Memorandum by the Research Councils UK
1. The MRC works closely with the National
Institute for Health Research (NIHR) and the UK Health Departments
to give a high priority to the translation of underpinning research
in genomics and genetics into improved healthcare, products and
services. MRC thus is a key player in the area of genomic medicine.
2. The ESRC plays a major role in funding research
addressing the implications of ethical, political, legal and social
dimensions for the application of genomics in healthcare settings.
3. The BBSRC's role is to support basic,
strategic and applied research, training and knowledge transfer
in the non-medical biological sciences. One of BBSRC's roles is
to underpin developments in human healthcare and as a consequence
of this underpinning role, BBSRC is not a major stakeholder in
the implementation of genomic medicine.
4. Research Councils UK is a strategic partnership
set up to champion the research supported by the seven UK Research
Councils. RCUK was established in 2002 to enable the Councils
to work together more effectively to enhance the overall impact
and effectiveness of their research, training and innovation activities,
contributing to the delivery of the Government's objectives for
science and innovation. Further details are available at www.rcuk.ac.uk
5. This evidence is submitted by RCUK on
behalf of the three Research Councils listed below and represents
their independent views. It does not include or necessarily reflect
the views of the Science and Research Group in the Department
for Innovation, Universities and Skills. It is structured around
answers to the specific questions posed in the call for evidence.
In addition, the AHRC will submit a separate response to this
Biotechnology and Biological Sciences Research
Economic and Social Research Council (ESRC)
Medical Research Council (MRC)
6. The RCUK Office in Washington DC has
provided detailed information about the situation in the United
States in Annex 1.
7. The Research Councils have invested heavily
in genetics and genomics research and infrastructure over many
years, including cross-Council programmes with ring-fenced funding.
£110 million was allocated to Research Councils in SR2000
for genomics and £136 million was allocated in SR2002 for
post-genomic, proteomic and systems biology research.
8. The framework for the support of innovation
in genomic medicine in the UK is effective compared with many
other European countries, although the situation in the US is
much more favourable (see Annex 1). However, given the speed of
scientific development, regulatory gaps sometimes do appear and
may inhibit translation from basic research to patient benefit.
There is a need for a review of the role of policy and regulation
in promoting innovation and optimising translation.
9. Genomic science is in a healthy state
and is developing very fast. This is an area in which international
collaboration is extensive and effective. UK work is internationally
competitive, thanks to a high level of investment by the Research
Councils and other funders over many years. This high level of
investment will need to be maintained to ensure that the developing
understanding feeds through into benefits for clinical care and
10. There are significant and increasing
opportunities for translation of genomic information into improved
therapies, via the identification of new molecular targets for
treatment and the ability to target treatments more precisely
at those most likely to benefit. Improved understanding of disease
mechanisms will also lead to new diagnostic or prognostic indicators
with clinical application.
11. Storage and interpretation of very large
and increasing volumes of data are major issues in genomics. There
are already many large databases for common use, and the European
Bioinformatics Institute in Cambridge plays a key role in curating
and annotating these, and in developing the bioinformatics methodology
to enable optimal exploitation of the data. Promoting interoperability
of related databases via common standards will be important, but
the Research Councils do not think a single common public database
of genomic information is realistic.
12. The research capacity programme of the
NHS Connecting for Health initiative will be very important in
ensuring that medical information can be used optimally to interpret
13. The use of genomics and gene expression
platforms at the level of the entire genome offers unique opportunities
for biomarker research and its translation to patient benefit
in terms of tailoring treatments for optimal efficacy and safety
according to an individual's genetic make-up.
14. Biobanks such as the UK Biobank and
Generation Scotland will build on current advances in genomics
to develop the knowledge of genetic and environmental influences
involved in health and disease to underpin discovery of new ways
to prevent and treat different conditions.
15. Genetic information has already had
a significant impact on the diagnostic classification of single
gene diseases, and increasingly will allow tailoring of treatments.
As the use of genomic information becomes more widespread in the
prevention and treatment of more common complex diseases, patients
will have to be informed much more clearly of the meaning and
consequences of any genotyping, and a much wider spread of practitioners
will need to be trained to offer advice based on genomic information.
16. For the purposes of this response, we
have taken genomic medicine to mean the application of scientific
understanding emerging from research carried out at the level
of the genome to medicine and public health, including increased
understanding of disease aetiology as well as applications in
diagnosis, treatment and prevention of disease.
Who is in charge of setting and reviewing policy
in this area?
17. A large variety of bodies, of differing
status, are involved in setting and reviewing policy relevant
to different aspects of genomic medicine. These include the Health
Departments, statutory bodies such as the Human Fertilisation
and Embryology Authority, Government advisory bodies such as the
Human Genetics Commission and the UK National Screening Committee,
Special Health Authorities and Agencies such as the National Institute
for Clinical Excellence (NICE) and the Medicines and Healthcare
products Regulatory Agency (MHRA), and non-government bodies such
as the Nuffield Council on Bioethics, the Research Councils, the
Wellcome Trust and other funding bodies. Learned societies (including
the Academy of Medical Sciences) and, internationally, the Human
Genome Organisation (HUGO), also play a major role. As the area
of policy-making is very wide, this variety of input is probably
a strength. Review and input is usually on an issue-specific level,
and this is perhaps the most sensible approach, given that the
issues in different fields and different disease settings are
liable to be very different.
Who provides scientific advice on policy development?
Who monitors and anticipates potential scientific developments
and their relevance to future policy? How effective are these
18. The Department of Health's Policy Research
Programme funds research to inform policy development. Learned
societies, Research Councils and the large funding bodies like
the Wellcome Trust provide scientific advice and play a major
role in monitoring and anticipating potential scientific developments
and their relevance to future policy. The mechanisms for monitoring
are usually ad hoc and are related to the peer review system and
the expert panels managed by grant-awarding bodies, although major
Foresight exercises have also played a role. The mechanisms work
reasonably well, and are sufficiently flexible to respond quickly
to new scientific advances. Where issues are of sufficient importance
to merit changes in law (eg the current discussion of stem cell
issues or the use of human tissues), the same bodies are also
active in providing scientific advice and input to government
Does the existing regulatory and advisory framework
provide for optimal development and translation of new technologies?
Are there any regulatory gaps?
19. Genomics-related technologies have been
predicted since the 1980s to be a basis for revolutionising clinical
practice but so far, despite long-term investment of public and
commercial funding, they have failed to live up to expectations.
Policy support and, increasingly, public financial support have
been provided for the more effective translation of fundamental
scientific findings to therapeutic applications, and yet the timescales
for emergence of effective novel treatments seem to be ever-lengthening.
20. In most industry sectors, the expectation
is that small and medium-sized enterprises (SMEs) will be more
innovative than large multinational companies, challenging existing
innovation models and succeeding with new approaches. However,
in the case of life science and genomics-related areas, the large
multinational companies have an unassailable dominance of the
translational processes for genomics-related technologies and
the role of regulatory systems in reinforcing this dominance is
increasingly being recognised.
21. The life science industry sector, which
includes genomics-related medical developments, has evolved over
the past thirty years in a symbiotic relationship with regulators
and regulatory systems: regulation to some extent constrains the
companies it applies to, but as it becomes more onerous, it increasingly
acts as a barrier to entry for new companies until only the incumbents,
of ever-increasing size, are able to operate profitably. This
situation mitigates against optimal development and translation
of new technologies.
22. Given the pace of fundamental scientific
developments relevant to genomic medicine, regulatory gaps appear
frequently. Recent examples include pharmacogenetics and stem
cell-based therapies. The technology in both these cases clearly
requires regulation to ensure its safety, quality and efficacyindeed
regulation is required before private investors can be assured
of a viable market for the medical developments in which they
may choose to invest. The response of regulators is usually to
seek precedents among existing instruments rather than to design
a regulatory system de novo. However, the choice of instrument
then locks the relevant technology into an innovation pathway
that may not be optimal for its future contributions to medicine.
In light of such limitations, there is a need for fundamental
review of the role of policy and regulation in guiding and constraining
innovation in genomics-related medicines. Regulatory systems to
control the safety, quality and efficacy of products operate mainly
at European level, with the European Medicines Agency (EMEA) and
the US FDA increasingly being the main locus of regulatory development
and reform. Any fundamental review of regulation as applied to
genomic medicine will therefore need to be undertaken at an international
In what way is science and clinical policy decision-making
informed by social, ethical and legal considerations?
23. Reviews of social, ethical and legal
issues by bodies with a national remit such as the Human Genetics
Commission and the Nuffield Council on Bioethics (funded in part
by the MRC) have a significant influence on science and clinical
policy decision-making. Research Councils contribute to such reviews,
and have been actively promoting research into social, ethical
and legal aspects of genomics for some time, the output of which
informs national debate and policy setting. The MRC and ESRC both
develop and promote ethical and legal guidance for researchers
and MRC has an internal ethics, regulation and public involvement
advisory committee. BBSRC Bioscience for Society Strategy Panel
provided social and ethical guidance for researchers. The Research
Councils also ensure that large scientific studies which raise
particular issues have their own source of ethical advice; for
example the UK Biobank has its own Ethics and Governance Council.
NHS ethics committees have an important role in monitoring ethical
acceptability of individual studies involving NHS patients or
data relating to them.
How does the framework compare internationally?
24. The policy framework for the support
of innovation in genomic medicine in the UK is effective compared
with many other European countries, although Denmark and Sweden
are claimed to be more effective than the UK. However, the situation
in the US is very much more favourable than in Europe, including
the UK, with an order of magnitude more investment, both public
and private, in translation of new technologies. More detail on
the US position is in the submission from the RCUK USA office
at Annex 1.
What is the state of the science? What new developments
are there? What is the rate of change?
25. The state of science appears healthy,
based on large-scale investment over many years by Research Councils
and other major funders, particularly the Wellcome Trust, and
the outputs of major international collaborative initiatives such
as the Human Genome Project, the HapMap project and the SNP (Single
Nucleotide Polymorphism) consortium. Following on from the completion
of the Human Genome Sequence and the subsequent SNP discovery
initiatives there is a large-scale research effort to identify
genetic factors involved in common complex diseases. The success
has been variable to date but large collaborative initiatives
and funding (such as the Wellcome Trust Case Control Consortium
and MRC funding for collections of DNA samples from large patient
cohorts) have led to a rapid increase in the identification of
potential genetic markers of complex disease risk from genome-wide
association studies. From these, many more genuine genetic influences
on disease risk or outcome are likely to be identified in the
near- to medium-term. The need for European collaboration on disease
specific cohorts has become increasingly important as there are
insufficient patients in the UK and the speed of DNA collections
will need to be accelerated. High throughput genotyping and sequencing
are the main technology platforms required to identify and screen
for variations in the genome which may give rise to disease or
influence treatment outcome. Both platforms are now readily available,
although costs are still rather high. Significant developments
in high throughput sequencing technology are rapidly reducing
the cost of large-scale sequencing and genotyping, and it is likely
that widespread genotyping or sequencing of individual genomes
will become feasible at reasonable cost in the medium term. This
raises the issue of how best to make high throughput sequencing
accessible to the scientific community and whether this should
be centralised as opposed to being distributed. In the field of
cancer research, genetic and genomic research has made significant
progress and it is generally accepted that we are on the cusp
of a new era of medicine that will be driven by genomic medicine
(eg the tailoring of therapy to particular genetic lesions in
26. Large-scale efforts to understand the
function of all mammalian genes and their relevance to human disease
are underway, using a range of model systems, and the rate of
research developments is very fast. Significant advances are also
being made in understanding the role of epigenetic modification
and other regulatory mechanisms in controlling gene expression
and function, and genetic discoveries will increasingly lead into
a systems biology approach to understanding human biological function
and disease aetiology. The importance of genes in microbes is
also now becoming recognised: about 90 per cent of the cells in
the human body are in fact resident microbes, which are essential
for human functioning.. The human microbiome project is now beginning
the project of cataloguing these genes.
27. Many of the high-throughput experimental
techniques in genomics became available for the first time in
the mid-1990s, but they were expensive to acquire and operate
and in the UK were therefore limited to the major pharmaceutical
companies. However, the techniques were available to other well-funded
laboratories around the world and the UK academic sector needed
to acquire and use these techniques to understand a wide range
of biological and biomedical problems at the genomic level. Visits
made by BBSRC staff to the United States confirmed that the UK
research community was in danger of becoming less internationally
competitive without access to facilities for these techniques.
28. In 1998 the Research Councils received
a generous allocation of funds from the Office of Science and
Technology which permitted the first large scale co-ordinated
investment in genomic research. BBSRC funded a series of special
initiatives starting in 1997, the main focus of which was to provide
the capital funding necessary to acquire the new technologies
(largely transcriptomics) as quickly as possible for those communities
most relevant to the BBSRC mission to ensure their continued competitiveness.
This was achieved through competitive funding of consortia built
around model organisms of interest to BBSRC in the Investigating
Gene Function Initiative. Funded consortia were based around model
plants (Arabidopsis, cereals) bacteria (E. coli, Streptomyces)
and animals (Drosophila, farm animals). The role of the consortia
was to acquire, use and develop the new technology and to provide
a source of expertise and advice to the scientific community about
these new techniques and to assist in their widespread implementation.
29. To ensure co-ordination of investments
with other research councils (who also received additional funding
to support genomics research starting in 1998-99), a cross-Council
genomics co-ordinating committee was established involving representatives
from BBSRC, CCLRC, ESRC, EPSRC, MRC and PPARC together with a
representative from DTI. The role of this group was to exchange
information about intended investments and future strategies,
encourage co-funding of research proposals and establish an evaluation
plan for the investments being made in genomics.
30. In addition to the direct support of
the acquisition and use of genomic technology, funding was also
provided by BBSRC to support the further development of the techniques
and to improve the analysis of data through the support of bioinformatic
31. Further initiatives were supported by
BBSRC through funding provided under spending reviews in 2000
and 2002 to support exploitation of the new technology, some of
which were relevant to genomic medicine. These include the Exploiting
Genomics Initiative and the Applied Genomics LINK programme, co-sponsored
with MRC and DTI, in which BBSRC supported 13 projects sharing
50 per cent of the costs of each project in collaboration with
the private sector.
A report on the outcome of this LINK programme has been published
recently as a cross-council case study for economic impact.
32. Between 1997-2007 BBSRC has spent approximately
£102 million on 352 grants through 12 separate initiatives
that acquire, support and exploit genomics research. In addition
to the special initiatives supported by BBSRC, an increasing number
of grant proposals involving genomic level investigations was
funded through the responsive mode. BBSRC spent £141 million
between 2003-07 on research in responsive mode that acquired,
supported or exploited genomics research. Both studentships and
fellowships that feature genomic approaches have been supported
to ensure the next generation of researchers are well trained
in genomic techniques. Some of these are likely to enter genomic
medicine. BBSRC spent £12.5 million on studentships in the
area of genomics between 2003-07. BBSRC spends close to a quarter
of its annual investment in research on projects that acquire,
support or exploit genomics research.
The ESRC used its spending review
allocation of £10 million to invest in research into the
implications for society of advances in genomics technologies.
This funding, together with subsequent further investment from
the Council's baseline, has established the ESRC Genomics Network.
This consists of three Research Centres and a Genomics Forum.
CesagenESRC Centre for Economic
and Social Aspects of Genomics, a collaboration between Cardiff
University and Lancaster University. The focus of Cesagen's work
is on the social, policy, economic, ethical and legal aspects
of genomics and associated developments.
EgenisESRC Centre for Genomics
in Society based at the University of Exeter. Egenis researches
developments in the field of genomics (and more broadly bioscience
and biotechnologies), and the social implications of these developments
from a social science, philosophical and biological stance.
InnogenESRC Centre for Social
and Economic Research on Innovation in Genomics, a collaboration
between the University of Edinburgh and the Open University. Innogen's
research has a strong focus on innovation, globalisation and stakeholder
engagement with regards to genomics and the life-sciences.
ESRC Genomics Policy and Research
Forum. The Genomics Forum has the remit to identify and exploit
synergies between the Genomics Centres, and promote work between
natural and social scientists. The Forum aims to actively engage
policy audiences, business, the media and the public more widely
with genomic science and technology debates.
33. By virtue of the investments made by
Research Councils and other funders, genomic research has become
commonplace over the last decade and has been fully integrated
into both experimental and theoretical approaches to studying
biology and applications to research involving disease aetiology,
diagnosis and development of therapeutics for the clinic.
Who is taking the lead in the consideration and
co-ordination of research and the development of new technologies?
34. Funding bodies take the lead in co-ordination
of research in the UK, and of the large international initiatives.
The Human Genome Organisation, the US National Institutes of Health
(NIH) and Genome Canada play a significant role in co-ordination
of international initiatives. European consortia funded under
the EU Framework Programmes play an important role in co-ordination
of research in Europe. Considerable benefits have been gained
from cross-Research Council initiatives on research in genomics
over more than a decade, ensuring for example the co-ordination
of research in human and animal model systems, with research into
ethical, social and legal issues being linked to, and informed
by, biological and biomedical advances. The commercial sector
plays a very significant role in the development of new laboratory
and medical technologies, often initially based on spin-out companies
from academic research.
How effective is the policy and investment framework
in supporting research in this area?
35. The framework for academic research
appears to be effective in maintaining the internationally competitive
position for UK research (see below). The Research Councils have
historically worked together to ensure complementarity of approach
and economies of scale where possible and will continue to do
so in future.
How does research in the UK compare internationally?
How much collaboration is there?
36. The direct outcome of the investments
in genomics over the last ten or more years has been the continued
competitiveness of UK research in the biological and biomedical
sciences. The performance of the UK scientific community in these
areas has been second only to the United States in international
International visibility, as demonstrated by invited speakers
to international conferences, is however decreasing compared with
10-15 years ago and the recent high levels of investment in Asian
countries is starting to feed through into increased international
impact. A continued high level of investment will be required
to maintain the UK's competitive position.
37. Several UK initiatives have the potential
to give the UK an advantage in the area of genomic medicine. The
UK Biobank initiative
is world leading, and has the potential to facilitate research
into identifying gene-environment interactions for a range of
common diseases in the population at large. The investment of
the Research Councils and the Wellcome Trust in supporting large-scale
genotyping and sequencing projects in centres of excellence within
the UK are all positive factors. The NHS "Connecting for
Health" initiative is important in enabling better use of
clinical information held throughout the NHS for research, and
ensuring that the UK can utilise the advantages for health research
that stem from a universal publicly-funded health care system.
38. The US Food and Drug Administration
has been very proactive in encouraging the submission of genetic
data from clinical trials under a voluntary scheme which takes
account of the fact that much of the science is at the exploratory
stage at present. Their activities, supported by the US Government,
have placed the USA at the forefront in progressing research towards
translation into medical practice. Europe and the UK are currently
following the USA lead in the area.
What are the current research priorities?
39. An important research priority for MRC
is to ensure that findings from genome wide association studies
of common complex diseases showing possible genetic influences
on disease risk are translated into useful information for health
care or disease prevention, for instance by improved understanding
of disease aetiology or mechanism, or the development of diagnostic
or prognostic biomarkers.
40. The widespread availability of genomic
and related data arising from high throughput techniques, together
with investments in bioinformatics and computational approaches
has allowed the development of computational models to explain
experimental observations and predict alternative possible outcomes.
This integration of mathematical modelling and direct experiment
is known as systems biology, and is currently one of the most
rapidly developing scientific areas. The UK has a significant
international lead in systems biology largely as a result of Research
Council investments through the spending review settlements of
2002 and 2004. The BBSRC strategy panels for Integrative and Systems
Biology, Tools and Technologies, the Healthy Organism, and Studentships
and Fellowships are able to develop and maintain an overview of
the resources, facilities, tools, technologies, and training required
to sustain the UK's lead in systems biology. Following the Comprehensive
Spending Review 2007 settlement, BBSRC is embedding a systems
approach to all areas of its remit, and this will underpin advancements
in systems approaches to medicine.
41. It seems that the rate of change in
pure scientific development terms might be faster than associated
governance, ethical and legal frameworks, and we therefore stress
the benefits of continuing to fund work on these alongside pure
biomedical research. Current research priorities for ESRC include:
The need to explore more fully the
relationship between a range of biological influences, including
genetics, and societal factors when understanding the precursors
and motivations involved in individual behaviour and make-up (ESRC
strategic plan p 14).
Collection of biomedical and genetic
data alongside large scale longitudinal social science data collection
as part of the UK Household Longitudinal Study (UKHLS in order
to better understand the interaction and influence of each over
the life course.
What is the role of industry? How much cross-sector
collaboration takes place?
42. The pharmaceutical industry is currently
examining the potential of pharmacogenetics (ie the role of genetic
factors in a patient's response to therapy) to impact on the field
of personalised medicine. There are already a number of cancer
treatments that are only effective in certain genetically-defined
tumour subtypes, and the pharmaceutical industry will play an
important role in the development of genetic testing to improve
treatment efficacy or avoid adverse reactions in other diseases.
For this reason, they have been acquiring DNA from individuals
participating in clinical trials on a large scale. These samples
will represent worldwide populations, the UK being a fairly minor
component, and there may be an opportunity to use these collections
to look for genetic factors involved in disease. There is good
cross-sector and industrial collaboration, but there is always
room for improvement here, as most major pharmaceutical companies
have only bought into this idea relatively recently.
43. The diagnostics industry will play an
increasingly important role in the translation of laboratory based
research into practical and cost-effective tests for clinically
relevant genetic variations. There is active collaboration between
Biopharma sector and academic scientists at the level of pre-competitive
discovery research, and between academic researchers and the biotechnology
sector in relation to technology development.3, 4
Is genomic information published, annotated and
presented in a useful way? Should there be a common, public database?
If so, who should fund, and have responsibility for, such an initiative?
44. Relative to conventional biological
research, genomic research data are generated in large volumes
and are often complex, involving many inter-related genes and/or
proteins. The European Bioinformatics Institute (EBI), an outstation
of the European Molecular Biology Laboratory, located near Cambridge,
holds large-scale databases of this nature, and has been instrumental
in setting the international standards through which such experiments
are conducted and results are annotated. It provides bioinformatic
research and technological solutions to the methods of curating
and making available data generated through genomic investigations.
This has ensured that results from large sections of the community
involved in genomic research are made available in a format that
is consistent with other laboratories world-wide and available
for anyone to access for research purposes. This has been further
encouraged through the expansion and development of data-sharing
policies by several Research Councils. Recent expansion of the
EBI to provide a new building to house larger numbers of staff
involved in service provision and research has been funded by
BBSRC, MRC and the Wellcome Trust. Further plans are currently
being drawn up for increased activity of biological data provision
in Europe through EBI using a collaborative funding approach from
European member states.
45. Any common public database would need
to be very complex to deal with the different types of platform
and data (eg nucleotide sequence vs array data vs single nucleotide
polymorphisms (SNPs) vs methylation vs proteome etc). Information
in genomic databases is of optimal use for research only when
collected alongside other information (genotypic, phenotypic,
social, economic data etc). The more detailed this information
is, the more useful it becomes for research purposes, but the
practical, ethical and legal issues increase (eg the cost of keeping
such resources, the potential for disclosure of participants'
personal data, the potential for use of the resource beyond what
was originally envisaged, and associated decisions about access
to the resource). Decisions about storage and the governance arrangements
for such studies are therefore critical.
46. On the face of it, it seems entirely
logical that there should be a standard depository for all information,
as it should cross-fertilise. However, capturing a wide range
of information (including social and economic) in relation/ addition
to the genetics in a single database would probably be impossible,
and a single database probably cannot answer all the potential
research questions. For this reason, the continuance of collection
of genetic data in a variety of databases will be important, as
will the promotion of common standards and practices to facilitate
Who should provide the framework for optimal evaluation
of data and translational opportunities? What policy and funding
mechanisms are in place for recognising and utilising potential
47. Currently the MRC and MRC Technology
play a major role in the evaluation of data and translational
opportunities, alongside other major funding bodies (eg Cancer
Research UK and the Wellcome Trust), university technology transfer
offices and patent agencies. There is effectively a "market
economy" which operates reasonably efficiently. The problems
of a gap in funding for translational research in the UK, as identified
in the Cooksey Report,
exist in this field as in other areas of applied medical research.
The MRC and NIHR are providing new investment and new funding
mechanisms for translational research, with additional resources
provided in the recent Comprehensive Spending Review, to help
bridge this gap.
Is other medical information recorded in a suitable
format to allow optimal interpretation of genomic data? How should
genomic data be brought together with other health information?
48. The increasing use of electronic storage
for health records has the potential for significantly increasing
the utility of medical information in genomic studies, and the
NHS Connecting for Health initiative is very important in this
regard. Standardisation of the way medical data and other phenotype
information is recorded remains a challenge.
49. The ESRC, Wellcome Trust, EPSRC and
MRC, wish to stimulate and support the use of electronic databases
for health research. Electronic patient records and longitudinal
cohort databases provide a rich data source with the potential
to answer key questions in biomedical, clinical and public health
research across the full range of infectious and non-communicable
diseases, as well as other medical conditions. As a result, the
four funding bodies are commissioning a range of research projects
and activities to encourage the use of health data for research
Research is due to begin in Autumn 2008 and will last between
one and five years. Support will be provided across three main
health research using electronic
patient records and major longitudinal cohort databases;
training programmes and workshops;
public engagement activities.
50. It is recognised that the utility of
the biological and genetic data is enhanced by the wealth of social
and economic data. Indeed, a key aim is to allow the genotype
to be studied with the phenotypebringing together economists,
sociologists, psychologists, epidemiologists, genetic scientists,
to work together in ways that combine all their skills and expertise
in the study of specific medical and psychological conditions.
51. The MRC and ESRC have been working with
Wellcome Trust to assist with the collection of biomarkers and
genetic material from a number of pre-existing national birth
cohort studies which contain a wealth of medical, social and economic
data. These include the 1958 Birth Cohort (National Child Development
Study, NCDS) and the 2000/2001 Birth Cohort (Millennium Cohort
Study). Plans, led by the ESRC, are being developed with MRC and
Wellcome Trust to co-ordinate some existing studies with other
cohorts (ALSPAC1990-91 Birth cohort, English Longitudinal
Study of Ageing (ELSA), 1970 and 1946 cohorts), and to launch
a new cohort study in 2012. Cooperation among funders in relation
to the governance of cohort data is particularly important and
an appropriate governance structure for this particular set of
longitudinal studies is currently being developed. The UK Household
Longitudinal Study (UKHLS) is a major new longitudinal study,
commissioned by the ESRC, of 40,000 households from across the
It will provide high quality, longitudinal social survey data
for academic and policy research and will also support the collection
of a wide range of biomarkers and health indicators, thereby opening
up prospects for advances at the interface between social science
and biomedical research.
What are the implications of the generation and
storage of genome data on personal data security and privacy,
and on its potential use or abuse in employment and insurance?
How should these be addressed?
52. The generation and storage of genome
data for research and medical practice will require systems to
be established to ensure personal data security and privacy, as
there are clear concerns on this issue among the general public
and government. The potential use or abuse of information in both
employment and insurance are issues which should be addressed
via both public consultation and by discussion with relevant professional
or trade associations. However, we should also consider the possible
negative "alarmist" impact of identifying disease associations
for which there is no current therapy, especially where there
is a high penetrance for a given allele in the population that
actually has a low relative risk. The ongoing Research Capability
Programme within the "NHS Connecting Patients for Health"
initiative and the systems put in place by the UK Biobank will
address the above concerns to some extent.
53. In terms of data storage and access,
safeguarding anonymity is a key issue and we suggest that genetic
information and phenotypic information should always be stored
in physically separate locations, with the key to data matching,
and data matching capacity, held by a third and neutral party
and for particular safeguards to be set up for accessing sensitive
data (eg the ESRC is commissioning a "Secure Data Service",
which could be of use in holding information related to health).
Governance arrangements should specify how linkage approval should
be made, for what purpose, and should ensure that the anonymity
of linked records is preserved.
What opportunities are there for diagnostics,
therapeutics and prognosticsnow and in the future?
54. The opportunities for diagnostics, therapeutics
and prognostics are clear and exciting. Improved understanding
of disease mechanisms and aetiology will lead to new prognostic,
diagnostic or therapeutic biomarkers and new therapeutic targets,
although many will take some time to materialise. The UK has been
at the forefront of academic research in genomics this field,
and it is important that this position is maintained and translated
into patient care. Diagnostics in relation to tumour markers is
already well-established and will continue to develop, allowing
more appropriate therapies to be used, especially where there
is only a narrow therapeutic window. There is considerable concentration
of effort, especially by large pharmaceutical companies, into
relatively few areas. The higher risk areas of research are still
undertaken in the public/charity sector. A further encouragement
or small Biopharma "roll out" from the public sector
would certainly be welcome.
55. However, the practical returns on the
identification of specific genetic risk in common complex diseases
are less clear, in view of the relatively low penetrance of most
susceptibility genes, the confounding aspects of environment and
lifestyle, and the resulting difficulties in drawing useful lessons
or identifying useful interventions.
It is possible that improved genomic understanding of the mechanisms
of disease aetiology may in time lead to novel forms of therapy,
but such gains may be piecemeal and unpredictable.
56. Developments in the field of pharmacogenetics,
including the identification of genes associated with positive
or adverse drug responses, are likely to follow a similar pattern
to the identification of disease susceptibility genes. In other
words, a number of relatively rare single-gene responses will
be identified that may prove useful in practice. However, genetic
explanation of more common variations in drug response, and the
development of effective tests, will likewise be confounded in
practice by factors including low penetrance and other sources
of personal variation. There is thus a likelihood of significant
but highly localised pharmacogenetic gains in the efficiency and
efficacy of drug use, but a revolutionary shift towards so-called
"personalised medicine" is far less likely.4
Who is responsible for translation to clinical
57. Progress in this area tends to be driven
by small Biopharma, although both large Biopharma and charity/Research
Councils are also playing an important role. In addition, the
NHS and the Medical Royal Colleges (eg in their role of providing
continuing professional development) have a role.
Given the pace of technological advance, how "future-proof"
is healthcare investment in this area? How does the UK compare
to other countries and what lessons can be learnt?
58. We have not addressed these questions,
which are somewhat outside our remit.
How meaningful are genetic tests which use genome
variation data? What progress has been made in the regulation
of such tests?
59. Genetic tests related to single gene
disorders and high penetrance genes such as BRCA1 are clearly
meaningful, and already play an important role in clinical practice
and for affected families and individuals. However, the meaning
of tests relating to more complex disorders still requires very
careful evaluation. There are many publicly available genetic
tests. For example, genetic testing for psychiatric disorders
is becoming commercially available with venture capitalists and
scientists seeking to establish niche markets by selling "direct-to-consumer"
testing. Psynomics (www.psynomics.com)
has developed a test that helps diagnose people with bipolar disorder
(Couzin, 2008). Companies such as SureGene (www.suregene.net/home.aspx),
are developing tests for other psychiatric disorders while NeuroMark
is marketing a test for pharmacogenetic responses to anti-depressant
treatment. The success of the business model in driving these
developments is likely to encourage further biotech companies
to circumvent existing psychiatric healthcare models in favour
of selling direct to the customer.
60. In the UK, recent media coverage
has raised public awareness and expectations of these scientific
developments as well as fears and concern about the commercial
availability of predictive and diagnostic testing. Psychiatrists
and other doctors have warned that the proliferation of such direct-to-consumer
testing will mislead and confuse consumers.
Providing individuals with an estimate of the risk of developing
psychiatric disorders is far from straightforward, and may not
account for the complex interaction of genetic and environmental
factors. There seem to be two critical potential difficulties:
1) the correct interpretation of the test, which is a particular
concern given the generally poor grasp of scientific method by
practitioners, counsellors and public, and 2) statistics and the
validity of the test, and public perception of that validity.
Both of these problems are compounded by the limited value in
delivering a test/genetic predisposition if there is no suitable
course of action for the individual to take. However, these considerations
have implications for how the utility of new genetic and genomic
techniques should be evaluated. Any assessment of utility must
take account of the complex meanings that attach to genetic testing,
and the ethical and social consequences that follow from the application
of such tests. This would be best achieved by adopting some of
the newer developments in health technology assessment which pay
explicit attention to the context of use, and which draw on new
methods of user engagementincluding both practitioners
and patients/consumersto ensure that new technologies meet
61. Annex 1 provides details on the US Government
legislation, in particular the Food and Drug Administration (FDA)
which has responsibility for assessing the safety and effectiveness
of genetic tests used for diagnosis or prediction of disease.
In what way do genome-wide association studies
contribute to the identification of biomarkers? How is the study
of genetic factors and biomarkers integrated for translational
are characteristics that are objectively measured and evaluated
as indicators of normal biological processes, pathogenic processes
or pharmacological responses to a therapeutic intervention.
They play a key role in understanding the aetiology and progression
of disease, as well as understanding the mechanism of action of
therapeutic agents and investigating the response of individual
patients to treatment. Biomarkers are an essential part of the
drug discovery process, being used at every stage from target
identification to patient stratification.
63. Genome-wide association studies provide
a comprehensive approach to identification of common genetic variants
(one type of "biomarker") across a population which
are either directly associated with the risk of disease (eg cancer
risk) or influence the inheritance of commonly measured quantitative
traits, (another kind of biomarker, eg plasma concentrations of
cholesterol as a risk factor for cardiovascular disease). These
studies will lead to the discovery of new genetic factors and
disease causing molecular pathways that will in turn lead to the
development of further biomarkers and open up new therapeutic
64. Genome-wide association scans will also
help screen for biomarkers associated with the clinical response
to treatment and may lead to the identification of SNPs and differentially
expressed genes that are related to, and are predictive of, the
responder status. The use of genomics and gene expression platforms
at the level of the entire genome therefore offers unique opportunities
for biomarker research and its translation to patient benefit
in terms of tailoring treatments for optimal efficacy and safety
according to an individual's genetic make-up.
What impact will genomic data have on data emerging
from projects such as UK Biobank, Generation Scotland and other
65. UK Biobank is developing a prospective
resource of 500,000 people aged 40-69 from around the UK, involving
extensive baseline information, physical measures, biological
samples and medical information. Generation Scotland (like many
other studies) is complementary to UK Biobank and will help to
develop the knowledge of genes which contribute to health or ill-health.
Such studies aim to help researchers better understand the causes
of disease and to find new ways to prevent and treat different
conditions. Understanding the genetic basis of disease is one
component of building a full picture of health processes. UK Biobank
and other biobanks provide the opportunity to investigate how
genetic factors combine with lifestyle and other factors to cause
66. The population-based, prospective approach
is complementary to other genomic research approaches. UK Biobank
will build on existing genomic information arising from genome-wide
association studies and other approaches, provide further opportunities
for genomic investigation and discovery, and, importantly, become
increasingly valuable (and cost-effective) to researchers to extend
studies into the assessment of the complex interplay between the
effects of different factors (eg genetic and environmental) in
the development of, and recovery from, disease. The suite of samples
stored will support study of a wide range of biomolecules and
will allow many types of assays (eg proteomic and metabolomic)
to be undertaken in addition to genetic analyses. Studies of the
scale and complexity of UK Biobank will be unique in having the
power to address these research questions which build on the outputs
of genomic research data.
What impact will genomic information have on the
classification of disease? How will it affect disease aetiology
and diagnostic labels?
67. Genetic information has already had
a significant impact on the diagnostic classification of a number
of single-gene disorders. However, even in single-gene diseases
such as cystic fibrosis, genetic techniques have been assimilated
into existing clinical methods of diagnosis and treatment, resulting
in modification rather than straightforward replacement of established
The incorporation of genetic and genomic information and techniques
into clinical practice, and the reformulation in practice of disease
categories, depend as much on how that information comes to be
used in the clinic as on basic scientific ideas of aetiology.
68. At the moment there is relatively little
genetic data that is clinically useful in relation to more complex
disorders. However, this is clearly going to change over the next
two decades with the likely integration of symptomatology-based
classification with classification related to the molecular basis
of disease, which may also lead to differentiation of disease
into sub-categories. For example, genetic epidemiology has already
proved influential in shaping the nosography of psychiatry and
developments in molecular genetics are beginning to provide evidence
to challenge the traditional classifications. This makes it increasingly
difficult for psychiatrists unambiguously to assign patients to
distinct categories of major psychosis.
69. The situation is far more complicated
when dealing with the much larger and epidemiologically more important
class of common complex diseases. In most such cases, however,
susceptibility genes confer only a relatively small increase in
the risk of developing symptomatic disease, while a wide range
of environmental, social and lifestyle factors may contribute
to the development of disease in the presence or absence of any
genetic predisposition. Consequently, the impact of such information
on the clinical classification and diagnosis of disease will depend
upon a wide range of variables, including the size of the genetic
contribution to risk and the availability of effective preventive
or therapeutic interventions. The context of use, and the meaning
and utility of genetic and genomic information in that context,
will be a key factor in determining how such information will
be incorporated into clinical practice and health care delivery.
How useful will genomic information be as part
of individualised medical advice? What provisions are there for
ensuring that the individual will be able to understand and manage
genomic information, uncertainty and risk?
70. From the patient's point of view, genomic
information may be interpreted in a number of ways. In some cases,
knowledge of a genetic predisposition may relieve feelings of
guilt or responsibility for an illness. In other cases, however,
identification of a genetic risk may entail an additional burden
of responsibility on the patient, not just directly for themselves,
but for their families and reproductive choices. Indeed, the language
in which medical and policy discussions are couched commonly tends
to suppose that patients have a duty to take appropriate preventive
or prophylactic action. But such action is not always in the patient's
There is also evidence that patients are less inclined to follow
the advice of healthcare professionals on changes to life style
and behaviour than to seek specific medical interventions.
Increased testing for susceptibility genes may consequently lead
to a corresponding increase in the demand for medical monitoring
Any such increase will obviously have resource implications for
the health services.
71. The language in which preventive advice
is offered may play an important role in the failure to effect
behavioural change among those deemed to be at increased genetic
risk. Patients often have a complex multi-causal understanding
of inherited risk and prevention that draws on knowledge of their
own family history and the health of relatives.
While lay ideas of kinship commonly differ significantly from
genetic accounts of relatedness, knowledge of family history nonetheless
provides a useful medium of communication between health care
advisors and patients. In this respect, overly rigorous insistence
on a strictly genetic understanding of relatedness may inadvertently
lead to a failure of communication and foreclose on a valuable
channel for offering meaningful advice on risk and prevention.
Should there be a regulatory code (mandatory or
voluntary) covering the provision of this advice?
72. It is clearly important to ensure the
quality of advice based on genetic and genomic information, and
effective training of those giving advice is essential (see below)
but we do not have a view on whether this might best be achieved
via a regulatory code.
What are the implications of developments in genomic
technologies for the training of medical specialists and other
health professionals? Are there any gaps that need addressing?
What is the assessment and planning for future needs in capacity?
73. Until recently, responsibility for providing
genetic health care and advice has largely devolved to genetic
medicine specialists and genetic counsellors. With increased knowledge
of the genetic dimensions of common complex diseases, however,
a much wider spread of practitioners are likely to find themselves
called on to offer advice on genetic matters. There will therefore
be a need not only to increase provision of specialist training,
but also to integrate appropriate training in providing genetic
health care into the core medical and nursing curriculum. The
meaning and utility of this additional information in a healthcare
setting is not determined solely by the possibility of estimating
the extent of the genetic risk that patients face. The training
of healthcare professionals (for example, via Continuous Professional
Development courses.) should not be confined to a scientific appreciation
of disease genetics. It should also emphasise the value of family
history as an effective means of structuring communication with
patients, and should stress the importance of understanding that
history from the patient's perspective as well as from a strictly
genetic point of view. In other words, the utility of information
on genetic factors also depends upon the practitioner's ability
to relate the risk of disease to the patient's life and circumstances,
including the social and moral complexities of family life. A
recent Academy of Medical Sciences Report
has highlighted similar issues relating to the identification
of environmental causes of disease and this could be an excellent
starting point. .
74. New exploratory research is needed in
order to assess the likely consequences of these developments
for individuals and family members, for medical practitioners,
genetic specialists and health professionals, and the potential
demands on healthcare services. For example, the ongoing collaboration
between Cesagen, Psychological Medicine, Medical Genetics, Social
Sciences, and the Wales Gene Park at Cardiff University will provide
an evidence based assessment of the likely personal and professional
consequences of new genetically-based diagnostic criteria and
risk information. It will also inform the ethical debate concerning
the consequences of risk evaluation for psychiatric conditions.
75. Overall, prognostic and diagnostic testing
will become increasingly important and medical practice will move
towards preventative treatment or lifestyle management.
1 For example, the Nuffield Council on Bioethics report
on Pharmacogenomics (2003). Back
Contributions provided by the ESRC Innogen Centre (http://www.genomicsnetwork.ac.uk/innogen/
based on findings that have been published in Tait, J (2007),
"Systemic Interactions in Life Science Innovation",
Technology Analysis and Strategic Management, 19/3:257-277; Tait,
J and Chataway, C (2007) The Governance of Corporations, technological
change and risk: Examining industrial perspectives on the development
of genetically modified crops. Environment and Planning-C: Government
and Policy, 25, 21-37; Tait, J Chataway, J and Wield, D (2006)
Governance, Policy and Industry Strategies: Agro-biotechnology
and Pharmaceuticals. In eds M Mazzucato and G Dosi, Knowledge
Accumulation and Industry Evolution. Cambridge University Press,
pp 378-401; Chataway, J, Tait, J and Wield, D (2006) The governance
of agro- and pharmaceutical biotechnology innovation: public policy
and industrial strategy. Technology Analysis and Strategic Management,
18(2), 1-17. Back
"A review of health research funding" Sir David Cooksey
Dec. 2006 http://www.hm-treasury.gov.uk/independent_reviews/cooksey_review/cookseyreview_index.cfm Back
See www.wellcome.ac.uk/Funding/Biomedical-science/Grants/Other-initiatives/WTD028245.htm Back
See http://www.iser.essex.ac.uk/ukhls/ Back
Contributions provided by the ESRC genomics forum: http://www.genomicsforum.ac.uk/ Back
Contributions provided by the ESRC Cesagen Centre: http://www.genomicsnetwork.ac.uk/cesagen/ Back
Observer, 3 February 2008; The Daily Telegraph, 4 February 2008;
The Express, 5 February 2008; The Times, 10 March 2008. Back
Observer, 3 March 2008; BBC News, 11 March 2008. Back
Descriptors: Biomarker: A characteristic that is objectively measured
and evaluated as an indicator of normal biological processes,
pathogenic processes or pharmacological responses to a therapeutic
intervention. Clinical biomarker: A biomarker that associates
a treatment to a patient subpopulation that has historically showed
a differential and substantial clinical response. These can be
based on genotypes, proteins, metabonomic patterns, histology,
imaging, physician clinical observations or even self-reported
patient surveys. Back
Trusheim, Berndt and Douglas (2007). Stratified medicine: strategic
and economic implications of combining drugs and clinical biomarkers
Nature Reviews Drug Discovery 6 287-293. Back
Kerr, A (2007), "(Re)constructing Genetic Disease: The Clinical
Continuum Between Cystic Fibrosis and Male Infertility."
Social Studies of Science 30: 847-94; Hedgecoe, A,M
(2003), "Expansion and Uncertainty: Cystic Fibrosis, Classification
and Genetics." Sociology of Health & Illness, 25,
50-70; Latimer, J et al. (2006), "Rebirthing the Clinic:
The Interaction of Clinical Judgment and Genetic Technology in
the Production of Medical Science." Science, Technology &
Human Values 31.5: 599-630. Back
Hallowell, N (1999), "Doing the Right Thing: Genetic Risk
and Responsibility." Sociology of Health and Illness 21.5: 597-621;
Hallowell, N (2006), "Varieties of Suffering: Living with
the Risk of Ovarian Cancer." Health, Risk & Society 8: 9-26 Back
Saukko, P, Richards, S., Shepherd, M. and John Campbel, J.(2006),
"Are Genetic Tests Exceptional? Lessons from a Qualitative
Study on Thrombophilia." Social Science and Medicine 63.7: 1947-59. Back
Bharadwaj, A, Lindsey, P, Atkinson, P and Clarke, A (2006),"Genetic
Iceberg: Risk and Uncertainty in Cancer Genetics and Haemochromatosis."
Innovative Health Technologies: Meaning, Context and Change. Andrew
Webster. Palgrave Macmillan; Lock, M et al. (2007), "Susceptibility
Genes and the Question of Embodied Identity." Medical Anthropology
Quarterly 21.3: 256-76. Back
Lock, M, Prest, J and Lloyd, S (2006), "Genetic Susceptibility
and Alzheimer's Disease: The Penetrance and Uptake of Genetic
Knowledge." Thinking About Dementia:Culture, Loss, and the
Anthropology of Senility. Ed Annette Leibing and Laurence Cohen.
New Jersey: Rutgers UP, 123-56. Back
Hall, R et al. (2007), "Assessing Family History of Heart
Disease in Primary Care Consultations: A Qualitative Study."
Family Practice 24: 435-42. Back
An Academy of Medical Sciences working group report chaired by
Sir Michael Rutter, November 2007-"Identifying the environmental
causes of disease: how should we decide what to believe and when
to take action?" Back