceptibility. Dr Eeles and others had recently applied for a grant from the EU to investigate these issues.

One potential application of genomic testing was to guide the targeting of expensive screening tests to subsets of the population who may have a higher than average risk of developing a particular disease. For example, identification of individuals from the general population who carried a significant alteration in the BRCA1 gene, who therefore have a greatly increased risk of developing breast cancer, could be used to target individuals for screening with magnetic resonance imaging which was more expensive and time-consuming, but also more sensitive than mammography.

Dr Eeles enumerated a number of issues to be considered at the clinical interface in efforts to bring genomic advances into health care. More research needed to be undertaken in risk prediction and gene-environment interaction. On the other hand, ongoing research should not stop clinical implementation in cases of clear benefit. Access to genetic testing by specialists and GPs needed to be clarified and the public and health professionals needed to be educated on the potential value and implications of genetic tests.

Dr Eeles finished with a word of caution, from herself and colleagues at the Cancer Genetics Group, against over-regulation of companies who sold genetic tests direct to the public. She offered the view that, at present, the information that these companies offered was of little value to consumers or healthcare professionals but that, with further research, such information would become useful in predicting disease in the future. Over-regulation may impair or stop progress towards this objective.

Epigenetic factors and their importance in genome-wide association studies (Professor Wolf Reik)

Professor Reik posed the question "who do we think we are?" The answer should be in our DNA. All the genes in the human genome were known but they were not used all at the same time. Different sets of genes were switched on or off during development of an organism to form different tissues and organs. Epigenetics was defined as gene expression states that were stable over rounds of cell division, but did not involve changes in the underlying DNA sequence of the organism.

Epigenetic modifications generally turned genes on or off, thus allowing or preventing the gene from being used to make a protein. As a result cells would differ in their protein content giving them different functions and forming diverse organs such as the brain and heart. Epigenetic factors started working as soon as the embryo was formed.

There were probably hundreds of epigenomes and what was really important was that epigenomes were not only influenced by genetic factors but also by the environment, nutrition, multigenerational inheritance and by pregnancy. All these factors played a major role in setting the shape that the multiple epigenomes had. There were many associations beginning to emerge between epigenetic marking and common diseases. Epigenetic factors had major influence in cancer, it was suspected they had a major role in obesity and psychiatric disorders and they were of key importance in the use of stem cell therapies. There were multiple examples of environmental influences resulting in altered epigenomes and possible disease such as maternal grooming resulting in anxiety and altered methylation of glucocorticoid receptors in children.

The challenge that we were facing was: if there were hundreds of epigenomes, how could we determine what they were? Given that the sequencing of a single genome took many years and vast sums of money, this may seem like an impossible task. However, next generation sequencing technology would make this a reality very soon.

The UK was a World leader in epigenetics research together with Japan and the US. However, we needed to build capability in epigenomics and combine genetic mapping with epigenome sequencing, as genetic variants interacted with epigenetic variants and the nature of this relationship was largely unexplored.

Population genomics and insights into the genetics of common diseases (Professor Peter Donnelly)

Professor Donnelly illustrated the pace of discovery of genes associated with common diseases by explaining that until October 2006 the number of common genetic variants that we knew reliably to be associated with common diseases was very low. At the end of 2006 the first results of a new generation of "genome-wide association studies" started to be reported. While in 2005 only a handful of common genetic variants were known reliably to be associated with common diseases, such as diabetes and macular degeneration, in the year up to September 2007 more than 50 were discovered that contributed susceptibility to a range of diseases including coronary heart disease, prostate cancer and inflammatory bowel disease. The pace of discovery was likely to continue to increase, owing to better ways of analysing the data generated in genome-wide association studies, to new and larger studies being carried out across a range of common diseases, and to finding ways of combining data from different studies.

Several factors had driven the current explosion of genetic variants associated with common diseases. At the beginning of the decade, the Human Genome Project provided a map where scientists could start placing variants. The SNP Consortium was a private-public partnership which aimed at finding single nucleotide polymorphisms (SNPs)—letters in the genetic code that varied between different human chromosomes. The International HapMap Project, a huge international collaboration, then looked at the correlation of patterns of genetic variation in different human populations. The most recent advance, and a direct cause of the recent explosion of data, was the ability to read as many as a million letters of the genetic code in different positions in an individual's genome in a single chip experiment.

The Wellcome Trust Case Control Consortium (WTCCC) undertook genome-wide association studies in seven different common diseases, comparing the pattern of SNPs across the genome of 2000 people with each disease with the pattern in 3000 healthy people in order to find sequence variants associated with predisposition to each disease. This was the largest of the first generation of genome-wide association studies and led to the discovery and confirmation of more than 30 novel disease associations to date, and around 20 more when combining data with other studies. After decades of largely unsuccessful efforts, scientists had finally found a method which was robust in terms of finding genes associated with common diseases that could then be reliably reproduced in other samples. Whilst it was agreed that these sequence variants were robust markers of disease risk, at present it was not known how most of these variants functioned to increase the risk of disease development. Understanding the mechanism by which these SNPs underlie disease risk was the subject of major ongoing global research efforts.

Relative risk was a measure used to describe how much a person's risk of disease was increased by a particular genetic variant. For virtually all the loci found from association studies, the estimated effect sizes were modest in some cases and small in most cases. This supported the view that many genes were likely to play a role in inherited susceptibility to common diseases and that environmental risk factors, such as lifestyle and environmental exposures, also had a major part to play. However, since scientists estimated the effect sizes of the measured genetic markers rather than the causative DNA change itself, it was likely that the effect sizes had been underestimated. This underestimation had consequences in the ability to use relative risk in disease prediction, since relative risks at particular loci may increase once the causative variants themselves have been identified.

It was also important to appreciate that although the relative risk conferred by individual markers was not great, combining information from many genetic markers and from conventional measures of disease risk may identify segments of the population who were at very significantly increased risk of individual diseases. While most individuals would have an average risk for most diseases almost everyone would be at very high risk for some diseases. Professor Donnelly estimated that 95 percent of people would be in the top five percent of genetic risk for at least one disease, 40 percent of people would be in the top one percent of genetic risk for at least one disease and five percent of people would be in the top 0.1 percent of genetic risk for at least one disease.

Professor Donnelly drew two main conclusions. First, at a time when the new markers of common diseases had only very recently been discovered, it was true that reliable disease predictions were not possible, and therefore the clinical utility of this new knowledge was uncertain. Nonetheless this may change as we learn more about genetic variants, and when we were able to predict disease for a range of, say, 50 diseases, each individual was likely to be at a high relative risk for a few of those diseases. It may therefore be useful to think of genomic tests, including those sold "direct to consumers", as a tool for individuals to identify the diseases for which they had the highest genetic risk, based on current knowledge. However, in the context of tests sold direct to consumers, if the information were to be of value it was essential that suppliers of the tests were able to carry out genomic tests accurately, and that they explained to their prospective customers the pitfalls and limitations of such tests, as well as the potential benefits.

The second conclusion was that while there was ongoing uncertainty regarding the clinical utility of genomic tests for disease prediction, the most important outcome of this new research may be in advancing understanding of the molecular causes of disease development, which was already providing new leads for ways in which to prevent and treat common diseases.

Organisation and analysis of genomic data (Dr Ewan Birney)

Dr Birney explained the key components that would be required for an information infrastructure for Genomic Medicine: a fundamental biology reference, patient-related information and clinical knowledge. He further identified four basic principles for a successful informatics infrastructure: (1) research infrastructures were best constructed openly and should be coordinated on a national and international level. The human genome was an example of open infrastructure which was extensively used worldwide; (2) patient information was not appropriate for public release; (3) informatics hardware costs halved approximately every two years while the sequencing capacity doubled every year; and (4) like most IT projects, an information infrastructure for Genomic Medicine would require complex management with the added difficulty that most informatics developers were not trained in genetics and therefore the pool of people with the appropriate expertise was very small.

With regards to the fundamental biology reference, Dr Birney mentioned that the reference genome sequence would be updated approximately every two years with minor updates (less than one percent of the sequence), but the updated regions would be disproportionately enriched for areas of interesting biology and likely disease-associated regions. The reference gene and biology resource were growing in stability and utility and were also making advances in non-protein coding genes, but the dynamic nature of these databases would necessitate a similarly dynamic structure for clinical genomic databases, capable of adapting to advancing knowledge. Dr Birney expressed the view that information infrastructure in genomics was at present well funded, though this needed constant investment from research councils and charities and was coordinated worldwide.

By contrast, it was not yet clear how patient information would be coordinated, assuming, for example, that we might have the capacity to sequence the entire population's genomes in five to ten years. This raised many questions: how should patient data be coordinated with the reference genome? How would raw genomic data be archived to allow for periodic recalling, for example if technology advances yielded new information? Should genomic information be part of SPINE (NHS care records system)? How would genomic information be delivered in a useful way to practising clinicians? Dr Birney suggested that useful answers might emerge from comparison and dialogue with pilot projects such as the informatics components of the 1,000 genomes project

Although resequencing projects have large storage requirements, Dr Birney did not believe that disc space would pose a problem for storage of genomic information compared to other high density medically important datasets. Dr Birney compared the disc space required for storing genomic information to that needed to store a complex X-Ray digitally, and far less space than that needed to store a CT scan. However, the challenge in storing genomic information about patients was that the software and the delivery would need to be custom made.

Finally, in resolving how to construct a usable "clinical knowledge base" Dr Birney pointed to a number of existing projects that could already provide partial or prototype solutions. These include dbGAP/EGA and the EU-funded Gen2Phen projects which linked genotype to phenotype; the Online Mendelian Inheritance in Man database (OMIM) which provided clinician-friendly data on genes and mutations underlying Mendelian (single-gene) disorders; and a growing number of locus-specific and in-house databases.

Governance of genomic data (Professor Graeme Laurie)

Professor Laurie identified six challenges for optimal governance of genomic data: consent, confidentiality, public confidence, commercialisation, collaboration and counselling.

Discussions on governance and genetics had taken place over a long period. One of the first reports to be published was by the Nuffield Council in 1993 titled "Genetic Screening: Ethical Issues". The Human Genetics Commission (HGC) also reported on a regular basis. We all share the same basic human genome although each of us had individual variations that distinguish us from other people. This highlighted our common interest in the fruits of medically-based genetics research and a common public good that could be achieved by optimum governance of genomic information. However, an underlying assumption was that genetic information was unique to an individual but that must not belie the fact that there is a range of private and public interests at stake.

Consent had become the dominant paradigm in governance of biomedical research, but there was a risk of over-dependency on consent. Professor Laurie expressed the view that consent was neither necessary nor sufficient to protect individual interests and over-reliance on consent may serve as an obstacle to important public interests.

There had been much recent discussion in the UK around confidentiality and privacy. Protection of privacy under the law in the UK was piecemeal. The Data Protection Act only protected an individual's information when the individual could be identified: anonymised information was not protected. Common law covered certain aspects of privacy such as doctor-patient confidentiality, and the Human Rights Act consolidated these protections. However, an individual's privacy was not an absolute right: there were exceptions when information could be processed to promote public interests. Professor Laurie raised the question whether there were sufficient flexibilities within existing law to promote such public interests while adequately protecting the public interest in individual privacy.

Security of genetic information was a serious public concern. There may be informatics solutions to providing security but these would not necessarily provide complete answers and did not address all of the public expectations with respect to their privacy. It was interesting to note how limited the current law was in protecting the interests of others, such as family members, especially when the genetic information of one individual may have direct consequences for other family members. Another important security issue was access to information: who had access, why, and, particularly, where?

Public confidence in governance and government was fundamental to progress in genomic medicine and genomic research. The UK Biobank Ethics & Governance Council was set up to oversee the legal and ethical implications of the UK Biobank project and to monitor and advise the funders of the project on these issues. The project had already recruited 100,000 participants of the projected 500,000 and broad consent was given by the participants based on robust confidentiality and a transparent ethics and governance framework. There were ongoing questions about data access in the future and commercialisation of the data which were incompletely resolved at this stage. It is the role of the Ethics and Governance Council to advise on these and other future developments.

With regards to commercialisation, Professor Laurie highlighted the need for transparent access policies in today's world of private investment in order to achieve fair, just and equitable sharing. Open access may work for certain aspects of research but not for others such as development of new drugs, or other discoveries and inventions that may be commercially viable. It may also carry unacceptable risks to individual privacy.

The UK Biobank was seen as setting the gold standard in collaboration. Professor Laurie also referred to the Public Population Project in Genomics (P 3G), an international collaboration which aimed to promote scientific interoperability between biobanks to ensure maximisation of scientific data generated, and to facilitate scientific interoperability and data sharing. The P3G project was also considering the governance regimes in different biobanks, asking whether harmonisation of heterogeneous governance and data protection regimes could facilitate progress and advance global interests in genomics.

Professor Laurie ended by stating that optimal governance was not yet with us. There were many examples of "self-help" good practice such as UK Biobank and Generation Scotland. He suggested that, in some cases, formal legal and ethical regimes were too rigid and perhaps did not strike the best balance of interests. There was an additional problem of a lack of regulatory "joined-up-ness" across the various elements of innovation trajectories, from initial conception through research, development, market and beyond.


Discussion took place in which Committee members, speakers and other attendees participated.

One participant gave the view that discussions on clinical management run the risk of being hijacked by genetic enthusiasts who overemphasised the importance of genetic factors and genetic testing. Other conventional and possibly more important factors in disease aetiology and management, such as lifestyle, social factors and family history could therefore be disregarded. In relation to drug therapy and pharmacogenetics, the current trial and error approach to prescribing might be equally cost effective in predicting efficacy and side effects as genetic testing, which may only lead to relatively small advances in clinical practice. Some participants agreed that the science was ahead of clinical practice.

A commonly expressed view was that new genetic tests were potentially of value but required evaluation before being brought into mainstream clinical practice. The importance of assessing the utility of genetic tests was highlighted by several participants, though it was pointed out that it was not clear who would fund research into clinical utility, as NIHR (National Institute of Health Research) excluded funding of laboratory-based research projects.

The issue of the practical end of implementation was raised. Up until the present, almost all genetic testing had been carried out in Regional Genetics Centres, and most genetic tests have been for single-gene disorders. Now that genetic tests were being introduced for more common diseases, the Regional Genetics Centres would not have the capacity to carry out all new tests. However, carrying out the test represented perhaps only half the cost of the test, the remainder including genetic counselling. Another participant concurred with the need for genetic testing to expand beyond Regional Genetics laboratories, but pointed out that there had been years of discussion about setting up molecular pathology laboratories, but this was prevented by "silo budgeting" to individual specialty laboratories. Data on new tests needed to be evaluated in a timely manner, and to achieve this, a new structure would be required to implement "health genomics".

The NHS was not set up to take on board the changes that were associated with the move of genetic testing into the mainstream medical specialties. At present, introduction of genetic testing into mainstream specialties was piecemeal and reliant on presentation of data on new tests to local funders who did not have the necessary expertise or knowledge to make informed decisions on these matters. A particular concern was the lack of genetics expertise in Public Health, which was largely focussed on environmental, rather than genetic issues.

It was pointed out that new, rolling funds would be required to pay for updates to genetic testing equipment funded under the White Paper "Our inheritance, our future" of 2003, as such equipment only had a lifespan of four to five years. The need to fund translational research for evaluating new tests and bringing them into service was also highlighted. The funding model that was in place in Wales for these activities was commended.

The procedure for bringing new genetic tests for single-gene disorders into NHS use was described. The UKGTN had already approved 173 such tests. A similar mechanism needed to be introduced for generating data on the utility of new genetic tests such as single nucleotide polymorphisms associated with common diseases and pharmacogenetic tests of drug utility and responsiveness. No solution was currently in place to meet this need. Attention was also drawn to the need for education of healthcare professionals on genetic testing and commented that the National Genetics Education and Development Centre had focussed to date on surveying attitudes of health professionals and on learning outcomes. However undergraduates needed to develop a concept map of where genetics fitted into healthcare so that they were prepared with appropriate knowledge when they started to practice.

With regards to IT, more money needed to be invested in informatics and more IT experts would be required to set up and manage genomics information systems if genomics was to be useful in healthcare.

On the question on the desirability of "genomicising" medicine arose, it was regarded as inevitable that much of the medical profession would not like to move towards genomics in healthcare, and the pressure for this change may need to come from the science. Patients should also be at the centre of any changes and should participate fully in these discussions. There was resistance to change, and a significant fraction of the £2.5 billion spend on pathology services could be saved if sovereignty of individual specialties were to be given up.

It was asked whether epigenetics could be applied to modifying disease processes. Epigenetic contributions to disease processes cannot at present be quantified as accurately as genetic contributions but it was felt that dialogue between geneticists and epigeneticists should be encouraged, though this might be outside the remit of the Inquiry.

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