(header) (header) (header)
The Stationery Office
(header)
  Home | Command Papers | House Papers | Departmental Papers | Search | Site Map | Contact Us | Links
(shadow) (shadow) (shadow) (shadow)
 

Contents

Previous

Next
The Investigation of Events that followed the death of Cyril Mark Isaacs
(rule)

CHAPTER 46

The benefits of post mortem research: clinical and ethical aspects of the
retention of organs and tissues

Introduction

This is the last of three chapters that address the fourth of my Terms of Reference. The chapter draws attention to the great advances in knowledge and improvements in the care of patients in succeeding generations that have resulted from post mortem research on the brain. These benefits have only been possible through post mortem research.
The chapter also considers the ethical and clinical basis on which research on the brain should continue in the light of my findings on retention of organs from Coroners' post mortems.
Post mortem research on the brain is essential for future improvements in prevention and treatment of neuropsychiatric diseases and to improvements in patient care. There is no alternative to post mortem study for continued progress in the understanding of disease processes that affect the brain. The importance of this field of research cannot be over-emphasised.

The benefits of research on the dead
Historically, the study of diseased organs and tissues after death has led to greater understanding of the processes that led to death. The findings from post mortems have advanced medical knowledge and the care of patients in ways that could not have been achieved by research on surgical specimens obtained during life.
There is abundant evidence in the medical literature that shows how much succeeding generations have benefited from the findings made from post mortems on the bodies of previous generations.
Research on the brain
In almost all organs disease processes can be studied through removal of small quantities of tissue at the post mortem. The brain is an exception to this general rule as it is the organ of the body least amenable to detailed study during a post mortem examination. The reasons for this were described in Chapter 7. If histological examination of the brain, or part of it, is necessary there will be a delay of four to six weeks while the brain is fixed. There is no satisfactory alternative method to expedite histological examination.
The clinical need and value of research on post mortem brains
In discussion with neurologists, psychiatrists, neuropathologists and many others during this investigation, I have been provided with specific examples of beneficial results from research on post mortem brains. Many studies have revealed mechanisms and processes in the brain that led directly to improvements in the range and effectiveness of treatments for conditions that had not previously been treatable, for example in Parkinson's disease.
Post mortem studies have also led to practical preventative strategies. The head protection that is now worn in amateur boxing bouts is designed to avoid brain damage from repeated blows to the head. These measures, and the limits set on the number of rounds in amateur and professional fights, are the direct result of research undertaken by Professor Corsellis. His research conclusively linked the resulting brain damage to their previous boxing careers, Chapter 33.
The recent death of a professional football player, renowned for his ability to head the ball into the goal when footballs were considerably heavier than they are today, illustrates that brain damage in sport from repeated minor head injuries was not confined to boxing.
It would be possible to draw up a very long list of research to illustrate how new knowledge and improvements in prevention, treatment and patient care are the direct result of research. Construction of such a list goes beyond my Terms of Reference. However, during the course of this investigation I have received illustrative examples from experts who have long experience in these specialised research fields. These will be found at Annex 114, and I am indebted to those who have provided these contributions. This annex can only include a few examples from an enormous research literature.
The value of brain research
This report has focused on what went wrong with post mortem research on the brain in some places. However, there have been many post mortem studies in which the organs were retained with the full knowledge and consent of the relatives. It is essential that the benefits to future generations from such research are recognised.
The observations and correspondence from eminent consultants in neurology, psychiatry and neuropathology and the papers they have provided prove, if any such proof was needed, that brain research in this country has been original, clinically valuable and of worldwide significance.
Brain archives
Another element in the success of brain research in this country has been the availability of brain collections and archives. These collections have been crucial to the success of brain research. To give one important example, without brain collections and archives it would not have been possible for variant CJD to have been recognised as a new disease in 1996.
There will inevitably be other situations where research on brain collections and archives will be the only way to find out if an apparently new disease is indeed new, or the re-emergence in a modified form of a disease that has been previously described.
Without brain collections and archives, research in neuropathology and neuropsychiatry will be seriously jeopardised. Brain archives and the information these contain must be recognised as essential research tools to improve the care of patients. The potential of DNA research on the brain has yet to be explored, and for this brain archives will be essential.

Histological research on retained brain tissues
One particular benefit of archived brain tissues is the opportunity these provide for further research into the histological features of neuropsychiatric disorders. At the Queen's Medical Centre, Nottingham, research of this kind is described as 'diagnostic review', Chapter 28. This research has a number of important purposes based on brain histology:

- advancement of knowledge;

- improvement of diagnostic accuracy;

- quality control and medical audit;

- continuing medical education and training.

Advancement of knowledge
Knowledge of neuropsychiatric disease has made major advances through research on histological diagnoses. New disorders, such as variant CJD, have been identified. In future, similar opportunities will undoubtedly occur.

Improvement of diagnostic accuracy
Through review of histology of the brains of patients with Alzheimer's disease, a different condition of dementia with Lewy bodies was identified. This discovery has resulted in changes in the drug treatment of patients with this condition to prevent drug-related deaths.
In the context of particular patients, re-appraisal of brain histology can benefit families when a second related individual becomes afflicted by a similar disease and the original diagnosis of the first relative is called into question.

Quality control and medical audit
Histological review is an important method of quality control in histopathological practice and thereby in the identification and avoidance of misdiagnoses.

Continuing education and training
Continuing medical education and the promotion of good medical practice can both benefit from regular histological self audit. This enables histopathologists to maintain and enhance their individual standards of practice and to compare the quality of their diagnoses with their peers.

Consented research on the brain
It is a challenging task to ask relatives for consent to brain retention, and the sensitivity required in making such requests should not be under-estimated. However, experience since the 1970s shows that relatives are willing to agree when the purpose of the research is properly explained to them.
One of the earliest studies in this country by Dr Bird at Cambridge benefited from the enthusiastic support from relatives of patients with Huntington's disease. Many relatives of patients with this progressive incurable disease were active supporters of Dr Bird's research. They spread information to other relatives and encouraged the donation of brains, Chapter 26.
Since 1982 the Cerebral Function Unit in Manchester has collected brains of patients with progressive dementias with the full consent of relatives, Chapter 8.
Other large prospective studies, for example CFAS, OPTIMA and HOPE, have adopted similar procedures, Chapters 26 and 30. In these investigations the relatives are fully informed about the purposes of the research before they are asked about brain retention towards the end of the life of the patient. Their written consent is recorded, but a further check is made after the patient's death to confirm that the relatives have not changed their mind.
The relatives' support for the research is often indicated by the fact that they are the first to contact the research team after the patient has died.
While the difficulties of obtaining consent must not be under estimated, many investigations have been successfully carried out since the 1970s with the full knowledge and agreement of the relatives.
There must be no recourse in future to collection of brains from Coroners' cases without the knowledge of the relatives.
'Control' brains
Many research teams report that it is much more difficult to collect brains from normal individuals as 'controls' for their research. In some places brains of 'controls' have been collected from hospital post mortems with consent. Prospective studies such as CFAS and brain banks for specific conditions such as Parkinson's disease, encourage relatives to donate their own brains as 'controls' and in this the teams have experienced some success.
While the collection of 'control' brains certainly presents greater difficulties, the principle must be the same as the collection of brains from patients with neuropsychiatric disease. Consent of the relatives is an absolute requirement.
Past unlawful practices
After the Human Tissue Act of 1961, the previous practice of collecting tissues and organs without the knowledge and consent of the relatives continued to be widespread and with little regard for legal and ethical considerations.
Retention of organs and tissues was part of the post mortem room culture of the time. Organ and tissue retention was not the subject of comment or discussion. No one thought use of organs and tissues was in any way wrong. The research was intended for 'the public good'. Good intentions do not, however, justify disregard of ethical principles or ignorance of the law.
There must in future be no resort to collection of brains, or of other organs, from Coroners' cases just because these are easy to obtain without the knowledge of the relatives.
Ethics committee approval
In the 1970s and 1980s, with the increase of the role and influence of Ethics Committees, there was a growing awareness in some places that research on the dead might also require the consent of the relatives. This recognition started with research that documented the patient's condition in life and investigated the brain after death.
In the 1980s, the 'in life' dimension of research resulted in some teams routinely submitting applications that included research on post mortem brains for Ethics Committee approval.
The 1991 NHS guidance made it clear that all research 'on the recently dead in NHS hospitals' needed Ethics Committee approval.
The joint team in Manchester continued collecting brains from Coroners' cases until 1996, without the knowledge of the relatives or of any Ethics Committee. In other places the practice of collecting brains from Coroners' cases continued even later, only to end with publication of the report of the Royal Liverpool Children's Inquiry.
For the future, Ethics Committees have an important responsibility to see that consent of the relatives is integral to the methodology of all studies that use organs and tissues, irrespective of whether these are obtained from hospital or Coroners' post mortems.
Research funding bodies
In the past, organisations that fund post mortem research relied on statements by the applicants that ethics approval had been obtained. For the future, research funding organisations should insist on seeing the terms of approval by the relevant Ethics Committee.
The risk to future research potential
This country has been one of the leaders in the international effort to carry out post mortem research in neuropsychiatric conditions. Several research teams working in different parts of the country have made major international contributions.
This country's research potential has been jeopardised by covert brain retention which relatives believe has betrayed their trust as well as disregarding the Human Tissue Act. Public confidence and trust in medical science has been undermined and with it the willingness of relatives to agree to post mortem research.
The rest of this chapter sets out ways in which public trust and confidence can be restored. This is in everyone's interest.
Restoration of trust
Introduction
With openness and integrity the following measures will provide further reassurance and the basis on which confidence can be rebuilt.

Consent by the relatives
The first and essential requirement is that the relatives must always be asked for their consent for the collection and use of post mortem brains in research, including the retention of 'control' brains.
Strict adherence to the principle of consent must be the key priority.
In other spheres of medical practice the patient's consent (or, for research involving children, their parents' agreement) must be obtained before any research can be ethically undertaken. The same principle must be applied to post mortem research, except that the consent will be obtained from the relatives after death in addition to any consent given in life by the deceased.
Relatives must also be asked if retention is to be for research, teaching or training purposes.

Consent forms
All hospital consent forms for post mortem examinations must include separate entries for consent for the examination and consent for retention of the brain and for other organs and tissues.
If the relatives ask for additional information about retention they must be told what is involved. If they wish, the relatives can place restrictions on what is retained and the purposes for which it is used.
Referral to an Ethics Committee
All research on brains and brain tissues from post mortems must be submitted to a properly constituted Ethics Committee. The Committee must be given all the relevant information. As part of its evaluation, the Ethics Committee must be able to check how consent will be obtained; this is particularly relevant to collection of 'controls'. The methods through which brains are obtained must be transparent and open to validation.

Checks by research funding bodies
When an application for research funds is received, the funding organisation should check what arrangements have been made to obtain consent from the relatives and the terms of the ethical approval obtained.

Checks on consent in mortuaries
A system should be established in each mortuary so that a named individual has responsibility for checking that consent has been given by the relatives before any organ or tissue is retained for research at the end of the post mortem.

Record keeping
Proper records must be maintained of all organs and tissues retained whether retention is for diagnosis, research or teaching purposes. Retention must be recorded in the post mortem report. This applies equally to hospital and Coroners' cases.
A named person in each NHS Trust should be responsible for ensuring the accuracy and completeness of all records of retained organs and tissues, and that these are kept up to date.

Reports
Regular reports on the progress of each research project using retained organs and tissues must be made to the Ethics Committee, the responsible NHS Trust and the organisation(s) funding the research.
Brains retained from Coroner's post mortems for diagnosis
When the brain is retained for diagnosis, the relatives must be informed and asked about what is to happen once the Coroner no longer needs the brain for his purposes.
In practice the choice for the relatives is limited to:

-  return of the brain to the relatives for burial or cremation;

-  disposal by the hospital on behalf of the relatives;

-  donation of the brain for research or teaching, including diagnostic review.

The relatives' choice must be unfettered. There will be many who prefer the second or third of the above options; for others, the return of the brain for burial is of paramount importance for religious reasons.
Research on other organs and tissues
The same measures should apply to retention of other organs and tissues. There are indications that given these conditions, relatives will consent to research on brains if the purpose of the research is fully explained to them. In one centre, consent is now obtained in the many cases where specialist teams have been set up to provide relatives with as full an explanation as they want about the purpose of research.
Provided the conditions are scrupulously observed there should be minimal risk of brains, or other organs, being collected for research unethically or unlawfully.
Summary
Research on post mortem brains has led to many important advances in knowledge and to the improvement of treatment and care for patients with neuropsychiatric diseases.
The value of post mortem research on the brain cannot be underestimated.
Brain collections and archives are essential to the future of neuropathology and neuropsychiatric research. The collections provide the only means by which new diseases can be distinguished from old diseases with new features.
Consent from relatives has been obtained in the past and is vital for the future. It is essential that the reasons for research are explained to them.
There must be no return to the collection of brains or other organs from Coroners' post mortems as a convenient and easy source of specimens for research.
Public trust and confidence has been undermined by retention of brains, organs and tissues from post mortems without the knowledge of the relatives.
A named person in each NHS Trust should be responsible for ensuring the accuracy and completeness of all records of retained organs and tissues.
Research undertaken 'in the public interest' cannot justify or excuse disregard of the Human Tissue Act.
Ethics Committees and research funding organisations are well placed to review the arrangements proposed for obtaining the consent of relatives.
The benefits of neuropsychiatry research, in which this country has made a very substantial contribution to international knowledge, have been put at risk.
The foremost priority must now be the restoration of public trust that all retention of organs and tissues will in future be with consent. A series of measures are proposed to achieve the restoration of confidence.


 
       
 

Contents

Previous

Next