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The Investigation of Events that followed the death of Cyril Mark Isaacs
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| This chapter describes some of the research grant applications made by the joint team. | |
| Due to the passage of time it has not been possible to trace several of the applications made by the team. Those that are available are described in detail since they provide contemporaneous information about features of the programme that are directly relevant to my investigation. | |
| The chapter also describes the application submitted to the Mental Health Foundation in 1988 which, for the first time, includes a direct reference to the involvement of the North Manchester Coroner's office in identifying suitable brains for the joint programme. | |
| A: Applications for research funds to the NWRHA | |
| March 1988 Second application | |
| The title of the application was 'Neuropeptide Synthesis in Alzheimer's Disease and Schizophrenia'. | |
| This application, Appendix 20, for a two-year grant was submitted by Dr Slater and Dr Deakin. The application referred to progress previously reported in June 1987 and February 1988. | |
| While the basic plan for collection of normal and diseased human brains was unchanged, there were some differences from the first application. A new dimension was the inclusion of comparative studies of animal brains. | |
| The procedure for brain collection from Manchester Hospitals was described as: 'Control human brains from subjects with no history of neurological or psychiatric illness will be obtained from hospitals in the Manchester area, via long-standing arrangements. Brains from subjects with Alzheimer's disease and schizophrenia will also be obtained from the Greater Manchester area. Pre-mortem consent is obtained for the removal of brains at post mortem examination'. | |
| Expenses for 'Travel costs, materials and fees for collecting human brains' of £250 per year were requested. | |
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The application did not mention Ethics Committee referral or the fact that by March 1988 the majority of the brains already collected had been retained from Coroners' cases. |
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| The NWRHA were informed that some funding had been secured from the Wellcome Trust and the Science and Engineering Research Council (SERC). | |
| July 1990 Progress report | |
| This report on the first research project grant applied for in May 1985 on 'An investigation of amino acid neurotransmitters in the temporal lobe of brain in Alzheimer's disease and schizophrenia' stated that the brains of cases of Down's syndrome had been investigated in addition to Alzheimer's disease, and that: | |
| 'One of the benefits of the NWRHA project grant was the opportunity it gave us to establish a successful local brain collection scheme which provides tissue for both our present and future investigations'. | |
| 20 August 1990 Third application | |
| This application requesting support for two years was submitted by Dr Claire Royston, Professor Deakin and Dr Slater. In 1988 Dr Royston had joined as a junior member of the team funded as a Wellcome Research Fellow. She also held an Honorary Senior Registrar appointment in Psychiatry. | |
| The title of the project was 'Computerized image analysis of the anatomy of glutamate and GABA systems in schizophrenia'. | |
| This proposal was to build on novel research results obtained from the work supported by the two previous NWRHA grants. The scientific plan had been developed and modified in the five years since the first application. | |
| Brain collection and Ethics Committee involvement | |
| The procedure for obtaining human brains is set out for the first time in the plan of investigation, and the involvement of Ethical Committees is also mentioned: | |
| 'A system for the collection of whole brains from schizophrenic and control subjects is established in collaboration with ethical committees and hospitals within the Greater Manchester region'. | |
| 'For the control subjects an exhaustive review of all available hospital case notes together with the General Practitioners case notes were made confirming that control subjects had no history of psychiatric or neurological illness nor had received any psychotropic medication. Collection of brains will continue to provide future tissue resources'. | |
| Coroners' cases | |
| There is, however, still no reference to Coroners' cases although by June 1990 75 per cent of the brains obtained from mortuaries in the Manchester area had been retained from Coroners' cases, Chapter 16. | |
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B: Applications to the Medical Research Council |
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| In 1988 and 1989 the Medical Research Council (MRC) received three project grant applications from Dr Slater who was the sole applicant. These were considered and funded through the Council's competitive project grant scheme. | |
| The three project grants | |
| All three projects involved investigation of the neurochemistry of the brain and were planned to compare the results obtained in diseased brains with those taken from neurologically normal people. | |
| March 1988 | |
| The title of the first project was: 'Cortical and basal ganglia neurotransmitters in Huntington's disease'. | |
| The application states: 'The study will be made using sections of frozen brain from normal (control) and HD (Huntington's disease) subjects'. | |
| 'We have control brains from subjects with no history of neurological disease which were obtained from hospitals in Greater Manchester through long-standing arrangements'. | |
| December 1988 | |
| The second project's title was: 'Amino acid neurotransmitters in Alzheimer's disease brains'. | |
| The application states: 'The study will be made using frozen brains from normal subjects, from cases of advanced AD (Alzheimer's disease) and from subjects with DS (Down's syndrome) of middle age with AD'. | |
| 'Brains are obtained through the cooperation of relatives, clinicians, pathologists, coroners' officers and mortuary staff in the Greater Manchester area. We have set up a brain collection scheme with teaching and long-stay hospitals which involves obtaining pre-mortem consent from patients and relatives for brain removal at death'. | |
| May 1989 | |
| The third project's title was: 'Calcium channel antagonist binding sites in normal and schizophrenic human brains'. | |
| The plan stated: 'The study will be made using frozen brain from normal (control) and schizophrenic subjects'. | |
| 'We have whole brains removed at post-mortem examination. Brains from subjects with schizophrenia and from neurologically normal subjects have been obtained during the past 18 months from hospitals in Greater Manchester through long-standing arrangements. Either the coroner's office or the hospital alerted us that a postmortem was taking place (with the consent of a close relative) on a subject with a psychiatric history'. | |
| This application was the second to refer to the involvement of the Coroner's office in identifying cases. The first such reference is in the application submitted in 1988 to the Mental Health Foundation, see below. In the application to MRC it is unclear if the reference to the 'consent of a relative' is also intended to apply to Coroner's cases. | |
| 1993 | |
| The MRC did not, at any stage, provide funds for the other general activities of the joint programme's brain bank, but in 1993 the MRC funded a small project grant of one year's duration in the Department of Psychiatry. The grant was awarded to J Graham, C J Taylor and Professor Deakin. No other details are available. | |
| C: The Wellcome Trust | |
| 1988-1991 A Wellcome Training Fellowship awarded to Dr Claire Royston on: 'The anatomy and development of amino-acid containing neurones and their role in schizophrenia'(1). | |
| Dr Royston had joined the research team as a junior Wellcome Research Fellow and Honorary Senior Registrar in 1988 to work with Dr Deakin and Dr Slater. | |
| 1991 A two-year project award to Dr Deakin on: 'Amino-acid receptors and the pathogenesis of Schizophrenia'. | |
| This project was later extended for a third year. | |
| D: The Mental Health Foundation | |
| 1988 Two project grant applications were made to the Mental Health Foundation. | |
| One application entitled 'Quantitative and anatomical studies of receptors for psychotomimetic drugs and of glutamate systems in schizophrenia' was made by Dr Deakin and Dr Slater. This was for a 3 year project grant on which Dr Simpson, a junior member of the team, would be the chief investigator. The grant was requested to start in September 1988. | |
| The summary of the project states: 'It is proposed to use immunocytochemical and autoradiographic methods to study glutamatergic systems in sections of schizophrenic and control brains in which neuroanatomy is preserved'. | |
| The source of brains is described in the section of the application headed 'The Investigation. Control brains, from subjects with no history of psychiatric or neurological illness, will be obtained from hospitals in the Manchester area through long-standing arrangements. The GP is automatically contacted to exclude cases with dementia, a previous psychiatric history or other relevant condition such as epilepsy or neurological diseases. A number of brains are presently stored in our laboratory and more will be obtained as needed. | |
| Brains from subjects with clinically diagnosed schizophrenia are obtained at regular intervals. We have the collaboration of clinicians and mortuary staff at Prestwich Psychiatric Hospital, North Manchester, in obtaining consent and brain removal at post mortem examination. Similarly, via the Rochdale Coroner, we obtain brains from the Lancashire area. We already have sufficient brains for the project to start. | |
| The brain bank laboratory (Addenbrooke's Hospital Cambridge) have recently supplied us with samples of schizophrenic (and normal) brain and this source will be used again during the project.' | |
| This application is significant as it is the first by the joint team to make any reference to the involvement of the Coroner in obtaining brains for the programme. | |
| The application does not mention whether the work had been referred to an ethics committee. However, the section on 'Consumables' includes a request for 'mortuary & travel expenses for brain collection' of £250 per year. | |
| 1988-1991 A second three-year grant application entitled 'Neurochemical Studies of Schizophrenia'(1) was awarded by the Mental Health Foundation to Dr Deakin, M Simpson and Dr Slater, but the protocol for this application is not available. | |
| E: Other NWRHA grants | |
| 1993 Faculty of Medicine/Regional Health Authority equipment grant. | |
| 1994 North West Regional Health Authority grant to Dr Slater and Professor Deakin for a project on: 'Cerebellar structures & neurochemical markers in schizophrenia'(1). | |
| F: The Stanley Foundation | |
| 1990-1992 Award to Dr Royston for: ' A morphometric study of the frontal cortex in schizophrenia'(1). | |
| For the grants and awards listed at C, E and F, only the titles and details recorded above are now available. | |
Summary |
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| The successful results of the first research grant awarded in 1985 by the North West Regional Health Authority led to the award of two further grants in 1988 and 1990. | |
| Three grant applications to the MRC by Dr Slater were awarded through the Council's competitive projects grant system. | |
| The third of the applications to the MRC was the first to include any reference to the collection of brains identified by the Coroner's office. | |
| The Wellcome Trust made two awards in 1988 and 1991. | |
| Two grants were awarded by the Mental Health Foundation. One of these is notable as the first reference to a Coroner in any application made by the joint team to a research funding body. No details are available of the second application to the Mental Health Foundation. | |
| Grants were obtained from a number of other funding organisations. | |
| The award of these grants at a time when competitive research grants were becoming increasingly difficult to obtain indicates that the scientific quality of the research was highly regarded by the team's peers. | |
| With these grants the team were able to expand the scope of the programme between 1988 and 1994. | |
| Further grants were obtained after the period of this investigation. | |
| References | |
| 1. Details of the grants and awards in paragraphs C, E and F were listed in the applications submitted to the NWRHA in August 1990. |