JMed Genet 1998;35:413-416 413 The North Community Genetics Project J Med Genet: first published as 10.1136/jmg.35.5.413 on 1 May 1998. Downloaded from Diana S Chase, E Janet Tawn, Louise Parker, Patricia Jonas, Claire 0 Parker, John Burn

Abstract through classical genetic family studies, but The aim of the North Cumbria Commu- requires an epidemiological approach to the nity Genetics Project is to establish a store study of large, preferably unselected, popula- of DNA, plasma, and viable cells from a tion cohorts. This necessitates a source of cohort of around 8000 Cumbrian infants. DNA and cells from a normal population and To meet this objective, specimens of um- also the ability to link results of DNA analysis bilical cord blood and tissue will be with important lifestyle factors and disease collected with maternal consent from outcome over an extended period of time. babies born at the West Hos- To date there has been only one attempt to pital, over a five year period do this, in a study where the emphasis was pri- from January 1996. These samples will be marily on child development, and although used in a series of genetic and epidemio- placental samples were collected DNA was not logical studies investigating the interaction initially extracted and no viable cells were between genes, the environment, and obtained.5 The North Cumbria Community health. There is little population move- Genetics Project aims to store samples of ment in West Cumbria and so it will be DNA, plasma, and viable cells collected from possible to follow many of the babies babies born at the West Cumberland Hospital, throughout their childhood and to investi- Whitehaven and to use them as a resource for gate the relationship between their genetic future genetic epidemiological research. The constitution and health outcome. West Cumbrian population is ideal for this type (7Med Genet 1998;35:413-416) of research resource because not only is it rela- tively stable, but the study builds on the exper- Keywords: population; gene/environment interaction; tise in child health epidemiology and genetics genetic and epidemiological research; DNA resource already established in the area. From the beginning it was recognised that for this innovative study, ethical debate, both An international effort is under way to with professionals and the public, would be sequence the whole of the human genome required to gain the goodwill and support nec- (Human Genome Project) and there are confi- essary for success. Before the project could Genetics Unit, dent predictions that by the year 2005 the http://jmg.bmj.com/ Westlakes Research proceed it required careful planning and entire genome will be mapped and all the genes preparation. Information leaflets, consent Institute, Moor Row, (about 80 000 in total) will be identified.' The Cumbria CA24 3JZ, forms, and questionnaires were produced and UK next task will be to assign functions to the the logistics of distributing these and collecting D S Chase genes. Mutations in some genes will be samples were established with regard to E J Tawn sufficient in themselves to cause disease; antenatal care and midwifery practices operat- C 0 Parker however, many diseases, including most can- ing in the area. Technical aspects of sample cers, are the result of interactions between sus- Sir collection and storage were devised and proce- on October 1, 2021 by guest. Protected copyright. James Spence ceptibility genes and factors in environ- Institute of Child the dures developed to ensure that confidentiality Health, University of ment. These multifactorial diseases affect a of the data was safeguarded at all times. In the Newcasde, Newcasde large proportion of the population. Heart event it was not until January 1996, several upon Tyne NEI 4LP, disease, for example, affects about half of the years after the idea was initially conceived, that UK population over 65 years of age and is the sin- sample collection began. L Parker gle most common cause of death in this age group.2 Asthma is an cause Department of Human increasing of Genetics, University of morbidity in childhood and in 1986 affected Public and professional consultation and Newcastle, Newcastle 6.5% of children by the age of 16 years, an ethical approval upon Tyne NE2 4AA, increase of 70% since 1974.3 In contrast, cystic The North Cumbria Community Genetics UK fibrosis, which is the most common autosomal Project was first conceived in autumn 1993 at P Jonas recessive disorder in European populations, meetings between the University of Newcastle J Burn affects about 1 in 2500 people.4 Identification (Department of Human Genetics and the Sir Maternity Department, of susceptibility genes may enable population James Spence Institute of Child Health) and West Cumberland screening programmes to be considered, thus Westlakes Research Institute (Genetics Unit Hospital, Whitehaven, allowing subjects potentially at risk to be given and the Department of Occupational Health Cumbria CA28 3JG, appropriate lifestyle advice and regular moni- and Medical Statistics). It was clear from the UK toring, with the objective ofreducing morbidity start that it required the full backing ofthe local P Jonas from disease, enhancing quality of life, and health professionals and the support of the Correspondence to: reducing premature mortality. This preventa- local community. Initial discussions with pae- Dr Chase. tive approach has implications for a more diatric and obstetric staff at the West Cumber- effective use of limited health care resources. land Hospital concentrated on the practicali- Received 13 October 1997 The identification of Revised version accepted for gene-disease associations ties of fitting the project into the current publication and the impact of environmental factors on antenatal care programme operated by the 2 December 1997 these associations will not be established midwifery staff. 414 Chase, Tawn, Parker, et al

Early in the development of this project a of any impact its activities could potentially presentation was made to the West Cumbria have on the local environment. Following the Local Research Ethics Committee to ensure report by Gardner et af showing a statistical were no objec- association between paternal preconceptional that there fundamental ethical J Med Genet: first published as 10.1136/jmg.35.5.413 on 1 May 1998. Downloaded from tions. The scientific justification was accepted irradiation received occupationally at the Sell- by the committee who encouraged the develop- afield reprocessing plant and the development ment of a full, detailed protocol. Three months of childhood leukaemia, considerable effort later such a protocol was presented to the was expended in developing child health stud- committee. This encompassed methodology ies in the area. Some of these studies have been for the collection and storage of samples from reported8 9 and are consistent with the realisa- newborns at the West Cumberland Hospital tion that the association does not represent a subject to informed maternal consent, together plausible causal mechanism.'" Factors related with a short lifestyle questionnaire to be to the nuclear industry will of necessity be part completed by the mother. The project was of the environmental and occupational charac- given approval subject to a consultation period teristics of the local population, but the project coordinated by North Cumbria Health Au- has a much wider remit and will focus on gene- thority. This took the form of three meetings. environment interaction in the aetiology and The first for health professionals was chaired pathogenesis of disease. BNFL have no role in by a general practitioner and was addressed by the management of the project and have not members of the project team. The second two sought such a role. were public meetings chaired by the Chief Because of the unique nature of the project Executive of the North Cumbria Health and the lack of published guidelines, a number Authority. These were poorly attended despite of recognised UK experts with experience in associated media coverage including a brief the ethics of genetic and epidemiological stud- television broadcast, a radio "phone in", as well ies were invited to form an Ethics Advisory as newspaper coverage both nationally and Group. This group meets regularly and has locally. The project was also discussed by the provided valuable insight. With this input we North Cumbria Health Authority, the West have established a project which matches the Cumbria Health Care Trust Board, and the recommendations outlined in the Statement on West Cumbria Community Health Council. the Principled Conduct of Genetic Research, Feedback from the consultation period re- devised by HUGO Ethical, Legal, and Social sulted in a revised protocol which was given full Issues Committee and adopted by the HUGO approval by the North Cumbria Health Council in March 1996." Authority in December 1994. A project liaison midwife was appointed in April 1995 to inter- Confidentiality face between the midwives and the research From the outset, confidentiality was identified team and to develop the infrastructure for as being of major importance. The project is a

recruitment of mothers. collaboration between the University of New- http://jmg.bmj.com/ In all the consultations, concern centred pri- castle and Westlakes Research Institute and marily around aspects of confidentiality and a this allows the separate storage of personal public concern about the dangers of eugenics. information and biological specimens. All the The rapid advances in genetic knowledge bring personal information is sent to Newcastle with them a potential danger that genetic where it is stored encrypted on a stand alone information could be used to disadvantage computer with restricted access, while all the people in such areas as life assurance.6 To allay

biological specimens are stored at Westlakes on October 1, 2021 by guest. Protected copyright. such fears, full information was provided about Research Institute. the purpose of the study and the safeguards Each pregnancy is allocated a different incorporated to ensure appropriate use of the project number which allows the mother's samples and data confidentiality. Assurances information to be linked with her child's were given that the public will be informed of sample. A mother with more than one child in progress on a regular basis. To this end, mem- the project would be allocated a separate bers of the project team regularly give presen- number for each pregnancy. Specimen tubes tations to local schools, women's groups, received in the laboratory do not carry any clergy, medical societies, etc. Local health pro- information about the baby but are identified fessionals, in particular midwives and general by the project number only. This ensures that practitioners responsible for antenatal care, are the samples are non-attributable at the point of invited to an annual Study Day which provides storage and analysis. an update on the project. In addition, a news- letter is distributed through public libraries, health centres, antenatal clinics, and general Study outline practitioners, and is mailed to individual PROJECT DOCUMENTATION people on request. The research team has designed three docu- Criticism of the project has been associated ments. almost exclusively with concern over a local issue, the involvement of the nuclear industry. Informationlconsentform It is acknowledged that without the support of This is a four page A5 leaflet which is given out British Nuclear Fuels plc (BNFL), which to all pregnant women at the first appointment operates a nearby nuclear installation at with their midwife. It gives basic information Sellafield, this project could not have been ini- about the project in a question and answer for- tiated. BNFL is committed to the investigation mat. There are two copies of the consent form, The North Cumbria Community Genetics Project 415

Table 1 Statement on acceptable research uses of collected samples taking part, it would avoid the need to contact each mother and seek permission to use her The primary aim ofthe project is to gain health benefits from the study of genes in the child's population. The overriding concern ofthe North Cumbria Community Genetics Project sample in every separate study, which

team is to safeguard confidentiality and minimise the possibility of harm to individual would incur substantial costs and would be J Med Genet: first published as 10.1136/jmg.35.5.413 on 1 May 1998. Downloaded from people or the community. difficult to administer. Individual people can Every application for research using these samples will be considered with regard to current views opt into the project as a whole but cannot opt and medical developments, and approval sought from the West Cumbria Local Research Ethics out of specific studies. If a mother wishes to Committee. withdraw from the project she can do so at any There are three categories of study that need to be distinguished. time. The mother's consent is on behalf of the (1) Studies that use anonymous samples to determine the frequencies ofalleles at child and the consent form clearly states that specific loci or ofpolymorphism variants. Subject to (3) below, there are likely to be few research using the samples collected may ethical difficulties with the use ofNCCGP samples for such work, and such anonymous samples (or DNA extracted from them) may be released to other groups subject to appropriate conditions, involve reference to the health records of including the precise specification of the uses to which the samples will be put and the herself and her baby. acknowledgement of the source of the samples. Previous discussion of such studies by the Ethics This is not a screening programme and indi- Advisory Group is not necessary, although the Group will be informed of any such arrangements that are made. vidual results are not reported back to the par- ticipants. Diagnosis of any health related prob- (2) Studies that involve linkage to data on individual subjects. These specific studies will be considered by the Ethics Advisory Group. Identification of individual people during the process lem will still be through family doctors and the and reporting of any such study will be done in such a way as to safeguard confidentiality. National Health Service, and is likely to be in (3) Studies that involve personality disorders, psychiatric disease, mild intellectual advance of any population study using these difficulties, and other sensitive areas. Such studies are particularly sensitive, and strong samples. In rare and extreme circumstances evidence of a specific health benefit would need to be shown. when there may be an immediate major health benefit, the West Cumbria Local Research one forming an integral part of the leaflet for Ethics Committee would be asked to consider the mother to keep and the other copy on a whether it is in the family's interest for an indi- separate perforated page that can be returned vidual result to be disclosed. to the midwife. SAMPLE COLLECTION AND PROCESSING Further information leaflet After the birth of the baby, the hospital This is an eight page A5 leaflet available on midwives take specimens of cord blood and request. It gives background information and cord tissue and place them in numbered tubes the scientific rationale of the project and is which are sent to the laboratory at Westlakes aimed at midwives, general practitioners, and Research Institute. In order to accommodate health visitors. future studies, a wide variety of samples is being banked (whole blood, plasma, extracted Mother's questionnaire DNA, cultured lymphocytes, and chopped This is an eight page A5 booklet with questions cord as a source ofviable cells), all ofwhich are about the health and lifestyle ofthe mother and stored frozen. her partner. An expectant mother can either http://jmg.bmj.com/ complete the questionnaire at an antenatal Progress clinic with the help of her midwife or the Recruitment of pregnant women into the project liaison midwife, or she can take it home project began in January 1996. Currently, to complete. about 90% of pregnant women approached agree to participate. Of those giving consent, In addition, information about the labour about 60% complete all or part of a mother's and birth details are abstracted from a hospital questionnaire. A preliminary analysis of the on October 1, 2021 by guest. Protected copyright. neonate form. We have designed a "Midwives' postcode data indicates that the distribution Resource Pack" which explains the practical pattern of these women reflects the main aspects of the project. A copy of this is kept in centres of population and does not appear to places such as the labour ward at the West vary significantly with geographical location. Cumberland Hospital and in health centres. It By November 1997, over 2500 women had is also available to any midwife who would like been recruited, almost 2000 samples collected, a personal copy. and 1200 questionnaires collated. Copies of all documentation are available The difficulties we have encountered so far from the authors on request. have largely been of a practical nature. There is no central booking system in West Cumbria INFORMED CONSENT AND ENROLMENT and pregnant women can attend one of many Expectant mothers receive a copy of the antenatal clinics at various geographical loca- information/consent form from their midwife, tions. The current trend is towards community but many women need to be reminded of the based antenatal care: many pregnant women project, or to talk it over with someone before now carry their own obstetric notes and may deciding whether or not to take part. The only come to a hospital clinic once or twice in project liaison midwife provides them with a their first pregnancy, and possibly not at all for point of contact and an opportunity to discuss subsequent uncomplicated pregnancies. The any queries they may have. project liaison midwife has proved to be essen- Consent is given for the collection and stor- tial in providing the interface for recruitment age of samples and personal information for and overcoming these difficulties. Occasionally use in any genetic and epidemiological research samples have not been collected by the study approved by the West Cumbria Local midwives owing to the uneven work load on the Research Ethics Committee. It was felt that labour ward, unexpected complications, or an although this might deter some people from emergency delivery, but this is rare. 416 Chase, Tawn, Parker, et al

Future studies The authors acknowledge the help ofthe Ethics Advisory Group whose members currently are Dr Angus Clarke, Dr Martin A wide range of health related research studies Richards, Dr Barry Walker, and Dr David King. The support of could benefit from access to these samples. In Professor Roger Berry, particularly in the initiation of the consultation with the Ethics Advisory Group, a project, is greatly appreciated. We wish to thank Dr Paul Daniel, Mr Julian Smith, Mrs Gail Barker, and Mrs Joan Killip for their J Med Genet: first published as 10.1136/jmg.35.5.413 on 1 May 1998. Downloaded from "Statement on Acceptable Research Uses of support in the development and execution ofthe project. We are indebted to the community and hospital based midwifery teams Collected Samples" has been drawn up (table without whom this project would not be possible, to Mr Stephen 1). Some studies may use the samples totally Bober and Dr Sheila Precious from the West Cumberland Hos- pital for their support, and to our many colleagues and members anonymously, for example to estimate the of the public who have contributed in helping to ensure a thor- number ofpeople in the population who have a ough exploration of the ethical and practical issues addressed in this project. This project is supported by British Nuclear Fuels specific genetic polymorphism. Other studies plc, Westlakes Research Institute, and the North of may need to link laboratory test data with Children's Cancer Research Fund. information contained in the mother's ques- tionnaire or with medical records ofthe mother 1 Jones SL. Genetics: changing health care in the 21st century. Jf Obstet Gynecol Neonatal Nurs 1996;25:777-83. or child. Whatever type of study is undertaken, 2 Central Statistics Office. Social trends. London: HMSO, the results will be published such that no indi- 1996. 3 Lewis S, Butland B, Strachan D, et al. Study of the aetiology vidual person can be identified. of wheezing illness at age 16 in two national British birth Currently, two research studies have been cohorts. Thorax 1996;51:670-6. 4 Traystman MD, Schulte NA, MacDonald M, Anderson JR, approved by the West Cumbria Local Research Sanger WG. Mutation analysis for cystic fibrosis to Ethics Committee. One uses the glycophorin-A determine the carrier status in 167 sperm donors from the Nebraska Genetic Semen Bank. Hum Mutat 1994;4:271-5. assay and estimates the number of somatic 5 Farrow A, Farrow SC, Little R, Golding J. The repeatability mutations affecting the gene for the MN blood of self-reported exposure after miscarriage. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and group antigen. The other is a study of a Childhood. IntrJEpidemiol 1996;25:797-806. microdeletion on chromosome 22, associated 6 Nuffield Council on Bioethics. Genetic screening - ethical issues. London: Nuffield Council on Bioethics, 1993. with DiGeorge syndrome. The results of each 7 Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Ter- study will be reported at a later date. rell JD. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear power plant in West Cumbria. BMJ 1990;300:423-9. Conclusion 8 Parker L, Craft AW, Smith J, et al. Geographical distribution of preconceptional radiation doses to fathers employed at The increasing awareness of the importance of the Sellafield nuclear installation, West Cumbria. BMJ gene-environment interaction in the aetiology 1993;307:966-71. 9 Wakeford R, Parker L. Leukaemia and non-Hodgkin's of a wide range of diseases has led to a need for lymphoma in young persons resident in small areas ofWest population based studies capable of linking Cumbria in relation to paternal preconceptional irradia- tion. BrJ Cancer 1996;73:673-9. epidemiological, genetic, and health outcome 10 Doll R, Evans HJ, Darby SC. Paternal exposure not to data. The North Cumbria Community Genet- blame. Nature 1994;367:678-80. 11 Knoppers BM, Hirtle M, Lormeau S. Ethical issues in ics Project has been set up to meet this objec- international collaborative research on the human genome: tive. the HGP and the HGDP. Genomics 1996;34:272-82. http://jmg.bmj.com/ on October 1, 2021 by guest. Protected copyright.