DEFINITION

  Genetic research is the study of inherited DNA variation. This research has the potential to generate unsolicited, predictive information about individuals and family members and therefore raises a number of ethical, legal and social concerns. Genetic research requires DNA information (genotypes) and clinical information (phenotypes) from large, extensively and consistently characterised populations. This differs from genomic research which uses DNA based technologies to study genes (eg the genes that are switched "on" or "off" in certain tissues) and does not require detailed phenotype information from populations. The information generated from genomic research is not related to inherited DNA variation and has a lower potential impact for individuals. This research therefore has different ethical, legal and social concerns. This submission provides information specifically relating to genetic research and genetic databases.

SUMMARY

  Genetic research, with the establishment, maintenance and use of genetic databases, is required to maximise the value of genomic information (eg the human DNA sequence and high-density maps of genetic markers), in the treatment, cure and prevention of disease.

  The UK has an opportunity through the National Health Service (NHS) system of "tracking" patients and using electronic medical records to establish a valuable genetic research database. This would capitalise on advances in genetic science and technology and has the potential to attract investment in supporting and sustaining the UK's pharmaceutical and life science sector.

  It is of vital importance that genetic research databases are established, maintained and used in an ethically responsible manner and that participants' privacy and confidentiality are protected. Consistent terminology and agreed guidelines for genetic research across the UK and internationally will facilitate the delivery of significant public health benefits, providing they are compatible with effective research utilising new technologies.

  To maintain public confidence in genetic research and its ability to deliver healthcare benefits, Glaxo Wellcome believes that the Human Genetics Commission (HGC) should consider government sponsored (or partly sponsored) public, physician and healthcare provider education initiatives to increase awareness and understanding of genetics-related technologies. This will promote informed public debate, greater appreciation of the risks and benefits of different DNA based applications, and enable genetic technology to be applied to the optimal delivery of healthcare as rapidly as possible.

  Public healthcare benefits to come from advances in genomic and genetic science will be delivered by the biotechnology and pharmaceutical industries. It is therefore important that these industries continue to be involved in the substantive debates relating to the ethical establishment, maintenance and use of genetic databases

INTRODUCTION

  1.  Glaxo Wellcome is a research-based company whose people are committed to fighting disease by bringing innovative medicines and services to patients throughout the world and to the healthcare providers who serve them.

  2.  In 1999, Glaxo Wellcome invested £1.269 billion in research and development, of which £507 million was in the UK. Currently, Glaxo Wellcome employs 9,270 staff in its research and development organisation, with 4,500 based in the UK and 2,700 in the USA.

GLAXO WELLCOME'S APPROACH TO GENETIC DATABASES

  3.  Glaxo Wellcome is at the forefront of genetic research to deliver significant healthcare benefits to patients and healthcare providers, and to build on its success as one of the world's leading pharmaceutical companies. This research requires the establishment, maintenance and use of genetic databases that can be divided into two broad areas: disease genetics and pharmacogenetics.

(a)  Disease Genetics

  4.  The objectives of disease genetic research at Glaxo Wellcome are to identify genes (called susceptibility genes) which alter the risk of developing common diseases with unmet medical needs including asthma, early onset heart disease, osteoarthritis, depression, chronic obstructive pulmonary disease (COPD), migraine, diabetes, Alzheimer disease and Parkinson's disease.

  5.  Understanding the function of the different forms of these genes in disease pathways will enable and facilitate a better understanding of disease and the identification of valid targets for medicine discovery programmes. These medicines are likely to act at the underlying causes of disease and it is anticipated that they will provide significant advances in the treatment, cure or prevention of these illnesses. The discovery and development of medicines is a long process and it is likely to take 10 to 15 years from the identification of a disease susceptibility gene to the availability of a new medicine.

  6.  To identify disease susceptibility genes, DNA samples from large, extensively and consistently characterised populations are required. Glaxo Wellcome has therefore established seven international collaborative family-based studies with academe (called Genetics Networks) to collect this information for asthma, early onset heart disease, metabolic syndrome (a constellation of risk factors for cardiovascular disease), COPD, osteoarthritis, depression and Parkinson's disease. For each network, these studies bring together expert clinicians from approximately 10 different clinical sites around the world and leading scientists in genetics.

(b)  Pharmacogenetics (the right medicine for the right patient)

  7.  The objective of pharmacogenetic research at Glaxo Wellcome is to correlate information from patients' DNA with their responses to medicines. Samples for pharmacogenetic research are being collected from clinical programmes on marketed medicines and development compounds in over 15 different disease areas, conducted in 40 countries around the world.

  8.  Over the next three to five years this research may lead to the development of medicine response profiles which would be undertaken, using a small blood or tissue sample from patients, before a particular medicine is prescribed. This profile will determine if the patient is likely to benefit and/or not experience serious side effects from the medicine.

  9.  This technology has the potential to:

(i)  optimise the utilisation of medicines as physicians will be able to prescribe medicines more accurately based on a predetermined efficacy and safety profile. This will increase the likelihood of successful treatment and may save costs for the NHS through more efficient use of medicines;

(ii)  enhance post marketing medicine surveillance systems by identifying genetic markers that could be used to determine those patients at risk of a particular side effect;

(iii)  streamline drug development by enabling more efficient phase III clinical trials to be conducted through the ability to apply greater focus to these studies and recruit patients likely to respond into these traditionally large studies.

  These concepts are outlined in a review published by Dr Allen Roses[5].

  10.  Glaxo Wellcome has adopted a pro-active approach to its genetic research policies (Appendix 1). We endeavour to conduct genetic research to high ethical standards and have put in place mechanisms to review our policies in the light of recommendations from policy guidance groups.

  What current projects involve collecting genetic information on people in the UK? What other projects are about to start? Are there collections of material (eg tissue samples) that could be used to generate databases of DNA profiles?

GLAXO WELLCOME PROJECTS IN THE UK

(a)  Disease Genetics (see paragraphs 4 to 6)

11.  Five international collaborative studies in asthma, depression, osteoarthritis, COPD and early onset heart disease involve clinical sites in the UK (Aberdeen, Birmingham, Cambridge, Cardiff, Leicester, Liverpool, London, Nottingham, Sheffield and Stoke-on-Trent). For each study, each clinical site plans to recruit approximately 200 to 400 patients and family members. Glaxo Wellcome plans to initiate further international genetic studies in disease areas with unmet medical needs.

(b)  Pharmacogenetics (see paragraphs 7 to 9)

  12.  Twenty-one pharmacogenetic studies involve approximately 60 clinical sites in the UK. This research is planned to continue and expand to include more development compounds in additional disease areas.

(c)  Collections of Material that could be used to Generate Genetic Databases

  13.  Glaxo Wellcome conducts genetic research according to the policies provided in Appendix 1. These policies are consistent with international principles for the ethical conduct of research involving human subjects. There are no other collections of biological material within Glaxo Wellcome with the appropriate phenotype information and the necessary informed consents to allow genetic databases to be generated to meet our objectives.

OTHER GENETIC DATABASE PROJECTS IN THE UK (IE NON-GLAXO WELLCOME DATABASES)

Academe

14.  There are a number of academic centres, not related to Glaxo Wellcome or our genetic research initiatives, that have established genetic research databases with clinical information and biological tissues (or DNA samples) from patients with particular diseases and their family members. However, due to the rapid evolution of ethics guidelines, Glaxo Wellcome believes that there are sometimes shortfalls in the informed consents for these studies, particularly for consents obtained prior to relatively recent evolutions in recommendations from policy guidance groups.

  15.  For example, the original informed consents may not adequately disclose possible collaboration with a commercial third party, possibly leading to commercialisation of the study results (as recommended by the Directive of the European Parliament and of the European Council of 6 July 1998 on the legal protection of biotechnological inventions). The consequences are two-fold: first the potential value of these databases for medicine discovery cannot be realised as it is not appropriate for Glaxo Wellcome to gain access to such databases; and second, an avenue of funding for further academic research is closed. The continual development and communication of informed consent principles based on best practice would help alleviate these problems.

THE NATIONAL HEALTH SERVICE (NHS), MEDICAL RESEARCH COUNCIL (MRC) AND WELLCOME TRUST (WT) PILOT PROJECT

  16.  The NHS, MRC and WT are planning a pilot study to establish a genetic "Databank" in the UK using the well developed NHS infrastructure for "tracking" patients and using electronic medical records. The MRC/WT are in the initial stages of determining the feasibility and structure of a large national sample of patients (500,000 to 1 million) identified from general practice. If initiated this would be a valuable resource for the UK and has the potential to attract investment in supporting and sustaining the UK's pharmaceutical and life science sector. If this were realised, the UK would also become a more attractive place in which to introduce innovative medicines and interventions.

  17.  Previously conducted epidemiology studies have not collected information to adequately phenotype subjects for multiple diseases; they have focused on one or a few diseases or have relied on physician reporting and patient self assessment. In addition the statistical power of these previous studies is often limited by sample sizes. Traditional genetic studies have collected extensively phenotyped patients but ascertainment has been based on the presence of the disease and extensive data on environmental factors are not usually collected.

  18.  This proposal for a genetic "Databank" in the UK has the potential to enable extensive longitudinal epidemiology studies of subjects prospectively and consistently phenotyped for the presence or absence of major complex diseases and for which DNA is available to classify subjects' disease on the basis of genotype. These studies would be used to better understand:

—  the natural history of diseases including onset and severity in multiple populations;

—  how multiple susceptibility genes interact with each other and environmental factors;

—  how various health interventions would impact the onset and course of disease;

—  the effectiveness of preventative therapies for disease; and

—  whether markers for rare serious side effects could be identified, thereby allowing medicines to be prescribed for those patients most likely to respond positively.

  19.  The pharmaceutical industry, including Glaxo Wellcome, has participated in discussions about this project and Glaxo Wellcome is keen to work with the NHS/MRC/WT on this initiative, to help ensure:

(a)  the "Databank" is established and maintained using ethical principles based on current best practice;

(b)  the information collected is optimised for the delivery of healthcare benefits; and

(c)  appropriate informed consents are obtained to enable researchers from public and commercial entities to access the "Databank".

  20.  This important genetic research resource should be made widely available to scientists in academic and commercial organisations so that healthcare benefits are delivered to patients as rapidly as possible. A research review committee would need to be established to review protocols in a similar way that ethics committees review protocols for clinical trials. Several different mechanisms for funding the ongoing data collection and infrastructure costs would need to be evaluated to ensure the longevity of the resource.

  Why are these genetic databases being assembled? How are these activities funded? What practical considerations will constrain developments? Are there alternative ways of fulfilling the objective?

GLAXO WELLCOME GENETIC DATABASES

  21.  Glaxo Wellcome is conducting genetic research to build on its success as one of the world's leading pharmaceutical companies and to deliver the significant public healthcare benefits that will accrue from the rapid advances in DNA science and technology (as outlined in paragraphs four to nine). This research is an important component of our strategy to discover new medicines and provide medicines of value to patients and healthcare providers. Genetic research undertaken by Glaxo Wellcome is funded entirely through the investments of Glaxo Wellcome in research and development.

PRACTICAL CONSIDERATIONS WHICH WILL CONSTRAIN DEVELOPMENTS

  22.  Practical considerations which will constrain developments include:

(a)  slower than expected technological advances, their implementation or application;

(b)  negative public perceptions and little public understanding relating to genetic research;

(c)  national/regional legislation, regulations, policy guidance or terminology which differs substantively.

(a)  Technological Advances

  23.  Completion of the sequence of the human genome and advances in single nucleotide polymorphism (SNP) map technology (including statistical analysis and rapid read out technology) will drive many of the healthcare benefits to come from genetic science. The widespread application of SNP map technology requires the development of inexpensive, high-throughput methods for scoring large numbers of SNPs from hundreds of patients and controls. Considerable efforts are now underway within the biotechnology research community to establish low-cost, high-throughput and accurate SNP scoring technologies. There is therefore a need for continued research and investment in this area to prevent technological hurdles from impeding scientific developments.

(b)  Public Perceptions and Knowledge

  24.  Although issues relating to public attitudes to human genetic databases are outside the terms of reference for this inquiry, it is of note that genetic databases are collections of biological tissue (or DNA samples) and clinical data from individuals. Public perceptions of "genetics" that are often fuelled by sensational media coverage of unrelated DNA related applications such as genetically modified foods can adversely affect participation in genetic research.

  25.  It is important that there is increased public awareness, education and understanding of genetics and genetics-related technologies so that there is informed public debate and greater appreciation of the risks and benefits of different DNA based applications. This will help potential participants in genetic research to make a balanced judgement regarding their involvement.

  26.  Over the next 10 years there is likely to be increased use of pharmacogenetic information prior to the prescription of medicines. Ongoing physician and healthcare provider education is therefore required for the full value of this technology to be realised in the provision of cost-effective healthcare in the UK.

  27.  Glaxo Wellcome believes that the HGC should therefore consider government sponsored (or partly sponsored) public, physician and healthcare provider education initiatives to meet the needs outlined in paragraphs 25 and 26.

(c)  National/regional Legislation, Regulations, Policy Guidance and Terminology

Intellectual Property

28.  To clarify and harmonise European Union (EU) law and practice in relation to the patent protection of biological inventions, the European Parliament approved the European Union Biotechnology Directive (98/44/EC) which came into force in July 1998. This Directive was substantially implemented into UK law by the July 2000 deadline.

  29.  Under this Directive, human DNA sequence in isolated form or otherwise obtained by a technical process with an associated industrial application is patentable. This clarification and harmonisation of the law provides an incentive for the investment in genetic research and biotechnology across the whole of the EU. For Glaxo Wellcome, it provides the basis for the large investments in research and development that are needed to turn DNA based inventions into medicines to treat, cure or prevent disease.

  30.  The Netherlands, supported by Italy, has filed a nullity action against the EU Biotechnology Directive and many countries including Germany have failed to implement the Directive into national law by the required deadline. Some of these countries may implement the Directive at a later stage (possibly with restrictive conditions on patenting) and some may wait for the outcome of the nullity action. If the nullity action is successful or a number of Member States fail to implement the Directive or implement it subject to restrictive conditions, investment in biotechnology within the EU could be adversely affected. In addition, academic institutions that license biotechnology intellectual property to supplement government grants may be denied a source of revenue.

Regulatory Guidelines for Medicines

  31.  Over the next three to five years Glaxo Wellcome anticipates that through pharmacogenetic research it will be possible to provide medicine response profiles with some of our medicines (see paragraphs seven to nine). For these benefits to be realised it is important that the pharmaceutical industry and drug regulatory authorities, including the Medicines Control Agency and the Medicines Devices Agency, work together to develop regulatory guidance on:

—  the use of pharmacogenetics in drug development;

—  the introduction of medicine response profiles;

—  the application of pharmacogenetics to post-marketing surveillance.

  Informal dialogue between the pharmaceutical industry and the European Agency for the Evaluation of Medicinal Products (EMEA) has begun and Glaxo Wellcome is keen to continue this dialogue so that the pharmaceutical industry and the regulatory authorities work together to ensure that patients can benefit from this new technology.

Policy Guidance

  32.  International (eg United Nations' Educational, Scientific and Cultural Organisation (UNESCO) International Bioethics Committee, World Health Organisation (WHO), Human Genome Organization (HUGO) Ethics Committee) and National groups (eg UK Medical Research Council) have issued, or are issuing, policy guidance on the use of biological samples in genetic research.

  33.  The guidance of the various groups is not always consistent. Inconsistent guidance at regional and national levels related to:

—  requirements for sample identification;

—  future/secondary consent;

—  disclosure of information; and

—  length of storage,

  may adversely impact genetic research, which is conducted on an international basis.

Terminology

  34.  Groups that issue policy guidance on genetic research and genetic databases often distinguish different types of databases according to the degree to which sample/data can be traced to an individual subject. However, these groups use different terminology that can make interpretation for practical research difficult.

  35.  The terminology provided in Appendix 2 is that proposed by an Industry Pharmacogenetics Working Group including representatives from Abbott, AstraZeneca, Bristol-Myers Squibb, Glaxo Wellcome, Janssen, Merck, Pfizer, Pharmacia, Roche, Schering AG, Schering-Plough and SmithKline Beecham. This industry group was established to advance the understanding and development of pharmacogenetics by addressing non-competitive ethical, regulatory and legal issues. One of the issues being addressed is inconsistent terminology which can provide process difficulties for ethics review boards and regulatory authorities in the evaluation of research protocols and consent forms, and in the regulatory review of market applications for medicines and medicine response profiles. The current terminology being used by Glaxo Wellcome is likely to be changed so that it is consistent with the terminology outlined in Appendix 2.

  What is the genetic information that is being collected? How is it being stored and protected?

Disease Genetics

  36.  For the disease genetic studies that Glaxo Wellcome has initiated (see paragraphs 4 to 6), clinicians expert in the particular therapeutic area define the clinical characteristics (phenotype) of the disease.

  37.  After patients and family members provide signed informed consent, the clinicians:

—  obtain detailed medical histories from the patient and family;

—  conduct a comprehensive clinical examination and series of specific tests to confirm (or rule out) the relevant diagnosis in the patient and family;

—  collect information about the precise characteristics of the disease in each affected person; and

—  draw a single blood sample for DNA analysis from each family member.

  38.  The patient/family data are coded (Appendix 2). The names that correspond to the codes can only be accessed by the clinical investigator (or designee) at the clinical site where the patients are recruited. These data are encrypted and sent electronically to a genetic epidemiology centre (Duke University North Carolina, Vanderbilt University or Boston University USA) where they are stored in password protected computers and only accessed by authorised personnel.

  39.  The coded blood samples are sent via a secure carrier to a sample reception centre at Duke University USA where they are kept in secure environments. Following sample receipt and entry into a computerised sample tracking system, samples are transferred to Glaxo Wellcome for ensuing genetic analysis and storage. A portion of the DNA sample is sent to the clinical site for research.

  40.  DNA is extracted from the samples and genotyped at specified DNA markers by an academic screening centre (eg Duke University USA, Queen Elizabeth Medical Centre, Perth, Australia). This information is then sent to the epidemiology centres where genetic epidemiologists look for associations between defined disease characteristics and the genotyped DNA markers.

PHARMACOGENETICS

  41.  For the pharmacogenetic research undertaken by Glaxo Wellcome (see paragraphs seven to nine), a healthcare professional takes a blood sample for DNA analysis from patients who provide signed informed consent.

  42.  The samples and medical information are coded. The patient names that correspond to the codes can only be accessed by the clinical investigator (or designee) at the clinical site where the patients are recruited. The samples are sent either directly to a third party for DNA extraction or sent to Glaxo Wellcome (in the UK or USA) before being sent to a third party for DNA extraction. The DNA samples may also be genotyped by a third party at specified DNA markers.

  43.  Coded samples are stored and tracked according to Good Laboratory Practice (GLP) procedures and coded clinical data are handled according to Good Clinical Practice (GCP) procedures. All samples (coded and anonymised) are stored in secure environments and only accessed by authorised personnel.

  44.  After the samples from the study are genotyped at specified DNA markers, the data are combined with the clinical trial information in order to find associations. These databases are password protected, only accessed by authorised personnel and subject to computer validation compliance.

  45.  For most Glaxo Wellcome pharmacogenetic research there are two research uses for the patient's sample (reflected in the consent form completed by the patient):

(a)  Coded samples/data (Appendix 2): To study genes that may affect the patient's response to the study medication. Genes related to the individual's disease or those likely to affect response to the medication are studied. If signed informed consent has not been provided for anonymised research once the genetic analysis is complete and the study results are reviewed the coded sample is destroyed. A coded sample can be destroyed earlier at the request of the patient.

(b)  Anonymised samples/data (Appendix 2): patients may give signed informed consent for their samples to be stored indefinitely and used for future study. The sample may be used for continued research into the patient's response to the study medication and it may be used for genetic research into other diseases and to study response to a range of medicines. Under these circumstances, to provide additional protection of patient privacy, these samples/data are anonymised. Glaxo Wellcome replaces the original code numbers relating to the sample and to the medical information with a random code number.

  How do the organisations involved see their responsibilities regarding privacy; consent; future use; public accountability and intellectual property rights?

OVERALL

  46.  Glaxo Wellcome, as a research based pharmaceutical company, conducts research that requires the collection of information, and in some circumstances biological tissues from groups of individuals and patients. Glaxo Wellcome seeks to conduct its research, including genetic research, in an ethically responsible manner. The rapid advances being made in genetic science and technology give rise to a constantly changing ethical landscape for genetic research. Glaxo Wellcome therefore diligently and actively tracks ethics discussions and policy guidance, and reviews its current procedures in the light of these developments.

  47.  To ensure Glaxo Wellcome actively contributes to ethics debates and is aware of ethics policy guidance relevant to genetic research, a Genetics Policy Adviser was appointed in 1998. This individual is responsible for ensuring appropriate Glaxo Wellcome representation in ethics debates and for tracking recommendations made by international, regional and national groups. In addition, Glaxo Wellcome actively seeks advice from internationally recognised independent ethicists on the procedures used in our genetic research.

PRIVACY

  48.  A Data Privacy Officer was appointed in 1998 to help Glaxo Wellcome in the protection of patient privacy and confidentiality in its research activities. In addition, this minimises the risk that Glaxo Wellcome's research objectives will be adversely affected by the impact that breaches of confidentiality may have on patient participation in our research programmes. In addition many of the procedures to protect patient privacy and confidentiality in genetic research are standardised GLP and GCP procedures that are subject to internal audit.

CONSENT

  49.  Research involving human subjects is conducted under stringent conditions that protect subjects from misuse of data. The process of informed consent is an important component of patient protection in this regard. It is the means by which potential participants make a judgement about the contribution that their involvement can make, relative to the risk or benefit to them as individuals. It is the policy of Glaxo Wellcome to obtain appropriate signed informed consents before any genetic research is conducted (Appendix 1) consistent with legislative requirements and international agreements on research involving human subjects.

  50.  New research uses for Glaxo Wellcome genetic databases that were established using previous Glaxo Wellcome policies are individually assessed in the light of recommendations from policy guidance groups (eg WHO, HUGO Ethics Committee, UK MRC). If necessary, subjects are re-consented for the new genetic research. In addition, Glaxo Wellcome will only access genetic information from third parties (eg academic institutions) if it has been collected with acceptable informed consents.

  51.  To support informed consent, Glaxo Wellcome has developed patient brochures and a videotape and offers them to investigators to help explain to patients, before they give signed informed consent, the objectives of pharmacogenetic research and the safeguards in place to protect patient privacy and confidentiality.

FUTURE USE

  52.  The key difference between coded and anonymised data/samples (Appendix 2) is that the latter samples/data cannot be linked back to the individual donor whereas the link between coded samples/data and the individual donor is maintained (Appendix 2). Anonymised samples/data provide an additional degree of confidentiality protection. This is often used in circumstances where the samples/data are kept indefinitely for future research purposes (see paragraph 45b).

  53.  Policy guidance groups, for example the UK and Sweden MRCs, are beginning to recommend that coded data/samples should be used rather than anonymised samples/data because:

Scientific Considerations

(a)  The scientific value of anonymised genetic databases may be compromised if additional information from the subjects is required, as this cannot be obtained for anonymised samples/data. For example, genetic epidemiological research requires phenotype information to be obtained from groups of individuals at time points over a number of years. This therefore requires that the link between the sample/data and the individual is maintained over the period of the research.

Ethical Considerations

(b)  The non-specific nature of future research detailed in the informed consent may be inadequate. Where a link is maintained between the sample/data and the individual donor, specific future uses can be re-consented. This raises practical difficulties however, particularly if that research is planned years after the samples were originally collected, there are a large number of subjects to re-contact and/or there are multiple ethics committees and countries involved.

(c)  The results of genetic research may produce information that is of value for the healthcare management of the individual donor. Under these circumstances, where the information is of recognised medical value, it may be ethically necessary to provide information to the subject or their physician. Currently, because of the early stage of Glaxo Wellcome's genetic research, no results of the research are provided to anyone (unless legally required). Once the significance of results have been confirmed, the group results are published and shared widely within the medical community in a timely and responsible manner.

(d)  Individuals are unable to withdraw from the study if their samples/data are anonymised.

  54.  Glaxo Wellcome recognises the need to maximise the scientific value of genetic databases in a way that adequately safeguards the interests of those subjects who participate in this research. Glaxo Wellcome is therefore actively monitoring these developments and their implications for our genetic research.

PUBLIC ACCOUNTABILITY

  55.  Glaxo Wellcome actively communicates the broad objectives of its genetic research in public meetings and publications. In addition, Glaxo Wellcome actively provides information to potential genetic research subjects, clinical investigators and ethics committees on the procedures in place to protect patient privacy and confidentiality (see paragraph 51).

  56.  Clinical development research programmes, including those which incorporate pharmacogenetics, are reviewed by regulatory authorities. In addition, individual genetic research protocols and consent forms for both disease genetics and pharmacogenetics are reviewed by ethics committees prior to study initiation. These procedures and processes help to ensure that research activities are conducted in an ethically responsible manner. In addition, genetic research data are subject to scrutiny by regulatory authorities where it forms part of an application to market a medicine.

INTELLECTUAL PROPERTY RIGHTS

  57.  For the discovery of a new medicine, considerable investment (approximately £350 million over 12 years) in research and development is required. Without patent protection there would be no incentive for making these large investments to bring new medicines through to the market and make them available for the benefit of patients. Where Glaxo Wellcome's research leads to a valuable invention that is novel, non-obvious and has utility, we seek full patent protection under the relevant laws.

  58.  Glaxo Wellcome makes DNA-based discoveries and inventions that can significantly improve public health. Many of these inventions result from extensive genetic research using DNA and clinical information supplied by groups of patients and individuals. The invention may often arise only by analysis of DNA and clinical data from statistically meaningful numbers of patients and not those from just one individual. It is clearly explained in the Glaxo Wellcome consent form that the genetic research may lead to a significant improvement in patient health of commercial value and that Glaxo Wellcome (in some instances with collaborative researchers) intends to claim exclusive rights to the results of that research.

  59.  In order to encourage and support the development of new knowledge, Glaxo Wellcome may choose to allow third parties, such as academic institutions, to use our patented inventions through favourable licence agreements.

  How do they see their activities in the area of genetic databases developing in the future? What advances in sequencing, screening and database technology are they anticipating?

  60.  It is anticipated that completion of the sequence of the human genome and advances in SNP map technology (see paragraph 23) will facilitate the identification of disease susceptibility genes and genetic markers to predict responses to medicines (this is outlined in a review published by Dr Allen Roses[6]).

  61.  In order to optimise the pharmacogenetic research and technology to enhance the prescription of well tolerated medicines, it will be necessary to establish a regulated, secure repository of blood samples for the first few hundred thousand patients who receive a new medicine. If a serious adverse event should occur in a few patients, it may then be possible to compare the DNA of patients who experienced the side effect with the DNA of matched patients who were free of the side effect. This would enable the identification of genetic markers (eg SNPs) that could be used to identify subsequent patients who are at risk of the side effect and should be managed appropriately (eg different medication, lower dose).

  What lessons should be learnt from genetic database initiatives in other countries?

  62.  Large State or partly State sponsored genetic database initiatives in Iceland, Sweden and Estonia illustrate the potential value for these countries that can be generated by utilising healthcare infrastructures as a resource for genetic research. The UK has a similar opportunity through the NHS/MRC/WT initiative (see paragraphs 16 to 20).

  63.  The genetic database initiative in Iceland was reported to involve informed consent procedures that would not be regarded as "best practice" by many groups. This has generated adverse publicity that may impact other genetic research activities. In addition, investment and use of data from this initiative may be compromised if the consent procedure makes the data unacceptable to research organisations such as Glaxo Wellcome. This illustrates the need for the UK initiative to be established using ethical principles based on best practice and for there to be informed public debate.

6   Roses AD (2000) Pharmacogenetics and the practice of medicine. Nature 405: 857-865 Back