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The Investigation of Events that followed the death of Cyril Mark Isaacs
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| The third of my Terms of Reference required an examination of other centres that appeared to have collections of brains obtained from Coroners' cases. | |
| The brain bank and research programme at Cambridge was identified as one of the centres that should be included in this investigation for the following reasons: | |
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| Nomenclature |
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| Since the mid 1970s the brain bank at Cambridge has been referred to by a number of different titles and has moved locations several times. Whatever the location or name at a given time, brain collection has continued as a recognisable entity. For consistency in this chapter the collection is referred to as the 'Cambridge brain bank'. | |
| Sources of information | |
| Addenbrooke's Hospital | |
| To investigate the procedures of the Cambridge brain bank, meetings were held with present and past staff of Cambridge University and Addenbrooke's Hospital, pathologists, morticians, brain bank staff and others who had been involved in, or provided brains for, the bank from the early 1970s. The meetings began on 4 February 2002 with: | |
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| Mr Day is in charge of the arrangements for the return of retained organs and tissues from Addenbrooke's Hospital to relatives. | |
| Professor Collins, as Head of Pathology, has overall responsibility for the brain bank. | |
| Mr Carr has day-to-day operational responsibility for the Pathology Department. | |
| At this meeting full co-operation in the investigation was offered. Subsequently, Mr Carr arranged other meetings with staff of the brain bank and mortuary. | |
Access to staff and records |
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| The records of the brain bank were made freely available and its filing system explained. The Mortuary Registers and reports of all post mortems at Addenbrooke's Hospital since the 1970s were made available. | |
| At my request, lists of brains transferred to the brain bank from the Manchester area were prepared from the hospital's computerised pathology record system. This database had been set up to identify all retained organs and other specimens received from post mortems at Addenbrooke's and those referred from other hospitals. This system enabled Addenbrooke's to identify the hospital from which each organ had been referred. All referring hospitals were notified, in case the relatives should ask for the organ or tissue to be returned to them. | |
| Further meetings about the Cambridge brain bank are listed at the end of this chapter. | |
| Coroners for the Cambridge district | |
| Meetings were held with Mr David Morris on 27 March 2002, and Mr John Smith, his predecessor as Coroner, on 16 April 2002. | |
| Mr Morris has been Coroner for South and West Cambridgeshire since 1999 when the boundaries of the coronial districts were changed. From 1987 to 1999, Mr Morris had been Coroner for Huntingdon. He is also Coroner for the separate district of Bedfordshire and Luton. | |
| Mr Smith was appointed Coroner for South and East Cambridgeshire (known together as 'South Cambridgeshire' District) in 1987. At that time Cambridge City was a separate district. When Mr Sterndale Burrows, the Coroner for Cambridge City, died in post in 1990 the districts of Cambridge City and South West Cambridgeshire were combined. Mr Smith was Coroner for Cambridge City and for his first district of South Cambridgeshire until 1998. The boundaries of the districts were altered when Mr Morris was appointed. | |
| The changes in the coronial boundaries in 1990 are significant, as Chapter 27 will show. | |
Source documents |
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| The brain bank records - these start in the early 1970s and include individual records on all brains that have been retained by the brain bank; the Mortuary Registers at Addenbrooke's Hospital; and post mortem reports to Coroners. | |
| History of the Cambridge brain bank | |
| The brain collection at Cambridge was in 1980 the only brain tissue bank in this country(1). At that time there were three other brain banks worldwide, two in the USA and one in Sweden. The Cambridge bank was one of the first deliberately to collect brains from other hospitals for research. Other brain collections, such as the Corsellis collection, had begun as accumulations of brains retained after diagnostic examination had been completed, Chapter 33. The value of such collections for research was later recognised. | |
The MRC Neurochemical Pharmacology Unit |
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| In the 1970s the MRC provided direct funding support for the Neurochemical Pharmacology Unit (NCPU) which, as its name implies, was established to undertake research into the chemistry of the brain. The Head of the Unit was Dr, now Professor, Leslie Iverson. | |
| Research publications by staff of the Unit show that some brains were collected specifically for research from 1970. However, the start of the Cambridge bank is given as 1974 when it was recognised by MRC within the Neurochemical Pharmacology Unit. | |
Operational heads of the brain bank |
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1974-1978 Dr E D Bird |
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| Dr Ted Bird, a medically qualified American citizen, was a member of the Scientific Staff of the unit. In the early 1970s, Dr Bird became interested to discover if neuro-chemical factors in the brain had any significance in Huntington's disease. When the possibility of a research study on Huntington's disease was first mooted, there were doubts about the feasibility of finding enough patients for a meaningful investigation of this progressive and incurable condition. | |
| Dr Bird was undeterred and, having explained his objectives to psychiatrists and pathologists, began to collect the brains of patients who died from this condition. Dr Bird was careful to explain his work to relatives and his research attracted the enthusiastic support of many relatives and of COMBAT, the voluntary organisation for relatives of those with Huntington's disease. Some relatives became very active in identifying for Dr Bird patients with the early symptoms of Huntington's disease. As a result Dr Bird received referrals from many parts of the country. | |
| Dr Bird and Dr Iverson published the results of their research on Huntington's disease in 1974(2). | |
| 1978-1985 |
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| After Dr Bird left Cambridge in 1978, and in the period before the MRC awarded a programme grant for its 'banking' activities in 1985, the Cambridge brain bank was headed first by Dr E Stokes in 1978, followed by Dr Martin Rosser between 1979 and 1983, followed by Dr Gavin Reynolds. During this period the bank remained within the Neurochemical Pharmacology Unit until the closure of the unit in 1985. | |
| In the early 1980s, in addition to collecting brains of cases of Huntington's disease and control cases, the bank diversified to obtain brains of patients with a range of neuropsychiatric conditions. This was before an application for support of the 'banking service' was made to the MRC. | |
| The programme grant application to the MRC of 1985 | |
| This application was submitted by Professor Gresham, Sir Martin Roth and Dr Ian Wilkinson. The purpose of the application was to formalise the arrangements in the brain bank which had evolved to provide: | |
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| Other topic-related proposals were submitted to the MRC at the same time. These were separate from, but dependent on, the brain banking proposals in the main programme application. | |
| The brain collection procedure as described in the application to the MRC | |
| This application refers to the bank providing a major service for tissue collection, dissection and storage. The procedures used had been: 'worked out over the last 13 years, and vary with the particular needs of the studies for which they are collected'. | |
| 'Once a patient has died, the body should be moved to refrigerated storage, ideally within 4 hours of death. When all appropriate consent has been obtained, the post mortem dissection is performed, usually within 72 hours of death'. | |
| There is nothing in the application submitted to the MRC that implies that brains were being obtained without appropriate consent. In the context of brains from patients with psychiatric disorders the protocol records: 'Freedom to seek the help of mortuary technicians at any time and their willing co-operation in the enterprise has been a major asset … a generous and co-operative network of support at Fulbourn Hospital (the local mental hospital) and Addenbrooke's Hospital has also been an important asset'. | |
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| The application included a request for funds to upgrade the mortuary at Fulbourn Hospital so that bodies did not have to be transferred to Addenbrooke's Hospital in Cambridge for brain removal. | |
| The MRC awarded the programme grant and the research applications linked to it. | |
| In 1985 Professor Paykel, who had recently been appointed as Professor of Psychiatry at Cambridge University, became head of the bank. While Professor Paykel was concerned with the overall direction and management of the bank as titular head, the day-to-day control was the responsibility of Dr C M Wischik, who had succeeded Dr Reynolds. | |
| This programme grant gave the bank a firmer financial base and enabled the banking service to continue. For the next three years the bank maintained the procedures that had been used to collect brains from a widening range of diseases as well as control brains. | |
Application to the MRC in 1987 to change the bank's objectives |
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| A new and different application was submitted to the MRC by Professor Paykel and Dr Wischik. This application was to change the objectives of the bank from collecting brains of many diseases to the collection of brains for particular research studies, principally on Alzheimer's disease. Thereafter the bank would have a reduced capacity to provide brain tissues for research to other investigators. It was envisaged that each research team should collect its own material. | |
| 1988 | |
| A significant redirection of the energies of the bank followed in 1988. Researchers at Cambridge and the brain bank became involved in a multi-centre epidemiological study of progressive dementias, the CFAS study(3). This is a long-term study that is still in progress. For CFAS and other studies of patients, a research nurse, Mrs Angela O'Sullivan, was appointed to work on the programme. | |
| One of Mrs O'Sullivan's main responsibilities is to work with, support and counsel patients enrolled in the study and their families. The study has many methodological similarities to the research of the Cerebral Function Unit in Manchester, Chapter 8. | |
| One of the objectives is to relate the progress of the patient's illness with post mortem findings. In this respect, Mrs O'Sullivan's responsibilities include discussing the possibility of examination of the brain with the family when the patient is approaching the end of life. A set of consent forms and leaflets have been in use for this purpose since 1988 which Mrs O'Sullivan uses for discussion with relatives. | |
| With the start of the CFAS study, the balance of the bank's work moved from the provision of brain tissue to supporting this and other large-scale prospective studies. | |
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The end of the MRC's support |
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| In September 1998 the MRC ended its support for the 'brain banking' functions of the bank but has maintained funding of the long-term prospective investigations of dementia and other similar studies. | |
| How the Cambridge brain bank system worked | |
| Source of brains |
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| For the Huntington's disease study from which the brain bank evolved, brains from patients with Huntington's disease and control brains were required. In 1974 Dr Bird and Dr Iverson published details of how the brains were obtained(2): 'Several consultant psychiatrists and pathologists throughout the United Kingdom provided invaluable assistance by seeking permission for post-mortem examinations of the brains of patients with Huntington's chorea and in the initial handling of the brain material'. | |
| 'Controls consisted of coroners' cases and hospital cases of various ages, on which necropsies had been performed in the University Pathology Department at Addenbrooke's Hospital, Cambridge'. | |
| The reference to collection of control brains from Addenbrooke's mortuary should be noted as throughout the 1970s and 1980s the bank continued the practice of obtaining control brains from post mortems on Coroner's cases at Addenbrooke's Hospital(1). | |
Post mortem procedures at Addenbrooke's mortuary |
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| There was no difference in the procedure between hospital and Coroner's post mortems at Addenbrooke's mortuary. All were carried out as full post mortems and the brain was routinely removed. The procedures are described in a text book on mortuary practice published by Professor Gresham, who was in charge of the mortuary until 1990, and the Head Mortician, the late Mr Arthur Turner, entitled 'Post Mortem Procedures'. | |
| The post mortem reports mostly did not record that a brain had been retained for the bank. Other organs retained for research or teaching were generally not mentioned, but some reports to the Coroner did record the retention of specimens that had a bearing on the cause of death. | |
How were suitable brains identified? |
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| Mr Hills, the Chief Technician in the brain bank, states that after he was appointed in August 1980 he visited the mortuary each morning, on behalf of the head of the bank, to see what post mortems were scheduled. If a post mortem was from a case that would be of interest to the brain bank, he reported to the person in day-to-day charge of the brain bank who reviewed the case. If it was of interest to the bank, a request for retention would be made to the pathologist to ask that the brain be set aside at the end of the examination for the brain bank's use. Mr Hills states that this practice continued throughout the 1980s. | |
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Mr Hills' account differs from that of the Chief Mortuary Technician, Mr Stevenson, whose recollection is that the request came directly from Mr Hills. Professor Gresham, Dr Wight and Mr Stevenson all confirm that brains were regularly retained from Coroner's cases, Chapter 27. |
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| Brains collected |
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| The brains collected by the Cambridge bank fall into two of the categories that were described in Chapter 7. When brains were initially retained for diagnosis a report would be sent to the Coroner or, for hospital post mortems, to the doctor who had looked after the deceased in life. Among these were brains and parts of brains referred from other hospitals for diagnosis. | |
| The second category of brains was collected specifically for research. These include the collections of brains of suicides and the 'control' brains. In the case of 'controls', the brains were chosen because the deceased had no neuropsychiatric disease. | |
| The brains received by the bank in the 1970s were referred for histology to Professor Corsellis at Runwell Hospital. | |
| In 1985 the collection arrangements were described in the MRC application. The brain bank records show that between 1981 and 1984, a total of 367 brains had been collected of which 145 were 'controls', 100 from Huntington's disease, 36 dementia, 25 schizophrenia, 19 Parkinson's disease and the remainder from patients with a variety of other conditions. | |
| Coroners' cases |
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| Two categories of brains were regularly obtained from Coroners' cases in the 1980s. | |
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Brains of suicide victims |
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| By definition, a death from suicide or suspected suicide must be reported to the Coroner. Among brains collected by the bank from Coroners' post mortems were those of victims of suicide. This collection started in February 1983 and continued over the next seven years. Forty-three brains were collected, including the brain of Mr David Webb, Chapter 27. | |
| (The suicide brains were stored and, apart from a few samples from early cases which were sent to other researchers as part of the brain bank's 'banking function', no research or examination of any kind was undertaken on them at Cambridge.) | |
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Normal controls |
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| The second category of brains frequently obtained from Coroners' post mortems were normal 'controls'. The first 'control' brain was collected in January 1980. The total number of brains obtained in this collection was 557, not all from Coroners' cases. Collection of 'control' brains is continuing but now strictly with the consent of the relatives. | |
The 'control' brains were individually examined. This included histology to make sure each was suitable for use as a control for a particular study. The extent of the examination of a brain depended on the purpose of the study for which it was to be used. For Coroners' cases, no report on the examination was sent to the Coroner. |
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| Mr Hills states that, when the brain of a Coroner's case was requested for the brain bank, the Coroner was asked. However, this cannot be confirmed as Mr John Smith, Coroner for South and West Cambridgeshire, was unaware of the retention of brains for the brain bank until he was appointed Coroner for the City of Cambridge in 1991, and Mr Morris, who was Coroner for Huntingdon, was similarly unaware. The question of whether Mr Sterndale Burrows, Coroner for the City of Cambridge in the late 1980s, was aware is discussed later in this chapter. | |
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The ending of brain collection from Coroners' cases |
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| When Mr Smith became Coroner for the City of Cambridge in 1991, the retention of brains and other organs from Coroners' post mortems, without the knowledge or consent of the relatives, was brought to his notice. | |
| Mr Smith investigated and then gave immediate and firm instructions that no organs were to be retained for research or teaching from bodies for which he was responsible without his knowledge, and then only with the consent of the relatives. | |
| It should be emphasised that no brains, including suicides and 'controls', have been collected from Coroners' cases without the consent of the relatives since Mr Smith issued his instructions. | |
| Ethical Committee approval for brain collection | |
| Studies on patients |
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| The 1985 application to the MRC does not make any reference to approval of the bank through an Ethics Committee. The MRC requirement at the time was that all studies on patients must be referred for Ethics Committee approval. In view of the MRC's conditions for grants in place at this time, it is unlikely that any studies that involved patients had not been submitted to, and approved by, an Ethics Committee. | |
| Professor Paykel's clear recollection is that all new research that started after he had transferred to Cambridge received full ethical approval. | |
Collection of 'control' brains |
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| Whether the Ethics Committees were also informed or consulted about the collection of 'control' brains by the bank is not clear in the main 1985 application for funding of the banking activities of the bank. The application does not mention EC approval. This aspect was explored with Addenbrooke's Hospital. In a letter dated 1 August 2002, Mr Carr stated: | |
| 'You are quite correct in assuming that there is full ethical approval for research on consented brains, but this never seems to have been the case with brains collected from Coroner's cases. I am fairly certain that had ethical approval been sought for the brains, then it would not have been given on the basis of a lack of evidence of consent having been sought'. | |
| Mr Carr's statement is supported by the recollections of Mr Rick Hills, the Chief Brain Bank Technician. | |
| It should be stressed that since Mr Smith insisted on the need for proper consent, all 'control brains' have been collected with the consent of the relatives and using the same research consent procedure that is deployed for collection of index brains in the CFAS and other long-term prospective studies. | |
| Why had brains and other organs been retained from Coroners' cases? | |
| The pathologists at Addenbrooke's believe that before 1991 there was an understanding with the late Mr Sterndale Burrows, and that he did not object to the removal of organs and tissues for teaching and research. Other staff dispute this and have told me that Mr Sterndale Burrows would not have agreed to organ retention without the consent of the relatives. The latter view was expressed by one of the Coroner's Officers who worked for Mr Sterndale Burrows in the late 1980s. | |
| Some of the staff of the mortuary told me that they were uneasy about the number of organs that were being retained, but did not bring their concerns to the Coroner's notice. There are no contemporaneous written documents that shed light either way. I do not have the information to reach a definitive conclusion. Mr Sterndale Burrows cannot rebut those who say they had his tacit agreement to organ retention. | |
Cases from other districts |
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| The mortuary at Addenbrooke's also received bodies from other districts. In this context, when Mr John Smith was Coroner for South Cambridgeshire District, the pathologists and mortuary staff had not asked him whether organ retention had his approval. Had they done so, they would have been reminded of the legal position that nothing should be removed from the body when the relatives expressed objections except when this was necessary to discover the cause of death. | |
| Although Mr Smith regularly visited the other mortuaries in his district, he did not visit the Addenbrooke's Hospital mortuary as frequently. This mortuary was in Mr Sterndale Burrows' district as Coroner for the City of Cambridge, and his staff had an office adjacent to the mortuary. | |
| Until Mr Smith became Coroner for the City of Cambridge in 1991 and became aware of what was happening in the Addenbrooke's mortuary, the retention of organs from Coroners' cases continued. | |
| Post mortem reports to the Coroner | |
| The post mortem reports sent to the Coroner listed any tissue samples or other investigations made by the pathologist that could have a bearing on the cause of death. The reports did not mention that brains had been retained for the brain bank. | |
| All the post mortem reports on the 43 suicide victims whose brains had been obtained for the bank were examined. The records of the brain bank confirm that these brains were retained but none of the post mortem reports mentions brain retention. These reports were made to the Coroners for Cambridge City, South Cambridgeshire and Huntingdon Districts(1). | |
| A number of post mortem reports on cases where the brain had been retained as a control were also cross checked against the brain bank records. Again, the post mortem reports were silent about brain retention for the bank. | |
| In this respect these post mortem reports were deficient as they did not alert the Coroners to what was going on. The reasons for this are discussed in Chapter 42. | |
Brains received from hospitals in the Manchester area |
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| Between April 1973 and November 1975, 28 brains were referred by pathologists from Prestwich and other hospitals in North Manchester to the Cambridge brain bank. Ten of these were the brains of patients who had died of Huntington's disease. The remaining 18 were cases of schizophrenia. Among these were a number of Coroner's cases. | |
| In all these cases, a report was sent back to the pathologist at Prestwich Hospital. | |
| In keeping with the Cambridge brain bank's policy, the pathologists in Manchester who were referring brains to Cambridge were regularly informed of changes to the protocol and encouraged to send further brains. The brain bank was diligent in keeping the referring pathologists informed of the progress of research work. This practice appears to have originated with Dr Bird and followed by his successors in the bank. | |
| Recent analysis of brains collected by the bank | |
| The bank has provided an analysis of the brains that were collected between 1980 and 2001(1). The following table provides details. |