Select Committee on Science and Technology Appendices to the Minutes of Evidence


Memorandum submitted by GeneWatch UK


  The Medical Research Council is part-funding a controversial new genetic research project called Biobank UK. The project aims to identify the links between genetic and environmental factors in common diseases by studying DNA samples taken from 500,000 volunteers between the ages of 45 and 69, linked with lifestyle and medical data.

  Biobank UK's

    —  aims are controversial;

    —  science is questionable; and

    —  there is a lack of legal safeguards to protect the volunteers taking part from misuse of their genetic information.

  The main aim of the project is to be able to identify individuals who are "genetically susceptible" to common diseases, so that medication or advice on lifestyle changes can be targeted at them. However, many scientists have argued that this approach is unlikely to contribute significantly to reducing the incidence of these diseases, and may even be damaging to health. Underlying these concerns are serious question-marks about the scientific validity of Biobank UK, including the danger of identifying spurious links between genetic and environmental factors and diseases. There are also serious concerns about confidentiality—particularly potential access to the data by the police—and the need to control commercial conflicts of interest and patent claims.

  Biobank UK involves significant resources and its full costs remain unknown. GeneWatch UK believes the project should be shelved until the controversies surrounding it have been democratically debated and resolved, and alternative approaches have been properly assessed.

  Some key questions for the MRC are:

    —  Why has there been no public, independent assessment of the scientific validity or likely value-for-money of Biobank UK? What are the full costs of the project expected to be?

    —  The journal Nature has reported that 36 projects given the top "alpha-A" rating following scientific peer review have been rejected for MRC funding this year because of Biobank UK. How was the decision made to fund Biobank UK rather than these projects? Did Biobank UK receive the top rating from its scientific peer reviewers?

    —  What assessment has the MRC made of the relative costs and benefits of population-based approaches to tackling the prevention of common diseases?

    —  What assessment has the MRC made of the relative costs and benefits of smaller, more detailed (case-control) studies as an alternative approach to identifying genetic factors in disease?


  GeneWatch UK is a policy research group concerned with the science, ethics, policy and regulation of genetic technologies. GeneWatch works to promote environmental, ethical, social, human health and animal welfare considerations in decision-making about genetic engineering and other genetic technologies. We welcome this opportunity to input to the Science and Technology Committee's scrutiny of the Medical Research Council.

  This evidence focuses on the issue of the planned genetic research project known as Biobank UK. Biobank UK will study the genetic information contained within DNA samples taken from 500,000 volunteers between the ages of 45 and 69. The genetic data will be linked with lifestyle information taken from an initial questionnaire and information about subsequent sickness, medication and causes of death taken from the volunteers' medical records. The MRC and Wellcome Trust announced the allocation of £45 million start-up funding to the project in April 2002.

  GeneWatch is not opposed to the use of biobanks in medical research (we believe small, focussed biobanks can and have been very productive sources of useful knowledge), but has repeatedly called for Biobank UK to be shelved due to concerns about both the scientific validity of the project and the lack of safeguards to protect the public from the misuse of genetic information. Our key concerns are that:

    —  prediction of future common illnesses by testing people's genetic make-up is unlikely to be a successful or cost-effective means of disease prevention;

    —  the serious scientific limitations of Biobank UK mean that genetic factors in disease or drug response will be hard to identify correctly, and spurious links between genes and diseases may be made;

    —  Biobank UK will not contribute directly to the development of new medicines but may allow commercial companies to go "gene fishing", patent gene sequences and gain excessive monopolies over future treatments;

    —  there is a lack of legal safeguards to protect participants from future misuse of their genetic information.

  Although the MRC and Wellcome Trust have conducted a number of consultations on aspects of Biobank UK, widely raised concerns have still not been addressed.

  A copy of the GeneWatch UK report "Giving Your Genes to Biobank UK: Questions to Ask", which covers the issues relating to lack of safeguards in more detail, is enclosed, together with three relevant GeneWatch briefings.

  The limited health benefits of Biobank UK and the lack of legal safeguards are considered in turn below.


  A major concern expressed by the public in recent consultations about the Biobank UK proposals is the "unclear benefits to individuals and society"[1] If Biobank UK fails to deliver the promised benefits significant resources will have been wasted that could have been better spent on other projects. Public trust in genetic research is also likely to be damaged if the downsides (such as potential negative impacts on civil liberties, see Section 3) outweigh any benefits to public health.

  Key questions for the MRC include:

    —  What total resources will be needed to fund Biobank UK and how will this impact on other medical research projects?

    —  What is the likelihood of Biobank UK meeting its aims and objectives?

    —  Is studying gene-environment interactions in this way likely to contribute significantly to improving public health?

    —  Why has the MRC refused to allow an independent body to assess the scientific validity of the project?

    —  What assessment has been made of the project's likely cost-effectiveness?

  These issues are considered in more detail below.

2.1  Allocation of MRC resources

  The MRC has reportedly already refused funding for some other top-rated research projects because of the resources required for Biobank UK[2], yet the basis on which the project has been given such high priority is unclear (see also Section 2.4). The total amount of public funding likely to be spent on Biobank UK also remains uncertain—the £45 million allocated to date is only a small part of the likely budget. No public assessment has been made of the costs of alternative approaches to studying the role of genes in common, complex diseases (see Section 2.2). Nor has the MRC considered alternative approaches to securing reductions in the incidence of these diseases (see also Section 2.3).

  Items which appear to be missing from the initial budget are listed in Appendix A.

  Key questions for the MRC:

    —  What are the full estimated costs of meeting the project's objectives, including the costs of collecting follow-up data, extending the time-frame and including nested studies?

    —  Will the MRC provide a detailed public breakdown of these costs?

    —  To what extent does the success of the biobank depend on securing commercial funding of future (smaller but more detailed) nested studies?

2.2  Will Biobank meet its aims and objectives?

  The Biobank UK Protocol[3] states that its main aim is "to investigate the separate and combined effects of genetic and environmental factors (including lifestyle, physiological and environmental exposures) on the risk of the common multifactorial diseases of adult life". The study will also examine whether or not the risk of adverse events relating to the use of certain medications varies according to an individual's genotype (genetic make-up).

  However, the science behind Biobank UK has been criticised by geneticists and others for three key reasons:

  1.  The study design (a "cohort" rather than "case-control" study) may be inadequate to identify the proposed gene-environment interactions;

  2.  The study is too large to allow sufficiently detailed lifestyle and environmental data to be collected to test hypotheses about the causes of complex diseases;

  3.  Medical records are inadequate to provide the necessary follow-up data for meaningful research.

  More detail on these concerns is given in Appendix B.

    "The scientific value of focusing on gene-environment interactions has not been established, and in any case, the technical advantages of cohort studies over case-control studies in detection of statistical interactions between genetic and environmental effects are less clear than has been assumed." David Clayton (Department of Medical Genetics, Cambridge University) and Professor Paul McKeigue (London School of Hygiene and Tropical Medicine)[4].

    "Garbage in, garbage out", Chief Executive, Gemini Genomics[5].

  Key questions for the MRC:

    —  Will the MRC make a detailed, public, scientific comparison of pros and cons of Biobank UK and the proposed alternative of a smaller case-control study?

    —  How does the MRC plan to address the likely poor quality of follow-up data obtained from medical records?

    —  How has the MRC decided what data to collect from the initial questionnaires, when it has not published any hypotheses for the role of gene-environment interactions in major diseases?

    —  Has the MRC made any assessment of how complexity could limit the statistical power of the study to detect gene-environment interactions?

    —  Why has the MRC not produced a detailed response to the issues raised at its Protocol Workshop, particularly the comments that the study would be "a poor vehicle for study of cardiovascular and metabolic disease"?

2.3  Contribution to public health

  The Medical Research Council (MRC) states that Biobank UK will[6]:

    —  help in the design of a new generation of drugs to counter most major diseases.

    —  help to explain why some patients respond well to particular drugs and others do not.

    —  be used to predict the likelihood that an individual would develop disease, so that medicines could be used to prevent the onset of disease, rather than as a treatment for symptoms once a disease develops.

  However, the biobank will not lead directly to the development of new medicines, nor provide detailed and reliable information on individuals' responses to particular drugs (see Section 2.2). The predicted benefits of Biobank UK therefore rest largely on an assumption that "The more precise identification of individuals at increased risk of disease through both exposure and genotype will allow improved targeting of various interventions"[7]. These interventions are likely to include both advice on lifestyle changes and preventative medication—used to prevent the onset of a predicted disease.

  However, this genetic approach to disease prevention is a highly controversial one. Scientists involved in developing the Biobank UK protocol have recognised that "the extent to which the targeting of interventions in accordance with genotype will ultimately prove useful is as yet unclear"[8]. Nevertheless, there is already sufficient knowledge about the role of genetic and environmental factors in common, complex diseases to make some estimates of the limited potential benefits of this approach. The key issues are outlined in Appendix C.

  If widespread genetic testing is not a useful or cost-effective way of reducing the incidence of common, complex diseases, then Biobank UK will be of little benefit to public health. The MRC has not provided any public justification as to why Biobank UK is a better use of resources than more research on population-based measures—such as the most effective ways to improve the diets of all school children.

    "[The Director of the US National Human Genome Research Institute] and many others have outlined scenarios where all individuals have a battery of genetic tests early in life so that the knowledge of `susceptibility' can be used to avoid development of disease. Biomedical sectors would profit from acceptance of the above approach, but it is doubtful whether it is the approach most likely to increase the health of populations." Professor Patricia Baird, Department of Medical Genetics, University of British Columbia, Canada[9].

    "Genetic tests for markers that may not result in disease for half a century or more could be new examples of a process of premature medicalisation of attaching the `disease' label before it has been established that prevention or treatment is clearly beneficial. . . Unless it is established that a genetic variant is a pointer to beneficial action, there is a potential for inappropriate medicalisation through the spread of poorly understood tests." Dr David Melzer (Research Associate) and Professor Ron Zimmern (Director, Public Health Genetics Unit), University of Cambridge[10].

    "Genetic research. . . might improve our understanding of individual susceptibility to disease, but it will not contribute to population cardiovascular disease control." Dr Robert Beaglehole, University of Auckland[11].

    " is vital that the more conventional approaches of epidemiology and public health, particularly as they relate to tobacco-induced diseases and other aspects of lifestyle, continue to be pursued with vigour. This is particularly important as there are still major uncertainties about the predictive role and cost of genomics for controlling common diseases." World Health Organisation, 2002[12].

  Key questions for the MRC:

    —  before funding Biobank UK, what assessment has the MRC made of the likely health benefits of widespread genetic testing for susceptibility to common, complex diseases?

    —  what assessment has the MRC made of the likely costs to the health service of a genetic approach to disease prevention, including estimates of the number of healthy people that would need to be tested and treated to prevent each case of disease?

    —  what assessment has the MRC made of the relative costs and benefits of population-based approaches to tackling disease prevention, compared to approaches based on targeting the "genetically susceptible"?

    —  given the major future implications for the National Health Service of using a genetic approach to "predict and prevent" future common, complex illnesses, why has there not been more public and parliamentary debate on the advantages and disadvantages of this approach?

2.4  Scientific peer review

  In the light of the extensive concerns about the scientific validity of Biobank UK noted above, GeneWatch UK believes the process of scientific peer review has been inadequate. Funding was allocated in principle to Biobank UK by the MRC and Wellcome Trust in June 1999. Yet the same bodies that proposed the project also organised its peer review and took the decision to allocate the funding. This has led to the unprecedented rejection of MRC funding for a large number of other project applications, which had been given the top alpha-A scientific rating following peer review[13].

  Key questions for MRC:

    —  In view of the scientific controversy surrounding the Biobank UK proposals, why did MRC/Wellcome Trust not seek an independent body to organise its peer review, independently of the MRC/Wellcome Trust?

    —  Did the project's peer reviewers include some of those who had been openly critical of its design?

    —  Did the project receive a top alpha-A rating by its scientific peer-reviewers?

    —  How was the decision made to fund Biobank UK, rather than the 36 alpha-A rated projects which have reportedly been rejected for MRC funding this year?

    —  In view of the significant public implications of the project, has MRC sought ways in which it could make the peer reviewers' comments public, without revealing their identities?

    —  If it cannot make them public, would the MRC be prepared to provide the peer reviewers' comments to the Committee, on an anonymous basis?

2.5  Value-for-money

  The value-for-money of Biobank UK will depend on:

    —  its overall costs (see Section 2.1);

    —  whether or not it can meet its own objectives in correctly identifying gene-environment interactions (see Section 2.2);

    —  whether or not these objectives, if achieved, would contribute significantly to public health (see Section 2.3);

    —  the comparative costs of alternative approaches to studying the role of genetic factors in common, complex diseases (such as a smaller but more detailed case-control studies, see Section 2.2);

    —  the comparative costs of alternative (non-genetic) approaches to securing reductions in the incidence of these diseases (see Section 2.3);

    —  the costs of any negative impacts on research due to lack of safeguards and loss of public trust (see Section 3).

  All these issues are highly disputed, yet there has been no public assessment or debate regarding the value-for-money of Biobank UK.

  Key questions for the MRC:

    —  Why have the MRC not sought an assessment of the project's value-for-money from an independent body?

    —  Has the MRC made any internal assessment of the project's likely cost-effectiveness?


  In addition to the concerns about the scientific validity and usefulness of Biobank UK noted above, the lack of proper legal safeguards for this type of research means that there are considerable potential downsides for participants and for society as a whole.

  Although many smaller biobanks already exist, Biobank UK needs urgent consideration because of its scale, the involvement of large sums of public money, and the potential that it could be the first step towards a larger, national biobank, involving the entire UK population[14],[15]. Unless the necessary safeguards are put in place before the recruitment of volunteers begins, there is potential for widespread loss of public trust in genetic research and perhaps medical research in general.

  Key issues are:

    —  the role of commercial companies in Biobank UK;

    —  the need for public involvement in deciding how the biobank is used;

    —  the potential for genetic discrimination;

    —  the potential for forensic use of personal genetic information and/or other breaches of confidentiality.

  These issues are considered in more detail below.

3.1  The role of commercial companies

  The Wellcome/MRC consultation with primary health care workers found that they felt that the patenting of genes should be avoided[16]. The Wellcome/MRC GP's focus group also wanted assurances that the involvement of commercial organisations would be strictly controlled[17]. In the same study, religious and community leaders raised concerns about profiteering by companies. A more recent public consultation for MRC/Wellcome Trust[18] reported that "The idea of access by commercial organisations raised concerns and generally the first reaction was to reject the idea" although the researchers then noted that "Further debate brought the realisation that if medicines are going to be developed, pharmaceutical companies must have access" and that some participants therefore "became resigned to their involvement".

  GeneWatch is particularly concerned that the MRC has not yet adequately addressed two key areas of concern regarding commercial involvement in Biobank UK:

3.1.1.   Gene patenting and profiteering

  Current legislation does not require people to be informed if their genes are patented. The patenting of gene sequences is controversial and allows unprecedented monopolies over future genetic tests and treatments, which can stifle future research and innovation and increase costs[19]. The Nuffield Council on Bioethics recently concluded that the granting of patents that assert rights over DNA sequences should become the exception rather than the norm[20]. In GeneWatch's view the patenting of genes should not be allowed, and new legislation is needed to regulate the commercial use of biobanks.

    "There should be no patenting of gene sequences, period. They were invented by nature." Affymetrix (US biotech company), 2002[21].

    "The intellectual property arena is nothing less than a minefield . . . if a gene sequence is patented, you can't necessarily design around it. What type of discovery associated with the gene sequence would entitle somebody to lock up a whole area of research and prevent competition?" Dr Elliot Sigal, Senior Vice President of Early Discovery and Applied Technology, Bristol-Myers Squibb's Pharmaceutical Research Institute[22].

3.1.2.   Commercial conflicts of interest

  Conflicts of interest are particularly likely if commercial companies are allowed to undertake research seeking to identify those who are genetically susceptible to diseases associated with their own products or pollution (eg tobacco companies seeking to identify those smokers who are genetically susceptible to lung cancer; employers seeking to identify employees who are susceptible to diseases associated with hazardous chemicals or radiation in the workplace). This could lead to attempts to avoid liability by blaming individuals' genetic make-up for diseases, the possible exclusion of some people from some hazardous environments, and resulting negative impacts on public health (see Section 3.3). People could quickly lose trust in this type of research if it is conducted against the interests of those that they are trying to help.

    "[Biobank UK] is a big gamble . . . People who opt into this study have to know exactly what is being done with this DNA. They need to know its relationship to any industrial exploitation." Professor Sir David Weatherall, Oxford University[23].

  Key questions for the MRC:

    —  does the MRC intend to allow gene sequences contained in Biobank UK to be patented?

    —  what steps does the MRC plan to take to prevent the patenting of gene sequences identified using Biobank UK leading to excessive monopolies over future genetic tests and treatments?

    —  what steps does the MRC plan to take to ensure any new medicines developed using genetic sequences identified in Biobank UK are accessible and affordable to the NHS?

    —  what steps does the MRC plan to take to control potential commercial conflicts of interest and ensure public involvement and support for the research projects undertaken?

3.2  Public involvement in research

  Some types of genetic research are particularly controversial—for example research on behaviour, race, criminality, or intelligence. There is particular controversy about the results of such research being used to influence future reproductive decisions (including the use of abortion and the concept of "designer babies"). People may also object to companies using their data for research where there may be potential conflicts of interest (see Section 3.1.2). The general type of consent (for "medical research") proposed for Biobank UK, increases the likelihood that people's genetic information will be used for research they disagree with. GeneWatch would like to see new democratic mechanisms established to ensure effective public involvement in deciding how biobanks are used and operate. This would also allow people more say in deciding the limits of any commercial involvement (Section 3.1).

  Key Questions for the MRC:

    —  Does the MRC expect research on genetics and behaviour, and other controversial topics, to be part of Biobank UK?

    —  Does the MRC expect companies with potential conflicts of interests (for example, the tobacco, fast food, insurance, chemical and nuclear industries) to undertake research using Biobank UK?

    —  How does the MRC expect decisions about such research proposals to be made?

    —  How does the MRC intend to keep the public involved in these decisions, so public trust in "medical research" is not compromised?

3.3  Genetic discrimination

  People will be asked to donate their samples to Biobank UK on the grounds that the research will benefit those who are susceptible to future illness because of their genetic make-up. Yet genetic tests developed using Biobank UK could be used in future to discriminate against people identified as "genetically susceptible"—for example by refusing them insurance or a job.

  A particular concern in relation to Biobank UK is that genetic tests will be developed to identify those at higher risk of cancer or other diseases when exposed to particular hazardous chemicals or radiation. Such genetic predictions are likely to be poor, so that many people with the high-risk gene would never have developed the disease, and many without the high-risk gene will still be at risk. However, employers may still perceive genetic screening as a means of reducing liability, potentially cutting the costs of compensation claims[24].

  Job-seekers have little power to influence decisions by employers and are likely to be particularly vulnerable to decisions to exclude them on the basis of genetic test results[25]. Existing employees, although somewhat protected by employment legislation, may also be the subjects of genetic discrimination rather than gaining more control over their environment. There is therefore widespread concern that this type of research could lead to the exclusion of people with a particular genetic make-up from hazardous workplaces, or from compensation, rather than reducing or removing the hazard and cleaning up the environment for all[26].

  Although genetic testing is not currently widespread, dozens of cases of exclusion from insurance or employment on the grounds of genetic test results have already been reported in the US[27],[28]. A recent US case involved the Burlington Northern Santa Fe Railroad Company testing employees who had reported wrist injuries for a common genetic variation associated with carpal tunnel syndrome. The company abandoned the testing after it was sued by the US Equal Employment Opportunity Commission on the grounds that the tests were discriminatory and carried out without consent[29],[30]. Research on genetic susceptibility to hazardous chemicals has not yet led to widespread genetic testing, but the option has been and is still being considered by some employers[31],[32] ,[33]. A recent survey by the Institute of Directors[34] found that 50% of employers who responded to the survey thought it would be appropriate to conduct genetic testing with an employee's consent "to see if they are at risk of developing an occupation-related disease due to exposure in the workplace". 16% thought it would be appropriate to make genetic testing compulsory in such circumstances.

  Currently, the costs and logistical and technical difficulties of screening are highly uncertain—however, one study concluded that screening 1,429 workers to hire 1,000 would be a cost-effective way of preventing an employee contracting chronic beryllium disease[35]. Excluded workers (potentially a high proportion of the workforce in some industries) are likely to suffer negative impacts on their health and economic prospects, and those who are employed may also suffer if exclusion policies are used as an alternative to improving health and safety standards. Such policies could also exacerbate health inequalities, since they will have a disproportionate effect on those manual workers and technicians who are dependent on employment in such industries.

  There are currently no laws in the UK to prevent insurers or employers using genetic test results to set insurance premiums or decide who gets a job, although there is a moratorium on the use of most genetic test results by the insurance industry.

    "Ethical considerations, and legal, are fundamental to the whole issue of genetic testing . . . The consequences for individuals with regard to insurance and employment are also of the greatest importance, together with the implications for stigma and discrimination." Expert Working Group to the NHS Executive and the Human Genetics Commission[36].

    —  Has the MRC urged the Government plan to sign and ratify the European Convention on Human Rights and Biomedicine (1997), which prohibits discrimination against a person on the grounds of his or her genetic heritage?

    —  Has the MRC urged the Government to legislate to ensure that genetic tests developed using Biobank UK are not used by insurers or employers in the future to set insurance premiums or to decide who gets a job?

    —  In the absence of such legislation, does the MRC feel confident that research seeking to identify those defined as "genetically susceptible" to environmental hazards, particularly in the workplace, will be of benefit to health?

    —  Does the MRC plan to warn volunteers donating samples that the results of the research might be used in this way?

    —  Does the MRC expect employers to undertake this type of research using Biobank UK, and if so, how will it address potential conflicts of interest?

3.4  Forensic uses and confidentiality

  There is also concern about potential failures of strict privacy and confidentiality for genetic information, including the need to clarify the grounds on which the police or the courts could gain access to the information. Addressing these issues is particularly important since the Government sees Biobank UK as a pilot project for a national genetic database, potentially involving all NHS medical records.

  A person's genetic-make up is unique, unless they have an identical twin. This means this information has powerful forensic uses. Biobank UK will also contain personal information about people's lifestyles, linked to their genetic information. Although there has been some discussion of computer and other systems that would need to be in place to keep the data secure, there are some additional factors that require particular consideration. These are:

3.4.1  Access to the data by the police, courts or government

  A recent case in Scotland highlighted the fact that the courts are able and willing to over-ride guarantees of confidentiality in research studies. In this case, a prisoner who had volunteered to take part in a study of HIV was convicted of knowingly infecting his girlfriend, who had taken part in a separate research project[37]. Samples from both projects were used by the prosecution to show that the prisoner's girlfriend had the same form of the virus as that found in the prison.

  Current legislation allows the police to ask the courts for access to such databases when this is deemed to be in the public interest or if it could prevent serious harm. There is a real danger that Biobank UK could come to be seen as a forensic resource to identify individuals associated with increasingly trivial offences. Political pressure for access to the data could also increase, particularly in times of terrorism or war, with potential negative impacts on civil liberties.

  GeneWatch believes legal clarification is need regarding when genetic information and other data in Biobank UK can be release without consent, particularly to the police, courts or government.

3.4.2  The inherent limitations to the "anonymisation" of genetic information

  Current research into the use of DNA techniques in crime detection includes ways of identifying commonplace characteristics so that in future a "genetic photo-fit" could be built up from a sample left at the scene of a crime[38]. Techniques are already available to attempt to predict whether or not a suspect has red hair, on the basis of a DNA sample, and to attempt to predict a man's surname from his DNA[39]. This type of research renders the idea of truly "anonymous" genetic information rather meaningless, particularly when DNA data is linked to other personal data, such a postcode or job. Both postcodes and employment information are likely to be used in research by third parties using Biobank UK, since they are the only data relevant to many of the environmental exposures that the biobank is claiming to investigate—but they may also help reveal an individual's identity. A public assessment is needed of the extent to which the data from Biobank UK, even when supplied on an "anonymised" basis, could be used to identify individuals. This issue is also of relevance to decisions about commercial access, since the public may have more concerns about some types of researchers discovering their identity than others. For example, academic researchers are likely to be more trusted than companies who might be using the database for marketing purposes, or than employers or insurers, who may—perhaps inadvertently—discover personal information about their own customers or employees.

  GeneWatch believes there is a need for specific legislation for the protection of personal genetic information before members of the public are asked to donate genetic samples to Biobank UK.

    "The linkage of genetic and health information and the potential for using the [Biobank UK] database for a wide variety of analyses aimed at determining susceptibility to disease raises important issues about confidentiality, security of data and informed consent. These concerns were raised as recently as Monday by GeneWatch, and they were the subject of a debate in the House of Lords yesterday. The Government takes these concerns seriously and will not allow the work to proceed until they have been satisfactorily addressed." The Rt Hon Alan Milburn, Secretary of State for Health.[40]

  Questions for the MRC:

    —  In what circumstances does the MRC envisage the police or government seeking access to the data in Biobank UK?

    —  Will the MRC be warning participants that the police will be able to apply to the courts for access "in the public interest"?

    —  What studies has the MRC undertaken in relation to the possibility that an individual's identity could be deduced from supposedly anonymous data released to third parties by Biobank UK (eg genotype plus postcode, or genotype alone)?

    —  Does the MRC plan to warn participants about the limitations to "anonymising" personal genetic information?


  Biobank UK should be shelved until the serious question-marks over its scientific validity have been resolved, and proper public safeguards have been put in place.

    —  Considerable resources will be needed to fund Biobank UK, over and above those already allocated, and this will impact negatively on other medical research projects.

    —  Biobank UK is unlikely to meet its aims and objectives, given the complexity of gene-environment interactions, and the likely poor quality of the data in it.

    —  Studying gene-environment interactions in this way is unlikely to contribute significantly to improving public health.

    —  There has been no truly independent assessment of scientific validity of the project or of whether it will be good value-for-money in terms of improving public health.

    —  There is considerable public unease about commercial involvement in Biobank UK, yet the MRC has provided no public information regarding limits or controls on such involvement.

    —  Gene patenting has not been ruled out, although it is highly controversial and could hinder future research and development and increase costs of future treatments.

    —  Serious conflicts of interest could arise if companies responsible for various exposures (via their products or pollution) are allowed to determine the research agenda—yet no steps have yet been taken to prevent this.

    —  There is a need to ensure public involvement in research decisions, so people's samples are not used for research they disagree with—yet plans for a general form of consent to "medical research" sidestep these concerns.

    —  There are currently no laws in place to prevent insurers or employers using genetic tests developed by Biobank UK to set insurance premiums or decide who gets a job—harming instead of benefiting those the biobank is claiming to help.

    —  There is an urgent need to clarify on what basis the police, courts or government might be given access to the data held in Biobank UK for forensic purposes.

    —  Insufficient consideration has been given to the possibility that an individual's identity could be deduced from supposedly "anonymous" information given to researchers from the biobank.

Annex A


Missing core funding

  The original set-up costs for Biobank UK were estimated to be £60 million, and costs were confirmed to the project's Protocol Development Workshop as being in excess of this[41]. Although £45 million has been allocated, it is GeneWatch's understanding that another £20 million is required to implement the Scientific Protocol as planned. The potential source of this funding remains unclear.

Costs of updating exposure records

  The Biobank's Protocol Development Workshop noted that there may be crucial changes in exposures (including environment and lifestyle) over time and recommended that returning to the cohort for updated exposure information should be budgeted for from the outset. It is now planned that all study participants will undergo some form of re-survey approximately five years after recruitment, however funds for this have not been included in the budget[42].

Nested project costs

  Even if follow-up questionnaires are funded, there is considerable scientific concern that the data collected within Biobank UK will be insufficient to be of scientific use (see Section 2.2). Participants in the Protocol Development Workshop noted that the true costs of meeting the academic objectives of the study might be in excess of £1,000 per participant, and that the costs of sub-group studies needed to be included from the outset. At the Workshop, a much more detailed nested study of between 20,000 and 100,000 individuals was proposed, without which many scientists believed that the usefulness of the biobank, particularly for studies of cardiovascular disease, was "very weak". Funds for this study, or other nested studies, have not been allocated, although they could be expected to cost many millions. It is clear that the MRC expects commercial bodies and perhaps medical research charities to contribute funds to nested studies. However, it is unclear to what extent such funds will be forthcoming. Over-reliance on commercial funding raises additional ethical issues (see Section 3.1).

Cost of extending follow-up period

  Even scientists that support the project believe that Biobank UK would have limited value as a ten-year study of the causes of disease. They see its value as providing a 20-30 year resource, particularly for nested case-control studies[43]. In addition to the absence of a budget for such nested studies, no budget has been given for the costs of extending the project for 20-30 years.

Administration and recruitment costs

  Concerns have been expressed by health professionals about the considerable time, effort and training required to properly administer the biobank, particularly the necessary input from GPs and nurses[44]. Although nurse time per patient is included in the budget, it is unclear whether the full costs to the NHS have been considered, particularly if participants need to be re-contacted for follow-up or nested studies.

Annex B


  In April 2001, the MRC, Wellcome Trust and Department of Health held a Protocol Development Workshop for Biobank UK[45]. The overall impression given by the Workshop was that the aim of the project to identify interactions between genes and other risk factors (environmental/lifestyle exposures) is highly unrealistic.

  The workshops on both cardiovascular disease and on diabetes and metabolic disorders both suggested that the potential of the project was poor or very weak, and that smaller cohorts and more focused and detailed research was necessary. The other workshops all produced lists of detailed (different) questionnaires that would be necessary to investigate the likely environmental/lifestyle factors involved in different diseases, and highlighted the probable need for repeated screening, history data, and a wide range of physiological measurements. Medical records were widely considered to be inadequate to provide the necessary data for meaningful research, and the need for considerably more money and time in order to obtain meaningful results was also highlighted.

  For example, "The opinion was very strongly expressed, that the current proposal for the 500K study (focusing on a relatively elderly cohort, and powered for incident cases of common cancers) would be a poor vehicle for study of cardiovascular and metabolic disease". Participants discussed the need to measure intermediate traits such as blood pressure, lipids and insulin and concluded that "The potential contribution of the proposed cohort to studies of cardiovascular disease was thought to be very weak without the more extensive phenotyping" and "If such an intermediate trait analysis were not possible, the possible uses of the study for diabetes/metabolic disease would be limited". Participants proposed a studying a smaller group of 20,000 to 100,000 people in more detail, however funds for such a study have not been allocated. Some scientists have argued that funding this type of smaller study on its own would not require the larger Biobank UK and would provide much better value-for money and a better test of the causes of disease[46]. However MRC has not provided an alternative budget or comparative assessment of this type of approach.

  In relation to mental illness and hearing and visual impairment, the Protocol Development Workshop noted that:

    —  GP recording and diagnosis of common psychiatric or neurological disease and hearing or visual impairment is known to be unreliable;

    —  It is estimated that fewer than 25% of all cases of dementia are known to their GP;

    —  Death certificates are of little or no value in studying mental illness;

    —  Direct screening of much or all of the cohort may be the only feasible approach for accurate follow-up.

  The issue of complexity has also been sidelined. The Biobank UK Protocol includes calculations of the statistical power of the study to detect the expected risks associated with genetic and environmental factors. However, the authors recognise that the situation will be complicated by variations in the risk associated with a particular gene (known as "penetrance"), interactions between multiple genes, interactions between different one environmental factor and another, and confounding factors (hidden variables in the population being studied). The real ability of the study to quantify the risks associated with particular genetic and environmental factors therefore remains highly questionable.

  The Protocol Workshop participants also considered the data on drug prescriptions and side-effects, and noted that:

    —  follow-up data on prescriptions would be difficult if people moved practice;

    —  data on drugs given only for a short period are likely to be less reliable;

    —  sufficiently detailed information on clinical response to drugs might be difficult to obtain from medical records;

    —  information on drug levels will not be possible, but is necessary for detailed study;

    —  it would not be feasible to obtain data on compliance in a study of this scale (it is estimated that only around one-half of people with chronic diseases take their medication as recommended[47]).

  People's response to medicines may certainly vary according to their genetic make-up, although many other factors are also likely to be involved. However, the ability to assess genetic variations in drug response without being able to measure drug levels in individual patients, and without accurate records of either drug intake or side-effects will be very limited.

  Because the links between genes and diseases are complex, it is common for genetic research to identify spurious links between genes and diseases, which cannot be replicated in subsequent studies[48]. If research in Biobank UK leads to many such spurious claims, it will not only be a waste of money but may also lead to poor or dangerous health interventions.

Annex C


  Current evidence suggests that, even if Biobank UK correctly identifies the links between genes, environmental factors and diseases (and this is doubtful, see Section 2.2), for most people genetic tests are likely to be poor predictors of future health[49].

  For example, one paper has found that the more common a genetic variation is in the population, the higher proportion of cases of a disease it may contribute to, but the lower predictive value it will have[50]. This means that for common, complex diseases many people with the "high risk" form of the gene will not get the disease and many people without it will.

  There are therefore concerns that for many people genetic testing combined with preventative medication ("predictive medicine") could do more harm than good—by worrying them and giving them medicines that they do not need—perhaps with unpleasant or even fatal side effects[51]. Giving preventative medicines to all those identified as "genetically susceptible" means that many people would be treated—perhaps for their whole adult life—who would never have suffered the predicted illness.

  The pharmaceutical company, GlaxoSmithKline has identified predisposition profiling—"the ability to assess an individual's risk for a disease or diseases so that medicine can be given to prevent illness"—as one key area of the new "predictive medicine" and has argued that integrating genetic testing and pharmaceutical products will increase market size for pharmaceutical products and services[52]. This marketing strategy—using genetic tests to target medication at those identified as at "high genetic risk"—is sometimes known as "pills for the healthy ill". As well as being expensive and causing unnecessary side effects, it could also take resources away from treating the sick and from preventing the underlying causes of many diseases (such as poor diets, lack of exercise, smoking and pollution). The costs to the NHS of using this approach to try to prevent common, complex diseases have not been evaluated.

  On the other hand, targeting lifestyle interventions at those identified as "genetically susceptible" could miss most potential cases of a disease, which many people other than those identified as "genetically susceptible" could suffer from. This "targeted" approach to limiting exposures will always have less effect than policies that seek to limit everyone's exposure, particularly as one type of exposure (such as smoking) is often associated with many different diseases. Genetic testing will also not necessarily increase targeted individuals' motivation or ability to change behaviour[53]. Finally, there is potential for genetic discrimination, for example via the exclusion of people with a particular genetic make-up from insurance or employment (See Section 3.3).

  As an example, at the current rate of increase, more than one in four adults will be obese by 2010 and at a higher risk of a range of major health problems including heart disease and adult-onset diabetes[54]. The cause is obviously not an increase in "genes for obesity", but unhealthy diets and lack of exercise—problems which need tackling across Government departments, using measures to integrate healthy eating and exercise into daily life, for example by expanding the Government's fruit in schools programme. Too much emphasis on susceptibility genes for obesity could lead to the underlying causes of the epidemic being ignored, and the targeting of expensive diet or anti-cholesterol pills to those identified as "genetically susceptible" instead. The approach of targeting interventions at a minority of high-risk individuals (even if such individuals have been correctly identified) is well known to be limited in comparison to population-based approaches[55].

  This does not mean that seeking to identify genetic factors in disease cannot sometimes provide health benefits. Finding a genetic factor that plays a role in a disease may in some cases help the development of new medicines, via an improved understanding of how that disease develops. It may also help identify the small minority of people at particularly high risk of the rare familial forms of heart disease and cancer. However, Biobank UK's main aim is not simply to identify a gene that may play a role in a disease (which may be done more efficiently in other ways), but rather to try to quantify the combined effects of genotype (genetic make-up) and exposure on the risk of disease. If widespread genetic testing is not a useful or cost-effective way or reducing the incidence of common, complex diseases, then Biobank UK will be of little benefit to public health.

1   "BioBank UK: A Question of Trust: A Consultation Exploring and Addressing Questions of Public Trust", Report prepared for the Medical Research Council and Wellcome Trust by People Science and Policy Ltd, March 2002. Available on Back

2   "Top projects suffer as medical funding falters", Nature, 418, 714, 15 August 2002. Back

3   "Protocol for BioBank UK: A Study of Genes, Environment and Health", The Wellcome Trust/Medical Research Council and Department of Health, February 2002. Available on Back

4   Clayton, D, McKeigue, PM (2001), Epidemiological Methods for Studying Genes and Environmental Factors in Complex Diseases, The Lancet, 358, 1356-1360. Back

5   Coghlan, A (2000), A Wild Gene Chase, New Scientist, 9 December 2000. Back

6 Back

7   Protocol, p8. Back

8   Burton, P, McCarthy, M, Elliott, P (2002), Correspondence-Study of Genes and Environmental Factors in Complex Diseases, The Lancet, 359, 1155-1156. Back

9   Baird, P (2001), The Human Genome Project, Genetics and Health, Community Genetics, 4, 77-80. Back

10   Melzer, D, Zimmern, R (2002), Genetics and Medicalisation, British Medical Journal, 324, 863-864. Back

11   Beaglehole, R (2001), Global cardiovascular disease prevention: time to get serious, The Lancet, 358, 661-663. Back

12   WHO(2002), Genomics and World Health. Back

13   Nature, 2002. Op Cit. Back

14   "Fury at plan to sell off DNA secrets", The Observer, 23 September, 2001. Back

15   House of Lords Select Committee on Science and Technology, Human Genetic Databases: Challenges and Opportunities, Session 2000-01, 4th Report. Minutes of Evidence, para 39 (Examination of Sir John Pattison, Department of Health). Back

16   Hapgood, R, Shickle, D & Kent, A (2001), Consultation with Primary Care Health Professionals on the Proposed UK Population Biomedical Collection, Wellcome Trust and MRC, April 2001. Back

17   Wellcome Trust and MRC (2000), Qualitative Research to Explore Public Perceptions of Human Biological Samples, October 2000. Back

18   "BioBank UK: A Question of Trust: A Consultation Exploring and Addressing Questions of Public Trust", Report Prepared for the Medical Research Council and The Wellcome Trust by People Science and Policy Ltd, March 2002. Back

19   Econexus and GeneWatch UK (2001), Patenting Genes-Stifling Research and Jeopardising Healthcare, April 2001-available online at Back

20   Nuffield Council on Bioethics (2002), The Ethics of Patenting DNA: A Discussion Paper, July 2002. Back

21   San Francisco Chronicle, 25 March 2002. Available on Back

22 Back

23   Highfield, R (2002), DNA Bank is a Big Gamble, Says Expert, The Telegraph, 6 May, 2002. Back

24   Schulte, PA, Lomax, GP, Ward, EM, Colligan, MJ (1999), Ethical Issues in the Use of Genetic Markers in Occupational Epidemiologic Research, Journal of Occupational and Environmental Medicine, 41(8), 639-46. Back

25   OTA(1990), Genetic Monitoring and Screening in the Workplace, US Office of Technology Assessment. Back

26   TUC(2001), TUC Response to the Human Genetics Commission: Ban Unfair Screening, 20 March 2001. . Back

27   US Department of Labor, Department of Health and Human Services, Equal Opportunity Commission, Department of Justice (1998), Genetic Information and the Workplace, 20 January 1998. Available on Back

28   Kaufert, PA (2000), Health Policy and the New Genetics, Social Science and Medicine, 51, 821-829. Back

29   "Protecting Individuals and Promoting Science", Nature Genetics, 28 (3), 195-196. Back

30   Gottlieb, S (2001), US Employer Agrees to Stop Genetic Testing, British Medical Journal, 322, 449. Back

31   Mohr, S, Gochfeld, M, Pransky, G (1999), Genetically and Medically Susceptible Workers, Occupational Medicine: State of the Art Reviews, 14 (3), 595-611. Back

32   OTA(1990), Genetic Monitoring and Screening in the Workplace, US Office of Technology Assessment. Back

33   US Department of Labor, Department of Health and Human Services, Equal Opportunity Commission, Department of Justice (1998), Genetic Information and the Workplace, 20 January 1998. Available on Back

34   Day, G (2000), Testing Times: Directors' Views on Health Testing at Work, Institute of Directors Research Paper. Back

35   Nicas, M, Lomax, GP (1999), A cost-benefit analysis of genetic screening to occupational toxicants. Journal of Occupational and Environmental Medicine, 41, 535-44. Back

36   "Laboratory Services for Genetics", Report of an expert working group to the NHS Executive and the Human Genetics Commission, August 2000. Back

37   Dyer, C (2001), Scientists Fear Breach of Confidentiality Will Threaten Research, The Guardian, 17 March 2001. Back

38   Human Genetic Commission (2002), Inside Information, May 2002. Section 9 (Forensic Uses). Back

39   "Surnames Found in DNA", BBC Online, 4 April 2000. Back

40   Speech by Rt Hon Alan Milburn MP, 16 January 2002. Back

41   "Report of the UK Population Biomedical Collection Protocol Development Workshop", held at the Royal College of Physicians, London on Tuesday 17 April 2001. The Wellcome Trust, Medical Research Council and Department of Health. Back

42   Protocol, p21. Back

43   Burton, P, McCarthy, M, Elliott, P (2002), Study of Genes and Environmental Factors in Complex Diseases (Letter), The Lancet, 359, 1155-1156. Back

44   Hapgood, R, Shickle, D & Kent, A (2001), Consultation with Primary Care Health Professionals on the Proposed UK Population Biomedical Collection, Wellcome Trust and MRC, April 2001. Back

45   "Report of the UK Population Biomedical Collection Protocol Development Workshop", held at the Royal College of Physicians, London on Tuesday 17 April 2001. The Wellcome Trust, Medical Research Council and Department of Health. Back

46   Clayton, D, McKeigue, P (2002), Study of Genes and Environmental Factors in Complex Diseases (Authors' reply), The Lancet, 359, 1157. Back

47   Audit Commission (2001), A Spoonful of Sugar: Medicines Management in NHS Hospitals. Back

48   Ioannidis, JPA, Ntzani, EE, Trikalinos, TA, Contopoulos-Ioannidis, DG (2001), Replication Validity of Genetic Association Studies, Nature Genetics, 29, 306-309. Back

49   Holtzman, NA, Marteau, TM (2000), Will Genetics Revolutionize Medicine?, New England Journal of Medicine, 343, 141-144. Back

50   Khoury, MJ, Wagener, DK (1995), Epidemiological Evaluation of the Use of Genetics to Improve the Predictive Value of Disease Risk Factors, American Journal of Human Genetics, 56, 835-844. Back

51   GeneWatch UK (2002), Genetics and Predictive Medicine: Selling Pills, Ignoring Causes, Briefing No. 18, May 2002. Available on Back

52   Gilham I, Rowland, T (2001), Predictive Medicine: Potential Benefits from the Integration of Diagnostics and Pharmaceuticals, International Journal of Medical Marketing, 2(1), 18-22. Back

53   Marteau, TM, Lerman, C (2001), Genetic Risk and Behavioural Change, British Medical Journal, 322, 1056-1059. Back

54   National Audit Office (2001), Tackling Obesity in England, 15 February 2001. Back

55   Rose, G (1985), Sick Individuals and Sick Populations, International Journal of Epidemiology, 14 (1), 32-38. Back

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