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The role of the Medical Research Council

The MRC is the Government's main agency for fostering and funding biomedical research. In keeping with this important role, the MRC has made a pivotal contribution to the development of clinical and basic research on the brain in this country. This has been achieved in two ways.  

First, the MRC has a distinguished record of supporting world class neuropsychiatric research in its designated research units, and by awarding programme and project grants to other research teams through the Council's competitive research funding systems. 

Second, and of equal importance, have been the Council's thematic reviews of different research fields to identify the most promising future lines of research. The subjects identified through these reviews then become priority areas for future Council funding.  

Through these mechanisms the MRC has kept this country's basic and clinical research competitive with the best in the world in many fields including the neurosciences.  

Sources of information

For this investigation the MRC has provided a written response about the policies and procedures for brain research and brain banking which have been developed over the last four decades.

The chapter also draws on contemporaneous notes of workshops and other MRC meetings, and programme and grant applications to the Council. The minutes of MRC meetings on brain research, brain banking and related subjects have been particularly informative, and have provided a contemporary insight to the thoughts of the research community in the 1970s and 1980s.  

The MRC's Topic Review issued in December 1995 entitled 'The MRC's Role and Guidelines for MRC-funded Brain Banks' provides a clear statement of the Council's policies in the mid 1990s(1). This followed from the work of the Brain Bank Review Committee set up in 1991. The review includes principles that all researchers funded by the Council were required to follow.

• Download Annex 110 (PDF, 842K)

Why did the MRC decide to support research on the brain?

The importance of studying the brain and of investigating the causes and effects on the brain of neuropsychiatric disorders such as Alzheimer's disease and schizophrenia, has long been recognised. The MRC's reasons for supporting post mortem research on the brain are set out in the 1995 Topic Review:  

'Systematic brain banking has added a new dimension to neuroscience, contributing to major advances in research into human neuroimmunological and neurodegenerative diseases. New treatments of Parkinson's disease and Alzheimer's disease were originally based on discovery of neurotransmitter abnormalities (in the 1960s and 1970s) in post mortem tissue obtained from clinically and neuropathologically diagnosed cases'.  

The section later continues: 'All pathological studies of the human brain depend on fundamental knowledge of the distribution of key components (receptors, transmitters, peptides, cytoskeletal proteins). These have been mapped over the last two or three decades using normal, banked tissue'.

Historical perspective of the MRC support for brain research

Starting in the 1950s, the MRC funded brain research though programme and project grants, and from the 1970s supported this field of research in its own units. The brain related programmes and projects that MRC has supported are far too numerous to list, but collectively the results achieved have made, and continue to make, a substantial contribution to new knowledge and to improve the care of patients with neuropsychiatric diseases.

MRC support for brain banks

For consistency in this report this collection has been referred to as the 'Corsellis collection' although in earlier years it was referred to as the Runwell collection.  

Research on brains from hospital post mortems was a novel development in 1950 when Dr Corsellis began to collect and study brains in the Pathology Department at Runwell Hospital. The MRC soon recognised the importance of this new field of research and in 1953 awarded Dr Corsellis a research grant, Chapter 33.  

MRC support for research on the Corsellis collection continued for the next four decades. In 1985 the MRC provided support through staff attached to the Division of Psychiatry at the Clinical Research Centre. The research programme of the Division was linked to studies based on the Corsellis collection, Chapters 31 and 32.  

The research at CRC was led by Dr Tim Crow and Dr Eve Johnstone. Dr Crow was subsequently appointed Professor of Psychiatry at Oxford University and Dr Johnstone was appointed Professor of Psychiatry at Edinburgh University.  

When the Clinical Research Centre closed in 1994, project grant support for research on the Corsellis collection was maintained by MRC. In 1995 Professor Crow received MRC support to use Magnetic Resonance Imaging on fixed brains to study: 'Developmental anomalies of cerebral asymmetry and corpus callosum in schizophrenia and psychoses'.  

The MRC recognised the importance of chemical mechanisms within the brain when it set up the Neuro Chemical Pharmacology Unit (NCPU) at Cambridge in 1971. As its name implies, the Unit was established to research the chemistry of the brain. The origins of the Cambridge brain bank were described in Chapter 26.  

The Huntington's disease project, also described in Chapter 26, began in 1970. This project came about because of the freedom MRC gives to senior scientific staff in all its units to undertake research projects of their own choosing in the context of the proposed programme of work approved by the Council.  

In 1975 the MRC awarded a grant specifically for investigation of Huntington's disease. From this beginning MRC support for the Cambridge brain bank evolved. The banking functions were formally recognised by the MRC in 1980. 

The MRC decided to close the NCPU in 1985, but awarded a five year programme grant to maintain the brain banking facility. This was administered through the Department of Psychiatry, which was headed by Professor Paykel. Other research applications were submitted in parallel, Chapter 26.  

In 1987 the MRC decided in principle to refocus the bank's activities on collecting brains for specific projects. This was a reflection of the Council's view that MRC brain banking activity should focus on systematic collection and distribution to underpin high-quality and peer reviewed research relevant to the Council's strategy. Research teams were expected to make their own arrangements for collection of brain samples relevant to their work rather than to rely on brain banks.  

The MRC approved the 'Cognitive Function and Ageing Study (CFAS)' in 1988. As its name implies, this is a long-term investigation of the ageing process. Cambridge was one of the six participating centres. The MRC changed the direction and emphasis of its support for brain research with the funding it provided for this and other prospective studies. For these studies a research nurse was appointed to the programme.  

The MRC carried out a further review in 1992 as a result of which the Council funding for the banking function at Cambridge came to an end in September 1998, but support for CFAS and other long-term prospective investigations is ongoing.  

Other brain banks the MRC had supported prior to 1991

The brain bank in this unit was funded by the MRC from 1978 until 1989 when post mortem studies in the unit ended. The brain collection was later transferred to the Department of Pathology in Edinburgh where it was no longer dependent on MRC support.  

The brain bank in this Department had received MRC support since 1980 for research on Alzheimer's disease, other dementias and schizophrenia, which included brain tissue collection, Chapter 30.  

This bank had been funded by the MRC since 1980. It was located within the Council's Neuro Chemical Pathology Unit.  

The London brain bank on Alzheimer's disease at the Institute of Psychiatry has been funded by MRC since 1988. 

Three banks to study the neurological effects of HIV were funded by the MRC in 1990. These are located at the Institute of Psychiatry, London, the Department of Neuropathology, Oxford, and the Western General Hospital in Edinburgh.  

Further details of all these banks can be found in the MRC 1995 Guidelines on Brain Banks(1) and Annex 110.

• Download Annex 110 (PDF, 842K)

MRC ethical guidance

The MRC's 1962/63 annual report was the starting point for the ethical structures that are now in place in this country. It reflected a signal change to the way that research on patients was to be conducted and the MRC was the first organisation in this country to formulate ethical principles to be observed by those undertaking medical research.   

Since that first statement in 1963 the MRC has progressively developed and strengthened its policies on the ethics of medical research. The MRC's statement provides full details and indicates the ethical requirements the Council place on all researchers who received MRC funding.  

At all times since 1962/63, the MRC has expected all researchers it supports to follow current ethical guidelines issued by the MRC and other organisations as appropriate and to comply with the MRC's conditions and grant rules.  

There are, however, five dates in the subsequent MRC chronology that are particularly relevant to this report. 

In 1972 the MRC issued a new statement on 'Responsibility in the use of medical information for research'. This provided guidance on investigations involving the transfer of medical information of identifiable patients. It made no reference to research on post mortem material. 

In 1985 the earlier statement was updated: 'Responsibility in the use of personal medical information for research; principles and guide to practice: a statement by the Medical Research Council'. Although this updated statement did not mention the use of human material, the role of Ethical Committees was referred to.

In 1992 a further update was issued: 'Responsibility in investigations on human participants and material and on personal information: guidance by the Medical Research Council'. This refers to human tissue although post mortem material was not specifically mentioned:  

'Where the approval of the appropriate local ethical body is appropriate, evidence of such approval must be forwarded with the application. In some cases this may lead to a dialogue ...about whether a particular proposal needs such approval, and the Council may require a letter from the relevant ethical committee chairman confirming that it does not'. 

In 1995 the 'Guidelines for MRC-funded Brain Banks' contained a section devoted to 'Consent for Removal and Retention of Tissue'(1) .  

On Coroners' post mortems the guidelines state: 'While HM Coroners do not require relatives' consent to authorise medico-legal autopsies and retention of tissue to establish the cause of death, the constraints on retention of tissue for other purposes such as research still apply'.  

On ethical aspects, the guidelines include: 'The requirements for decency and respect for the dignity of human remains are important ethical considerations'.  

'Health Departments' guidance makes it clear that Local Research Ethics Committees should be consulted about proposals involving the recently dead'.  

In April 2001 the Council updated its guidance in its Ethics Series in: 'Human tissue and biological samples for use in research'(2).   

This guidance emphasises: 

- 'Informed consent is required from the donor (or the next of kin, if the donor has died) whenever a new sample is taken wholly or partly for use in research';

- 'All research using samples of human biological material must be approved by an appropriately constituted research ethics committee';

- 'Researchers should treat all personal and medical information relating to research participants as confidential'.

• Download Appendix 7 (PDF, 2074K)
• Download Appendix 33 (PDF, 490K)
• Download Appendix 34 (PDF, 583K)
• Download Appendix 35 (PDF, 358K)

Project grant regulations

The MRC's regulations issued in 1979 state: 

'(1) If the proposals involve procedures for the removal of human tissue at post-mortem examination applicants are required to confirm they will conform with the relevant Code of Practice. 

(2) Any procedures undertaken during the course of a project that involves the removal of human tissue at post-mortem examination (Human Tissue Act 1961) must be carried out in accordance with the guidance issued by the Health Departments/Local Authority'.  

The first of these regulations was amended in 1983 so that the applicants had to confirm 'at the time of their application that they will conform with the relevant Code of Practice'.

• Download Annex 110 (PDF, 842K)

MRC discussions on brain banking

The MRC considered collection of brains for research and banking procedures on a number of occasions. Ethical aspects of brain research, taking account of the policies described above, were discussed several times starting in the 1970s.  

1976 Workshop on brain banking

The MRC hosted a workshop chaired by Professor Corsellis on 5 July 1976. This was attended by many of the UK leaders of brain researchers at that time. 

At the start of the workshop the MRC made clear 'that although the Workshop was held under the auspices of the MRC, it was not intended that the Council should monopolise brain banking in the UK or be responsible for all of its support financially'.  

It was also agreed that 'discussion should be restricted to the banking of human post-mortem tissue, except for biopsy specimens in the case of Creutzfeldt-Jacob disease'.  

The section of the workshop report headed 'Collection of brains' records 'The meeting noted that the major source of supply was the Hospital Pathology Department. Mortuary technicians generally appreciated some payment for their efforts to provide specimens.'  

'Coroners courts provided a further source of supply of post-mortem brains. In law the Coroner has the absolute right of disposal of any part of the body, but in practice there were frequently ethical and religious objections to this. These could sometimes be circumvented by the Coroner requesting the further examination of brain material as an extension of his own investigations. There were certain advantages inherent in suicide cases.'  

It is clear from the record of that meeting that those present believed that Coroners had authority to allow the retention for research of any organs and tissues, although Coroners would take account of the objections of the relatives.

• Download Appendix 36 (PDF, 367K)

National pituitary collection programme

Chapter 5 outlined the national pituitary collection programme. This began as an MRC-funded research project before the enactment of the Human Tissue Act in 1961. No documents were available about collection arrangements that took place in the early years of the research project.  

The legality of retention of tissues on the authority of the Coroner was questioned eighteen months later at a meeting of the MRC Human Pituitary Collection Committee held on 16 December 1977. 

A member of the Committee reported that he 'had been approached by a number of pathologists supplying pituitaries who were disturbed by the difference in procedure between hospital post-mortems and Coroner's post-mortems regarding the permission of relatives for the removal of tissues. Some pathologists were uneasy about the situation and were concerned about possible adverse publicity.'  

'After discussion the Steering Committee agreed that interpretation of the Human Tissues (sic) Act was quite clear and the spirit of the act was not being broken by present procedures because as Coroners were in legal possession of the bodies of those whose deaths were reported to them, they were legally entitled to say whether human tissues (i.e. pituitaries) could be taken from the bodies and used for medical education and research.....DHSS would discuss and clarify with the Home Office the whole situation. For its own part, the Steering Committee agreed that the Chairman should write to the Coroner's Association making them aware of the various points which had been raised'.  

In this connection Circular HC(77)28 had been issued to the NHS in August 1977. This addressed directly the question of the removal of pituitaries for the national collection programme. Referring to the Human Tissue Act, it stated: 'specific consent is not required by the Act'. 

At a meeting between MRC and DHSS officials on 17 January 1978, discussion about the prospects for collecting more pituitaries referred to the need for 'Reassurance that pathologists and mortuary technicians were legally safeguarded'... 'the Council had always understood that the method of collecting pituitaries for the MRC Collection conformed with the necessary requirements'.

On 17 April 1978 the MRC wrote to the DHSS about an approach to the Coroners Society to encourage the collection of pituitaries from Coroners' cases, but it is not clear if the letter to Coroners was ever sent.   

At the next meeting of the Steering Committee on 23 May 1978, the Committee was informed that the DHSS 'had drafted a letter to pathologists advising them of the legal position regarding the removal of glands'.  

Further correspondence followed and on 15 December 1978 the MRC was informed that the Regional Medical Officers had considered the matter. 'Their opinion was that the problem had generally settled down and they did not wish to draw attention to it again unless the need should arise'. 

The correspondence between the MRC and the DHSS apparently ends at this point but further advice about pituitary collection was sent to the NHS on 25 April 1980. This letter was issued after the DHSS had taken over responsibility from the MRC and encouraged an increase in pituitary collection.

• Download Appendix 5 (PDF, 243K)
• Download Appendix 37 (PDF, 296K)
• Download Appendix 38 (PDF, 192K)
• Download Appendix 39 (PDF, 309K)
• Download Appendix 40 (PDF, 249K)
• Download Appendix 41 (PDF, 64K)
• Download Annex 23 (PDF, 151K)

Review of MRC brain tissue banks, 22 October 1991

The first meeting of this Committee reviewed the operation and procedures of nine brain tissue banks supported by the MRC, and for comparative reasons, information about three other banks in the UK and three in Europe. In their comments to the Committee, one bank noted: 'Although always in short supply, normal tissues were obtainable through a network of links with coroners and London hospitals'. 

At the same meeting another bank referred to the need to obtain 'the confidence and consent of patients and their families'.  

The Committee 'recognised that Banks would wish to refuse to supply material for uses which did not have appropriate ethical approval', but made no specific comment about ethical approval for the collection of brains or brain samples.  

The Committee recommended that an expert working party should help the MRC set up 'a national register of stored and available brain-tissues'. 

• Download Appendix 43 (PDF, 453K)

MRC funding of brain research at Manchester University

n 1988 and 1989 the MRC awarded grants to three brain-related projects in the Department of Physiology at Manchester University. These did not involve the MRC in supporting the general activities of the joint programme's brain bank.  

Dr Paul Slater was the applicant in all three projects. These 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.  

These applications were described in Chapter 11 and were supported by the MRC. 

In 1993 a small project grant of one year's duration was also awarded to the Department of Psychiatry, the details of which are not available.

• Download Appendix 23 (PDF, 782K)
• Download Appendix 24 (PDF, 726K)
• Download Appendix 25 (PDF, 831K)

Summary

In 1962-63 the MRC led the way in developing the first set of principles for ethical evaluation of research in human beings. These were published in 1964.  

The MRC's approach to, and involvement in, brain banks and brain banking can be seen to follow the general evolution of professional practice over the four decades since the enactment of Human Tissue Act in 1961.  

To ensure that ethical principles were observed, the Council imposed a requirement that all grant holders must obtain clearance from Ethics Committees. This was made explicit in the 1979 regulations.  

Despite the clarity of the MRC's regulations, this investigation has identified two research teams that received support from the Council but disregarded the Council's requirements.

While the Council regularly updated its guidance on the ethical responsibilities of researchers, it was not until 1995 that specific guidance on brain banks was given. This drew attention to the need for Ethics Committees to be routinely consulted on research relating to the recently dead.  

Following the publication of the Redfern Report(3) in 2001, the MRC published further guidelines on 'Human tissue and biological samples for use in research'. This provides a comprehensive and clear set of principles for the lawful and ethical use of human tissues.  

All researchers supported by the Council are expected to follow the policies, regulations and procedures that the MRC has developed. Through these the Council has sought fully to comply with all legal, ethical and administrative requirements.  

The Medical Research Council recognised the importance of post mortem research on the brain as early as 1953 when the Council provided support for Dr Corsellis.  

In 1970 research into Huntington's disease was undertaken at the MRC's Neuro Chemical Pharmacology Unit at Cambridge.  

In 1979 the MRC formally supported the Cambridge brain bank, and some MRC support continued until September 1998.  

In 1987 the main focus of the brain collection at Cambridge changed to the prospective collection for a long-term study of Cognitive Function and Ageing (CFAS).  

The MRC funded two other brain banks before 1980 and five more between 1980 and 1990.  

The MRC was also active in supporting research projects and programmes in other centres.  

In 1991 the MRC set up a Brain Bank Review Committee. Following the Committee's deliberations, the Council published 'Guidelines for MRC-funded Brain Banks' in 1995.  

In 1988 and 1989 the MRC supported three project grants in the joint programme at Manchester University.  

The use in research of brains obtained from Coroners' post mortems was brought to the MRC's notice and discussed at a number of meetings convened by the Council starting in 1974.  

When the legality of collecting brains was discussed in the 1970s, the view was taken that the collection of brains, pituitaries and other tissues from Coroners' cases was lawful. It was believed that Coroners had authority and discretion to agree to the retention of tissues for research and teaching.  

On the collection of pituitaries, legal advice was specifically obtained about the National Collection Programme and the DHSS was consulted after legal doubts had resurfaced in 1977. The DHSS Circular issued earlier that year gave reassurance that specific consent was not required.  

The MRC's 1995 guidance drew attention to the limitations to the authority of the Coroner to order the retention of organs and tissues unrelated to the cause of death.  

Applications submitted to the MRC on behalf of the Cambridge brain bank in 1985 and by the joint team at Manchester in 1988 did not mention that brains had been collected from Coroners' cases. There may have been other applications that similarly slipped through the net. 

Research applications to the MRC or to other funding organisations should contain all the relevant information. However, when research involves ethically sensitive matters, it may in future be necessary for the Council to check key features, as envisaged in the 1992 Statement of Responsibility.  

The restoration of public confidence must be given high priority. This is discussed in Chapter 46. As part of the process it may be necessary for the MRC to check more frequently on the terms of ethical approval and to make direct enquires about the source of human organs and tissues and the consents that have been given by the patient and/or relatives. 

References

1.  The MRC's Role and Guidelines for MRC-funded Brain Banks, 1995.  

2.  Human Tissue and Biological Samples for Use in Research, 2001.  

3.  The Royal Liverpool Children's Inquiry Report, 2001.