GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Thursday 27 March 2008
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
CASE OF:
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(DAY FORTY-EIGHT)
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
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 not 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.
I N D E X
Page No
Housekeeping matters 1
ANDREW JEREMY WAKEFIELD, Affirmed
Examined by MR COONAN 3
THE CHAIRMAN: Good morning, everyone. First of all, could I first of all just remind everyone to make sure their mobile phones are switched off while in this chamber.
This is the hearing of Dr Wakefield, Professor Walker-Smith and Professor Murch. Dr Wakefield is present and is represented by Mr Kieran Coonan QC, assisted by Mr Neil Sheldon, counsel, instructed by RadcliffesLeBrasseur Solicitors. Professor Walker-Smith is present and is represented by Mr Stephen Miller QC, assisted by Ms Andrea Lindsay-Strugo, counsel, instructed by Messrs Eastwoods Solicitors. Professor Murch is present and is represented by Mr Adrian Hopkins QC, assisted by Mr Richard Partridge, counsel, instructed by Messrs Berrymans Solicitors. Miss Sally Smith QC, assisted by Mr Owain Thomas, instructed by Field Fisher Waterhouse represents the General Medical Council.
First of all, a couple of announcements. As there are a lot of members of the public and press in this room I think it is important to go through the emergency evacuation procedures. (Procedures recited).
A couple of other announcements, first of all, this is for Mr Coonan, Mr Miller and Mr Hopkins. Yesterday we were circulated a document, which I believe you are all aware of, by Ms Smith. This is only supposed to be a helpful exercise, a chronology of the events at the hearing and giving the page numbers in the transcripts. Ms Smith?
MS SMITH: Sorry sir, in fact it is best described as an index rather than a chronology. It is simply an index of the page numbers.
THE CHAIRMAN: Mr Miller, Mr Coonan, are you happy with that?
MR MILLER: Yes, we had it some time ago, thank you.
MR HOPKINS: As far as I know we have not received it. Is it a recent document?
MS SMITH: No, it is not recent in fact, it was produced by us several weeks ago. I do apologise if it never filtered through to Mr Hopkins. Just so he knows, there is nothing remotely controversial about it, it is simply an index so the Panel and indeed everybody knew where to find the evidence of a particular witness on a particular day.
THE CHAIRMAN: Basically, it only gives the page numbers in the transcripts of the evidence we have heard. I am sure you will be able to get a copy today.
MS SMITH: I have just been reminded, and now remember that in fact Mr Hopkins’ solicitors do have it because they made representations as to one or two omissions from it that they wanted inserted.
MR HOPKINS: I have been corrected, apparent we do have it.
THE CHAIRMAN: Thank you very much. Now that is out of the way can I announce a couple of corrections, as you know we have been using the last two days as our reading days and looking at all the documents and various things there are certain things that have come to our notice. First of all, Mr Coonan, for your purposes, it is in the heads of charges and admissions, in the yellow sheets, page 15, this is head of charge 17(c)(iii). It reads: “He did not qualify for the research study as he failed to meet the inclusion criteria set out in paragraph 2(c)(ii) above” and it should actually read: “He did not qualify for the research study as he failed to meet the inclusion criteria set out in paragraph 5(c)(ii) above”. It is just a typo but I thought for the purpose of the transcript it is better we clarify that and that it is corrected.
MR COONAN: Thank you.
THE CHAIRMAN: The second one is for the purposes of Mr Miller, that is on document D1.
MR MILLER: I have got it immediately to hand. Could you give me a clue as to what it is?
THE CHAIRMAN: There are two heads of charge, I think you have been very careful in this document, this is your admissions list and you have been very careful to put it on every allegation either “admitted” or “not admitted” but there are two allegations against which you have not put either of the two things and I believe the Panel Secretary has already been in touch with you, allegation 18(a)(i), which is about Child 12, I believe that is admitted.
MR MILLER: That is right, sir.
THE CHAIRMAN: The other one is 20(a)(i), and that is about Child 8, and that is not admitted I think.
MR MILLER: I spoke to the Panel Secretary yesterday. We cleared up 18(a)(i). I am afraid I had not cleared up 20(a)(i), can I look at that and come back to you very shortly.
THE CHAIRMAN: Yes. But looking at my documents I think it is not admitted.
MR MILLER: We looked at the transcript and could not find anything dealing with it at all there but we did not then follow it up, which we should have done but we do it as soon as possible.
THE CHAIRMAN: Thank you. The third one is about Professor Murch, and that is for Mr Hopkins. That is once again on the yellow pages, page 88, head of charge 18(vi), I think the date is written wrongly on this, it is written “admitted but found proved only to January 1999”, it should be January 1997
MR HOPKINS: Sir, could I check that a little later, but we have made a note of it?
THE CHAIRMAN: Absolutely. Those are the things which came to our notice which I wanted to clarify. Mr Coonan has already accepted that but I am sure Mr Miller and Mr Hopkins will inform us in due course of the position. Just to confirm, Ms Smith, I think you had concluded the case for the GMC?
MS SMITH: Yes, I closed my case on the last occasion. You may have noticed, sir, that I am getting further and further away from the witness and I did find it a little distant before, so I am quite happy to see how I feel at the end of the morning but perhaps I could make an application then if I need to to bring our tables a bit further forward because, as I say, the distance seems to be growing, if it gets any further I shall be next door.
THE CHAIRMAN: I am sure if you do have any practical difficulties of such a nature let us know and we will be very sympathetic to your request to do anything you need to do. Mr Coonan?
MR COONAN: Sir, in a few moments I shall be calling Dr Wakefield to give evidence. Before I do that, and to help the Panel, I am going to ask that you be provided with what I am going to call for shorthand purposes a route map of where we are going. I will not say anything more for the moment but perhaps they can be distributed to you. (Same handed and marked as D7) This document is not intended to have any legal significance, it is simply, as I say, a route map. You can see at a glance – I will not take you through it now but it is self-evident – when I call Dr Wakefield to deal with the evidence that has been laid before you in both a schematic and chronological way. I shall also be attempting to link that approach with the charges, where possible, because we are conscious – you may be, I know not – that the evidence requires focus because you have been provided with a mass of material and this approach is intended and designed to make sense of it, so I hope the Panel finds that helpful. My approach in chief with Dr Wakefield would be to follow this sequence, although it may be that I might take one or other out of order and if I do I shall let you know.
THE CHAIRMAN: Can I check, Ms Smith, are you happy with the quality of the sound that is coming to you?
MS SMITH: Yes, thank you.
THE CHAIRMAN: If you can hear it then everybody can.
MR COONAN: I hope the Panel can hear it too.
THE CHAIRMAN: We can definitely hear it.
MR COONAN: Sir, having said that, and with that introduction, I shall call Dr Wakefield.
ANDREW JEREMY WAKEFIELD, Afffirmed
THE CHAIRMAN: Good morning Dr Wakefield. Can I first of all thank you for agreeing to give us the benefit of your evidence this morning. I think you have heard me explain to the other witnesses the way we will proceed in this hearing, and the same procedure will be followed, examination in chief, cross-examination by the other counsel and also by counsel on behalf of the GMC. After re-examination, if any, the Panel will ask questions and after that if there is any further re-examination to be done that will be done. That will be the order.
Can I also say, if at any stage you find that it is starting to get stressful or are you getting tired or anything like that, give me a hint and I am sure we will be very sympathetic to giving you a break at that stage.
I think on that note can I ask Mr Coonan to proceed.
Examined by MR COONAN
Q Dr Wakefield, would you give the Panel, first of all, your full name and your current professional address?
A Andrew Jeremy Wakefield, MB BS, FRCS, FRCPath. I am currently Executive Director at Thoughtful House Center for Children, Bee Caves Road, Austin, Texas.
MR COONAN: I am going to ask you to produce an updated CV. There is a previous CV at Volume 3, page 940B. (Same handed and marked as tab 9 of D2).
THE CHAIRMAN: Legal Assessor?
THE LEGAL ASSESSOR: Various people seem to have things in tab 9, the Chairman does not but I do and Dr Webster has. It is described as a “discharge letter.”
MR COONAN: That file you have there is D2 with a series of tabs so if there is a document D3 it should be separate in that file in D2.
THE LEGAL ASSESSOR: Very well.
MR COONAN: (To the witness) Dr Wakefield, do you have the updated CV?
A I do.
Q I will take first of all to page 3, and we see your name and your professional address that you have given, and you are now 51 years old, is that right?
A That is correct.
Q Your current position is Executive Director of Thoughtful House Center for Children, I will come back to that in a moment. Over the page you set our your qualifications, which you summarised in the first few minutes of your evidence. Can we look at a number of features of that, please? Your Fellowship of the Royal College of Surgeons in 1985 and then the Fellowship of the Royal College of Pathologists, was that by publication?
A Correct.
Q That was in 2001: do you have formal pathology qualifications as opposed to the Fellowship by publication?
A No.
Q Do you have any formal paediatric qualifications?
A No.
Q During the time either before or indeed during the time that we are concerned with, have you acted as a pathologist as such?
A No.
Q We will look at the detail of that later. The previous history, your medical career, is then summarised on page 2, taking the earliest dates first, I am looking at those appointments. Were they all clinical appointments on page 2?
A Yes, they were all clinical appointments.
Q Page 3, between November 1986 and November 1988 you were a Wellcome Research Fellow at the surgical unit in Toronto, is that right?
A Correct.
Q Was that a clinical appointment?
A That was a research appointment.
Q What was the focus of the research?
A Experimental small-intestinal transplantation.
Q When you left Canada, you took an appointment as a Wellcome research fellow at the Royal Free School of Medicine, did you not?
A Yes, I did, on a voluntary basis. I was working on the liver transplant programme there and again at King’s I did some work on a voluntary basis on the liver transplant programme in a clinical capacity and I undertook several clinical locums during that period as well.
Q Apart from those clinical locums in that period, thereafter as you practised as a clinician or not?
A No.
Q If you have not practised as a clinician, how would you describe that practice?
A I am involved in clinical and experimental research.
Q Taking you to that appointment between November 1988 and September 1990, if you turn the page, page 4, was that fellowship extended for three years?
A Yes, it was. Based upon the recommendation of the Royal Free, the Wellcome Trust extended that fellowship for a three-year period.
Q I am just looking at the milestones because I want to look at the detail of this later. The milestones begin with your appointment as a senior lecturer in experimental gastroenterology in the departments of medicine and histopathology at the Royal Free and that was from January 1993 to April 1997, is that right?
A Yes, that is correct.
Q Were you then promoted to Reader?
A Yes.
Q Were you a reader from May 1997 until November 2001 at the Royal Free?
A Yes.
Q Were you appointed honorary consultant in experimental gastroenterology at the Royal Free from January 1994 again to November 2001?
A Yes.
Q Did you leave the Royal Free in 2001?
A Yes.
Q Up to that point, as your CV indicates, you were Director of Research and Chairman of the Inflammatory Bowel Disease Study Group; is that right?
A That is correct.
Q I want to go back and look at the detail of that in a moment. So, you were Chairman and Director of Research for about 12 years.
A Yes.
Q After your appointment at the Royal Free, you became senior medical adviser to the charity, a UK registered charity, called Visceral. What was the nature of that charity?
A Visceral as a registered UK charity was established in order to fund clinical experimental research into, in particular, inflammatory bowel disease, Crohn’s disease and ulcerative colitis and childhood developmental disorders and the possible association between those two elements.
Q Would there have been trustees for that charity?
A That is correct.
Q Can you identify for us and give us the name of any relevant trustee/
A The Chairman from its inception was Mr Nicholas Lander of Hampstead. Other trustees at various times included Professor Roy Pounder, Professor Christine Lee(?), Dr Peter Harvey and others.
Q Then, from 2004 until the current moment, you have been the Executive Director at Thoughtful House. In that role, do you exercise clinical responsibility?
A No.
Q What is, if I can put it this way, the fundamental raison d’être of Thoughtful House?
A Since encountering the children in particular with developmental disorders, with autism, over the years, my colleagues and I, firstly at the Royal Free and then elsewhere, tried to put together/assimilate a plan for what these children needed clinically in order to treat their underlying medical disease, educationally, the optimal form of education that these children might receive in order to benefit. If you could get a child well, for example, from their physical debility, then you had a chance, if you could then give them the best educational input, to get the best for that child and then to combine those two elements, medical care and education, with research in order to ask, “Are we doing this the best way? Is there a better way we can do it?” and “How do we communicate our findings to the world at large?”
Q Is that the nature of the exercise in which you are currently engaged?
A Yes.
Q Moving on through the CV, on page 5, there is a summary of your research and development interests. I am not going to take you through that in detail but elements of that will emerge as we go through the chronology and you can refer back to pages 5 and 6. Pages 5 and 6 are, as I say, a summary of the research and development interest; is that right?
A Yes.
Q On page 7, you set out that you had supervised higher degree students, you have been a reviewer to a number of scientific journals and then, on page 8 through to the end of the CV on page 17, we see a total number of publications up certainly to 2006 of 137 – 137 publications – of which you are either the first or last author of the paper; is that right?
A I think in many I am first or last author; I think in some I am somewhere in between.
Q I am not going to ask you to speak to these 137 but I am going to ask you at this stage to simply identify those publications which, in your view, have been and remain perhaps seminal to the work that we are going to be looking at on measles, inflammatory bowel disease and autism. Can you do that for us, please. I will take this in chronological order. Is the first one number 8?
A Yes, it is.
Q You take it in your own way but obviously, as you appreciate, I have the anticipation of what you will say. The quickest way to do it is for me to suggest and for you to say if there are any in between. What about 27?
A Yes, that would be the next one.
Q And 36?
A Yes.
Q Looking at page 11, can I ask you to scan the papers at pages 49 through to 53 and identify any of those which, in your view, are seminal to your work thus far.
A On reflection, 49 is an important paper that I should introduce and 53.
Q Would you turn over to page 13 where you see publication number 80. Is that The Lancet to which the Panel have had their attention drawn so far?
A That is correct.
Q Again for my purposes, would you move on to page 15 and look at publication number 108.
A Yes, that is correct.
Q Finally, 119.
A Yes.
Q I have taken you to those and you have agreed with them. Do you think there are any others which, as I say, fall under the description of seminal for the purposes of charting your work during the relevant time?
A No, I think those are the key ones from which everything else derived.
THE CHAIRMAN: Mr Coonan, would you repeat the numbers again just to make sure that I have them right.
MR COONAN: Yes. I think that Dr Wakefield identified number 8, number 27, number 36, number 49, number 53, number 80, The Lancet paper, number 108 and number 119. I can tell the Panel now that we shall return to those documents later.
(To the witness) Dr Wakefield, you can put the CV to one side, please, because I am now going to look in a little more detail at the background leading up to your appointment. Would you take volume 1 of the Panel bundle, that is FTP 1, at page 16, the first document that I am going to ask you to look at in relation to your academic appointment. In this letter on 10 December 1992, you appear to have been appointed as Senior Lecturer in the University Departments of Medicine and Histopathology from 1 January 1993 and the letter continues,
“The appointment carries with it the honorary status of senior registrar …”
and the rest of the details I do not think matter for our purposes. The second page of this document is missing but the document is copied to those people at the top of the page. Did you understand that to carry with it a particular title?
A The appointment was a joint one between the Departments of Medicine and Histopathology and this was based upon the suggestion of the then Professor of Histopathology, Peter Scheuer. Peter Scheuer resigned soon after the appointment was made and Professor Revell took his place. For that reason, the title was Senior Lecture in the Departments of Medicine and Histopathology and, since that time, I used the title “Senior Lecture in Medicine and Histopathology” for that reason.
Q That is the starting point of the academic appointment. Would you move on in the same bundle, please, to page 314. This is a letter dated 14 November 1996, a three-paged letter written by Miss Lewis, the Assistant Secretary, addressed directly to you and I am going to read out the relevant parts.
“I am writing on behalf of the School Council and on the recommendation of Professor Pounder and Professor Revell to offer you renewal of your appointment as Senior Lecture in the Departments of Medicine and Histopathology on a permanent basis from 1 January 1997”.
The next paragraph,
“The appointment which carries with it the honorary status of Consultant at the Royal Free will terminate at the end of the university session in which you retain the age of 65”.
The third paragraph I draw your attention to, please, for comment.
“Your appointment is made on the condition that you hold and continue to hold an honorary NHS contract at a designated hospital. The holding of an honorary NHS contract is essential …”
I am sorry, there appears to be a problem.
MS SMITH: Both Mr Miller and I heard you saying “central”. It is “essential” rather than “central”. We may have been incorrect.
MR COONAN: I think that the Panel can see what the word says, it says “essential”. I will read the sentence again in case the sense of it was blunted by that intervention.
“The holding of an honorary NHS contract is essential to the proper performance of your clinical teaching duties”.
(To the witness) Two things. First of all, what did you understand your title to be in relation to that renewal?
A I had now been appointed a permanent member of staff as a senior lecturer, an academic, in the Departments of Medicine and Histopathology and, with that, I had now an honorary consultant appointment which was subsequently held with the Hampstead NHS Trust.
Q Did the comment made in the third paragraph have any significance for you?
A Yes, it was clearly important. A lot of the research in which I was involved, clinical and experimental research, required, by necessity, access to medical records, it required the priviledges and the responsibilities of an NHS consultant without any clinical sessions or direct clinical responsibilities for patient management.
Q We will come back to the honorary NHS contract in a few minutes. In terms of your academic title, may we now look at page 370A and the purpose of looking at this document is not for the content of the letter, although we will have to look at this letter later on, much later on, but I want you to look, please, at the title that you use at the bottom under your signature, “Senior Lecturer in Histopathology and Medicine”. Is that the title that you had used ever since your academic appointment back in January 1993 albeit then as senior lecturer?
A That is correct and for the specific reason that the appointment was a joint one between medicine and histopathology.
Q Later on, we will see that an issue arose about that title but, up until the time when that issue arose, had anybody objected to the use of that title?
A Not as far as I am aware.
Q That is your position as senior lecture appointment and renewal. I want now to move to promotion to Reader in May 1997 and we start, please, by looking at page 87. Just a few preliminaries here, please, once you have the letter. First of all, it is a letter written by Professor Fine. Can you remind us, at that time which was October 1995, was Professor Fine Professor Medicine?
A Yes, by this stage the Royal Free Hospital had merged with University College Hospital and Professor Fine became the overall head of the Department of Medicine, the joint Departments of Medicine.
Q It is written to Professor Zuckerman, the Dean, and as the first line makes clear Professor Fine wishes to propose the promotion of yourself to reader in gastroenterology. This letter, as I recall it, was never read out into the transcript and so I am going to do that in fairness to you, because that was not done first time round.
Professor Fine writes as follows:
“Dr Wakefield’s research career started in 1985 when, having gained a Wellcome Trust Travelling Research Fellowship and a Royal Society of Medicine Travelling grant, he went to work with Dr Zane Cohen and Dr Benrie Langer in the University of Toronto School of Medicine on the vascular biology of small intestinal allograft rejection. During this time he developed a strong interest in vascular biology and was struck not only by the limited ,merits of small intestinal transplantation, but also by the failure to have answered the basic questions about why we were transplanting in the first place – that is, what were the origins of the intestinal diseases. He was struck by the similarities in the macroscopic appearances of Crohn’s disease and rejecting intestinal' allografts. Subsequently he developed the hypothesis that Crohn’s disease is due to a persistent viral infection of the mesenteric microvascular endothelium, that initiates a process of vasculitis and microthrombotic occlusion of the affected vessels.. He returned to England to identify a unit in which he could test this hypothesis and joined the liver transplant programme at the Royal Free in 1988, still funded by the Wellcome Trust. His work has focused on three main areas.”
Just pausing there, did you see this letter at about the time this was written and sent to Professor Zuckerman?
A I have no memory of having seen this letter.
Q Certainly so far as the introductory paragraph is concerned is there any comment you want to make about that?
A No, it is accurate.
Q Then we look under the heading of “Crohn’s Disease”:
“Over the course of the next two years, Dr Wakefield studied tissues of Crohn’s disease using novel techniques in order to clarify the vascular pathogenesis of this condition. Using 3-dimensional imaging technology, he was able to demonstrate quite clearly that Crohn’s disease was associated with multifocal microvascular occlusion caused by foci of granulomatous vascular injury, an appearance that was not readily apparent in routine 2-dimensional histopathology. This paper was published in The Lancet. Upon repetition and extension of these early studies, he reaffirmed the fact that Crohn’s is a disease associated with a widespread granulomatous and lymphocytic inflammation of blood vessels. This view is now accepted widely. During this time the Wellcome Trust extended his Fellowship for another two years. The establishment was somewhat shaken when he promoted the hypothesis that Crohn is due to a persistent viral infection of the microvascular endothelium of the gut. He suggested that this may be due to a persistent measles virus infection based upon our knowledge of the behaviour of measles virus during the acute infection and its capacity to persist in human tissue. At an early stage he recruited a large number of well recognised experts in a variety of fields, including virology, molecular biology, vascular biology and haemostasis. He formed the Inflammatory Bowel Disease Study Group of which he was the founder and chairman. The group has worked together extremely effectively over the last five years. In the last two years the group, under his leadership, has provided preliminary evidence for and recently confirmed persistent measles virus infection of the intestine affected by Crohn’s disease. This is the first time measles virus persistence outside the central nervous system has ever been confirmed and the work has required the development of a number of specialised technologies. These include novel protocols for immunogold electron microscopy and in situ polymerase chain reaction.”
Any comment you want to make about those observations by Professor Fine?
A No.
Q
“Two years ago Dr Wakefield recognised the need to bring epidemiologists into the group in order to answer some very basic questions about early measles virus exposure, and the subsequent development of Crohn's disease, since this is a recognised risk factor for measles virus persistence and subacute sclerosing panencephalitis. He was alarmed at the increasing incidence of Crohn's disease in children in the face of increasing measles vaccine uptake. He identified a number of longitudinal birth cohort studies being conducted in this country, which would provide us with prospective and therefore unbiased data about early infectious events, and the subsequent development of inflammatory bowel disease. He was also able to use measles vaccine efficacy cohorts established by Dr Norman Begg at the Public Health Laboratory Service in 1964, which would provide data on the role of measles vaccine in inflammatory bowel disease. The culmination of this work is the submission of a paper to The Lancet showing that there is a highly significant increase of both Crohn's disease and ulcerative colitis in children who received live measles vaccine. He is currently in negotiation with Dr Kenneth Calman at the Department of Health on the best way forward in view of these compelling data. The government is now persuaded that his group may have made significant inroads into understanding inflammatory bowel disease and that they have identified the likely cause of this condition.”
Pausing there, are there any observations about Professor Fine’s observations in that paragraph?
A None except to say he may have been a little enthusiastic about the Department of Health’s interpretation, but otherwise no.
Q “Ulcerative colitis
In parallel with these studies, Dr Wakefield’s group has a major interest in the pathogenesis of ulcerative colitis, a more enigmatic condition, in view of the absence of granulomas … This paper has been accepted by The Lancet. This work shows that the origins of ulcerative colitis are also vascular and it may well be that infectious agent has a role to play in this disease as well. He has, in collaboration with a group from Turin, shown that anti-measles IgM antibodies are significantly raised in patients with both Crohn's disease and ulcerative colitis, but not inflammatory and non-inflammatory controls.”
Then the third category of activity, Professor Fine writes this:
“In view of his exciting observations, Glaxo Group Research approached Dr Wakefield with a view to initiating a collaborative study of NSAID enteropathy. Over the past four years he attracted major grant funding to study this phenomenon. He recruited an extremely able histopathologist, Dr Andrew Anthony, to address this problem and he has made inroads into elucidating the mechanism of nonsteroidal induced intestinal injury …
In summary, Dr Wakefield has proved to be a dedicated, highly focused investigator who has achieved an international reputation. He has a full time research commitment, running a team that comprises 50 collaborators. His principal aims over the next five years are (1) to develop an animal model of measles virus enteritis for future therapeutic intervention; (2) to understand the mechanisms of interaction between measles virus and the endothelium, particularly in terms of its procoagulant and pro-adhesive interactions; (3) continuing epidemiological studies into the role of measles virus in Crohn's disease and particularly measles vaccination and revaccination in predisposing to inflammatory bowel disease; (4) detecting in situ immune responses to measles virus in the intestine of patients with Crohn's disease and ulcerative colitis; (5) understanding the potential pathogenic role of ANCA in ulcerative colitis and characterising further the target antigens for these antibodies.”
Then under the heading of “Teaching”:
“As a teacher of postdoctoral students, research registrars and academic colleagues, Dr Wakefield is regarded very highly. His lectures and seminars are superbly structured and his charismatic style makes him a lecturer and speaker who is in constant demand.
Dr Wakefield has no current clinical responsibilities. His presence in the Division of Gastroenterology in the Joint Department of Medicine has galvanised a considerable amount of clinical research and his ongoing collaboration with Professor Pounder has always been a productive one.
I recommend his promotion to Readership with enthusiasm and conviction.”
We know that you were appointed to Reader effective from 1 May 1997; I just want to look, please, at two aspects of this letter. In the last paragraph where it says that you had no current clinical responsibilities, was that an accurate description?
A Yes.
Q In the rest of the last paragraph Professor Fine writes that you had “galvanised a considerable amount of clinical research”. That is him writing and using that term, but leaving aside Professor Fine’s actual meaning, what is understood by you to be attached to the term “clinical research”, what does it mean?
A Clinical research from my perspective involved the collaborative interaction with clinical colleagues directly involved in patient care, in this case doctors looking after patients with inflammatory bowel disease for the purpose of jointly and collaboratively determining the mechanism and origins of their disease process, and indeed, I should add, also how they might benefit from interventions with novel treatments.
Q Just before leaving this letter, again the same approach, are there any other observations you want to make about Professor Fine’s analysis and opinion about your activities and indeed intentions at that stage?
A No, it is a very kind letter. I am not sure I deserve it, but there it is.
Q The appointment letter can be found in volume 2 of FTP2 at page 427A. The appointment letter is dated 21 April 1997 from Miss Lewis, the assistant secretary. She writes:
“You may use the title ‘Reader in Experimental Gastroenterology’ with effect from 1 May 1997.”
If you then move to page 428A, not for the content of the letter but for the title description, you will remember that you told the Panel of the title that you used when you were a senior lecturer on volume 1, page 370A. We now see you as a reader in histopathology and medicine. Can you help the Panel about the use of that particular style?
A Again, I was based in histopathology and medicine and the macro continued to express that. It was in fact, I think, an error on my part that was later picked up and amended to reader in experimental gastroenterology.
Q Dr Wakefield, I am asking you to deal with these matters because they appear in the documents, that is why I do that. You mentioned that the matter was picked up – indeed it was. If you go to page 674 in volume 2 this is from Professor Revell to you. I am not concerned with the first four lines for present purposes, but in the last couple of lines he points out that the correct title was reader in experimental gastroenterology as opposed to reader in medicine and histopathology; that is what you were referring to, is that right?
A That is correct.
Q The same point was made by Professor Zuckerman at page 674B, and for these purposes I am just looking at the last two lines of 674B, a letter dated 22 January 1998, “Reader in Experimental Gastroenterology” as opposed to “Reader in Medicine and Histopathology”.
A May I just point out I do not have those pages, 674A or B.
THE CHAIRMAN: These were the pages that were introduced.
MR COONAN: They were. (To the witness) It is just the last two or three lines of the letter itself, Dr Wakefield, that I am concerned about at this moment, where the same point is picked up by Professor Zuckerman, is that right?
A Correct.
Q If you turn to page 755A, you say in that letter that you will be moving out of the office in the Department of Histopathology on 9 March. Did you subsequently deal with the point ---
A Yes.
Q --- if you look at the bottom of the same page, do you see the title?
A Yes.
Q So you have, in effect, changed the title to deal with the point raised, is that right?
A Correct.
Q Since the point has been raised I will just ask you globally, were they right to raise that point?
A Technically, absolutely, yes.
Q What is your position in relation to that?
A I wanted to reflect for their purposes, since they had offered me this unique and interesting joint appointment between the two departments, that both departments should be recognised, no more than that, and that is why I continued to recognise both departments in this letter but applied the correct job title to it, “Reader in experimental gastroenterology”.
Q That is all I am going to ask you about the academic side and we come on to the honorary consultant appointment. Initially, you told the Panel – I am going back to FTP1, page 16 – that the senior lectureship was accompanied by appointment as senior registrar: did you have to apply to become a senior registrar?
A I cannot remember the mechanism by which that came about.
Q But certainly, as we know, you became an honorary consultant. The first document I would like you to look at is page 41 of volume 1, and it is from Dr Harvey, Chairman of the MAC – can you give us the full title of that, please?
A The Medical Advisory Committee.
Q At the Royal Free?
A Correct.
Q Written to Mr Cooper, the Chief Executive, in November 1993:
“I am happy to say that the CSC …”
Can you help us with that?
A No, I am afraid not.
Q “ … approved an honorary consultant contract, with no clinical sessions, for Mr Andrew Wakefield, the full title being ‘Consultant in Experimental Gastroenterology’. I enclose his job description as tabled at CSC. Will put this through MAC in December.”
First of all, have you any recollection of ever seeing that letter?
A No.
Q The job description may be found at either pages 40 or 42 (I think there is another copy). Could we look at page 40? There is some handwriting on the top left and top right: was any of this writing yours?
A No.
Q I note just under the heading “Mr Andrew Wakefield FRCS” the title, “Senior Lecturer in Medicine and Histopathology”. Did that accord with your working title at that time?
A It accorded with my understanding, yes.
Q It sets out two headings, under the second one, “Honorary Consultant in Experimental Gastroenterology with zero clinical sessions”. As a matter of your understanding and practice at that time, was it correct that you had zero clinical sessions?
A Yes.
Q I am just going to read to remind ourselves of the content of this document:
“Mr Wainwright is the Research Director of the Inflammatory Bowel Disease Study Group, involved exclusively with laboratory-based research.”
Is that correct?
A It may require some explanation but, yes, it is essentially correct.
Q “His job entails being Chairman and Research Director of the Inflammatory Bowel Disease Study Group at the Royal Free Hospital School of Medicine. The Inflammatory Bowel Disease Study Group is a collaborative research effort involving some 50 clinicians and scientists based at the Royal Free Hospital and worldwide.”
Is that correct?
A Yes.
Q “The post involves developing both long-term research strategies for the investigation of ulcerative colitis and Crohn’s disease and non-steroidal enteropathy, combined with the day to day running and supervision of research projects involving two PhD students, four MD students and one MS student. Mr Wakefield is also in charge of the day to day activities of a number of graduate scientists working with the group.”
Is that correct?
A Yes.
Q “In addition, the job involves raising funds for the group from government run bodies, research-based charities and other government departments. The overall aim of the job is to provide leadership and strategic research initiatives that will make the Royal Free Hampstead NHS Trust and Royal Free Hospital School of Medicine the world leader in inflammatory bowel disease research. His research involves the laboratory investigation of resected human tissues.”
Is that correct?
A Yes.
Q “… but, he will not be involved either in the clinical management of patients with inflammatory bowel disease or the routine histopathological reporting of tissues from these patients.”
Pausing there a moment: did you ever see this document prior to the preparation or this hearing?
A I do not remember this document. I am perfectly prepared to accept that at some stage I may have seen it but I have no memory of it.
Q In terms of what was written by the author of it, when it says in terms “he will not be involved either in the clinical management of patients or the routine histopathological reporting of tissues from these patients”, is that an accurate description going forward of what your involvement generally would be, as you understood it?
A Yes, it was, the key term is “clinical management” and the connotation attached to that, and my understanding of that phrase then – not necessarily in this letter but more generally – and now is that that refers to the executive decision-making process that is involved in the diagnosis of disease and its treatment.
Q The second limb of that sentence, “will not be involved in the routine histopathological reporting of tissues from these patients”, was that an accurate description?
A Yes, it is.
Q Finally, “He not be involved in the out-patient or in-patient management of patients in the Royal Free Hampstead NHS Trust”. Again, what is your comment about that?
A Again, the use of the word “management” remains exactly the same. It is that I would not be involved, and was not involved, in the executive decision-making process that involved the investigation or treatment of patients.
Q “He will not practise as a consultant surgeon, physician or gastroenterologist as part of this appointment.”
Did that accord with your understanding?
A Yes.
Q Do you have any comment to make about the daily timetable?
A No, none at all.
Q Your letter of appointment can be seen at page 44, dated 21 January 1994, again this is from John Cooper the Chief Executive:
“Dr Mr Wakefield,
I am directed by the Royal Free Hampstead NHS Trust to offer you an appointment as Honorary Consultant in Experimental Gastroenterology at the Royal Free Hospital with effect from 1 January 1994 linked to your paid employment with the Royal Free Hospital School of Medicine.
The terms and conditions of the appointment are those of the Royal Free Hampstead NHS Trust as amended from time to time, insofar as they relate to honorary appointments.”
I do not think there is a dispute that the terms and conditions is a different concept reference than the document we have been looking at so, that is said to be your job description, do you understand? The important point for my purposes is this, in the next paragraph:
“The Trust requires you to be a fully subscribed member of a recognised professional defence organisation …
You are required to be registered with the General Medical Council …”
And then this:
“No specific clinical sessions are designated under the terms of this honorary appointment.”
Do you understand that to be a correct assertion?
A Yes.
Q Were any clinical sessions, specific or otherwise, ever identified for you thereafter?
A No.
Q Over the page, it is self evident you accept the appointment, I think that should be “on the terms and conditions set out in this letter” and is that signed by you? Is that your signature on page 2, dated 1 February 1994?
A It is.
Q Dr Wakefield, can we just step back and look at the concepts underlying this appointment? Whether or not you saw at the time or subsequently the precise terminology of the document which has been described as a “job description”, I want to ask you about your role generally as a researcher against the background of this appointment as an honorary consultant, and particularly given your role as head and director of the Inflammatory Bowel Disease Study Group. Did you understand that you had clinical responsibility for any one or other patient?
A I did not have such a responsibility.
Q Would you, as you understood it, be entitled to attend clinical meetings?
A Absolutely, that was an essential part of my work.
Q Can you explain to the Panel why?
A In all hospitals, as the medical members of the Panel will know, and particularly in teaching hospitals, interaction with colleagues is an essential part of the learning process and the dissemination of information, and the Royal Free was no different from any other hospital in this respect. Participation in clinical meetings, listening to the clinical history, listening to the patient’s story, deducing clues from that story, from the tests that had been taken out on that patient in a clinical context were absolutely essential to the formulation of medical hypotheses, and without those clinical interactions medical hypotheses have no foundation whatsoever and clues should always come from the clinical arena, and therefore for the clinical scientist (which I was effectively at that stage) our hypotheses and the progress of our work meant that it was essential that such interactions took place.
Q If the expression “ward rounds” or “grand rounds” been used, would you understand it to be part of your remit to attend those?
A Yes, grand rounds were invited meetings which were open to all-comers to attend, both academics, medically qualified or not, medical students and others, and they were an essential part of the learning process.
Q What about the attendance at outpatient appointments?
A Again, just as it is essential for medical students to attend outpatient appointments, it is essential for me in the learning process, and this refers later to my attendance at Professor Walker-Smith’s outpatients, to sit and to listen, to assimilate the patient’s history that Professor Walker-Smith was adducing, and to derive from it the clues that are essential to how we define a hypothesis and how we conduct the science to test that hypothesis.
Q Attendance at out-patient appointments or grand rounds or clinical meetings may be one thing but what about you, as it were, participating by opening your mouth and making inquiry or even suggestion, what about that?
A If I can give you an example, that at grand rounds, or indeed in the departmental rounds conducted by Professor Dame Sheila Sherlock, these were open to academics, non-medically qualified academics as well as medically qualified doctors, and opinions were sought, for example molecular biologists would attend and their opinion on certain tests that might be necessary or useful in the assessment of patients was sought and given. It was entirely up to the clinician then to determine whether they acted on that advice or not, but nonetheless it was perfectly acceptable, and, indeed, part of routine practice that opinions were sought and expressed in that sort of setting.
Q Would that extend to a discussion involving your input in relation to individual patients?
A If the circumstances necessitated it, yes, but please understand, this was not in any way an executive decision-making role. I had no place in making such decisions about patient’s treatment. I think as Professor Booth has pointed out in his expert evidence, it was perfectly reasonable to suggest, and particularly to offer an opinion when one was sought.
Q One of the aspects of such suggestions might be the suggestion of treatment options. Would you see that as part of your general remit?
A If information came to light to me that was not immediately evident to the clinicians, then it is my duty to pass that information on to the clinicians and again it is entirely within their remit, not mine, to make an executive decision about whether that treatment option is used or not. This may have happened from time to time but this did not involve me in the management, as I have defined it before, of patients.
Q What about – and I am asking this question very much in a general sense against the background of your honorary consultant appointment – contact with parents?
A The context of contact with parents was that I received calls and letters, many such calls and letters. I never proactively sought them or went out and called parents spontaneously, they came to me. Having come to me as a conduit for potentially accessing help for their children, then that was entirely my duty as a doctor and that I did by referring them on to Professor Walker-Smith suggesting, for example, that, in order to be seen clinically, then they would need an NHS referral from their general practitioner or their paediatrician to Professor Walker-Smith in order for him to determine whether or not they needed further clinical investigation.
Q We will look at those connections in more detail later on. Again, against the backdrop of the terms of your consultant appointment, what about contact with general practitioners? Did you see that as something that you were permitted to do?
A Absolutely. Again, communication in medicine is absolutely essential and it is particularly important when one is dealing with a very complex issue as we were with the children with autism with bowel systems and various other problems. It was important if the general practitioner sought it or if the parent asked for me to make contact with them to explain in generic terms what it was that we were involved in, then I was very happy to do that. Not to make recommendations about an individual child in any way but to explain to them in a generic way the background to our thinking and why it might be appropriate if they feel necessary to make such a referral to Professor Walker-Smith.
Q Did you at any stage have your own clinic?
A No, I did not and this has been a source of some confusion. Would you like me to deal with that now?
Q We might as well deal with it now because we are going to deal with individual cases later. Deal with it generically now.
A You will have seen very stamps in the records referring to the “Wakefield Clinic”. Neither Professor Walker-Smith nor I really have any idea how that came about. It certainly was not my clinic. I never had clinical responsibility for these children. We believe, or I believe because I cannot speak for Professor Walker-Smith, that it was an administrative action on behalf of the nurses who run the outpatients clinic and potentially came about because Professor Walker-Smith had not only a paediatric inflammatory bowel disease clinic, a paediatric food allergy clinic and a general paediatric gastroenterology clinic and, in order to differentiate the clinic that saw the autistic children in particular from these others, it was given by the nursing staff the label “The Wakefield Clinic”. There is no other connotation associated with that name.
A SPEAKER FROM THE FLOOR: Excuse me, could I interrupt. I have some very important evidence to what Dr Wakefield is talking about.
THE CHAIRMAN: I am sorry but may I stop you there because I do not think that would be allowable. These are proceedings which are run under rules and regulations prescribed within the law. I am afraid that I cannot ---
A SPEAKER FROM THE FLOOR: Is it possible for me to give it to somebody?
THE CHAIRMAN: I am sorry, I will have to ask you to keep quiet.
A SPEAKER FROM THE FLOOR: I am sorry about that. I am not sure of the procedure.
MR COONAN: Sir, I was going to make a suggestion. I have one more small topic to do and then I will have completed section one of the route map and, if you were thinking about a break then, that would be convenient for me.
THE CHAIRMAN: I think that this will be appropriate because I feel, particularly when the doctor is in the witness chair, that we really need to be quite careful to make sure that we do not expose him to undue stress. There is always a stress involved.
MR COONAN: It is not so much that, it is just that I was coming to a convenient moment.
THE CHAIRMAN: I think this will probably be an appropriate time for our benefit as well as, I am quite sure, for Dr Wakefield’s benefit.
MR COONAN: May I then deal with the last aspect of section one. (To the witness) Dr Wakefield, I do not know whether it is in front of you or you can be given it but I wish to refer to the yellow pages relating to the charges. (Same handed to the witness) I want you to look, please at heads 1 and 2. Heads 1(a), (b) and (c) are admitted as statements of fact. You can see that on the document. They were admitted on your behalf on the first day. Head 2 remains not admitted. In the light of your evidence, I would like you to assist the Panel, please, as to the essential basis why you do not admit head 2 as drafted.
A There are three elements to this, Mr Chairman. The first is the word “stipulation”. No such word appears in any description of my job. The second is the emphasis of “any involvement” and I believe that to be over-emphatic and potentially pejorative, and I think the third thing is that it required for me to define what I understand by the term “clinical management” and I have done so.
Q Again, if you would like to turn up – keep that page open – page 40 of volume 1 again and I look again at the last four or five lines that you have looked at and commented on already. If you look at heads of charge 2, do you find the word “any” in head of charge 2 replicated on page 40?
A No.
Q Do you maintain the position that you do not admit head of charge 2?
A That is correct.
MR COONAN: Sir, that is all I ask and that, I think, for my purposes completes section one of the route map.
THE CHAIRMAN: Thank you very much, indeed. According to my watch, it is about 11.05. We will now break for a short while and resume at 11.25. (To the witness) Dr Wakefield, I remind you that you are under oath and therefore, during this break, please make sure that you do not discuss this case with anyone including your lawyers. I am quite sure that someone from the office will look after you with refreshments during this break.
(The Panel adjourned for a short while)
MR COONAN: Dr Wakefield, we are going to move on now to section 2 and I am going to ask you some questions in general terms about your role as a researcher, so that we get a flavour of the relevant personnel, how you interacted with them and so forth.
First of all, would you deal, please, with the various personnel, Professor Revell, Professor Fine and Professor Pounder and what their roles were during the period from, say, 1994 to 1998.
A Certainly. Professor Revell was the Professor of Histopathology; he took over from Peter Scheuer. The unit had an expertise historically in liver disease but Professor Revell came in as new blood with a particular interest in bone and joint disease and therefore we did not directly share any overlap in our working relationship. Professor Roy Pounder is an academic gastroenterologist with a large clinical practice in peptic ulcer disease and inflammatory bowel disease and he was my direct line manager. Professor Fine was his superior and was the overall head of the joint Departments of Medicine of UCL and the Royal Free.
Q Who was the Professor of Histopathology?
A Professor Revell.
Q Were the two departments, medicine and histopathology, sited together?
A No, histopathology was on the second floor of the hospital and medicine was on the tenth floor of the hospital.
Q Where was your office?
A My office was initially on the second floor. I had a laboratory on the second floor as well in the Department of Histopathology and laterally I moved to an office in the Department of Medicine where I also had a laboratory.
Q Just so that we understand it, physically, where were the wards in relation to where your office was and the Departments of Medicine and Histopathology were?
A The wards were on the tenth floor.
Q In some of the documentation we have looked at already, principally Professor Fine’s letter, there is a reference to a team of researchers. Can you help the Panel about that. Were you head of the team of researchers?
A Yes. One has to understand that this was a collaborative group; I had no direct line management for many of those collaborators. They are professors and senior lecturers in their own right in collaborating institutions. I bought them together under, if you like, a common umbrella of the Inflammatory Bowel Disease Study Group specifically for the purpose of contributing their respective expertise to answering the problems that we had raised.
Q Let us look at the IBD Study Group. When was that set up?
A I think it was established shortly after my appointment as a senior lecturer. I do not have the documents in front of me, so I cannot be absolutely certain.
Q Did it have any connection with any of the publications that you have highlighted?
A Yes, it did. Following the publication of the first Lancet paper on the possible vascular basis of Crohn’s disease, the group was then formed and subsequent papers were published under the title of the Inflammatory Bowel Disease Study Group.
Q So that we can get an idea of the publication you are talking about, do you still have the CV there?
A I do.
Q Would you turn to page 8 – and this is in D2 now at tab 9.
A This is paper 8?
Q Yes, paper 8. I think you are saying to the Panel that it was set up following that paper. Again, when we touch on matters of science, can you take this fairly slowly because the subject matter, if you do not mind my saying so, is a little dense. What was the IBD Study Group set up to do?
A Broadly, it was set up to investigate the origins, the cause if you like, and the mechanism of inflammatory bowel disease, Crohn’s disease and ulcerative colitis, two related chronic inflammatory bowel diseases.
Q As we will hear, this was clearly set up before Professor Walker-Smith ever came to the Royal Free.
A That is correct.
Q Did you have in that group before 1995, before his arrival, his equivalent as it were at that early stage?
A No, we did not.
Q Within that group, what was your specific role as opposed to being head or director or chair in terms of your everyday activity?
A My role would involve the generation/articulation of hypothesis related to causation and mechanism of these diseases. It would require communication and interaction with my immediate staff and collaborators to seek input and criticism on those ideas and their ultimate formulation into either a grant application or a paper based upon the data that derived from those studies.
Q Would you have any direct or indirect role with the histopathologists?
A Very much so, yes.
Q How did that work? Again, speaking generally now.
A A large part of my work involved tissue analysis and, in order to examine the possible vascular blood vessel origins of Crohn’s disease, that really was in many respects a histopathological exercise and one of the key players in that was Dr Paul Dhillon, now Professor Paul Dhillon who is an outstanding histopathologist but also a doctor with a particular interest in bowel disease.
Q It might be timely to remind ourselves as to what histopathology is.
A Histopathology involves the microscopic examination of tissue sections that are cut from either biopsies or larger tissues taken from patients at surgery for the purpose of making a diagnosis or staging a disease, for example such as colon or breast cancer, and determining again response to treatment.
Q Would you yourself actually look at tissues?
A Very much so. It was a particular interest of mine although I had no role in making any clinical diagnosis. It was an essential part of the work that we did and indeed we introduced some novel applications of techniques for perfusion fixing tissues in a way that removed artefact so that, when they were looked at down the microscope, they resembled far more the state that they were in in the living patient than after removal from the body.
Q What about the equipment that was available to look at the tissues?
A This involved an array of different microscopes which enabled you to look at different things. Electron microscopes that allowed you to look at things at very, very high power and look at the cellular and sub-cellular structures. Those are the sorts of routine pieces of equipment that we would use on a day-to-day basis.
Q May we turn to look at some of the other personnel and I am going to take this from about September/October 1995 because, as the Panel have heard, that is when Professor Walker-Smith joined the Royal Free. How did it come about from your understanding and knowledge that Professor Walker-Smith joined the Royal Free?
A The Panel may remember that healthcare underwent reorganisation under Professor Tomlinson some years ago and I think that this was certainly around or before 1994. I was aware of Professor Walker-Smith. I hope I do not embarrass him by saying this but he was effectively the founding father of paediatric gastroenterology as far as I was concerned and many other people were concerned and had an outstanding reputation in the field. At that time, I became aware that both St Bartholomew’s Hospital where Professor Walker-Smith worked and Hackney Children’s Hospital were under threat of closure and it seemed an extraordinary situation to me that this world-renowned unit was going to lose its clinical base as a result of this rationalisation. The Royal Free was not similarly under threat and so I took it upon myself to call Professor Walker-Smith, I think it was around Christmastime 1994 – I stand to be corrected on that – and suggested the possibility that he might like to bring his group together, quite independently of me, to the Royal Free to continue his clinical and research activities which I saw as absolutely essential. I think that really, in summary, is how it came about.
Q Quite apart from your estimation of Professor Walker-Smith’s reputation, did you know any other members of his team at that time who were at Barts?
A Yes, I did. I was aware of Dr Simon Murch; he had published some fascinating work, particularly in The Lancet following up independently but very much in line with or congruent with the work that we were doing on a possible vascular basis for Crohn’s. Dr Murch was a very good researcher and was part of an outstanding team of clinical scientists under Professor Walker-Smith and it seemed that it would be a tragedy for that team to be disbanded, and that it would be possible if they came to the Royal Free to keep them together under one group.
Q Prior to the time that Professor Walker-Smith joined the Royal Free had you and he worked together on any of the publications that you are able to identify?
A No, not at all, I think we had had very little communication.
Q As it came to pass Professor Walker-Smith and, as he then was, Dr Murch joined the Royal Free. Of some of the other personnel, Dr Thomson, where did he arrive from?
A Dr Thomson came to the Royal Free soon after the transfer. He came – again I stand to be corrected – I believe from Birmingham with a particular expertise in endoscopy and colonoscopy, and I was not aware of him before that time.
Q Dr Berelowitz, did you know of him before September/October 1995?
A Only by name.
Q Dr Sue Davies, did you know her?
A Sorry, Dr Berelowitz I did not know of for the first many years that I was at the Royal Free. I likely became aware of him during the course of 1995 as I became more interested in the issue of developmental disorders in children. Sue Davies, again I think Sue Davies joined the Royal Free. I knew nothing of her before that time and at some stage, I think largely because of the work with the children with autism, she became closely associated with the group.
Q Dr Harvey, was he there already by October 1995?
A Yes, indeed.
Q What was his role, clinical or otherwise, up to that stage?
A I knew of Dr Harvey, clearly. We had no interaction prior to the referral of children with developmental disorders but he is a senior consultant neurologist in the hospital.
Q And Dr Lloyd Evans?
A I had no knowledge of Dr Lloyd Evans until I was asked to try and engage him in the work by Dr Berelowitz.
Q Finally for my purposes, I think you have referred already to him, but Dr Dillon, was he already there by October 1995?
A Yes, he was, and I had had a long-standing interaction with Dr Dillon in the context of inflammatory bowel disease.
Q Linked with that, what about Dr Andrew Anthony?
A Dr Andrew Anthony was a trainee in clinical histopathology and then he transferred to experimental gastroenterology and worked on my team. He came from King’s and worked on my team for many, many years as an outstanding experimental pathologist. He has now returned to the clinical arena and I think he may even be a consultant by now.
Q That is, just in general terms, the shape of personnel and your role as a backdrop before we begin to look at any of the detail, but just one other aspect of your work as a researcher relates to the guidelines that may be in existence or were in existence at the relevant time. Some guidelines have been collated together and they appear in volume 4 of the Panel bundle; can we just very briefly look at that volume. Do you have that there?
A Yes.
Q The first tab, just to look at, is tab 3, “Research involving patients” published by the Royal College of Physicians in January 1990. In relation to your activities during the relevant period – and for these purposes I am going to take it as between 1995 to 1998 – were you aware of the content of this document?
A I was aware of its existence because my guidance in matters of ethics and clinical research came from Professor Roy Pounder who was a Fellow of the Royal College of Physicians. We will have referred to elements of this document; I certainly have not read it all at any stage, but we will have referred to specific elements of it in the design of particular studies or when particular questions arose.
Q I am not going to take you to any detail of this at all but I am going to ask you this in general terms. Have you looked at this policy since that time, at least for the purposes of this case?
A Yes, I have.
Q What do you say to the Panel as to whether or not you, in your view, complied with the guidelines of this document?
A In the conduct of our research at the Royal Free involving NHS patients we complied, in my opinion, entirely consistently with this document.
Q Tab 4 relates to the practice of ethics committees, as does tab 5. Were you familiar with those two documents at the time with which we are concerned, in other words between, say, 1994 and 1998?
A I cannot say specifically that I remember these documents.
Q Similarly tab 8, the same point.
A The same point. Again, we were given a brief instruction manual from the Royal Free ethics committee which we used as our template or our guideline, if you like, and that to some extent removed the need to go to these documents in detail but certainly, again, when ethical issues arose my guidance was Professor Roy Pounder in the first instance.
Q Is that the document that Dr Pegg referred to which he said was no longer available?
A That was attached to the pro forma document, yes.
Q I want to move to a wholly separate small topic of funding generally. Where were you paid a salary from?
A I was paid a salary from the University of London via the Royal Free Medical School.
Q So far as research generally is concerned would that always or sometimes involve the generation of funding or grants for that research?
A Yes, research cannot be conducted without research funding. It is the duty, the responsibility, of the head of the team usually to identify sources of research funding to write the grants and obtain that funding, and that then goes to employ non-permanent members of staff such as lab technicians or research fellows for a defined period of time in order to conduct a particular piece of research.
Q So they have to be recruited.
A Yes.
Q Again, speaking generally, where would the funds once granted be paid?
A They would be paid into the Royal Free Hospital School of Medicine for administration by the finance department such as, for example, salaries, reagents, pieces of equipment, anything. There were also the special trustees which was an alternative source where one could place research funding and was administered, to my belief, in exactly the same way.
Q The next small matter again is in a general sense patents. We will look at these in detail later but how did it come about that in the field of research, certainly in the Royal Free, patents were on the agenda?
A There was a period in academic medicine when – I think it was during Margaret Thatcher’s era – medical schools were told that it was their responsibility to identify intellectual property, discoveries that might be of potential value, that might bring in revenues to the medical school, that may be used to conduct further research or bring benefit to the medical school in other ways. It was passed down to us that the duties and the responsibilities of the individual researchers were to identify, on behalf of the medical school, what might constitute intellectual property and to protect that in the interests of the medical school. There was very little guidance on how that should be done but it clearly involved the issues of copyright or patent.
Q In terms of protecting the intellectual property it could be, is this right – you tell us if it is or not – exploited on behalf of the school?
A Correct.
Q That is all I am going to ask you about section 2, I am now going to move to section 3. I want to ask you globally this question, Dr Wakefield: of the research and development of your or the team’s, however you want to put it, hypothesis or hypotheses – and I want to take you to the end of 1995 for the purposes of this section – I am going to ask you please to look again for these purposes at page 8 onwards in the CV, D2, tab 9. Do you have the CV there, Dr Wakefield?
A I do.
Q For the purposes of addressing this question I am going to take you to such seminal studies that you had been involved in or were aware of, up to about the middle of 1995. Can I start with the first document you identify, which is publication number 8 on page 8 of the CV. The title, for the purpose of the transcript, is “Wakefield and Others: The Pathogenesis of Crohn's disease”, published in The Lancet in 1989, is that right?
A Correct.
Q I am going to avoid having to look at these documents, so if it becomes necessary then of course we can let the Panel have them, but I want you please to tell the Panel what these publications told you so that we build up a picture of the hypothesis that you arrived at later in the year, do you follow?
A Right.
Q The starting point is publication number 8; what did that tell you?
A Working in small bowel transplantation I became aware of similarities between the rejecting graft and the appearance of Crohn's. A large part of graft rejection involves an attack against the blood vessels of the graft, particularly in the model that we were looking at. Was it possible, therefore, that Crohn's disease rather than being primarily a bowel disease was actually a disease of the blood vessels that supplied the bowel? This is a small leap in terms of distance but conceptually it is a huge leap. What we did is to develop a number of techniques which allowed us specifically to look at the tiny blood vessels that ramify through the intestine and to demonstrate that very, very early on in the course of the disease these blood vessels were damaged, they were blocked off – rather like a heart attack but something that was taking place over a much longer period – and they were being destroyed or damaged by a particular disease process. This disease process, the granuloma or granulomatous reaction that you have heard about, is in simple terms a response of the body to get rid of something or to contain something that it cannot effectively get rid of, and in doing so, in trying to get rid of it, it causes damage to the host tissue itself. Clearly, causing damage to the blood vessels of the bowel could be catastrophic, leading to death of the bowel tissue itself. That in essence is what that first study showed us, that very early on there was this blood vessel injury.
Q Did that lead to any particular programme?
A Yes, it did, it shifted the emphasis. Crohn's disease and ulcerative colitis have all the characteristics of an infectious disease process or processes. Historically the belief had been that the infection was coming from the lumen of the intestine, through which the food passes, and this shifted attention away from that to the possibility that it was a blood-borne infection that was lodging in the blood vessels to the bowel. That completely changed the perspective of what that infectious agent might be and so I went looking for evidence of infections that had a propensity to infect the blood vessels of the bowel and cause this kind of damage. Measles virus was top of the list.
Q Was a programme set up to deal with that inquiry?
A Yes, it was. We looked for a number of infections but measles was top of the list and we exploited a number of techniques that enabled us to look in the tissues themselves for evidence of measles virus or elements of measles virus.
Q Would you turn to page 9 of the CV and look at paper 27? Is that the link with what you have just been saying?
A That is correct. At this stage it was essential to recruit to the collaboration experts in measles virus detection, and these included Dr John Stephenson at Porton Down, at the Centre for Applied Molecular Research, and Dr Louise Cosby from Queen’s University, Belfast. They individually, independently, had techniques which would help us answer this question and, using those techniques, initially by sending tissues to Dr Cosby in Belfast, she found evidence of the virus, and then we repeated it at the Royal Free. Similarly with Dr Stephenson, we looked for evidence of the measles virus protein and, certainly, the data generated from that was consistent with measles virus being present. That did not make it the cause but it certainly made it a very interesting candidate.
Q Just in a word – it may be obvious – were there public health ramifications potentially from that evidence?
A Not directly; however, one had to judge it against the background of what was happening to these diseases at the population level. Undoubtedly there had been a very large increase in the numbers of cases of Crohn's disease and ulcerative colitis, but Crohn's in particular, being diagnosed in the population. Crohn's is a disease of the latter half of the 20th century, virtually unheard of before that, and now the lifetime cumulative risk for developing Crohn's disease is about one in 100, so really it had gone from being a very rare disease to a relatively common disease. That required explanation in the context of a possible causal association with the measles virus.
Q Again I am just dealing with this chronologically for the moment. Whilst that document 27 was published in 1993, one of the documents you highlighted earlier this morning was document 36, when Ekbom is the first author. Was Ekbom a Royal Free practitioner?
A No he was from the University of Uppsala in Sweden.
Q Did that publication shed any further light on the matters which you had identified in document 27?
A Very much so. If there was a causal relationship between measles virus and inflammatory bowel disease it could not be a simple one. Measles was ubiquitous; why was everyone not developing inflammatory bowel disease? What we knew about measles is it is the pattern of exposure to the virus that determines the outcome, for example, exposure very early in life, under the age of one, poses a greater risk of chronic infection and a fatal encephalitis, SSPE that we have heard talked about. So, taking that as a model the question is, is there an association between the pattern of exposure to measles and the development of a later disease. The majority of children clearly would get measles at school at a time when the outcome might be entirely different: acute measles, recovery and no problem. Dr Ekbom in Sweden had access to outstanding epidemiological records or data, where he was asking the question quite independently of us, “is there an association between early infectious exposure and later inflammatory bowel disease?”, then independently he came to the conclusion that there was, and that virus was measles and so we collaborated together on this matter to look at that further.
Q So as of 1994, which was the Ekbom publication, what was the shape, if any, of hypothesis at that stage?
A The shape of the hypothesis was that an atypical and unusual pattern of exposure to the measles virus in some form, either early in life, in utero, perhaps in combination with another infection, might be a risk factor for later inflammatory bowel disease. That disease may not develop for 30 years but, like chicken pox, it might sit around and come back and shingles much later, and that that infection set up chronicity, established itself in the blood vessels of the bowel and later damaged those, resulting in the clinical features of Crohn’s disease, or ulcerative colitis.
Q So that was the hypothesis?
A Yes.
Q The next milestone was document 49: again, can you just summarise it for us? What did that tell you? This was published in The Lancet, one of two publications in The Lancet, in 1995?
A This was a study of ulcerative colitis and Crohn’s. Ulcerative colitis and Crohn’s are related diseases. They have distinct differences but a lot of overlap and one of those overlaps is they may occur in the same family, indeed, identical twins we had as patients, one twin had Crohn’s, the other had ulcerative colitis so they were in some way related. One of the characteristics of ulcerative colitis, when you take the colon out of a patient with severe colitis is there is a dramatic cut-off in the disease. There can be death and damage and ulceration to a discrete point and then it stops dead, and what was fascinating to us was that that junction, why did it stop dead, had never been explored. What we found, the hypothesis that we tested, is that that cut-off was a particular territory of a blood vessel, that one blood vessel supplied an area that got damaged and destroyed and the other was completely protected, and so doing some radiographic studies we demonstrated that this cut-off was a watershed, if you like, of two different blood vessels and that leant credence to the idea that there was a common blood vessel of vascular origin that was the link, if you like, between Crohn’s Disease and ulcerative colitis.
Q The last public that I want to ask you to comment on is No. 53, also a Lancet publication in 1995.
A One of our concerns was Crohn’s Disease does not usually start until you are 30, that is the peak age of onset. Crohn’s Disease in children historically was extremely unusual and in discussion with Professor Walker-Smith his first referral with Crohn’s Disease occurred in the 1960s. Crohn’s in adults had been around for a lot longer, and therefore the question arose … I should say there has been a substantial increase in the incidence of Crohn’s in children from that point on, and that has been seen in many, many developed countries. Therefore, the question was had we changed the pattern of exposure to measles in such a way that we have incurred a greater risk, and is that change in pattern, the shift from natural measles to vaccination?
Q What did document or publication 53 actually tell you, because that is obviously written – you will see the title in terms of a question, what did it tell you?
A What it suggested, it showed that there was a significant association between exposure to measles vaccination and inflammatory bowel disease compared to the unexposed population, those who did not get vaccinated but had natural measles. This same association was not seen for celiac disease, if you like, as a controlled disease.
Q If you take into account the development of the work in those publications that you have highlighted and factor in, if you will, any additional reading that you had done, what was the high water mark of your thinking in these areas by about the middle of 1995?
A We were concerned that there may be a causal association between a changing pattern of exposure to measles and these diseases, and clearly that had major implications. The data was by no means conclusive. It is interesting to note, and I know that it has been referred to in these proceedings, that there has been little or no support for this, in fact we were not the first to demonstrate measles virus in Crohn’s disease. I presented at a lecture in Wertsberg in Germany some years ago to a measles group and I was told there that they had had a Japanese researcher some years ago, Professor Miyamoto from the Wakayama Institute in Japan, who had identified a quite separate measles virus protein in Crohn’s Disease tissues and he subsequently published on this, so we were not the first. So what you had, if you like, was independent groups, the Wakayama group, our group, Ekbom’s group and Balzola in Turin suggesting that there was an association between measles virus and inflammatory bowel disease, and clearly that needed to be looked at in some detail.
Q So that we are clear about this, so far no question of autism at all?
A None at all.
Q So far no question of regressive behavioural disorder?
A Not at all, no.
Q Just before we move to the next stage, the 1995 publication at document 53 I think in fact is in Volume 1 at page 62, can you just confirm that, Dr Wakefield, but it is in a galley proof form attached to the previous page, which is a letter which we will come back to look at shortly, but in so far as it may be easier to read and look at the final version I am going to invite the Panel to receive that paper in its proper published form, not just simply in its galley proof form. Sir, it is available for distribution. (Same handed and marked as tab 10/D2). Since I have been asking you about the high water mark point in mid-1995 we see on the first page of this 1995 publication, under the summary heading, just cast your eye down because I will not take the time and trouble to read it all out but does that reflect what you have just been telling the Panel?
A Yes.
Q The next stage is to look at the question of introduction of autism and behavioural disorders against the background of the studies which you have identified for us thus far. Again, I am going to take this up to the end of 1995. Was any publicity given to the 1995 publications?
A Yes there was, there was a press briefing at the Royal Free and it received considerable attention in the national media.
Q How did the press briefing at the Royal Free come about, if we can just deal with that for a minute?
A When, as I understand it, Professor Zuckerman moved to the Royal Free he established a Media Committee and I was aware of that committee. The purpose of the Media Committee was to promote within the institution, beyond the institution, findings of significance, of importance that may attract attention and funding to the hospital and it was identified by that committee that this might be such a publication and so we were called in and we had several meetings, and it was decided to hold a press briefing and that was due to coincide, booked to coincide with the actual publication of the paper.
Q Media coverage what about that?
A There was extensive media coverage. It was arranged by the Media Committee, they sent out an embargoed press release and the media were invited and they came and it was deemed to have been successful. I have no yardstick against which to judge its success or failure.
Q Was there any television coverage?
A Yes.
Q Do you remember any particular piece of coverage?
A There is nothing that I remember in particular, I have to say.
Q At any rate, if I can deal with it in terms of publicity or media coverage generally speaking: what was the first thing of any significance that happened following the publication of this paper?
A The major and most important thing was that I received a series of calls from parents, some reporting that their children had developed Crohn’s Disease or inflammatory bowel disease after vaccination that they thought this was associated, but more significantly parents, and one parent in particular on 19 May 1995, Mrs 2, being the first parent to call me reporting that her child had regressed into autism following the MMR vaccination and I remember saying to her, “I’m sorry, I have no idea how to help you. I know nothing about autism”, it was so rare. When I was at medical school we were not even taught about it, and she said, “My child also has terrible bowel problems and I believe that the bowel problems and the behavioural problems are related, when one is bad the other is bad; when one is good the other is not so bad”. She was an extremely articulate woman. She told a story which made a great deal of sense, particularly to gastroenterologists because we had for some years, many years, been aware that with certain gastrointestinal liver diseases the brain is impacted, and the patients become, for example, encephalapathic, their brain function deteriorates with their bowel disease, so the gut/brain link in gastroenterology to gastroenterologists had been there all along and one such example is celiac disease. Another example that people are very aware of is liver failure. The more jaundiced you become the more uncoordinated and disorientated you become; you become ultimately – leading to coma and death, and the way that you treat this to reverse the coma, to reverse the disorientation, to reverse the confusion, you treat the bowel, so the bowel/brain link to the gastroenterologists made a great deal of sense. I had no knowledge of autism or any basis for it in autism but the story was compelling and certainly merited attention.
Q You some of other parents who were contacting you. Did they tell you a similar story?
A Yes. Mrs 2 said to me that she was in contact with many parents who had had exactly the same experience; that their children had developed chronic bowel problems and autistic regression, often following the MMR but not necessarily, and that these two they believed were linked, and that in seeking help for the gastrointestinal aspects of their problem they had largely been told, “Well your child is autistic, they are bound to have bowel problems” and that I have to say did not make a lot of sense to me in the field of gastroenterology.
Q What advice did you give Mrs 2, if any, at that stage (we are still in 1995)?
A I really could not offer anything at all. I had no clinical role but I knew someone who could, and that was Professor Walker-Smith.
Q Who was still at Barts?
A Who was still at Barts, and if anyone could shed light on this problem it was going to be him, and my only concern at that stage was for the clinical wellbeing of this child and therefore I said to her, “I suggest that you request of your doctor a referral to Professor Walker-Smith at Barts who may well be in a position to shed some light on this.”
Q Did you think, or do you now think, that in giving her that advice that you have just explained you were in any way acting improperly, or unprofessionally, or in breach of your terms of appointment?
A Absolutely not. I think that if I had not given her that advice; if I had not responded in the way that I did then this Committee would have every reason to have me before it. It is my duty as a physician and as a human being to respond to the plight of this mother, and if I can point the direction to someone who might be in a position to help her then that is my absolute obligation.
Q Having given her the advice that you did, did you have any contact or role at that stage with Child 2’s general practitioner?
A I do not think I had any contact with him, no.
Q We have heard that the doctor who referred Child 2 was Dr Wozencroft. Did you have any contact with Dr Wozencroft?
A No.
MR COONAN: Just so that this is uncontroversial, in fact it may be helpful if I introduce this now. Sir, we have a schedule which sets out the referral and admissions of each of these children and I shall be referring to it later on. The other parties have seen it. It is intended to be a working document. If there is any error, it can be corrected. It may be helpful if it is distributed now. (Same handed to the members of the Panel and marked as D8)
(To the witness) Dr Wakefield, I just want for our present purposes to look, please, at Child 2 and it is simply for reference purposes at this stage. We have heard evidence from Dr Wozencroft that Child 2 was referred to Professor Walker-Smith by letter dated 29 June 1995 and that the first outpatient appointment for Child 2 was on 1 August 1995. At that stage, June/July/August 1995, what was the impact of what Mrs 2, possibly others, had been saying to you on the development of the hypothesis as it stood in the earlier part of the year when The Lancet paper had been published? Do you follow the point?
A It was absolutely fundamental to the articulation of the hypothesis. Here is a mother, amongst other mothers, who had taken it upon themselves to educate themselves about how the gut and the brain might be injured and interact to produce the condition that their child suffered from. I will give you an example. Mrs 2 said to me, “I think this may be due to an abnormality in his vitamin B12 absorption”. That made a great deal of sense because vitamin B12’s malabsorption from a diseased intestine is something that we know a great deal about and vitamin B12 deficiency can lead to major neurological problems. So, the common denominator plausibly in these children might have been a vitamin B12 abnormality and that formed part of the hypothesis. Other things that the parents reported over the same period, often following the measles, mumps and rubella vaccination, often regression following in some cases measles infection itself. These are interesting and plausible because, as we know, measles and measles-containing vaccines can lead to inflammation of the brain, encephalopathy, and deterioration. So, was this again another common dominator in these children or an alternative common denominator that needed to be looked at? As I have said before, the key to the formulation of medical hypothesis must come – must come – by necessity from the history and the examination of the patient and, if they do not, then there is no foundation for that hypothesis because that is where it will stake its roots and this is a classic example of that process, the iterative nature of science.
Q I am not concerned currently with the detailed assessment of Child 2 and subsequently the admission of Child 2. I am just concerned here, as I have said, with the development of your hypothesis. As the Panel have been told, following the outpatient appointment on 1 August 1995, Child 2 was not then admitted and Professor Walker-Smith – and it is a matter of record – took the view that there was no evidence of inflammatory bowel disease. Do you remember that evidence?
A Absolutely.
Q Did you continue to be in touch with Mrs 2?
A Yes, I did. Again, she continued to make contact with me: (1) to bring me up to date with her appointment with Professor Walker-Smith which was the opinion that I had suggested and I was perfectly content that he had seen the child and assessed Child 2. He had left a question mark over the origin of the symptoms in Child 2. Nonetheless, I had helped to that extent. Other parents made contact as well and their stories I shared with Professor Walker-Smith and so the process developed.
Q Professor Walker-Smith joined the Royal Free about two months later following the outpatient appointment. Did you raise any particular matter in relation to what the parents had been saying to you with him?
A We were in discussion about the transfer and about these children and it was decided, I believe and I stand to be corrected, that there was a need to take this further clinically, that there was something going on that Professor Walker-Smith at this stage had not got to the bottom of. Nonetheless, it made sense to accept any referrals of these children after Professor Walker-Smith had transferred. There seemed little point to start seeing the child in one hospital and then continue seeing them in another. So, a decision was made by Professor Walker-Smith to see these children, or any children with similar symptoms who merited an outpatient appointment, beyond the point of his transfer.
Q Did you have any discussions with Professor Walker-Smith about the autism element of the histories that you were receiving from parents?
A Very much so. It turned out to be an interest of Professor Walker-Smith’s already and he published in The Lancet some years before when he was in Australia on a paper that had linked possible bowel disease to autism and so had, if you like, predicted this possibility some years before.
Q Let us just stand back for a moment because we have been looking at the chronological development. At about the end of 1995, can you set out for the Panel the proposition or hypothesis that you were interested in investigating by that stage.
A Yes. We believed that there may be a group of children who for some reason, either genetics or other, were susceptible to a peculiar adverse reaction to measles in some form, either wild measles or a measles-containing vaccine, and that this process, this disease if you like, involved possible infection or damage to the intestine that led secondarily to an injury to the brain or alternatively, at the same time that the bowel was injured by this virus or these viruses, the brain was similarly injured. The possibility also that if it were a primary bowel disease, the injury might be mediated by an abnormality of vitamin B12 absorption such that the neurological consequences flowed form that and that, in essence, was the hypothesis. We sought to examine or we proposed an examination of the possibility that an underlying genetic abnormality might relate to a specific set of proteins in the blood called “complement” – and I will not go into details of what they are but I will be happy to do that if anyone asks – because workers in the United States of America had associated genetic deficiencies in these complement proteins with autism or regressive autism.
Q When you say “we”, to whom are you referring?
A By this stage, it was a growing group of people who initially started with my interaction with Professor Walker-Smith that grew to involve members of his team and my own team to a greater or lesser extent and it was fairly amorphous at this stage but that was the core of what we felt might be going on.
Q Was the development of that hypothesis that you have set out for the Panel arrived at before you had any contact with Richard Barr at Dawbarns?
A Absolutely. My first contact with Richard Barr at Dawbarns was early in January 1996.
Q I will come on to deal with your contact with him later. Again, by this stage, the end of 1995, were you aware of a group called Jabs?
A I must have heard of Jabs, yes.
Q Were you aware that any of the parents who contacted you were in possession of a Legal Aid certificate?
A Absolutely not. Litigation was not even mentioned.
Q By the end of 1995, had you drafted any document which was going to address the hypothesis that you have just described?
A Yes, we had. Through a serious of meetings following Professor Walker-Smith’s transfer, we had set out and I had drafted a protocol which involved clinical investigation and some research aspects and I think that the existing reference to that now is in the application for ethical committee approval 172/96.
Q Let us just identify that before you comment further because we are going to have to look at this in a different context. Volume 1. The sequence begins at page 200. That is the proforma for the purpose of the application and my question arising out of what you have just said is whether you can identify the document within this clip of material which was at least at some stage in the process of being drafted by the end of 1995.
A Yes, I can. On page 211, there is, I have to say, a rather inadequate draft form that was prepared as early as – and you can see the date at the bottom – 12 October 1995 which was the first, if you like, attempt to put this together, a new paediatric syndrome enteritis and disintegrative disorder following measles rubella vaccination and this is the one that Dr Pegg subsequently referred to as the one I think that needed amending.
Q I am not concerned with the application for the moment but, if you move on within this clip and start at page 212, was that a document which had been, as it were, drafted either in a previous form/earlier form in late 1995?
A Yes, that is the document to which that original information consent form page, the prior page, was associated but in a very much earlier draft.
Q We see – and again I am jumping ahead – an earlier draft of that which was in the hands of Mr Barr who sent it to the Legal Aid Board and we will look at that later.
A That is correct.
Q Again, what was the significance then of first of all addressing the hypothesis which you had developed by the end of 1995 and then creating a proposed clinical and scientific study at that stage? What were you then seeking to do?
A Do you mean by that what was I personally seeking to do or the larger group of collaborators?
Q I think that is fair observation. First of all, you personally
A What I was seeking to do was to take these parents’ stories at first hand apply whatever skills I had to determining its validity in terms of, could we shed light on the origins of their disease? Could we begin to understand its mechanism and possible causation in exactly the same way as we had addressed Crohn’s disease and ulcerative colitis earlier and, in doing so, could we help ultimately in treatment or prevention?
Q From your standpoint, addressing the elements of the hypothesis that you were particularly concerned about, would you classify that as research?
A Yes.
Q We have come pretty well to the end of 1995 in terms of your hypothesis and I want now, please, to turn to a separate topic within this section which is running in parallel with the development of your hypothesis and that relates to your relationship with the Department of Health, again taking the period up to exactly the same point in time, the end of 1995.
A Yes.
Q May we start, please, as long ago as 1992 and would you look at the Panel bundle volume 1 and start at page 12. These letters – and there are about nine or ten that I want to ask you to comment on – were either read out wholly or partly but many months ago and, in fairness Dr Wakefield, I am going to ask you to look at these and there may be sections that I will read out. The purposes of looking at this, although there is no charge in relation to this material at all, with you is so that you can explain to the Panel why it was that the letters were written and what you understood the response from mainly the Department of Health to be – do you understand? – and how it therefore influenced your thinking and your approach. That is the purpose of looking at this documentation. Looking at 1992, at that time, what was the nature of your research interests?
A By this stage we had examined the possible vascular origins of Crohn's and we had generated some preliminary data associating measles with that blood vessel injury, raising the possibility that we may be looking at a causal association.
Q I think in the third paragraph you flag up something that you told the Panel earlier this morning.
A Yes.
Q The increase as you judged it in the incidence of Crohn's disease in children over the past 15 to 20 years, is that right?
A In paragraph 3, yes.
Q Then over the page you set out the purpose of telephoning Dr Salisbury; can you just summarise your thinking behind saying this, Dr Wakefield?
A There was a potential issue – indeed there were two potential issues. One is that Crohn's disease was developing in children as a new disease that had only emerged since the introduction of the measles vaccine and therefore it raised the possibility that there may be an association between the two. In addition, in raising this possibility, there were implications for public health and I thought that Dr Salisbury, as he was then, would be interested in this matter as head of immunisation at the Department of Health.
Q In the middle of the first paragraph on page 13 you say:
“My concern is that although measles and in particular the vaccine may ultimately have no association with Crohn's disease whatsoever, what will be picked up by the press is the apparent association between the increasing incidence of the disease and the vaccine. Therefore I think it would be imperative for us to meet in the near future to discuss the way forward.”
Reading between the lines there, what were you telegraphing?
A What I was hoping to do was to establish some kind of working relationship or dialogue with the Department of Health that would help resolve this issue as expeditiously as possible, either to say yes, there is an association or no there is not in order to avoid a public health problem.
Q In the last paragraph on page 13 you raise the question of funding. The point was raised in the previous session that that might have been misplaced; normally the question of funding ought to be raised with the Medical Research Council. Have you any comment to make about that?
A Yes, indeed, and I accept that. I felt though that the Department of Health may be particularly interested in helping to resolve this question and that they may wish to allocate resources to it, either to conduct their own studies or to work with us on examining this issue. I was wrong and I accept that and the issue was not pursued.
Q Page 17, please. It is now seven months since the first letter. Again, I am not going to read it all out but what was the thrust or the reason for writing to the Department of Health – this was to Professor Peckham.
A I believe that Professor Peckham was in charge of health service research and someone had recommended that I write to him on this matter, particularly in relation to the issue of funding. That was the purpose of my letter.
Q If you look at the last paragraph on page 18, would you like to comment on that?
A As I say, we are now some months on and I am surprised, I suppose, at the apparent lack of interest from the Department of Health and I am trying to urge them to help resolve this issue as quickly as possible.
Q Then on page 19 you get a reply from the Department on 16 June 1993, and the view of the Department in the third paragraph is to the effect that it was felt that this was an area which merits further exploration.. Was that a response that you were pleased with at that stage?
A Yes, I regarded this as quite a positive response. I have to confess I am not sure why this line of inquiry faded out – we had a proposal prepared at that stage but there seems to have been no further correspondence beyond that stage and it would be most unusual, having requested funding and prepared a protocol, for it not to have gone to them, so I simply cannot say what happened beyond that.
Q If you look at page 21 this is your reply to that letter on page 19. You say:
“I am presently preparing an outline of our research programme which I will send to you in the near future.”
Are you saying that you did send that?
A If I said I would send it I think I would have sent it but, as I say, I cannot shed any further light on why this correspondence came to an end.
Q Can we move on to page 47? 4 October 1994, so it is now exactly two years since this correspondence started. Again, can you just take a moment or two, please, just to familiarise yourself with the contents of the letter – I am not going to waste time by reading it all out, it is probably quicker if you read it and then I shall ask you some questions about it. (Pause for reading). Have you read it?
A Yes.
Q Two points. You say at the beginning of the second paragraph that you are well aware of the value of measles vaccination. Was that true?
A Yes, indeed, and I had my children vaccinated with MMR.
Q As indeed you say in the same sentence. Then you say:
“However, you are currently conducting a programme of revaccination of children who were vaccinated in early life.”
Can we just pause there for a minute? We heard evidence from Dr Salisbury about the various programmes and so forth; can you remind us, what was the programme of revaccination about, was it MR, MMR and so on, can you just remind us?
A Revaccination for measles started in Sweden and was successful in getting rid of a lot of measles. This was not the policy in the UK prior to this time but there was a proposed programme of mass vaccination, a mass vaccination campaign, in the face of what was perceived to be a possible epidemic of measles that had been planned. This was to use the measles rubella vaccine rather than single measles or MMR. The rationale for that was not entirely clear but by this stage I had corresponded with Dr Salisbury two years previously, he had expressed interest in having a meeting but no such meeting had been convened and I had written again. We are now two years down the line without having a meeting, with further scientific data from my group and others making an association between measles and inflammatory bowel disease and, in the face of that, the government intending to do a revaccination programme. My specific concern, other than the fact that we had not been able to discuss this in a meaningful way, was that there had been no safety studies conducted anywhere in the world of two-dose measles vaccine regimes, and I had established this by speaking to the Swedish vaccine doctors.
Q Did you set out your concern in that second paragraph?
A Yes.
Q Because, as you say, at the time of writing this letter this was after the publication of the Ekbom paper which you have drawn the Panel’s attention to this morning, is that right?
A Correct.
Q As a footnote can you just help the Panel with the last two lines where you say this:
“I am even more concerned that re-challenge with the same antigen later in life will lead to the onset of Crohn's disease.”
What is that a concept of?
A If you are exposed to measles, let us say the vaccine, on one occasion you may establish a chronic infection, but it may be no problem at all. However, your immune system has been primed to respond to it. When you are re-exposed there is the possibility that the immune system will then attack the body at sites of infection and cause disease; this is not just a theoretical concern, this is a real concern, and that possibility had not, as far as I was aware, been taken into account in their deliberations about revaccination.
Q When you say on the penultimate line, “I fear we face a potential catastrophe in the form of an epidemic of Crohn's disease” was that an assertion that was honestly held by you at that time?
A Absolutely, yes.
Q Did you send copies of that to the Minister of Health, page 48, and to the Chief Medical Officer?
A Correct.
Q On page 49 and page 50 we see there that your letter that we have just been looking at at page 47 prompts an agreement in principle to arrange a meeting.
A Yes.
Q Were you pleased with that?
A In some respects, yes. However, the meeting was arranged to occur after the revaccination programme, somewhat defeating the object of the meeting.
Q At page 51 we see minutes of a meeting, again on Crohn's disease, because all this is concerning Crohn's disease, is it not?
A Correct.
Q Held on 10 January 1995. Again, it may be obvious but there is no harm in emphasising it, was this anything to do with autism, MMR or regression?
A No.
Q The last document I want you to look at at this point is at page 58. This is a letter written by you to the Deputy Chief Medical Officer on 26 January 1995, following the meeting we have just been looking at, and you say that the meeting did not, to your mind, provide a clear way forward. Again, in so far as it is relevant, Dr Wakefield, what did you intend to convey by that, what did you understand to be the position?
A The meeting was rather unsatisfactory. We were given 20 minutes each to speak on the different ideas about the cause of Crohn's disease. 20 minutes is not very long, but fair enough, that would have been possible except that Professor Herman Taylor from St George’s who was there, talking about a tuberculosis organism as a possible cause, was given an hour and a half to speak, which left no time for further discussion really, so it was a little frustrating in that respect. Nonetheless, there was no clear agenda that came out of that meeting, at least in the short term, that gave us a way forward, particularly cohesive interaction between the Department and my group and others that allowed us to work together to resolve this problem.
Q The last document, please, is at page 61 with the attached galley proof that I flagged up earlier at pages 62 to 68. It is dated 12 April 1995 and, again, perhaps I could take this shortly, I do not think anything turns on it. Did you send an advance copy of this 1995 paper to the Department?
A Yes.
Q What was your reason for sending an advance copy of that paper?
A At every stage we had tried to appraise the Department of Health in advance of publication of papers that might be of concern to them or involve them directly, and this was one such example of doing that, letting them know that this paper had been accepted by The Lancet, that it carried a message with a question mark that may be unpopular but nonetheless needed their attention.
Q Forgive me, I cannot remember if I asked you this but that paper in particular, might it have carried public health implications?
A Yes, indeed, it was suggesting, again as I say as a question, that there may be a possible association between exposure to measles vaccine and inflammatory bowel disease, and we felt that it was only responsible to let the Department know about that in advance of publication.
Q Again that brings me almost to the last question on this section, in your dealings with the Department between 1992 and 1995 did you feel then or do you feel now that you were acting in any way improperly or unprofessionally?
A On the contrary, we were trying at every stage to appraise them of our thoughts and the issues arising from those that we believed may have been of concern to them.
MR COONAN: Sir, I note the time. That conveniently completes that section and you may think it a proper moment to break.
THE CHAIRMAN: Yes, indeed. We will now break for lunch and resume at two o’clock. Dr Wakefield, once again may I remind you that you are under oath and in the middle of giving evidence, therefore please do not discuss this case with anyone.
A May I ask, is it possible to have lunch with my wife if we do not discuss the case?
THE CHAIRMAN: There is absolutely no problem about it but do not discuss about this case.
(Lunch adjournment)
THE CHAIRMAN: Mr Coonan, before you continue your examination in chief, can I make a request to you to try to finish today any time after 4 o'clock, wherever you find a natural break.
MR COONAN: Could you give me some guidance now, if it is your intention to have a break, so I can find a natural break in my questioning.
THE CHAIRMAN: I do not want Dr Wakefield to give evidence for two hours, I think that is too long, he will need a break, so anywhere in-between wherever you find a suitable point.
MR COONAN: If you leave it to my judgment that I will do that.
(To the witness) Dr Wakefield, the next stage is the material which is contained in what we have called section 4 of the route map, and I am going to ask you, please, about your research interests, and indeed your research activity, on the one hand and clinical activity on the other, and section 4 is concerned specifically with the period from January 1996 to August 1996, but so there is no mystery about it, the date of August is taken because you may remember there is a date of August on the first page of the EC application proforma, that is possibly taken arbitrarily but that is the way I seek to deal with it. Just by way of preliminary, when I ask you these questions I am deliberately not dealing at this stage with the Legal Aid Board and/or Dawbarns involvement because that is a separate issue which I will come to later, do you understand?
A Yes.
Q Nor is it intended to cover a detailed examination of the children’s cases because that is set out in section 9 to come later, so I am concerned with general propositions here: we were looking at the first part of section 3 and the development of a hypothesis and you had been receiving information from parents and you had discussions with Mrs 2 and those involvements, you have told the Panel, had influenced your thinking and the development of the hypothesis. When we turn in to the beginning of the new year, in January 1996, were you still in contact with Mrs 2?
A Yes.
Q Did you understand – and I am not tying you down to any particular week or month – the condition of Child 2 to remain the same?
A No, on the contrary, his condition deteriorated, clinically at least, according to his mother’s interpretation and her representation to me, with progressively severe gastro-intestinal problems, behavioural problems, often related to food and although his course had been fluctuating there was a definite downturn at some point in that year.
Q Did you continue to be in contact with other parents, or they with you?
A They certainly contacted me, yes.
Q Did the hypothesis that you had developed up to the end of 1995 remain as a working hypothesis?
A It was developed further in various respects, but the core hypothesis remained the same, yes.
Q Did you have any discussions with other people at the Royal Free at about the beginning of 1996?
A At some stage through discussions with Professor Walker-Smith’s team and myself it was decided that we needed to introduce an expert in childhood developmental disorder in order to help us understand this better. If Professor Walker-Smith’s team were going to see these children clinically, there were clearly other clinical issues that needed to be addressed, behavioural aspects for one, neurological aspects were another, and so what used to happen is that we would meet regularly, I would meet with – my team would meet with Professor Walker-Smith’s team – I think it was a Tuesday lunch time but again I stand to be corrected – on a regular basis to discuss matters of common interest, including this, and at some stage, and I think it was probably earlier than this, Dr Mark Berelowitz was recruited to help us and expressed an interest in doing so and became a collaborator on that programme. Likewise, Dr Peter Harvey. We did not have a paediatric neurologist at the Royal Free. I had approached, at Dr Berelowitz’s behest, I approached Andrew Lloyd-Evans but he was not specifically interested in taking part. Dr Harvey on the other hand was and agreed to become a collaborator on this project.
Q You have used the expression “project” and “programme”, I want now to stand back and examine, and for you to help the Panel, please, what it was that was in existence in terms of a structured project or programme by the beginning of 1996, or thereabouts, but in advance of the EC172/96 application. What was the nature of the structure or the approach that was being adopted?
A There was the coming together of two elements broadly, one the clinical investigations, the protocol for clinical investigation of these children according to what the clinicians perceived to be their medical problem. Then what I brought to it was certain research aspects, principally related to analysis of biopsy tissue, to look for evidence of viral infection, to try and characterise the disease process, any disease process that might be present in these children in the intestine and various other research elements which I am happy to discuss either now or later.
Q Let us just look at the clinical aspects of the protocol that you have described. What was it, as far as ulcerative colitis is concerned, what did you understand or understood then, what prompted the emergence of the clinical protocol?
A Firstly, it was the overwhelming clinical need that was perceived by the clinicians for the care of these children, and I have to emphasise that was the driving force throughout. These children were unwell. They suffered a variety of complex symptoms, many of which had eluded their own primary physicians and other experts, and those needed to be addressed in a comprehensive way.
Q I want to ask you how this was created, what was the process by which that was created?
A The way it was created was to bring in the relevant experts, such as Dr Berelowitz, Dr Harvey and others, and get their input into the various clinical elements that might be necessary and as is often the case, particularly in teaching hospital practice, this kind of clinical investigation is protocol driven, and I think Dr Casson has referred to just this, that there was a ward book for protocols, which is in effect, if you like, as I understand it, a check list to make sure that tests are covered or at least considered that may be clinically relevant and so this was the formulation if you like of a clinical and scientific protocol.
Q Did Dr Thomson have any role to play in the creation of that clinical protocol?
A Yes he did, he was extremely helpful and he had come, as I said I think, from Birmingham Children’s Hospital and one of the aspects that was under consideration is the need for the conduct of lumbar punctures in these children, that was the clinical aspect, and it was deemed necessary in the face of a child who was normally developing or had near-normal development who had undergone developmental regression, loss of skills, and Dr Thomson brought with him, alluded to, the Birmingham Children’s Hospital protocol, and this was a clinical protocol which described the tests that were necessary to be conducted in such a child, and in respect of lumbar puncture these included looking for lactate in the spinal fluid.
Q Just take this slowly.
A I am so sorry: lactate in the spinal fluid, lactic acid, as evidence of a mitochondrial dysfunction, a dysfunction of those sub-units of cells that are responsible for energy production. Also in that same protocol, under cerebrospinal fluid was analysis for viral antibodies. If I remember correctly it mentioned measles virus antibodies, so there were two elements, clinical elements of the Birmingham Children’s Hospital protocol that were entered into the Royal Free Protocol for the investigation of these children.
Q What was your own role (if any) in the creation of the clinical side of the protocol? I will come to the research side in a minute but what was your role in the clinical side of it?
A I had no specific role. My role was as a coordinating investigator who brought these elements together into a single document and my role beyond that was specifically in contributing the research aspects to that protocol.
Q We will deal with the research aspects in a minute. I want to ask you, please, about the question of disintegrative disorder and autism in relation to this clinical protocol – this is way before any EC172/96 application, do you understand?
A Yes.
Q What was the relevance, if any, of those features in this protocol? We have not talked about the operation of it yet, we are talking about the creation of it: what was the role of them?
A In terms of the developmental diagnosis, or possible developmental diagnosis, in these children there was one area where we felt we absolutely needed to bring in an expert and Dr Mark Berelowitz had worked as a protégé of Sir Michael Rutter and was able to help us on this, and he gave a presentation with a colleague of his, I think it was at one of our Tuesday joint collaborative meetings with Professor Walker-Smith’s team, and he produced a document, which I have no longer, which is a graph which described the developmental trajectory of normal children, of children with autism and of children with disintegrative disorder, or Heller’s disease, and he demonstrated that in children with autism the features are usually evident from very early on and there is failure to progress and ultimately the diagnosis is made. In contrast, in children with disintegrative disorder there was a period of normal development followed by regression and loss of skills, and he concluded, based upon this, that the best diagnostic label to apply to these children could be that of a childhood disintegrative disorder. I should just add, there were other reasons why he did that, and he referred to Sir Michael Rutter’s chapter in a textbook of child psychiatry, and in that it described the features that differentiate autism, classical autism from disintegrative disorder, and those included, for example, loss of faecal and urinary continence, or loss of bowel and bladder control. Ataxia, unsteadiness, the child becomes clumsy, they walk and then they no longer want to walk, they bump into things. They can eat with a utensil and then they cannot do that any more. They have poor hand/eye coordination and this was reminiscent of the features in the children that we were seeing, and that will become evident as we go through them, and so for that reason as well he suggested that disintegrative disorder was the appropriate label to apply. There was one final element to this that he alluded to in that same chapter of Professor Rutter’s and that was the description in several papers of disintegrative disorder occurring in children after exposure to measles virus, and in particular development of measles encephalitis, and given the history in the children that we were hearing about, and beginning to see, of disintegration or regression following a measles exposure in some form or other, once again this lent credence to the idea that a label of disintegrative disorder was most appropriate.
Q Quite apart from what Dr Berelowitz said, rightly or wrongly, did you yourself read the chapter in Sir Michael Rutter’s book?
A Yes, I did and in fact I adopted the great majority of it for inclusion in the protocol because it seemed to sum up the situation very well.
Q We will look at the EC172/96 documentation in due course, and I shall return to this topic then. So far as the clinical protocol is concerned, taking it in the early part of 1996 and going forward to August, how did you view what Professor Walker-Smith and his clinical team were doing? Did you view their role as being research or as being clinical investigation?
A First and foremost clinical investigation and this is in large part the strength of the reputation of that team, that they had an outstanding clinical track record. Also, they were very experienced researchers and had jointly and severally published an extensive volume of literature in paediatric gastroenterology and so they had very important input by way of advice into the research aspects, but principally I took responsibility for those.
Q So far as the research aspects are concerned, again we are looking at this going forward now, what was anticipated to be your role research-wise?
A There were several elements to this that were tacked on effectively to the clinical procurement of samples. The first was the analysis of biopsy material taken at colonoscopy and upper endoscopy but principally at colonoscopy, for the evidence for viral infection, for example, or the characterisation of the disease process by looking at sub-sets of individual cell sin the intestine or the characteristics of the damage to the intestine if any was present. The second was to look to see in the blood whether there was evidence of a genetic predisposition to this as identified by the American researchers looking at complement genetics, and this involved taking blood cells and analysing DNA, that was an intended part of the research programme. A further part of the research programme was to take a small amount of the cerebrospinal fluid that had been obtained during the clinical procedure and analyse that for the presence of cytokines. Cytokines are molecules in the body that communicate signals one cell to another that either switch on inflammation or switch off inflammation so they are key mediators in the body’s inflammatory and immune processes. Finally, with Dr John Linell, who was a vitamin B12 expert, we were to look at abnormalities of the enzyme systems that control vitamin B12 metabolism.
Q You have described the two limbs of the programme – that is my use of the term and I intend that to be neutral for the present purposes. May I look with you, please, at some of the elements which are, as you have described them, clinical investigation. First of all, the colonoscopy. Who was it who would decide whether a given patient would have a colonoscopy?
A Almost exclusively Professor John Walker-Smith with these first children, yes.
Q Whose decision – again, for present purposes we are looking at this early period – would it be to decide whether a child had a lumbar puncture even for the clinical reasons you indicated before?
A Again, it would be Professor Walker-Smith.
Q Did an MRI investigation feature in this clinical protocol?
A Yes, it did. MRI was included after discussion with Dr Peter Harvey and referral to various other protocols for the investigation of children who underwent similar deterioration, other publications, and the clinical merits of such an investigation were to rule in or rule out a structural abnormality of the brain, as I understand it.
Q Whose decision would it be to decide whether a given child had an MRI investigation?
A Again, it would be Professor Walker-Smith.
Q Was an EEG an element in the clinical protocol?
A Yes, it was and again this was included to investigate evidence of abnormal electrical conduction or activity in the brain.
Q Who was it who had the overall decision to include these elements, the colonoscopy, the lumbar puncture, the MRI and the EEG, in the clinical protocol?
A The overall decision, having consulted with the various experts, was with senior clinical investigator, Professor Walker-Smith.
Q Was it anticipated that you, again going forward, would have any role to play in any of the decisions whether colonoscopy, lumbar puncture, MRI or EEG should take place?
A No, absolutely not. I had no clinical decision-making role at all.
Q Even at this early stage, I am going to ask you, please, to consider this proposition. It may be suggested that although you had, as you have described, a research interest and although Professor Walker-Smith and his team had a clinical basis, say, for investigating a given child with one or other of these investigations, assume that for the minute, nonetheless what was going on here was to all intents and purposes research by everybody including the clinicians, that everybody was engaged in research. What would you say to that?
A I would say “no”. As I have said before, the first and foremost consideration was the clinical well being of the child. None of the tests, clinical or otherwise, would have been conducted had they not been clinically indicated. We are talking about one of the most eminent paediatric gastro-enterologists in the world and his clinical decision to investigate these children is without parallel, I would imagine, and, if it is good enough for him, it is most certainly good enough for the rest of us. That is not placing the burden of responsibility. This was done in collaboration after long, long consideration. There was no rush to this. The deliberation started effectively with the first appearance of Child 2 in May 1995 and the culmination of this programme did not start for many, many months after that. It was carefully thought out, done with due consideration and diligence, with collaboration, with interaction with colleagues and I have no doubt whatsoever that the clinical priorities were first and foremost and the research in which I was involved was an adjunct to that and in no way the driving force.
Q So much for the creation of the clinical protocol and the background to that creation. I want to ask you, please, now about the operation of it. At that stage, the early stage, did you see a copy of any written document setting out the clinical protocol?
A It must have been that one was in draft preparation. Indeed, I was responsible for drafting various copies as we went through this process, so there must at some stage have been such a protocol, yes.
Q May I just leap ahead briefly, please, and just turn to volume 1. If you look at the EC172/96 documents beginning at page 200 and, if you go to page 231, leaving aside the detail of this – and we will have to look at it later – principally, in relation to the clinical protocol early on in 1996, did it have any similarity to the sequencing structure that we see set out on this doctor which went to the ethics committee in September 1996?
A Yes, it did. The clinical elements of this protocol had been established from a relatively early stage.
Q May I ask you this if we look at page 231. In terms of the operation of it, you see that, on the Monday column, there is a reference to “MRI radiology” which looks – and I am going to assume that it is correct – like an asterisk on this photocopy. Do you see that?
A Yes.
Q And, at the bottom of the page, the asterisk and “Dr Wakefield to arrange”.
A That is correct.
Q Do you accept that it is likely that there is an asterisk next to MRI?
A Yes, I do.
Q Can you help the Panel, please. What was to be your role in arranging the MRI in the terms of the clinical protocol operating in early 1996.
A Certainly. It has been suggested, Mr Chairman, that I was involved in ordering tests. This document explicitly states that I was arranging them. That does not mean ordering them. When we started this work, it added a considerable workload to Professor Walker-Smith’s team which was already amongst the busiest, as we have heard, in the country in terms of dealing with other paediatric gastroenterology problems. I offered, in purely a clerking role, to arrange those tests. In other words, if there had been a clinical decision to undertake the MRI and likewise the EEG, then I would simply go to the department with the form completed so that that test could be conducted. I had no role whatsoever in making the clinical determination of whether that test should or should not take place, but I did offer to arrange for the test to be done when such a decision had been taken.
Q Do those comments relate also to the reference to EEG with an asterisk under the Tuesday column?
A They do.
Q Can you help, please, about the Thursday column; is there an asterisk there?
A By Dr Harvey, yes.
Q What role did you have in that?
A The other thing that I offered to do was to make contact with the secretary of Dr Harvey and Dr Berelowitz respectively by the weekend to let them know that a particular patient would be coming in the following week. That decision would have been taken at Professor Walker-Smith’s clinical meeting earlier or indeed in the earlier outpatient appointment of that child and I offered to let them know not by way of a clinical referral, that was not my place, this was not a formal clinical referral, that was done by the clinical team. This was merely to indicate to the secretary that this patient was coming in next week and could they make time to see them.
Q Do you accept that there is an asterisk in the Wednesday column next to Dr Berelowitz?
A Yes.
Q Are your observations in relation to Dr Harvey and Dr Berelowitz the same?
A Yes.
Q Just to complete the picture, is there an asterisk next to the reference to the Schilling test on Thursday?
A Yes, there is.
Q What was to be your role there?
A Again, it was identical. It was, if the decision had been taken clinically to perform the Schilling test, then I would hand in the form at the department and in effect this is one test that, other than with Child 2 which I did not organise, was never undertaken.
Q Again, we will come on to that in more detail later. Under the Sunday column at the bottom, is there an asterisk there on this photocopy?
A Yes, there is.
Q What was that intended to signify?
A This was to inform my lab technician that Dr Casson or one of his colleagues would be taking blood on a child who had been admitted and to procure a sample for storage.
Q May I go back to the Monday column. You have dealt with the reference to the “MRI radiology” with an asterisk. Was that asterisk intended to apply to the reference to lumbar puncture?
A No, absolutely not. The lumbar puncture, as can be seen from the protocol, was planned to follow on directly from the colonoscopy under the same sedation. So, there was no need for it to be arranged, it was planned to follow on consecutively from a prior investigation.
Q By the reference to protocol, you are referring to this document?
A That is correct.
Q Again, just fast forwarding matters, at any stage, were you involved in any decision making for any child to have a lumbar puncture?
A No.
Q Did you – and I have of course one eye focused on some of the charges – cause any of these children to undergo a lumbar puncture?
A No.
Q Did you have any broad administrative role apart from that which you have described by reference to this document?
A I was the nominated coordinating investigator and, as such, it was my job to maintain lines of communication between various collaborators. So, to that extent, I had an additional role, yes.
Q May we look together, please, at one further dimension of the operation of the protocol in its early days. Would you take for present purposes so that we can set the scene D8 which is the schedule chronology and referrals which was handed in this morning. For current purposes, may I ask you, because otherwise all this will blur into one, just to put a notional line immediately above the entry for the 9 August 1996, August 1996 being the first date on the EC application document. I want to look with you, please, at what had been happening with these children in broad and general terms prior to the first day on the EC172/96 application form. We can see – and we have dealt with already – that, on 29 June 1995, Child 2 had been referred and had an outpatient appointment in August. Child 3 had been referred and had an outpatient appointment in February and April. Child 1 had been referred and had an outpatient appointment by June. Child 2 has had a second outpatient appointment and Child 4 had been referred. Child 3 has had a second outpatient appointment and Child 1 has been admitted and investigated before that date appears on the EC172/96 document. It is against that background of those referrals and outpatient appointments and the one investigation that I want to ask you these next questions. You have referred to continuing contact with parents. Did you have any contact with Child 2’s parent? You said that you did. Child 3?
A Almost certainly in some way, yes.
Q Child 4? (After a pause) I do not want this to be a memory game and we will look at the documents in due course but, if you cannot remember …
A Yes, I am sure I did. The great majority of these early referrals came through me.
Q When parental contact was made, what was your general approach to the parents in the beginning of 1996?
A The first and most important thing was to listen and to try and gauge the story that they were telling and then to say to them that, if they would like a clinical referral, then they really must go through the normal channels of contacting their general practitioner and getting him to make an NHS referral to Professor Walker-Smith and that is the way that this has to be done in order for any further assessment or evaluation to take place.
Q And this is a generic question: what were those parents, in other words as we can see from this schedule, Child 3, 1, 2 and 4, telling you in broad terms about their children?
A They were telling what turned out to be a remarkably consistent story of a normal child whom they had lost, who had lost speech, communication, play, interaction with their siblings, who had sometimes become incontinent of faeces or urine, had developed pain and diarrhoea, had developed intractable constipation or alternating constipation and diarrhoea, who was bloated, was off their food, was losing weight, was failing to thrive, was suffering recurrent infections, was requiring multiple doses of antibiotics and who ultimately had been diagnosed as autistic or having some form of atypical autism, who despite often the very caring approach of their general practitioners and others, had not found resolution for what was causing their child’s symptoms. Given the, I suppose, somewhat privileged position of working in a teaching hospital where we see patients who suffer from, as I have given the example, liver disease where there is a gut/brain interaction par excellence, then I was at least able to say, “Well, I know someone who may be able to offer some insights into this and that is Professor Walker-Smith”.
Q When you were giving advice in general terms to these parents generally were you motivated or driven by a research interest yourself?
A To understand that we have to go right back to May 19 with Child 2, and the motivation there was quite clearly purely getting help for this child. Professor Walker-Smith and I had no interaction, he was coming to the Royal Free but we had no collaboration, I knew nothing about these children, but I could clearly see there was a clinical need for evaluation by an expert. Clinical care for the children remained paramount, and getting help for them. As I say, the research was an adjunct to anything that Professor Walker-Smith and his team considered might be necessary in a clinical context. In a research capacity I was fascinated by the possibility that something might be done to unearth what was going on down the line, if it became feasible to do so, to help these children in their plight, but it was very much secondary to the primary consideration of getting care for them.
Q Again, because there are so many interlocking strands here one topic we have not looked at is the legal aid/Dawbarns topic. I want to introduce it to this extent at this stage: when you were giving the advice to the parents in the early part of 1996 as you have described were you motivated yourself by any litigation interests?
A Absolutely not. Again, starting in May, litigation was not even on the horizon when many of these calls were coming in, in May 1995. My relationship with Barr only started at the beginning of 1996 and evolved from that point forward, but the reason that these parents were contacting me was nothing to do with litigation and litigation was certainly not my primary concern.
Q Again, I want to ask you this formally, when you were advising these parents were you at any stage instigating a referral?
A I was directing them to the correct channels that needed to be sought in order to get a referral, and if they did that then it could be argued that I had initiated that process by sending them in the right direction, but I was not making a referral or insisting to any doctor that there should be a referral, I was leaving it entirely up to them.
Q There may be a range of descriptions that one actually can put to you for comment. I have used the word instigation, you have mentioned the term initiation; how about this term, solicitation?
A Not, absolutely not. All the calls were initiated by the parents to me asking for help, and that was the process.
Q In due course when we look at the individual children we will see that you had contact with the GP in some cases. What was your role when that happened?
A When the parents contacted me I described to them the rather complex issue with which they were dealing and I told them that they needed to seek a referral. I said if it would help and if your doctor is interested I would be very happy to describe to them the background thinking of the group, what we believe may be going on and therefore what may be the basis if he so deems it necessary for such an investigation. I could not talk to the specific child, the patient, I did not know them, I had only heard what their mother had told me, but I did offer if that was the case, if they wanted me to speak to their doctor, then I would happily do so to provide a generic background on what was being done in the interests of communication between colleagues that might facilitate the process. That was the extent of my involvement.
Q I want to turn, please, to another aspect of this early period and we can see that in relation to Child 1 it is the first child who was admitted on 21 July 1996. We see also a few days later that Child 1 was investigated and we have just put down the colonoscopy and the EEG investigations; there may have been others but those are the two important ones for present purposes. In relation to Child 1 did you carry out any specific research activity?
A Yes, I did. His biopsies were examined for evidence of measles virus and for various characteristics of the disease process which he turned out to have, a focal, active inflammation of the intestine. This was done under the ethical approval 162-95 which was awarded to Professor Walker-Smith when he arrived at the Royal Free.
Q Can we look at that, please, it is volume 1, page 86A to C. I want to pick it up first of all at 86C, from Maureen Carroll, the secretary at the Ethical Practice Sub-Committee at the Royal Free. It is dated 5 September 1995:
“I am pleased to be able to inform you that your recent submission to the EP Sub-Committee has now received approval by Chairman’s Action.”
Code number 162-95 has been given and then at 86A Professor Walker-Smith had written to Baroness Gardner who was then the chair of the Ethics Committee, setting out what had been happening at Barts during his time there.
“As you know my department transfer to the Royal Free on 1 September. For some years at Barts during the course of colonoscopy in children we have had ethical permission to take two extra mucosal biopsies for research purposes. During colonoscopy children routinely have multiple biopsies taken for diagnostic purposes. The parents have signed a form as attached granting permission. These biopsies are used for a variety of ‘research’ investigations such as cytokine production where on occasion information of direct and immediate importance to the child’s illness has been obtained as well as of research importance.
I would be grateful if you would grant permission for this to continue after our move to the Royal Free.”
On page 86B is there in fact a model consent form for those research biopsies, is that right?
A Correct.
Q Just going back, in relation to Child 1, who was the first child who was investigated, so the Panel have it absolutely clear, Dr Wakefield – I am not suggesting they have not but for my purposes it is important that they do – your research in relation to the biopsy analysis of tissue in relation to Child 1, are you saying that that was, as far as you were concerned, covered by 162-95?
A Yes. It may be an appropriate time and it may help the Committee just to say that the allegations against my colleagues and against me have laboured for many months now under the misapprehension and inevitable misrepresentation that the pilot study, The Lancet paper of 12 children, and 172-96 are the same thing. They are not and they never were the same thing. One was a preliminary clinical investigation with research elements, conducted under an existing ethical approval from Professor Walker-Smith, and the other was a research application. It is the erroneous confluence of those two elements that has led to a great deal of confusion. To some extent that is understandable and it has only been resolved, certainly in my mind, by the introduction of documents by Professor Walker-Smith and his team during the early part of the last session, but nonetheless – and I hope to make this clear over the course of my evidence – these two, 172-96 and The Lancet paper are not and never were the same thing.
Q Dr Wakefield, we will indeed be looking at these documents that were introduced by Professor Walker-Smith and, for the record, as the Panel will in fact recall, pages 86A to 86C were indeed introduced by Professor Walker-Smith during the course of the last session, is that not right?
A That is correct.
Q I want to ask you to look, please, at two documents for present purposes from the children’s records. Could take the Royal Free notes for Child 3, page 40? It is a letter from Professor Walker-Smith and of course he can be asked about this document, but it was written to you and it is dated 4 April 1996, again right in the middle of this early period. The first paragraph I need not trouble you with, but it is the latter paragraph, please, I would like your comment on:
“I have not yet booked for a colonoscopy until we have got the full details of the investigative protocol worked out.”
When you received this letter what did you understand that phrase “investigative protocol” to refer to?
A I understood it to mean the full details of the clinical protocol which this child might be put through in order to establish what is going on. It may well have also referred – it is not my document and Professor Walker-Smith can talk to this – to research elements, but it is in fact an example of the diligence applied to working out the clinical protocol for these children, that he was not prepared to admit this child for investigation until everybody was happy that the full details of that protocol had been worked out. That is not a reference to research, that is a reference to working out the full details of the investigative protocol.
Q Thank you. Child 2, please, the Royal Free notes. Could you look at page 158? Dr Wakefield, I need hardly say we will be looking again at these documents in the context of the individual children for other reasons, but on 28 June 1996, again a letter from Professor Walker-Smith to you. It is obviously not your document but you received it and I am asking you, please, for a response to the second sentence on the first line: “I think he is now the most appropriate child to begin our programme.” What did you understand that phrase to refer to?
A It will become clear when we go to the documents on this child that he had undergone considerable deterioration clinically in the period between his first outpatient appointment with Professor Walker-Smith at Barts and this letter. The decision was taken on clinical grounds that this child now needed to undergo full investigation. By this stage the protocol, the clinical and the research protocol, the analysis of biopsies, was complete and it was therefore considered by Professor Walker-Smith, who will talk to this letter in time, that this child was the most appropriate to enter this protocol.
Q Thank you, that is all I am going to ask you about that document for the moment. Finally this, you have offered some observations about the application of 162-95 in relation to Child 1 who was the first to be investigated as an inpatient and you have spoken about the existence and operation of a clinical protocol with a research dimension that you have spoken about. Did that clinical protocol with the research dimension continue even after EC172-96 was put in by way of application to the Ethics Committee?
A In fact what happened, and I see this from the documentation, is that it was modified. In January 1997, by the time we had virtually completed the analysis of the first 12 children in the pilot study, it was deemed by the clinicians that the neurological investigations, that is the lumbar puncture, the MRI and later the spinal fluid analysis, revealed nothing of any clinical merit, it provided no insight into the cause of the child’s problems, and therefore it should be discontinued in the child’s interest. In other words, it was not in any way research driven. To that extent the protocol was modified.
Q Up to January/February 1997, spanning the period August to December 1996, what is your position, are you saying that the clinical protocol that you have been describing thus far continued during that period?
A Yes.
Q The clinical protocol with the added research elements that you have described.
A Yes.
MR COONAN: Thank you very much. Sir, I see the time and again that is the end of that section and again may be a convenient moment.
THE CHAIRMAN: Yes, indeed. It is five minutes past three so we will have a 15 minutes break and resume at 20 minutes past three. Dr Wakefield, once again you are still under oath so please do not discuss.
Short adjournment.
MR MILLER: I am sorry to interrupt, but it is very cold down at this end of the room. Professor Walker-Smith has got bronchitis and that is why he has gone to get his scarf. It is very cold and where Ms Smith is it is even colder, is there any prospect, even for this short period, of turning up the heating a little bit?
THE CHAIRMAN: I am sure the Panel Secretary will sort something out.
THE PANEL SECRETARY: It has been done already.
THE CHAIRMAN: Mr Coonan?
MR COONAN: The next section will be section 5, and I just want to make two observations about this, first of all one in relation to timing. I am not sure that we will finish section 5 this afternoon but I just make that observation, and again by way of introduction, and Dr Wakefield can follow this but I say for the Panel’s assistance in an attempt, as I said earlier, to tie in the relevant charges to the sections, you are now facing heads of charge 5 and 6, down to 6(g)(iv). I am just explaining why I am going to deal with it in this way. Heads of charge 5 to 6(g)(iv) although it applies to section 5, also applies to what is to become section 6, which is the approval issue, and so I shall ask Dr Wakefield to deal with those heads of charge at the end of section 6.
The balance of the charges relating to the research and ethics committee approval, that is to say 6(g)(v) and head of charge 7, I will deal with at the end of section 8. I hope Dr Wakefield has followed that.
THE CHAIRMAN: Dr Wakefield, if there is anything you feel is not quite clear please ask.
THE WITNESS: Thank you.
MR COONAN: (To the witness) Dr Wakefield, we are looking at your evidence in relation to what we have called section 5, and for these you will need volume 1, pages 200-235. Would you look first of all, so we get our chronological bearings, at page 200 the date which is written in of 6 August 1996, and you will see obviously why I took the line on the chronology schedule. Just before we go through any of this in any detail, would you formally identify, if you can, whether that writing of the date is familiar to you?
A Yes, it is.
Q Whose writing is it?
A It is Professor Pounder’s writing.
Q Would you stand back: we have been looking in general terms at the operation of a clinical protocol throughout the early part of 1996, up to, according to the chronology of referrals, 9 August, just before 9 August, and you have described the operation from your standpoint of your standpoint, your research role. The central question is why in or about August or September, which was the date when it was submitted, was it thought necessary or appropriate to put in an application for ethical committee approval which became known in due course as 172/96? What was the thinking which led up to the application?
A My colleagues will answer for themselves, but from my perspective this introduced brand new research elements, elements which were not approved under the existing analysis of biopsies approval. For example, the measure of cytokines in cerebrospinal fluid, complement genetics, the measurement of the activity of vitamin B12 related enzymes for example, so for that reason I felt it …
Q We will look at those in detail. You are saying there were extra research elements not covered by the existing EC162/95(?)
A Correct.
Q Before we get to that I am going to ask you to go through some of the elements in this document so that we get the full flavour of what it is about. Rather than laboriously take you through every line or paragraph in it, could I ask you please, and take this as slowly as you may, what was the central issue or hypothesis which this document, this application was designed to elucidate?
A That in a group susceptible, genetically susceptible children there was an association between exposure to a measles-containing vaccine and the onset of neurological and gastrointestinal symptoms that may in some way be associated with an abnormality of vitamin B12 metabolism.
Q Is summary set out on page 201 under item 3, “Objective”?
A Yes.
Q I want to ask you about the title. What is that a reference to?
A This is a title which refers to a new paediatric, or a possible new paediatric syndrome associated with bowel inflammation, a disintegrative disorder and measles/rubella vaccination.
Q What do you mean by measles/rubella vaccination?
A This goes back to the history of autism and the original instruction we received from Dr Berelowitz. There are several viral exposures that are associated with autism in children and disintegrative disorder, rubella is one, congenital rubella syndrome is associated with autism so mothers exposed when pregnant during a critical period give birth to children who have a higher risk of autism and this has been established in several different studies. We were also alerted to the association between measles and disintegrative disorder, so these are the two viruses in which we were principally interested, so these are the elements of measles-containing vaccines, or MMR or MR vaccines, that we felt may be relevant.
Q The short question is, is the title of the project intended to refer to MMR and nothing but MMR?
A No, in fact there is a mistake in this title and if you go to the full research protocol I might be able to explain that, would that be helpful?
Q Yes, please.
A If you go to page 212, “A new syndrome: enteritis and disintegrative disorder following measles and measles/rubella vaccination?” and the measles there refers to natural measles infection and it does so and it was included precisely because Professor Sir Michael Rutter referred in his chapter to the several papers that had made an association between natural measles infection and development regression into disintegrative disorder, and then the two elements of measles or measles-containing vaccines, measles and rubella that might be present in the MR vaccine or the MMR vaccine were also included because those were the viruses of interest.
Q I want to deal with the scientific background to this, which begins at the bottom of page 201 and carries on to page 207, so can we view that as, as it were, a complete document?
A Yes.
Q It strictly begins at the top of page 202.
A Correct.
Q The top part, under “Introduction” you say there that the syndrome has been linked anecdotally but consistently with either measles or measles/rubella vaccination. Again, is that a reference to the point you were making earlier?
A Yes.
Q Under the heading of “Disintegrative disorder”, that section there, can you help me, please, as to where that came from?
A This is largely abstracted from Professor Rutter’s textbook.
Q Just so you and the Panel know, we have copies of that extract if it is required to be distributed, it is Rutter, third edition, pages 581-582, I think you are familiar with that, are you?
A Correct.
Q So in looking at the objective of this study, to what extent were you looking or intending to look at autism on the one hand and disintegrative disorder on the other?
A As we had been told, and as I continue to believe, these conditions are often difficult, if not impossible, to separate out. Indeed, the prevailing thinking now is that they are a continuum They are part of the same condition that has been historically dichotomised because of a different age of onset but their clinical features are very, very similar. The additional features that separate out disintegrative disorder as it was relayed to us are those of gastro-intestinal symptoms, loss of continence, loss of bowel and bladder control, loss of coordination and a pervasive and often permanent loss of skills, and again this described the children with whom we were dealing very well.
Q Just so that the Panel understand, at the time you were putting this together, you were not holding yourself out as an expert on autism, were you?
A Not at all, no.
Q And you were not holding yourself out as an expert on disintegrative disorder?
A No.
Q Then we can, again getting our bearings in the totality of this document, see that at pages 212 to 231 … We can see that it is a complete document because the bottom of the page numbering running through from 1 to 20.
A Yes.
Q It is again that document which certainly started in the latter part of 1995 being drafted.
A Yes.
Q Would you go back now to page 208 and I take you halfway down the page where there is a paragraph numbered 7 in bold print “RADIOLOGICAL INVESTIGATIONS” and then another heading in lower case headed “Subjects” without any paragraph number and a reference to selection criteria. First of all, did you intend at least in relation to this study for there to be selection criteria?
A Yes. When you reach the stage of what is effectively a hypothesis-testing study, then one has to try as best one can, with the evidence available at the time, to refine the population to the population of interest and, in order to do so, one has selection or entry criteria which apply.
Q Looking at the three bullet points, “presence of disintegrative disorder”, “symptoms and signs of intestinal dysfunction” and a “parental request for investigation to be undertaken”, leaving aside the last one, so far as the first two are concerned, were there in fact selection criteria, properly so called, in the operation of the clinical protocol which preceded this document?
A No.
Q Do you accept that the proposition that one introduces selection criteria into a project suggests at least that it is research?
A It carries that connotation. Just to be clear for the Panel’s sake, the children were included in The Lancet study because of their signs and symptoms. Those are not, in scientific terms, selection criteria. Selection criteria apply to this form of study. So, there is a subtle difference but an important difference.
Q We will come to The Lancet later but I want to try and understand the nature of the document that was the subject matter of the application for EC approval. You have described the existence of selection criteria. Was one element of the selection criteria in this application for EC approval a requirement for a particular form of vaccination?
A Absolutely not. There was no requirement for any exposure.
Q Under paragraph 8, “SUBJECTS: How many are needed? 25”. Can you help the Panel as to why the figure of 25 was arrived at and what the significance to be attached to that is or may be?
A When designing this kind of study, you have to arrive at a number of children or individuals who will be investigated and that is necessarily arbitrary. Nonetheless, what you want to do is to include a sufficient number and, if there is something there, albeit unusual, you are not going to miss it. Alternatively, you do not keep going beyond an unreasonable number just trying to find something. If there is nothing there in the first 25, then there is no merit in continuing. So, it is arbitrary but one has to define a number for the purpose of the study and for the purpose of the ethical committee.
Q Then we move to page 209 to the issue of “CONTROLS: NIL”. In this study, as described in this document, as an intended study, why were controls not needed?
A For the great majority of the analyses, that is those undertaken on biopsy material, controls were already available. They were available under Professor Walker-Smith’s existing approval 162/95, so there was no need to seek further controls over and above that application and much of that material was contained within the tissue bank or the freezer in the Department of Paediatric Gastroenterology that allowed analysis and comparison with control populations.
Q Was there any other proposed investigation in this study going forward that needed controls?
A There was nothing that required controls that was not already retained in a archive. For example, Dr Linell had paediatric urine samples archived for comparison of various vitamin B12 metabolites. Complement genetics. The population prevalence of many of these genetic abnormalities is known but certainly could not be determined. If we had 25 controls who were not autistic, we could not make any statistical comparisons of complement genetics. That was really more of a fishing exercise in terms of research, a pilot analysis to see if it would lead anywhere. In summary, the answer is “no”, no further controls over and above those that already existed were required.
Q May I go back, please, to the question of disintegrative disorder. We see a reference to it under the heading of “Selection Criteria”. Do you see there on page 208 the presence of disintegrative disorder and then, on page 209, at the top of the page,
“All subjects will be under the age of 16, and all will manifest disintegrative symptoms and signs to differing extents.”
Again, in terms of the way in which this is drafted as an intended study, was it intended that the children would have a positive diagnosis of disintegrative disorder?
A No. That was a possible diagnosis, indeed the most likely diagnosis based upon the history that was provided. It is a very difficult diagnosis to operationalise and to distinguish from autism and Professor Sir Michael Rutter has said himself that, in disintegrative disorder with onset of under 30 months, it may be difficult if not impossible to discriminate between autism and disintegrative disorder. So, it is to some extent observer dependent and a difficult diagnosis to pin down and therefore, in this particular paragraph, we clarified it to “… and all will manifest disintegrative signs and symptoms to differing extents”.
Q Moving on to the other elements of this document as a whole, we see on page 210 the introduction in paragraph 14 to a handout and consent forms and, right at the last line, “(Copy of handout and consent form to be retained in patient’s hospital notes)” and then, over the page to page 211, a document to which you have already referred this morning with the date of 12 October 1995 at the bottom. Can you just remind us now in the context of putting in this application what the significance or intention lying behind this document was or may have been.
A It was probably one of the few things that was retained from the original draft. It was cut and pasted in and, reading it now, it is inadequate and Dr Pegg clearly thought that it was inadequate and it was extensively revised before final approval.
Q Then we move on to page 232, reference to a handout, and it goes over the page because it has been typed in on to the computer, at page 233. Again, can you remember when that was put together?
A Not precisely, no.
Q Dr Wakefield, what is the message being given to the parents in this handout in relation to the study which was described when submitted to the ethical committee? Were you describing for the parents that everything that was going to be done was to be characterised as research?
A No, not at all and that will have been made clear to them by Professor Walker-Smith in their first outpatient appointment. Their reason for seeking help was for their child’s clinical condition, the primary reason for providing help was the child’s clinical condition and that will have been explained. The existence of an adjunct research programme to that was well known to these parents and they were very keen that their children should be included if it might help elucidate the nature of the problem in their child or indeed help other children. So, there was not stage, none at all, at which they were told, persuaded or even believed that this was purely a research programme.
Q If you look at the last page in the 20-paged document at page 231, you will see the grid of investigations which was submitted to the ethical committee and again, could I ask you to comment, please, on the fact that, on the Monday, the lumbar puncture and colonoscopy were to take place, I think you have said, if clinically indicated but Dr Harvey was in effect slated to see the child in question after those events had taken place. Have you any observation you want to make about that sequencing which was pencilled in?
A This is a clinical matter, but I do have some observations because I was party to the discussions. The provisional diagnosis in these children was one of disintegrative disorder, and that was principally on the basis of the developmental regression following normal development. That was a provisional diagnosis which was suggested by someone expert in the field to our minds, and that was Dr Berelowitz. Investigation of disintegrative disorder includes lumbar puncture and there are many texts which make reference to this, including the biochemical analysis of the spinal fluid and viral analysis of the spinal fluid. Perhaps the most informative text on this is a textbook by Professor Sir David Hull where he refers to this group of children who undergo regression and talks about the value of lumbar puncture in their investigation, including viral antibody analysis. This is not a textbook intended for other than general paediatricians, and nor does he recommend at any stage in that textbook that a paediatric neurologist or other should be consulted. Professor Walker-Smith obtained a history of developmental regression, and in those circumstances he was perfectly entitled, as far as I understood it then and understand it now, to determine that these children on the provisional basis of a diagnosis of disintegrative disorder should undergo the investigations as set out in the protocol.
Q In so far as Professor Walker-Smith took decisions, are you content to leave that to him to explain?
A Absolutely.
MR COONAN: Sir, I am in your hands but I notice the time and I am coming to an important part of this; I am not going to finish it by four o’clock. It is still section 5 but involves going through the detail of paragraph 4 of page 201, that is the design of the study, and going through pages 213, 214 and then a big chunk going through 221, 222 to 223, in other words all the investigations in much more detail.
THE CHAIRMAN: Obviously there is a fair bit to go yet. I am also concerned that Dr Wakefield has been on the chair since morning and it is probably enough for the day. It is probably right and in everybody’s interest at this stage to call a halt.
We will resume at 9.30 tomorrow morning. Dr Wakefield, you are on oath and I know it is difficult, you are going to remain on oath overnight and perhaps after tomorrow over the weekend as well. It does not actually mean that you cannot see anybody and spend time with your family or anybody, but just do not discuss about this case.
(The Panel adjourned until 9.30 am on Friday, 28 March 2008)
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