Tuesday, January 31, 2012

Day 2 GMC Fitness to Practice hearing for Andrew Wakefield



Tuesday 17 July 2007

Regents Place, 350 Euston Road, London NW1 3JN

Chairman: Dr Surendra Kumar, MB BS FRCGP

Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster

Legal Assessor: Mr Nigel Seed QC


WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry


(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)


MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.

MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield who was present.

MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith who was present.

MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch who was present.


Page No






THE CHAIRMAN: Good morning, everyone. Can I first of all remind you, once again, that if there are any mobile phones in this chamber can you please ensure that they are switched off. I had said that we were going to ask for the case to be opened by Ms Smith, but before that I think there were a couple of heads of charge that Mr Miller and Mr Hopkins were going to tell us about. What is the situation with those?

MS SMITH: Yes, sir, and I can in fact deal with those now, if Mr Miller and Mr Hopkins are happy to do so. As far as Professor Walker-Smith’s charges are concerned, the first was at paragraph 6(e)(iv).

THE CHAIRMAN: That is on page 38.

MS SMITH: Yes. There was a suggestion of a proposed amendment by Mr Miller. We do not accept that amendment and so the non-admission must remain.

THE CHAIRMAN: Thank you, so that remains a contested issue.

MS SMITH: Yes. The next was paragraph 10(d), and as far as that is concerned you will recall that that was an issue in relation to Dr Casson’s precise status. We have checked that as against his witness statement and we would be happy to amend if Mr Miller would be content with that, to say:

“Dr Casson, who was a senior registrar and lecturer in the department of gastroenterology.”

THE CHAIRMAN: I am sorry?

MR MILLER: It is “honorary senior registrar in the department of gastroenterology”, certainly.

THE CHAIRMAN: I think actually the way the head of charge is written at the moment is:

“On 28 August 1996 your registrar Dr Casson …”.


THE CHAIRMAN: Are we going to have a more substantial amendment rather than “your registrar” and maybe “honorary lecturer”?

MR MILLER: “Your registrar” goes, sir.

“Dr Casson, honorary senior registrar and lecturer in the department of gastroenterology.”

MS SMITH: Yes, and we are content with that.

MR MILLER: And that is repeated in head 10(i).

THE CHAIRMAN: I think that is repeated in 10(i) as well.


MS SMITH: The last one which was raised by Mr Miller was in relation to head 35(m) and with regard to that we do not accept that it is appropriate to amend, so that one must remain as a non-admission. That is head 35(m).

THE CHAIRMAN: Head 35(m) remains as it is.


MR MILLER: And not admitted, sir.

THE CHAIRMAN: Not admitted. As to head 10(e) and 10(i) can I just look at the Panel members and see if they are content? (Agreed)

MS SMITH: Would it help if I ran through them again? Would you like them all again?


MS SMITH: Just the last ones. It is 10(d) and 10(i) and they are both changed to delete “your registrar” and to insert, “who was honorary senior registrar and lecturer in the department of gastroenterology.” As far as head 35(m) is concerned, there was a proposal for an amendment in relation to that by Mr Miller which is not accepted by the prosecution, so that remains as it is and Professor Walker-Smith has, in those circumstances, not admitted it.

THE PANEL SECRETARY: I am sorry, Chairman, it is simply that I had no amendment at all to 35(m), so I do not know what it is you are talking about. It is obviously my mistake, but I did have a proposed amendment to head 35(n), the deletion of “under your clinical care.”

MS SMITH: Yes. The (n) one is the one that Mr Miller has made in respect of many of the heads of charge and that is correct, that Mr Miller is not admitting that. As far as (m) is concerned, Mr Miller indicated that he was prepared to admit that Professor Walker-Smith wrote to Dr Mills enclosing a copy of the protocol, but not that he wrote to the general practitioner Dr Shore. We would not agree, at any rate at this stage, to that amendment, and so it is deemed not admitted.


THE CHAIRMAN: So head of charge 35(m) remains as it is on the charge sheet and remains a contested issue?


THE CHAIRMAN: So far as heads 10(b) and 10(i) are concerned, I have had a nod of approval from my Panel members, it is coming as an agreed amendment and we are happy to accept that it will now be admitted under those circumstances.

MR MILLER: Thank you, sir.

MS SMITH: Thank you. There is one other, sir, and that relates to Professor Murch and it is head 16(c)(iv).

THE CHAIRMAN: Would it be possible for you to give me the page number?

MS SMITH: Yes, it is page 79, sir. The issue that was raised by Mr Hopkins was that he was not happy to admit that the note that was referred to in that paragraph was the admission clerking note. We have proposed, and I understand that he would agree, that instead of “clerking note” it should read “clinical note.” So, instead of “his admission clerking note” it reads “his clinical note indicated that he had …”.

THE CHAIRMAN: I take it that that amendment as proposed by Mr Hopkins is acceptable to you?

MS SMITH: Yes, it is.

THE CHAIRMAN: Again, I am going to look towards the Panel members. (Agreed) Yes, it is acceptable and therefore it is now admitted, Mr Hopkins?

MR HOPKINS: It is. As I understand it, “admission clerking” is deleted and you insert “clinical”, and we are happy with that.

THE CHAIRMAN: Yes. “Admission clerking” has now been replaced by the word “clinical”?

MR HOPKINS: Yes, and we are happy to make admission to that amended paragraph.

THE CHAIRMAN: Thank you very much indeed. I think that is helpful. I have been given an understanding that there are some legal issues that are floating around, so I wonder whether you could update the Panel with the situation?

MS SMITH: Yes. Sir, first of all, we were late coming in and I do apologise for that and
I thank you for your indulgence. I am going to ask you for a little more indulgence. There is indeed an issue that has arisen which it is essential that is discussed at this stage and in order to save you coming in and out I wonder whether I might ask whether you would rise for one hour. I cannot anticipate that it will take very much less than that. If it did, of course we would send a message that we were ready before then.

THE CHAIRMAN: You could not possibly give us an idea about the legal issue? If you feel that we should not know it, well, then it is a different matter.

MS SMITH: I think if I may, sir, I will simply say that it is an issue that has arisen this morning and we need to discuss it and we need to discuss it with the Legal Assessor, and
I hope you will understand if I do not say more than that at this stage.

THE CHAIRMAN: No, I fully appreciate that, and I take it, Mr Coonan, Mr Miller and
Mr Hopkins, that remains your view as well?

MR COONAN: It is a very sensible suggestion, sir.

MR MILLER: We agree, sir.

THE LEGAL ASSESSOR: Legal Assessor, I suspect you would be in agreement with that suggestion as well, coming from four counsel.

THE LEGAL ASSESSOR: Yes. I am in a minority of one if I take a different view.

THE CHAIRMAN: Thank you very much indeed. In that case, we will now adjourn for one hour. It is ten past ten and we hope to resume around ten past eleven, but if you are ready earlier I am sure you will be able to pass on a message to us, or alternatively we just wait to hear from you.

MS SMITH: Thank you very much, sir.

THE CHAIRMAN: Thank you again.

(The Panel adjourned for a short time)

THE CHAIRMAN: Good afternoon to you all. The one hour has been rather a long one hour, but never mind, I think we understand the reasons.

MS SMITH: Well, sir, perhaps I can say two things: the first is you will be pleased to hear that I am at long last now going to open this case to you.

THE CHAIRMAN: Thank you.

MS SMITH: I thank you very much indeed for your patience. We all appreciate how frustrating it is, particularly when you do not know why you are being kept waiting, and so perhaps I can just first of all tell you what the issue was that was concerning us.

The delay arose because I am referring in my opening to you to some documents which were produced by the Legal Services Commission. They were documents that were produced in the context of the MMR group litigation, which was funded by the Legal Services Commission. Two parents, in the very last few days (I think Thursday and Friday), contacted the GMC’s solicitors, and one other has contacted the former MMR solicitors (who are now Messrs Irwin Mitchell), raising concerns that some of the documents which the Legal Services Commission had provided to the GMC were privileged documents, in other words the subject of litigation privilege in the MMR proceedings. We responded at once to those parents, and indeed since to Irwin Mitchell, telling them that we were going to use the documents unless we were restrained by a court order from doing so, because we have always taken the view that the documents were admissible in these proceedings and that they had been provided to us very properly by another statutory body in the proper exercise of that statutory body’s powers. It has now been confirmed – and this is what we were waiting to hear this morning – by Irwin Mitchell that they do not propose to take any steps to make an application to the High Court to try and prevent the GMC from using that material.

I should say, in case you are wondering why it has all been left until today, it is an issue that was raised and ventilated between the General Medical Council and Irwin Mitchell a year ago in June 2006. Irwin Mitchell, and this is not a criticism of them, this is just a statement of fact, have had the opportunity to apply for a court order, they have not done so, and the recent concerns which were expressed were utterly unpredictable as far as the GMC were concerned, but in fact, now we have discussed with them, Irwin Mitchell’s position remains wholly unchanged.

So I will be opening the case and telling you about those documents.

THE CHAIRMAN: Can I first of all thank you on behalf of this Panel for updating us with the situation, and I am very grateful to you.

MS SMITH: Thank you, sir.

THE CHAIRMAN: So the ball is now in your court and you can open the case.

MS SMITH: Thank you, sir, and this is the main case.

Sir, as you know these three doctors are charged with serious professional misconduct.
Before I begin on the substantive part of the case, there are a number of important issues and principles which I want to underline at this stage. The first is it is a case, as you will be aware, that is being heard under the old rules, because it was referred for adjudication prior to November 1 2004, and therefore at this stage you are determining the facts. When you are hearing those facts, which the GMC contend amount to the charge of serious professional misconduct, you should have always in the forefront of your mind some basic principles.
I know you are aware of them and I am sure that the Legal Assessor will in due course also be formulating them for you, but they are these: first of all, the GMC are prosecuting this case, it is therefore up to them to prove the facts to you. The defence do not have to prove anything. The standard of proof is that you must be satisfied beyond a reasonable doubt, that is so that you are sure, and if you have a reasonable doubt, then it should be resolved in favour of the doctor.

It is no secret that the background to this case has already attracted an enormous amount of controversy and media comment, and it may be that there will be more to come. I know that you are aware, but I underline, that all of it is utterly irrelevant to the task that you have to perform. You should put it all out of your minds and consider the case only on the basis of the charges which have been brought and the evidence that you hear in this room over the ensuing hearing.

Now, as you know, the other important matter is there are three doctors in this case. They played different roles. During the course of my opening I am going to try to identify to you in broad terms the role that was played by each, but when considering the evidence you should consider it against each doctor separately, and you should remember that evidence against one is not evidence against the others.

So, first of all, I am going to just spend a little time on what the case is about overall. It sounds complex, inevitably, when the charges are read, given the number of topics that are involved and the number of individual children who were investigated and about whom you have heard different heads of charge, but it boils down to what we say are simple allegations of misconduct in relation to what we say was a research project, the subject of which was the investigation of a postulated new syndrome comprising gastrointestinal symptoms and behavioural disorder with the measles and measles/rubella vaccines.

There are very clear guidelines that require doctors to apply to ethics committees for permission to do research on their patients and to give an honest and accurate account and information to the ethics committee and to abide by the requirements of the committee when they are carrying out that research. There are particular requirements, as you might expect, relating to research on young children, because of their vulnerability. Our case quite simply is that these three doctors did not comply with those guidelines, and, as a result of that, very vulnerable children were subjected to inappropriate and invasive treatment.

Equally, there are another set of rules. The publication of research is underpinned by requirements that doctors reporting research projects are accurate, honest and responsible in the manner of their reporting. Our case is that with regard to Dr Wakefield and
Professor Walker-Smith they did not comply with those requirements when they were writing up their project for publication in The Lancet medical journal, and, as a result of that, they were in breach of the trust that both the scientific community and the public at large place in the integrity of medical practitioners.

Furthermore, there are yet more rules. There are requirements in relation to the declaration of potential conflicts of interest about which the scientific community and the public are entitled to know in order to make their own judgements about the significance of a research project, and our case is that, with regard to Dr Wakefield, he failed to comply with those requirements in failing to disclose both his deep involvement with the MMR litigation and his receipt of Legal Aid Board money to fund his research, and by that failure he deprived his readers of information that they should have had.

So it is a case about the breach of some of the most fundamental rules in medicine, essentially focused on misconduct in the carrying out of the research on the children by the three responsible consultants in charge of the research project, and the manner in which two of those doctors reported the project which was subsequently printed in The Lancet medical journal.

You will be aware, I know, that the statutory remit of the GMC is to investigate serious professional misconduct and it is about protecting patients and the public and upholding high standards of probity and integrity in the medical profession. It is not about stifling scientific freedom to publish properly conducted research, but the operative words that you should bear in mind when you are hearing this case are the words “properly conducted”. This Panel hearing is even less an appropriate forum for the determination of scientific disputes or debating scientific theories. This case is concerned with events which took place nearly ten years ago. Much has been said and written on the subject of MMR in that time. We are not concerned with that. We are concerned with the conduct of the research project and not with the ensuing controversy over the safety of MMR. So we emphasise at this stage that these are professional misconduct hearings. They are not some sort of broad-ranging public inquiry.

Now, I am going to, at the risk of tedium, run through the charges quickly in summary. You have heard them read out, necessarily over rather a long period of time, and of course there is always a danger when you hear things read out over a long period of time of forgetting, by the time you get to the end, what the beginning was, and failing to be able to see the wood for the trees. So I am going to concentrate on the wood, and, as I say, just summarise the charges that you have heard.

With regard to Dr Wakefield, they are that he conducted a research project into a possible causal link between MMR vaccine and bowel and behavioural disorders involving highly invasive tests on eleven children. He did not have approval from the ethics committee to do so because the children did not qualify for the study in the terms which had been approved, and the ethics committee did not approve the carrying out of the investigations, because they were told that those investigations were clinically indicated. The project involved carrying out lumbar punctures without any specialist assessment, either neurological or psychiatric, prior to doing so, to ensure either that the children qualified for the research criteria or that they were clinically indicated. He contravened the conditions imposed by the ethics committee with respect to the research project he undertook, that he involved himself in the clinical care of some of these children although he had no paediatric qualifications, nor clinical duties under the terms of his employment, and, in particular, with regard to one child he was involved in his treatment with an experimental substance prior to carrying out investigations with regard to the safety of that substance.

The Legal Aid Board were funding litigation in relation to alleged damage caused by the MMR vaccine, and pursuant to that litigation the charge is that Dr Wakefield obtained funding from the Legal Aid Board for the research project, and he is charged with failing to disclose to the ethics committee this source of funding and his involvement in the MMR litigation, both of which were interests which should have been disclosed as potential conflicts of interest.

Connected to this charge you have heard read out a further charge that Dr Wakefield was dishonest in his use of Legal Aid Board funds he had been granted.

With regard to the remainder of the charges, he submitted the results of his research for publication in The Lancet journal, wrongly stating that he had ethics committee approval for the investigations he described, without declaring disclosable interests which could have given rise to a perception of a conflict of interests, namely his involvement in the MMR litigation, his receipt of Legal Aid Board money, and his involvement in the patenting of his invention of a substance to be used both as a therapeutic measure and as a single vaccine for the elimination of the measles virus. Also in relation to the publication in The Lancet journal, he included in that article dishonest descriptions of the nature of the research project, the way in which the children who were the subject of the research had become involved, and he did that in circumstances when he knew that if the paper was accepted for publication it would have major implications for the health of the children in this country.

Subsequently, at a scientific meeting convened by the Medical Research Council to examine the evidence relating to measles, measles vaccine and chronic intestinal infection, when he was expressly asked about the issue of bias in generating the series of children written up in The Lancet journal, he gave a dishonest description of how the children came to be investigated.

Last of all, that he obtained blood samples from children in wholly inappropriate circumstances, that is in the context of a children’s birthday party, and that he subsequently recounted that incident in humorous terms in a lecture, thereby abusing his position of trust, we say, as a doctor, and bringing the medical profession into disrepute.

So those in encapsulated form are the charges that he faces.

Turning to Professor Walker-Smith, the charges are that he conducted a research project involving highly invasive tests on children when he did not have approval from the ethics committee to do so, because the children did not qualify for the study, and the ethics committee did not approve the carrying out of the investigations because they were told that those investigations were clinically indicated.

The project involved the carrying out of lumbar punctures, again without any specialist assessment, either neurological or psychiatric, prior to doing so, to ensure either that the children qualified for the research criteria or that those tests were clinically indicated, and also involved the authorisation by Professor Walker-Smith of colonoscopies for purportedly clinical reasons. The vast majority of those research tests, we say, were contrary to the clinical interests of the children on whom they were performed.

Secondly, he contravened the conditions imposed by the ethics committee with respect to the research project he undertook. In respect of one child he was involved in his treatment with an experimental substance prior to carrying out investigations with regard to its safety; that he submitted the results of his research for publication in The Lancet journal, wrongly stating that he had ethics committee approval for the investigations that he described, and including dishonest descriptions of the nature of the research project and the way in which the children who were the subject of the research had become involved in it, in circumstances again where he knew that that paper, if accepted for publication, would have major implications for the health of the children in this country.

Subsequently, in answer to queries made by the editor of The Lancet journal as to the circumstances in which the children had come to be referred to him, the charge is that he expressly and dishonestly denied that any children had been invited to participate although, we say, two had been invited by him to do so. In relation to one child, who is not one of the children written up in The Lancet article, there is a charge that he undertook invasive investigations, again which were not clinically indicated, which were contrary to that child’s best interests, and were carried out in response to parental pressure for the purposes of the research that he and Dr Wakefield were undertaking.

Lastly with regard to Professor Murch, that he conducted a research project involving highly invasive tests on children when he did not have approval from the ethics committee to do so, and that in pursuance of that research project he carried out on some of the children colonoscopies which were not clinically indicated; that he contravened the conditions imposed by the ethics committee with respect to the research project he undertook, and that he submitted the results of his research to The Lancet journal for publication, wrongly stating that he had ethics committee approval for the investigations that he described.

So, as I say, those in summary are the charges that you have heard read out in very much more detail.

The first thing to talk to you about is the roles of these three doctors. Dr Wakefield, at the beginning of the time with which we are concerned in this case – that is in 1996 – was employed as a senior lecturer in the Department of Medicine and Histopathology at the
Royal Free Hospital school of medicine. He had trained as a surgeon in gastroenterology, and subsequently, as the appointment that I have just set out to you reflects, he pursued a career in research. It is relevant to the matters with which he is charged that he did not have paediatric qualifications, and he had not worked as a clinician, as opposed to a research doctor, for several years.

During the period with which we are concerned he was promoted, in May 1997, to reader in experiment gastroenterology, and again that is a research post in the school of medicine. In addition to that, as you will know is frequent when an NHS hospital trust has a school of medicine attached to it, he had an honorary clinical contract in the Royal Free NHS trust; that was in experimental gastroenterology. But there were express stipulations attached to that honorary contract making it clear that Dr Wakefield’s role was a research role, and he did not have clinical responsibility for patients.

Earlier on in his career, in the early 1990s, Dr Wakefield had undertaken research on the blood supply of the small intestine of patients with inflammatory bowel disease, in particular that form of inflammatory bowel disease known as Crohn’s disease. In particular, in simple terms, he had researched into the issue of whether damage to the cells lining the blood vessels of the gut could be caused by the measles virus. He had published that research in 1993 in the Journal of Medical Virology.

Subsequently he had gone on in his research, as research does, and that had led him to suggest that the measles vaccine, as opposed to the wild measles virus, was a causal factor in the development of Crohn’s disease. Ultimately his researches had led him to develop the hypothesis that underlines the background to the charges that are brought against these three doctors. That in brief terms was the hypothesis that there was a link between the gut disorders, the cause of which he attributed to the measles vaccine, and behavioural disorders on the autistic spectrum, in that by some method the bowel disorder led to malabsorption of vitamin B12, which damaged the brain. That is the hypothesis that was set out in the application he made to the ethics committee in considerable scientific detail, and we will be looking at that application shortly.

So far as the other two doctors are concerned, Professor Walker-Smith and Professor Murch, at the time with which we are concerned, were professor of paediatric gastroenterology and senior lecturer, respectively, primarily employed in their academic posts again by the
Royal Free Hospital school of medicine, but both with honorary clinical contracts with the Royal Free Hospital NHS trust. By contrast to Dr Wakefield, their honorary clinical contracts carried with them extensive clinical responsibilities.

With regard to the respective roles in the study with which we are concerned, all the children about whom you will be hearing were patients of Professor Walker-Smith. It is our case that they were referred to him, some were seen by him in out-patients, and all were admitted under our care. It is our case that he was ultimately clinically responsible for them.

Professor Murch’s role was more specific and, it is accepted by the GMC, more peripheral. Some of the children were referred to him by Professor Walker-Smith to undergo colonoscopy, a procedure which Professor Walker-Smith himself did not undertake.

In theory Dr Wakefield was the lead researcher. I say in theory because you will see when we come to consider the medical records that there was a close collaboration between Dr Wakefield and Professor Walker-Smith. It is not suggested that there is anything improper about that in itself, but we do say that it led to the blurring of the boundaries between research and clinical medicine, so that in practice Dr Wakefield became not only closely involved in the referral circumstances of these children, but in some cases very inappropriately involved in the clinical care of children when he was not, as I have said, paediatrically qualified, and the restrictions on his clinical practice reflected both that lack of qualification and also a broader prohibition on clinical as opposed to research work.

I am going to revert to this issue when I am considering the individual children, but at this juncture I quote one of the experts from whom you will be hearing, our psychiatric expert Professor Sir Michael Rutter: “The ambiguity concerning the respective roles of Dr Wakefield and Professor Walker-Smith pervades all documents, and I find myself unable to set out quite what was happening and quite who was taking which decisions”. But in any event the important aspect for the first matters which you will be considering is that all these three doctors were named as the responsible consultants on the application for ethical approval for the study undertaking. The implications of that role I am going to be reverting to shortly, because they underpin the beginning of the story that I am going to tell you.

From this stage onwards I am going to be inviting you to refer now and again to bundles of documents. I say with slight heart-sink, because I cannot see signs of them, that you should have available to you four separate bundles of documents which are labelled chronological documents, part 1, part 2 and part 3, and then the last one, part 4, contains ethics guidelines. It is that that I am going to be referring to first. I see you have them. If you could have your bundle 4 available I will take you to the relevant parts in a moment.

I want to tell you first of all about the ethics committee application for a study which became known as project 17296. The best place to start the story is in September 1996, when an application was submitted to the ethics committee at the Royal Free Hospital. Before I go into the details of this, can I say that I am very conscious that I am speaking to a committee with varying degrees of medical qualification. I hope you will all forgive me if I am saying things which are elementary to some of you but, as I say, this case has a complex background and it is important that everybody understands the background before we get into the detail of the facts.

The position is that patients who are referred to a clinician, who then undergo treatment or investigations which are clinically indicated by virtue of their symptoms and their history, and are thus part of the normal patient care which we all have when we go into hospital, do not require ethical approval. The reason for that is elementary. The fact that the treatment or investigation is part of the normal accepted care of a patient, with that particular condition and history, means that it is ethically justified.

In contrast to that, all medical research, that is investigations carried out to gain information in relation to an already formulated research hypothesis, has to be approved from a properly constituted NHS research ethics committee and that approval is fundamental to the performing of the research on the patient, to the funding issues associated with it and to the ultimate writing up of any results and their submission to a scientific journal.

The guidelines at the time, which are in the bundle 4 that I have asked you to get out, are helpful; they set out some helpful definitions. Sir, I am going to ask you to look at those first before we go on to the actual circumstances of this ethics committee application and the first is a general document which was produced in 1990 by the Royal College of Physicians entitled Research Involving Patients. The one thing I would say is that you should bear in mind that it deals with general definitions in respect of all patients and there are special considerations over and above those that apply in relation to children and which I will be looking at in a short while.

If you would go in bundle 4 to page 23, you will find those guidelines. As I say, these were published in 1990 and the definitions page is on page 29. Would you go straight to paragraph 2.2, “What constitutes research in patients?”

“2.2 When an activity is undertaken solely with the intention of benefiting
an individual patient, and where there is a reasonable chance of success, the activity may be considered to be part of ‘medical practice’. The progressive modification of methods of investigation and treatment in the light of experience is a normal feature of medical practice and is not to be considered as research.

2.3 In contrast, where an activity involving a patient is undertaken with the
prime purpose of testing a hypothesis and permitting conclusions to be drawn in the hope of contributing to general knowledge, this is ‘research’. The fact that some benefit, expected or unexpected, may result from the activity does not alter its status as research.

2.4 The distinction between ‘medical practice’ and ‘research’ is often less
clear than is suggested above because both are practised simultaneously. A doctor who makes careful records of the outcome of treatment, the effectiveness of a diagnostic investigation or the use of some resource in the course of his ordinary work may be considered to be engaging in quality control – now often referred to as ‘medical audit’ – rather than research. In general, however, where an effort is made to formalise the acquisition of information gained in the course of medical practice this may be considered to be at least a component of research. A retrospective review of case records is usually to be regarded as research, particularly where this is undertaken systematically according to a formal protocol or when an individual other than the person who constructed the records undertakes the analysis. Any activity which affects the patient in any way which is additional to ordinary medical practice is to be regarded as research.”

We then go on to a section of “Innovative treatment”,

“2.5 Sometimes special circumstances of an individual patient’s illness”

and I underline myself in parenthesis the word “individual”,

“lead a clinician to step outside what is accepted as normal medical practice. We distinguish between innovative treatment of this sort and research.

2.6 In innovative treatment, the sole motive for the action is to choose the best
possible course of action for the individual patient even though it be unconventional. It remains innovative treatment rather than research even if, as a byproduct, useful information is gained. Responsibility for employing innovative treatment remains that of the clinician who remains subject to the usual constraints which direct ordinary medical practice.

2.7 Where a clinician contemplates a marked digression from normal medical
practice in an individual case, with the prime purpose of acquisition of information for application in future patients, the activity clearly becomes research and must be subject to all the considerations of proper consent and scrutiny by Research Ethics Committees which are described in this report.

2.8 Innovative treatment may quite rapidly become part of medical practice
without being the subject of formal research, for example where a speculative new procedure is thought to be successful in a previously hopeless situation. Usually, however, when a doctor finds that a major innovation is being called into regular use and the procedure is not yet incorporated into medical practice generally, it will be expected that the innovation should become the subject of formal research without delay so that its true worth can be established.”

Would you turn on to page 36 where you will see the role played in the definitions of clinical and research medicine by the “Risk/benefit analysis”, and at that time a distinction between therapeutic and non-therapeutic research. Again, before I read this, I emphasise that it is general and, as you will see shortly, the analysis of risk benefit in children is very much stricter and the situation more complex because of the consent issues involved.

This is page 36 where you see it says, “Risk/benefit analysis” and at

“5.8 A key decision in the assessment of proposed research is whether the risk
or inconvenience caused to the patient is justifiable in relation to the value of the information sought. This process is sometimes referred to as risk/benefit analysis. We believe that it assists Committees to arrive at good decisions if they are provided with as precise an estimate as possible of both the risk and the benefits inherent in research.

5.9 The term ‘risk’ refers both to the probability of a harm resulting from
an activity and to its magnitude. For example, ‘low risk’ is taken to mean a low probability of serious harm or, alternatively, a higher probability of minor harm. Furthermore, ‘risk’ often stands for the combined probabilities and magnitudes of several potential harms.

5.10 In some procedures, studies or experiments, the risk is so small that it can
be ignored. We would equate this with the level of risk accepted in everyday life. Examples might be the measurement of height and weight, the collection of a urine sample or the giving of a single venous blood sample by an adult.”

The reason why “by an adult” is there is because, as you will be hearing shortly, the assessment of risk of taking a blood sample in respect of a child is different.

“In this report we refer to ‘less than minimal risk’ when discussing risk of this order.

5.11 The term ‘minimal risk’ is used to cover two types of situation. The first
is where the level of psychological or physical distress is negligible though there may be a small chance of a reaction which is in itself trivial, e.g. a mild headache or feeling of lethargy. The second is where there is a very remote chance of serious injury or death, comparable to the risk of flying as a passenger on a scheduled aircraft.

5.12 It should be noted that the research involving procedures which carry
a risk which is more than minimal will only be permissible where it is explicitly justified. We discuss the question of benefit in research and ‘therapeutic research’ below.”

Then you will see the heading “Benefit”,

“5.13 A benefit refers to any sort of favourable outcome of the research and is
the opposite of a harm. Benefit is often concentrated in the value to society as a whole of the information resulting from the research but it may be expressed as an advantage to the individual patient. The outcome of research is never certain at the outset and it is thus proper to consider the probability of possible benefit as well as its magnitude. In practice, ‘benefit’ often stands for the combined probabilities and magnitudes of several possible favourable outcomes.

5.14 Studies are sometimes categorised as ‘therapeutic research’ or ‘non-
therapeutic research’ according to whether or not it is considered that the individual patient might obtain some benefit from participation (other than the benefit of the addition to general knowledge which would be to the advantage of all patients in the long run). An example of therapeutic research is a study to determine whether a new drug does or does not benefit patients with asthma or heart attacks. The patient might benefit from participation or he might not. The outcome cannot be guaranteed: if it could, this would not be research. An example of non-therapeutic research might be an investigation into the effect of anaesthesia of different types on the function of the liver. Here, although a treatment is under study, the individual patient does not stand to benefit from participation.

5.15 We recognise the difference between therapeutic and non-therapeutic
research in the context of risk/benefit analysis and an individual patient’s choice whether or not to participate in the research. In practice, however, the difference is often not clear cut. For example in research involving the comparison of two treatments in a group of patients, it is not known in advance whether one will turn out to be superior to the other and even then it is often just as likely that the individual patient would receive the treatment which emerged as inferior”

and they go on to deal with comparative studies.

“Two points need to be made in the present context. First, Research Ethics Committees should expect the same standards of risk limitation in therapeutic research as apply in non-therapeutic research. Secondly, the requirement to inform the patient about what is proposed and to seek his consent is the same in therapeutic research as in any other form of research involving patients.”

Those definitions were set out in another document which is a document expressly provided by the Royal College of Physicians for the guidance of ethics committees considering research applications. That was again in 1990 and, if you turn on to page 89 – and I am taking you to this document because it sets out in rather simpler terms what I have just referred you to and it is the document that you will be hearing was used by the Royal Free Ethics Committee to inform them of the matters that they had to consider at the relevant time – you will see that it is in similar terms,

“3.1 The definition of research continues to present difficulties, particularly with regard to the distinction between medical practice and medical research. The distinction derives from the intent. In medical practice the sole intention is to benefit the individual patient consulting the clinician, not to gain knowledge of general benefit, though such knowledge may incidentally emerge from the clinical experience gained. In medical research the primary intention is to advance knowledge so that patients in general may benefit; the individual patient may or may not benefit directly.”

Then it too refers to “Innovative therapy”,

“3.2 Thus, when a clinician departs in a significant way from standard or accepted practice entirely for the benefit of a particular individual patient, and with consent, the innovation need not constitute research, though it may be described as an experiment in the sense that it is novel and unvalidated”

and, if you look down at the footnote at the end,

“In this context, an ‘experiment’ is a procedure adopted on the chances of its succeeding. ‘Research’ is a systematic investigation to establish facts or principles and generalisable knowledge”.

Going on with the paragraph,

“But extension of such an experiment into wider use or general application should, prima facie, be regarded as research. Clinicians should be prepared to justify their innovative therapy both ethically and scientifically.

3.3 Any investigation in humans designed to develop or contribute to generalisable knowledge raises ethical issues, although these may be small. Because such studies may involve subordination of at least the immediate interest of the individual participant to the objective of the advancement of knowledge, they should be subject to ethical review. The College considers that this applies to non-medical as well as medical research”,

and then the classes,

“3.4 There are two major classes of research:

i which involves making observations without any direct interference with the subject (non-intrusive or non-invasive), such as research involving the use of personal medical records.”

So, even in a case where a patient cannot be said to be directly affected, if research is being done on that patient’s records, then consent has to be obtained from the ethics committee. Secondly, and this is the sort of research with which we are concerned,

“ii that which involves interference with the subject” and that is of any kind “(psychological intrusion, including intrusion on privacy, or physical invasion). Such interference, psychological or physical, raises ethical issues which may be sometimes large or very small; both should be subject to ethical review.”

Then at the end,

“3.5 Research may also be classed as: (a) research which may benefit the individual participant (therapeutic research), and (b) research that will not or is unlikely to benefit the individual participant (non-therapeutic research). Whilst Ethics Committees will be concerned with both, they will naturally give particularly close attention to non-therapeutic research.”

So that is the general position relating to all patients upon whom either clinical care or research is exercised.

Children, as I have said, fall into a special sub-category. They do so for two reasons: One is because they are sometimes too young to consent for themselves. In normal clinical medicine, of course, their parent consents for them. At this time concerns were expressed as to whether, if the research was completely non-therapeutic (i.e. did not benefit the individual child), in law a parent could consent, because arguably non-therapeutic research could not ever be said to be in that child’s best interests. That was an issue that was alive at the time. The second reason is that children are vulnerable. They can easily be upset – this is a statement of the obvious – by things an adult would not be, and therefore, when it comes to applying considerations of definitions of risk, particular care has to be exercised.

The guidance for the ethics committee in those circumstances is at page 111 of your bundle 4. This is “Special classes of research” and “Research involving children”.

“It may well be appropriate to give medical treatment to unwilling children if the parent or guardian consents”,

that is normal medical treatment,

“but the position would not necessarily be the same for research.”

It then sets out the problem that I have already said to you:

“In legal terms … a person is of full age, and accordingly recognised as an adult, from the eighteenth birthday. Under that age, the capacity to consent to research probably depends on the degree of understanding on the part of the individual involved”,

and it quotes the relevant statutes.

“… the consent of a person between 16 and 18 years of age to surgical, medical or dental treatment shall be as effective as it would be if he or she were of full age, so that parental consent is not then necessary. ‘Treatment’ includes diagnostic and ancillary procedures, including the administration of an anaesthetic, and thus probably includes therapeutic research”,

i.e. research which has some benefit for the individual patient,

“but it would not be prudent to rely solely on the subject’s consent to non-therapeutic research, and below the age of 18 parental consent should always be sought in addition to that of the subject.”

If you go into the next paragraph, the fourth sentence down:

“Non-therapeutic research in children should not carry greater than minimal risk … except in the rarest circumstances”,

and it then says, I note in passing, for reasons which I will revert to later,

“There must be no financial or other inducement to parent, guardian or child.”

Then it sets out the pragmatics at paragraph 13.4:

“To the extent that it is feasible, which will vary with age, the willing co-operation [agreement] of the child should be sought, after [he or she] has been frankly informed of any possible discomfort or inconvenience. Older children may be assumed to be capable of giving informed consent preferably also with the consent of the parent or other legal guardian. ‘Children should in no circumstances be the subjects of research holding no potential benefit for them unless with the objective of elucidating physiological or pathological conditions peculiar to infancy and childhood, or of providing potential benefit to the family, and where it involves no more than minimal risk’.”

It also goes on:

“Where a child obviously objects to such research, ie he or she withholds assent or agreement, or resists, this must be respected. Research should always be planned to ensure that there is negligible distress or harm to the child, eg a venepuncture might be accepted whereas a lumbar puncture would not be in this type of work.”

That guidance set out in the Royal College of Physicians’ Guidance for Hospital Ethics Committees derives from the last guidance which I am going to ask you to look at, which is the British Paediatric Association Guidelines for the Ethical Conduct of Research on Children in August 1992. That is at page 176. That gets you to the title page of that document, and if you turn on to page 182 you will see on that page the beginning of the guide.

“The guidelines are based on six principles.

1. Research involving children is important for the benefit of all children and should be supported, encouraged and conducted in an ethical manner.

2. Children are not small adults; they have an additional, unique set of interests.

3. Research should only be done on children if comparable research on adults could not answer the same question.

4. A research procedure which is not intended directly to benefit the child subject is not necessarily either unethical or illegal”,

So that would be one involving non-therapeutic research.

“5. All proposals involving medical research on children should be submitted to the local research ethics committee.

6. Legally valid consent should be obtained from the child, parent or guardian as appropriate …”.

Then if you go on to page 184:

“Children are unique as a research group for many reasons. They are the only people, in British law, on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened, and unable to express their needs or defend their interests. Potentially with many decades ahead of them, they are likely to experience in their development and education, the most lasting benefits or harms from research.”

Then setting out the assessment of risk in respect of children, page 188. As I say, remember that this is children particularly:

“Risks may be estimated as minimal, low or high

Minimal (the least possible) risk describes procedures such as questioning, observing and measuring children, provided that the procedures are carried out in a sensitive way, and that consent has been given. Procedures with minimal risk include collecting a single urine sample (but not by aspiration), or using blood”,

and you will note that is using it, not taking it,

“from a sample that has been taken as part of treatment”,

i.e. using some blood for research purposes when blood has had to be taken as part of normal patient care. So that is the minimal risk.

“Low risk describes procedures that cause brief pain or tenderness, and small bruises or scars. Many children fear needles and for them low rather than minimal risks are often incurred by injections and venepuncture.

High risk procedures such as lung or liver biopsy, arterial puncture, and cardiac catheterisation are not justified for research purposes alone. They should be carried out only when research is combined with diagnosis or treatment intended to benefit the child concerned.

It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them, or only a slight or very uncertain one. Higher risks in research and novel treatments are accepted when children are enduring very harmful disease. Illness and anxiety alone may put pressure on families to assent to heroic experimental procedures. In cases of severe or chronic disease, therefore, the harms to the child of the condition, of the medical treatment, and of the stress through taking part in research need to be assessed, so that all avoidable distress may be relieved.

Despite careful selection, children in clinical trials have social and emotional problems which are mainly unpredictable. Provision for the necessary continuing emotional support should be build into research design.”

So there you see, as I say, the particular consideration that is given to protect vulnerable children in the research setting.

The ethics committee itself generally, first of all, and then in respect of the Royal Free. The way in which ethics committees are run is governed by health service guidelines which are known as the Red Book. NHS hospitals in 1996 and to this day have local research ethics committees, known as LRECs. If any doctor wants to carry out a research project he has to seek ethical approval from the committee and if the research project involves either NHS patients or the use of the records of NHS patients, and no NHS body can agree to or countenance a research proposal without the approval of the committee.

The LRECs are established by the district health authority in which the hospital resides, but they are independent advisory bodies. They have something between eight to 12 members on the committee and those members include hospital medical staff, nursing staff, GPs, and lay members, and the rules at that time were that they had to have at least one who was totally unconnected with healthcare. There is never any guarantee as to the breadth or the type of medical expertise of those members who are medically qualified.

If we look at the Red Book we can see the nature of the information that the committee requires in considering a research project, and that is again in bundle 4, page 138.


3.1 To arrive at its decision on whether a research proposal is acceptable on ethical grounds the LREC will need to consider a great deal of information. The proposals which reach the LREC should be of a standard to enable the committee to discharge its functions without having to correct basic errors. Researchers and their supervisors are not absolved of responsibility for their work by the existence of the LREC.

3.2 The points to consider in any particular proposal will depend on the nature of the study … As a minimum, and there will be other points to consider, the LREC will need to know:

i. Has the scientific merit of the proposal been properly assessed.
ii. How will the health of the research subjects be affected.
iii. Are there possible hazards and, if so, adequate facilities to deal with them.
iv. What degree of discomfort or distress is foreseen.
v. Is the investigation adequately supervised and is the supervisor responsible for the project adequately qualified and experienced.
vi. What monetary or other inducements are being offered to the NHS body, doctors, researchers, subjects or anyone else involved.
vii. Are there proper procedures for obtaining consent from the subjects or where necessary their parents or guardians.
viii. Has an appropriate information sheet for the subjects been prepared.”

Then it goes on to types of research:

“3.3 LRECs should consider the ethical implications of all research proposals which involve human subjects including for example questionnaires. All proposals will belong to one of two categories, therapeutic or non-therapeutic research. Therapeutic research carries the prospect of direct benefit to the research subject. Non-therapeutic research, whilst designed to advance scientific knowledge and therefore be of collective benefit, is not expected to give a direct benefit to the research subject. Non-therapeutic research may involve ‘healthy’ as well as ‘patient volunteers.

3.4 Where people volunteer to take part in non-therapeutic research they should know that they cannot expect to derive any direct benefit from that participation. The LREC will therefore want to be satisfied that the risk to which they are submitting themselves can be justified by the expected collective benefit.”

If you go on to the bottom of that page there is “Consent”:

“3.7 The procedure for obtaining consent will vary according to the nature of each research proposal. The LREC will want to be satisfied on the level and amount of information to be given to a prospective subject. Some methods of study such as randomised control trials”,

and that does not apply in the circumstances that you are looking at,

“need to be explained to subjects with particular care … The LREC will want to look at such proposals particularly carefully. They will also want to check that all subjects are told”,

and this applies to all research,

“that they are free to withdraw without explanation or hindrance at any stage of the procedure and with no detriment to their treatment”,

i.e. to their normal clinical care.

“An information sheet, to be kept by the subject, should be required in the majority of cases.

3.8 Written consent should be required for all research (except where the most trivial of procedures is concerned). For therapeutic research consent should be recorded in the patient’s medical records.”

If you then go on again to page 141:


3.15 The LREC should examine any financial aspect of a research proposal which may influence the patient’s judgement in consenting, or the researcher’s judgement in his/her treatment of subjects, in such a way as to call the ethics of the research into question. Clearly any payments to subject or researcher must be considered, but it is also possible that benefits to an institution or department may raise similar ethical questions”,

and then there is a reference to payments across multi-site research, which is not relevant.

“3.16 Payment in cash or kind to volunteers should only be for expense, time, and inconvenience reasonably incurred. It should not be at a level of inducement which would encourage people to take part in studies against their better judgement, or which would encourage them to take part in multiple studies.”

So that is the basic situation as far as financial considerations. Then if you turn on to page 143 you see the Special Considerations for Research on Children. It sets out again what we are now seeing for the third time:

“4.1 Research proposals should only involve children where it is absolutely essential to do so and the information required cannot be obtained using adult subjects.”

There is then reference to the seeking of consent.

“When seeking consent to examination or treatment (which may include research which is intended to benefit the patient, ie therapeutic research)”.

It then deals with older young people should be able to give their consent independently; children under sixteen may be able to give full consent providing they have sufficient understanding; even for therapeutic research purposes it is unacceptable not to have the consent of the parent.

“Where the proposal is for non-therapeutic research, all of the above applies but in addition”,

and we say this is important and you should bear it in mind when you hear the facts of the case,

“the child must be subject to no more than minimal risk as a result of his/her participation.

The LREC should note that those acting for the child can only legally give their consent provided that the intervention is for the benefit of the child. If they are responsible for allowing the child to be subjected to any risk (other than one so insignificant as to be negligible) which is not for the benefit of that child, it could be said they were acting illegally. It should also be noted that the giving of consent by a parent ….. cannot override the refusal of consent by a child who is competent to make that decision.”

So that is the legal position which I briefly referred to earlier. All those principles and guidelines underpin the proper practice of medicine and medical research. It should not need to be said, but perhaps in this case it may do, that those rules apply to all doctors, however senior and however experienced within their specialism, and to all hospitals, whether they are local or tertiary referral centres, and they apply to all research, whether that research is good, bad or indifferent in quality, and they apply to all scientific theories researched by doctors regardless of the value of the theory should it ultimately be proved.

Now, turning to the particular circumstances of the Royal Free Ethics Committee, in 1996 (the period with which you are concerned) it conformed to the set up as I have indicated to us is set out in the Red Book. The chairman was Dr Pegg, who was a consultant anaesthetist at the hospital, as it happens, but, as I say, the specialism of the doctor involved is not a relevant issue. They can be any specialism and they all have to consider all research projects. There were two lay members, a pharmacist, the hospital chaplain, the nursing director and seven medically qualified members of varying specialisms, including general practice. The ethics committee application with which we are concerned was in a standard form used by the Committee, and, once submitted, it was processed in the normal way, that is it was sent to individual members of the Committee who could raise questions prior to a discussion at a Committee meeting. If they did raise questions, those questions would be addressed by the chairman and by the researchers involved. A meeting would take place. After that meeting the application could be rejected or accepted, or most commonly accepted subject to changes requested by the Committee.

I am now going to look at the application for project 17296, which is the project with which you are concerned. You can put away your bundle 4 for now and extract instead, if you would, bundle 1 of your chronological bundles. I should tell you, because you may be doing some reading for yourselves later, that these three bundles, which are all labelled chronological bundles, have every document that the prosecution propose to rely on in this case in chronological order.

If you would turn in that bundle to page 200, that is the standard application form which was filled in in respect of this project, and you will see first of all at the top of it “Responsible Consultant(s)” and the names of the three doctors and the departments from which they came. By putting their names to that title “Responsible Consultant”, it is our case that these three doctors identified themselves as being in charge of the project that is described in this document and responsible for all the information in respect of queries by the Committee.

Ensuing correspondence in relation to this project was conducted, as you will hear, and I will outline to you the different roles, but it was conducted with both Dr Wakefield as the principal researcher and with Professor Walker-Smith as the principal clinician. It is accepted that Professor Murch was not directly involved in the communications with the Ethics Committee, and thus to that extent he was peripheral to the decisions that were made, but nonetheless he was copied in to central communications, which I will identify to you, and it is our case that he had a responsibility arising from his role as responsible consultant.

If you go on down the page, you will see that the research workers involved are then referred to, and then at the bottom the collaborating departments, and they are set out as Dr Harvey in the Department of Neurology and Dr Berelowitz in the Department of Psychiatry.

If you go on to the next page 201, top of the page, you will see that the application form requires the title of the project, and the title is given as “A new paediatric syndrome: enteritis and disintegrative disorder following measles/rubella vaccination”. Just looking at that title, “enteritis” is a broad term covering inflammation of the stomach and the intestinal lining. Disintegrative disorder is a very rare disorder; normally developing children suddenly over a period of months show behavioural changes and developmental regression, usually after the age of two, often with loss of coordination and bowel or bladder function. It differs from autism in the loss of motor and self-help skills and in the lack of the complex stereotype behaviour patterns which characterise autism. It has a very poor prognosis, disintegrative disorder, with an overall picture that looks like autism, with a severe mental handicap. Sometimes it plateaus. Sometimes deterioration continues with worse motor dysfunction and seizures and neurological signs.

So that was the condition that they were applying to the Ethics Committee to look at in what they describe as a new syndrome.

It goes on “following measles/rubella vaccination”. Now, I am going to touch on this now and I am going to be referring to it in rather more detail later. Prior to 1988 children in the UK had the single measles vaccine. In 1988 the combined triple vaccine for measles, mumps and rubella (MMR) was introduced. By 1992 it was apparent that young children had good immunity from measles because a high proportion had had MMR (measles, mumps and rubella) vaccine. However, there was an older group of children from the ages of five to fifteen who were very susceptible to catching measles because this was the group who had not had the MMR and had also not been vaccinated in such high numbers with the single measles vaccine, and it was thought that there was a serious risk of an epidemic in relation to those school age five to fifteen year old children. It was decided that something should be done to avoid this. There was not enough MMR to vaccinate them. The reason for that was that the MMR vaccine had been produced by a number of companies containing a particular strain of the mumps vaccine which had had to be withdrawn because of safety concerns. That restricted the supply of MMR, and therefore in 1994 school age children were given the measles/rubella vaccine, in other words MR. That was a nationwide campaign known as Operation Safeguard, and it was implemented to vaccinate in schools all children aged five to fifteen with MR. It took place over six weeks and the vaccination programme then reverted solely to MMR. So the point of it for present purposes is that this was referring to the MR vaccine, the vaccine which was given, as I say, to older children over a short period of time.

If you then go on to the objective, that sets out the scientific hypothesis which it was intended to test by the study. Those are not my words, they are the words of the application to the Ethics Committee:

“We will test the hypothesis that in genetically susceptible children, measles vaccination is associated with persistent enteric (and possibly [central nervous system]) infection, enteritis and malabsorption of vitamin B12. In the rapidly myelinating brain, which is particularly susceptible to vitamin B12 deficiency, the latter predisposes to encephalopathy.”

THE CHAIRMAN: Is this on page 202?

MS SMITH: 201, sir, at the top of the page, under the heading, paragraph 3, “Objective”. Encephalopathy of course is a disease affecting the functioning of the brain, and the postulation that was set out there was that the encephalopathy could in the future be treated by replacing the B12, which was deficient because of malabsorption. That was the theory. So that was what the proposed project was said to be basically about. You will note that the hypothesis was concerned with a postulated new syndrome which was explicitly associated with vaccination. The study was exclusively concerned with vaccinated children.

If you go on down that page, still on page 1, at paragraph 4 you will see “Design of the study”:

“Children, referred either by their GP, or via the vitamin B12 unit at the Chelsea and Westminster Hospital, who manifest disintegrative disorder and symptoms and signs of intestinal disease [were to] be admitted ….. under the care of
Professor Walker-Smith [for the period of a week].”

The consent of their parents was to be obtained, and they were to undergo a series of investigations. I will summarise those, although I hope fairly, as a structured assessment for disintegrative disorder, the condition that I described to you; routine (and I say that is a word that is significant for reasons I will revert to) ileocolonoscopy and upper gastrointestinal endoscopy. That is a procedure for the examination of the large intestine and also the ileum, which is the lower three parts of the small intestine, by endoscope, i.e. a tube with a light and a camera, during the course of which biopsies would be taken. They were then to undergo a barium meal and follow-through. That is a series of X-rays of the oesophagus, the stomach and the duodenum during and after the treatment of a particular barium solution. They were to undergo MRIs, that is magnetic resonance imaging; EEGs (electroencephalograms), which is a method of measuring brainwaves, and other electro physiology tests. They would have lumbar punctures. That is a procedure whereby spinal fluid is removed from the spinal canal for the purposes of diagnostic testing. A special needle is placed into the lower back at the level of the lumbar vertebra into the spinal canal, and the fluid is removed and then sent to the laboratory for testing. They were to have (and these are the last two bullet points) a series of blood and urine samples taken for testing.

You will see at the end, at the last bullet point in paragraph 4, there is a reference to a full protocol being attached. I will go to that in a few minutes. It sets out the detailed nature of the studies envisaged, and it may be important to note they include virological studies on the tissue removed at biopsy during the colonoscopies in order to carry out testing for the presence of measles virus.

So that is what the children were to undergo during a week’s stay in hospital. Of course, of particular significance to the matters that you have to consider, and to the charges, because of their invasive nature and the associated risks attached to them, colonoscopies and lumbar punctures.

Would you excuse me for a moment, sir.

THE CHAIRMAN: Ms Smith, while you have been interrupted already, can I also just make a suggestion that wherever you do find a natural place, if you would like to give us a short break, but wherever you find it convenient for yourself.

MS SMITH: I can only hope that this is not the moment at which everyone is beginning to feel bored, because that indeed is what Mr Thomas was pointing out to me, that I had reached a natural break, so perhaps this is the moment, sir.

THE CHAIRMAN: Thank you very much indeed. I think we will have a fifteen minute adjournment and we will resume at quarter-to four.

(The Panel adjourned for a short time)


MS SMITH: Thank you, sir. If we can go on with the ethics committee application form, we are on page 201, and I had just gone through with you the tests that the children were to undergo during their week’s stay in hospital, and I was going to turn on to paragraph 5 right at the bottom of page 201. “Scientific Background”, is the heading. There is a request:

“Please give a brief review of the relevant literature”

and there are various questions asked, which again are part of the standard form as to the scientific background of the study.

If you turn on to page 202 – I am not going to read the whole of this, you will be pleased to hear, but I am going to refer you to parts of it – you will see that some of it involves very technical explanations of the investigations that are to be undertaken. You see “Introduction” at the top:

“There are indications of the emergence of a new syndrome comprising disintegrative disorder and a possible enteritis associated with vitamin B12 deficiency. The syndrome has been linked – anecdotally but consistently – with either measles or measles/rubella vaccination. It appears to occur in previously well and developmentally normal children following exposure to these vaccines.”

Then it sets out in rather more detail the description of disintegrative disorder.

“Disintegrative disorder (or Heller’s disease) occurs when normally developing children suddenly, or over a period of several months, show marked behaviour changes and developmental regression after age 2, often in association with some loss of co-ordination and bowel or bladder function” –

and then it says:

“(Reviewed by Rutter et al …)” –

and I will return to that in a moment.

“Behavioural changes include social withdrawal, reduced response to sounds, complete loss of communication, unusual sensory behaviours and development of simple rituals and hand and finger stereotypes, much like those of autistic children. However, disintegrative disorder differs from autism in the loss of motor and self-help skills and usually, too, in the lack of more complex stereotype behavioural patterns (although simple motor stereotypes may occur). This rare disorder can sometimes be linked to measles encephalitis, cerebral lipoidoses, leukodystrophies or other neurological conditions but in most cases no clear cause is ever identified. Even in cases where progressive neurological disorder is eventually identified, initial medical tests are often negative and sometimes diagnoses of hysterical reactions are considered. Thus, it is important to repeat medical investigations if a child’s conditions does not improve.

Two different courses are typical of children with regressions occurring after the first few years. Most common are regressions that extend over several months and then plateau, resulting in a developmental and behavioural pattern that looks much like autism with severe mental handicap. In some cases, deterioration continues, with increased motor dysfunction, development of seizures and localized neurological signs.

Another disorder that overlaps in symptomatology but that does not have quite so poor a prognosis is Landau-Kleffner syndrome or acquired aphasia with epilepsy. Children with this disorder lose receptive and expressive language, usually over a period of months, typically in conjunction with the development of seizures or transient EEG abnormalities. Some social withdrawal and unusual behaviours may occur, but usually relatively normal social relationships are maintained with parents and others known to the child. Non-verbal cognitive functioning remains intact. In most cases, the outlook for these children is better than for children with disintegrative psychoses or autism, and sometimes language is eventually regained.”

Thus we say that is a lengthy description of disintegrative disorder as defined by Rutter et al, with a very clear differentiation spelled out in it between that disorder and autism. The reference to Rutter is in fact to Professor Sir Michael Rutter, who will be the GMC psychiatric expert in this case and who will indeed support the distinctions that were drawn by the doctors between disintegrative disorder and autism.

You will then see under that there is a heading “Complement, measles and disintegrative disorder:” I am going to deal with this very briefly. Complement is the substance in the blood which usually acts with antibodies to produce some sort of biological effect. There is a very technical explanation, as you will see, but if you go straight on in that section you will see the last sentence, on page 203, just above the heading “Enteritis”:

“The study will seek to identify and characterise inherited abnormalities of complement (C4B) genotype, based upon the hypothesis that abnormal complement regulation is central to the susceptibility and subsequent expression of disease.”

So there again a clear indication, we say, of a research study.

Then there is the heading “Enteritis:” and an analysis of what the research seeks to do, and following on from it lengthy descriptions of the B12 studies that were envisaged. Then you go on to page 204 and you see “Working hypotheses”:

“The possible link between an environment insult (measles/rubella vaccine) in a previously healthy child, who may be genetically susceptible to responding inappropriately to the viruses via abnormal complement regulation, and the subsequent development of enteritis, Cbl-deficiency and disintegrative disorder, permits several working hypotheses to be proposed.”

It then sets out in diagrammatic form the two theories as to how measles vaccination in a well genetically susceptible child could lead to disintegrative disorder. Again, as I say, these are two theories, they are plainly research motivated. The first is what is called – and you will see number 1) at the top of page 205 – the enteritis hypothesis, in which measles vaccination may have led to an enteritis that may cause malabsorption, which then has an effect on the brain, leading to a disintegrative disorder – and that is described as the enteritis model for disintegrative disorder. The second, you will see under 2, is the encephalitis/enteritis hypothesis. That suggests that vaccination leads to a persistent virus infection of both the gut and the brain. You see at the end of that page, 205:

“Evidence for the role of these hypothetical pathways can be generated by the proposed study.”

I reiterate that the science behind this project is not a matter for this committee; its only relevance, we say, is that it shows that the investigations were clearly research driven, and whether scientific theories are good, bad or indifferent, if they require investigations to be carried out for research rather than clinical purposes, they must be ethically conducted, and that includes obtaining the relevant research ethics committee’s approval.

If we go on, you will see there are two pages of the medical references associated with the research hypothesis, which are set out as required by the application form. Then if you go on to page 208 and go straight down to paragraph 7 you will see “Subjects”, and there are set out the selection criteria for the project: the presence of disintegrative disorder, symptoms and signs of intestinal dysfunction, parental request for investigation to be undertaken.

You will see under “How many are needed?” at the bottom of the page it was envisaged that there would be 25 children. If you turn over to page 209 you see that they were to be children under the age of 16, manifesting disintegrative symptoms and signs to differing extents. They were to be accompanied by their parents; they were to have a designated nurse in attendance throughout the week, and you will see:

“Invasive procedures and MRI will be carried out under either standard sedation or general anaesthesia (ileocolonoscopy and biopsy and the lumbar puncture will [all] be performed on the same morning), as indicated.”

Then a specific reference to what we say would indeed be a requirement for a research study:

“Parents will be aware that they can withdraw their child from the study at any stage.”

You go on to where a question is asked about controls, and of course, as you will be aware, controls in a scientific study are those who are selected as normal as comparators to those who are being researched; but in this instance it is specifically said that there would be no controls in the study.

You then go on under paragraph 10:


and then the question:

“How are the substances for this study being provided,” –

and the central part for your consideration –

“and how is the study being funded?”

The answer that has been provided under that is:

“Clinical research at the Royal Free Hospital” –

and then the words in brackets “(E.C.R.)”.

“ECR” stands for “extra-contractual referral”. It is the system which deals with situations where NHS patients are referred to a distant hospital rather than a local hospital, for clinical treatment. In such circumstances, I should say, at this time – things have moved on and funding is now done in a different way – but at this time the patient’s own health authority did not have a block contract with the hospital trust for the provision of services, and by agreeing to an ECR, an extra-contractual referral, the patient’s own health authority agrees to pay for the referral out of NHS funds on a one-off basis, despite the fact that it is to a distant hospital with whom they do not have a contract. It only applies to clinical treatment. The health authority did not have the remit to make an ECR arrangement or payment to fund research.

There is no reference, you will note, to the research accounts, which I will be telling you about shortly, which Dr Wakefield held with the special trustees of the Royal Free Hospital trust, and no reference to any Legal Aid Board funding.

If we go on with the application form, “PROCEDURES OR SAMPLES …”, and you see set out venepunctures, the amount of blood that was to be taken, the tissue biopsies, the amount that was to be performed, urine collection cerebrospinal fluid, which could of course only come from a lumbar puncture. We then see underneath:

“Would the procedure(s) or sample(s) be taken, especially for this investigation, or as part of normal patient care?”

The answer was:

“Yes: in view of the symptoms and signs manifested by these patients, all of the procedures and the majority of samples are clinically indicated. Additional intestinal biopsies (5 per patient) will be taken for viral analysis. DNA for genotyping will use blood cells isolated from the routine blood sample, and will not require an additional sample.”

We say that is a significant part of the application form, because even at that stage it places the investigations, such as colonoscopy and lumbar puncture, explicitly and firmly in the sphere of clinical treatment as opposed to research.

If you go on you will see queries in relation to discomfort, and the standard form requires the researcher to say:

“What discomfort or interference with their usual activities may be suffered in all or any of the subjects?”

The answer was:

“Ileocolonoscopy, upper endoscopy and lumbar puncture are invasive procedures … performed routinely at the Royal Free Hospital by members of the Department of Paediatric Gastroenterology. In order to avoid or reduce discomfort, ileocolonoscopy is performed under sedation given as an injection, or under a general anaesthetic. Lumbar puncture is performed under a local anaesthetic injected into the skin of the lower back. The injection itself produces a mild and brief stinging sensation. Thereafter, the procedure is painless.”

Then attached to that application, if you turn on to page 212, was a lengthy document entitled “Proposed clinical and scientific study”, with the same heading:

“A new syndrome: enteritis and disintegrative disorder following measles and measles/rubella vaccination?”

I am not going to go through it in detail because it replicates and elaborates on the information in the application. It was attached to the back of it and it sets out in considerably more detail – as I say, involving the extracts that I have read to you from the ethics application – the science behind the project.

I would like you, if you would, to go to page 221, and you will see that that sets out the heading “The proposed studies will involve:”

“1. Identification and characterisation of any intestinal pathology in affected children by:”

and it then sets out again in a little more detail the same studies as those which are set out in the ethics application form. You can see that if you turn on they are set out in a list in detail down pages 221 and 222 at the top of the page. If you go on to 223 you will see under “Practical issues”:

“i. Firstly, and significantly, this is a demanding protocol both for the child, and for those clinicians carrying out invasive procedures in particular. Due consideration should be given to this when planning the details of the admission. However, it is essential that we characterise as comprehensively as possible, the pathogenesis of this condition – control of any underlying intestinal immunopathology may open up new therapeutic avenues for the treatment of affected children. Our ability to confirm or exclude a role of measles or measles/rubella vaccine also has major implications for public health.”

It is our case that that paragraph makes crystal clear a research intent.

If you look on in that document, for reasons which will become apparent, it may be important to note that attached to it, at appendix 1 at page 226, you will see that there are several pages of it, all the way to page 230, and it includes amongst other studies the virological studies which were envisaged as part of the project. You will recall that I referred you in the application form to a specific reference to appendix 1 to the protocol.

If we turn on to 231, the end of the virological studies, you will see that that is a timetable, and it sets out the investigations over the period of days when these various tests were envisaged. You will see that those with an asterisk by them have at the bottom,
“Dr Wakefield to arrange”, and those are in fact the neurological tests. There is an asterisk by “white cells isolated for DNA extraction” and, under the Monday column, “MRI (Radiology) lumbar puncture Malcolm Ward”; under Tuesday, “EEG (Neurology) Evoked responses”; under Wednesday, “Dr Berelowitz Dept of Adolescent and Child Psychiatry”; and under Thursday, “Dr Harvey Malcolm Ward”. You will recall that Dr Harvey is the neurologist and Dr Berelowitz is the psychiatrist. So, all those tests which Dr Wakefield was responsible for arranging were neurological tests. Those with a cross beside them were “paediatric gastroenterology to arrange as indicated” and you will see that, on Wednesday, there is a gastrointestinal investigation with a barium meal and follow through X-ray with a cross beside it. On Monday, there is no cross but they are the other gastrointestinal investigations, “bloods, colonoscopy and upper GI endoscopy”. So, that was the timetable that was envisaged and those were how the responsible consultants themselves envisaged arranging that timetable.

If you go back to page 211, you will see the information sheet that was submitted to the ethics committee apparently for the parents, “Information to be given to parents …”, “A new paediatric syndrome …” and significantly what it says underneath is,

“The inflammatory Bowel Disease Study Group and the Department of Paediatric Gastroenterology … have an established record in research into inflammatory disorders of the intestine. This study hopes to add further to your understanding of the possible link between intestinal problems and behavioural disorders in a group of children who may have responded abnormally to measles and/or rubella vaccine”

and asking,

“If you agree to let your child take part …, please sign the attached consent form and return it in the enclosed envelope”

and thanking them for their part in the work with a request that they contact Dr Wakefield if they have any questions, and that was accompanied by a handout which is on page 232 and you will see that that says,

“Through parents such as you, Doctors at the Royal Free Hospital School of Medicine, have been alerted to the possible existence of a new disease: this comprises the development of autistic features in children who were apparently developing normally, and intestinal symptoms such as pain, diarrhoea and failure to thrive. The problem has been associated anecdotally, but consistently, with measles or measles/rubella vaccination. We, at the Royal Free, have now looked into the background medical and scientific literature concerning this problem, and have formulated the hypothesis that in certain (perhaps genetically susceptible) children, live-virus vaccines may produce long-term inflammation of the intestine and failure to absorb, in particular, vitamin B12. In the developing brain this vitamin is vital, and young children are very sensitive to B12 deficiencies. Such deficiencies may lead to failure of normal brain development and regression of behaviour similar to that you have possibly observed in your child”

and then it says this which we say is significant,

“We would like to carry out a series of tests which, we believe, will help us to establish the features of this possible disease. Our aim is to characterise the problem so that, for the future, we may be able to treat affected children and improve their wellbeing.”

We say that that is a clear reference to research and a clear reference to non-therapeutic research, i.e. research not for the significant benefit of that child but for future benefits.
It then sets out the tests – I am not going to go through them; we have been through them twice now already – but in suitable parent friendly language, it describes what is going to be done over a stay, a standardised set of tests including ileocolonoscopy, lumbar puncture, MRI, EEG and various blood and urine tests.

That application was received in the normal way by the ethics committee; it was assigned the reference number 172-96 and I think that is the easiest way of referring to it and it is how
I am going to refer to it in the future and it will become a familiar number to you.

As we have seen in the earlier part of my opening, there are two issues of importance in scrutiny of a research project and they are the ethical justification for invasive tests and the extent to which the project entails intervention over and above clinical care and, when this was circulated to the members of the ethics committee, those two issues made one member, a lay member of the committee, express disquiet and, in the same bundle, if you look on to page 241, this is the form that is sent round to members of the ethics committee for them to put their comments on when they have read the applications and this one was signed by
Mr Stevens and you will be hearing from Dr Pegg, the Chairman, that Mr Stevens was in fact an administrator; he was the assistant to the Chief Executive of the hospital at that time, i.e. he was not medically qualified, he was a lay member, and you will see what he says in his manuscript notes at the bottom,

“The project requires children to undergo an intensive regime. It would be helpful for this to [be] debated at the committee in order to confirm that the benefits of the regime in terms of clinical care of the individual children involved and the contribution to knowledge about the ‘syndrome’ support the proposed approach.”

After those inquiries had been made, Dr Pegg sought clarification from Dr Wakefield and a letter was then written to Dr Pegg from Professor Walker-Smith which was copied to
Dr Wakefield and to Professor Murch; it is dated 11 November 1996 and it begins at page 291.

“Dear Dr Pegg,

Many thanks for your letter.”

We do not have that letter; it may be that it will emerge during the course of the hearing but, in any event, we can see the broad terms of it from the response that Professor Walker-Smith writes.

“1. Despite extensive enquiries we could not find what ARSAC means.”

You need not worry about that; I will come to that at some point. It is of no real significance in the case at all.

“2. Clearly this is an intensive regime with procedures that could be regarded as ‘high’ risk although they are particularly used for the investigation of children with chronic inflammatory bowel disease. These children suffer from a disease with a ‘hopeless prognosis’ in relation to their cerebral disintegrative disorder. They have often not had the level of investigation which we would regard as adequate for a child presenting with such a devastating condition. In relation to their gastrointestinal symptoms which will be present in all the children we investigate, these have often been under-investigated. We have so far investigated 5 such children on a clinical need basis, all in fact have proved to have evidence of chronic bowel inflammation. One child has already had a significant response to enteral feeding. Certainly there is a measurable benefit to the child:

a) Establishing a diagnosis and excluding metabolic and other causes
b) Commencing on a therapeutic regime

The whole study is parent/patient driven as every case referred has been initiated by the GP by the parents of the child.

I can confirm that children would have these investigations even if there were no trial. I must make clear that we would not be investigating children without gastrointestinal symptoms.

We agree that consent always involves discussion and signature of the researcher. We will change the protocol.

With Kind Regards”

and it is signed by Professor Walker-Smith and you will see that it was copied to both Dr Wakefield and Dr, as he then was, Murch.

It is our case that that letter is extremely misleading in a number of respects when the information that it contains is compared with the children to whom he refers. In particular, Professor Walker-Smith’s statements that the children suffered from cerebral disintegrative disorder with a hopeless prognosis which had not had an adequate level of investigation, you should bear in mind when you hear the individual details relating to these children but, for the present purposes and the purpose that I will draw your attention to now, the significance of the letter of the application to the ethics committee was firstly in the acknowledgement that the regime was an intensive one involving high-risk procedures coupled with confirmation that these children would have had these investigations even if there were no trial, i.e. we say that that was a clear indication by Professor Walker-Smith copied in to the other two responsible consultants that the tests were justified as part of the normal clinical care of these children and were not part of the research project, and that indeed, as you will hearing from Dr Pegg, was what he understood from that letter. As far as he was concerned, the key question was whether these tests would have been done “anyway” and that is the word used by Professor Walker-Smith, i.e. regardless of any research project and because they were clinically indicated. Because Professor Walker-Smith confirmed that that was the case, the application was regarded by the ethics committee as one where the only element for which permission by the ethics committee was being required was the gathering of information on those children as a research project, in other words the gathering of the information was the research project, with the aim of subsequent publication in a scientific paper.

You have to bear in mind that research ethics committees cannot be experts in all the subjects on which applications are made. As I have already told you, they are made up of a mixture of lay people and doctors but there is no guarantee that there will be a doctor from any particular discipline involved in consideration of the application of any given research project. So, in the end, they have to trust the applicants to give them accurate information and it is our case that Professor Walker-Smith, with the full knowledge of Dr Wakefield and Professor Murch, provided in that letter information which was in fact wholly inaccurate and thus, we say, in breach of the trust which is imposed in them when they make themselves responsible consultants for a research project. The application subsequently proceeded throughout on the basis of the assurances that had been sought and had been given.

The ethics committee met on 13 November and, if you turn on to page 294, you will see the minutes relating to that meeting. They start on page 293, “Minutes of a meeting held on
13th November 1996”. I should say, as I have not mentioned previously, that you will see from those present that in fact Professor Murch was indeed by then a member of the ethics committee but, if you turn on to page 294, you will see that quite properly he was not there when this research application was considered because of course it would not be appropriate for a member of the committee to be there deciding upon his own project or the project in which he was involved.

You will see in the middle under 5,

“The Following Applications were discussed”

and then the project with which we are concerned, 172-96, and you will see the words,

“Not approved: Improvements required on patient information sheet and”

and this is the important part,

“clarification as to whether this is a study or a normal patient investigation.”

I should say at this juncture that there exists in the ethics committee file a letter addressed to Dr Wakefield from the secretary of the ethics committee indicating that approval was given to the project at that meeting, the meeting of 13 November. If that letter was sent, it was sent in error and we say that this was made perfectly clear by the subsequent correspondence.

The committee met again a month later – they have monthly meetings – on 18 December 1996 and, at that meeting, the project was noted to be approved subject to modifications on the patient consent form and the removal of one test which you may hear reference to, the Shilling test, which involved the use of radioactive material and that is the test for which an ARSAC licence would have been needed and it was not pursued by the researchers.

Dr Pegg wrote to Professor Walker-Smith on 7 January 1997 making those conditions relating to the Shilling test and modifications on the patient consent form and that letter is on page 358 of the bundle you are in, bundle 1, and I will read that letter to you; it is an important one.

“Dear Professor Walker-Smith,

I refer to your recent application to the Ethics Committee regarding the above project and I am pleased to inform you that the project was approved at the meeting on
18th December 1996. This approval is for two years from the date of this letter. Extension of this period will be dependent on the submission of a brief synopsis of the progress of the project together with an estimation of the time required for its ultimate completion.

As you may be aware this application was discussed at length at two committee meetings and the approval has been issued on the following:

1) Only patients enrolled after the date of the December meeting”,

so that will be 18 December 1996

“will be considered to be in the trial.

2) The Shilling test to be removed from the protocol

3) The consent form to be modified so that the possible complications of lumbar puncture are explained.

The Ethics Committee will require an annual report on the progress of the study and a copy of the completed study together with any subsequent publication. In addition the Committee must be informed, by the completion of the relevant form, of any untoward or adverse events which occur during the course of the study. The person who provided independent review of the original protocol should also be sent information regarding adverse events.

A copy of the patient consent form and information sheet must be lodged in the clinical notes”,

and then he goes on to an issue relating to confidentiality and patient information in the study and requested assurances that the Data Protection Act had been complied with. That letter is from Dr Pegg, who is the chairman of the committee.

Professor Walker-Smith wrote back to that letter on 9 January 1997, and that is at page 362, saying:

“Dear Dr Pegg

Many thanks for your letter. I accept its contents and we will modify our protocol as you recommend and give an annual report of the progress of the study.

We will place a copy of the patient consent form and information sheet in the clinical notes.”

That letter was copied to Dr Wakefield, so we say that if he were under any illusion as to the terms on which the ethical committee had granted their approval, it was clear to him from Professor Walker-Smith’s undertaking that the protocol was to be modified, that some request had been made by the ethics committee in relation to it.

Sir, I see it is half past four. I have reached the end of that section and I was going on to summarise the position in relation to the ethics committee. It is a convenient moment to stop if it is a convenient moment for the Panel.

THE CHAIRMAN: This indeed is a convenient time, I think.

MS SMITH: Thank you, sir.

THE CHAIRMAN: So we will now adjourn for the day, and shall we resume at 9.45 tomorrow morning?

MS SMITH: 9.45. Thank you very much, sir.

(The Panel adjourned until 9.45 a.m. on Wednesday, 18 July 2007)

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